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ClinicalElectrophysiologyA Handbook for Neurologists

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ClinicalElectrophysiologyA Handbook for Neurologists

Peter W. Kaplan, MB, FRCPDepartment of NeurologyThe Johns Hopkins University School of Medicine &Johns Hopkins Bayview Medical CenterBaltimore, MA, USA

Thien Nguyen, MD, PhDDepartment of NeurologyThe Johns Hopkins University School of Medicine &The Johns Hopkins HospitalBaltimore, MA, USA

A John Wiley & Sons, Ltd., Publication

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This edition first published 2011, C© 2011 Peter W. Kaplan and Thien Nguyen

Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has beenmerged with Wiley’s global Scientific, Technical and Medical business to form Wiley-Blackwell.

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The contents of this work are intended to further general scientific research, understanding, and discussion only and arenot intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment byphysicians for any particular patient. The publisher and the author make no representations or warranties with respect tothe accuracy or completeness of the contents of this work and specifically disclaim all warranties, including withoutlimitation any implied warranties of fitness for a particular purpose. In view of ongoing research, equipment modifications,changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment,and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions foreach medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage andfor added warnings and precautions. Readers should consult with a specialist where appropriate. The fact that anorganization or Website is referred to in this work as a citation and/or a potential source of further information does notmean that the author or the publisher endorses the information the organization or Website may provide orrecommendations it may make. Further, readers should be aware that Internet Websites listed in this work may havechanged or disappeared between when this work was written and when it is read. No warranty may be created orextended by any promotional statements for this work. Neither the publisher nor the author shall be liable for anydamages arising herefrom.

ISBN: 978-1-4051-85295

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Set in 8.5/11 pt Frutiger Light by Aptara R© Inc., New Delhi, IndiaPrinted in Singapore

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Contents

Preface, viiiIntroduction, ix

Part 1: Central Nervous System Disorders

Section A: Altered consciousness: confusion, delirium and unresponsiveness; agitationhallucination and abnormal behavior1. Diffuse and frontal fast activity—beta, 42. Diffuse slow activity—theta, 63. Diffuse slow activity—delta, 84. Frontal intermittent rhythmic delta activity, 125. Occipital intermittent rhythmic delta activity, 146. Triphasic waves, 167. Low-voltage fast record without dominant alpha frequencies, 188. Alpha coma, 209. Spindle coma, 22

10. Low-voltage suppressed pattern, 2411. Burst/suppression, 2612. Diffuse slowing—toxic encephalopathy—baclofen, 2813. Diffuse slowing—metabolic encephalopathy—lithium, 3014. Diffuse slowing—metabolic encephalopathy—hypoglycemia, 3215. Diffuse slowing—limbic encephalopathy, 3416. Focal arrhythmic (polymorphic) delta activity, 36

Section B: Periodic patterns of epileptiform discharges, or seizures17. Pseudoperiodic lateralized epileptiform discharges, 4018. Bilateral independent pseudoperiodic epileptiform discharges, 4419. Generalized periodic epileptiform discharges, 46

Part 2: Seizures

Section A: The Diagnosis of confusional events due to seizures20. Frontal lobe simple and complex partial seizures, 5221. Temporal lobe simple and complex partial seizures, 5422. Parietal lobe simple partial seizures, 5623. Occipital lobe simple partial seizures, 58

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vi Contents

Section B: Status epilepticus24. Complex partial status epilepticus—frontal , 6225. Complex partial status epilepticus—temporal, 6426. Simple partial status epilepticus—parietal, 6627. Simple partial status epilepticu—occipital, 6828. Generalized nonconvulsive status epilepticus, 70

Part 3: Conditions of Prolonged Unresponsiveness

Section A: Locked-in syndrome, minimally conscious state, vegetative state, and coma: disordersof consciousness and responsiveness29. Clinical definitions of impaired responsiveness, 76

Section B: Prolonged unresponsive states30. Locked-in syndrome—brainstem hemorrhage, 8231. Vegetative state—postanoxia, 8432. Minimally conscious state—after large, multifocal strokes, 8833. Catatonia—psychogenic unresponsiveness/conversion disorder, 9034. Somatosensory evoked potential Prognosis in anoxic coma, 9235. Somatosensory evoked potential Prognosis in head trauma, 94

Section C: Evoked Potentials in Consultative Neurology36. Somatosensory evoked potentials in midbrain lesion—absent cortical responses, 9837. Somatosensory evoked potentials in diffuse cortical anoxic injury—absent cortical and subcortical responses, 10038. Somatosensory evoked potentials in prolonged cardiac arrest—absence of all waves above the brachial

plexus, 10239. Somatosensory evoked potentials after prolonged cardiac arrest—absence of all responses except

cervical N9, 10440. Somatosensory evoked potentials—median and tibial after traumatic spinal cord injury, 10641. Visual evoked potentials in worsening vision, 10842. Brainstem auditory evoked potentials—in worsening hearing, 110

Part 4: Peripheral Nervous System Disease

Section A: weakness and/or respiratory failure in ICU and on the ward43. Causes of paralysis and respiratory failure in the ICU, 11544. The clinical evaluation of neuromuscular disorders, 11645. Laboratory evaluation of neuromuscular disorders, 117

Section B: Segmental weakness and/or sensory loss46. Evaluation of segmental peripheral neurological disorders, 120

Section C: Respiratory failure/diffuse weakness47. Amyotrophic lateral sclerosis/motor neuropathy, 12248. Critical Illness neuromyopathy, 12449. Brachial plexopathy, 12850. Femoral neuropathy, 13051. Sensory neuropathy/ganglionopathy, 13252. Lumbar radiculopathy, 134

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53. Guillain-Barre Syndrome—demyelinating polyneuropathy, 13654. Myasthenia gravis—neuromuscular junction, 14055. Myositis—irritable myopathy, 14256. Statin-induced myopathy—toxic myopathy/myalgia, 146

Part 5: The Casebook of Clinical/Neurophysiology Consults

57. Occipital blindness and seizures—why?, 15058. Unresponsiveness—coma, vegetative state, or locked-in state?, 15259. Unresponsiveness—organic or psychogenic?, 15460. Patient with a frontal brain tumor—psychiatric depression, paranoia, tumor growth, or status

epilepticus?, 15661. Patient with idiopathic generalized epilepsy on valproate—Metabolic encephalopathy or status

epilepticus?, 15862. Unresponsiveness—psychogenic, encephalopathy, or limbic encephalitis?, 16063. Respiratory weakness—toxic or metabolic?, 16264. Failure to wean from a ventilator/internal ophthalmoplegia—bulbar dysfunction, neuromuscular

junction problem, or polyneuropathy?, 16665. Progressive sensory loss and painful gait—radiculopathy, toxic or infectious neuropathy,

or myopathy?, 17066. Slowly progressive leg and arm weakness—radiculopathy, plexopathy, ALS, or CIDP/AMN?, 17467. Progressive thigh pain and leg weakness—radiculopathy, vasculitis, neuropathy, or amyotrophy?, 178

Index, 181

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Preface

Clinical Electrophysiology was designed for residents,neurology attendings, and intensive care specialists. Itwas conceived as a bridging tool that enables the clini-cal electrophysiological investigation to be tied in with theneurological consultation. This helps the clinician to orderthe appropriate electrical test, understand the meaningof the interpretation, and then integrate these findingswith the clinical question to arrive at a diagnosis. It mayfurther provide information on the differential diagnosis,the prognosis (where warranted), further relevant investi-gations, and some brief comments on treatment. A briefclinical reference list is included.

In making this portable aid, we placed emphasis on theinpatient clinical setting, giving the appropriate symp-toms and signs, and pertinent electrophysiology resultsthat might be found. The discussion that follows is spe-cific to the figure given. Hence, for example, confused pa-tients may have any of a number of EEG findings, but thediscussion and prognosis are directed only to the one pat-tern under discussion, for example, triphasic waves. Diag-nostic questions (particularly on chronic conditions) thatwould largely be encountered in the outpatient clinic, orinvestigated after patients’ discharge, are not included.Hence, chronic neuropathies, palsies, Parkinson’s disease,and most genetic conditions are omitted. Similarly, condi-tions without electrophysiologic relevancies or those war-ranting other types of tests (CT, MRI, and ultrasound)are not included. Although a comprehensive tome ad-dressing all neurological testing would clearly be useful,it would not be easily portable.

For immediate relevance to neurology consults, weavoided general discussions of the neurological exami-nation, disease entities and electrophysiology in general,as there are a number of excellent books that addressthese issues in detail. We recommend, of course, supple-

mental use of these tomes as they are essential to theunderstanding of clinical neurology.

The book is organized by the presenting neurologi-cal problem, for example, confusion, coma, abnormalmovements, or difficulty weaning off a respirator, limbnumbness, or weakness. Within these topics, there maybe some general diagnostic considerations, definitions ofterms, but of principal importance, we provide a test re-sult that may be encountered. For example in a comatosepatient, we give an EEG showing an invariant alpha fre-quency pattern. There follows an interpretation of theillustrated finding, differential diagnosis, prognosis, andreferences. In this way, the “vignette” starts with a clinicalproblem and reaches a diagnostic, prognostic, or thera-peutic end.

Because the handbook is “problem-oriented,” it is nota comprehensive treatment of neurologic problems. Itis briefer and covers mostly what a hospital clinicianmight encounter on neurology consultation rounds ina typical year. The last section, however, is a “case-book,” which provides several rarer, but classic, clinico-neurophysiological problems. The casebook format pro-vides more clinical information and leaves the reader totest him or herself as the case unfolds. More informationon the electrophysiological findings can be found in therespective section in the handbook.

Please use the book, if helpful, in wording your consultsand in providing references. Do give us feedback into anyshortcomings and major areas that we failed to include.We hope you find it a useful aide-memoire as you addressclinical challenges.

Peter W. Kaplan, MB, FRCPThien Nguyen, MD, PhD

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Introduction

We have designed this handbook to accompany you onyour rounds. We believe that the handbook works best inthe “middle step” of the neurology consultation process.In the first step, historical data are collected and an ex-amination is performed to arrive at an opinion, possiblythen suggesting complementary tests. If electrophysio-logical tests are requested, it is at the next step that thehandbook is helpful in addressing the significance of thefindings, the differential diagnosis, prognosis, and in pro-viding some brief therapeutic directions. In the final step,a concluding opinion can then be formulated. In othercases, the handbook can be used to review the meaningof a particular test result that has already been received,so as to be able to provide further information to thepatient’s treating physicians.

Too often, the nature and significance of test resultscan remain uncertain: do they represent a “red herring”?Are they helpful in eliminating or confirming a particu-lar diagnosis among many? What do they tell us aboutprognosis?

Standard textbooks abound to help with taking thehistory of a neurological complaint, performing physi-cal examinations, or discussing the many disorders thatcan be diagnosed. Other texts may discuss in detail thetechniques and interpretation of EEG, evoked potentials,NCVs, and electromyography. The handbook bridges thegap between the electrophysiological laboratory and thebedside.

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PART 1

Central nervous system disorders

Section A: Altered consciousness: confusion, delirium,and unresponsiveness; agitation, hallucination,and abnormal behavior

These are some of the “altered states” that prompt neu-rology consults. Patient problems rather than specific,prepackaged “diagnoses” generate consults. Hence, clin-ical training rather than standard texts is the majorsource of learning the physician’s approach to manag-ing problem-oriented questions.

Unfortunately, the causes (or diagnoses) underlying aparticular complaint are legion–-consider the potentialcauses of “dizziness,” for example, low blood pressure orneurilemmoma, migraine or brainstem stroke, low bloodsugar or otolith disease, and multiple sclerosis or Me-niere’s disease.

Clearly the constellation of symptoms and signs (andthose absent) from the patient’s description of clinicalfeatures (the syndrome) will pare down the possibilitiesand direct the diagnostic evaluation and investigation.Excellent texts are available that can address “lists” ofprobable alternatives to particular complaints. Maybe thefuture will lie in the use of a palm-held computer intowhich the complaint/symptom will be logged, followedby associated (or not) clinical features, resulting in thegeneration of a “probability list,” which can be used evenwhile one is rounding on patients.

In this section, we address certain states of altered con-sciousness or behavior that fall short of coma. Locked-instates, minimally conscious states, akinetic mutism, andvegetative states are a different order of “unresponsive-ness,” and are found in their own section further on.Those examples contained here involve acute or subacuteglobal diminution in the level of consciousness, vigilance,memory, and cognitive processing in keeping with en-cephalopathies (“altered mental status”) or “acute con-

fusional states” due to toxic/metabolic, infectious, or ictaldisturbances.

Some definitions in current use are as follows:

Delirium: An acute alteration in cognitive function withimpaired short-term memory, sleep cycle inversion,sometimes with increased motor activity in the formof agitation and tremulousness (think withdrawal ordelirium tremens), often with amnesia.

Confusion: A general term that usually needs further def-inition. Often, however, it is used to refer to a state ofimpaired language output, orientation, the ability tofollow commands and to retain information.

Altered mental status: This could subsume the above.Also a non-specific term, which could apply to psy-chosis, coma, or dementia. It also needs further speci-fication.

Encephalopathy: A Greek-derived term for diffuse braindysfunction-–also non-specific. But then globally con-fused patients are often perforce “nonspecifically”cognitively impaired (a clue in itself).

Or there may be a clinical question at the outset: Is thisnonconvulsive status epilepticus (NCSE)? This is specificand provable one way or the other. One might considerthe variety of clinical features seen with NCSE and obtainan EEG.

So where to go? Once the probable type of highercortical disturbance has been tested, for example, witha mini-mental status examination, more detailed testingof the patient’s orientation, language, memory, abilityto follow commands, to interpret events (the “cookiethief” picture), and then a probability list of diagnoses

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2 Section A: Altered Consciousness

can be produced. This might include a consult with thefollowing:

Possible toxic/metabolic en-cephalopathy. Suggest the exclu-sion of systemic infection in thispatient with chronic diminishedtolerance to the many causesof encephalopathy (e.g. cerebralatrophy; dementia). Consider alsoinvestigation of ictal/post-ictalpossibilities (with an EEG).

If in the course of investigating altered consciousness orabnormal behavior in a patient, the EEG reveals an epilep-

tiform abnormality, turn then to the section on seizures(Part 2) for further electroclinical correlations and sugges-tions.

The easier questions to answer are often those cen-tered on a request for prognosis. In particular instancessuch as after anoxia, “ball-park” answers can be pro-vided, or even some highly exact ones. For example, theprognosis in a lethargic patient 3 days after CRA can begiven with much support from the literature, and fromEEG and SSEPs (somatosensory evoked potentials). Forthese types of questions and for those patients in coma,locked-in states, and vegetative states, please refer toPart 3 on these disorders. A brief overview on progno-sis and evaluation can also be found in the section onEvoked Potentials in Consultative Neurology.

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1. Diffuse and frontal fast activity—beta

MICU, CICU, NICU, SICU, WARD, ER

CLINICAL CORRELATES: A patient may have been referredto the electrophysiology laboratory for one of several clin-ical reasons, and the EEG reveals medium to high-voltagediffuse beta frequencies. In a patient with little history, itwould suggest drug intoxication and the need for a toxinscreen. The patient may be normal, drowsy, or rarely ag-itated.

ETIOLOGY: Benzodiazepine, chloral hydrate, or barbi-turate treatment or intoxication. Occasionally, sedativewithdrawal states. With high medication doses, the pa-tient may be sedated to the point of unarousablility (betacoma, usually >30 µV on EEG). It can occur with brain-stem injury [4].

CLINICAL EVALUATION: Record all medications to whichthe patient has access. Look for medication/sedative ef-fects; alternately, the patient may be agitated rarely withdelirium.

ANCILLARY TESTING: Toxin screen for barbiturates orbenzodiazepines. MRI of brainstem structures.

DIFFERENTIAL DIAGNOSIS: For the EEG pattern, it mayoccur with benzodiazepines, barbiturates, sedative with-drawal, childhood mental retardation and cerebral palsy,brainstem injury.

PROGNOSIS: There is little dependable literature on thesignificance of this finding. The prognosis/reversibility,when this is due to medications, is excellent. In childrenthere is a report of continuous beta spindling in cerebralpalsy and mental retardation (extreme spindles). The spin-dle beta patterns are associated with a good prognosisregardless of etiology, with the exception of children noton barbiturates or benzodiazepines.

Clinical Electrophysiology. By C© Peter W. Kaplan and Thien Nguyen.Published 2011 Blackwell Publishing Ltd.

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Section A: Altered Consciousness 5

This EEG shows a medium- to high-voltage diffuse fastbeta pattern. In this case, it is prominent anteriorly, partic-ularly in light sleep and following arousal. Occasionally, itmay show a spindling pattern. On EEG, in general, thereare beta frequency bands typically seen at 18–25 Hz,less frequently at 14–16, and in one report at 35–40 Hz.It is considered high voltage when it exceeds 25 µV[1–4]. It was originally, probably incorrectly, believed tobe associated with epilepsy, minimal brain dysfunction,dyslexia, hyperactivity, or other behavioral dysfunction.Conversely, this pattern is typical of a medication effect.

REFERENCES:

1. Frost JD, Carrie JRG, Borda RP, Kellaway P. The effectsof Dalmane (flurazepam hydrochloride) on human EEG

characteristics. Electroencephalogr Clin Neurophysiol 1973;34:171–175.

2. Kellaway P. Orderly approach to visual analysis: Ele-ments of the normal EEG and their characteristics in chil-dren in adults. In: Ebersole JS, Pedley TA (eds.), Cur-rent Practice of Clinical Electroencephalography, 3rd edn.Philadelphia, PA: Lippincott/Williams and Wilkins 2003;100–159.

3. Kellaway P. The development of sleep spindles and of arousalpatterns in infants and their characteristics in normal and cer-tain abnormal states. Electroencephalogr Clinc Neurophysiol1952;4:369.

4. Otomo E. Beta activity in the electroencephalogram in casesof coma due to acute brainstem lesion. J Neurol NeurosurgPsychiatry 1966;29:383–390.

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2. Diffuse slow activity–theta [1–4]


Acute encephalopathies—frequently the elderly, multior-gan failure. Static encephalopathies, mild diffuse corticaldysfunction.

CLINICAL CORRELATES: Psychomotor slowing, confu-sion, clouding of sensorium. Brainstem function isintact.

ETIOLOGY: In the ICU, causes typically include toxicand metabolic dysfunction, and systemic infection. Of-ten seen in elderly patients with cerebral atrophy withthe above causes, as well as in dementias, static en-cephalopathies, mental retardation, and learning dis-ability.

CLINICAL EVALUATION: Higher cortical function, generalneurological examination.

ANCILLARY TESTING: CT or MRI may show subcorticalatrophy; evidence of head injury; chronic encephalopathy.Test for organ failure—hepatic, renal, respiratory, or otherorgan dysfunction.

DIFFERENTIAL DIAGNOSIS: From the EEG perspective,check that the patient is not just drowsy or asleep duringthis EEG segment (normal drowsy pattern), and ensurethat the EEG recording contains adequate noxious stim-uli to ensure full arousal during the EEG.

PROGNOSIS: Due to static encephalopathy, it reflects achronic state of cortical dysfunction and has no particularprognostic import. If seen with organ dysfunction, thenthe electroclinical picture may be reversible. Even afteranoxia, patients with this theta pattern often improveclinically and on EEG [3,4].


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This EEG shows widespread theta activity. There is vari-able intrusion of alpha and delta frequencies; alpha canbe seen with maximal arousal. The eye blink artifact seenevery several seconds bifrontally indicates the awakestate of the patient. Diffuse theta is onlyless frequent thanother EEG patterns seen in confusion/encephalopathicstates (possibly due to ascertainment bias).

REFERENCES:

1. Chatrian G-E, Turella GS. Electrophysiological evaluation ofcoma, other altered states of diminished responsiveness and

brain death. In: Ebersole JS, Pedley TA (eds.), Current Practiceof Clinical Electroencephalography. Philadelphia, PA: RavenPress 2003:405–462.

2. Gloor P, Kalabay O, Giard N. The electroencephalogram indiffuse encephalopathies: EEG correlates of grey and whitematter lesions. Brain 1968;91:779–802.

3. Silverman D. Retrospective study of the EEG in coma.Electroencephalogr Clin Neurophysiol 1963;15:486–503.

4. Yamashita S, Morinaga T, Ohgo S, et al. Prognostic valueof EEG in anoxic encephalopathy after CPR. Relationshipamong anoxic period, EEG grading and outcome. Intern Med1995;34:71–76.

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3. Diffuse slow activity—delta [1–3]


Seen in elderly patients with multifactorial causes, sub-cortical white matter cerebral atrophy, after closed headtrauma. Occasionally occurs with drugs.

CLINICAL CORRELATION: Patients are often deeply ob-tunded. They may have significant brainstem compro-mise, but not invariably.

ETIOLOGY: Young patients with severe metabolic dys-function, deep mid-line lesions, and those of the corpuscallosum.

CLINICAL EVALUATION: General neurological examina-tion. Glasgow Coma Scale.

ANCILLARY TESTING: CT or MRI may show subcorticallesions or atrophy; evidence of head injury. ConsiderSSEPs (somatosensory evoked potentials) for prognosis

after trauma. If toxicity is suspected and no other historyavailable, consider drug/toxin screen.

DIFFERENTIAL DIAGNOSIS: From the EEG perspective,only an atypical Stage 4 sleep pattern occasionally resem-bles this pattern. Ensure that the EEG recording containsadequate noxious/arousal stimuli to exclude sleep as anexplanation.

PROGNOSIS: There is little dependable literature on out-come, probably because of ascertainment bias. Progno-sis depends on the etiology. Reversible metabolic/organfailure causes have the best prognosis. There is a re-port of complete recovery after drug overdose [4]. Withhead injury, normal outcomes are less frequent. Se-rial EEGs over time may provide indications of recoveryand allow monitoring for subclinical seizures after headtrauma.


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This EEG shows widespread, arrhythmic delta activity at1–4 Hz (as well as theta and alpha frequencies) over allbrain regions. There is relatively little spontaneous vari-ability or reactivity to stimuli. This pattern is surprisinglyless common than many other EEG patterns of deepcoma.

The second EEG example shows more pervasive slow0.5- to 4.0-Hz delta activity and lesser amounts of thetaactivity. The high-frequency filter was set at 15 Hz tominimize muscle artifact in the figure.

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10 Section A: Altered Consciousness

REFERENCES:

1. Chatrian G-E, Turella GS. Electrophysiological evalua-tion of coma, other altered states of diminished re-sponsiveness and brain death. In: Ebersole JS, Ped-ley TA (eds.), Current Practice of Clinical Electroen-cephalography. Philadelphia, PA: Raven Press 2003;405–462.

2. Gloor P, Kalabay O, Giard N. The electroencephalogram indiffuse encephalopathies: EEG correlates of grey and whitematter lesions. Brain 1968;91:779–802.

3. Silverman D. Retrospective study of the EEG in coma. Elec-troencephalogr Clin Neurophysiol 1963;15:486–503.

4. Blume WT. Drug effects on EEG. J Clin Neurophysiol2006;23:306–311.

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4. Frontal intermittent rhythmic delta activity [1–5]


Seen in elderly patients with multifactorial causes: cere-bral atrophy, dementia, and intercurrent infection.

CLINICAL CORRELATION: Patients are often lethargic orconfused, disoriented, but usually conversant and canfollow motor commands; myoclonus and seizures are un-usual. The patient localizes to pain and brainstem reflexesare usually intact. This EEG pattern is usually seen as alphaactivity and wakefulness diminishes.

ETIOLOGY: Concurrent metabolic and infectious prob-lems are frequent [1–5]. Of 68 patients, 78% had hy-pertension, diabetes, or renal insufficiency [5]. One-thirdto half of the patients had both renal failure and hyper-glycemia with background theta activity; most patientshad some cerebrovascular disease and were awake [5]. Inchildren, it was previously thought to indicate increasedpressure around the third and fourth ventricles.

CLINICAL EVALUATION: Examine cognitive function, testfor neck stiffness, external evidence of trauma, fetor, ordehydration.

ANCILLARY TESTING: Electrolytes and CT/MRI for cere-bral atrophy. Consider obtaining a chest x-ray, urine, andblood cultures to look for infection.

DIFFERENTIAL DIAGNOSIS: FIRDA (frontal intermittentrhythmic delta activity) may be mistaken for an eye move-ment artifact. Gently preventing eye movements duringthe EEG or use of eye movement EEG montages can dif-ferentiate between the two. Use eye leads above andbelow the eyes.

PROGNOSIS: Largely depends on the underlying cause;may be of value if etiology is known [2–5]. There isa good prognosis with urinary tract infections and re-versibly toxic drugs. Prognosis is less favorable withthe less reversible organ failures (hepatic) and sys-temic infections [4]. Given its demographic in agedpatients, the overall prognosis is that of underlyingconditions.

TREATMENT: The underlying acute and chronic condi-tions, for example, dementia and intercurrent infection.


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This EEG shows runs of frontal intermittent delta activitywith preservation of waking background alpha and thetafrequencies. It usually appears at 2–4 Hz and is seen syn-chronously and symmetrically. Eye leads placed below theeyes can differentiate eye movement artifact from frontal(brain) slowing.

REFERENCES:

1. Chatrian G-E, Turella GS. Electrophysiological evaluation ofcoma, other altered states of diminished responsiveness andbrain death. In: Ebersole JS, Pedley TA (eds.), Current Practiceof Clinical Electroencephalography. Philadelphia, PA: RavenPress 2003;405–462.

2. Fariello RG, Orrison W, Blanco G, Reyes PF. Neuroradiologi-cal correlates of frontally predominant intermittent rhythmicdelta activity (FIRDA). Electroencephalogr Clin Neurophysiol1982;54:194–202.

3. Alehan F, Dabby R, Lerman-Sagie T, Pavot P, Towne A. Clinicaland radiologic correlates of frontal intermittent rhythmic deltaactivity. J Clin Neurophysiol 2002;19:535–539.

4. Daly D, Whelan JL, Bickford RG, Maccarty CS. The elec-troencephalogram in cases of tumors of the posterior fossaand third ventricle. Electroencephalogr Clin Neurophysiol1953;5:203–216.

5. Watemberg N, Alehan F, Dabby R, Lerman-Sagie T, PavotP, Towne A. Clinical and radiologic correlates of frontalintermittent rhythmic delta activity. J Clin Neurophysiol2002;19:535–539.

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5. Occipital intermittent rhythmic delta activity [1–5]

WARD, PEDs, OUT Pt

Occasionally seen in pediatric patients with a history ofgeneralized seizures.

CLINICAL CORRELATES: This pattern exists almost exclu-sively in children. The patient is interactive on arousal.

At the time of EEG, most patients have had atonic–clonic seizure leading to the referral. During theEEG, patients are usually awake or drowsy, or less fre-quently asleep [3]. There is often a past history of child-hood absences [1,4,5], but recent data indicate an asso-ciation with localization-related epilepsies [3].

ETIOLOGY: It has been reported with salmonella, Hunt-ington disease, and subacute sclerosing panencephalitis[3], and may occur in Angelman syndrome.

CLINICAL EVALUATION: Take a careful history forseizures. Mean age 8 years (3–16 years).

ANCILLARY TESTING: The brain MRI is normal.

PROGNOSIS: Children whose EEGs contain 3/secondspike-and-wave as well as occipital intermittent rhyth-mic delta activity (OIRDA) may remit within 10 years inmore than 50% of cases, and not manifest tonic–clonicseizures; those without OIRDA, but with photoparoxys-mal EEG responses, rarely remit spontaneously (6%), andmore frequently have convulsions.

TREATMENT: Patients with seizures can benefit from anti-epileptic drugs.


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This EEG shows runs of OIRDA with preservation of wak-ing background alpha and theta frequencies. It usuallyoccurs at 2–4 Hz, synchronously and symmetrically withsome waxing and waning. It is seen in awake and drowsyrecordings of EEG. The background is usually alpha, butmay be theta in about a quarter of patients [1]. Halfthe studies also have focal, concomitant epileptiformdischarges. Rarely, OIRDA is brought out by hyperventila-tion and can co-occur with frontal intermittent rhythmicdelta activity (see this rhythm).

REFERENCES:

1. Loiseau P, Pestre M, Dartigues JF, Commenges D, Barberger-Gateau C, Cohadon S. Long-term prognosis in two

forms of childhood epilepsy: Typical absence seizures andepilepsy with rolandic (centrotemporal) EEG foci. Ann Neu-rol 1983;13:642–648.

2. Daly DD, Markand ON. In: Daly DD, Pedley TA (eds.), CurrentPractice of Clinical Electroencephalography, 2nd edn. NewYork: Raven Press 1990;335–370.

3. Watemberg N, Linder H, Dabby R, Blumkin L, Lerman-Sagie T. Clinical correlates of occipital intermittent rhyth-mic delta activity (OIRDA) in children. Epilepsia 2007;48:330–334.

4. Riviello JJ, Foley CM. The epileptiform significance of inter-mittent rhythmic delta activity in childhood. J Child Neurol1992;7:156–160.

5. Gullapalli D, Fountain NB. Clinical correlation of occipi-tal intermittent rhythmic delta activity. J Clin Neurophysiol2003;20:45–51.

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6. Triphasic waves [1–7]


Seen with toxic/metabolic illness, often with infection andcerebral/subcortical atrophy.

CLINICAL CORRELATES: Patients are usually lethargic; my-oclonus and seizures are unusual. The eyes are open orclosed, may open to stimuli. The patient is confused, maybe able to speak, but is somnolent. In lighter coma, thepatient can follow commands, localize to pain, and haveintact brainstem reflexes.

ETIOLOGY: Concurrent metabolic and infectious prob-lems are frequent: hepatic failure, uremia, systemicinfection, hyperosmolarity, hypoxia, and hypoglycemia[2–6]. Triphasic waves (TWs) are seen with drug toxicity,for example, lithium, cefepime, baclofen, ifosfamide,levodopa, metrizamide (controversy whether this isNCSE), valproate (with or without raised ammonia), sero-tonin syndrome, Creutzfeldt-Jakob disease, Alzheimer’sdisease [2–6].

CLINICAL EVALUATION: In nontraumatic coma, examinecognitive function, test for neck stiffness, look for hepaticfetor, and look for systemic evidence of liver insufficiency(spider naevi, caput medusae, palmar erythema, leukony-chia).

ANCILLARY TESTING: Electrolytes, ammonia level, liverprofile, toxin screen, and MRI for white matter disease.

DIFFERENTIAL DIAGNOSIS: TWs are blunter and usuallyof lower frequency than the discharges of nonconvulsivestatus epilepticus (NCSE). TWs may increase (rarely de-crease) with arousal. Background activity can be presentwith either TWs or NCSE. TWs resolve with benzodi-azepines, but the patient fails to improve. Fifty-nine per-cent of patients with TWs may have nonmetabolic en-cephalopathies [2].

PROGNOSIS: This largely depends on the underlyingcause; the EEG may be of prognostic value if the eti-ology is known [2–6]. There is a good prognosis withurinary tract infections, reversibly toxic drugs and hyper-ammonemia in patients on valproate. The prognosis isless favorable with less reversible organ failure (hepatic)and systemic infections [4]. There is a poor prognosis af-ter anoxia [6]. Given its demographic in aged patients,the overall prognosis (from all causes) is poor with a 77%mortality [3]. In 100 patients with severe liver disease, 45died within 1 week before the advent of liver transplants[7].

TREATMENT: If NCSE is suspected as a differential diag-nosis, then a trial of lorazepam 2–4 mg may improveNCSE clinically and either on EEG; benzodiazepines mayworsen encephalopathies.


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This EEG shows generalized TWs, typified by a bluntedor small upgoing (negative) first phase, rapid descend-ing dominant (positive) second phase, less steep, ascend-ing third phase. It is best seen in a referential mon-tage and often brought out by arousal. The frequencyof TWs is 1.5–2.5 Hz, of moderate to high amplitude(100–300 µV); the activity is seen in clusters. There is of-ten theta/delta background activity. TWs are often domi-nant anteriorly, with an anteroposterior lag on a referen-tial montage [2]. The background is slower if seen withhepatic insufficiency. Toxic and metabolic causes cannotbe distinguished on EEG [2].

REFERENCES:

1. Bickford RG, Butt HR. Hepatic coma: The EEG pattern. J ClinInvest 1955;34:790–799.

2. Sundaram MB, Blume WT. Triphasic waves: Clinical correlatesand morphology. Can J Neurol Sci 1987;14:136–140.

3. Bahamon-Dussan JE, Celesia GG, Grigg-Damberger MM.Prognostic significance of EEG triphasic waves in patientswith altered state of consciousness. J Clin Neurophysiol1989;6:313–319.

4. Young GB, Bolton CF, Archibald YM, Austin TW, Wells GA.The EEG in sepsis-associated encephalography. J Clin Neuro-physiol 1992;9:145–152.


6. Yamashita S, Morinaga T, Ohgo S. Sakamoto T, KakuN, Sugimoto, S, Matsukura S. Prognostic value of EEGin anoxic encephalopathy after CPR: Relationship amonganoxic period, EEG grading and outcome. Int Med 1995;34:71–76.

7. MacGillivray BB. The EEG of liver disease. In: Remond CA(ed.), Handbook of Electroencephalography and Clinical Neu-rophysiology, Vol. 15. Amsterdam: Elsevier 1976;77–87.

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7. Low-voltage fast record without dominantalpha frequencies [1]

SICU, MICU, NICU

Seen after head trauma or in alcohol abuse. May be anormal variant.

CLINICAL CORRELATES: The patient may be cognitivelynormal. Conversely, there may be confusion or lethargy.

ETIOLOGY: Head trauma, normal variant, hydrocephalus,alcoholism.

CLINICAL EVALUATION: General neurological examina-tion. Check for history of closed head trauma, bilateralsubdural, epidural, or scalp fluid collections. Ask after ahistory of alcoholism. Smell for alcohol fetor.

ANCILLARY TESTING: CT or MRI for bilateral fluid col-lections, diffuse atrophy, evidence of head injury. If sus-pected and no other history available, drug/toxin screen.

DIFFERENTIAL DIAGNOSIS: From the EEG perspective, al-coholism and closed head trauma are the frequent patho-logical causes. It rarely occurs postictally and with hydro-cephalus.

PROGNOSIS: Little dependable literature on significanceof this finding. Significance depends on clinical context(e.g., postictal states can suppress voltage). By itself, ithas no prognostic significance.


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This EEG shows a low-voltage fast beta pattern. Thereis no posterior or diffuse alpha, theta, or delta activity.Ensure that the EEG recording has the usual interelec-trode distances as decreased distance lowers recordedvoltage and can produce a similar pattern. Ensure thatarousal stimuli have been applied and that eye closurewas noted. This pattern is seen in 6–7% of the normaladult population. Alpha/background activity voltage di-minishes with age, partly due to increased skull thickness

and bone. Posttraumatic patients with this pattern areoccasionally deeply obtunded.

REFERENCE:

1. Maulsby RL and Kellaway P . The Normative Electroencephalo-graphic Data Reference Library. Final report. NAS 9–1200.Washington, DC: National Aeronautics Space Administration1968.

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8. Alpha coma

CICU, MICU, NICU, SICU, ER

After cardiorespiratory arrest, head trauma.

CLINICAL CORRELATION: By definition, the patient has tobe in coma. The patient is eyes closed, but her or shemay open to stimuli. Arms posture or withdraw to pain;brainstem reflexes—pupil reactions, vestibulo-ocular re-flex, gag, spontaneous breathing—are often present inalpha coma.

ETIOLOGY: It is most frequently reported after CRA(10–23%) [1], less frequently after infection, metabolicdysfunction, head trauma, drugs (e.g., carbamazepine),seizures, stroke, heat stroke, and hypoxia. Cardiores-piratory arrest, infection, metabolic dysfunction, headtrauma, seizures, stroke, hypoxia, and drugs.

CLINICAL EVALUATION: Examine for brainstem reflexesand assess Glasgow coma scale. Look for evidence ofrare toxic or metabolic causes if CRA is not known.

ANCILLARY TESTING: CT/MRI might show laminar necro-sis. Consider Complete metabolic pane and toxin screen,and somatosensory evoked potential (SSEP) for prognosis.

DIFFERENTIAL DIAGNOSIS: In paralyzed patients, ensurethat the patient is not awake. Tip-off is lack of EEG re-

activity to stimuli, anterior distribution of alpha activity,and if the patient is not paralyzed, presence of eye blinkartifact. Alpha frequency patterns (AFPs) can be seen inthe locked-in syndrome, but are usually reactive and overthe posterior head region. The patient is awake. It rarelyoccurs with an apallic syndrome. There is a slight resem-blance to REM sleep patterns. Posterior AFPs can occur inGrade 1 postanoxic coma (posterior, reactive) with goodprognosis [1].

PROGNOSIS: After anoxia/CRA or stroke, the prognosisis almost universally poor; meta-analysis indicates 88 and90% mortality, respectively. After hypoxia without cardiacarrest 61% mortality; after drugs only 8%. If the EEGshows reactivity, most patients awaken, but few have ameaningful recovery [2]. Almost all patients without EEGreactivity die [1,2].

Consider SSEPs for further prognosis-–if the N20 is ab-sent, then the outcome is death or persistent vegetativestate [1]. Interpret with caution after anesthetics or early(<24 hours) in the clinical course.

TREATMENT: No effective treatment. The EEG patternevolves into other patterns. The effect of hypothermiais unknown.


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This EEG shows generalized AFP [3] but also some higherfrequency beta activity. There is also anterior rhythmicactivity with sharp waves. This EEG segment has used ahigh-frequency filter of 15 Hz to minimize artifact in theillustration.

In alpha coma, the alpha frequencies appear diffusely,but may be more prominent anteriorly. The record usuallyshows no reactivity to stimuli. AFP may be transient andevolve from a burst-suppression pattern or other pattern,or to another pattern, as in this case. Similar patterns mayinclude slower frequencies in the fast theta range [4] butwith similar implications.

REFERENCES:

1. Berkhoff M, Donati F, Bassetti C. Postanoxic alpha (theta)coma: A reappraisal of its prognostic significance. Clin Neu-rophysiol 2000;111:297–304.

2. Kaplan PW, Genoud D, Ho TW, Jallon P. Etiology, neurologiccorrelations and prognosis in alpha coma. Clin Neurophysiol1999;110:205–213.

3. Westmoreland BF, Klass, DW, Sharbrough FW, ReaganTJ. Alpha coma. Electroencephalograpic, clinical, patho-logic and etiologic correlations. Arch Neurol 1979;32:713–718.

4. Young GB, Blume WT, Campbell VM, Demelo JD, Leung LS,McKeown MJ, McLachlan RS, Ramsay DA, Schieven JR. Alpha,theta and alpha-theta coma: A clinical outcome study utiliz-ing serial recordings. Electroencephalogr Clin Neurophysiol1994;91:93–99.

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9. Spindle coma [1–5]

SICU, CICU, MICU

Seen with head trauma, cardiac arrest, seizures, stroke,and drugs.

CLINICAL CORRELATION: By definition, the patient hasto be in coma. Eyes closed but may open to stimuli.Arms posture or withdraw to pain; brainstem reflexes—pupil reactions, vestibulo-ocular reflex, gag, spontaneousbreathing—usually present in patients with spindle coma.

ETIOLOGY: It is most frequently reported after head in-jury; midbrain and brainstem strokes; encephalopathy,hypoxia, drugs, and seizures.

EVALUATION: Examine brainstem reflexes and assessGlasgow coma scale.

ANCILLARY TESTING: MRI may reveal pontomesen-cephalic pathology. Otherwise test for drug or toxicologyscreen. For prognosis after CRA, suggest somatosensoryevoked potentials (SSEPs).

DIFFERENTIAL DIAGNOSIS: In paralyzed patients, ensurethat the patient is not asleep. When due to drug causes,

or if seen postictally, patients may be hypersomnolent orstill experiencing sedative medications that induce sleep.

PROGNOSIS: Overall mortality is 23%. There is a poorprognosis after cerebrovascular accidents (72% mortal-ity); better after hypoxia (38%), CRA (20%), trauma(15%), drugs/seizures (0–10%) mortality. All patientswith reactive spindle coma survived [1]. Spindle comais rare in children and about a third recovers withoutdeficits—causes include head trauma, drowning, en-cephalitis, seizures and drugs. Consider SSEPs for fur-ther prognostication if caused by CRA. If the corticalSSEP N20 is absent in an anoxic-ischemic etiology, thenthe predictable outcome is death or persistent vegetativestate [3]. Interpret with caution after anesthetics or early(<24 hours) in the clinical course. See also the section onSSEPs.

TREATMENT: No specific treatment. This EEG pattern mayevolve to other patterns. The effect of hypothermia on thesignificance of this finding is unknown. Some physicianshave used methylphenidate to induce arousal, but this isviewed as controversial.


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This EEG shows bursts of frontocentral 10-Hz spindleson a delta background. The pattern may be reactive orunreactive to stimuli. It may be a transient pattern, whichevolves to a waking alpha or other pattern.

REFERENCES:

1. Britt CW. Nontraumatic “spindle coma”. Clinical EEG andprognostic features. Neurology 1981;31:393–397.

2. Chatrian G-E, White LE. Sleep EEG patterns in certain co-matose states after injuries in the head. ElectroencephalogrClin Neurophysiol 1963;15:272–280.

3. Hansotia P, Gottschalk P, Green P, Zais D. Spindle coma: In-cidence, clinicopathological correlates and prognostic value.Neurology 1981;31:83–87.

4. Kaplan PW, Genoud D, Ho TW, Jallon P. Etiology, neurologiccorrelations and prognosis in early spindle coma. Clin Neuro-physiol 2000;111:584–590.

5. Horton EJ, Goldie WD, Baram TZ. Rhythmic coma in children.J Child Neurol 1990;5:242–247.

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10. Low-voltage suppressed pattern

CICU, MICU, NICU, SICU

Usually after cardio-respiratory arrest may occur withanesthesia [1–4].

CLINICAL CORRELATION: When an EEG shows minimalactivity, the patient shows no movements, reaction topain, or other clinical cortical responses. GCS = 3. Brain-stem reflexes may be present.

ETIOLOGY: Usually it occurs after cardiac arrest and lessfrequently anoxia, high-dose central nervous system sup-pressant drugs; however, EEG usually shows some burstsof higher voltage activity during a 20-minute recording.

CLINICAL EVALUATION: The need to establish cause ofcoma is paramount. Ascertain any history before comaonset; exclude anesthetic, barbiturate, or drug effect.

ANCILLARY TESTING: CT, MRI, organ failure, tox screenfor cause of coma.

Somatosensory evoked potentials/cortical potentialsif absent, indicate zero prognosis for return of con-

sciousness. After CRA, MRI might show laminarnecrosis.

DIFFERENTIAL DIAGNOSIS: Rarely the pattern occurs inpatients with high doses of cortical suppressants (bar-biturates, benzodiazepines, propofol); however, the EEGthen usually shows some bursts of higher voltage activityduring a 20-minute recording.

Technical problems may cause a flat EEG: check thebiological calibration and recording/display sensitivity.

PROGNOSIS: After anoxia/CRA head trauma or strokeprognosis is zero for return to consciousness (check cal-ibration, recording parameters for “electrocerebral inac-tivity” and for suppressant drugs). In rare cases patientsmay persist in a vegetative state.

TREATMENT: No effective treatment. Pattern has terminalsignificance. The effect of hypothermia on the prognosticsignificance of this pattern is not clear.


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This EEG shows generalized suppression with no corticalactivity above 2 µV. There are residual muscle and ECGartifacts. The tracing shows no reactivity to noxious stim-uli. Ascertain that no technical cause for absent corticalactivity is present. This pattern may have evolved froma burst-suppression, alpha coma, or other pattern. Thepresence of this pattern is not synonymous with braindeath (which is a clinical diagnosis). EEG reports may re-flect “electrocerebral inactivity” (if performed correctly toinclude core temperature above 35◦C, absence of anes-thetic drugs, use of double-interelectrode distance, test-ing of each electrode’s impedance and presence, min-imum 30-minute recording, and appropriate high- andlow-frequency filtering).

REFERENCES:

1. Bassetti C, Scollo-Lavizzarri G. Prognostic value of EEGin post-anoxic coma after cardiac arrest. Eur Neurol1987;26:161–170.

2. Pagni CA, Courjon J. Electroencephalographic modificationsinduced by moderate and deep hypothermia in man. ActaNeurochir 1964;13:35–49.

3. Synek VM. Prognostically important EEG coma patterns indiffuse anoxic and traumatic encephalopathies in adults.J Clin Neurophysiol 1988;2:161–174.

4. Wijdicks EFM, Hijdra A, Young GB, Bassetti CL, WiebeS. Practice parameter: prediction of outcome in comatosesurvivors after cardiopulmonary resuscitation (an evidence-based review): Report of the quality standards subcom-mittee of the American Academy of Neurology. Neurology2006;67:203–210.

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11. Burst/suppression

CICU, MICU, SICU, NICU

Seen after CRA, with anesthesia or during the manage-ment of status epilepticus [1–5].

CLINICAL CORRELATE: Eyes closed, but may open con-gruent with the EEG bursts of epileptiform activity; pa-tients may have facial or limb myoclonus; eyelid twitch-ing, vertical nystagmus; chewing movements and tonicposturing. Caveat for general neurological/brainstem ex-amination: corneal reflexes and eye opening may be dif-ficult to determine because eye opening may be due toepileptic bursts of activity. In the context of coma, thispattern indicates an overwhelming, diffuse cerebral in-sult [1].

ETIOLOGY: This EEG pattern is seen after CRA, hypother-mia, and intoxication with CNS suppressants (e.g., barbi-turate overdose) [1–5]; end-stage CNS disease.

CLINICAL EVALUATION: Examine brainstem reflexes andassess Glasgow coma scale. The physical examination isoften compromised by the patient’s movement, which iscaused by the epileptic activity.

ANCILLARY TESTING: Review causes of CNSsuppression—toxin screen; history of anoxia/CRA.

Consider CT/MRI for evidence of laminar necrosis,herniation, or other massive CNS insult. For prognosisafter CRA, somatosensory evoked potentials (SSEPs).

DIFFERENTIAL DIAGNOSIS: The EEG during anesthesia,treatment with propofol, midazolam, or barbiturates canproduce these patterns.

PROGNOSIS: After anoxia/CRA, prognosis is almost uni-versally poor-–no better than persistent vegetative state(PVS) [5]. If the pattern persists after 48 hours in theabsence of sedatives or hypothermia, no patients returnto consciousness. The effect of hypothermia is unclear,and itself may induce this pattern. Consider testing withSSEPs for further prognostic help. If the N20 is absent,then the outcome is death or PVS. Interpret bust suppres-sion with caution after anesthetics or early (<24 hours)in the clinical course. It is rarely seen with pachygyria,Ohtahara’s syndrome, and early myoclonic encephalopa-thy when bursts typically last 2–6 seconds, and suppres-sion periods last 2–10 seconds.

TREATMENT: After CRA, no palliative effect. In our expe-rience, no return to consciousness after CRA whateverthe management.


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This EEG shows generalized bursts of polymorphicepileptiform discharges lasting from less than a second toseveral seconds, interspersed with periods of suppression(activity <20 µV) usually lasting 2–10 seconds, but theycan be longer [1].

REFERENCES:

1. Prior PF. The EEG in Acute Cerrebral Anoxia. Assessmentof cerebral function and prognosis in patients resuscitatedafter cardio-respiratory arrest. Amsterdam: Excerpta Medica1973;314.

2. Haider I, Matthew H, Oswald I. Electroencephalographicchanges in acute drug poisoning. Electroencephalogr ClinNeurophysiol 1971;30:23–31.

3. Pagni CA, Courjon J. Electroencephalographic modificationsinduced by moderate and deep hypothermia in man. ActaNeurochir 1964;13:35–49.

4. Synek VM. Prognostically important EEG coma patterns indiffuse anoxic and traumatic encephalopathies in adults.J Clin Neurophysiol 1988;2:161–174.


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12. Diffuse slowing—toxic encephalopathy—baclofen[1–6]

MICU, WARD, ER

Seen with toxins, for example, baclofen, cefepime, andifosfamide. EEG pattern can also be seen with metabolicproblems, liver and renal insufficiency.

CLINICAL CORRELATES: Depending on the severity ofdrug toxicity, patients may complain of sedation, nausea,vomiting, vertigo, or depression. Some patients, partic-ularly the elderly, may be drowsy and confused to thepoint of stupor. The eyes may be open or closed, andmay open to stimuli. The patient can usually speak. Con-fusion, flapping tremor, and myoclonus may dominatethe picture. In lighter coma, the patient can follow com-mands, localize to pain, and have intact brainstem re-flexes. In deeper coma from baclofen, the patient mayrequire vasomotor and ventilator support. There may begeneralized seizures.

ETIOLOGY: The principal impairment is that due to cen-tral nervous system toxicity. In the case given here, ba-clofen, a γ-amino butyric acid (GABA) analog which bindsto bicuculline-insensitive GABA-B receptors in the brain-stem, is the most commonly used drug for spinal cordspasticity. Baclofen may be therapeutic at lower doses,but toxic at higher oral or intrathecal doses.

CLINICAL EVALUATION: Standard general neurologicalexamination, with particular attention to myoclonus,seizures, and the need for cardiovascular and ventilatorysupport.

ANCILLARY TESTING: Look for electrolyte abnormalities,other causes of toxicity—high ammonia level, an abnor-

mal liver profile, a positive toxin screen, other neurolepticdrugs. Test specifically for particular drugs.

DIFFERENTIAL DIAGNOSIS: Clinical—Toxic encephalo-pathies may cause confusion and sedation, but several(lithium, baclofen, tricyclic antidepressants, ifosfamide,and some antibiotics) may also induce tremors, my-oclonus, and seizures. Lithium may be suspected by theclinical signs of cerebellar, basal ganglia, and peripheralnerve dysfunction.

EEG—Similar EEG pictures can be produced bycephalosporins and bismuth. Classical triphasic waves(TWs) (e.g., with hepatic or even renal failure) are blunterand usually of lower frequency than the discharges ofnonconvulsive status epilepticus (NCSE). TWs may in-crease (rarely decrease) with arousal. Background activitycan be present with either TWs or NCSE. TWs resolvewith benzodiazepines, but the patient fails to improve.Fifty-nine percent of patients with TWs may have non-metabolic encephalopathies [2].

PROGNOSIS: This largely depends on the degree of drugtoxicity and the concurrent organ failure that accompa-nies it (acute renal failure). Baclofen, cefepime, and ifos-famide toxicities are largely reversible.

TREATMENT: The cornerstone is supportive ICU care andtreatment of organ failure. If NCSE is suspected as a differ-ential diagnosis, then a trial of lorazepam 2–4 mg may im-prove NCSE clinically and either on EEG; benzodiazepinesmay worsen encephalopathies.


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This EEG shows a mixture of diffuse, slower frequenciesin the theta and delta range, as well as generalized tripha-sic waves (see also triphasic waves). Cases of baclofen tox-icity have shown increased slow activity, decreased fastfrequencies, periodic activity, TWs, semiperiodic epilep-tiform discharges, generalized epileptiform, and burst-suppression patterns. TWs are often dominant anteriorly,with an anteroposterior lag on a referential montage.Toxic and metabolic causes of diffuse slowing and TWscannot be clearly distinguished on EEG.

REFERENCES:

1. Abarbanel J, Herishanu Y, Frisher S. Encephalopathy associ-ated with baclofen. Ann Neurol 1985;17:617–618.

2. Sundaram MB, Blume WT. Triphasic waves: Clinical cor-relates and morphology. Can J Neurol Sci 1987;14:136–140.



5. Fakhoury T, Abou-Khalil B, Blumenkopf B. EEG changesin intrathecal baclofen overdose: A case report and re-view of the literature. Electroencephalogr Clin Neurophysiol1998;107:339–342.

6. Boutte C, Vercueil L, Durand M, Vincent F, Alvarez JC. EEGcontribution to the diagnosis of baclofen overdose. Clin Neu-rophysiol 2006;36:85–89.

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13. Diffuse slowing—metabolicencephalopathy—lithium [1–6]

MICU, WARD, ER

CLINICAL CORRELATES: Depending on the severity oflithium toxicity, patients have variable degrees of lethargy,but often exhibit evidence of cortical (slowing or even de-mentia), corticospinal (spasticity), extrapyramidal (rigidityand tremor), cerebellar (ataxia), and peripheral nerve im-pairment. Myoclonus and seizures frequently occur withsignificant toxicity. The eyes may be open or closed, andmay open to stimuli. The patient is confused and maybe able to speak. Confusion, rigidity, and myoclonus maydominate the picture. In lighter coma, the patient can fol-low commands and localize to pain; brainstem reflexespresent.

ETIOLOGY: The principal CNS impairment is that due tolithium toxicity, but concurrent metabolic problems (acuterenal failure), intercurrent infection and fever complicatethe picture and contribute to long-term morbidity.

CLINICAL EVALUATION: Examine for evidence of neuro-logical deficits in the broad spectrum of CNS/peripheralnervous system-affected systems. This will include eval-uation of the level of consciousness, cognitive function,nystagmus, tone (rigidity and spasticity), limb coordina-tion (tremor and ataxia), and reflexes. Recent infection ordehydration is frequent precipitants of lithium toxicity.

ANCILLARY TESTING: Look for electrolyte abnormalities,other causes of toxicity—ammonia level, liver profile,

toxin screen, other neuroleptic drugs. Obtain an MRI forwhite matter disease. The clinical state may persist afternormalization of the lithium level and lag as lithium levelsare being corrected.

DIFFERENTIAL DIAGNOSIS: On EEG, triphasic waves(TWs) are blunter and usually of lower frequency thanthe discharges of nonconvulsive status epilepticus (NCSE).TWs may increase (rarely decrease) with arousal. Back-ground activity can be present with either TWs or NCSE.TWs resolve with BZPs, but the patient fails to improve.Fifty-nine percent of patients with TWs may have non-metabolic encephalopathies [2].

PROGNOSIS: This largely depends on the degree oflithium toxicity and the concurrent organ failure thataccompanies it (acute renal failure). Mortality and pro-longed morbidity with ICU support over several weeks tomonths are not rare.

TREATMENT: For lithium toxicity, supportive ICU care andtreatment of organ failure determine outcome. Theremay be a need to treat associated myoclonus and seizureswith benzodiazepines and AEDs—consider levetiracetam.If NCSE is suspected as a differential diagnosis, thena trial of lorazepam 2–4 mg may improve NCSE clini-cally and either on EEG; benzodiazepines may worsenencephalopathies.


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This EEG shows a mixture of diffuse, slower frequen-cies in the theta and delta range, as well as generalizedtriphasic waves (see also triphasic waves). TWs are of-ten dominant anteriorly, with an anteroposterior lag ona referential montage. Toxic and metabolic causes of dif-fuse slowing and TWs cannot be clearly distinguished onEEG.

REFERENCES:

1. Smith SJM, Kocen RS. A Creutzfeldt-Jacob like syndromedue to lithium toxicity. J Neurol Neurosurg Psychiatry1988;51:120–123.



4. Young GB, Bolton CF, Archibald YM, Austin TW, Wells GA.The EEG in sepsis-associated encephalography. J Clin Neuro-physiol 1992;9:145–152.


6. Kaplan PW, Birbeck G. Lithium-induced confusional states:Nonconvulsive status epilepticus or triphasic encephalopathy?Epilepsia 2006;47:2071–2074.

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14. Diffuse slowing—metabolicencephalopathy—hypoglycemia [1–3]

MICU, WARD, ER

CLINICAL CORRELATES: Depending on the severity of hy-poglycemia, patients have variable degrees of confusion,lethargy, merging into coma. Seizures occur with severehypoglycemia. In lighter coma, the patient can followcommands, localize to pain, and even in coma the brain-stem reflexes are usually present—Babinski reflexes.

ETIOLOGY: Hypoglycemia. Causes include excess insulin,oral hypoglycemic agents, and patients with liver failure.

CLINICAL EVALUATION: Examine for evidence of insulininjections. A nonlateralizing neurological downward pro-gression is seen with increasing hypoglycemia, rangingfrom confusion to deep coma with relative preservationof brainstem reflexes, but with Babinski responses. Re-cent infection or dehydration is frequent precipitants.

ANCILLARY TESTING: Look for electrolyte abnormali-ties and other causes of encephalopathy (toxic andmetabolic). The clinical state may persist after normaliza-tion of serum glucose level, and thus lag as hypoglycemia

is being corrected. Glucose given intravenously in somecoma patients may precipitate thiamine deficiency.

DIFFERENTIAL DIAGNOSIS: Clinical—The encephalo-pathic changes are etiologically nonspecific and diagnosisis usually routine because blood chemistry testing isroutine. In hypoglycemia, myoclonus, movement dis-orders, and rigidity are less frequent than in toxicencephalopathies.

EEG—Low-voltage records and/or slowing are nonspe-cific and can be seen with other acute CNS insult includ-ing hypoxia and after seizures.

PROGNOSIS: This largely depends on the degree and du-ration of hypoglycemia. Prolonged, severe low glucosecan result in mild to moderate permanent diffuse cere-bral deficit, vegetative states, or death.

TREATMENT: Glucose infusion and supportive ICU care.There may be a need to treat associated myoclonus andseizures with benzodiazepines and AEDs.


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This EEG shows monomorphic 5-Hz theta activity, noposterior waking alpha, and has periods of bilateral sup-pression. The glucose level was 12 mg/100 mL.

REFERENCES:

1. Lefebre CH, Lefebre B, Skotzek B. An unusual case of in-sulinoma with confusional states and tonic-clonic seizures

diagnosed with the help of long-term video-EEG record-ing. Electroencephalogr Clin Neurophysiol 1990;75:S81(abstract).

2. Scarpino O, Maurao AM, Del Pesce M. Partial complex seizuresand insulinoma: A case report. Electroencphalogr Clin Neuro-physiol 1985;61:90 (abstract).

3. Prull G, Busch H, Erbsloh F. EEG follow-ups in severe neu-rological states after hypoglycemia. Electroencephalogr ClinNeurophysiol 1970;29:210.

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15. Diffuse slowing—limbic encephalopathy [1–6]

CLINICAL CORRELATES: There is a variable clinical pre-sentation with confusion, hallucinations, paroxysmal al-tered limb and axial tone, hyperoral behavior, and unre-sponsiveness. There may be catatonia, dyskinesias, short-term memory loss, prominent psychiatric symptoms, aprominent behavioral syndrome with “stickiness” and ag-gressivity, psychosensory complaints and vegetative com-plaints, also hypoventilation and autonomic problems.

ETIOLOGY: It was early characterized as a T cell-driven im-mune response against limbic structures, and has beenseen in paraneoplastic or nonparaneoplastic effects ofcancers of the lung, breast, thyroid, ovarian teratomas,testicular, and others. Rarely, there is a viral limbic en-cephalitis or seizures in the limbic structures from variouscauses.

CLINICAL EVALUATION: General neurological examina-tion looking for abnormalities in tone, hyperoral behavior,and subtle seizures. Look for psychiatric features.

ANCILLARY TESTING: Obtain an enhanced MRI lookingfor focal abnormalities of the limbic system. Investi-gate for systemic malignancy with evaluation of lungs,breasts, thyroid and ovaries, body CT, PET (positron emis-sion tomography) scan for tumor localization. Test cere-brospinal fluid for viral, neoplastic, and paraneoplastic an-tibodies against N-methyl-D-aspartate receptors, voltage-gated potassium channels.

DIFFERENTIAL DIAGNOSIS: Clinical—Toxic, metabolicproblems (drugs, hyperammonemia, hypocalcemia),celiac disease, Whipple’s disease.


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EEG—Toxic and metabolic encephalopathies producesimilar patterns.

This EEG shows a medium-voltage waxing and waningtheta/delta activity, seeming to shift in frequency over thefrontal regions. No epileptiform discharges are evident.The patient was catatonic.

REFERENCES:

1. Brierley JB, Corsellis JAN, Hierons R, Nevin S. Subacute en-cephalitis of later adult life mainly affecting the limbic areas.Brain 1960;83:357–368.

2. Chong JY, Rowland LP, Utiger RD. Hashimoto encephalopa-thy: Syndrome or myth? Arch Neurol 2003;60:164–171.

3. Bataller L, Kleopa KA, Wu GF, Rossi JE, Rosenfeld MR, Dal-mau J. Autoimmune limbic encephalitis in 39 patients: Im-munophenotypes and outcomes. J Neurol Neurosurg Psychi-atry 2007;78:381–385.

4. Izuka T, Sakai F, Ide T, Monzen T, Yoshii S, Iigaya, M,Suzuki K, Lynch DR, Suzuki N, Hata T, Dalmau, J. Anti-NMDA receptor encephalitis in Japan. Neurology 2008;70:504–511.

5. McKeon A, Marnane M, O’Connell M, Stack JP, Kelly PJ, LynchT. Potassium channel antibody-associated encephalopathypresenting with a frontotemporal dementia-like syndrome.Arch Neurol 2007;64:1528–1530.

6. Graus F, Saiz A. Limbic encephalitis. An expanding concept.Neurology 2008;70:500–501.

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16. Focal arrhythmic (polymorphic) delta activity

DEFINITION: Slow-frequency (<4 Hz) delta activity with-out sustained rhythmicity, favoring one hemisphere,often 100- to 150-µV amplitude.

CLINICAL CORRELATES: A patient may have been referredto the electrophysiology laboratory for focal weaknesswith fluctuating lateralized motor/sensory symptoms.Often, there is focal weakness of the face, arm, and leg;asymmetric reflexes and sensory examination.

ETIOLOGY: This is almost always due to a structural ormass lesion: cerebral infarction, intracranial hemorrhage,abscess, infection, tumor, or focal atrophy. It can rarelyoccur with ischemia that is not severe enough to causeinfarction. It may occur postictally after a focal seizure;this usually resolves rapidly.

CLINICAL EVALUATION: In a general neurological exam-ination, look for cranial nerve, motor or sensory abnor-mality, evidence of seizures. If there is an abscess, lookfor an ear or a sinus source of infection.

ANCILLARY TESTING: Obtain imaging to look for struc-tural lesion. Select also MRI sequences sensitive to mildischemia.

DIFFERENTIAL DIAGNOSIS: On EEG, the significance offocal slowing varies with the clinical context [1–5]. Inmost patients with structural abnormalities (e.g., an MCAstroke on MRI), there will be continuous, arrhythmic fo-cal delta activity, often with the loss of overlying fasterfrequencies. With subcortical structural lesions that spareoverlying cortex (intra-cranial hemorrhage, abscess), con-tinuous delta may occur with preserved overlying fast ac-tivity. This can also be seen with extraaxial compressivemeningiomas. When the structural abnormality in the

white matter undercuts the cortex (producing arrhythmicdelta activity), the concurrent compromise (infarction) ofthe overlying cortex will also attenuate the focal corticalfaster (alpha and beta) frequencies [1–3].

With large focal strokes involving cortical and subcor-tical areas, the overlying delta activity may be of lowervoltage [2]. With large strokes and edema with pressureon midline structures, there may be focal delta with bi-lateral diffuse delta from midline compromise.

In patients with smaller subcortical lesions, the delta ac-tivity may be less persistent or intermittent. Deeply seatedlesions may induce more widespread hemispheric or evenbihemispheric slowing [4], but often with some preserva-tion of overlying faster activity. Conversely, lacunes evenwith hemiparesis usually have a normal EEG.

With subclinical ischemia, occasionally insufficient toproduce infarction or shortly following a transient is-chemic attack, there may be focal delta activity withvarying persistence. In some patients, relatively small sub-cortical strokes will produce intermittent focal delta, butwith interspersed periods of relatively normal activity inthe same region with preserved, overlying faster (cortical)activity (alpha/beta) frequencies.

In some cases, intermittent phase-reversing focal deltaactivity with intervening preservation of alpha and betaactivities in the same region may represent a more distantepileptic focus, even while a spike or sharp componentis absent. In this way, the EEG findings with a particu-lar imaging finding and clinical history may suggest that(a) only a stroke is present; (b) there may be a strokewith a suggestion of seizures; (c) there is subclinical focalischemia even without frank infarction (critical vascularstenosis); (d) consider a focal structural lesion with masseffect on the midline, and/or herniation; and (e) that theremay be postictal slowing, with a relatively minor under-lying structural problem.


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This EEG shows a medium- to high-voltage focal rightfrontal nonrhythmic (polymorphic) delta activity with pre-served faster frequencies, and with little change in EEGpattern on arousal. There are also occasional right frontalsharp waves.

REFERENCES:

1. Gloor P, Kalabay O, Giard N. The electroencephalogram indiffuse encephalopathies: EEG correlates of gray and whitematter lesions. Brain 1968;91:779–802.

2. Gloor P, Ball G, Schaul N. Brain lesions that produce deltawaves on EEG. Neurology 1977;27:326–333.

3. Goldensohn ES. Use of the EEG for evaluation of focal in-tracranial lesions. In: Klass D, Daly D (eds.), Current Practiceof Clinical Electroencephalography. New York: Raven Press,1979.

4. Arfel G, Fischgold H. EEG-signs in tumors of the brain. Elec-troencephalogr Clin Neurophysiol Suppl 1961;19:36–50.

5. Bazil CW, Herman ST, Pedley TA. Focal electroencephalo-graphic abnormalities. In: Ebersole JS, Pedley TA (eds.), Cur-rent Practice of Clinical Electroencephalography, 3rd edn.New York: Lippincott Williams & Wilkins 2003:303–347.

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Section B: Periodic patterns of epileptiformdischarges or seizures

Periodic discharges (PDs) on the EEG represent a metro-nomic expression of individual epileptiform discharges.PDs are viewed as being an irritative pattern that canbe found before or after seizures. They are usuallynot accompanied by motor signs, and they includePLEDs, BIPLEDs, PLEDs-plus, generalized periodic epilep-tiform discharge and stimulus-induced rhythmic peri-odic or ictal discharge. Periodic lateralized epileptiformdischarges (PLEDs) are surface-negative discharges withspike, sharp, and polyspike components, with slow-wave complexes. They must be seen on an EEG record-ing lasting at least 10 minutes. Most patients withPLEDs (83–87%) will have seizures. Patients with bi-lateral independent synchronous PLEDs (BIPLEDs) also

have seizures (78%). With GPEDs, 32–90% may haveseizures [1, 2]. Together, these multiple case series [3]show the close relationship between PLEDs and seizures(74–90%), and between PLEDs and status epilepticus(SE) (10–66%). Most patients (94%) had seizures, andtherefore PLEDs have been viewed by some as possi-bly being a “terminal phase of SE.” Conversely, oth-ers believe that PLEDs per se are not ictal, arguingthat their static, nonevolving patterns are an irritativephenomenon and do not represent frank seizure activ-ity [4, 5]. Thus, depending on the situation, PDs canbe seen as lying along an ictal–interictal continuum[5,6].

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17. Pseudoperiodic lateralized epileptiform discharges

MICU, CICU, NICU, SICU

Seen in childhood and adults with structural CNS lesions,strokes, tumors, or infections.

Definition

PLEDS: An acute or chronic EEG pattern consisting ofdischarges with sharp or sharp-and-slow waves; spikes,spike-and-slow waves, or multiple spike-and-slow waves,or complex bursts of multiple spikes with slow waves[3,7–13].

Frequency: PLEDs vary from 3/second to 8/minute [3,7],usually at 1 Hz and last up to 600 ms, vary from 50 to300 µV. They should be present for at least a 10-minuteepoch during a standard EEG recording or be presentcontinuously during a specific behavioral state [9].

CLINICAL CORRELATES: The patient is usually obtundedand may have an asymmetric neurologic examinationreflecting the lateralized, structural, cerebral abnormal-ity underlying the PLEDs. Features may wax and wane.Usually, there is a history of recent seizure or changein mental status. There is a close temporal associationwith seizures—approximately 74–90% [3,7–13]. Theremay be focal limb movements, head or eye deviation,vocalization, chewing, psychic phenomena including vi-sual or auditory hallucinations, confusion, or autisticbehavior [7].

ETIOLOGY: Cerebral infarctions, abscesses, and tumors.Viral and other encephalitides.

CLINICAL EVALUATION: Assess the level of conscious-ness. Look for lateralized neurological signs, limb move-ments or twitching, eye deviation. Look for evidence of

old stroke or new infection, as well as for sinus or earsource of infection (vesicles of herpes simplex virus (HSV)).

ANCILLARY TESTING: Strokes, abscesses, and tumors canbe imaged with head CT. MRI may reveal the early ap-pearance of a viral encephalitis, showing a proclivity forcertain brain regions: HSV for frontal and temporal cor-tex; varicella zoster vasculopathy in white matter andgray–white matter junctions; cytomegalovirus around thelateral ventricles; togavirus encephalitis (e.g., West Nile,Japanese, Eastern and Western Equine encephalitides)around deep-seated white matter, thalami, substantia ni-gra. Consider cerebrospinal fluid studies for viruses, otherinfections, but particularly HSV.

DIFFERENTIAL DIAGNOSIS: From the EEG perspective, inpartial SE, the discharges are of higher frequency, andclinically, the patient may manifest evidence of an irrita-tive cortical lesion with limb jerks, contraversive head andeye movements, a more clearly defined onset and offset,and with cycling of clinical features. The differentiationbetween an ictal and an interictal state is largely based onthe extent of visible clinical manifestations, the frequencyof EEG discharges (usually faster than about 1/second),and the appearance of discrete clinical seizures or an ictalevolution. It is not to be confused with absence status andtriphasic waves, which are generalized EEG phenomena.

PROGNOSIS: This depends on the underlying etiology.Usually, PLEDs are transient, lasting from several hoursto days or, less commonly, weeks. PLEDs may heraldthe appearance of a viral encephalitis. PLEDs are oftenconsidered to be an “irritative” phenomenon along an“ictal–interictal continuum.”

TREATMENT: The use of AEDs may prevent superaddedappearance of clinical seizures, but do not address theunderlying cerebral disease. Often parenteral benzodi-azepines along with a longer-acting AED are tried. More


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Section B: Periodic Patterns of Epileptiform discharges or Seizures 41

intensive attempts at PLED suppression with higher dosesof benzodiazepines or anesthetic agents are unsuccessful,and run up against the tradeoff of iatrogenic problemsof hypotension and cardiac dysrhythmia, versus the per-ceived benefit of seizure suppression. Intensive treatmentPLEDs (as opposed to seizures) is controversial.

This EEG shows pseudoperiodic lateralized epileptiformdischarges PLEDs at less than 1/second, with some back-ground activity.

REFERENCES:

1. Husain AM, Mebust KA, Radtke RA. Generalized pe-riodic epileptiform discharges: Etiologies, relationship tostatus epilepticus, and prognosis. J Clin Neurophysiol1999;16:51–58.

2. Yemisci M, Gurer G, Saygi S, Ciger A. Generalized peri-odic epileptiform discharges: Clinical features, neuroradio-logical evaluation and prognosis in 37 adult patients. Seizure2003;12:465–472.

3. Snodgrass SM, Tsuburaya K, Ajmone-Marsan C. Clinicalsignificance of periodic lateralized epileptiform discharges:Relationship with status epilepticus. J Clin Neurophysiol1989;6:159–172.

4. Young GB, Goodenough P, Jacono V, Schieven JR. Periodiclateralized epileptiform discharges (PLEDs): Electrographicand clinical features. Am J EEG Technol 1988;28:1–13.

5. Pohlmann-Eden B, Hoch DB, Cochius JI, Chiappa KH. Pe-riodic lateralized epileptiform discharges—a critical review.J Clin Neurophysiol 1996;13:519–530.

6. Chong DJ, Hirsch. Which EEG patterns warrant treatmentin the critically ill? Reviewing the evidence for treatment ofperiodic epileptiform discharges and related patterns. J ClinNeurophysiol 2005;22:79–91.

7. Chatrian GE, Cheng-Mei S, Leffman H. The significance ofperiodic lateralised epileptiform discharges in EEG: An elec-trographic, clinical and pathological study. ElectroencephClin Neurophysiol 1964;17:177–193.

8. de la Paz D, Brenner RP. Bilateral independent pe-riodic lateralized epileptiform discharges. Arch Neurol1981;38:713–715.

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42 Section B: Periodic Patterns of Epileptiform discharges or Seizures

9. Kuriowa Y, Celesia GG. Clinical sigificance of periodic EEGpatterns. Arch Neurol 1980;37:15–20.

10. Reiher J, Rivest J, Grand-Maison F, Leduc CP. Periodic lat-eralized epileptiform discharges with transitional rhythmicdischarges: Association with seizures. Electroenceph ClinNeurophysiol 1991:78:12–17.

11. Westmoreland BF, Klass DW, Sharbrough FW. Chronicperiodic lateralized epileptiform discharges. Arch Neurol1986:43:494–496.

12. Brenner RP. Is it status? Epilepsia 2002;43:103–113.13. Gilden DH. Brain imaging abnormalities in CNS virus infec-

tions. Neurology 2008;70:84.

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18. Bilateral independent pseudoperiodic lateralizedepileptiform discharges [1–6]

MICU, CICU, NICU, SICU

DEFINITION: An acute EEG pattern consisting of dis-charges with sharp or sharp-and-slow waves, spikes,spike-and-slow waves, or multiple spike-and-slow waves,or complex bursts of multiple spikes with slow waves,seen over each hemisphere with different and indepen-dent frequency [1–3].

Frequency: It varies from about 1/second to 12/minute,may last up to 600 ms, amplitude up to about 200 µV, butmay differ over each hemisphere. Like periodic lateralizedepileptiform discharges, they should be present for atleast a 10-minute epoch during a standard EEG recording,or be present continuously during a specific behavioralstate.

CLINICAL CORRELATES: The patient is usually deeply ob-tunded; coma in 72%; brainstem reflexes usually present.Rarely, there are limb or facial movements or twitches.

ETIOLOGY: Usually caused by significant multifocal cere-bral damage. This occurs typically from encephalitis,anoxia, or multifocal structural disease.

ANCILLARY TESTING: Head CT or MRI to look for struc-tural lesions or evidence of infection. Imaging with CTreveals typical causes such as anoxia (28%), CNS infec-tions (28%), and strokes. It is also seen in epilepsy. It isassociated with seizures in more than 60% of patients.

DIFFERENTIAL DIAGNOSIS: In partial SE, the dischargesare more frequent and clinically display more “irritative/

positive” features of cortical stimulation, that is, limbmovement, contraversive head and eye movements.Seizures have a more clearly defined onset, with cyclingof clinical features. Differentiation between an ictal andan interictal state is largely based on the degree of visibleclinical manifestations, the frequency of EEG discharges(usually faster than about 1/second), and the appearanceof discrete seizures or an ictal evolution. Absence statusand triphasic waves (TWs) are generalized phenomenabut more symmetric. Although TWs may be asymmetric,they do not display a pseudoperiodic pattern. Bilateralindependent pseudoperiodic lateralized epileptiform dis-charges (BIPLEDs) do not typically react to noxious stimuli,while TWs often do.

PROGNOSIS: Poorer prognosis than with PLEDs, largelybecause the prognosis is determined by the underlyingetiology. Usually, BIPLEDs are a transient phenomenon,lasting from several hours to days, or less commonly,weeks. The use of AEDs may prevent superadded ap-pearance of clinical seizures. BIPLEDs (like PLEDs) areoften viewed as an “irritative” phenomenon along an“ictal–interictal continuum.”

TREATMENT: The patient is often given a trial of par-enteral benzodiazepines along with a longer-acting AED.More intensive attempts at BIPLED suppression with morebenzodiazepines or anesthetic agents to achieve the ben-efit of seizure suppression are usually unsuccessful andrun up against the tradeoff of iatrogenic hypotensionand cardiac dysrhythmia.


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Section B: Periodic Patterns of Epileptiform Discharges or Seizures 45

This EEG shows BIPLEDs every 1 to 3 seconds with thetabackground activity.

REFERENCES:

1. Chatrian GE, Cheng-Mei S, Leffman H. The significance ofperiodic lateralised epileptiform discharges in EEG: An elec-trographic, clinical and pathological study. Electroenceph ClinNeurophysiol 1964;17:177–193.

2. de la Paz D, Brenner RP. Bilateral independent periodiclateralized epileptiform discharges. Arch Neurol 1981;38:713–715.

3. Kuriowa Y, Celesia GG. Clinical sigificance of periodic EEGpatterns. Arch Neurol 1980;37:15–20.

4. Snodgrass SM, Tsuburaya K, Ajmone-Marsan C. Clinicalsignificance of periodic lateralized epileptiform discharges:Relationship with status epilepticus. J Clin Neurolgphysiol1989;6:159–172.

5. Westmoreland BF, Klass DW, Sharbrough FW. Chronicperiodic lateralized epileptiform discharges. Arch Neurol1986;43:494–496.

6. Husain AM, Megust KA, Radtke RA. Generalized peri-odic epileptiform discharges: Etiologies, relationship to sta-tus epilepticus and prognosis. J Clin Neurophysiol 1999;16:51–58.

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19. Generalized periodic epileptiform discharges

MICU, CICU, NICU, SICU, ER

Seen after cardiac arrest, status epilepticus or infection[1–3].

CLINICAL CORRELATES: There are often face or limbmyoclonias, eye or eyelid twitching, or vertical nystag-mus. Correlation with seizures approximately 90% [2].Eyes are usually closed, but may open to stimuli. Armsmay posture or withdraw to pain; brainstem reflexes—pupil reactions, vestibulo-ocular reflex, gag, spontaneousbreathing—present to absent.

ETIOLOGY: In the context of coma, this pattern indicatesan overwhelming, diffuse cerebral insult. This pattern isseen after CRA, anoxia, or massive central nervous sys-tem (CNS) infection. Generalized periodic epileptiformdischarges (GPEDs) may occur as an end-stage of convul-sive status epilepticus. It is rarely seen with acute drugtoxicity. Rare causes are syphilis and Creutzfeldt-Jakobdisease (CJD).

CLINICAL EVALUATION: Examine brainstem reflexes andassess Glasgow coma scale. Look for myoclonias.

ANCILLARY TESTING: Suggest electrolytes, toxin screenfor toxic, or metabolic dysfunction. Imaging for infectiouscauses (e.g., herpes simplex virus or other encephalitides).

DIFFERENTIAL DIAGNOSIS: Epileptiform discharges aresharper and more frequent than triphasic waves or other

encephalopathies. The GPED pattern is also consistentwith some types of generalized nonconvulsive statusepilepticus.

PROGNOSIS: After anoxia/CRA, the prognosis is almostuniversally poor. If there is background activity above20 µV, prognosis is better. The effect of hypothermiais unclear. Consider somatosensory evoked potentials(SSEPs) for further prognostication if the cause is CRA.If the cortical N20 is absent on SSEPs, then the out-come is death or persistent vegetative state. Interpret theEEG (and SSEPs) with caution after anesthetics or early(<24 hours) in clinical course.

If there is no anoxia/CRA, then this may represent statusepilepticus and the prognosis is better [3]. A trial of anti-epileptic drugs is warranted. When etiology is unknownand the pattern does not follow on convulsive statusepilepticus, and it is not due to CNS infection or CJD,then the prognosis is guarded and probably poor. Rareexceptions with better prognosis are when it is due tosyphilis. With baclofen (where EEG shows backgroundactivity and discharges are less frequent), there is a betterprognosis for reversibility. The overall mortality in largepatient series with toxic, metabolic, infectious, and anoxiccauses is approximately 50% [2].

TREATMENT: For seizures, consider a trial of lorazepam4–8 mg, then phenytoin load; propofol, midazolam, orbarbiturates are usually futile. In our experience afterCRA, there is no return to consciousness.


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Section B: Periodic Patterns of Epileptiform Discharges or Seizures 47

This EEG shows GPEDs without background activity.GPEDs are generalized epileptiform discharges occu-

pying more than 50% of a 20-minute recording, syn-chronously and symmetrically over both hemispheres [1].They occur at short intervals of approximately 0.5–3.0 Hzversus long intervals seen in SSPE.

REFERENCES:

1. Husain AM, Mebust KA, Radtke RA. Generalized pe-riodic epileptiform discharges: Etiologies, relationship to

status epilepticus and prognosis. J Clin Neurophysiol 1999;16:51–58.

2. Yemisci M, Gurer G, Saygi S, Ciger A. Generalized periodicepileptiform discharges: Clinical features, neuro-radiologicalevaluation and prognosis in 37 adult patients. Seizure 2003;12:465–472.

3. Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C,Rowan AJ, Handforth A, Faught E, Calabrese VP, UthmanBM, Ramsay RE, Mamdani MB. A comparison of four treat-ments for generalized convulsive status epilepticus. Veteransaffairs status epilepticus cooperative study group. N Engl JMed 1998;339:792–798.

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PART 2

Seizures

Section A: The diagnosis of confusional eventsdue to seizures

A consult may be requested for a patient with the suddenonset of poorly described symptoms that involve sensory,motor, autonomic, or limbic features. A patient may de-scribe, for example, perceptions of light flashes, or im-ages; or may describe bizarre clicks, buzzes, sounds, ormusic; other patients may have just dizziness and ver-tigo, with nausea and sweating. When these events arebrief and stereotyped, the possibility of their being par-tial seizures arises. With partial seizures, clinical signs andsymptoms may simulate a great variety of perceptionsor functions, although with a “nonphysiological” qual-ity and evolution. The suspicion of an ictal cause stemsfrom the stereotypy of the events, presence of confusionwhen present, and often the occurrence of more typicalepileptic features such as automatisms or secondary gen-eralization. An account of these typical clinical featuresof seizures can be found in textbooks on epilepsy and theimitators of epilepsy [1].

With an increased index of suspicion, an EEG may berequested, but the imperfect sensitivity and specificity ofEEG should be understood. Also, even epileptiform fea-tures on an EEG may be misconstrued, either becausethey are benign variants or artifacts, or because the par-ticular event under consideration is due to a concurrentproblem (e.g., vertigo from inner ear problems in a pa-tient with epilepsy and a “Positive EEG”). The sensitivityof EEG varies for particular seizure or epilepsy types, withthe duration of the recording, and whether sleep andwakefulness were both obtained.

Regarding routine 20- to 30-minute outpatient, day-time EEG samples (the “standard” EEG, often withoutsleep), the pickup rate for true epileptiform abnormali-ties is 50% or less. For repeated EEGs up to 4, or for pro-longed EEGs exceeding an hour, with sleep, the pickuprate rises above 70% for partial seizures and 90% forgenetic, idiopathic epilepsies. The gold standard for diag-nosis of epileptic events is epilepsy monitoring for several

days, but the cost–benefit must be weighed for infre-quent events. For events occurring several times weeklyor more, a few days of monitoring may suffice. For pa-tients who are already in hospital, it is usually easier toembark on epilepsy monitoring. This would include pa-tients who are on the general services or in intensive careunits. In patients with confusion at the time of the EEG,the test is more sensitive and will often reveal whethera diffuse cortical, diffuse cerebral, focal structural, fo-cal epileptic, or diffuse epileptic process is present. EEGsare good at differentiating psychiatric confusion (normalEEG) from either encephalopathic (different patterns ofdiffuse abnormality) or epileptic causes.

The simplest ictal problem to diagnose is status epilep-ticus because the altered clinical state and ictal EEG occurat the same time. That said, there may be lack of consen-sus on where on an ictal–interictal continuum the patientmay lie. See the discussion in the next section for a dis-tillation of these issues. In a nutshell, if seizures are seenon the EEG and the symptoms or signs of interest arepresent, then status can be diagnosed.

Of similar use is the EEG that shows discrete seizures.There, the diagnosis is as readily made, but the clinicalimplications differ because of the greater urgency in theneed for treatment of status epilepticus. Clusters of fre-quent convulsive seizures may also pose morbid risk, butthe diagnosis is seldom in doubt. Clusters or frequent par-tial seizures pose intermediate urgency. The therapeuticdiseases vary from no antiseizure treatment for discretereactive seizures (e.g., alcohol, tramadol, or other trig-gers) to intensive anesthesia for convulsive status epilep-ticus. Many texts are available for the management ofseizures and epilepsy.

The most difficult pickup and lowest yield for EEG isthe event for which there is little information from ei-ther the patient or bystanders (“Patient found down”),which clinically has resolved days before the EEG and

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50 Section A: The Diagnosis of Confusional Events Due to Seizures

is an isolated incident. In this case, the fishing expedi-tion with EEG is only helpful if the EEG shows paroxys-mal abnormalities of sudden phase-reversing delta slow-ing, or of greater help, epileptiform discharges. In adults,epileptiform discharges rarely occur without a diagnosisof epilepsy (either prior or subsequent); in other words,the false-positive rate is less than 5%.

The section to follow will show different EEG patternsthat may occur in patients either confused or with recentconfusion. The undifferentiated term “confusion” asan indication for doing an EEG is used to cast a widernet, although clearly more specific histories with “lip-smacking, foaming at the mouth, or head turning withhemi-body jerking” are more likely to yield a helpful EEG(whether it shows epileptiform abnormalities or not).The consultation request may come under a number offorms:

a. As a request for evaluation of a relatively nonspecificsymptom, for example, flashes of light, fear, and armjerking.

b. Because of a history of epilepsy or known seizures thatprompt a request for reevaluation.

c. An in-hospital witnessed new event (or event similarto prior ones) suggests a seizure.

d. Ongoing, in-hospital clinical features suggesting sta-tus epilepticus.

e. A consultation request stemming from a prior EEGthat may have shown epileptiform features.

The EEG figures provided in this section will thereforevary from the isolated temporal lobe spike-slow wave dis-charge that is highly suggestive of temporal lobe epilepsy,to the diagnostic illustrations of seizures, to figures show-ing the many types of status epilepticus. In this way thephysician can fashion a consultation answer that incor-porates the respective significance of the initial clinicalquestion, the need for EEG (or the results therefrom),and the history and examination findings obtained dur-ing the consultation. In this way, the significance of eitherthe history or the EEG may be enhanced by the relativespecificity of the other. In other words, an EEG showingstatus epilepticus will trump a nonspecific history of con-fusion or coma, while a clear temporal lobe EEG spikewave will confirm a history of automatisms, or in anotherclinical setting, may at least strengthen the suspicion oftemporal lobe epilepsy in a patient with poorly describedstaring episodes.

To best serve this function, the chapter figures beginby demonstrating epileptic discharges over the differentbrain regions, then in the next section show what seizuresmay look like over these same regions, and finally endwith illustrations of status epilepticus arising from thedifferent brain areas.

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20. Frontal lobe simple and complex partialseizures [1–5]

CLINICAL CORRELATES: Frontal lobe seizures are fre-quently mistaken for psychogenic (nonepileptic) events.Consciousness often is spared, and the manifestationscan include emotional, sexual, and delusional content.Supplementary motor area seizures produce uni- or bi-lateral tonic posturing, a “fencing” posture, or suddeninvoluntary posturing of an arm or leg causing the pa-tient to reach out for the other limb. The history can bedifficult to obtain—auras may consist of bizarre bilateralor unilateral proximal limb or head somatosensory per-ceptions, numbness, and tingling. When the person hasno recollection of subsequent events, then the seizureis complex partial. Motor events can include myoclonicjerks. Onset in area 6 can produce vocalization, speecharrest, and palilalia. There may be adversive head move-ments in almost half of the patients. The patient mayexperience forced thinking, fear, screaming, complex pos-tural changes, autonomic changes, tonic spasms, or evenimmobility. Automatisms can consist of movements re-sembling boxing, cycling, and fishing. There may be dropattacks, grimacing, thrashing, kicking, violent struggling,weeping, laughing, dystonic posturing, and tapping. Dis-sociative episodes can by inseparable from psychiatricconditions. Events are usually brief (90% <3 minutesand most <30 seconds) and may arouse the patient fromsleep.

ETIOLOGY: Any focal structural lesion-–cortical dys-plasias, hamartomas, gliosis, arteriovenous malforma-tions; idiopathic and familial syndromes.

CLINICAL EVALUATION: Examination is often normal be-tween seizures if the causative lesion is small and nonde-structive. Look for lateralized, frontal release signs, later-alized differences in reflexes, or a Babinski sign.

ANCILLARY TESTING: Obtain an enhanced MRI for evi-dence of focal cerebral lesions such as dysplasias, low-grade astrocytomas, and cavernous angiomas. Positronemission tomography scans can produce a 96% sensi-tivity and 74% accuracy using quantitative analysis asopposed to 69 and 43%, respectively, with qualitativestudies [4].

DIFFERENTIAL DIAGNOSIS: Clinical—When the symp-toms or manifestations are psychic or sexual, or thepatient has dissociations, a psychiatric diagnosis is usu-ally evoked. The movements are occasionally mistakenfor movement disorders, or they may be overlooked.Patients may go for years undiagnosed if there is onlysimple partial or brief complex partial symptomatology.Enquire after events during sleep, blood on the pillow,unexplained accidents. Post-, pre-, or ictal headache mayoccur.

EEG—Frontal, rhythmic slow activity can be misread forfrontal seizures. Further, there may be spread to the tem-poral areas. Nocturnal frontal epilepsy may have normalinterictal studies.

PROGNOSIS: Many patients will remit with anti-epilepticdrugs (AEDs) if the underlying cause is not progres-sive, but a lower proportion than with temporal lobeepilepsy. Management is directed at cause, at suppress-ing seizures and educating the patient and family on thepersonal, social, and professional implications of seizuresand epilepsy. Just over 50% may become seizure freewith extratemporal lesional surgery [5]. Epilepsia par-tialis continua (a form of frontal motor status) may belargely impervious to medical treatment for months, oc-casionally responding to subpial transection or resectivesurgery.

TREATMENT: Consider AEDs for repeated events andimaging to look for a cause. Surgery can be consideredfor refractory epilepsy.


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Section A: The Diagnosis of Confusional Events Due to Seizures 53

The EEG shows a run of bifrontal epileptiform dis-charges that are more distinct on the right-hand side.

REFERENCES:

1. Jobst BC, Siegel AM, Thadani VM, Roberts DW, Rhodes HC,Williamson PD. Intractable seizures of frontal lobe origin.Epilepsia 2000;41:1139–11452.

2. Williamson PD, Spencer DD, Spencer SS, Novelly RA, Matt-son RH.. Complex partial seizures of frontal lobe origin. AnnNeurol 1985;18:497–504.

3. Morris HHI, Dinner DS, Luders H, Wyllie E, Kramer R. Supple-mentary motor seizures: Clinical and electroencephalographicfindings. Neurology 1988;38:1075–1082.

4. Swartz BE, Khonsari A, Brown C, Mandelkern M, SimpkinsF, Krisdakumtorn T. Improved sensitivity of 18-FDG-positronemission tomography scans in frontal and “frontal plus”epilepsy. Epilepsia 1995;36:388–395.

5. Talairach J, Bancaud J, Bonis A, Szikla G, Trottier S, VignalJP, Chauvel P, Munari C, Chodkievicz JP. Surgical therapy forfrontal epilepsies. In: Chauvel P, Delgado-Escueta AV, HalgrenE, Bancaud J (eds.), Frontal Lobe Seizures and Epilepsies.New York, NY: Raven Press 1992;57:707–732.

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21. Temporal lobe simple and complex partialseizures [1–5]

CLINICAL CORRELATES: There may be a history of poorlydescribed onset (aura), occasionally with deja vu, a senseof fear, smell, a rising epigastric sensation, butterflies inthe stomach, or dizziness—all representing a simple par-tial seizure. When the person has no recollection of sub-sequent events, then the seizure is complex partial (withstaring, appearing like he/she is in another world, lip-smacking, lip-licking, or swallowing, fidgety hand move-ments such as rubbing or picking) or secondarily gener-alized with head deviation and tonic–clonic movements.Ask for foaming at the mouth, tongue biting and falls.Seizures are usually brief (90% <3 minutes) and mayarouse the patient from sleep. There may be a variabledegree of confusion, often with a puzzled look. In lat-eral, neocortical temporal lobe seizures, epigastric aurasare rare, and more frequently there are auditory halluci-nations, or (with left-sided foci) more prolonged speechimpairment. A history should be sought for trauma, cen-tral nervous system infection, episodes of staring, ac-cidents, and burns, which suggest earlier instances ofseizures.

ETIOLOGY: Any focal structural lesion-–infections,trauma, strokes, atrophy, sclerosis, cortical dysplasias,cavernous angiomas, dysembryoplastic neuroepithelialtumors, hamartomas, gliosis, arteriovenous malforma-tions.

CLINICAL EVALUATION: The clinical examination is usu-ally normal. Rare exceptions include the neurocutaneous,genetic syndromes, evidence of trauma, or from symp-tomatic causes. In older patients, there may be evidenceof strokes or mass lesions.

ANCILLARY TESTING: Obtain an enhanced head CT orMRI for evidence of cerebral lesions. In the evaluation forseizure surgery in medically refractory patients, positronemission tomography (PET) and single-photon emissioncomputerized tomography (SPECT) scans may have aplace.

DIFFERENTIAL DIAGNOSIS: When the symptoms arethose of dizziness and vertigo, presyncope or syncopemay be suspected. The movements are rarely mistakenfor other conditions-–they are usually overlooked. Pa-tients may go for years undiagnosed if there are onlysimple partial or brief complex partial symptomatology.There is less belief, currently in a temporal lobe “per-sonality.” The elderly may have “atypical” episodes withbehavioral alterations. Enquire after events during sleep,blood on the pillow, unexplained accidents. Post-, pre-,or ictal headache occurs.

PROGNOSIS: Most patients will remit with antiepilep-tic drugs (AEDs) if the underlying cause is not pro-gressive. Management is directed at cause, suppressingseizures and education on social/professional implicationsof seizures. With unilateral refractory foci, temporal lobesurgery can render almost three quarters of selected pa-tients seizure-free.

TREATMENT: AEDs are indicated for repeated unpro-voked events (epilepsy). Investigate the underlying causeswith MRI as older patients may have strokes, tumors, orinfection, while younger patients may have trauma, in-fection, arteriovenous malformation (AVMs), angiomas,focal atrophy (mesial temporal sclerosis), dysembryoplas-tic neuroepithelial tumors, and many other causes. Forchronic, refractory cases, refer for evaluation of seizuresurgery.


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This EEG shows a single spike-slow-wave phase-reversing epileptiform discharge over the right temporalregion with concomitant slowing. This helps confirm adiagnosis of temporal lobe seizures. Discharges may in-crease in sleep.

REFERENCES:

1. Marks WJ, Jr, Laxer KD. Semiology of temporal lobeseizures: Value in lateralizing the seizure focus. Epilepsia1998;39:721–726.

2. Gloor P. Experiential phenomena of temporal lobe epilepsy.Facts and hypotheses. Brain 1990;113:1673–1694.

3. Manford M, Fish DR, Shorvon SD. An analysis of clinical seizurepatterns and their localizing value in frontal and temporal lobeepilepsies. Brain 1996;119:17–40.

4. Mikati M, Holmes G. Temporal lobe epilepsy. In: Wyllie E.(ed.), In the Treatment of the Epilepsy: Principles and Paractice,2nd edn. Baltimore: Williams & Wilkins 1996;401–414.

5. Jackson GD, Berkovic SF, Tress BM, Kalnins RM, Fabinyi GCA,Bladin PF. Hippocampal sclerosis can be reliably detectedby magnetic resonance imaging. Neurology 1990;40:1869–1875.

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22. Parietal lobe simple partial seizures [1–4]

CLINICAL CORRELATES: Typical features are pain in thelimbs, face, chest, and rarely in the abdomen. Theremay be a slow jacksonian sensory march, usually prox-imally, starting more often in the hand than in the foot,proceeding over seconds up the arm and to the face,headache (simple sensory partial seizures). There is vari-able loss of consciousness (complex partial seizures). Dis-comfort may be characterized as “pins and needles,”a lack of feeling, “numbness,” or perception of alteredshape of the limb. Other symptoms include visual illusionsand aphasia, vertigo, head and eye deviation, dysmor-phic perception of a limb, which include movement andalterations of body image. With spread to motor areas,subtle clonic, myoclonic, or dystonic movements may oc-cur along with gestural automatisms or asymmetric tonicposturing. Negative phenomena such as drop attacks,dysphasia, and paralysis are described.

ETIOLOGY: Any focal structural lesion-–infections,trauma, strokes, atrophy, sclerosis, cortical dysplasias,cavernous angiomas, dysembryoplastic neuroepithelialtumors, hamartomas, gliosis, arteriovenous malforma-tions, and porencephalic cysts. One-third of patientshave tumors.

CLINICAL EVALUATION: The clinical examination is nor-mal in about half of patients. Look for subtle hyper-reflexia, difference in limb and nail size, impairmentin two-point discrimination, right–left orientation, visualfield defects, and spatial orientation. There may be evi-dence of neurocutaneous, genetic syndromes, evidence

of trauma or of other symptomatic causes. In older pa-tients, there may be evidence of strokes or mass lesions.

ANCILLARY TESTING: Obtain an enhanced head CT orMRI for evidence of cerebral lesions. In the evaluation forseizure surgery in medically refractory patients, positronemission tomography PET and SPECT scans may have aplace.

DIFFERENTIAL DIAGNOSIS: Clinical—This is an imitatorof other painful conditions in that seizures are rarelyuniquely or principally painful. Post-, pre-, or ictalheadache occurs. Seizures are very rarely the cause forpain at all, but particularly outside the limbs and head.There is usually an identifiable progression, often withsecondary generalization and an imageable substrate.Seizure etiology is suggested by the stereotyped, briefprogression often with other manifestations of seizures.

EEG—This pattern strongly resembles the mu and al-pha frequency physiological patterns, but will extinguishwith limb movement or eye opening. Also, it is morearcuate and may resemble wicket spikes.

PROGNOSIS: Partial seizures often respond to antiepilep-tic drug (AEDs); occasionally the underlying lesion (e.g.,malignancy) can cause nonictal and a more refractorypain. Surgery for refractory cases may markedly improveor produce seizure control—75% with tumors and 65%without.

TREATMENT: Consider a trial of AEDs.


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This EEG shows runs of high-frequency sharp wavesat more than 10 Hz over the right parietal derivations.Clinical symptoms may occur before or after EEG onset.Background activity is usually present. A high-frequencyfilter of 35 Hz was used to minimize muscle artifact inthis illustration.

REFERENCES:

1. Salanova V, Andermann F, Rasmussen T, Olivier A, QuesneyLF. Parietal lobe epilepsy. Clinical manifestations and outcome

in 82 patients treated surgically between 1929 and 1988.Brain 1995;188:607–627.

2. Williamson PD, Boon FA, Thadani VM, Darcey TM, SpencerDD, Novelly RA, Mattson RH. Parietal lobe epilepsy: Diag-nostic considerations and results of surgery. Ann Neurol1992;31:193–201.

3. Seigel AM, Williamson PD, Roberts DW, Thadani VM, DarceyTM. Localized pain associated with seizures originating in theparietal lobe. Epilepsia 1999;40:845–855.

4. Cascino GD, Hulihan JF, Sharbrough FW, Kelly PJ. Parietallobe lesional epilepsy: Electroclinical correlation and operativeoutcome. Epilepsia 1993;34:522–527.

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23. Occipital lobe simple partial seizures [1–6]

CLINICAL CORRELATES: The eyes are usually open. Thepatient may perceive “positive” visual phenomena (one-half to three-fourths of patients). These include dots,flashes, and other simple shapes. These may have color,move and develop into more formed visual images of ob-jects, or brief scenes. Perceived objects may include ballsof light, revolving images, and accompanying auditoryhallucinations. Transient blindness (40%) or hemifield losscan occur. The patient may be seen to have conjugate eyedeviation (adversion) and nystagmus, usually contraver-sive to the occipital epileptic focus; head deviation to thesame side may occur. Seizures in the occipital lobes (repre-senting 5% of symptomatic focal epilepsies) can produceseveral clinical features. There may be subjective percep-tion of dots, flashes, colored lights, scotomas, amauro-sis, hemianopsias, or zig-zags of light (involvement ofBrodmann area #17); the patients may note that theireyes/environment are deviating to one side (stimulationof posterior temporoparietal or frontal saccadic regions)[4], often with visual jerking (oscillopsia), eye flutter, orblinking [1–3]. There may be concomitant blinking, dizzi-ness, vertigo, nausea, or headache.

ETIOLOGY: In younger patients, there are genetic focalepilepsies. Symptomatic causes include strokes, trauma,cortical dysplasia, AVMs, cavernous angiomas, and othertumors.

CLINICAL EVALUATION: Examine the visual for field de-fects (20–60%), although a significant number of pa-tients are unaware of their loss. Look for sudden ictal eyemovements, blinking, adversion, and other automatisms.

ANCILLARY TESTING: Obtain MRI for structural cause inthe occipital lobe—stroke, mass lesion, or infection. Con-sider visual field testing.

PROGNOSIS: Many patients respond to antiepileptic drug(AEDs), particularly cryptogenic and stroke patients. Theremay be seizure freedom in a third to almost half ofpatients with surgically resected lesional occipital lobeepilepsy.

TREATMENT: AEDs are indicated for repeated seizures.Imaging can reveal an underlying cause (MRI with en-hancement).


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The EEG shows high-frequency polyspike dischargesevolving over the left occipital region at 6–16/sec

REFERENCES:

1. Salanova V, Andermann F, Olivier A, Rasmussen, T, Ques-ney LF Occipital lobe epilepsy: Elecroclinical manifestations,electrocorticographay, cortical stimulation and outcome in 42patients treated between 1930 and 1991. Brain 1992;113:1655–1680.

2. Williamson PD, Thadani VM, Darcey TM, Spencer DD,Spencer SS, Mattson RH. Occipital lobe epilepsy: Clinical

characteristics, seizure spread patterns, and results of surgery.Ann Neurol 1992;31:3–13.

3. Tusa RJ. Saccadic eye movements, supranuclear control. BullSoc Belge Ophtalmol 1989;237:67–111.

4. Kaplan PW, Lesser RP. Vertical and horizontal epilepticgaze deviation and nystagmus. Neurology 1989;39:1391–1393.

5. Kaplan PW, Tusa RJ. Neurophysiologic and clinical corre-lations of epileptic nystagmus. Neurology 1993;43:2508–2514.

6. Allen IM. A clinical study of tumors involving the occipitallobe. Brain 1930;80:194–243.

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Section B: Status epilepticus

The diagnosis of tonic–clonic (convulsive) status epilep-ticus (CSE) is usually apparent (and yet there are evencase series of aggressively treated pseudo-status epilepti-cus). Some clinical clues to true status epilepticus (SE) arefoaming at the mouth, upgoing toes, and the absence offeatures suggestive of nonepileptic seizures [1, 2]. Fre-quently after convulsions, the creatine phosphokinase(CPK) is raised and blood pH is low. Clinical details can befound in standard texts. CSE is a neurological emergency,and management involves intubation and parenteral ben-zodiazepines (we prefer lorazepam 4–8 mg given undercontrolled conditions with blood pressure monitoring andventilation). If seizures persist, an anesthetic agent is of-ten then required, such as propofol, midazolam, or pen-tobarbital. Along the way, phenytoin is often loaded toprevent recurrence of seizures. The utility of intravenousvalproate or levetiracetam is still under study. Most hos-pitals, intensivists, and neurology departments have theirrespective preferred practices or protocols, applicable inthe inpatient setting.

Nonconvulsive status (NCSE) is harder to diagnoseand can supervene under a number of guises [3].Although subtle myoclonus, gaze deviation, catalepsy,and psychiatric features are some of the variety ofpresentations, the most common ones are eyes-open

mutism with facial and limb twitching. The clinicalsetting also provides a clue. In the emergency room (ER)it may be gaze deviation, myoclonus, and mutism; inpsychiatric settings, catatonia, mutism, or psychiatricregression; in patients with mental retardation, it may be“regression of behavioral milestones” and misbehavior.Common forms are focal frontal, bifrontal, or temporalin patients with structural abnormalities or prior epilepsy;generalized forms (on EEG) can occur with neurolep-tics, benzodiazepine abuse, and withdrawal, alongwith an intercurrent infection [4]. Some generalizedforms (on EEG) have spread from a unilateral frontalfocus.

NCSE overall has a lower morbidity than CSE with mor-talities around 3% in patients with known epilepsy andlow antiepileptic drug (AED) levels. In ICU/organ failureassociated with NCSE (in coma), mortality rises pari passuwith the general patient condition [5]. Treatment is there-fore less imperative and may often stop short of anes-thetic agents, but often warrants use of benzodiazepines.The various case vignettes given will provide the spectrumof clinical and therapeutic issues. Particular approaches tothe various types of SE are best sought in relevant reviewsand texts.

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24. Complex partial status epilepticus—frontal [6–10]

CLINICAL CORRELATES: Consciousness is often pre-served. There may be staring and mastication movementswith tongue protrusion; hypermotor automatisms; wax-ing and waning attention; inattentiveness, perseveration,and aphasia. Psychiatric symptoms include hallucinations,delirium, paranoia, and depression. Posterior frontal focimay produce inhibitory motor seizures that can simulatea transient ischemic attack.

ETIOLOGY: It can be any focal structural lesion–-typicallystrokes, trauma, known epilepsy, infections.

CLINICAL EVALUATION: The patient’s eyes are usuallyopen, along with psychiatric or behavioral manifesta-tions, or conversely with bifrontal NCSE, obtunded orin coma, occasionally with eye deviation and nystagmus.

ANCILLARY TESTING: Obtain enhanced MRI for evidenceof focal cerebral lesions such as strokes, infection, ortumors.

DIFFERENTIAL DIAGNOSIS: Clinical—When the symp-toms or manifestations are psychic or sexual, or the pa-tient has dissociations, a primary psychiatric diagnosis is

usually incorrectly invoked. The movements are occasion-ally mistaken for movement disorders or they may beoverlooked.

EEG—Frontal, rhythmic slow activity can be misreadfor frontal seizures. Further, there may be spread to thetemporal areas.

PROGNOSIS: De novo frontal lobe status in any awakepatient may remit with doses of an AED. In comatosepatients, comorbid conditions are frequent and patientsare usually older; hence, the prognosis is poorer withmorbidity in at least 25% of patients. Epilepsia partialiscontinua (a form of frontal motor status) may be largelyimpervious to medical treatment for months, occasionallyresponding to subpial transection or resective surgery. Seealso “Frontal lobe simple and complex partial seizures.”

TREATMENT: Benzodiazepines and other parenteralAEDs. Phenytoin, valproate, or levetiracetam has beenused. Anesthetic agents are usually avoided in theawake patient. Parenteral benzodiazepines, phenytoin,valproate, levetiracetam, and then anesthetic agents areusually considered in unconscious ICU patients on a case-by-case basis.


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Section B: Status Epilepticus 63

The EEG shows the left frontal spike and poly-spike-slowwaves in a mildly confused patient.

REFERENCES:

1. LaFrance WC, Jr, Benbadis SR. Avoiding the costs of un-recognized psychological nonepileptic seizures. Neurology2006;66:1620–1621.

2. Nonconvulsive status epilepticus. PW Kaplan, FW Drislane(Eds). Demos Publications. New York, 2009.

3. Kaplan PW. Behavioral manifestations of nonconvulsive sta-tus epilepticus. Epilepsy Behav 2002;3:122–139.

4. Thomas P, Beaumanoir A, Genton P, Dolisi C, Chatel M.“De Novo” absence status of late onset: Report of 11 cases.Neurology 1992;42:104–110.

5. Schneker BF, Fountain NB. Assessment of acute morbidityand mortality in nonconvulsive status epilepticus. Neurology2003;62:1066–1073.

6. Thomas P, Zifkin B, Migneco O, Lebrun C, Darcourt J, An-dermann F Nonconvulsive status epilepticus of frontal origin.Neurology 1999;52: 1174–1183.

7. Lim J, Yagnik P, Schraeder P, Wheeler S. Ictal catatonia as amanifestation of nonconvulsive status epilepticus. J NeurolNeurosurg Psychiatry 1986;49:833–836.

8. Rohr-Le Floch J, Gauthier G, Beaumanoir A. Confusionalstates of epileptic origin. Value of emergency EEG. Rev Neu-rol 1988;144:425–436.

9. Lee H, Lerner A. Transient inhibitory seizures mimickingcrescendo TIAs. Neurology 1990;40:165–166.

10. Kaplan PW. Focal seizures resembling transient ischemicattacks due to sub-clinical ischemia. Cerebrovasc Dis1993;3:241–243.

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25. Complex partial status epilepticus—temporal [1–4]

CLINICAL CORRELATES: The eyes may be open or closedand may open to stimuli. The patient is confused, disori-ented, but usually conversant and may follow commands.The level of consciousness ranges from fully awake withsubjective cloudiness to coma. The patient usually local-izes to pain; brainstem reflexes intact. Typically in nonco-matose patients, there is eyes-open mutism, subtle facialand limb myoclonus, and often catalepsy. Features sug-gestive of complex partial status epilepticus (CPSE) versusgeneralized nonconvulsive status epilepticus (GNSE) arecomplaints of a dreamy state, fear, bizarre smells, dejavu, autonomic complaints such as sweating, piloerec-tion, tachycardia, evidence of aphasia (versus mutism).There may be staring, lip-smacking, lip-licking, or swal-lowing, fidgety hand movements such as rubbing or pick-ing, or secondarily generalized with head deviation andtonic–clonic movements. Patients may have prolongedconfusional psychiatric and other behavioral abnormali-ties. More obtunded patients may be lethargic, with con-tralateral decreased movement; limb automatisms; eyedeviation with or without nystagmus.

ETIOLOGY: Any focal structural lesion—infections,trauma, strokes, atrophy. It is common in patients withknown temporal lobe epilepsy with poor compliance orlow antiepileptic drug (AED) levels.

CLINICAL EVALUATION: The clinical examination willshow evidence of confusion, lapses in attention, motorautomatisms in eyes-open ambulatory patients. Inlethargic or comatose patients in the ICU, there maybe subtle movements of the limbs or eyes. Test forneck stiffness. Pay particular attention to the history ofcerebral structural abnormality (stroke, trauma, abscess),epilepsy, medication non-compliance, and intercurrenturinary or respiratory infection.

ANCILLARY TESTING: Obtain an enhanced head CT orMRI for the evidence of cerebral lesions. Prolonged EEGmonitoring may be needed in refractory status epilep-ticus. In de novo patients, consider drugs, encephalitis,and strokes with intercurrent medications and infections(urinary tract infection or pneumonia).

DIFFERENTIAL DIAGNOSIS: Other causes of obtundationwith lateralized neurological features, for example, oldstrokes with encephalopathy. Psychogenic unrespon-siveness is not rare. Look for side-to-side head or eyemovements, pelvic thrusting, alternating motor limbcomponents.

EEG—Triphasic waves (TWs) are blunter, usually oflower frequency and generalized. Periodic lateralizedepileptiform discharges (PLEDs) are of lower frequency,rarely with automatisms, myoclonus, eye or contraver-sive head deviation. CPSE usually resolves with BZPs, butPLEDs are resistant to regression and the patient rarelyimproves during treatment.

PROGNOSIS: Prognosis is almost always good when tem-poral lobe status epilepticus (TLSE) occurs in knownepilepsy patients with low AED levels. Prognosis is alsogood in mildly obtunded patients without multiorganproblems. Very rarely TLSE produces lasting cognitivedeficits. In comatose ICU patients, 25–50% of patientshave significant morbidity or death.

TREATMENT: Trial of lorazepam 2–4 mg followed bysupplementation of the AED the patient may be on.Look for EEG and clinical improvement. Ensure that thereis respiratory coverage/support in protected environmentfor IV BZPs. Phenytoin, valproate, or levetiracetamhas been used. Anesthetic agents are usually avoidedin the awake patients. Parenteral benzodiazepines,phenytoin, valproate, levetiracetam, and then anestheticagents are considered in unconscious ICU patients on a


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case-by-case basis. This treatment may require prolongedEEG monitoring.

This EEG shows focal epileptiform discharges over theleft temporal region at 2–3 Hz, minimally affected bynoxious stimuli or arousal. Often there is multifrequencybackground activity over uninvolved scalp areas, exceptwhen the patient is in coma.

REFERENCES:

1. Williamson PD. Complex partial status epilepticus. In: EngelJJ, Pedley TA (eds.), Epilepsy: A Comprehensive Textbook.Philadelphia, PA: Lippincott-Raven Publishers 1997;681–699.

2. Young GB, Chandarana PC, Blume WT, McLachlan RS,Munoz DG, Girvin JP. Mesial temporal lobe seizures pre-senting as anxiety disorders. J Neuropsychiatry Clin Neurosci1995;7:352–357.

3. Fish DR. Psychic seizures. In: Engel JJ, Pedley TA (eds.), Epilepsy:A Comprehensive Textbook. Philadelphia, PA: Lippincott-Raven Publishers 1997;543–548.

4. Kirshner HS, Hughes T, Fakhoury T, Abou-Khalil B. Aphasiasecondary to partial status epilepticus of the basal temporallanguage area. Neurology 1995;45:1616–1618.

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26. Simple partial status epilepticus—parietal [1–3]

CLINICAL CORRELATES: Repeated or continuous proximaltingling or burning sensations. Seizures start more oftenin the hand than in the foot and proceed over secondsup the arm and to the face. There may be a variableimpairment of consciousness (secondary generalization).Discomfort may be “pins and needles,” lack of feeling,“numbness,” or perception of altered shape of the limb.Pain may occur in other regions, for example, the face,chest, or rarely the abdomen. With spread to motor areas,subtle myoclonic or dystonic movements may occur. Seealso “Parietal lobe simple partial seizures.”

ETIOLOGY: Any focal structural lesion—infections,trauma, strokes, atrophy, sclerosis, cortical dysplasias,cavernous angiomas, dysembryoplastic neuroepithe-lial tumors, gliosis, arteriovenous malformations, andporencephalic cysts. One-third have tumors.

CLINICAL EVALUATION: The clinical examination is nor-mal in about half of patients. Look for subtle hyper-reflexia, difference in limb and nail size, impairment intwo-point descrimination, right–left orientation, visualfield defects, and spatial orientation. There may be ev-idence of neurocutaneous, genetic syndromes, evidenceof trauma or from symptomatic causes. In older patients,there may be evidence of strokes or mass lesions. Inobtunded patients in the ICU in whom the EEG showsseizure activity over the parietal area, the condition isnot clearly distinguishable from spread, or overlap fromfrontal or temporal foci.

ANCILLARY TESTING: Obtain an enhanced head CT orMRI for the evidence of cerebral lesions. In the evalua-tion for seizure surgery in medically refractory patients,

positron emission tomography (PET) and SPECT scansmay have a place.

DIFFERENTIAL DIAGNOSIS: Clinical—This is a rare imita-tor of other conditions in that seizures are rarely uniquelyor principally painful. Post-, pre-, or ictal headache occurs.Seizures or status epilepticus is very rarely the cause forpain at all, but particularly outside the limbs and head.Seizure etiology is suggested by the stereotyped, briefprogression often with other manifestations of seizures.

EEG—This pattern strongly resembles the mu and al-pha frequency physiological patterns, but will extinguishwith limb movement or eye opening. Also, it is morearcuate and may resemble wicket spikes.

PROGNOSIS: Status epilepticus often responds toantiepileptic drugs (AEDs); occasionally the underlying le-sion (e.g., malignancy) can cause nonictal, more refrac-tory pain. Surgery for refractory cases may markedly im-prove or produce seizure control—75% with tumors and65% without.

PROGNOSIS: In awake patients, prognosis is good.Seizures or status often responds to AEDs; occasion-ally the underlying lesion (e.g., malignancy) can causenonictal, more refractory pain.

TREATMENT: In simple partial status, consider oral use ofAEDs—benzodiazepines, or other rapid onset oral AEDs.Look for EEG and clinical improvement. Ensure that thereis respiratory coverage/support in protected environmentfor intravenous benzodiazepines. Anesthetic agents areusually avoided in the awake patient. Parenteral benzodi-azepines, phenytoin, valproate, levetiracetam, and thenanesthetic agents can be considered in unconscious ICUpatients on a case-by-case basis. This treatment may re-quire prolonged EEG monitoring.


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This EEG shows runs of high-frequency sharp waves morethan 12 Hz over the right parietal area. There is muscleartifact obscuring both frontal regions. The use of a high-frequency filter set at 35 Hz helped differentiate muscleartifact above 20 Hz from polyspikes over the parietalregion at 10–15 Hz.

REFERENCES:

1. Matthews R, Franceschi D, Xia W, Cabahug C, Schuman G,Bernstein R, Peyster R. Parietal lobe epileptic focus identified

on SPECT-MRI fusion imaging in a case of epilepsia partialiscontinua. Clin Nucl Med 2006;31:826–828.

2. Feinberg TE, Roane DM, Cohen J. Partial status epilepticusassociated with asomatognosia and alien hand-like behaviors.Arch Neurol 1998;55:1574–1576.

3. Hopp J, Krumholz A. Parietal lobe status epilepticus. In:Kaplan PW, Drislane F (eds.), Nonconvulsive Status Epilep-ticus. New York: Demos Publications, in press.

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27. Simple partial status epilepticus—occipital [1–4]

CLINICAL CORRELATES: The eyes may be open or closed.The eyes often conjugately deviate away from the seizurefocus along with nystagmus in the same direction. Rarely,gaze is ipsiversive. Occipital epileptic activity may be con-tinuous or exist as multiple seizures with return to base-line and eyes to midline between seizures. Patients maybe aware of the seizure and describe the perception ofmovement, jumping, or visual hallucinations. There maybe amaurosis. Patients may be confused and conversant;others may be more obtunded. The level of consciousnessranges from fully awake with visual symptoms to coma.Alternately, the patient may be unresponsive with headand eye deviation and epileptic nystagmus away fromthe temporo-parieto-occipital focus, which is usually athigh frequency (>10 Hz) at seizure start, but slows toabout 3 Hz when the patient is obtunded, constitutinga complex partial seizure. This may be followed by thesecondary generalization. Ongoing partial occipital sta-tus may occur as multiple isolated but frequent seizures(up to every several minutes) without return to baseline,or as a waxing and waning epileptiform spike or sharpwave complex, continuously, usually at 0.75–1.5 Hz. Seealso “Occipital lobe simple partial seizures.”

ETIOLOGY: Any focal structural lesion—infections,trauma, strokes, atrophy, sclerosis, cortical dysplasias,cavernous angiomas, dysembryoplastic neuroepithe-lial tumors, gliosis, arteriovenous malformations, andporencephalic cysts. One-third have tumors.

CLINICAL EVALUATION: Evaluate for eye movements. Testfor visual field defects. Patients may demonstrate nystag-mus, head and eye deviation.

ANCILLARY TESTING: Request a head CT/MRI fortemporo-occipital junction structural abnormalities.

DIFFERENTIAL DIAGNOSIS: Clinical—Other encephalo-pathies and TLSE occur only rarely with nystagmus, head,and eye deviation.

EEG—Periodic lateralized epileptiform discharges(PLEDs) are of lower frequency. Occipital, intermittentrhythmic delta activity is blunted and rarely sustained.

PROGNOSIS: Good. In an awake patient, status epilep-ticus usually responds to antiepileptic drugs (AEDs). Incomatose patients, comorbidities and neurologic statedictate a poorer outcome.

TREATMENT: Consider a trial of oral benzodiazepine(BZPs). Others advocate using lorazepam 2 mg (undercontrolled conditions), followed by supplementation ofthe AED, if the patient is on an AED. Look for EEG andclinical improvement. Ensure that there is respiratory cov-erage/support in a protected environment for IV BZPs.Anesthetic agents are usually avoided in the awake pa-tient. Parenteral benzodiazepines, phenytoin, valproate,levetiracetam, and then anesthetic agents are usuallyconsidered in unconscious ICU patients on a case-by-case basis. This treatment may require prolonged EEGmonitoring.


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This EEG shows focal epileptiform discharges over theoccipital region, initially at 10–12 Hz. There is progres-sive slowing of the occipital discharge frequency, with anincrease in voltage. Eye deviation occurred shortly afterictal onset.

REFERENCES:

1. Sowa MV, Pituck S, Prolonged spontaneous complex visualhallucinations and illusions as ictal phenomena. Epilepsia1989;30:524–526.

2. Sawchuk KS, Chruchill S, Feldman E, Drury I. Status epilepticusamauroticus. Neurology 1997;49:1467–1469.

3. Barry E, Sussman NM, Bosley TM, Harner RN. Ictal blindnessand status epilepticus amauroticus. Epilepsia 1985;26:577–584.

4. Kaplan PW, Tusa RJ. Neurophysiologic and clinical correlationsof epileptic nystagmus. Neurology 1993;2508–2514.

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28. Generalized nonconvulsive status epilepticus [1–9]

CLINICAL CORRELATES: The eyes may be open or closed,or may open to stimuli. The patient is typically con-fused, disoriented, but usually conversant when he orshe present to the ER and may follow simple or evencomplex commands. The level of consciousness rangesfrom fully awake, with subjective cloudiness, to coma.In the ICU, the patient is usually lethargic and may havemyoclonus and intercurrent tonic–clonic seizures.

ETIOLOGY: In awake or mildly confused patients, con-current metabolic problems such as hyperammonemia oruremia are not typical. Conversely, there are often infec-tious problems such as urinary tract infection (URI) or up-per respiratory tract infection (URTI), medication burden,cerebral atrophy, and abuse of benzodiazepines. Patientswith known generalized epilepsy may have nonconvul-sive status epilepticus (NCSE) with low antiepileptic drug(AED) levels. In ICU patients there is usually a combina-tion of strokes, atrophy, toxic, metabolic, or other centralnervous system (CNS) insults, and the generalized non-convulsive status epilepticus (GNSE) may be secondarilygeneralized on the EEG.

CLINICAL EVALUATION: Perform a global physical andneurological examination, looking for neck stiffness(meningoencephalitis), external evidence of trauma(hemorrhage, contusion). In mildly affected conditions,the patient often localizes to pain and brainstem reflexesare almost always intact. Typically in noncomatose pa-tients, there is eyes-open mutism, subtle facial and limbmyoclonus, and often catalepsy.

Pay particular attention to the medication list: look forlithium, recent antibiotics (cefepime), baclofen, benzodi-azepines, phenothiazines, recent intercurrent urinary orrespiratory infection. In ICU/comatose patients, there maybe global decrease in Glasgow coma scale, with or with-

out brainstem reflexes and with localizing or nonlocaliz-ing CNS signs.

DIFFERENTIAL DIAGNOSIS: Clinical—Encephalopathiesand psychogenic unresponsiveness. Beware of locked-instates, vegetative states, and abulia (see these sections).

EEG—Triphasic waves (TWs) are blunter and usually oflower frequency than discharges of NCSE. TWs may in-crease (rarely decrease) with arousal, while NCSE epilep-tiform discharges rarely do. EEG background activity canbe present in either TWs or GNSE. TWs resolve with BZPs,but the patient typically fails to improve, while those withNCSE typically improve clinically after IV BZPs.

PROGNOSIS: This largely depends on the underlyingcause. Excellent in de novo, reactive causes and in geneticidiopathic generalized epilepsy (IGE) (childhood absenceepilepsy (CAE), juvenile myoclinic epilepsy (JME)) whendue to low AEDs. Prognosis is less clear in atypical absencestatus in syndromes such as Lennox–Gastaut syndrome,Landau–Kleffner syndrome, epilepsy with electrical sta-tus epilepticus (ESES), or Ring 20 chromosome where theunderlying condition is often associated with cognitiveimpairment or decline. Prognosis is poor when present-ing as electrographic status in postanoxic coma or withmultiorgan failure. Given the demographic distribution ofaged patients, the overall prognosis (all causes exceptingICU/coma patients) is good.

TREATMENT: In lightly affected patients, consider oralbenzodiazepines or rapid-acting oral AED. In more af-fected patients, consider a trial of lorazepam 2–4 mg tolook for EEG and clinical improvement. Parenteral agentsmust be given in a protected environment. In awake pa-tients, IV valproate or levetiracetam has been used. Inobtunded patients, further treatment may require EEGmonitoring and other AEDs or anesthetic agents, usuallyin an ICU.Clinical Electrophysiology. By C© Peter W. Kaplan and Thien Nguyen.

Published 2011 Blackwell Publishing Ltd.

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The tracing shows bursts of polyspike-slow waves withsuppressed background in a comatose patient after car-diac arrest.

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72 Section B: Status Epilepticus

This EEG shows bursts of generalized polyspike-wave dis-charges with intervening background in a mildly confusedpatient, several months after a brief cardiac arrest.

REFERENCES:

1. Kaplan PW. Behavioral manifestations of non-convulsive sta-tus epilepticus. Epilepsy Behav 2002;3:122–139.

2. Agathonikou A, Panayiotopoulos CP, Giannakodimos S,Koutroumanidis M. Typical absence status in adults: Diagnos-tic and syndromic considerations. Epilepsia 1998;39:1265–1276.

3. Baykan B, Gokyigit A, Gurses C, Eraksoy M. Recurrent absencestatus epilepticus: Clinical and EEG characteristics. Seizure2002;11:310–319.

4. Thomas P, Valton L, Genton P. Absence and myoclonic statusepilepticus precipitated by antiepileptic drugs in idiopathicgeneralized epilepsy. Brain 2006;129:1281–1292.

5. Dziewas R, Kellinghaus C, Ludemann P. Nonconvulsion statusepilepticus in patients with juvenile myoclonic epilepsy: Typesand frequencies. Seizure 2002;11:335–339.

6. Drislane FW, Schomer DL. Clinical implications of general-ized electrographic status epilepticus. Epilepsy Res 1994;19:111–121.

7. Treiman DM. Electroclinical features of status epilepticus.J Clin Neurophysiol 1995;12:343–362.

8. Thomas P, Beaumanoir A, Genton P, Dolisi C, Chatel M. “Denovo” absence status of late onset: Report of 11 cases. Neu-rology 1992;42:104–110.

9. Kaplan PW. Prognosis in nonconvulsive status epilepticus.Epileptic Disord 2000;2:185–193.

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PART 3

Conditions of prolonged unresponsiveness

A frequent call for neurological consultation from inten-sive care units and chronic care centers is for the eval-uation of chronically unresponsive patients. The clinicalquestion usually revolves around whether the patientis comatose, vegetative, locked-in, or possibly minimallyconscious. Rarely, there may be catatonia—a psychiatricstate of inertia. Because the management and progno-sis can be markedly different among these diagnoses, anaccurate determination is essential. One study has high-lighted this problem by finding that many patients diag-nosed as being in a vegetative state (VS) were locked-insyndrome (LIS). At the very least it is important to knowif the patient is awake, hearing and suffering (LIS), orunconscious (coma or persistent vegetative state). Thereare some regional, national, or statewide regulations that

affect the care or its discontinuation in one or other ofthese conditions, such as with the minimally consciousstate (MCS).

Coma aside, clinical examination will determine and di-agnose all states of prolonged unresponsiveness. In somepatients, electrophysiology can support one or otherpossibility, or even exclude other considerations (psy-chogenic unresponsiveness, nonconvulsive status epilep-ticus (NCSE)), but electroencephalography (EEG) findings,particularly with persistent vegetative state (PVS), may bequite variable (see PVS case). A printed set of character-istics of these states allows a comparison of the variousclinical features. Following are some outlines and consid-erations in the various states of unresponsiveness.

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Section A: Locked-in syndrome, minimally conscious state,vegetative state, and coma: disorders of consciousnessand responsiveness

These conditions often present major challenges to thediagnostician when doing neurological consultations.The respective diagnoses usually have markedly differentclinical and prognostic implications. A patient with LISis sentient, can be awake and alert, and can hear andremember what is said. She or he can feel and sufferboth mentally and physically. Comatose patients are notknown to suffer or remember events during periodsof unconsciousness. MCSs lie in between, and less isknown about memory and prognosis.

The diagnostic challenge is in the gathering and inter-pretation of clinical signs at the bedside, and garneringmore information than can usually be gathered duringa brief consultation. Problems arise because the bedsideevaluation of remaining brain function in severely brain-damaged patients often varies from time to time, and canbe based on quite limited, elicited patients’ reactions. Theclinical diagnosis depends on conclusions drawn fromreactions to external conditions present during exami-nation. LIS, MCS, and VS are largely clinical diagnosesthat may be made without electrophysiological testing.However, there is an increasing amount of data on howsuch tests may help differentiate wakefulness from coma.There is less information on the differentiation of con-sciousness from unconsciousness in the awake patient.As many observers have noted, consciousness in not anall-or-none condition.

Table 29.1 summarizes differences among these states.

Table 29.1 Glasgow coma scalea

Best motor responseObeying commands 6Localizing to pain 5Withdrawing to pain 4Abnormal flexion (decorticate) 3Extensor response (decerebrate) 2

None 1

Best verbal responseb

Oriented 5Confused conversation 4Inappropriate words 3Incomprehensible sounds 2None 1

Eye openingSpontaneous 4To speech 3To pain 2None 1

Adapted from Teasdale and Jennett [2].

aThe score for the scale is summed across three componentsand ranges from 3 to 15. A lower score indicates more severeneurological deficits.b Intubated patients cannot be given a score for the verbalcomponent, so their total scores accordingly range from2 to 10.

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29. Clinical definitions of impairedresponsiveness [1–11]

Consciousness

Consciousness, an awareness of self and the environ-ment, until recently has been assessed in patients by theirability to follow some commands. It cannot be measureddirectly by electrophysiological tests, and the evaluationdepends on interpretation of clinical findings. The pri-mary components of consciousness are those of arousaland awareness. Arousal is maintained by ascending brain-stem connections that project to the thalami and thenceto the cortices. Usually, the presence or absence of brain-stem reflexes helps to localize the source of unresponsive-ness to problems involving the brainstem, or higher up, inthe cortex. However, brainstem reflexes can be selectivelyabolished by focal strokes or trauma, rendering the pa-tient de-efferented. In this state, the patient is awake butnot able to produce movement or manifest some brain-stem functions. The second component of awareness de-pends on the extent of cerebral cortical integrity, alongwith the subcortical connections among cortical regions.Disruption of significant amounts of cortical connectivityresults in various degrees of decreased function to thepoint of producing an MCS, a VS, or coma. Arguably,these represent a continuum of dysfunction, which hasbeen categorized along testable criteria.

Not conscious and not awake: coma

Coma is characterized by the absence of arousal, usu-ally with eyes closed, and without evidence of aware-ness of self or the surroundings. It is a variable state ofeyes-closed unresponsiveness to verbal, auditory, visual,tactile, or other noxious stimuli. The patient may retainbrainstem reflexes (particularly after briefer cardiorespira-

tory arrests (CRAs)) and severe toxic/metabolic problems,or conversely lose these reflexes with the primary brain-stem causes of coma. Coma is transient, progressing towakefulness or death, usually over days.

It contrasts with VS in that stimulation will fail to eliciteye opening or apparent wakefulness, nor will the patientcycle through identifiable periods of sleep and wakeful-ness. This state must persist for at least an hour, and sur-viving patients either awaken or gradually evolve to VSover 2–4 weeks. Table 29.1 provides the Glasgow comascale.

Imaging may reveal common structural causes, involv-ing the brainstem or both cerebral hemispheres, or un-cover bihemispheric compressive disease causing brain-stem herniation. For the most part, the etiology ofcoma determines outcome. Structural (stroke, hemor-rhage) and irreversible toxic insults carry the worst prog-nosis; head trauma outcomes may be intermediate, whilereversible metabolic issues or seizures often enable com-plete recovery.

Minimally conscious and awake:minimally conscious states

An MCS, first described in 2002, is a state of severelyaltered consciousness. There are minimal but definitebehavioral manifestations, demonstrating reactions toand awareness of the environment. Such patients mayhave varying degrees of attention, have purposeful visualtracking, and may communicate. Criteria include hav-ing one or more of following simple commands, speechor gestures indicating a yes or no answer, actions thatare reactive to external stimuli, or uttering intelligiblewords. Distinctions may be difficult because patients withMCS can have a fluctuating examination, and hence haveperiods in which there is less evidence of response ortracking. More recently, functional magnetic resonanceimaging (fMRI) has demonstrated activity in brain areas of


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Section A: Locked-in syndrome, minimally conscious state, vegetative state, and coma 77

minimally conscious patients in patterns similar to thoseseen in healthy people. These findings are believed tocorrespond to conscious cognitive processing. Althoughthese patients show overall little clinical evidence of con-scious interactive ability, they must show clear evidenceof self-awareness or awareness of the environment asdemonstrated by following simple commands, yes or noresponses by speech or gestures, intelligible speech, pur-poseful behavior not due to reflexive responses. Akineticmutism, which may be due to bihemispheric damage,resembles the MCS, but many authors avoid this term.

Unconscious and awake:vegetative states

In VS, the patient is awake but shows no evidence ofawareness of self or the environment. There is cyclingof wakefulness and sleep, but without evidence (duringwakefulness) of cognitive processing of external stimuli;the patient is awake but not conscious. A persistent VSis that which persists for at least 1 month. It does notimply irreversibility. A permanent VS is irreversible andusually occurs about 3 months after nontraumatic braininjury, or 12 months after brain trauma. Such prognosti-cations are most robust after anoxic injury, somewhat lessso after brain trauma, and even less certain with othernontraumatic causes of unconsciousness.

Conscious and awake: locked-insyndrome

Introduced by Plum and Posner, this state consists oftetraparesis and the inability to speak. It is due to theinterruption of corticospinal and corticobulbar pathways.Patients will be able to sustain eye opening, be aphonicand tetraparetic. They have awareness of self and theenvironment and are able to communicate by the uppereyelid, blinking vertical or lateral eye movements so as tosignal yes/no answers.

Electrophysiological investigationsof deeper levels of impairedresponsiveness—diagnosisand prognosis

In patients with unresponsiveness, there is a wide varietyof electrophysiological findings.

ComaEEG – The EEG of coma often correlates with the depth ofcoma. As the level of consciousness falls, EEG-dominant

frequencies slow to theta and delta range. In coma dueto medications, there may be particular EEG patterns offaster activity in the beta range (e.g., from barbituratesand benzodiazepines), or conversely bursts of slowing.

Some marked toxic or medication effects can produce amarked suppression of voltage. Drugs or medications ex-cepted, marked suppression or flat-line tracings forebodea poor to no positive prognosis for recovery of conscious-ness. The EEG findings also often reflect the etiology ofcoma and hence the prognosis. For anoxia with cardiacarrest, minimal or no EEG brain activity indicates no returnto consciousness. Somewhat less grim is a pattern of un-reactive alpha or theta frequencies that carry a prognosisof less than 15% chance of return to consciousness. Spin-dle patterns, however, predict overall a better probabilityof return to consciousness and is the most favorable ofthe CRA/anoxia patterns. Similar hierarchies of prognosisexist for traumatic coma. Evoked potentials (EPs) also playa role in coma prognosis. Like EEG, their relevance needsto be seen in the light of the coma etiology. Somatosen-sory evoked potentials (SSEPs) are helpful in predictingoutcome after head trauma and CRA/anoxia. When thereare no cortical responses after CRA/anoxia (tested >12hours after coma onset and without hypothermia), onecan predict with 100% accuracy that the patient will notregain consciousness. The prognosis is somewhat betterwith traumatic causes of coma; occasionally some pa-tients with absent potentials regain awareness. The bestoutcomes are seen with reversible causes of coma. Notsurprisingly, SSEPs are usually present (as they are dur-ing anesthesia). Short-latency auditory evoked potentialshave also value in the prognostication in traumatic comaand CRA, but are less sensitive than SSEPs and are nownot often used. Long-latency auditory responses (N70)have been used to differentiate patients who awaken andare conscious versus those who will be vegetative afterdrowning, but these results have not been widely repli-cated. Mismatch negativity testing by some investigatorshas been helpful in predicting a return to consciousness,but more recent studies are less hopeful.

With P300 cortical responses, the vulnerability to ambi-ent or other testing artifacts has led to little use recently,but older data would suggest that their presence is pre-dictive of return or presence of consciousness.

More recent investigation with fMRI and other condi-tioned imaging modalities indicates that these tests holdgreater potential for diagnosis or prognostication. At thismoment, these tests are neither bedside nor inexpensiveprocedures.

Patients typically evolve over hours to days from co-matose states. A typical progression would be from comato alertness, coma to death, or in a minority of patients

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78 Section A: Locked-in syndrome, minimally conscious state, vegetative state, and coma

Table 29.2 Different behavioral characteristics in states of prolonged unresponsiveness

LIS(awake)MCS(awake, minimallyconscious)

VS(awake, notconscious)

Coma(not awake, notconscious)

Visual reaction Blink Object recognitionVisual present

Startle None

Eye opening Volitional Spontaneous Spontaneous Variable according to depth

Spontaneous movement None AutomaticObject manipulation

Reflexive or simplesequences

Posturing

Reaction to pain Pupil dilation Localization PosturingWithdrawal

Posturing

Follows commands By eye movement/blinking

Inconsistent butreproducible

Affective reaction Yes Contingent Random None

Speech None Intelligible words RandomVocalization

None

Communication Yes/NoNo pausesWith eye movements

UnreliableGestural or verbal Yes/Noresponses

None None

Adapted from Fins et al. [4].

from coma to VS. In some reports, progression fromcoma to VS is not accompanied by a change in EEG. Insome cases, EEG change will not be reflected in a clinicalchange.

VSEEG – For VS, the EEG may range from normal (in aminority of patients) to a pattern of continuous, general-ized, polymorphic delta slowing (the majority of patients)unreactive alpha, theta, or spindle coma patterns,reactive theta background or diffuse suppression to thepoint of being isoelectric, or exhibiting “electrocerebralsilence.” The authors concluded that EEG was of limitedvalue in VS.

EPs – In some VS patients, auditory EPs were normal,while in many patients, cortical responses were unob-tainable on SSEP testing. In other patients, there wasprolongation of central conduction time with normal N20amplitudes. This was thought to reflect selective synapticdelay in thalamic nuclei.

LISThere may be EEG evidence of wakefulness or sleep ac-tivity, and SSEP evidence (on occasion) that there is inter-ruption of ascending sensory stimuli through brainstemor midbrain structures. Such testing does not evaluateconsciousness, and both EEG and SSEP may not reliablyseparate VS from LIS in some patients. Positron emis-

sion tomography (PET) scans may reveal high cerebralmetabolic rates in LIS. The different behavioral character-istics can be found in Table 29.2.

“Functional” electrophysiology andfunctional imaging evaluation ofimpaired responsiveness

Longer latency “cognitive” evoked potentials obtainedby “oddball” auditory stimuli, N70 and P300 potentials,have been used with greater or lesser success in differ-entiating the conscious patient from the unconscious.Technical problems may impair the ability to demonstratethe presence of such cognitive-processing potentialseven in intact persons, and the absence of potentialsmay also be seen in patients with more diffuse cerebralproblems, but who might be conscious. Nonetheless, thisarea of event-related cognitive processing remains under-explored in the LIS, with VS, MCS, and coma disorders.

As with MCS and VS, functional imaging holds thegreater potential for prognostication. Investigations haveranged from studies of brain death with single pho-ton emission computed tomography (SPECT) where cere-bral perfusion or metabolism tracers reveal a “hollowskull phenomenon” to a 50–70% fall in gray mat-ter metabolism in traumatic or anoxic coma (predic-tive of poor outcome), to PET scanning in VS that may

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Section A: Locked-in syndrome, minimally conscious state, vegetative state, and coma 79

Table 29.3 Prognosis after anoxic coma using five EEG grades(from 408 cases from the literature)

EEG category Recovery (%)

Survival withpermanent

neurologicaldamage (%) Death (%)

Grade 1 79 10 11Grade 2 51 13 36Grade 3 26 7 67Grade 4 0 2 98Grade 5 0 0 100

Adapted from Scollo-Lavizzari and Bassetti [10]. Permission tobe obtained.

be predictive of functional recovery (albeit rarely) toconsciousness. fMRI has been used to study responses tolanguage stimuli, with selective activation seen in somepatients.

However, even with functional imaging there maybe problems as patients cycle through periods of lowarousal and sleep and hence produce decreased values onthese imaging techniques. Thus, for “activation” scans,EEG monitoring is essential to avoid such physiological“down” periods.

Table 29.4 Determination of the index of global corticalfunction assessed between 1 and 3 days after anoxic coma onset

VEPs SSEPsGood

outcome (%)

Grade 0 Normal NormalGrade 1 Increased peak II

latencyPeak VII present

Normal N20,P24, and P27N30 present 60

Grade 2 Increased peak IIIlatencyPeak VII absent

Normal N20 andP24N30 absent 40

Grade 3 Increased peak IIIlatencyNo subsequentactivities

No subsequentactivitiesNo corticalactivities

15

Grade 4 No reproducibleVEPsERG present

No corticalactivitiesP14 present 0

Adapted from Guerit et al. [9]. Permission to be obtained.SSEP, somatosensory evoked potential; VEP, visual evokedpotential.

Prognosis using electrophysiology

Electrophysiology is optimally used in guiding early di-agnostic investigation, and excluding other differentialconsiderations, including severe encephalopathy, NCSE,or psychogenic issues.

For prognosis, EEG can be used early on after an irre-versible insult such as ischemia/anoxia from CRA to helppredict outcome and the chances for good, poor, or norecovery (Table 29.3). After anoxic coma, EPs also providereliable prognostication of a poor or negative outcome.Combined with EPs, an index of global cortical function(see Table 29.4) can also be generated to provide a gradedprognostication, but frequently the EP testing resourcesare not available in many hospitals, excepting some aca-demic centers. Imaging techniques are still largely exper-imental, but may be useful in individual cases.

When patients reach the chronic stages with LIS, VS,PVS, or MCS, electrophysiology does not accrue furtherprognostic value.

REFERENCES:

1. Kaplan PW. Electrophysiological prognostication and braininjury from cardiac arrest. Semin Neurol 2006;26:403–412.

2. Teasdale G, Jennett B. Assessment of coma and impairedconsciousness: A practical scale. Lancet 1974;2:81–84.

3. Booth CM, Boone RH, Tomlinson G, Detsky AS. Is this patientdead, vegetative, or severely neurologically impaired. JAMA2004;291(7):870–879.

4. Fins JJ, Master MG, Gerber LM, Giacino JT. The minimallyconscious state. Arch Neurol 2007:64(10):1400–1405.

5. Kampf A, Schmutzhard E, Franz G, Pfausler B, Haring H-P,Ulmer H, Felber S, Golaszewski S, Aichner F. Prediction ofrecovery from post-traumatic vegetative state with cerebralmagnetic-resonance imaging. Lancet 1998;351:1763–1767.

6. Multi-Society Task Force on PVS. Medical aspects of the per-sistent vegetative state (first of two parts). N Engl J Med1994;330:1499–1508.

7. Laureys S, Owen AM, Schiff ND. Brain function in coma,vegetative state, and related disorders. Lancet Neurol2004;3:537–546.

8. Hansotia PL. Persistent vegetative state. Arch Neurol1985;42:1048–1052.

9. Guerit JM, De Tourtchaninoff M, Soveges L, Mahieu P.The prognostic value of three-modality evoked potentialsin evoked potentials (TMEPs) in anoxic and traumatic coma.Neurophysiol Clin 1993;23:209–226.

10. Scollo-Lavizzari G, Bassetti C. Prognostic value of EEGin post-anoxic coma after cardiac arrest. Eur Neurol1987;26:161–170.

11. Zandbergen EGJ, Hijdra A, Koelman JHTM, Hart AA, Vos PE,Verbeek MM, de Haan RJ; PROPAC Study Group. Predictionof poor outcome within the first three days of post anoxiccoma. Neurology 2006;66:62–68.

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30. Locked-in syndrome—brainstem hemorrhage [1–4]

NICU, CICU, MICU, SICU

CLINICAL CORRELATES: There is no purposeful limb ortrunk reaction, no speech and no mouth or jaw move-ments. The patient may be in any of several states, rang-ing from conscious to a clouded sensorium, a minimallyconscious, or be comatose along a continuum. The eyesmay be open or closed, or may open variably to com-mands stimuli, or open spontaneously. Movement belowthe neck may be reflexive.

CLINICAL EVALUATION: Examine the brainstem reflexes,reactivity to stimuli (look for minimal vertical eye move-ments to commands). The clinical assessment is largelydirected at determining if there is meaningful yes/no re-sponse to external stimuli. This indicates consciousness.Often, more prolonged observation is needed, as familiesoften report “meaningful” responses not seen by nursesand physicians. Assess the patient’s score on the Glasgowcoma scale (Tables 29.1 and 29.2).

ANCILLARY TESTING: These states often trigger consultsand requests for further investigations for conscious-ness, persistent vegetative state (PVS), locked-in syn-drome (LIS), or prognosis. Consider electrolytes, toxinscreen, somatosensory evoked potential (SSEP), and CTor MRI depending on the differential diagnosis (see Tables29.3 and 29.4).

DIFFERENTIAL DIAGNOSIS: Unreactive patients may bemistaken for patients experiencing no conscious percep-tion (Table 29.2). These patients could be aroused fromsleep to wakefulness. Functional magnetic resonanceimaging (fMRI) may be found to differentiate consciouspatients, but clinical examination is still the basis of di-agnosing these “similar” states [1,3,4]. Clinically othercauses of de-efferentation are severe peripheral nervous

system disease such as with amyotrophic lateral sclero-sis (ALS) or other end-stage causes of total peripheralparalysis.

Coma—A clinical state of eyes-closed unresponsive-ness from which the patient cannot be aroused (distinc-tion from sleep) without purposeful response to externalstimuli. If the cause is unknown, obtain CT/MRI. If unin-formative, look for toxic or metabolic causes.

Vegetative state—The patient is awake (eyes open) butunconscious. The diagnosis of the state is clinical; forcauses the evaluation is the same as above. The common-est etiologies are post-cardiorespiratory arrest (CRA) andafter head trauma, less commonly after hypoglycemia.

Locked-in syndrome—De-efferented state—awake,conscious but minimal evidence of reaction (verti-cal/horizontal eye movements to questions). Imaging willusually show a stroke in or evidence of trauma to the mid-brain/pontine area. Rarely, it occurs as an end-stage ofsevere, widespread peripheral paralysis (e.g., ALS, myas-thenia gravis (MG), and botulism). It occurs rarely in theintensive care unit (ICU) and operating room (OR) in par-alyzed patients (vecuronium, pancuronium) who are in-adequately sedated or anesthetized.

Catatonia—A state of psychic and motor unrespon-siveness. It is characterized by mutism, akinesia, andnegativism and may be seen with schizophrenia, post-traumatic stress disorder, bipolar disease, depression,drug abuse, and overdose. It can occur with strokes,metabolic and autoimmune conditions, encephalitis, ad-verse reactions to medications, and sudden withdrawalfrom benzodiazepines. It may be caused by decreasedcentral dopaminergic activity from psychiatric, toxic,medical, or unknown origin.

DISCUSSION: fMRI may be found to differentiate con-scious patients from vegetative state (VS), but clinicalexamination is still the basis of diagnosing these “similar”states [1,3,4]. Clinically other causes of de-efferentationare severe peripheral nervous system disease such as


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Section B: Prolonged unresponsive states 83

with ALS or other end-stage causes of total peripheralparalysis.

PROGNOSIS: Chronic patients may survive with support-ive care, but usually succumb to infection or organ fail-ure. Treatable causes include when it is due to paralyzingagents, which are reversible, and myasthenia gravis so asto reverse limb and speech paralysis. Structural damage tothe midbrain and pons and end-stage ALS are irreversiblecauses of LIS. These conditions are highly distressing tothe patient’s family, physicians, and nurses, and all maybenefit from sensitive and extensive discussions. Considergetting input from an ethics committee.

TREATMENT: Supportive care with chronic ventilationsupport. All caregivers should be made aware that thepatient is sentient, can hear, and experience mental andphysical anguish and suffering.

This electroencephalography (EEG) shows 10- to 12-Hzactivity superimposed on 0.5- to 1.2-Hz delta frequen-cies, while the patient is being asked to move her eyes.

In other cases, there may be EEG evidence of wakeful-ness or sleep activity, and SSEP evidence (on occasion)that there is interruption of ascending sensory stimulithrough brainstem or midbrain structures. Such testingdoes not evaluate consciousness, and both EEG and SSEPmay not reliably separate VS from LIS in some patients(see Tables 29.3 and 29.4). PET scans may reveal highcerebral metabolic rates in LIS.

REFERENCES:

1. Cartlidge N. States related to or confused with coma. J NeurolNeurosurg Psychiatry 2001;71(Supplement 1): i18–i19.

2. Gutling E, Isenmann S, Wichman W. Electrophysiology in thelocked-in-syndrome. Neurology 1196;46:1092–1101.


4. Young GB. Major syndromes of impaired consciousness. In:Young GB, Ropper AH, Bolton CF (eds.), Coma and ImpairedConsciousness: A Clinical Perspective. New York: McGraw-Hill1998:39–78.

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31. Vegetative state—postanoxia [1–12]


CLINICAL CORRELATES: There is no purposeful limb ortrunk reaction to outside command. There is neitherspeech nor language. The eyes may be open, closed,or may open unreliably to sound, stimuli, or open spon-taneously. Movement below the neck may be reflexive.

ETIOLOGY: It is most commonly found after cardiac ar-rest, with the initial presentation being that of coma. Itcan be seen after severe head trauma; following causesof diffuse intracerebral edema with widespread ischemiafrom vascular compromise; and more rarely with drown-ing, carbon monoxide poisoning, hypotension, and/oranoxia during anesthesia. Also, it occurs with severe, dif-fuse encephalitis, and strokes producing bilateral frontalischemia.

CLINICAL EVALUATION: Examine the brainstem reflexesand look for reactivity to stimuli (look for minimalvertical eye movements to command seen in locked-insyndrome). The clinical assessment is largely directedat determining if there is meaningful yes/no responseto external stimuli. This indicates consciousness. Often,more prolonged observation is needed, as families oftenreport “meaningful” responses not seen by nurses andphysicians. Assess the patient’s score on the Glasgowcoma scale.

ANCILLARY TESTING: These states often trigger consultsand requests for further investigations for “conscious-ness,” “locked-in syndrome (LIS),” psychogenic unre-sponsiveness, or prognosis. Consider electrolytes, toxinscreen, somatosensory evoked potentials (SSEP), and CTor MRI depending on the differential diagnosis below.

EEG—The EEG may range from normal (in a minor-ity of patients) to a pattern of continuous generalizedpolymorphic delta slowing (the majority of patients);unreactive alpha, theta, or spindle coma patterns; re-active theta background or diffuse suppression to thepoint of being isoelectric, or exhibiting “electro-cerebralsilence”.

EPs—In some vegetative state (VS) patients, auditoryevoked potentials (EPs) were normal, while in many pa-tients, cortical responses were unobtainable on SSEP test-ing. In other patients, there was prolongation of centralconduction time with normal N20 amplitudes. This wasthought to reflect selective synaptic delay in thalamicnuclei.

DIFFERENTIAL DIAGNOSIS:

Coma—This is a clinical state of eyes-closed unrespon-siveness from which the patient cannot be aroused (dis-tinction from sleep) without purposeful response to ex-ternal stimuli. If the cause is unknown, obtain CT/MRI. Ifuninformative, look for toxic or metabolic causes.

Locked-in syndrome—LIS is a de-efferented state: thepatient is awake, conscious but shows minimal evi-dence of reaction to external stimuli (vertical/horizontaleye movements to questions). Imaging will usuallyshow a stroke in or evidence of trauma to the mid-brain/pontine area. Rarely, it occurs as an end-stage of se-vere, widespread peripheral paralysis (e.g., amyotrophiclateral sclerosis (ALS), myasthenia gravis (MG), and bo-tulism). It occurs rarely in the ICU and operating room(OR) in paralyzed patients (vecuronium, pancuronium)who are inadequately sedated or anesthetized.

Catatonia—A state of psychic and motor unrespon-siveness. It is characterized by mutism, akinesia, and neg-ativism and may be seen with schizophrenia, posttrau-matic stress disorder, bipolar disease, depression, drugabuse, and overdose. It can occur with strokes, metabolic


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Section B: Prolonged Unresponsive States 85

and autoimmune conditions, encephalitis, from adversereactions to medications, and sudden withdrawal frombenzodiazepines. It may be caused by decreased centraldopaminergic activity from psychiatric, toxic, medical, orunknown origin.

PROGNOSIS: Chronic patients may survive with support-ive care, but usually succumb to infection or organ failure.The underlying structural causes of VS are irreversible.Functional outcome given, these limitations can vary, andearly in the course, patients may return to conscious-ness or emerge to a minimally conscious state. WhenVS has existed for a month, it is referred to as a per-sistent VS, and if present for 3 months after anoxia or1 year after head trauma, it is regarded as permanent(PVS). These conditions are among the most distress-ing disorders seen in neurology, and the patient’s family,physicians, and nurses may benefit from sensitive and ex-tensive discussions. They may seek input from an ethicscommittee.

TREATMENT: Supportive care is usually initially providedin an ICU. With enduring states, when the patients maynot require ventilation support, they can be supported inintermediate care units or high-level chronic care units.

In this patient in posttraumatic PVS, the EEG showsvoltage suppression over the right hemisphere and diffusemonomorphic 4- to 6-Hz theta activity bilaterally.

REFERENCES:

1. Cartlidge N. States related to or confused with coma. J Neu-rol Neurosurg Psychiatry 2001;71(Supplement 1):i18–i19.


3. Young GB. Major syndromes of impaired consciousness. In:Young GB, Ropper AH, Bolton CF (eds.), Coma and ImpairedConsciousness: A Clinical Perspective. New York: McGraw-Hill 1998:39–78.


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7. Fins JJ, Master MG, Gerber LM, Giacino JT. The minimallyconscious state. Arch Neruol 2007;64(10):1400–1405.

8. Kampf A, Schmutzhard E, Franz G, Pfausler B, HaringH-P, Ulmer H, Felber S, Golaszewski S, Aichner F. Predictionof recovery from post-traumatic vegetative state with cere-bral magnetic-resonance imaging. Lancet 1998;351:1763–1767.

9. Multi-Society Task Force on PVS. Medical aspects of the per-sistent vegetative state (first of two parts). N Engl J Med1994;330:1499–1508.

10. Hansotia PL. Persistent vegetative state. Arch Neurol1985;42:1048–1052.



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32. Minimally conscious state—after large, multifocalstrokes [1–10]


CLINICAL CORRELATES: There is no purposeful limb ortrunk reaction in response to outside command, and nei-ther speech nor language. The eyes may be open, closed,or may open variably to sound, stimuli, or open sponta-neously. Movement below the neck may be reflexive.

ETIOLOGY: It is most commonly seen after CRA, but canoccur with strokes or head trauma. Coma is usually seenfirst. Minimally conscious state (MCS) can be seen withdiffuse intracerebral edema associated with widespreadischemia from vascular compromise, and more rarely af-ter drowning, carbon monoxide poisoning, hypotension,and/or anoxia during anesthesia. Also, it may occur aftersevere, diffuse encephalitis, and strokes producing bilat-eral frontal ischemia.

CLINICAL EVALUATION: Examine the brainstem reflexesand look for reactivity to stimuli. The clinical assessmentis largely directed at determining if there is meaningfulyes/no response to external stimuli. This indicates con-sciousness. Often, more prolonged observation is neededas families often report “meaningful” responses not seenby nurses and physicians. Assess the patient’s score on theGlasgow coma scale (Table 29.1).

ANCILLARY TESTING: These states often trigger consultsand requests for further investigations of “con-sciousness,” “locked-in syndrome (LIS),” psychogenicunresponsiveness, or prognosis. Consider, in addition to,electrolytes and a toxin screen, somatosensory evokedpotentials. A head CT or MRI may help to uncover thecause.

EEG: This patient had extensive postinfarction encephalo-malacia in the right frontal, parietal, basal ganglia, andleft frontal lobes.

DIFFERENTIAL DIAGNOSIS

Coma—A clinical state of eyes-closed unresponsivenessfrom which the patient cannot be aroused (distinctionfrom sleep) without purposeful response to external stim-uli. If the cause is unknown, obtain a CT/MRI. If uninfor-mative, look for toxic or metabolic causes.

Locked-in syndrome—De-efferented state: awake,conscious but minimal evidence of reaction (verti-cal/horizontal eye movements to questions). Imaging willusually show a stroke in or evidence of trauma to themidbrain/pontine area. Rarely, it occurs as an end-stageof severe, widespread peripheral paralysis (e.g., ALS, MG,and botulism). It occurs rarely in the ICU and OR in para-lyzed patients (vecuronium, pancuronium) who are inad-equately sedated or anesthetized.

Catatonia—A state of psychic and motor unrespon-siveness. It is characterized by mutism, akinesia, and neg-ativism and may be seen with schizophrenia, posttrau-matic stress disorder, bipolar disease, depression, drugabuse, and overdose. It can occur with strokes, metabolicand autoimmune conditions, encephalitis, after severeadverse reactions to medications and sudden withdrawalfrom benzodiazepines. It may be caused by decreasedcentral dopaminergic activity from psychiatric, toxic, med-ical, or unknown origin.

PROGNOSIS: Chronic patients may survive with support-ive care, but usually succumb to infection or organ failure.The underlying structural causes of MCS are irreversible.Given these limitations, functional outcome can vary. Pa-tients may return to vegetative state. The patient’s family,physicians, and nurses may benefit from sensitive and ex-tensive discussions. They may seek input from an ethicscommittee.

TREATMENT: Supportive care is usually initially providedin an ICU. With enduring states, when the patientsmay not require ventilation support, it can be provided


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in intermediate care units or high-level chronic careunits.

This EEG shows marked suppression over the left hemi-sphere and medium- to high-voltage mixed activity withslowing over the right hemisphere. As noted above, EEGsin patients with MCS can show a variety of patterns.

REFERENCES:




4. Fins JJ, Master MG, Gerber LM, Giacino JT. The minimallyconscious state. Arch Neurol 2007;64(10):1400–1405.

5. Kampf A, Schmutzhard E, Franz G, Pfausler B, Haring H-P,Ulmer H, Felber S, Golaszewski S, Aichner F. Prediction ofrecovery from post-traumatic vegetative state with cerebralmagnetic-resonance imaging. Lancet 1998;351:1763–1767.



8. Cartlidge N. States related to or confused with coma. J Neu-rol Neurosurg Psychiatry 2001;71(Supplement 1):i18–i19.


10. Young GB. Major syndromes of impaired consciousness. In:Young GB, Ropper AH, Bolton CF (eds.), Coma and ImpairedConsciousness: A Clinical Perspective. New York: McGraw-Hill 1998:39–78.

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33. Catatonia—psychogenic unresponsiveness/conversion disorder [1–5]

ER, Psychiatry

CLINICAL CORRELATES: Often the patients’ eyes areclosed and resist opening. Limb tone may be normal orincreased without spasticity. There are few if any sponta-neous limb movements, particularly when the patient isunder direct observation. Reflexes are normal and thereare no Babinski reflexes. Patients may not react to noxiousstimuli. Brainstem reflexes are intact.

ETIOLOGY: These include psychogenic unresponsivenesswith a conversion reaction. It is occasionally seen withmalingerers or patients with Munchhausen syndrome.Organic causes include encephalitis, schizophrenia, andother psychiatric problems. Similar clinical states are seenwith serotonin and neuroleptic malignant syndrome, andin nonconvulsive status epilepticus (NCSE).

CLINICAL EVALUATION: Look for eye opening and an in-advertent conjugate shift in gaze around the room. Theremay be stereotyped movements, rigidity, or loss of motorfunction. With catalepsy (waxy flexibility), patients canhold rigid and unusual poses for hours (“arm stays sus-pended in the air after the examiner lifts it up”). Thepatient may resist movement (gegenhalten). There maybe nonsense speech or repeat statements. Avoid painfulstimuli beyond routine noxious input such as from salinedrops to elicit corneal responses, cotton swab for in-tranasal stimulation to look for facial grimacing, and plan-tar responses. Deep nail-bed pressure is unwarranted. Inunclear cases, caloric stimulation has been used.

ANCILLARY TESTING: Usually the diagnosis is suspected.For unclear cases, assess for the other clinical states, andthence the respective underlying etiologies. In atypicalcases of drug toxicity or encephalitis, tests for these

should be considered. Imaging is rarely informative.Sodium amytal “interview” has been used in the past.For the differential diagnosis of serotonin or neurolepticmalignant syndromes, consider obtaining a toxin screen,CPK, and liver enzymes. Suggest a psychiatry consulta-tion.

DIFFERENTIAL DIAGNOSIS:

Some operational definitions of other states of prolongedunresponsiveness are as follows:

Coma—A clinical state of eyes-closed unresponsivenessfrom which the patient cannot be aroused (distinctionfrom sleep) without purposeful response to externalstimuli.

Vegetative state—Awake (eyes open) but unconscious.Locked-in syndrome—De-efferented state: awake, con-

scious, but minimal evidence of reaction to externalinput (vertical or horizontal eye movements to ques-tions).

Clinical—Consider neuroleptic malignant syndrome,serotonin syndrome, lithium, baclofen toxicity, NCSE.Also, think of locked-in-syndrome, persistent vegeta-tive state, or a minimally conscious state.

EEG—The EEG in psychogenic cases shows a reactivewaking alpha pattern. In NCSE, there is seizure activityon the EEG. Periodic lateralized epileptiform dischargesand other periodic discharges may be seen with en-cephalitis, multifocal brain disease, recent seizures, andconfusional states after a stroke or structural brainlesion with seizures. Patients with encephalitis mayshow diffuse slow EEG activity. Drug toxicities andthe neuroleptic malignant syndrome may have tripha-sic waves on EEG. Some cases of conversion reactionor psychogenic unresponsiveness respond to benzodi-azepines, amobarbital, or zolpidem.


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DISCUSSION: Patients with psychogenic unresponsive-ness often trigger neurology consults. As noted above,although there are varying levels of cooperation and re-sponse to external cues, the patient may exhibit waxyrigidity, be strikingly impervious to stimuli, but occasion-ally show rapid directed conjugate eye movements.

This EEG shows normal waking, posterior, alpha activitythat is reactive to eye opening and closure.

REFERENCES:

1. Valenstein M, Maltbie A, Kaplan PW. Catatonia in the ED.Ann Emerg Med 1985;14:359–361.

2. Bush G, Fink M, Petrides G, Dowling F, Francis A. CatatoniaII. Treatment with lorazepam and electroconvulsive therapy.Acta Psychiatr Scand 1996;93:137–43.

3. Swartz CM, Bottum KM, Salazar LS. Suppression of catatonia-like signs by lorazepam in nonconvulsive status epilepti-cus without seizure termination. Am J Geriatr Psychiatry2002;10:348–350.

4. Ono Y, Manabe Y, Hamakawa Y, Omori N, Abe K. Steroid-responsive encephalitis lethargic with malignant catatonia.Intern Med 2007;46:307–310.

5. Suzuki K, Miura N, Awata S, Ebina Y, Takano T, Honda T,Shindo T, Matsuoka H. Epileptic seizures superimposed oncatatonic stupor. Epilepsia 2006;47:793–798.

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34. Somatosensory evoked potential prognosis inanoxic coma [1–8]

CICU, MICU, Burns ICU, SICU, Ward

CLINICAL CORRELATES: When somatosensory evokedpotentials (SSEPs) are used for prognosis, the patientshould be in coma, and have no purposeful movementor posturing. There may be preservation or absence ofbrainstem reflexes.

ETIOLOGY: For prognostication, SSEPs are most reliableafter CRA/anoxia and then after head trauma.

CLINICAL EVALUATION: Examine brainstem reflexes andassess Glasgow coma scale. Obtain cause of coma.

ANCILLARY TESTING: EEG, CT, or MRI; protein S-100B(S-100B); neuron-specific enolase. Consider toxicologyscreen, although benzodiazepines rarely suppress corti-cal responses completely.

DIFFERENTIAL DIAGNOSIS: Clinical context isparamount. The absolute prognostic value lies onlywith CRA or anoxia. The value in head trauma is lessabsolute—see below. Ensure that the patient is incoma and ascertain the cause before providing clinicalcorrelation and prognosis. Severe nonstructural causesof coma may impair cortical SSEP responses. Also,mechanical interruption of ascending SSEP volley mayoccur at the cervical level in an awake patient, as maysevere peripheral neuropathies (e.g., diabetic).

PROGNOSIS: SSEPs are often used after EEG and in con-cert with the clinical examination to provide clinical infor-mation on the degree of anatomic pathway impairment,and to provide prognosis.

a. In post-CRA/anoxic coma, meta-analysis has con-firmed the 100% predictive value of a negative out-

come (persistent vegetative state or death) if N20s areabsent. See above caveats.

b. For head trauma, prognosis is unclear. Some pa-tients may recover [2], but absent N20 still indicatesa poor outcome—100% if bilaterally absent. Con-versely, a bilaterally normal SSEP and brainstem au-ditory evoked potentials (BAEP) indicated a Glasgowoutcome score of 4 or 5 (good outcome) with a posi-tive predictive value of 98% in 100 patients [3]. Corti-cal N20 prolongation progressively occurs with brain-stem herniation from raised Intracranial pressure (ICP)[5]; others disagree.

c. In central nervous system-depressant drug poison-ing (overdose with amitriptyline, meprobamate, bar-biturates, and nitrazepam), N20 can be delayed anddispersed, but not abolished, and distinguishes toxicfrom “therapeutic” coma [4].

d. With anesthesia (propofol, isoflurane, and nitrous ox-ide), N20 amplitudes may be reduced, but are notabolished [6].

e. In nonanoxic, nonstructural coma, prognosis is highlyvariable, but better than trauma or anoxia; data arefew. Hepatic coma, with cerebral edema and a raisedICP, abolished the cortical N20, with a fatal outcome[7].

f. In poor-grade subarachnoid hemorrhage (SAH) pa-tients after aneurismal surgery, bilateral N20 absencewas fatal [8].

This SSEP study shows a peripheral response from thestimulus, a response at Erb’s point (as the afferent volleygoes past the recording electrode—N9), a near-field po-tential N13 as the impulse enters and turns cephalad atthe cervical dorsal route entry zone, and subcortical (far-field) P13/N18 potentials probably arising from thalamicor thalamocortical structures. There is no cortical N-20potential after stimulation of each side. This indicates ab-sence of cortical somatosensory activity.


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The validity of SSEPs during myoclonic postanoxic sta-tus is not clear. It is best to study patients with a Glasgowcoma scale 3–5.

REFERENCES:


2. Sleigh JW, Havill JH, Frith R, Kersel D, Marsh N, Ulyatt D. SSEPsin severe traumatic brain injury: A blinded study. J Neurosurg1999;91:577–580.

3. Morgalla MH, Bauer J, Ritz R, Tatagiba M. Coma. The prog-nostic value of evoked potentials in patients with traumaticbrain injury (in German). Anaesthesist 2006;55:760–768.

4. Rumpl E, Prugger M, Battista HJ, Badry F, Gerstenbrand F,Dienstl F. Short latency SSEPs and BAEPs in coma due to CNS

depressant drug poisoning. Electroencephalogr Clin Neuro-physiol 1988;70:482–489.

5. Reisecker F, Witzmann A, Loffler W, Lebhuber F, Deisen-hammer E, Valencak E. SSEPs in comatose patients: Com-parison with clinical findings, EEG and prognosis. EEGEMG Z Elektroenzephalogr Elektromyogr Verwandte Geb1985;16(2):87–92.

6. Clapcich A, Emerson RG, Roye D, Xie H, Gallo EJ, DowlingKC, Ramnath B, Heyer EJ. The effects of propofol, small-doseisoflurane and nitrous oxide on ortical somatosensory evokedpotential and bispectral index monitoring in adolescents un-dergoing spinal fusion. Anesth Analg 2004;99:1334–1340.

7. Yang SS, Chu NS, Wu CH. Disappearance of N20 and P25components of SSEP and ominous sign in severe acute hep-atitis. J Formos Med Assoc 1993;92:46–49.

8. Ritz R, Schwerdtfeger K, Strowitzki M, Donauer E, KoenigJ, Steudel WI. Prognostic value of SSEP in early aneurysmsurgery after SAH in poor grade patients. Neurol Res2002;24:756–764.

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35. Somatosensory evoked potential prognosis inhead trauma

NICU, MICU, SICU

CLINICAL CORRELATES: For coma prognosis the patientshould be in coma, eyes-closed, and have no purposefulmovement. There may be posturing and preservation orabsence of brainstem reflexes.

ETIOLOGY: Head trauma.

CLINICAL EVALUATION: Examine brainstem reflexes andassess Glasgow coma scale. Obtain cause of coma.

ANCILLARY TESTING: EEG, CT, or MRI for review of theextent of central nervous system trauma, herniation, andedema. Consider tox screen.

CLINICAL CONSIDERATIONS: After closed head injury(CHI), there are various combinations of somatosensoryevoked potential (SSEP) abnormality, sustained from di-rect and countercoup cerebral and brain stem injury, brainedema, intracerebral, subdural and subarachnoid hemor-rhage, diffuse axonal injury (DAI), effects of anesthesia,spinal cord trauma and loss of peripheral SSEP input fromperipheral nerve, brachial plexus, and afferent radicularavulsion. Close clinical correlation is needed to avoid over-interpretation of SSEP deficits.

DIFFERENTIAL DIAGNOSIS: Clinical context isparamount. Ensure that technical and peripheralfactors do not account for absent responses, for ex-ample, avulsion of nerve routes, cervical compromise(tetraplegia). Determine if the accident was unwitnessed,

whether hypoxia and hypotension might have occurred(see coma with anoxia). Anesthetics and sedativesprolong N20 latencies but do not abolish them.

PROGNOSIS [1–5]: Cortical responses may be obtaineddown to a core body temperature of 28◦C. A reliable ab-solute prognostic value of SSEPs with head trauma (with-out anoxia or hypotension) is seen only with sustainedbilateral absence of N20 potentials (poor outcome), orconversely a preserved N20 with little prolongation. Sus-tained bilaterally absent N20 has been reported to be100% poor outcome [3]. Good Glasgow outcome scoreis seen with bilaterally normal SSEPs and BAEPs (positivepredictive value 98% in 100 patients) [1]. Reversible, bi-lateral absence of cortical potentials can occur from acircumscribed contusion [2], but is rare. Initial SSEPs cor-relate with long-term outcome in CHI with DAI—bilateralabsent N20s predicted death in 100% [4]. Blinded andunblinded studies support this prognostic value [3,4]. N20prolongation progressively occurs with brainstem hernia-tion from raised ICP [5]; others report that ICP does notcause SSEP deterioration, but that it is due to deteriora-tion of brain function.

This SSEP study shows a peripheral response from thestimulus at the wrist, a response at Erb’s point (as theafferent volley goes past the recording electrode—N9), anear-field potential N13 as the impulse enters and turnscephalad at the cervical dorsal route entry zone, andsubcortical (far-field) P14/N18 potentials probably arisingfrom thalamic or thalamocortical structures.


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REFERENCES:

1. Morgalla MH, Bauer J, Ritz R, Tatagiba M. Coma. The prog-nostic value of evoked potentials in patients with traumaticbrain injury (in German). Anaesthesist 2006;55:760–768.

2. Pohlmann-Eden B, Dingenthal K, Bender HJ, Koelfen W. Howreliable is the predictive value of SEP patterns in severe braindamage with special regard to the bilateral loss of corticalresponses? Int Care Med 1997;23:301–318.

3. Sleigh JW, Havill JH, Frith R. Kersel D, Marsh N, Ulyatt D. SSEPsin severe traumatic brain injury: A blinded study. J Neurosurg1999;91:577–580.

4. Claassen J, Hansen H-C. Early recovery after closed trau-matic head injury: SSEPs and clinical findings. Crit Care Med2001;29:494–502.

5. Konasiewicz SJ, Moulton RJ, Shedden PM. SSEPs and ICP insevere head injury. Can J Neurol Sci 1994;21:219–226.

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Section C: Evoked potentials in consultative neurology

Evoked potentials involve laboratory or bedside testingof central nervous system function by stimulating end-organs (for vision, hearing, or sensation) and collectingsummated averages of the brain’s responses.

Visual evoked potentials

Visual evoked potentials (VEPs) are the easiest, take lessthan 20 minutes in the cooperative patient, and can beused to detect demyelination in vision from one or theother eye. In hysterical blindness, VEPs can establish (evenin an uncooperative patient with closed eyelids) that lightcan travel from each eye to the visual cortex, and this testtoo can take less than an hour. Longer latency cognitivepotentials are more difficult to set up and are little usedclinically at present.

Brainstem auditory evokedpotentials

Brainstem auditory evoked potentials (BAEPs) delivers“clicks” or tones via tubal ear inserts or headphones tothe eardrum. These studies can also assess brainstem de-myelination and have been used to assess potential sur-vivability from irreversibility or partially reversible damageto the brainstem from anoxia, cardiac arrest, or trauma. Inthis function, they are less used than are somatosensoryevoked potentials (SSEPs). If all responses beyond waveI are absent in a comatose patient after cardiac arrestwithout known deafness or peripheral hearing loss, theyare a reliable prognostic indicator of death or persistentvegetative state (PVS).

BAEPs using longer latency responses at about 70 or100 ms after the auditory stimulus, “oddball” stimuli,or mismatched negativity are being increasingly studied.

In these paradigms the time window for summated andaveraged acquisition is lengthened to encompass thesedelayed responses. Because these potentials probablyrepresent higher orders of cognitive processing (andawareness), they are being explored as surrogates of con-sciousness or awareness. Investigators have found themto be useful in differentiating awake patients after un-derwater anoxia who may either evolve to consciousnessor conversely remain in a PVS.

Somatosensory evoked potentials

SSEPs, typically responses obtained from median nervestimulation (in the arm), can be used to delineate wherethere is a peripheral interruption of input at the brachialplexus in plexus avulsion (trauma), for investigating pyra-midal pathway impairment in the neck and brainstem,and to test for possible demyelination along the ascend-ing somatosensory pathway. Perhaps most frequently inthe inpatient hospital setting, SSEPs are used to evaluateprognosis after anoxic coma.

In coma, SSEPs play a special role in firmly establish-ing a poor or negative outcome. After CRA, the absenceof cortical responses accurately predicts a nonreturn toconsciousness with 100% accuracy. Unconscious patientsmay deteriorate and die, or enter an unconscious vege-tative state. Outcome after head trauma can also be as-sessed accurately with SSEPs. Conversely, and not surpris-ingly, reversible causes of coma are not prognosticatedwell by this test—cortical responses in SSEPs persist incomatose, anesthetized patients and many patients withtoxic or metabolic coma.

The handbook will examine particular patient “scenar-ios” and problems that would prompt neurological con-sultation, and meld in the electrophysiological findingsinto a diagnosis or prognosis where most applicable.

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36. Somatosensory evoked potentials in midbrainlesion—absent cortical responses

CLINICAL CASE: A 44-year-old woman with hyperten-sion, severe headache, and seizures became unresponsiveto stimuli. Examination revealed a comatose patient, withclosed eyes, and pupils fixed at 5 mm. There were no doll’seyes responses, corneal reflexes, response to nasal stim-ulation or gag, and no spontaneous respiration. Imagingrevealed an intracerebral hemorrhage in the pons andmidbrain.

COMMENT: With the absence of most brainstem reflexes,the presence of an irreversible cause of coma, and SSEPsshowing no conduction beyond the midbrain, the inten-sive care physicians met with the family. Together theyelected to withdraw care.


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Section C: Evoked Potentials in Consultative Neurology 99

This median nerve SSEP shows evidence of bilateralascending somatosensory signal through the brachialplexus Erb’s point (N9), progressing through the cervi-cal dorsal root entry zone (N13), and producing evidenceof far-field projections from subcortical, medial lemniscal

somatosensory regions (P13/N18). There was no evidenceof further signal reaching the somatosensory cortex (ab-sent N20). This corresponded to the CT head scan, whichshowed an intracranial hemorrhage in the midbrain andpons.

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37. Somatosensory evoked potentials in diffusecortical anoxic injury—absent corticaland subcortical responses [1]

CLINICAL CASE: A 26-year-old woman was found in car-diac arrest after a drug overdose. She was pulseless, ap-neic, and had dilated pupils. In the ICU, examination re-vealed no spontaneous or evoked movements and shehad no brainstem reflexes.

COMMENT: With the absence of brainstem reflexes, witha history of a documented anoxic/ischemic cause of

coma, and with evidence from median nerve somatosen-sory evoked potentials (SSEPs) showing no conduction tocortical structures above the midbrain (absent N20 re-sponses), there was no possibility of return to conscious-ness. The intensive care physicians met with the familywho elected to withdraw care.


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This median nerve SSEP shows evidence of bilateralascending somatosensory signal through the brachialplexus (N9), progressing through the cervical dorsal rootentry zone (N13), and evidence of far-field projectionsfrom subcortical, medial lemniscus somatosensory re-gions (P14/N18), but no evidence of the stimulus reachingthe somatosensory cortex (absent N20).

The EEG showed spindle activity over the frontal re-gions bilaterally.

REFERENCE:

1. Zandbergen EGJ, Hijdra A, Koelman JHTM, Hart AAM, VosPE, Verbeek MM, de Haan RJ. Prediction of poor outcomewithin the first three days of post anoxic coma. Neurology2006;66:62–68.

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38. Somatosensory evoked potentials in prolongedcardiac arrest—absence of all waves above thebrachial plexus [1,2]

CLINICAL CASE: A 52-year-old man was found in asystoliccardiac arrest after a drug overdose. In the cardiac inten-sive care unit (CICU), examination revealed no sponta-neous or evoked movements, and no brainstem reflexes.

COMMENT: This patient had no evidence of cortical orbrainstem function by clinical examination. The absence

of cortical responses on median nerve somatosensoryevoked potentials (SSEPs) helped the family come to adecision with the CICU physicians on the withdrawal ofcare. Absent SSEP cortical responses appear to play akey role in the decision-making process for withdrawalof care.


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This median nerve SSEP shows evidence of bilateral as-cending somatosensory signals only through the brachialplexus at Erb’s point (N9) and the cervical dorsal root en-try zone (N13) on the left. In contrast to the prior study,there is no evidence of conduction through subcorticalor cortical regions (neither P14/N18, nor N20 responses).On the right, there is no conduction above the brachialplexus under Erb’s point.

REFERENCES

1. Zandbergen EGJ, Hijdra A, Koelman JHTM, Hart AAM, VosPE, Verbeek MM, de Haan RJ. Prediction of poor outcomewithin the first three days of post-anoxic coma. Neurology2006;66:62–68.

2. Geocadin RG, Buitrago M, Torbey MT, Chandra-Strobos N,Williams A, Kaplan PW. Neurological prognostication andwithdrawal of life sustaining therapies in patients resuscitatedfrom cardiac arrest. Neurology 2006;67:105–108.

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39. Somatosensory evoked potentials after prolongedcardiac arrest—absence of all responses exceptcervical N9 [1,2]

CLINICAL CASE: A 36-year-old man with cardiac diseasehad a pulseless cardiac arrest. In the ICU, he had nobrainstem reflexes, no response to noxious stimuli, andno spontaneous movements. Head CT showed markeddiffuse cerebral edema with effacement of all cerebraland cerebellar sulci, superior spinal canal, fourth ventricle,and tectal and suprasellar cisterns. The EEG showed aGrade V pattern postanoxic coma grade, with little if anylow-voltage cortical activity, at 2–4 µV.

COMMENT: With the absence of brainstem reflexes,a documented anoxic/ischemic cause of coma, andsomatosensory evoked potentials (SSEPs) showing noresponses above the brachial plexus, the probability forreturn to consciousness was zero. In this study, all conduc-tion above the cervical dorsal root entry zone was abol-ished. The intensive care physicians met with the family,who elected to withdraw care.


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This median nerve SSEP shows evidence bilaterally ofascending somatosensory signal through the brachialplexus (N9) only. There is no evidence of signal throughstructures cephalad to the brachial plexus. Hence, therewas no response from the cervical dorsal root entry zone,subcortical and cortical somatosensory pathways.

REFERENCES:

1. Zandbergen EGJ, Hijdra A, Koelman JHTM, Hart AAM, VosPE, Verbeek MM, de Haan RJ. Prediction of poor outcomewithin the first three days of post anoxic coma. Neurology2006;66:62–68.


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40. Somatosensory evoked potentials—median andtibial after traumatic spinal cord injury

CLINICAL CASE: A 22-year-old woman sustained a gun-shot wound to the neck. Examination revealed a flaccidtetraplegia, retained facial and neck muscle movements,and the absence of sensation below the neck. The headCT was normal. Neck CT revealed a hematoma and bonefragments in the vertebral canal at C5. A neck CT an-

giogram showed patent vertebral and carotid arterieswithout evidence of arterial dissection.

COMMENT: Together, these studies revealed the total so-matosensory interruption in the neck, consistent with theflaccid tetraplegia. Surgery was not attempted.


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This set of median nerve somatosensory evoked poten-tials (SSEPs) shows no evidence (bilaterally) of ascendingsomatosensory signal beyond the brachial plexus (N9).The tibial nerve SSEP also revealed no evidence of re-

sponses cephalad to the popliteal fossa (PF); lumbar (LP)potentials could not be obtained. Together, the studiesreflect the total transection of cuneate and gracile as-cending somatosensory pathways in the neck.

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41. Visual evoked potentials in worsening vision

CLINICAL CASE: A patient with a prior history sugges-tive of multiple sclerosis and several episodes of relapsingand remitting neurological symptoms noted the suba-cute onset of blurring of vision in her right eye. Examina-tion revealed right optic disc pallor and diminished visualacuity.

COMMENT: Visual evoked potentials (VEPs) have foundtheir principal use in the documentation of demyelina-tion in the anterior optic pathway in multiple sclerosis(MS) [1]. Papilledema typically does not produce changesin latency or amplitude unless there is actual or pend-ing visual loss. Compression of the anterior visual path-ways and intrinsic optic nerve tumors may distort the VEPwaveform morphology, but usually produces less latencydelay than with demyelination [2, 3]. Clearly, the besttesting modality for such lesions is MRI. Several other dis-eases may have inconsistent findings, including albinism(decreased amplitude, but without latency change), al-coholism and Wernicke–Korsakoff syndrome, and pro-longation in chronic demyelinating polyradiculopathy [4].Some delay in patients with diabetes may be resemble thechanges seen in MS. Head injury and raised intracranialpressure may also affect VEPs [4], but VEPs have not beenused much for these problems. VEPs can be used to moni-tor leukodystrophies. With adrenoleukodystrophy [5] andvitamin E deficiency in cystic fibrosis [6], VEPs have beenused to monitor worsening, or conversely, the improve-ment with therapy. A cortical response after stimulationwith light-emitting diode goggles may be helpful in thediagnosis (or not) of hysterical blindness.

This VEP, performed with small and then large checksizes, demonstrates delayed latencies of the P100 to120–122 ms on the right, compared with 99–100 mson the left, with a laboratory norm of 108 ms ±3 SDs.The right side is clearly delayed, reflecting demyelinationof the right anterior optic pathway (consistent with rightoptic neuritis and a recurrence of MS).

REFERENCES:

1. Brooks EB, Chiappa KH. A comparison of clinical neuro-ophthalmological findings, and pattern-shift visual evokedpotentials in multiple sclerosis In: Courjon J, Maugiere F, RevolM (eds.), Clinical Applications of Evoked Potentials in Neurol-ogy. New York: Raven Press 1982.

2. Kupersmith MJ, Siegel IM, Carr RE, Ransohoff J, Flamm E,Shakin E. Visual evoked potentials in chiasmal gliomas in fouradults. Arch Neurol 1981;38:362–365.

3. Haliday AM, McDonald WI, Mushin J. Visual evoked re-sponses in the diagnosis of multiple sclerosis. Br Med J1973;4:661–664.

4. Chiappa KH (ed.), Evoked Potentials in Clinical Medicine, 2ndedn. New York: Raven Press 1990;645.

5. Kaplan PW, Tusa RJ, Shankroff J, Heller J, Moser HW. Visualevoked potentials in adrenoleukodystrophy: A trial with glyc-erol trioleate and lorenzo oil. Ann Neurol 1993;34:169–174.

6. Kaplan PW, Rawal K, Erwin CW, D’Souza BJ, Spock A. Vi-sual and somatosensory evoked potentials in vitamin E de-ficiency with cystic fibrosis. Electroencephalogr Clin Neuro-physiol 1988;71:266–272.


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Left VEP measurements

Left VEP measurements

Right VEP measurements

Right VEP measurements

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42. Brainstem auditory evoked potentials—inworsening hearing

CLINICAL CASE: A patient with a history of multiple scle-rosis and episodes of relapsing and remitting neurologicproblems complained of sudden decrease in hearing onthe left. Examination revealed decreased perception ofnoise in the left ear.

COMMENT: Brainstem auditory evoked potentials (BAEPs)have been used in evaluation of cerebellopontine angletumors, acoustic neuromas, intrinsic brain stem lesions,and MS. For these indications, BAEPs have largely beensuperceded by brain MRI. In addition to other audiologictests, BAEPs have been useful in evaluating the effects ofototoxic drugs.

In coma and brain death, BAEPs are used to supple-ment the clinical examination and other electrophysiolog-ical studies, such as somatosensory evoked potentials andthe EEG. Regarding hearing, peripheral causes (cochlearand 8th nerve disorders) have little effect on BAEP laten-cies. In MS, BAEP abnormalities are often associated withnormal hearing. In one series, 45% of MS patients withabnormal BAEPs had unilateral BAEP abnormalities [1],usually ipsilateral to the side of the lesion. With all theabove caveats, BAERs can be used to document or inves-tigate changes in waveforms, thus reflecting quantitativefunction changes in the brainstem peripheral and cen-tral auditory pathways. Wave I–III delay is most sensitiveto acoustic neuromas, and if normal can obviate a brainMRI [2]. In MS patients with nonbrainstem disease man-ifestations, BAEPs when abnormal can help by signaling

abnormalities in the brainstem, thus helping further de-fine the disease and signal multiple anatomical diseasesites. If the clinical history, imaging, or cerebrospinal fluidis inconclusive, BAEPs might indicate objective evidenceof brainstem involvement.

Finally, BAEPs enable the monitoring of treatmenteffects or disease progression. With MS, most abnor-malities involve wave V amplitude (87% of cases),the II–V interval (superior olivary nucleus and inferiorcolliculus). Occasionally, rarefraction clicks can distin-guish affected cases [3]. BAEPs may follow the clin-ical progression/regression of central pontine myeli-nolysis [4], metachromatic and adrenoleukodystrophy,Pelizaeus–Merzbacher disease, and other hereditary de-generative central nervous system disorders [2], and mayhelp (when normal) distinguish toxic/metabolic comafrom brainstem causes.

In head injury and raised intracranial pressure, BAEPshave had variable success among different patient seriesin predicting outcome. In suspected severe brain dysfunc-tion, BAEPs may be used to follow comatose patients inwhom anesthetic agents or raised ICPs complicate theinterpretation of the clinical comatose state [4].

In infants, BAEPs are used as a screening tool for hear-ing defects in infants at-risk, such as after bacterial menin-gitis, exposure to ototoxic drugs, kernicterus, and prema-turity. Testing has been advocated on all ICU infants priorto discharge and in developmentally delayed infants andchildren who may be blind or deaf.


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II

II III

III

V

V

V

V

c

1

5

7

6

4

3

2

rT

1.5N: 3000

msµV

3000msµV

0.5

1.5N: 3000

msµV0.5

1.5N: 3000

msµV0.5

1.5N:

0.5

I

I

VV

V

This BAEP shows normal peaks I–V ipsilateral to the rightear stimulation (bottom two tracings). On the left (uppertwo traces), the peaks are less well defined, peak III isnot seen, and there is prolongation of the I–V interpeakinterval. This indicates prolongation in the pons-midbrainregion. These results support brainstem demyelination asthe locus for hearing loss and hence a further exacerba-tion of MS.

REFERENCES:

1. Chiappa KH, Harrison JL, Brooks EB, Young RR. Brainstemauditory evoked responses in 200 patients with multiple scle-rosis. Ann Neurol 1980;7:135–143.

2. Chiappa KH. Evoked Potentials in Clinical Medicine, 2nd edn.New York: Raven Press 1990.

3. Emerson RG, Brooks EB, Parker SW, Chiappa KH. Effects ofclick polarity on brainstem auditory evoked potentials in nor-mal subjects and patients: Unexpected sensitivity of wave V.Ann N Y Acad Sci 1982;388:710–721.

4. Stockard JJ, Sharbrough FW. Unique contributions of short-latency somatosensory evoked potentials in patients withneurological lesions. Prog Clin Neurophysiol 1980;7:231–263.

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PART 4

Peripheral nervous system disease

Section A: Weakness and/or respiratory failure in ICU andon the ward

Generalized somatic weakness and respiratory failure arecommon manifestations of neuromuscular disorders inthe ICU and on the ward. Weakness has a wide differ-ential diagnosis and may present a major challenge tothe consulting clinician. The most common ICU-acquiredneuromuscular disorder is critical illness neuromyopa-thy (Case 43), while prolonged neuromuscular junctionblockade and rhabdomyolysis are fairly rare causes. Otherneuromuscular disorders such as myasthenia gravis, mo-tor neuron diseases, and inflammatory myopathies maycause weakness in ICU patients, but these and othersimilar disorders often occur outside the ICU and mayeventually lead to ICU admission. In floor patients, weak-ness and respiratory failure usually involves neuropathies,radiculopathies and less frequently myopathy, myositis,vasculitis, and the effects of malignancy. ALS is not rare.Nonetheless, most floor consults are on patients withweakness after prolonged illness due to general debility,bed rest, and lack of mobility. A careful, detailed med-ical history and examination are essential to diagnosingneuromuscular disorders and the proper interpretationof ancillary tests such as electrodiagnostic studies. Thegoals are to determine whether the disease is acquiredor inherited, to identify whether the process is focal(i.e., mononeuropathies or radiculopathies) or general-ized (polyneuropathies or myopathies), and to localize theaffected neurologic regions (i.e., brain/spinal cord, nerveroot, plexus, nerve, neuromuscular junction, or muscle).A systematic approach to the neurological examination iscrucial to discerning these details and is discussed below.Physical findings seen in various neurological disordersare summarized in Case 44.

Cranial nerve involvement can be helpful in narrow-ing the differential diagnoses. Cranial nerve dysfunctionis common in neuromuscular transmission disorders (i.e.,diplopia, ptosis, dysarthria, dysphagia, and bilateral facialweakness in myasthenia gravis) and motor neuron dis-

eases (i.e., dysarthria, dysphagia, and tongue weaknessin ALS). It is rare in neuropathies (with the exception ofbilateral facial weakness in patients with Guillain-Barresyndrome) and myopathies (with the exception of bilat-eral facial weakness which occurs in myotonic dystrophyand ophthalmoplegia in oculopharyngeal dystrophies andmitochondrial disorders).

Bedside manual muscle testing should always be per-formed and quantitated. The pattern of muscle weaknessmay be helpful. Weakness is proximal in most myopathiesand some motor neuron diseases, but it is distal in mostpolyneuropathies. Ptosis and extraocular weakness areseen in myasthenia gravis, oculopharyngeal dystrophy,and mitochondrial myopathies. Facial weakness is char-acteristic of facioscapulohumeral dystrophy, but may beseen in sarcoidosis or familial amyloidosis. Tongue weak-ness with atrophy and fasciculation occurs in motor neu-ron disease. Tongue weakness without fasciculations mayoccur in myasthenia gravis.

Muscle testing should try to determine whether weak-ness is accompanied by focal or generalized atrophy, orwhether there is lack of muscle atrophy. Neuromusculartransmission disorders and demyelinating neuropathiesusually do not cause muscle atrophy. Muscle fatigueduring repetitive motion suggests neuromuscular trans-mission disorders, although it can also occur in otherdiseases.

Increased muscle tendon reflexes or hyperreflexia indi-cates upper motor neuron dysfunction, as seen in spinalcord lesions and motor neuron diseases. Hyporeflexia in-dicates neuropathy, but may also be seen in Lambert-Eaton myasthenic syndrome and lower motor neuronforms of motor neuron diseases. Distal areflexia is char-acteristic of axonal neuropathies, but generalized are-flexia points to a demyelinating process. Hyporeflexiathat improves during repetitive motion can be observedin Lambert-Eaton myasthenic syndrome. A focal reflex

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114 Section A: Weakness and/or Respiratory Failure in ICU and on the Ward

loss with sensory deficit suggests a lesion in a particularnerve, plexus, or root. Reflexes are generally normal inmyopathies.

Sensory examination should include analysis of largemyelinated fibers (i.e., testing proprioception, vibratorysense, and in ambulatory ward patients, a Romberg test)and small fibers (i.e., pain and temperature sensation).Sensory complaints are characteristic of diseases affect-ing the sensory axons of peripheral nerves, plexus, ornerve roots. Isolated large fiber sensory loss may suggesta lesion in the dorsal columns (e.g., subacute combineddegeneration in vitamin B12 deficiency).

Coordination should be analyzed with the patient’seyes open and closed to look for sensory or cerebellarataxia.

Gait and posture testing where possible in ward pa-tients should be observed for lordosis (i.e., stiff-personsyndrome), a waddling gait (i.e., with myopathies), and asteppage gait (i.e., with polyneuropathies). The inabilityto rise from the floor or a chair suggests hip extensorweakness, whereas the inability to step up or down froma stool is consistent with a hip flexor or quadriceps mus-cle weakness. Clearly, these are not testable in most ICUconsults.

Electrophysiologic tests (i.e., nerve conduction stud-ies, electromyography, and repetitive stimulation tests)are valuable in diagnosing neuromuscular diseases (Case45). Electromyography (EMG) can establish a peripheralnervous system disorder versus a central nervous systemprocess (i.e., myelopathy) or psychogenic cause. It mayalso help differentiate among various peripheral nervoussystem disorders mentioned above. In addition to local-izing the anatomy of the abnormality, EMG may provideinformation that will further narrow the differential diag-nosis to a specific disease. Note that the time of onsetof EMG/nerve conductien velocities (NCV) changes willdepend on the distance and time needed for axonal de-generation to spread from the lesion to the muscle understudy. This typically requires 10–21 days for fibrillationsand positive waves to appear in the denervated muscle.For example, EMG and nerve conduction studies may helpdifferentiate a neuropathic process into a demyelinating,axonal, sensory, or a motor neuropathy, thus minimizingancillary investigations to the relevant diagnostic or con-firmatory tests. On some occasions, electrophysiologicaltesting can establish and follow the time course of dis-ease progression or regression and be used to follow theeffects of treatment.

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43. Causes of paralysis and respiratoryfailure in the ICU

1. Myelopathies2. ALS and other motor neuron disorders3. Guillain-Barre syndrome4. Toxic and vasculitic neuropathies5. Chronic inflammatory demyelinating polyneuropathy6. Porphyria7. Myasthenia gravis and, rarely, Lambert-Eaton myasthenic

syndrome and other myasthenic disorders8. Tick paralysis9. Botulism

10. Organophosphate poisoning11. Prolonged neuromuscular junction blockade12. Periodic paralysis13. Critical illness neuromyopathy14. Inflammatory myopathy15. Toxic myopathy and other causes of rhabdomyolysis16. Acid maltase myopathy17. Muscular dystrophies, congenital myopathy,

mitochondrial myopathy18. Endocrine and electrolyte imbalance


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44. The clinical evaluation of neuromuscular disorders

Characteristic MyelopathyMotor neurondisease Polyneuropathy

Diseases ofneuromuscularjunction Myopathy

Bulbar function Normal Opthalmoplegia,dysarthria,dysphagia in MG

Usually normal,but may be involvein Guillain-Barresyndrome

Dysarthria, dysphagia,and tongue weakness

Often normal, but mayinvolve myositis andcertain inheritedmyopathies

Pattern ofweakness

Variable,usuallysymmetric

Variable,symmetric inmost, but oftenasymmetric in ALS

Distal > proximal Proximal > distal,fluctuates, often involvesextraocular muscles

Proximal > distal

Muscle tone Increased Increased, butoccasionallydecreased

Decreased Normal Normal

Fasciculations Normal, butsometimes inspondyloticmyelopathy

Yes Sometimes No No

Deep tendonreflexes

Increased Variable,decreased in most,increased in ALS

Decreased orabsent

Normal in postsynaptic(myasthenia gravis),decreased in presynapticdisorders (Lambert-Eatonsyndrome and botulism)

Normal initially, may bedecreased in later stagewith severe weakness(ankle reflexes are oftenpreserved until very late)

Babinski’s sign Upgoingtoes

Upgoing toes Normal Normal Normal

Sensory loss Yes, oftensensory level

No, except inKennedy’s disease

Usually present No No

Pain Back pain No Often No Variable, usually noBowel/bladderdysfunction

Yes No No No No


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45. Laboratory evaluation of neuromuscular disorders

TestMotor neurondisease Polyneuropathy

Diseases ofneuromuscular junction Myopathy

Serum creatinekinase (CK) level

May be mildlyelevated

Normal Normal Increased

Nerveconductionstudies

Normal orlow-amplitudecompound muscleaction potential(CMAPs), normalsensory nerve actionpotential (SNAPs)

Slow nerve conductionvelocities orlow-amplitudeCompound muscleaction potential (CMAPs)and sensory nerve actionpotentials (SNAPs)

Normal Normal

Electromyography Decreased number ofmotor units (reducedrecruitment), acute orchronic denervation/re-innervation

Decreased number ofmotor units (reducedrecruitment), acute orchronic denervation/re-innervation

Normal, but may havevoluntary motor units withsmall amplitude and shortduration

Voluntary motor unitswith small amplitudeand short duration

Repetitive nervestimulation

Usually normal, butsmall decrementalresponses may occur

Normal Decrement of CMAP at lowrates of stimulation, largeincrement at fast rates inpresynaptic disorders(30–100% in Botulism;>200% in Lambert-Eatonmyasthenic syndrome(LEMS)); normal at fast ratesin presynaptic disorders(normal or <25% in MG)

Normal

Muscle biopsy Neurogenicdenervation,fiber-type grouping,group atrophy

Neurogenic denervation,fiber-type grouping

Normal Myopathic changes


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Section B: Segmental weakness and/or sensory loss

Segmental weakness and sensory loss are common com-plaints in neuromuscular disorders in the ward. Attemptsshould be made to characterize the pattern of weakness:generalized, asymmetric, multifocal, proximally, distally,or lower versus upper extremity (Case 46).

Certain patterns of muscle weakness point to a periph-eral nerve, plexus, or root lesion. With peripheral nervecauses, all muscles distal to the level of the lesion arevulnerable, but they are not necessarily equally affected.When multiple limb muscles are weak, localization de-pends on recognizing the common innervating nerve. Afocal neuropathy (i.e., radial nerve palsy) or spinal nerveroot lesion causes weakness limited to the distribution ofthe involved nerve or root. A complete plexopathy, suchas traumatic brachial plexopathy, may cause weakness ofthe entire limb. However, a partial lesion may cause weak-

ness only in the distribution of the affected plexus com-ponents. With some neuropathies, reflexes are typicallydecreased, often with sensory loss in the affected area.Anterior horn cell diseases often begin with focal weak-ness resembling a mononeuropathy, but will develop intoa more widespread pattern as the disease progresses, cul-minating in generalized weakness. With the exception ofextraocular muscle involvement in myasthenia gravis, it israre for neuromuscular junction disorders or myopathiesto cause focal weakness.

Electrophysiologic tests (i.e., nerve conduction stud-ies, electromyography, and repetitive stimulation tests)are particularly valuable in localizing focal and segmentaldisorders, such as radiculopathies and nerve entrapment.These should be used to supplement the history and ex-amination.

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46. Evaluation of segmental peripheralneurological disorders

Characteristic Mononeuropathy Plexopathy Radiculopathy

Pattern of weakness Weakness in muscles innervatedby a single nerve

Weakness in muscles innervatedby different roots and nerves

Weakness in muscles innervatedby the same root, but bydifferent nerves

Reflex Decreased reflexes in musclesinnervated by a single nerve

Decreased in muscles innervatedby roots from affected plexus,but by different nerves

Decreased in muscles innervatedby the same root, but bydifferent nerves

Sensory Follows a single nerve territory Follows patchy distribution ofmultiple roots and nerves

Follows the territory of theinvolved roots

Electromyography Denervation in musclesinnervated by a single nerve;normal paraspinous muscles

Denervation in musclesinnervated by multiple roots andnerves; normal paraspinousmuscles

Denervation in musclesinnervated by the same root, butby different nerves; denervationin the affected paraspinousmuscles

Sensory-evokedresponses

Low-amplitude and/orprolonged SNAP latency

Low-amplitude SNAP in nervesfrom the affected plexus

Normal SNAPs

Motor nerve studies Slow in affected nerve;low-amplitude CMAP orconduction block could be seen

Normal or low-amplitude CMAPin nerves from the affectedplexus

Normal or low-amplitude CMAPin nerves from the affectedplexus

Proximal responses(F-waves, H-reflexes)

Slow or absent in affected nerves Slow or absent in nerves fromthe affected plexus

Slow or absent in nerves fromaffected roots


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Section C: Respiratory failure/diffuse weakness

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47. Amyotrophic lateral sclerosis/motor neuropathy

CLINICAL CORRELATES: Slowly progressive limb weak-ness over weeks to months, hyperreflexia, dysphagia, fas-ciculation, respiratory symptoms, and intact sensations.

ETIOLOGY: Motor neuronopathy.

CLINICAL EVALUATION: Look for slowly progressive limbweakness that may be asymmetrical: dysphagia, fascic-ulation, atrophy, and pathologic hyperreflexia. Body andlimb sensations are normal.

ANCILLARY TESTING: Complete blood count, electrolytesincluding calcium and phosphate, liver function tests, thy-roid studies, creatine kinase, erythrocyte sedimentationrate, anti-nuclear antibody, rheumatoid factor, vitaminB12, anti-GM1 antibody, serum protein electrophoresiswith immunofixation, and 24-hour urine protein elec-trophoresis with immunofixation. Brain MRI wheneverbulbar disease is present. Cervical and lumbosacral spineMRI to evaluate lower motor neuron (LMN) disease in thearms and legs. Normal cerebrospinal fluid (CSF). Screen-ing for heavy metals in the blood and urine if there isknown occupational exposure. Lumbar puncture and CSFanalysis when there is clinical suspicion for Lyme dis-ease, HIV infection, chronic inflammatory demyelinat-ing polyneuropathy, or neoplasm. Sensory and motornerve conduction studies and electromyography (EMG)are a standard part of the evaluation of motor neurondisease [1].

DIFFERENTIAL DIAGNOSIS: Asymmetrical weakness sug-gests inflammatory myopathy, neuromuscular junctiondisorders (i.e., myasthenia gravis), thyrotoxicosis, acutepolyneuropathies, cervical spondylosis with nerve rootcompression, multifocal motor neuropathy (MMN), and

motor neuron diseases. Myopathies do not have theseEMG findings, asymmetrical weakness, and hyper-reflexia. Myasthenia gravis (MG) may clinically comprisedysarthria, dysphagia, and limb and facial weakness with-out ptosis or ocular dysmotility, and thus mimic bulbaramyotrophic lateral sclerosis (ALS). Upper motor neuron(UMN) or LMN bulbar signs, absence of ocular findings,and lack of diurnal variation of symptoms argue againstMG. Thyrotoxicosis may include UMN signs related topyramidal tract dysfunction and LMN signs related to aperipheral neuropathy and mimic ALS. MMN, also knownas MMN with conduction block, is characterized by LMNsigns often with a bibrachial pattern. Motor nerve con-duction studies in MMN usually often shows conductionblock (focal demyelination). Sensory conduction is nor-mal. Raised GM1 antibodies occur in 30–80% of patientswith MMN. UMN signs, diffuse acute or chronic denerva-tions, and the absence of conduction block would argueagainst MMN. Lack of history of polio argues against thiscause. The clinical hallmark of a selective motor deficit,the combination of UMN and LMN signs, asymmetricalweakness, bulbar involvement, and an EMG showingacute or chronic denervation/re-innervation in three ormore segments point toward ALS [2,3].

PROGNOSIS: ALS is a progressive neurodegenerative dis-order that causes muscle weakness, disability, and even-tually death, with a median survival of 3–5 years [4].While the rate of progression between individuals is vari-able, the history should reflect gradual and progressiveworsening over time without intervening remissions orexacerbations. The progressive course of ALS eventuallyproduces one or both of the life-threatening aspects ofthe disease, neuromuscular respiratory failure, and dys-phagia.

TREATMENT: There is no cure for ALS. Expert con-sensus guideline recommendations by the AmericanAcademy of Neurology [5] cover breaking the news of the


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Section C: Respiratory failure/diffuse weakness 123

Nerve and site

Sural.RPoint B 3.2 ms

4.1 ms

3.1 ms

14 µV

11 µV

17 µV

2.2 ms

2.5 ms

2.1 ms

105 mm

Motor nerve conduction

Sensory nerve conduction

Nerve and site

Peroneal.R

Peroneal.L

Median.R

Wrist

Wrist

Ulnar.R

Tibial.R

Tibial.LTibial.L

Ankle

Ankle

Ankle

Fibula (head)Popliteal fossa


NR ms

NR ms

5.4 ms

6.1 ms

5.4 ms

0.7 ms12.5 ms

3.0 ms4.6 ms

m/s

mm

1.2 mV

1.0 mV

1.2 mV

1.0 mV1.0 mV

2.1 mV2.6 mV

mV

mV

mm

mm

mm

mm

240 mm90 mm

mm90 mm

m/s

m/s

m/s

m/s

45 m/s50 m/s

m/s56 m/s

130 mm

110 mm

48 m/s

52 m/s

50 m/s

Lateral malleolus-Point B

Digit II (index finger)-Wrist

Digit V (little finger)-Wrist

Median.RWrist

WristUlnar.R

Peaklatency

Amplitude Segment Latencydifference

Distance Conductionvelocity

Latency Amplitude Distance Conductionvelocity

diagnosis, nutrition, respiratory management, palliativecare, and the use of riluzole. Respiratory managementand nutrition are important symptomatic issues facing pa-tients with ALS. Symptomatic management is the main-stay of treatment for ALS. Therapy should be offered in amultidisciplinary environment where physical therapists,occupational therapists, and speech therapists can assistwith the management of dysarthria, dysphagia, activitiesof daily living, and functional decline. Patients treatedby multidisciplinary ALS centers have improved survivalcompared with those followed by general neurology clin-ics. Only riluzole has been approved by the Food andDrug Administration for extending survival in ALS. Pa-tients most likely to benefit from riluzole include (1) ALSby El-Escorial criteria, (2) symptoms present for less than5 years, (3) vital capacity greater than 60% of predicted,and (4) no tracheostomy.

NCV: These sensory nerve action potentials are normal;right median and ulnar motor responses are absent. Bothtibial and right peroneal CMAP amplitudes are reduced.Concentric needle EMG examination shows diffuse acutedenervation (i.e., fibrillations and positive sharp waves).There are reduced or neurogenic recruitment and volun-tary motor units with long duration and large amplitude.Many motor units are polyphasic.

In general, the abnormalities are most marked inthe weak limbs, but may occur in asymptomatic limbs.Fasciculation potentials may be seen in asymptomaticlimbs.

In summary, acute or chronic denervation/re-innervation involving ventral nerve roots or spinal cord

segments. These findings are consistent with an activepolyradiculopathy (such as carcinomatous meningitis), adiffuse myelopathy, or progressive motor neuron disease.The absence of radicular pain and sensory deficit suggestsALS.

REFERENCES:

1. Daube JR. Electrodiagnostic studies in amyotrophic lateralsclerosis and other motor neuron disorders. Muscle Nerve2000;23:1488.

2. Brooks BR. El Escorial world federation of neurology criteriafor the diagnosis of amyotrophic lateral sclerosis. Subcommit-tee on motor neuron diseases/amyotrophic lateral sclerosisof the World Federation of Neurology Research Group onneuromuscular diseases and the El Escorial clinical limits ofamyotrophic lateral sclerosis workshop contributors. J NeurolSci 1994;124(Suppl):96.

3. Brooks BR, Miller RG, Swash M, Munsat TL; World Federationof Neurology Research Group on Motr Neuron Diseases. ElEscorial revisited: Revised criteria for the diagnosis of amy-otrophic lateral sclerosis. Amyotroph Lateral Scler Other Mo-tor Neuron Disord 2000;1:293.

4. Mitsumoto H, Chad DA, Pioro EP. Amyotrophic lateral sclero-sis. Contemporary Neurology Series, volume 49, Philadelphia,PA: FA Davis 1998;480.

5. Miller RG, Rosenberg JA, Gelinas DF, Mitsumoto H, NewmanD, Sufit R, Borasio GD, Bradley WG, Bromberg MB, BrooksBR, Kassrkis EJ, Munsat TL, Oppenheimer EA. Practice param-eter: the care of the patient with amyotrophic lateral sclerosis(an evidence-based review): Report of the quality standardssubcommittee of the American Academy of Neurology: ALSPractice Parameters Task Force. Neurology 1999;52:1311.

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48. Critical illness neuromyopathy

CLINICAL CORRELATES: Diffuse limb weakness, impairedsensation, and hyporeflexia. Failure to wean off ventilator.

ETIOLOGY: Neuropathy.

CLINICAL EVALUATION: For critical illness polyneuropa-thy/myopathy, look for [1] setting of critical illness such assepsis, multiorgan failure, and the systemic inflammatoryresponse syndrome [2], difficulty weaning from ventila-tor not related to cardiopulmonary causes [3], exposureto paralytic and/or steroids [4], and limb weakness (usu-ally the legs). Patients show facial expression to pain evenwhile the limbs cannot withdraw. There is relative spar-ing of cranial nerves, depressed or absent reflexes andelectrophysiologic evidence of axonal motor and sensorypolyneuropathy, or irritable myopathy.

ANCILLARY TESTING: Complete blood count, electrolytesincluding calcium and phosphate, liver function tests,thyroid studies, creatine kinase, erythrocyte sedimenta-tion rate, anti-nuclear antibody, rheumatoid factor, vita-min B12, serum protein electrophoresis with immunofix-ation, and 24-hour urine protein electrophoresis withimmunofixation. Brain MRI whenever bulbar disease ispresent. Cervical and lumbosacral spine MRI to evalu-ate lower motor neuron disease in the arms and legs.Anti-AChR and anti-MuSk antibodies. Rule out other neu-ropathic process including Guillain-Barre syndrome, por-phyria, and heavy metal intoxication. Sensory and motornerve conduction studies and electromyography (EMG)are a standard part of the evaluation of critical illnesspolyneuropathy.

DIFFERENTIAL DIAGNOSIS: See Table 48.1. Neuromuscu-lar transmission disorders manifest with ptosis, unrespon-

Table 48.1 Causes of paralysis and respiratory failure in ICU

1. Myelopathies2. ALS and othe motor neuron disorders3. Myasthenia gravis and rarely, Lambert-Eaton myasthic

syndrome an other myasthenic4. Tick paralysis5. Botulism6. Organophosphate poisoning7. Prolonged neuromuscular junction blockade8. Guillain-Barre syndrome9. Toxic and vasculitic neuropathies

10. Chronic inflammatory demyelinating polyneuropathy11. Porphyria12. Critical illness neuromyopathy13. Inflammatory myopathy14. Toxic myopathy and other causes of rhabdomyolysis15. Acid maltase myopathy16. Muscular dystrophies, congenital myopathy, mitochondrial

myopathy17. Endocrine and electrolyte imbalance

sive pupils, or ophthalmoplegia. Review of the patient’sdrug list will help to eliminate the possibility of toxic my-opathy or even exogenous toxins (organophosphates).The diagnosis is critical illness neuromyopathy. A musclebiopsy with myosin loss would be helpful in confirmingthe diagnosis.

PROGNOSIS: Mortality is approximately 26–71% depen-dent on the severity of the underlying primary disease[3]. Recovery can take months, with up to 50% of thepatients having complete recovery; many have persistentfunctional disability with reduced quality of life. Electro-diagnostic testing may demonstrate residual nerve dys-function several years after initial presentation [4].

TREATMENT: No specific therapy. Weaning of steroidsis recommended. Supportive management and


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Section C: Respiratory Failure/Diffuse Weakness 125

Nerve and site

Sural.L

Sural.R

Point B

Point B

3.5 ms

NR ms

NR ms

NR ms

NR ms

µV

µV

µV

µV

4 µV 2.5 ms

ms

ms

100 mm

mm

mm



Nerve and site

Peroneal.L

Peroneal.R

Median.L

Wrist

Wrist

Ulnar.L

Tibial.L

Tibial.LTibial.R

Ankle

Ankle

Ankle


AnkleFibula (head)Popliteal fossa

3.1 ms

3.2 ms

3.6 ms

4.7 ms

4.4 ms

14.2 ms16.5 ms

4.3 ms13.2 ms

49 m/s

mm

1.4 mV

1.4 mV

1.3 mV

0.5 mV0.4 mV

1.9 mV1.4 mV

6.8 mV

1.9 mV

mm

mm

mm

mm

Needle EMG data

Insertional

Deltoid MiddleBiceps BrachiiTriceps Med HGastroc Med HdTibialis AntTibialis AntGlut Med

RRRRRLL

NormalNormalNormalNormalNormalNormalNormal

1+NoneNoneNoneNoneNoneNone

1+1+NoneNoneNoneNoneNone

NoneNoneNoneNoneNoneNoneNone

SDMDMDNormMDNormSI

SDMDMDNormMDNormSI

NormNormNormNormNormNormNorm

Generic200 uV

Tria: ↑ Off Rate: Hz

10:49:1910 msAmp: 1, 20–10kHz


EARLY

ActivationActivation

RateConfigDurationAmplitudeFasc+WaveFibsIns Act

EARLYEARLYNormNormNormNorm

250 mm100 mm

mm290 mm

m/sAntecubital 8.4 ms 230 mm4.9 mV 49 m/s

m/s

m/s

m/s

40 m/s43 m/s

m/s39 m/s

15.2 ms 1.3 mV 80 mm 40 m/s

40 m/s

m/s

m/s

ms mm m/s

ms mm m/s



Wrist-Digit II

Wrist-V Digit

Dorsum of hand-Forearm

Median.LDigit II

V Digit

Radial.LForearm

Ulnar.L

Peaklatency



Latency Amplitude Distance Conductionvelocity

200 uV 1.- 5 ms

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126 Section C: Respiratory Failure/Diffuse Weakness

rehabilitation are required—intensive pulmonary hygieneand prevention of skin breakdown, contractures, anddeep vein thrombosis, and superimposed compressiveneuropathies. Long-term—physical rehabilitation, assis-tive devices, and pain medications.

NCVS: These show marked reduction of compound mus-cle action potential amplitudes, with relatively preserva-tion of conduction velocities and latencies, decreasedsensory nerve action potential amplitudes. With theasymmetric deficit, these suggest an acquired axonalpolyneuropathy. It is a mixed motor and sensory neuropa-thy. Needle EMG may show fibrillation potentials and pos-itive sharp waves (denervation) with normal motor units.EMG may show early recruitment, short duration, smallamplitude voluntary motor units (myopathic changes). Itis often clinically difficult to distinguish between critical

illness polyneuropathy and critical illness myopathy—thetwo may occur together—“critical illness neuromyopa-thy” [1,2].

REFERENCES:

1. Op de Coul AA, Verheul GA, Leyten AC, Schellens RL, TeepenJL. Critical illness polyneuromyopathy after artificial respira-tion. Clin Neurol Neurosurg 1991;93:27.

2. Bednarik J, Lukas Z, Vondracek P. Critical illness polyneuromy-opathy: The electrophysiological components of a complexentity. Intensive Care Med 2003;29:1505.

3. Kane SL, Dasta JF. Clinical outcomes of critical illness polyneu-ropathy. Pharmacotherapy 2002;22(3):373–379.

4. Fletcher SN, Kennedy DD, Ghosh IR, Misra VP, Kiff K, CoakleyJH, Hinds CJ. Persistent neuromuscular and neurophysiologicabnormalities in long-term survivors of prolonged critical ill-ness. Crit Care Med 2003;31:1012.

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49. Brachial plexopathy

ER, ward

CLINICAL CORRELATES: Acute arm pain, followed by pro-gressive weakness, predominantly of the shoulder gir-dle muscles. Patchy numbness in the hand and forearm,worse in the thumb.

ETIOLOGY: Brachial plexopathy.

CLINICAL EVALUATION: Look for distribution of weak-ness, onset of symptoms, pain, sensory loss, and de-pressed or absent deep tendon reflexes supplied by theplexus.

ANCILLARY TESTING: Complete blood count (infection),creatine kinase, erythrocyte sedimentation rate, anti-nuclear antibody, rheumatoid factor, anti-GM1 antibody(for multifocal motor neuropathy), serum protein elec-trophoresis with immunofixation (lymphoma), and 24-hour urine protein electrophoresis with immunofixation(myeloma). Cervical spine and brachial plexus CT or MRIto look for structural problems. Nerve conduction studiesand needle electromyography localize terminal segmentsof nerves and the distribution of abnormalities.

DIFFERENTIAL DIAGNOSIS: Frequent causes are trauma,neuralgic amyotrophy, hereditary brachial plexopathy,neoplastic and radiation-induced brachial plexopathy,thoracic outlet syndrome, diabetic-related brachialplexopathy, and iatrogenic plexopathies. The presenceof sensory loss, diminished reflexes, and radiating painrepresents peripheral nervous system disorders suchradiculopathy, plexopathy, or neuropathy. The patternof a sensory loss and weakness within a defined nerveroot or nerve suggests a plexopathy. Acute onset, in theabsence of trauma, favors a metabolic or inflammatoryprocess. The absence of a chronic progression of symp-toms, the presence of pain, and the absence of a historyof cancer and radiation treatment argue against radia-

tion associated plexopathy. This most likely representsidiopathic brachial plexitis or neuralgic amyotrophy.

PROGNOSIS: Long-term prognosis is good. Pain resolveswithin weeks. Improvement in muscle strength lags be-hind; most patients recover completely within a fewmonths [1]. With marked axonal involvement/affecteddistal muscles, recovery can be protracted. Recurrence ofidiopathic neuralgic amyotrophy was reported in 26%;median time to recurrence is approximately 2 years [2].

TREATMENT: No specific treatment. Glucocorticoids mayhelp with pain [2], but may not affect outcome. Physicaland occupational therapies help avoid contractures.

NCVs: The right median and lateral antebrachial cuta-neous sensory responses are absent; right ulnar andmedial antebrachial cutaneous SNAP amplitudes are re-duced. The right radial SNAP amplitude is reduced; leftulnar, medial and lateral antebrachial cutaneous, me-dian, and radial sensory responses are normal. The ab-normal SNAPs indicate a plexopathy or multiple neu-ropathies (not a particular nerve or nerve root). The rightmedian and axillary CMAP amplitudes are markedly re-duced. These findings suggest a possible upper trunklesion. Needle electromyography examination shows dif-fuse denervation in all muscles tested on the right exceptthe paraspinous and rhomboid muscles. This points toa diffuse multifocal process involving all neural elementsof the brachial plexus, with more severe involvement ofthe upper trunk of brachial plexus and the anterior in-terosseus nerve, consistent with neuralgic amyotrophy(or brachial plexopathy).

REFERENCES:

1. Tsairis P, Dyck PJ, Mulder DW. Natural history of brachialplexus neuropathy. Report on 99 patients. Arch Neurol1972;27:109.

2. van Alfen N, van Engelen BG. The clinical spectrum of neural-gic amyotrophy in 246 cases. Brain 2006;129:438.


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Nerve and site

Ulnar.RWrist 3.2 ms 4 µV 2.6 ms 120 mm



Median.RWristAntecubital

4.2 ms8.7 ms

0.5 mV0.4 mV

mm m/s255 mm 57 m/s

47 m/sDigit V (little finger)-Wrist

Ulnar.LWrist 3.1 ms 13 µV 2.3 ms 120 mm 50 m/sDigit V (little finger)-Wrist

Median.RWrist NR ms µV ms mm m/sDigit II (index finger)-Wrist

Median.LWrist 4.1 ms 17 µV 2.5 ms 130 mm 52 m/sDigit II (index finger)-Wrist

Radial.L

Lateral antebrachialcutaneous.R

Forearm 1.9 ms 27 µV 1.3 ms 70 mm 54 m/sDorsum of hand-Forearm

Elbow NR ms µV 14.7 ms mm m/sForearm-Elbow

Medial antebrachialcutaneous.RElbow 2.5 ms 5 µV 2.0 ms 100 mm 50 m/sForearm-Elbow

Lateral antebrachialcutaneous.LElbow 3.0 ms 17 µV 2.3 ms 115 mm 50 m/sForearm-Elbow

Medial antebrachialcutaneous.LElbow 2.5 ms 20 µV 2.0 ms 110 mm 55 m/sForearm-Elbow

Radial.RForearm 1.9 ms 15 µV 1.3 ms 70 mm 54 m/sDorsum of hand-Forearm

Peaklatency



Nerve and site Latency AmplitudeNormallimits

Normal limits Distance Conductionvelocity

Normallimits

Ulnar.R

Axillary.RErb’s point 3.6 ms 0.4 mV mm m/s

Axillary.LErb’s point 3.3 ms 5.1 mV mm m/s

OtherNormalNormal

NormalNormal

Normal

Normal

NormalNormal

Normal

Normal

NormalNormal

NormalNormalNormal

Normal

NormalNormal

Normal

Normal

NormalNormalNormal

Normal Normal

Normal

NormalNormal

NormalNormal

NormalNormal

Normal

Normal

NormalNormal

NormalNormal

Normal

Normal

NormalNormal

Muscle1st dorsal interosseous.RAbductor pollicisbrevis.RPronator teres.RFlex. digit. prof.RBrachioradialis.RTriceps.RBiceps.RDeltoid.RC-5 Paraspinous.RInfraspinatus.RRhomboid minor.RSupraspinatus.R

NormalNormal

NoneNone

NoneNone

NoneNone

NoneNone

NoneNone

NoneNone

+1 +1+2+2

+2+1+2+2

+2 +2

+2 +2

+2+2+1+2

None

None None

None

NoneNoneNoneNoneNoneNoneNoneNone

None

None

None

ReducedReduced

Reducedno units

no units

no units

no units

no units

DurationRateActivationFascFibs+ Wave ConfigAmplitudeVolitional MUAPsSpontaneous activityInsertional

Needle EMG examination

Insertional

WristBelow elbowAbove elbow

2.4 ms6.4 ms8.5 ms

5.7 mV3.3 mV2.8 mV

mm m/s270 mm90 mm

64 m/s50 m/s

Median.LWristAntecubital

4.0 ms8.5 ms

7.4 mV6.8 mV

mm m/s250 mm 54 m/s

Ulnar.LWristBelow elbowAbove elbow

2.3 ms6.2 ms8.4 ms

8.7 mV6.1 mV5.6 mV

mm m/s265 mm85 mm

65 m/s55 m/s

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50. Femoral neuropathy

CLINICAL CORRELATES: Severe leg weakness, numbnessin the anterior thigh and leg, and inability to walk afterpelvic surgery. Patellar reflexes absent.

ETIOLOGY: Femoral neuropathy secondary to pelvicsurgery, direct trauma, compression, stretch injury, is-chemia, and diabetes.

CLINICAL EVALUATION: Weakness of the quadricepsmuscle and a decreased patellar reflex. Wasting of thequadriceps in advanced and chronic cases. When theiliopsoas muscle is involved, the lesion is above the in-guinal ligament. In isolated femoral neuropathies, thethigh adductors are normal (innervated by the obturatornerve). Sensory deficits—numbness of the medial thighand the anteromedial calf. Pain with hip extension witha retroperitoneal hematoma.

ANCILLARY TESTING: Complete blood count (drop afterhematoma). CT for hematoma, MRI to detect bony ab-normalities. Nerve conduction studies and needle elec-tromyography (EMG) localize terminal segments of nervesand the distribution of abnormalities.

DIFFERENTIAL DIAGNOSIS: The history of pelvic surgeryexcludes the more indolent and most other neuropathies.The presence of sensory loss and diminished patellar re-flexes is consistent with peripheral nervous system disor-der such radiculopathy, plexopathy, or neuropathy. Theweakness and sensory loss are limited to muscles andarea innervated by the femoral nerve. Likewise, the EMGlocalizes the lesion to the femoral nerve. The involvementof the iliopsoas muscle suggests an intrapelvic compres-sive femoral neuropathy.

PROGNOSIS: Recovery is good and typically occurs over3–6 months [1].

TREATMENT: With a retroperitoneal hematoma, evacua-tion of the hematoma is occasionally done, but usuallynot. If possible, anticoagulant agents should be stoppeduntil the hematoma has resolved. Outcomes for thesepatients are worse than for those with a hematoma dueto trauma. If the compression is due to a tumor, thentherapy, either surgery or chemotherapy, is directed atthe neoplasm. Possible surgical decompression is donefor mass lesions. With vasculitic causes, immunosuppres-sive therapy may help. Management comprises intensivephysiotherapy [2] and knee bracing. Some clinicians sug-gest surgical exploration when symptoms fail to improvein 14 weeks [3,4].

NCVs: These show an absent right saphenous sensorynerve action potential (SNAP) and a normal left saphe-nous SNAP (which excludes an L4 root lesion). Thereare normal and symmetric femoral motor studies. Wal-lerian’s degeneration may take up 10 days for axonal de-generation to complete. Needle EMG shows acute den-ervation in the right quadriceps and iliopsoas muscles,but it is normal in the thigh adductors and anterior tib-ialis muscles. Normal thigh adductors would exclude alumbar plexopathy. Involvement of the iliopsoas musclessuggests an intrapelvic femoral nerve lesion occurringfrom compression of retractor compression against thepelvic wall during pelvic surgery and is not a compres-sion of the femoral nerve at the inguinal ligament, suchas occurs during lithotomy positioning. Evaluation fora femoral nerve dysfunction includes nerve conductionstudies (NCS) and needle EMG. NCS should include sen-sory studies of the saphenous nerve and motor studies ofthe femoral nerve. When evaluating femoral NCS, resultson the symptomatic side should be compared to those onthe asymptomatic side. On EMG, the quadriceps shouldshow neuropathic changes. The iliopsoas is involved if


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Nerve and site

Sural.RPoint B 3.2 ms 14 µV 2.2 ms 105 mm

mm m/s



48 m/sLateral malleolus-Point B

Saphenous.RMedia Tibia 2.8 ms 4 µV 2.8 ms 110 mm m/sMedial Malleolus-Medial Tibia

Saphenous.LMedia Tibia NR ms µV

1.4 mV

ms mm 0 m/sMedial Malleolus-Medial Tibia

Peaklatency



Nerve and site AmplitudeLatency Distance Conductionvelocity

Peroneal.LAnkle 3.6 ms

250 mm 40 m/s1.5 mVFibula (head) 14.2 ms

100 mm 43 m/s1.4 mVPopliteal fossa 16.5 ms

mm m/s1.9 mVPeroneal.R

Ankle 4.3 ms

290 mm 39 m/s1.4 mVFibula (head) 13.2 ms

80 mm 40 m/s1.3 mVPopliteal fossa 15.2 ms

mm m/s1.4 mVTibial.L

Ankle 4.7 ms

mm m/s1.3 mVTibial.R

Ankle 4.4 ms

mm m/s3.1 mVFemoral.R

Groin 6.1 ms

mm m/s5.6 mVFemoral.L

Groin 5.7 ms

Other

Normal

NormalNormal

NormalNormal

PolyphasicNormalNormalNormal

NormalSI

NormalNormal

NormalNormal

NormalNormalNormalNormal

NormalNormal

SINormalNormal

Normal

NormalNormal

NormalNormal

IncreasedIncreasedIncreased

MuscleVastus lateralis.RRectus femoris.RIliopsoas.RThigh adductor.RMed gastrocnemius.RGluteus medius.RL5-paraspinous.RVastus lateralis.R

RapidRapid

GDGDMD

NormalNoneNone

NoneNone

+3+2

+3+2+2 +2

NoneNoneNoneNoneNoneNone None

NoneNoneNone None

NoneNoneNone

Normal

NormalNormal

NormalNormal

NormalNormal

Normal

NormalNormal



Insertional

the lesion is in the pelvis (above the inguinal ligament).The adductor magnus and brevis, which share lumbarinnervation with quadriceps and iliopsoas, are spared (in-nervated primarily by the obturator and sciatic nerves).

REFERENCES:

1. Goldman JA, Feldberg D, Dicker D. Femoral neuropathy sub-sequent to abdominal hysterectomy: A comprehensive study.Eur J Obstet Gynecol Reprod Biol 1985;20:385–392.

2. Celebrezze JP Jr, Pidala MJ, Porter JA, Slezak FA.Femoral neuropathy: An infrequently reported postopera-tive complication. Report of four cases. Dis Colon Rectum2000;43:419–422.

3. Georgy FM. Femoral neuropathy following abdominal hys-terectomy. Am J Obstet Gynecol 1975;123:819–822.

4. Brasch RC, Bufo AJ, Kreienberg PF, Johnson GP. Femoral neu-ropathy secondary to the use of a self-retaining retractor. Re-port of three cases and review of the literature. Dis ColonRectum 1995;38:1115–1118.

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51. Sensory neuropathy/ganglionopathy [1–3]

ER, MICU, WARD

CLINICAL CORRELATES: Progressive dysphagia, weightloss, and facial dysesthesias. No weakness, dry eyes andmouth. There is marked loss of large and small fiber sen-sory modalities in a length-dependent fashion, hypore-flexia, and ataxic gait.

ETIOLOGY: Sensory neuropathy or ganglionopathy.

CLINICAL EVALUATION: Look for a specific pattern ofjoint, muscle, and sensory loss in a non-length-dependentpattern, leading to distinct clinical, neurophysiological,and neuropathological findings. Normal strength andsensory ataxia.

ANCILLARY TESTING: Liver function tests (hepatitis),erythrocyte sedimentation rate, anti-nuclear antibody,rheumatoid factor, paraneoplastic panel, serum proteinelectrophoresis with immunofixation, 24-hour urineprotein electrophoresis with immunofixation, anti-Ro,anti-La, anti-Sm, and anti-ribonucleoprotein antibodies.Obtain cerebrospinal fluid (CSF) to evaluate for inflam-mation (including elevated CSF protein and mononuclearcells) and infection (i.e., Lyme disease, syphilis, andcytomegalovirus). Consider skin biopsy for pattern ofsensory fiber loss.

DIFFERENTIAL DIAGNOSIS: Autoimmune (i.e., paraneo-plastic ganglionopathy, paraproteinemia, or polyclonalgammopathy), drugs (thalidomide, pyridoxine, cis-platinum, doxorubicin, etc.), inflammatory (Sjogren’ssyndrome, acute sensory polyneuropathy, chronic in-flmmatory sensory polyneuropathy, etc.), hereditary(hereditary sensory axonal neuropathy, Fabry’s disease,Friedreich’s ataxia, spinocerebellar degeneration), in-fections (i.e., syphilis, Lyme, and herpes zoster), andidiopathic ganglionoapthy. Inherited ganglionopathyusually manifests a slow progression and positive familyhistory. Look for possible neurotoxic drugs: thalidomide,cis-platinum [1], high-dose pyridoxine. Focal sensory

ganglionitis may occur in viral or bacterial infections (her-pes zoster and, possibly, Borrelia burgdorferi). Sensoryneuronopathy occurs with inflammatory or autoimmunediseases, ataxic neuronopathy (with Sjogren’s syndrome).Sjogren’s syndrome includes dry eyes and mouth (siccasyndrome); articular symptoms, inflammatory arthropa-thy, or occasionally rheumatoid arthritis [1]. Thesewith gait impairment and proprioception loss suggestSjogren’s syndrome sensory neuronopathy

PROGNOSIS: It depends on the etiology, but it is generallypoor. In Sjogren’s syndrome, progression is usually slowand insidious. Symptoms will often be stable over manyyears.

TREATMENT: There is no definitive treatment [2]. Treat-ment is focused on symptomatic pain relief. There hasbeen poor response to most immunotherapy.

NCVS: The motor system is spared clinically and electro-physiologically. There is a widespread decrease in sen-sory nerve action potential (SNAP) amplitudes, with noproximal–distal gradient. The amplitude of SNAPs in theupper limbs is lower than in the lower limbs. The non-length-dependent distribution of sensory loss in a man-ner suggests a dorsal root ganglionopathy, often called asensory neuronopathy or ganglionopathy [1].

REFERENCES:

1. Govoni M, Bajocchi G, Rizzo N, Tola MR, Caniatti L, Tug-noli V, Colamussi P, Trotta F. Neurological involvementin primary Sjogren’s syndrome: Clinical and instrumentalevaluation in a cohort of Italian patients. Clin Rheumatol1999;18(4):299–303.

2. Venables PJ. Sjogren’s syndrome. Best Pract Res Clin Rheuma-tol 2004;18:313–329.

3. Jonsson R, Haga HJ, Gordon T. Sjogren’s syndrome. In: Koop-man WJ (ed.), Arthritis and Allied Conditions: A Textbookof Rheumatology, 14th edn. Philadelphia, PA: LippincottWilliams & Wilkins 2001:1736–1759.


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Nerve and site

Sural.LPoint B 3.5 ms 4 µV 2.5 ms 100 mm

mm m/s



40 m/sLateral malleolus-Point B

Sural.RPoint B 3.5 ms 4 µV 2.5 ms 100 mm 40 m/sLateral malleolus-Point B

Median.LDigit II NR ms µV

6.7 mV

ms mm m/sWrist-Digit II

Ulnar.LV Digit NR ms µV ms mm m/sWrist-V Digit

Radial.LForearm NR ms µV ms mm m/sDorsum of hand-Forearm

Peaklatency




Peroneal.R

Ankle 5.4 ms

310 mm 40 m/s6.0 mVFibular Head 13.2 ms

90 mm 45 m/s5.7 mVPop Fossa 15.2 ms

mm m/s4.3 mV

Peroneal.L

Ankle 5.3 ms


100 mm 71 m/s3.8 mVPop fossa 14.2 ms

mm m/s14.5 mV

Tibial.R

ankle 4.7 ms

mm m/s16.9 mV

Tibial.L

ankle 4.6 ms

mm m/s4.4 mV

Median.L

wrist 3.0 ms

mm

5.4 ms

Latencydifference

7.8 ms

2.0 ms

5.3 ms

7.5 ms

1.4 ms

4.7 ms

4.6 ms

3.0 ms

3.0 ms

EDB-Ankle

Segment

Ankle-Fibular Head

Fibular Head-Pop Fossa

EDB-Ankle

Ankle-Fibular Head


AH-ankle

AH-ankle

APB-wrist

250 mm 54 m/s3.4 mVantecubital 7.6 ms 4.6 mswrist-antecubital

m/s3.8 mV wrist

Ulnar.L

wrist 3.0 ms

Other


NormalNormalNormalNormalNormal


NormalNormalNormal


Muscle

Nurve M-Latency F-LatencyPeroneal.L 5.5 61.7

Tibial.L 5.3 61.5Tibial.R 4.5 56.8

Peroneal.R 4.4 59.9Median.L 3.4 30.1

Iliopsoas.LRectus femoris.LTibialis anterior.LGastrocnemius (Medialhead).L

NormalNormal

NoneNoneNoneNone

NoneNone

NoneNone

NoneNone

NoneNoneNone None

NoneNoneNormalNormal



F-wave studies

Insertional

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52. Lumbar radiculopathy [1–3]

ER, MICU

CLINICAL CORRELATES: Pain radiating down the rightbuttock to the lateral thigh and pretibial area, worse withambulation. Right foot weakness with footdrop; frequenttripping and falls. Gait difficulty.

ETIOLOGY: Lumbar radiculopathy or neuropathy.

CLINICAL EVALUATION: Look for pain in a dermatomaldistribution (radicular pain), sensory loss and weaknessin corresponding dermatomal distribution, and absent ordepressed reflexes. Sitting, coughing, or sneezing mayexacerbate the pain. Often, an assessment of the L5 re-flex (medial hamstrings) is helpful. Provocative maneu-vers, such as the straight-leg raising test, may provideevidence of increased dural tension, indicating underly-ing nerve root pathology.

ANCILLARY TESTING: Erythrocyte sedimentation rate,anti-nuclear antibody, and rheumatoid factor. Considera lumbar spine MRI to detect bony abnormalities, discherniation, nerve root compression, and structural ab-normalities. Nerve conduction studies and needle elec-tromyography (EMG) localize terminal segments of nervesand the distribution of abnormalities.

DIFFERENTIAL DIAGNOSIS: Myelopathy, radiculopathy,plexopathy, single or multiple neuropathy, demyelinat-ing conditions, and spondylolysis. Sensory loss and di-minished reflexes suggest a peripheral nervous systemprocess. Pain radiation in the buttock to the lateral thighand leg suggests an L5 dermatomal distribution (cf. thedistribution of sensory impairment in the lateral leg anddorsum of the foot). Weakness of ankle and toe dorsi-flexion represents an L5 nerve root process. However, ab-sent ankle reflexes and ankle plantar flexion weakness

suggest possible superimposed involvement of the S1radiculopathy. A plexopathy or sciatic neuropathy cannotbe excluded. EMG confirms an L5–S1 nerve root lesion byinvolvement of muscles outside sciatic nerve distributionand proximal to the lumbosacral plexus (i.e., paraspinousmuscles). To differentiate between an L3 radiculopathyand a femoral neuropathy, weakness in the hip adduc-tors in addition to the quadriceps group indicates an L3radiculopathy. With isolated femoral neuropathy, only thequadriceps group would be weak.

PROGNOSIS: It depends on the cause. Most radicu-lopathies arise from nerve root compression by lumbarspondylosis or disc herniation, and prognosis is excel-lent with medical treatment (80–90% of patients can betreated medically) [1,2]. Surgery is indicated when nonop-erative treatment has failed. Noncompressive radiculopa-thy from diabetes, infectious (zoster, Lyme, etc.), granulo-matous, and infiltrating neoplastic disorders has a worseprognosis.

TREATMENT: Surgical intervention considered with signif-icant/severe [1] and progressive motor deficits and caudaequina syndrome [3] with bowel and bladder dysfunc-tion. Symptoms limited to pain and sensory loss aremanaged medically [3]. Bed rest and anti-inflammatoryagents (steroidal and/or nonsteroidal) with analgesics;muscle relaxants are helpful for significant spasms. Occa-sionally, oral steroids may reduce pain and inflammationfrom compression, but no controlled study exists to sup-port this use; anecdotal reports suggest some usefulness.Slowly mobilize after 7–14 days. Generally, patients im-prove over 1–3 months with conservative treatment. Ifnot, refer for surgical evaluation.

NCVS: This EMG/nerve conduction study shows anabsent right peroneal motor response. The right tibialcompound motor action potential (CMAP) amplitudeis moderately reduced. The mild slowing right tibial


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Nerve and site

Sural.RPoint B 3.2 ms 14 µV 2.2 ms 105 mm


48 m/sLateral malleolus-Point BSural.LPoint B 3.1 ms 11 µV 2.2 ms 105 mm 48 m/sLateral malleolus-Point BMedian.R

Ulnar.RWrist 4.6 ms 11 µV 3.5 ms 130 mm 49 m/sDigit II (index finger)-Wrist

Wrist 3.1 ms 17 µV 2.3 ms 110 mm 49 m/sDigit V (little finger)-Wrist

Peaklatency



mm m/s


mV


Peroneal.R

Ankle NR ms

mm m/smVFibular Head ms

mm m/smVPop Fossa ms

mm m/s4.3 mV

Peroneal. L

Ankle 5.3 ms


100 mm 71 m/s3.8 mVPop Fossa 14.2 ms

mm m/s1.0 mV

Tibial.R

ankle 4.7 ms

mm m/s16.9 mV

Tibial.L

ankle 4.6 ms

mm m/s4.4 mV

Median.L

wrist 3.0 ms

ms

Latencydifference

ms

ms

5.3 ms

7.5 ms

1.4 ms

4.7 ms

4.6 ms

3.0 ms

EDB-Ankle

Segment

Ankle-Fibular Head


EDB-Ankle

Ankle-Fibular Head


AH-ankle

AH-ankle

APB-wrist

250 mm 54 m/s3.4 mVantecubital 7.6 ms 4.6 mswrist-antecubital

Other

Normal Normal

NormalSISI

NormalSI

SISI

NormalSI

SISI

Normal

NormalNormal

Normal

NormalNormalNormal

MuscleGastrocnemius.RTibialis anterior.RRectus femoris.RIliopsoas.RGluteus Maximus.RL5-paraspinous.RGastrocnemius.L

RapidRapid

MDGD

GDNoneNone

NoneNone

+2+3

+2+3

None NoneNoneNone

+2+2

None None+2+2 None

NoneNone

RapidRapid

Rapid

MD

MD



Insertional

Nurve M-Letency F-Letency

Tibial.R 6.8 66.4

Tibial.L 4.9 53.4

Peroneal.L 5.8 48.3

Median.L 3.2 25.4

F-wave studies

motor studies are appropriate for the significant loss inCMAP amplitude and probably related to loss of large,fast-conducting fibers. Together, these suggest severalabnormalities: (1) L5 and S1 root lesion, (2) lumbosacralplexopathy, and (3) sciatic nerve lesion. Bilateral sural andsuperficial peroneal sensory studies are normal. Lesionsof the sciatic nerve or the lumbosacral plexopathy areunlikely because they would cause reduced or absentsuperficial peroneal and sural sensory nerve action po-tential amplitudes. Needle EMG shows acute or chronicdenervation/re-innervation in the L5–S1 myotome, anddenervation in L5 paraspinous and gluteus medius andmaximus muscles. These confirm an L5–S1 nerve rootlesion by involvement of muscles outside sciatic nervedistribution and proximal to the lumbosacral plexus (i.e.,paraspinous muscles). Hence, these findings indicate a

severe right L5 radiculopathy with moderate involvementof the right S1 root.

REFERENCES:

1. Weinstein JN, Lurie JD, Tosteson TD, Skinner JS, Hanscom B,Tosteson AN, Herkowitz H, Fischgrund J, Cammisa FP, AlbertT, Deyo RA. Surgical vs nonoperative treatment for lumbardisk herniation: The Spine Patient Outcomes Research Trial(SPORT) observational cohort. JAMA 2006;296:2451–2459.

2. Mazanec D, Okereke L. Interpreting the Spine Patient Out-comes Research Trial. Medical vs surgical treatment of lumbardisk herniation: Implications for future trials. Cleve Clin J Med2007;74:577–583.

3. Nakagawa H, Kamimura M, Takahara K, Hashidate H,Kawaguchi A, Uchiyama S, Miyasaka T. Optimal duration ofconservative treatment for lumbar disc herniation dependingon the type of herniation. J Clin Neurosci 2007;14:104–109.

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53. Guillain-Barre syndrome—demyelinatingpolyneuropathy

MICU, CICU, NICU

CLINICAL CORRELATES: Rapid onset of progressive (overdays) ascending numbness, tingling of the extremities,weakness. Gait difficulty, shortness of breath, no bowelor bladder dysfunction. Recent flu-like illnesses.

ETIOLOGY: Demyelinating process.

CLINICAL EVALUATION: Normal cranial nerves. Extremityweakness—worse in the legs and worse proximally. Ten-don reflexes absent. There may be mild distal pinprick andvibratory sensory loss; it is worse in the legs in compari-son to the arms. Look for autonomic signs—variability inrespiration, blood pressure, and cardiac rhythms.

ANCILLARY TESTING: Cervical spine MRI (myelopathy).Consider heavy metal screen, autoimmune panel, serumprotein electrophoresis/immunofixation electrophoresis(SPEP/IFE), porphyria (delta-aminolevulinic acid (d-ALA),prophobilinogen (PBG)), serum CK level, pulmonaryfunction test for indications of respiratory failure, andelectrocardiogram (ECG) for cardiac assessment. Anal-ysis of cerebrospinal fluid (CSF) for albuminocyto-logic dissociation—CSF protein raised typically 100–1000mg/dL with normal or low CSF-WBC count.

DIFFERENTIAL DIAGNOSIS: Myelopathy, acute polyneu-ropathies, neuromuscular junction defect, or a myopa-thy. Acute spinal cord compression and acute transversemyelitis can resemble Guillain-Barre syndrome (GBS). Thelack of a sensory level and sphincter dysfunction arguesagainst a myelopathy. Normal cervical MRI excludes amyelopathy at this level. Neuromuscular junction prob-lems including botulism, myasthenia gravis, and Lambert-Eaton myasthenic syndrome can cause acute weakness.Muscle disorders, for example, acute polymyositis andcritical illness neuromyopathy, can result in diffuse para-lytic weakness.

In this patient, there was rapid progression of acute dif-fuse weakness over a few days. Areflexia and mild sensoryloss are out of proportion to the severity of weakness.Normal serum CK level, sensory loss, and electromyogra-phy (EMG) findings are not consistent with a myopathy orneuromuscular junction defect. Diminished sensory find-ings suggest an acute neuropathy.

Acute polyneuropathies include arsenic poisoning,n-hexane, or glue-sniffing neuropathy. Vasculitis, Lymedisease, tick paralysis, porphyria, sarcoidosis, lep-tomeningeal disease, paraneoplastic disease, and criti-cal illness polyneuropathy cause peripheral neuropathy.Diffuse areflexia suggests demyelination. The diagnosisof GBS arises from a history of an acute monophasicillness with a rapidly progressive polyneuropathy, weak-ness, and areflexia. Weakness is usually proximal in thelegs, but may begin in the face or arms (10%) [1]. Weak-ness varies from mild gait difficulty to complete paralysisincluding bulbar and respiratory muscle weakness. Thirtypercent develop breathing difficulty, necessitating venti-latory support. Autonomic dysfunction occurs in 70%,with blood pressure instability, cardiac arrhythmias, ileus,and loss of sweating [2]. Severe dysautonomia must bemonitored and may cause sudden death.

PROGNOSIS: Eighty percent recover completely or haveminor deficits [3]; 15% persistent mild deficits (mild footdrop, balance problems, moderate weakness, painfuldysesthesias); 3% remain wheelchair bound. Risk factorsfor poor prognosis: older age, rapid onset <7 days, venti-latory support, distal motor response amplitude reduction<20% normal; preceding diarrheal illness [4, 5]. About2% of the patients develop chronic relapsing weaknessof chronic demyelinating polyradiculopathy [6].

TREATMENT: ICU ventilatory and autonomic monitoringand support. American Academy of Neurology practiceparameters recommend plasma exchange or intravenousimmunoglobulins (IVIG) [7]. Plasmaphoresis and IVIG are


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Nerve/Sites

L Median - Dig II

L Median - APB

1. Dig II

1. Wrist

1. Wrist

1. Ankle

2. FibHead

3. Knee

R Peroneal - EDB

1. Ankle

2. Elbow

2. B.Elbow

3. A.Elbow4. Axilla

L Peroneal - EDB

3. Axilla

L Ulnar - ADM

Wrist

APB

ADM

EDB

EDB

Wrist

Lat Mall

2.05

2.20

2.65

4.15

8.45

10.45

3.10

6.60

8.15

10.45

5.75

13.45

15.20

5.80

9.4

4.9

4.826

10

4.6

2.9

2.4

0.8

21.5

10

9

32.5

10

60.5

50.0

61.4

64.5

39.1

43.3

51.3

0.8

0.8

0.8

2.5

17.0

6.8

16.6

12.5

11

11

61.0

50.0

41.5

1. Dig VL Ulnar

1. Calf

L Sural

Rec. Site Latencyms

AmplitudeµV

Distancecm

Velocitym/s

Nerve/Sites

Motor NCS


F-Wave

Nerve

L PeronealL Median

L Peroneal: No Response1

1

1

2

2

2

3

3

3

4

4

4

5

5

5 Wrist 150ms 5mV

Motor NCS L Median - APB

Elbow 250ms 5mV

Axilla 350ms 5mVR Peroneal: No Response

L Ulnar: No Response

0.0030.00

Fminms

MuscleInsertional Spontaneous Activity Volitional MUAPsInsertional + Wave Fibs Fasc Activatior Rate Duratior Amplitude Config Other

Iliopsoas.LRectus femoris.LTibialis anterior.LGastrocnemius(Medial head).L







NoneNoneNoneNone

NoneNoneNoneNone

NoneNoneNoneNone

NoneNoneNoneNone

Sensory NCS

Rec. Site Latencyms

AmplitudemV

Distancecm

Velocitym/s

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of equivalent efficacy; combining the two treatments isnot beneficial. Steroid treatment alone is not beneficial.During the recovery, patients often need intensive reha-bilitation. Neuropathic pain may respond to antiseizuremedications (gabapentin, pregabalin, topiramate, etc.),antidepressants (amitriptyline, duloxetine, etc.), or anal-gesics including opiate drugs.

NCV: This study shows prolonged bilateral peroneal distallatencies, absent left ulnar and bilateral peroneal F-wavelatencies. Conduction blocks in the left ulnar nerve acrossthe elbow and left median across the forearm. The asym-metrical nature of the abnormality suggests an acquiredprocess. Concentric needle EMG is normal. The combinedpicture demonstrates a demyelinating polyneuropathy(e.g., early acute inflammatory demyelinating polyneu-ropathy or a GBS.

REFERENCES:

1. Ropper AH. The Guillain-Barre syndrome. N Engl J Med1992;326:1130.

2. Zochodne DW. Autonomic involvement in Guillain-Barre syn-drome: A review. Muscle Nerve 1994;17:1145.

3. Ropper AH, Wijdicks EFM, Truax BT. Guillain-Barre Syndrome.Philadelphia, PA: FA Davis 1991.

4. McKann GM, Griffin JW, Cornblath DR, Mellits ED, FisherRS, Quashey SA. Plasmapheresis and Guillain-Barre syndrome:Analysis of prognostic factors and effect of plasmapheresis.Ann Neurol 1988;23:347.

5. Rees JH, Soudain SE, Gregson NA, Hughes RAC. Campylobac-ter jejuni infection and Guillain-Barre syndrome. N Engl J Med1995;333:1374.

6. Asbury AK. New concepts of Guillain-Barre syndrome. J ChildNeurol 2000;15:183.

7. Hughes RA, Wijdicks EF, Barohn R, Benson E, Cornblath DR,Hahn AF, Meythaler JM, Miller RG, Sladsky JT, Stevens JC;Quality Standards Subcommittee of the American Academy ofNeurology. Practice parameter: immunotherapy for Guillain-Barre syndrome: Report of the Quality Standards Subcom-mittee of the American Academy of Neurology. Neurology2003;61:736.

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54. Myasthenia gravis—neuromuscular junction [1–4]

CICU, MICU, NICU

CLINICAL CORRELATES: Fatigable limb weakness, doublevision, droopy eyelids, dysphagia, slurred speech, and fa-cial weakness. Symptoms fluctuate.

ETIOLOGY: Neuromuscular junction defect such asLambert-Eaton myasthenic syndrome, botulism, andmyasthenia gravis (MG).

CLINICAL EVALUATION: Look for uni- or bilateral facialweakness, diplopia on sustained upward gaze, horizontaldiplopia on sustained lateral gaze, ptosis on extendedupward gaze, nasal speech, and weakness in the upperextremities, worse in the triceps muscle. Body and limbsensation and limb reflexes are normal.

ANCILLARY TESTING: Serum CK level, thyroid-stimulating-hormone (TSH), complete blood count,and metabolic panel. Brain MRI normal. Abnormal repet-itive stimulation study-–see below. Obtain respiratoryfunction tests—negative inspiratory force (INF), firstsecond of the forced exhalation (FEV1), vitalk capacity(VC)—anti-AChR and anti-MuSk antibodies. Considerchest CT with contrast to evaluate for thymoma.

DIFFERENTIAL DIAGNOSIS: Lambert-Eaton myasthenicsyndrome, botulism, penicillamine-induced myasthenia,congenital myasthenic syndromes. Motor neuron diseaseis unlikely with normal reflexes, lack of fasciculation,young age.

MG usually affects the eye muscles early in the coursewith double vision and drooping of the lids, but cancause extremity weakness, difficulty speaking, swallow-ing, and breathing difficulty, necessitating ventilatory sup-port. Weakness is often better after rest or in early morn-ing; worse after exercise or later in the day. With MG,there is weakness and muscle fatigue (not “tiredness”).Electromyography (EMG)/NCV confirm postsynaptic neu-romuscular disorder; sensitivity is about 75% [1].

PROGNOSIS: Nearly all are able to lead normal lives [3].

TREATMENT: Depending on presentation:

� Symptomatic treatment—Mestinon provides short-term benefit, lasting hours.

� Rapid immunomodulating treatment—Plasmapheresisand IVIg alter the abnormal antibody response.

� Chronic immunomodulating treatment—Corticosteroids and other immunosuppressivedrugs suppress the abnormal antibody response,including the production of anti-AChR and anti-MuSKantibodies.

� Surgical removal of the thymus gland—The thymusgland is abnormal in about 75% of patients with MG.In about 15% there may be a thymus gland tumor,seen on CT or MRI of the chest. Surgical resection mayprovide benefit in patients without tumors [4].

NCVS: Sensory nerve action potentials and motor nerveconduction studies are normal. Repetitive nerve stimula-tion (RNS) at a rate of 3 Hz shows marked baseline decre-ments greater than 20% in three nerve–muscle pairs.An RNS study is considered positive if the decrement isgreater than 10%. An improvement of the compoundmotor action potential decremental response (a smallerdecrement of 13.6% compared with the decrement of22.1% at rest) after brief exercise, reflecting postexer-cise facilitation. Concentric needle EMG is normal. Thesefindings are consistent with a postsynaptic neuromuscu-lar junction defect, such as MG.

REFERENCES:

1. Meriggioli MN, Sanders DB. Myasthenia gravis: Diagnosis.Semin Neurol 2004;24:31.

2. Vernino S, Lennon VA. Autoantibody profiles and neurologicalcorrelations of thymoma. Clin Cancer Res 2004;10:7270.

3. Drachman DB. Myasthenia gravis. N Engl J Med 1994;330:1797.

4. Gronseth GS, Barohn RJ. Practice parameter: thymectomy forautoimmune myasthenia gravis (an evidence-based review):Report of the Quality Standards Subcommittee of the Ameri-can Academy of Neurology. Neurology 2000;55:7.Clinical Electrophysiology. By C© Peter W. Kaplan and Thien Nguyen.

Published 2011 Blackwell Publishing Ltd.

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Rep Nerve Stim

Muscle/Train

EMG Summary TableSpontFib PSW Fasc MUs MUs MUs AmpDur - -FR

Recruit Duration

Baseline

Rep Nerve Stim R Orb Oculi, CN VII

Post Exercise

@ 1:00

@ 2:00

@ 3:00

@ 5:00

Amplitude PolyP Other

R. Deltoid, Axillary, C5-6 0 0 0 Nl Nl Nl Nl Nl Nl Nl Nl

R Orb Oculi, CN VIIBaselinePost Exercise@ 1:00@ 2:00@ 3:00@ 5:00L Orb Oculi, CN VIIBaselineR Trap, CN XIBaseline

2.83.33.23.42.73.0

3.9

12.0

−22.1−13.6−24.3−26.5

−25−22

−17.5

−23.5

−57.6−60.7

−49−71

−48.1−44.9

−36.9

−27.4

10011711512297.4110

100

100

9.99.7

10.510.89.9

10.1

10.3

75.6

−29.1−14.9

−29−30.4−33.7−27.3

−21.3

−25.9

−46.3−37.3−32.5

−70−41.9−30.3

−21.3

−32.3

10098.210610999.4102

100

100

333333

3

3

0:00:000:00:440:02:550:03:590:04:550:07:56

0:00:00

0:00:00

AmpmV

4-1%

Lowest-1%

Fac%

AreamVms

4-1%

Lowerst-1%

Fac%

Ratepps

Time

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55. Myositis—irritable myopathy

CICU, MICU, NICU

CLINICAL CORRELATES: Slowly progressive limb weak-ness over weeks to months, swallowing difficulty, musclepain, and respiratory symptoms. Purplish rash seen onthe backs of the hands and across the face, and painfulnodules.

ETIOLOGY: Myopathy.

CLINICAL EVALUATION: Look for slowly progressive proxi-mal limb weakness, dysphagia, and respiratory weakness.Rash along the face, neck, chest, “shawl” distribution,arms, abdomen, thighs, patch on the thighs bilaterally.Normal sensation.

ANCILLARY TESTING: Complete blood count, creatine ki-nase (CK), lactate dehydrogenase, aldolase, and aspar-tate aminotransferase, erythrocyte sedimentation rate,anti-nuclear antibody, rheumatoid factor, anti-Ro, anti-La,anti-Sm, and anti-ribonucleoprotein antibodies. Myositis-specific autoantibodies directed against helicase (anti-Mi-2 antibodies), cytoplasmic RNA synthetases (anti-Jo-1 an-tibodies), other cytoplasmic proteins, ribonucleoproteins,and certain nuclear [1]. Muscle biopsy showing healthymuscle fibers surrounded and invaded by inflammatorycells (“primary inflammation”), worse perifascicularly indermatomyositis. MRI of the limb to identify an optimalsite for muscle biopsy. Malignancy screening is recom-mended due to its association with inflammatory myopa-thy, especially adult dermatomyositis. Evaluate respiratoryfunction tests (i.e., INF, FEV1, and VC) for respiratory fail-ure.

DIFFERENTIAL DIAGNOSIS: Muscle weakness with orwithout muscle enzyme elevation can be caused bymyelopathy, lower motor neuron disease, radiculopathy,

plexopathy, neuropathy, myasthenia gravis, muscular dys-trophies, and various metabolic, endocrine, inflammatorymyopathy, and a variety of inherited, metabolic, drug-induced, endocrine, and infectious myopathies. Normalsensory modalities, reflexes, and an irritable myopathy onelectromyogram (EMG) are against myelopathy, radicu-lopathy, plexopathy, and neuropathy. The absence of di-urnal fluctuation, pupillary, ptosis, or ophthalmoplegicfindings are against a neuromuscular junction disorder.Presentation of proximal muscle weakness and elevatedmuscle enzymes suggests a possible myopathy. Familyhistory, sex (e.g., higher predominance in males), anddistribution of weakness do not suggest a muscular dys-trophy. The possibility of Churg–Strauss syndrome shouldbe considered if there is eosinophilia. The distinctive pur-plish rash seen on the backs of the hands and acrossthe face and painful nodules are most suggestive of der-matomyositis. Calcinosis, telangiectasias of scleroderma,and photosensitive rashes may be confused with systemiclupus erythematosus. A muscle biopsy can be helpful tomake the definitive diagnosis.

PROGNOSIS: Long-term follow-up data on inflammatorymyopathy are scant: 60% are chronic; 20% had poly-cyclic disease courses; and 20% had monophasic courses.Malignancy is seen with inflammatory myopathy, espe-cially adult dermatomyositis. Myositis-specific autoanti-body testing helps with prognosis and treatment [2, 3]:patients with anti-Jo-1 antibodies may have an incom-plete response to treatment and a worse long-term weak-ness. Some with anti-signal recognition particle (SRP)antibodies have a fulminant onset of proximal muscleweakness, very high serum CK levels, and muscle biop-sies that show muscle fiber necrosis and regeneration butlittle to no inflammation. Early glucocorticoid treatmentmay help some patients. With anti-Mi-2 antibodies (onlyseen in dermatomyositis (DM)), there may be a fulminantonset and florid cutaneous findings. They may respondwell to treatment and have a good long-term prognosis


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Peroneal.R

Tibial.R

Tibial.L

Peroneal.L

Median.L

Ulnar.L

Needle EMG data

AnkleFibular HeadPop Fossa

5.4 ms13.2 ms15.2 ms

5.4 ms7.8 ms2.0 ms

mm310 mm90 mm

m/s40 m/s45 m/s

6.7 mV6.0 mV5.7 mV

EDB-Ankle

ankle 4.7 ms 4.7 ms mm m/s15.7 mV AH-ankle


wrist

Deltoid MiddleBiceps BrachiiTriceps Med HGastroc Med HdTibialis AntTibialis AntGlut Med

RRRRRLL

Ins Act FibsInsertional Activation

+Wave Fasc Amplitude Duration Config Rate ActivationNormalNormalNormalNormalNormalNormalNormal

1+NoneNoneNoneNoneNone1+

1+1+NoneNoneNoneNone1+


SDMDMDNormMDNormSD

SDMDMDNormMDNormSD

NormNormNormNormNormNormNorm


EARLYEARLYEARLYNormNormNormNorm

3.0 ms 3.0 ms mm

Generic 10:47:45

10 msAMP: 1, 20-10kHz50 uV

Trig:↑ Off Rate: Hz 50 uV 1.- 5 ms

Generic 10:49:20

10 msAmp: 1, 20-10kHz200 uV

Trig:↑ Off Rate: Hz 200 uV 1.- 5 ms

m/s3.8 mV wrist

Ankle-Fibular HeadFibular Head-Pop Fossa


5.3 ms12.8 ms14.2 ms

5.3 ms7.5 ms1.4 ms

mm310 mm100 mm

m/s41 m/s71 m/s

4.5 mV4.3 mV3.8 mV

EDB-AnkleAnkle-Fibular Head

wristantecubital

3.0 ms7.6 ms

3.0 ms4.6 ms

mm250 mm

m/s54 m/s

4.4 mV3.4 mV

APB-wristwrist-antecubital


Nerve and site

Sural.R

Sural.L

Ulnar.L

Median.Lwrist

wrist

Point B

Point B 4.2 ms 11 µV Lat malleolus-Point B 3.4 ms 120 mm 35 m/s

3.7 ms 15 µV Lat malleolus-Point B 2.8 ms 110 mm 39 m/s

3.2 ms 14 µV index finger-wrist 2.6 ms 140 mm 54 m/s

3.2 ms 14 µV index finger-wrist 2.6 ms 140 mm 54 m/s

Peaklatency

Latencydifference

Conductionvelocity

DistanceAmplitude Segment

Nerve and site Latency Latencydifference

Conductionvelocity


TREATMENT: Goals to improve muscle strength; avoid ex-tramuscular complications. In DM, aim for resolution ofcutaneous disease manifestations. There is no standardglucocorticoid regimen, but two general principles apply:(1) initiation of treatment with high doses for the firstseveral months to establish disease control and (2) slowtaper to the lowest effective dose for a total duration oftherapy between 9 and 12 months.

Some clinicians initiate a glucocorticoid-sparing agentin a severely ill patient at the same time as steroid

treatment is begun to reduce the cumulative dose ofprednisone and diminish glucocorticoid-induced mor-bidity. Others reserve these agents for patients whofail treatment with glucocorticoids alone. The first-lineglucocorticoid-sparing agent is usually either azathio-prine or methotrexate. The response to azathioprine andmethotrexate may take 4–6 months.

NCV: The sensory and motor nerve conduction studiesare normal. Concentric needle EMG shows spontaneous

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activities (positive and fibrillation at rest), early recruit-ment, and many voluntary motor units with smallamplitude and short duration consistent with a myo-pathic process such as an irritable myopathy. Considerdermatomyositis because of the rash. EMG can distin-guish myopathic weakness from neuropathic disorders(e.g., motor neuron disease and myasthenia gravis) inwhich the EMG is normal. The EMG may be normalbecause of the patchy nature of muscle inflammationand placement of the needle electrode in an uninflamedsite. The electromyographer should sample weak musclesand multiple muscles in several limbs before concludingthere are no myopathic changes. The EMG usually showsirritability by (1) increased insertional activity and spon-taneous fibrillations, (2) abnormal myopathic voluntary

motor units—low amplitude, short-duration polyphasicmotor potentials, and (3) high-frequency dischargesconsistent with early recruitment of motor units.

REFERENCES:

1. Targoff IN. Myositis specific autoantibodies. Curr RheumatolRep 2006;8:196.

2. Noss EH, Hausner-Sypeck DL, Weinblatt ME. Rituximab astherapy for refractory polymyositis and dermatomyositis. JRheumatol 2006;33:1021.

3. Lambotte O, Kotb R, Maigne G, Blanc, FX, Goujard C, Del-fraissy JF. Efficacy of rituximab in refractory PM. J Rheumatol2005;32:1369.

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56. Statin-induced myopathy—toxicmyopathy/myalgia

ER, MICU

CLINICAL CORRELATES: Myalgia and muscle cramps,worse in the lower extremities. Taking statin drug forhyperlipidemia.

ETIOLOGY: Myopathy.

CLINICAL EVALUATION: Look for myalgias (with or with-out CK elevation), creatine kinase (CK) elevation, cramps,stiffness, muscle tenderness, exercise intolerance, proxi-mal muscle weakness, often marked rhabdomyolysis withmassive CK elevation, and occasionally life-threateningmyoglobinuria with the risk of renal failure.

ANCILLARY TESTING: Complete blood count, CK,lactate dehydrogenase, aldolase, and aspartate amino-transferase, thyroid studies, erythrocyte sedimentationrate, anti-nuclear antibody, rheumatoid factor, anti-Ro,anti-La, anti-Sm, and anti-ribonucleoprotein antibodies.Myositis-specific autoantibodies directed against helicase(anti-Mi-2 antibodies), cytoplasmic RNA synthetases(anti-Jo-1 antibodies), other cytoplasmic proteins, ri-bonucleoproteins, and certain nuclear antigens [1].Consider MRI of limbs to identify optimal site for musclebiopsy. Evaluate respiratory function tests (i.e., INF, FEV1,and VC) for respiratory failure.

DIFFERENTIAL DIAGNOSIS: Myopathy and myalgia symp-toms can occur with inflammatory myopathies, lipidand glycogen storage disease, neuropathies and neu-romuscular junction diseases, genetic dystrophies, toxic,metabolic, endocrine, and nutritional myopathies,

polymyalgia rheumatica, and infection-associated myosi-tis (viral, bacterial, and parasitic). The lack of long-tracksigns and fasciculations is against amyotrophic lateralsclerosis and other motor neuron diseases. The presenceof the reflexes is against Guillain-Barre syndrome and sim-ilar neuropathies, including critical illness neuromyopathy.Disturbances of neuromuscular transmission often havepupillary, ptosis, or ophthalmoplegic findings. The lackof exposure to organophosphate, muscle spasm, or in-creased sweating would argue against organophosphatepoisoning. The clinical presentation, elevated serum CK,and an irritable myopathy on electromyography (EMG)suggest a myopathy. With a history of exposure to sim-vastatin, statin-associated myopathy is the likely diagnosis[1,2].

PROGNOSIS: Myalgias and weakness resolve; serum CKsnormalize over days to weeks after stopping the drug. In44 cases, 58% of patients had resolution of symptoms inless than 1 month and 93% had resolution in less than6 months [2,3].

TREATMENT: Failure to discontinue the statin or reducethe dose leads to progression of the myopathy and, insome patients, rhabdomyolysis. The myalgias may per-sist for months after drug discontinuation but eventuallydisappear in most patients. Clinical recovery with normal-ization of serum CK level follows drug discontinuation.No other treatment is necessary except for supportivecare in patients with rhabdomyolysis.


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Nerve and site

Sural.R

Sural.L

Ulnar.L

Median.Lwrist

wrist

Point B

Point B 4.2 ms 14 µV Lat malleolus-Point B 3.4 ms 120 ms 35 m/s

3.7 ms 15 µV Lat malleolus-Point B 2.8 ms 110 ms 39 m/s

3.2 ms 14 µV index finger-wrist 2.6 ms 140 ms 54 m/s

3.2 ms 13 µV index finger-wrist 2.6 ms 140 ms 53 m/s

Peaklatency

Latencydifference

Conductionvelocity



Peroneal.R

Tibial.R

Tibial.L

Peroneal.L

Median.L

Ulnar.L


5.4 ms13.2 ms15.2 ms

5.4 ms7.8 ms2.0 ms

mm310 mm90 mm

m/s40 m/s45 m/s

6.3 mV6.0 mV5.7 mV

EDB-Ankle



wrist 3.0 ms 3.0 ms mm m/s3.4 mV wrist

Ankle-Fibular HeadFibular Head-Pop Fossa


5.3 ms12.8 ms14.2 ms

5.3 ms7.5 ms1.4 ms

mm310 mm100 mm

m/s41 m/s71 m/s

4.5 mV4.3 mV3.8 mV

EDB-AnkleAnkle-Fibular Head

wristantecubital

3.0 ms7.6 ms

3.0 ms4.6 ms

mm250 mm

m/s54 m/s

4.4 mV3.4 mV

APB-wristwrist-antecubital


Nerve and site Latency Latencydifference

Conductionvelocity


Needle EMG data

Deltoid MiddleBiceps BrachiiTriceps Med HGastroc Med HdTibialis AntTibialis AntGlut MedIliopsoas

RRRRRLLL

Ins Act FibsInsertional Activation

+Wave Fasc Amplitude Duration Config Rate ActivationNormalNormalNormalNormalNormalNormalNormalNormal

1+NoneNoneNoneNoneNone1+1+

1+1+NoneNoneNoneNone1+1+


SDMDMDNormMDNormSDSD

SDMDMDNormMDNormSDSD

NormNormNormNormNormNormNormNorm


EARLYEARLYEARLYNormNormNormNormNorm

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NCVs: Sensory and motor nerve conduction studies arenormal. Needle EMG shows early recruitment and manyvoluntary motor units with short duration and low ampli-tude; some motor units are polyphasic. Low-grade spon-taneous activities (i.e., fibrillation and positive waves)are noted in most muscles including the paraspinousmuscles. These findings are consistent with a myopa-thy with mild irritability. Irritable myopathies include in-flammatory myopathy, rapidly progressive muscle dystro-phies, critical illness myopathy, parasitic myopathy (trichi-nosis), toxic myopathy, and myotubular myopathy. With a

history of recent statin drugs, these findings suggest astatin-associated myopathy.

REFERENCES:

1. Thompson PD, Clarkson P, Karas RH. Statin-associated my-opathy. JAMA 2003;289:1681.

2. Thompson PD, Clarkson PM, Rosenson RS. An assessment ofstatin safety by muscle experts. Am J Cardiol 2006;97:69C.

3. Hansen KE, Hildebrand JP, Ferguson EE, Stein JH. Outcomesin 45 patients with statin-associated myopathy. Arch InternMed 2005;165:2671.

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57. Occipital blindness and seizures—why? [1–4]

CLINICAL CASE: A 43-year-old man with sickle cell dis-ease and hypertension (203/110) was found to have aposterior reversible encephalopathy syndrome (PRES). Hehad a sudden onset of headache and total blindness whilestanding, followed by several convulsions. On MRI he hada posterior watershed T2-weighted serpiginous hypoden-sity and vasogenic edema.

CLINICAL EVALUATION: His eyes were open and he wasunresponsive to voice and noxious stimuli, but with in-tact brainstem reflexes, and with a left gaze preference.Routine blood panel and cerebrospinal fluid were normal.The CT angiogram showed vasoconstriction of segmentsof the posterior cerebral artery territory.

TREATMENT: The patient received intensive treatment tolower his blood pressure using captopril and labetolol. Hewas given diazepam, followed by phenytoin. The PRESregressed.

DIAGNOSIS AND COMMENT: Visual cortex ischemia fromhypertension-induced vasospasm with visual cortexseizures resulted in sudden blindness. PRES is an uncom-mon condition, more frequently seen in younger patientswho sustain a sudden rise in blood pressure. It is seen ineclampsia, renal causes of hypertension, and after treat-

ment with drugs used to suppress organ rejection, orfor cancers (L-asparaginase, vincristine). Reversible occip-ital ischemia as may occur with eclampsia can result inreversible or irreversible occipital blindness. Vision can re-turn because vasospasm abates with the lowering of thehypertension. Sickle cell disease can contribute to tissueischemia because of the lower oxygen-carrying capacityof sickle cells and the anemia itself. Visual cortex seizuresare a rare cause of reversible blindness.

The EEG shows a buildup of left occipital, high-frequency sharp waves evolving to slower rhythmicdelta activity before stopping, indicating occipital seizurescaused by PRES as the cause of his visual complaints

REFERENCES:

1. Bartynski WS. Posterior reversible encephalopathy syndrome,part I: Fundamental imaging and clinical features. AJNR2008;29:1036–1042.

2. Williams J, Mozurkewich E, Chilimigras J, Van De Ven C. Criti-cal care in obstetrics: Pregnancy-specific conditions. Best PractRes Clin Obstet Gynaecol 2008;22(5):825–846.

3. Sawchuk KS, Chruchill S, Feldman E. Status epilepticus amau-roticus. Neurology 1997;49:1467–1469.

4. Kaplan PW, Tusa RJ. Neurophysiologic and clinical corre-lations of epileptic nystagmus. Neurology 1993;43:2508–2514.


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58. Unresponsiveness—coma, vegetative state, orlocked-in state? [1–7]

CLINICAL CASE: This 34-year-old woman had headacheand neck pain for 1 week, and then noted for 10 minutesthat she could not move and felt tingling in her arms andlegs. She called for an ambulance when she had difficultybreathing. In the ER, she was unresponsive to voice andstimulation, except to open or close her eyes, possiblyto commands. Head CT scan showed no hemorrhage,and MRI/MRA and an angiogram showed a basilar arteryocclusion with a stroke in the cerebellum and pons, andbilateral vertebral artery dissection. Intra-arterial TPA re-stored vertebrobasilar flow.

However, the next morning, her condition deterio-rated; Doppler studies showed thrombosis of the prox-imal basilar artery and reversal of normal flow. MRIshowed extension of a hemorrhagic infarction into thepons, cerebellar hemispheres, and midbrain with mildhydrocephalus.

From the EEG, is she in coma, a vegetative state (VS),or a locked-in state?

DEFINITIONS:


Vegetative state—The person is awake (eyes open) butunconscious.

Locked-in syndrome (LIS)—A de-efferented state:awake, conscious, but minimal evidence of reaction (ver-tical/horizontal eye movements to questions).

TYPICAL FEATURES: The common theme is the paucityof reaction to stimuli. The patient may be in any of sev-eral states, ranging from conscious, clouded, minimallyconscious to comatose along a continuum. Eyes maybe open, closed, or open variably to command, stim-uli, or open spontaneously. Movement below the neckis minimal or reflexive. See alternate sources for clin-ico/pathological information on these conditions.

CLINICAL EVALUATION: Examine brainstem reflexes, re-activity to stimuli (even minimal vertical eye movementsto command). The assessment is largely directed at de-termining if there is a meaningful response to externalstimuli that would suggest consciousness. Often moreprolonged observation is needed, as families often report“meaningful” responses not seen by nurses and physi-cians. Assess Glasgow coma scale.

DIFFERENTIAL DIAGNOSIS: Minimally conscious state,VS, LIS, or coma.

DIAGNOSIS AND COMMENT: From the clinical description(the patient was unable to move, but was able to followcommands with eye movements as yes/no answers), andfrom an EEG confirming the presence of sleep and wakecycles, the diagnosis was LIS.

Patients with an obvious cause of unresponsiveness(CRA) still often pose diagnostic and prognostic chal-lenges. In persistent vegetative state (PVS) or VS (<1month) as well as with LIS, electrophysiology has yieldeda wide range of findings, but few studies have been per-formed. Further, studies may show evolving results overtime. A small series of eight patients had EEG patternsof alpha, slow activity, or triphasic waves across PVS andcoma. fMRI has been found to differentiate consciousfrom unconscious patients, but clinical features still un-derpin the diagnosis of these various diagnostic entities.


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Part 5: The Casebook of Clinical/Neurophysiology Consults 153

The EEG shows sleep spindles, diffuse theta, positiveoccipital sharp transients of sleep (POSTS) and vertexsharp waves. The pattern is reactive to stimuli produc-ing alpha frequencies and abolition of sleep spindles andthe POSTS.

REFERENCES:

1. Cartlidge N. States related to or confused with coma. J NeurolNeurosurg Psychiatry 2001;71(Supplement 1):i18–i19.

2. Gutling E, Isenmann S, Wichman W. Electrophysiology in thelocked-in-syndrome. Neurology 1996;46:1092–1101.


4. Young GB. Major syndromes of impaired consciousness. In:Young GB, Ropper AH, Bolton CF (eds.), Coma and ImpairedConsciousness: A Clinical Perspective. New York: McGraw-Hill1998;39–78.

5. American Academy of Neurology Quality Standards Sub-committee. Practice parameters: Assessment and manage-ment of patients in the persistent vegetative state. Neurology1995;45:1015–1018.

6. Bernat JL. Chronic disorders of consciousness. Lancet2006;367:1181–1192.

7. Guerit JM. Neurophysiological patterns of vegetativeand minimally conscious states. Neuropsychol Rehabil2005;15:357–371.

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59. Unresponsiveness—organic or psychogenic? [1,2]

CLINICAL CASE: This 21-year-old patient was transportedfrom an outside psychiatric institution with several weeksof history of florid hallucinations and a dream-like state,but no prior psychiatric history. After a week of headache,irritability, she had become delusional and unresponsive,becoming catatonic. At a psychiatric unit, she had a mildpneumonia; cerebrospinal fluid (CSF) showed 8 whiteblood cells (WBCs). We found her eyes opening to voice,intact brainstem reflexes, no vocalization, but posturingto pain. She had rigidity and catalepsy (waxy flexibility) ofher arm, which remained transiently suspended in the airwhen placed there by the examiner. Initial EEG showedtheta/delta activity, and treatment with valproate and lo-razepam produced neither EEG nor clinical change. CSFrepeat showed 13 WBCs, normal protein, and no bac-terial growth. Tests for HSV, Epstein-Barr virus (EBV), cy-tomegalovirus, Varicella Zoster virus (VZV), enterovirus,fungi, Bartonella, Brucella, West Nile, Eastern, and West-ern equine encephalitis were normal. The brain MRI wasnormal.

DEFINITIONS:


Vegetative state—Awake (eyes open) but unconscious.Locked-in syndrome (LIS)—De-efferented state:

awake, conscious, but minimal evidence of reac-tion (vertical–horizontal eye movements to questions).

Catatonia—A state of psychic and motor unresponsive-ness. It may be seen with schizophrenia, posttraumaticstress disorder, bipolar disease, depression, drug abuse,

and overdose. It can occur with strokes, metabolicand autoimmune conditions, encephalitis, adverse re-actions to medications, and sudden withdrawal frombenzodiazepines.

DIFFERENTIAL DIAGNOSIS: This includes en-cephalopathies. Coma, vegetative state (VS), minimallyconscious state (MCS), LIS, and catatonia can be differen-tiated on the basis of clinical criteria by bedside testing.In coma, there is no evidence of clinical response tostimuli, including careful observation of eye movementsto commands. LIS patients will have open eyes and canoften make vertical eye movements to commands. Apatient in MCS may require more prolonged observation,but again looking for evidence of some ability by thepatient to follow commands, or answer (by signs orother). VS patients cycle through eyes-open wakefulnessand sleep, but cannot react reproducibly to externalcommands. Catatonic patients from psychiatric causesmay manifest eyes-closed resistance to opening or haveoccasional sideways glances. Patients with neurolepticmalignant (NMS) or serotonin syndrome (SS) are usuallydrowsier, are lethargic, will move purposefully to nox-ious stimuli, and have brainstem reflexes. Also, toxic,metabolic, and the NMS and SS can be confirmed byother clinical criteria, and tests for electrolyte, ammonia,liver function, and toxins.

ANCILLARY TESTING: Consider toxin screen, CPK, andliver enzymes. Imaging is rarely informative, except toexclude causes of coma, LIS, MCS, or VS. Obtain CSF forviral, fungal, bacterial, and paraneoplastic antigens.

DIAGNOSIS AND COMMENT: She had limbic statusepilepticus from mycoplasma pneumonia. On admis-sion, the patient was thought to have a diffuse en-cephalopathy/encephalitis given the nonlateralizing neu-rological examination, normal MRI of the brain, and the


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CSF studies showing less than 12 WBCs. All CSF, viraland autoimmune antigen panels were negative. Becauseof the pneumonia, she was tested for mycoplasmosis,which came back strongly positive. There are rare casesof nonconvulsive status epilepticus with mycoplasmosis,thought to arise from a cross-reactivity of brain structureswith the mycoplasma surface antigens. This interactionmay impair thalamocortical circuits. Of hospitalized pa-tients with mycoplasma pneumonia, 7% can have cen-tral nervous system symptoms including seizures; overall23% have serious sequelae. In this patient’s case, sheclinically and electroencephalographically had a limbicencephalopathy. The patient was treated with high-dosebenzodiazepines, which normalized the rhythmic 2- to4-Hz EEG pattern shown above. The patient returned to

talking and following commands within 5 minutes. Shewas given a 4-week course of doxycycline for the my-coplasma pneumonia.

This EEG shows shifting rhythmic, monomorphicfrontal, and diffuse theta/delta activity.

REFERENCES:

1. Koskiniemi M. CNS manifestations associated with My-coplasma pneumoniae infections: Summary of cases atthe University of Helsinki and review. Clin Infect Dis1993;17:S52–S57.

2. Heatwole CR, Berg MJ, Henry JC, Hallman JL. Extreme spin-dles: A distinctive EEG pattern in Mycoplasma pneumoniaeencephalitis. Neurology 2005;64:1096–1097.

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60. Patient with a frontal brain tumor—psychiatricdepression, paranoia, tumor growth, or statusepilepticus? [1–4]

CLINICAL CASE: A 45-year-old man with a resected leftfrontal glioma had a history of complex partial seizures.An urgent consult was sought for the sudden onset of de-pressive thoughts, paranoia, and mild expressive aphasiawith some waxing and waning of severity.

CLINICAL EVALUATION: He was alert but appeared puz-zled, was searching for words, and frequently looked overat his wife. He would suddenly raise his eyebrows and wasfidgety. MRI revealed no change from that of a few weeksbefore, prior to the behavioral change. The antiepilepticdrug (AED) level was “subtherapeutic.”

TREATMENT: His levetiracetam dosage was increased,and he was given 2 mg of lorazepam. The psychiatric,depressive, and inattention symptoms regressed.

DIAGNOSIS AND COMMENT: He had left frontal epilepti-form activity causing hallucinations and paranoia, all ofwhich regressed with AEDs.

Left frontal epileptic foci may produce bizarre psy-chiatric, complex motor, behavioral, and languagedisturbances. The depressive and paranoid featureshave long been recognized, but remain relatively rarephenomena.


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The EEG shows continuous left frontal epileptiform dis-charges at about 1 per second.

REFERENCES:

1. Thomas P, Zifkin B, Migneco O, Lebrun C, Darcourt J, An-dermann F. Nonconvulsive status epilepticus of frontal origin.Neurology 1999;52:1174–1183.

2. Lim J, Yagnik P, Schraeder P, Wheeler S. Ictal catatonia asa manifestation of nonconvulsive status epilepticus. J NeurolNeurosurg Psychiatry 1986;49:833–836.

3. Rohr-Le Floch J, Gauthier G, Beaumanoir A. Confusionalstates of epileptic origin. Value of emergency EEG. Rev Neurol1988;144:425–436.


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61. Patient with idiopathic generalized epilepsy onvalproate—Metabolic encephalopathy or statusepilepticus? [1–5]

CLINICAL CASE: A 68-year-old man with metastatic lungdisease, and JME onset in his teens, had had severaladmissions in middle age for confusional states. Duringthese events, he had been found to be in absence sta-tus (generalized nonconvulsive status epilepticus—GNSE)[1]. When he was on increased dosage of valproate be-cause of seizures and status epilepticus that could notbe controlled on other antiepileptic drugs, he had awaxing–waning confused state. EEG was performed anda basic metabolic panel was sent.

DIFFERENTIAL DIAGNOSIS: In this case, the differentialconsiderations were among (a) toxic encephalopathyfrom medication, (b) compromised hepatic function withhyperammonemia, (c) an hypoxia from his compromisedpulmonary status, or (d) GNSE for which he had beenhospitalized many times before.

DIAGNOSIS AND COMMENT: He has a hyperammonemicencephalopathy from his valproate, and is not in noncon-vulsive status (NCSE).

The EEG tracing now shows a slow background withtriphasic waves (TWs) that are clearly distinguishablefrom his epileptiform discharges in the same tracing.Along with the raised ammonia, but unchanged liver en-zymes, the diagnosis would be valproate-induced hyper-

ammonemia (and not another cause of toxic/metabolicencephalopathy or NCSE).

TREATMENT: Valproate dosage was lowered as was hisdietary protein, and his confusion and TWs regressed.

DISCUSSION: Epileptiform discharges are rarely seenalong with TWs in the same patient. Much literature hasbeen written on distinguishing characteristics betweenthe two entities: TWs and spike-wave complexes (seethe case with TWs). In the past there has been specu-lation that TWs were a reflection of epileptiform activityappearing in a severely compromised encephalopathicbrain, hence the blunter, broader morphologies. Thereare however differences between them that include thereactivity of TWs to stimuli (increase TWs). Furthermore,TWs often appear in elderly patients with diffuse atro-phy and white matter disease, as well as with a numberof toxic/metabolic problems, suggesting a component ofsubcortical contribution to their appearance. As TWs donot appear in childhood, it is possibly because of the dif-ference in thalamocortical transmission in the youngerage group. Although still poorly understood, TWs mayrepresent projected rhythms from the thalamus, whichare altered along the path of the reverberating thalamo-cortical circuit.


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The EEG shows occasional generalized spike-slow wavedischarges (see the end of the 2nd second and beginningof the 6th second of the EEG sample). These dischargeswere of short duration (spike to beginning of slow wave,with clear initial spike), and a field extending to the an-terior frontal region, with occasional frontocentral phasereversals (similar to his interictal recordings). However,there are also now brief flurries of TWs on a slow back-ground. The TWs are in the posterior centrofrontal re-gion, have a minimal first phase, and a wider 1st to 2ndphase duration, with overall broader complexes than theepileptic discharge (see the 5th second). Hepatic aspar-tate aminotransferase and alanine aminotransferase (ALT)were unchanged from a baseline and from when he waspreviously fully alert, but the serum ammonia was 170mg/mL.

REFERENCES:


2. Baykan B, Gokyigit A, Gurses C, Eraksoy M. Recurrent absencestatus epilepticus: Clinical and EEG characteristics. Seizure2002;11:310–319.

3. Thomas P, Valton L, Genton P. Absence and myoclonic statusepilepticus precipitated by antiepileptic drugs in idiopathicgeneralized epilepsy. Brain 2006;129:1281–1292.



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62. Unresponsiveness—psychogenic, encephalopathy,or limbic encephalitis? [1–10]

CLINICAL CASE: A 51-year-old woman was transportedfrom an outside hospital with a 10-month history ofdelirium, a dementia, partial seizures, sudden dystonicmovements, and hyponatremia. Outside hospitals haddiagnosed temporal lobe seizures on epilepsy monitor-ing, and had found normal thyroid antibodies, no 14-3-3 protein, normal paraneoplastic antibody panel, and anegative work-up for celiac disease, sarcoid, Whipple’sdisease, lupus, and systemic cancer. The MRI showedcortical laminar enhancement of the lateral, mesial, andinsular temporal cortices more on one side than theother. Cerebrospinal fluid (CSF) protein was raised, cellsnormal, no viral antigens; serum sodium was 128. Ex-amination revealed a minimental status examination of26/30—marked and generalized memory impairment,but she could recite serial 7s and “WORLD” backward.She had bizarre, sudden grimacing with stiffening andasymmetric dystonic postures of both arms lasting lessthan 10 seconds of which she was unaware. She wason antiepileptic drugs and had tried a 3-day course ofsteroids.

DIFFERENTIAL DIAGNOSIS: Hashimoto’s thyroid antibodyencephalopathy, paraneoplastic encephalopathy, celiacdisease, Whipple’s disease, viral encephalitis, central ner-vous system lupus, nonconvulsive status, medicationtoxicity.

CLINICAL CORRELATION: There were no dystonic or otherabnormal movements during the EEG.

DIAGNOSIS AND COMMENT: The patient had anantibody-mediated, voltage-gated anti-potassium chan-nel nonparaneoplastic limbic encephalitis (VGKC) withseizures, paroxysmal dystonias, paranoia, confusion, andhyponatremia.

The constellation of partial seizures, movement disor-der, and delirium in the absence of CSF cells or anti-bodies to viruses suggested a steroid-responsive thyroidantibody or paraneoplastic syndrome. This was testedfor, but results were negative. Workups for other raresyndromes affecting cognition, causing encephalopathy,seizures, and movement disorders, such as Whipple’s andceliac disease, were also negative. In addition, the pres-ence of unexplained hyponatremia strongly suggesteda potassium channel antibody-associated encephalopa-thy (VGKC)—an immunotherapy-responsive form of lim-bic encephalitis. High-dose steroids were started with agradual taper; VGKC-Ab was remeasured; she was againscreened for malignancy, and subsequently had IVIG andthen plasmapheresis on subsequent relapses.

The hyponatremia from syndrome of inappropriate an-tidiuretic hormone (SIADH) is well recognized in this con-dition and improves with immunotherapy-induced fall inVGKC-Ab.


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This EEG shows runs of frontal 2–3 Hz rhythmic, occa-sionally notched delta activity, not clearly related to sleep,arousal, or change in clinical state. There is a low-voltagefast background EEG pattern.

REFERENCES:

1. Vincent A, Buckley C, Schott J, Baker I, Dewar BK, De-tert N, Clover L, Parkinson A, Bien CG, Omer S, Lang B,Rossor MN, Palace J. Potassium channel antibody-associatedencephalopathy: A potentially immunotherapy-responsiveform of limbic encephalitis. Brain 2004;127:701–712.

2. Alamowitch S, Graus F, Uchuya M, Ren R, Bescansa E, Delat-tre JY. Limbic encephalitis and small cell lung cancer. Clinicaland immunological features. Brain 1997;120:923–928.

3. Brierley JB, Corsellis JAN, Hierons R, Nevin S. Subacute en-cephalitis of later adult life mainly affecting the limbic areas.Brain 1960;83:357–368.

4. Chong JY, Rowland LP, Utiger RD. Hashimoto encephalopa-thy: Syndrome or myth? Arch Neurol 2003;60:164–171.

5. Dunstan EJ, Winer JB. Autoimmune limbic encephalitis caus-ing fits, rapidly progressive confusion and hyponatremia.Age Aging 2006;35:536–537.

6. Bataller L, Kleopa KA, Wu GF, Rossi JE, Rosenfeld MR, Dal-mau J. Autoimmune limbic encephalitis in 39 patients: Im-munophenotypes and outcomes. J Neurol Neurosurg Psychi-atry 2007;78:381–385.

7. Stubgen JP. Nervous system lupus mimics limbic encephalitis.Lupus 1998;7:557–560.

8. Iizuka T, Sakai F, Ide T, Monzen T, Yoshii S, Iigaya M, SuzukiK, Lynch DR, Suzuki N, Hata T, Dalmau J. Anti-NMDA recep-tor encephalitis in Japan. Neurology 2008;70:504–511.

9. McKeon A, Marnane M, O’Connell M, Stack JP, KellyPJ, Lynch T. Potassium channel antibody-associated en-cephalopathy presenting with a frontotemporal dementia-like syndrome. Arch Neurol 2007;64:1528–1530.

10. Thieben MJ, Lennon VA, Boeve BF, Aksamit AJ, KeeganM, Vernino S. Potentially reversible autoimmune limbic en-cephalitis with neuronal potassium channel antibody. Neu-rology 2004;62:1177–1182.

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63. Respiratory weakness—toxic or metabolic?

CLINICAL CASE: A 26-year-old woman was admitted tothe hospital with nausea, vomiting, abdominal pain, andweight loss for 3 weeks. She developed lower extrem-ity weakness with paresthesias in her feet 2 days priorto admission. On the day of admission, she was unableto move her legs and had worsening weakness in theupper extremities. She could not feel her lower extrem-ities. One day into her hospitalization, she became in-creasingly confused. She later developed respiratory fail-ure. There was no bowel or urinary incontinence. At thetime of her hospital admission, examination showed 0/5strength in the legs, 4/5 in the proximal upper extremi-ties, and 4−/5 distally. Reflexes were diffusely depressed.There was markedly reduced pinprick sensation in thelegs and loss of vibratory and proprioception sensation;no Babinski’s sign. Cervical and thoracic MRIs were nor-mal, as were CPK, complete blood count, and completemetabolic panel. Heavy metal screen and cerebrospinalfluid were normal.

DIFFERENTIAL DIAGNOSIS: The differential diagnosis in-cludes not only acute polyneuropathies, but alsomyelopathy, neuromuscular junction defect, and my-opathy. Acute polyneuropathies include arsenic poison-ing, n-hexane or glue-sniffing neuropathy, vasculitis,Lyme disease, tick paralysis, porphyria, sarcoidosis, lep-tomeningeal disease, paraneoplastic disease, and criticalillness polyneuropathy. Arsenic poisoning, porphyria, andacute severe vasculitic neuropathy should be considered.An axonal polyneuropathy is not consistent with clas-sic Guillain-Barre syndrome (GBS), but an axonal formacute motor axonal neuropathy (AMAN) still needs to beconsidered. The abdominal pain and psychosis suggestpossible acute intermittent porphyria (AIP). Absent Babin-ski’s signs, lack of a sensory level, and no bowel/urinary

incontinence are against a myelopathy. The spine MRIis also normal. The sensory finding is against a motorneuron disease. Neuromuscular junction disorders maypresent acutely, but usually cause bulbar weakness, pap-illary dysfunction, ptosis, or ophthalmoplegia. The sen-sory loss and hyporeflexia also argue against myastheniagravis. There is no exposure to suggest organophosphatepoisoning. Myopathies are also unlikely because of thehyporeflexia and sensory loss. In summary, this patienthas a rapidly progressing axonal polyneuropathy such asarsenic poisoning, porphyria, GBS (i.e., AMAN), or acutesevere vasculitic neuropathy. The abdominal pain and psy-chosis possibly suggest porphyria.

DIAGNOSIS AND COMMENT: The asymmetric, axonal mo-tor polyneuropathy with abdominal pain, psychosis andraised d-ALA and porphobilinogen indicate AIP. Patientswith AIP usually present with abdominal pain, psychi-atric symptoms such as hysteria, and mainly axonal mo-tor polyneuropathies. Most patients are completely freeof symptoms between attacks. AIP displays neurovisceralsymptoms but no skin manifestations. There may be au-tonomic neuropathies (e.g., constipation, colicky abdom-inal pain, vomiting, and hypertension), peripheral neu-ropathy, seizures, delirium, coma, and depression. Theabdominal pain is severe and lasts for several days. Severeabdomen pain of short (<1 day) duration or chronic ab-dominal pain is unusual. The pain is often epigastric andcolicky in nature. Constipation is common and can bevery severe. Frequently, nausea and vomiting are present.AIP patients may have central nervous system signs, con-sisting of seizures, mental status changes, cortical blind-ness, coma, and psychiatric symptoms. Finally, patientsoften experience peripheral neuropathies that are pre-dominantly motor and can mimic GBS. The weaknessusually starts in the lower limbs and ascends, but neu-ropathies can be observed in any nerve distribution. Are-flexia or hyporeflexia is often present on examination.Patients also may have cortical blindness. Diffuse pain,


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164 Part 5: The Casebook of Clinical/Neurophysiology Consults

especially in the upper body, can be observed. Patientsmay develop autonomic neuropathies, such as hyperten-sion and tachycardia. The fundamental step in diagnos-ing AIP is to demonstrate increased urinary porphobilino-gen secretion, particularly during an attack. Betweenattacks, the enzyme uroporphyrin-1-synthetase maybe decreased.

PROGNOSIS: Most patients (60–80%) have a single acuteattack. Avoidance of precipitating factors helps preventattacks [1,2].

TREATMENT: The treatment for acute attacks of porphyriais to decrease heme synthesis and reduce the produc-tion of porphyrin precursors [3]. High doses of glucose(400 g/day) can inhibit heme synthesis and are useful fortreatment of mild attacks. Severe attacks, especially thosewith severe neurologic symptoms, should be treated withhematin in a dose of 4 mg/kg per day for 4 days. Paincontrol is best achieved with narcotics. Laxatives and stoolsofteners should be administered with the narcotics toavoid exacerbating a coexisting constipation. The patientshould receive a high-carbohydrate diet during the at-tack. If the patient is unable to eat, intravenous glucoseshould be administered. Between attacks, eating a bal-anced diet is more important than eating one rich inglucose.

NCVs: Bilateral sural sensory nerve action potential ampli-tudes were mildly reduced. There was conduction blockin the left peroneal nerve across the knee, found again1 week later, with an absent left peroneal response. Leftulnar, median, and radial sensory responses were nor-mal; both peroneal and tibial compound motor actionpotential (CMAP) amplitudes were reduced along withleft ulnar and median CMAP amplitudes. Right ulnar andmedian motor studies were normal. Needle electromyo-graphy showed acute denervation in the lower and up-per extremities. These findings are indicative of an asym-metric, motor polyneuropathy with predominantly axonalfeatures

REFERENCES:

1. Anderson KE, Bloomer JR, Bonkovsky HL, Kushner JP, PierachCA, Pimstone NR, Desnick RJ. Recommendations for the diag-nosis and treatment of the acute porphyrias. Ann Intern Med2005;142(6):439–450.

2. Kauppinen R, Mustajoki P. Prognosis of acute por-phyria: Occurrence of acute attacks, precipitating factors,and associated diseases. Medicine (Baltimore) 1992;71(1):1–13.

3. Mustajoki P, Tenhunen R, Pierach C, Volin L. Heme in thetreatment of porphyrias and hematological disorders. SeminHematol 1989;26:1.

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64. Failure to wean from a ventilator/internalophthalmoplegia—bulbar dysfunction, neuromuscularjunction problem, or polyneuropathy?

CLINICALCASE: A 35-year-old man woke up with dou-ble vision, and by the evening, had droopy eyelids andblurred vision. The next morning, he had nausea andvomiting followed by slurred speech and swallowing dif-ficulty. Examination showed bilateral external ophthal-moplegia and ptosis. Pupils were dilated and unreactiveto light or attempted accommodation. Corneal reflexeswere depressed. There was bilateral facial weakness ofthe upper and lower face; tongue was weak without fas-ciculation. There was no gag. Neck flexion and extension(Medical Research Council 4/5) and pelvic and shouldergirdle muscle (5−/5) were mildly weak. Tendon reflexeswere depressed (1/4). Body and limb sensation, and limbreflexes were normal. The creatine kinase (CK), completeblood count, and metabolic panel were normal; brain MRIwas normal.

DIFFERENTIAL DIAGNOSIS: Viral syndrome, encephalitis,Guillain-Barre syndrome, and acute neuropathies are themost common. Myasthenia gravis, botulism, inflamma-tory myopathy, diabetic complications, hyperemesis gravi-darum with hypokalemia, hypothyroidism, and laryngealtrauma are rarer considerations.

The progression of symptoms over several days sug-gests a subacute process, but the presence of reflexesand normal sensory examination are against Guillain-Barre syndrome and acute neuropathies. The prominentinvolvement of bulbar weakness, normal serum CK eleva-tion, and electromyography (EMG) findings are not seenwith a myopathy. A neuromuscular junction dysfunctionremains high on the differential diagnosis. The lack offatigable weakness, depressed corneal reflexes, and un-reactive pupils support a diagnosis of a presynaptic neu-romuscular junction dysfunction, namely botulism in thiscase. This is in agreement with the modest increment on

repetitive stimulation at high frequency and after a shortperiod of exercise.

DIAGNOSIS AND COMMENT: The compound muscleaction potential (CMAP) increment with rapid, repetitivestimulation is modest (30–100%) in botulism in compar-ison to marked increment (usually >200%) in Lambert-Eaton myasthenic syndrome. The above findings are con-sistent with botulism.

Botulism is rare but potentially fatal. Botulism should besuspected with (1) rapid, descending muscular weakness(ocular to bulbar to extremities), (2) subacute bilateralophthalmoplegia, particularly with pupil dilatation, (3)generalized weakness associated with autonomic symp-toms, and (4) a history of contaminated food ingestionor a wound.

PROGNOSIS: Before 1950, mortality with botulism wasreported to be about 60% [1]. It is now less than 8% inthe USA because of critical care and respiratory support[2,3]. Heightened awareness, better recognition, and ear-lier administration of antitoxin also play a role in thisimprovement. Recovery is usually protracted, and maycontinue for as long as 5 years.

TREATMENT: Supportive treatment is essential. This in-cludes artificial ventilation, feeding, prophylaxis for deepvein thrombosis, and physical therapy for prevention ofmuscle and tendon contractures. Efforts to neutralize thetoxin should be immediate with trivalent antitoxin (A, B,and E)—most effective early in the disease—unlikely tobe effective more than 3 days after exposure [4]. Cleans-ing the gastrointestinal tract by enema or lactulose andneomycin are useful, especially in infants. Guanidine and3,4-diaminopyridine can help.


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Nerve and site

Median.RWrist

Wrist

Muscle / train

Baseline

Baseline

Baseline

L. Deltoid, Axillary, C5-6

Wrist

Wrist

Elbow

B.Elbow

Ankle

L. Biceps, Musculoe, C5-6

L ADM, Uln, C8-T1

L Median - APB

L Peroneal - EDB

L Ulnar - ADM

L ADM, Uln, C8-T1

L ADM, Uln, C8-T1

EMG summary table

Nerve / sites

Motor NCS (Demy)

Fib

Latms

PSW Fasc MUs FRRecruit Other

2–3–

MostMost

2–3–

Early0NR

0NR

0

4.252.70

2.70

2.55

59.8

155

2.80

81100

1154.355.00

5.004.05

100

100

100

100

100

1.3

1.71.1

1.11.9

24.7

45.2

9

100

134100

49.6100

7

0.7

0.90.7

0.40.8

6.35

NR Early MostMost Most

MostNININI

PolyP–

–

–

AmplitudeDurMUs MUs Amp

DurationSpent

L APB, Med, C8-T1Baseline

AmpmV

AmpmV

Distcm

Velm/s

AreamVms

Rel Area%

Durms

Rel Dur%

Rel Amp%

1.1 15.8 –3.6 100 3.0 111 100 50 0:00:00

0:00:00

0:00:00

0:00:00

50

50

50

100

100

100

–32.3

–27.6

–28.1

–17.4

99.6

2.1

5.5

1.6

0.8

2.2

100

100

100

–0.3

67.3

–0.2

44.7

18.4

2.1

0.6

0.5

0.7

TimeRatepps

Fac%

Lowerst-1%

4-1%

AreamVms

Fac%

Lowest-1%

4-1%

Ulnar.R

Sural.R3.2 ms



Lateral mallcolus-Point B

17 µV

14 µV

11 µV

3.1 ms

4.1 ms

Rep nerve stim

Point B

Peaklatency


2.2 ms 105 mm

130 mm

110 mm

48 m/s

52 m/s

50 m/s

2.5 ms

2.1 ms


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NCVs: Sensory nerve action potentials are normal. CMAPamplitudes are mildly reduced. Repetitive stimulation at3 Hz of the median and facial nerve at rest shows a 13%decrement. There is an 80% increment of the medianCMAP amplitude after rapid, repetitive stimulation (50Hz). Similarly, there is a 70% increment of the medianCMAP recording at the abductor pollicis brevis muscle af-ter a short period of exercise. Needle EMG of the selectedmuscles is normal. These findings are consistent with aneuromuscular junction disorder of the presynaptic type,supported by postexercise CMAP facilitation and a sig-nificant increment (>50%) of the CMAP amplitude afterrapid, repetitive stimulation of the motor nerves.

REFERENCES:

1. Centers for Disease Control and Prevention. Botulism in theUnited States 1899–1996. Handbook for Epidemiologists,Clinicians and Laboratory Workers.

2. Abrutyn E. Botulism. In: Fauci AS, Isselbacher KJ, BraunwaldE (eds.), Principles of Internal Medicine, 14th edn. New York:McGraw-Hill 1998;904.

3. Varma JK, Katsitadze G, Moiscrafishvili M, Zardiashvili T,Chokheli M, Tarkhashvili N, Jhorjholiani E, Chubinidze M,Kukhalashvili T, Khmaladze I, Chakvetadze N, Imnadze P.Hoekstra M, Sobel J, Hennessy TW, Rotz LD. Signs andsymptoms predictive of death in patients with foodbornebotulism–Republic of Georgia, 1980–2002. Clin Infect Dis2004;39:357.

4. Arnon SS, Schechter R, Maslanka SE, Jewell NP, Hatheway CL.Human botulism immune globulin for the treatment of infantbotulism. N Engl J Med 2006;354(5):462–471.

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65. Progressive sensory loss and painful gait—radiculopathy, toxic, infectious neuropathy, ormyopathy?

CLINICAL CASE: A 27-year-old man with HIV has severalweeks of progressive leg pain and is now unable to walk.Examination shows that he has painful feet (includingsoles), sensitive to light touch, with a symmetric distalsensory loss to all modalities just below the knee. Thereis mild distal weakness of ankle dorsiflexion and plantarflexion. Deep tendon reflexes are absent in the anklesand reduced in the knees. There is normal CPK, completeblood count and metabolic process; cerebrospinal fluidshows a mild pleocytosis and protein elevation.

DIFFERENTIAL DIAGNOSIS: The differential for painfulneuropathy includes acute inflammatory demyelinat-ing polyradiculoneuropathy, diabetic neuropathy, HIV-1-associated multiple mononeuropathies, nutritional neu-ropathy, toxic neuropathy, other HIV-related neuropathies(differentiated by HIV-associated distal painful sen-sory, neuropathy’s slower progression), alcoholic neu-ropathy, and a metabolic neuropathy. A paraneoplas-tic sensory neuropathy, paraproteinemic neuropathy,cytomegalovirus-related mononeuropathy, human T-cellleukemia virus type 2 (HTLV-2)-related neuropathy, andvasculitic neuropathy are less common.

DIAGNOSIS AND COMMENT: HIV-positive serology, neu-ropathic pain, and paresthesias with gradual spread-ing proximally in the lower extremities should suggestHIV-associated distal symmetric peripheral neuropathy(DSPN).

There are a number of distinctive neuropathic syn-dromes, which can be classified according to the timingof their appearance during HIV infection, their etiology,and whether they are primarily axonal or demyelinating.The most common of these is peripheral neuropathy, alsoreferred to as DSPN. DSPN usually manifests as bilat-eral tingling and numbness in the toes. The neuropa-thy gradually spreads proximally in the lower extremities,

with only rare involvement of the upper extremities. Thespread of sensory symptoms usually occurs over weeksto months. Neuropathic pain is common and may bethe presenting symptom. Neurologic examination showssensory loss to all sensory modalities (vibration, pinprick,temperature) in a stocking distribution, while deep ten-don reflexes are reduced or absent at the ankles andoccasionally at the knees in more severe cases. Distalweakness in the lower extremities can occur, althoughmost patients have only sensory symptoms and signs.Sensory findings in the hands are more commonly asso-ciated with drug toxicity. HIV-related DSPN may evolvefrom painful to painless numbness. Skin biopsy for epi-dermal nerve fiber density analysis has been shown tocorrelate with neuropathy severity, level of neuropathicpain, and sensory amplitudes on electrodiagnostic stud-ies. Nerve biopsy is not usually required but is occasion-ally performed in severe cases to exclude a concurrentmononeuropathy multiplex. Biopsies show axonal losswith frequent foci of inflammation in the endoneuriumor around perineurial blood. Other HIV-associated neu-ropathies include acquired inflammatory demyelinatingpolyradiculoneuropathy, cauda equina syndrome, diffuseinfiltrative lymphocytosis syndrome, autonomic neuropa-thy, mononeuropathies, herpes zoster radiculitis, and sen-sory ganglionopathy.

PROGNOSIS: HIV-associated distal painful neuropathy is aprogressive disease. The effect of highly active antiretro-viral therapy (HAART) on the distal symmetrical polyneu-ropathy is unclear, although there is some evidence show-ing improved quantitative sensory measures in patientsresponding to HAART [1,2].

TREATMENT: Treatment is directed at the cause andthe symptoms. Treatment of the cause includes dis-continuing potentially neurotoxic drugs (i.e., stavudine(d4T) or didanosine (ddI) or thalidomide). Managementof DSPN is symptomatic, aimed at the painful dyses-thesias. Gabapentin, topiramate, antidepressants topical


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Nerve and site

Sural.L

Median.L

V Digit

Point B

Point B NR ms

NR ms

3.8 ms

3.5 ms

2.8 ms

Wrist-Digit II


Wrist-V Digit



18 µV 51 m/s2.7 ms

mm

mm m/s

m/s

40 m/s

49 m/s130 mm

120 mm

150 mm

2.5 ms

ms

3.8 ms

ms

4 µV

9 µV

µV

µV

Digit II

Forearm

Tibialis anterior.L

Gastrocnemius(Medial head.L)

Nerve and site Conductionvelocity

Amplitude


Tibial.L

Tibial.R

Ankle14.2 ms16.5 ms

4.4 ms

4.3 ms13.2 ms

8.4 ms3.2 ms

3.2 ms

15.2 ms

4.7 ms

3.6 ms

0.4 mV0.5 mV1.4 mV

1.4 mV

1.3 mV

1.3 mV

6.8 mV4.9 mV

1.8 mV

1.8 mV

1.4 mV

mm

mm

mm

mm

43 m/s26 m/s

33 m/s

48 m/s

43 m/s

40 m/s

m/s

m/s

m/s

m/s

m/s

100 mm280 mm

290 mm

mm

mm

230 mm

80 mmFibula (head)Popliteal fossa

Ankle

Ankle

Ankle

Peroneal.L

Peroneal.R

Median.L

Wrist

Wrist

Antecubital

Ulnar.L

DistanceLatency

Muscle

Insertional

Insertional Fibs

None None

None

None

None

Fasc

None

NoneNone

+Wave

Normal Normal

Normal

Normal

Normal

Normal

Normal

Normal

DurationRateActivator

Spontaneous activity Volitional MUAPs

Amplitude Config Other

Normal

Normal

NormalNormal

Radial.L

Ulnar.L

Sural.R

Amplitude Segment Distance Conductionvelocity

Latencydifference

Peaklatency




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capsaicin and anti-inflammatory therapies, tramadol, andopioid therapy may be considered. The effect of HAARTremains unclear.

NCVs: Bilateral sural sensory responses are absent and theleft ulnar sensory nerve action potential amplitude is re-duced. Left median and radial sensory responses are nor-mal, but both peroneal and tibial compound motor actionpotential amplitudes are reduced. Left ulnar and medianmotor studies are normal. Thus, electrodiagnostic stud-

ies show a length-dependent, symmetric, sensorimotorpolyneuropathy with predominantly axonal features.

REFERENCES:

1. Martin C, Solders G, Sonnerborg A, Hansson P. Antiretro-viral therapy may improve sensory function in HIV-infectedpatients: A pilot study. Neurology 2000;54:2120.

2. Pomerantz R. Residual HIV-1 disease in the era of highly activeantiretroviral therapy. N Engl J Med 1999;340:1672.

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66. Slowly progressive leg and arm weakness—radiculopathy, plexopathy, ALS, or CIDP/AMN?

CLINICAL CASE: A 45-year-old man had 2 years of pro-gressive right leg weakness. Over the past year he has be-gun to trip. Months ago, his right arm began to weakenwithout pain or sensory loss. Examination showed mildweakness (4+/5 MRC) of the right foot eversion and dor-siflexion; mild weakness (5−/5) of the right thenar mus-cles; fasciculations in the right quadriceps, and no rightbrachioradialis, biceps and ankle reflexes. All other re-flexes, sensory testing, creatine kinase, complete bloodcount and metabolic panel, brain and cervical/lumbarspine MRI were normal. Anti-GM1 antibody titers werehigh.

DIFFERENTIAL DIAGNOSIS: The clinical diagnosis mightinclude amyotrophic lateral sclerosis (ALS), radiculopa-thy, plexopathy, multifocal motor neuropathy (MMN),a chronic inflammatory demyelinating polyradiculoneu-ropathy (CIDP), Lewis-Sumner syndrome (MADSAM),mononeuritis multiplex hereditary motor sensory neu-ropathy type 2, a hereditary neuropathy with liability topressure palsies, or a toxic neuropathy. The electromyo-graphy (EMG) findings, asymmetrical weakness, and re-duced reflexes in the affected nerves exclude a myopa-thy. The lack of sensory deficit suggests ALS or MMN.Multifocal motor neuropathy—MMN (or multifocal mo-tor neuropathy with conduction block)—is characterizedby lower motor neuron signs. The absence of upper mo-tor neuron sign, acute denervations in only affected my-otomes, and the presence of conduction block argueagainst ALS.

DIAGNOSIS AND COMMENTS: Multifocal motor neuropa-thy. Motor nerve conduction studies in MMN often showevidence of conduction block, representing focal demyeli-nation. Sensory conduction through the same segmentof nerve is normal. Elevated titers of anti-GM1 antibod-ies are evident in 70–80% of patients with MNN. Whileconduction blocks may be seen in demyelinating neu-ropathies such as CIDP, the normal sensory responsespoint toward a diagnosis of MMN [1]. MMN with conduc-tion block is an acquired immune-mediated demyelinat-ing neuropathy with slowly progressive weakness, wristdrop, grip weakness, impaired dexterity, foot drop, fas-ciculations, and cramping, without significant sensoryinvolvement. Weakness is a result of nerve conductionblock, usually the radial, common peroneal, median, orulnar nerves. MMN may resemble ALS, but muscle atro-phy, bulbar symptoms, and more rapid progression are of-ten not seen in MMN. Elevated anti-GM1 antibody titersoccur in 50% of patients with MMN. Unlike ALS, MMNusually responds to intravenous immunoglobulin (IVIg) orcyclophosphamide, even after onset of symptoms [2, 3].Anecdotal reports suggest that rituximab, interferon-β,azathioprine, and cyclosporine may be efficacious.

PROGNOSIS: Usually good with 70–80% of patients re-sponding to treatment with intravenous immunoglobulinor cyclophosphamide, even after many years [4]. Unre-sponding patients may experience only slowly progressiveweakness, with more than 90% of patients remainingemployed.


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Nerve and site

Sural.R

Sural.R

Point B

Point B

Ulnar.R

Median.R

Radial.RForearm

Tibial.R

5.4 ms

13.2 ms

15.2 ms






10 µV

9 µV

17 µV

11 µV

26 µV1.7 ms

3.1 ms

3.1 ms

3.2 ms

4.1 ms

4.7 ms

4.6 ms

5.3 ms12.8 ms14.2 ms

3.0 ms7.6 ms

3.0 ms wrist 3.0 ms

3.0 ms

4.7 ms

1.7 ms

2.1 ms

2.5 ms

2.1 ms

2.2 ms 105 mm

105 mm

130 mm

110 mm

100 mm

48 m/s

52 m/s

50 m/s

59 m/s

48 m/s

5.4 ms

90 mm

310 mm

310 mm100 mm

250 mm 54 m/s

71 m/s41 m/s

45 m/s

40 m/s

mm

mm

mm

mm

m/s

m/s

m/s

m/s

m/s

m/s

mm

mm

7.8 ms

2.0 ms

4.6 ms

5.3 ms7.5 ms1.4 ms

4.6 mswrist-antecubital


AH-ankle

AH-ankle

Ankle-Fibular HeadEDB-Ankle


Ankle-Fibular Head

EDP-Ankle

APB-wrist

3.8 mV

16.9 mV

14.5 mV

2.1 mV

1.1 mV

2.0 mV

4.4 mV

4.3 mV4.3 mV

3.8 mV

1.4 mV

ankle

Tibial.L

ankle

Pop Fossa

Fibular Head

Ankle

Peroneal.R

Pop Fossa

antecubitalwrist

wrist

MusclePeroneus longus.R

L5-paraspinous.R

Abductor pollicis br.L

+3

+3+3

None

NoneNoneNone

NoneNoneNoneNone

None

+2+3

+3+3

None

NoneNoneNone

None

NoneNoneNone

None

NoneNoneNone

NoneNoneFasc Rate

RapidRapid

RapidRapid

SISI SI

SI

SISISI

SIGD

GDGD

MDActivationFibs

Spontaneous activity Volitional MUAPs

NoneNoneNone

NoneNoneNoneNone

None

+2+ Wave

NormalNormal


NormalNormalNormal

Normal

NormalNormal Normal

Normal

Normal

Normal Normal

Normal Normal Normal

Normal

Normal

NormalNormal

NormalNormal

Normal

Normal

NormalConfigAmplitudeDuration Other

NormalDeltoid.RBiceps.R

First dorsal intero.R

Pronator teres.RAbductor pollicis br. RGastrocnemius.L

lliopsoas.RRectus femoris.RGastrocnemius.R

Tibialis anterior.R

InsertionalInsertional

Median.L

Ulnar.L

Fibular HeadAnklePeroneal.L

Wrist

Wrist

Peaklatency

SegmentAmplitude Latencydifference




Nerve and site Latency SegmentAmplitude Latencydifference



Motor NCS Median-APS

2

24

3 Wrist 150 ms 5 mV

50 ms 5 mV

50 ms 5 mV

Axilla 3

Bbow 25

5

5

3

3

2

4

4

1

1

1

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NCVs: Sensory nerve action potentials are normal. Thereare multiple conduction blocks in the right median nervein the forearm and right peroneal nerve above the knee.Concentric needle EMG examination shows acute dener-vation (i.e., fibrillations and positive sharp waves) in theright upper and lower limbs. There are also reduced (neu-rogenic) recruitment and voluntary motor units with longduration and large amplitude; many are polyphasic. Insummary, there are multifocal motor neuropathies withconduction blocks.

REFERENCES:

1. Chaudhry V, Corse AM, Cornblath DR, Kuncl RW, Freimer ML,Griffin JW. Multifocal motor neuropathy: Electrodiagnosticfeatures. Muscle Nerve Feb 1994;17(2):198–205.

2. Nobile-Orazio E, Cappellari A, Priori A. Multifocal motor neu-ropathy: Current concepts and controversies. Muscle Nerve2005;31(6):663–680.

3. Hughes RA. European federation of neurological soci-eties/peripheral nerve society guideline on management ofmultifocal motor neuropathy. Report of a joint task force ofthe European federation of neurological societies and the pe-ripheral nerve society. J Peripher Nerv Syst 2006;11(1):1–8.

4. Felice KJ, Goldstein JM. Monofocal motor neuropathy: Im-provement with intravenous immunoglobulin. Muscle Nerve2002;25(5):674–678.

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67. Progressive thigh pain and legweakness—radiculopathy, vasculitis,neuropathy, or amyotrophy?

CLINICALCASE: An 82-year-old woman had worseningright thigh pain over 2 weeks, followed by right leg weak-ness and difficulty walking. She had diabetes mellitus.Examination showed weakness in the right quadriceps(4+/5 MRC), of right thigh adduction (4/5), and hip flex-ion (4+/5) only. Reflexes were 1/4 in the right knee only.There was normal body and limb sensation; normal crea-tine kinase, complete blood count, and metabolic panel;normal brain and lumbar spine MRI, and no fever.

DIFFERENTIAL DIAGNOSIS: The differential diagnosis in-cludes compressive radiculopathy, ischemic lumbar plex-opathy, vasculitis, lumbar spondylolysis and spondy-lolisthesis, or less commonly cauda equina syndrome,mononeuritis multiplex, or neoplastic lumbosacral plex-opathy. Some of these findings occur with postpolio syn-drome, radiation-induced lumbosacral plexopathy, andobstetric–gynecologic complications or complications fol-lowing any pelvic surgery. Sensory loss and diminishedreflexes suggest a peripheral nervous system process.Quadriceps muscle, thigh adduction, and hip flexionweaknesses exclude a femoral neuropathy, but point to-

ward either a radiculopathy or plexopathy. The absentknee reflexes correspond to an L4 nerve roots and/orplexus lesion. Electromyography (EMG) showing acutedenervation in L2–L4 paraspinous muscles and otherL2–L4 innervated myotomes suggests a plexoradiculopa-thy. The most common type of diabetic polyradiculopathyinvolving high lumbar radiculopathy involving the L2, L3,and L4 roots is a syndrome called diabetic amyotrophy.

DIAGNOSIS AND COMMENT: The patient has diabeticamyotrophy [1]. Diabetic amyotrophy carries a goodprognosis with functional recovery in 12–24 months in60% of patients [2, 3]. Mild weakness, discomfort, andstiffness often persist for years. Occasional relapses oc-cur. Management is directed at good glycemic control.Intravenous human immunoglobulin (IVIg) [4], cyclophos-phamide, and methylprednisolone may improve some pa-tients, but are controversial [4]. Neurologic recovery maybe slow, and physical therapy can improve functional mo-bility (e.g., transfers and ambulation), the use of assistivedevices, and to avoid contractures.


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Ulnar.L

Radial.L

Saphenous.RMedia Tibia

Forearm

V. Digit 3.5 ms 3 µV Wrist-V Digit 2.5 ms 120 mm 40 m/s

2.8 ms 15 µV Dorsum of hand-Forearm 2.7 ms 150 mm 51 m/s

NR ms µV Medial Malleolus-Medial Tibia ms mm 0 m/s

Saphenous.LMedia Tibia 2.8 ms 4 µV Medial Malleolus-Medial Tibia 2.8 ms 110 mm m/s


Nerve and site

Sural.L

Sural.R

Median.LDigit II

Point B

Point B NR ms µV Lateral malleolus-Point B ms mm m/s

NR ms µV Lateral malleolus-Point B ms mm m/s

3.8 ms 8 µV Wrist-Digit II 3.8 ms 130 mm 49 m/s

Peaklatency

Latencydifference

Conductionvelocity



Peroneal.L

Tibial.L

Tibial.R

Peroneal.R

Median.L

Ulnar.L


3.6 ms14.2 ms16.5 ms

1.4 mV0.5 mV0.4 mV

Ankle 4.7 ms 1.4 mV

Ankle 4.4 ms 1.3 mV

Wrist 3.2 ms 1.8 mV mm 43 m/s

48 m/sm/s

40 m/s33 m/s

m/s

m/s

m/s

43 m/s26 m/s

m/s


4.3 ms13.2 ms15.2 ms

1.8 mV1.4 mV1.3 mV

WristAntecubital

3.2 ms8.4 ms

6.8 mV4.9 mV

mm280 mm100 mm

mm

mm

mm290 mm80 mm

mm230 mm

Nerve and site Latency Conductionvelocity

DistanceAmplitude


Vastus lateralis.RRectus femoris.RIliopsoas.RThigh adductor.RMed gastrocnemius.RGluteus medium.RL3-paraspinous.RVastus lateralis.L

Muscle FibsSpontaneous activity Volitional MUAPsInsertional

Insertional +Wave Fasc AmplitudeDuration Config OtherRateActivationIncreasedIncreasedIncreasedIncreasedNormal

IncreasedIncreasedNormal

+3+2+2+2

None+2+2

None

+3+2+2+2

None+2+2

None


GDGDMDMD

NormalMDMD

Normal

NormalNormal

SISI

NormalSISI

Normal

RapidRapid

NormalNormalNormalNormalNormalNormal

NormalNormal

SISI

NormalSISI

Normal

NormalNormal

PolyphasicPolyphasic

NormalPolyphasicPolyphasic

Normal

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NCVs: The sensory and motor distal latencies, conductionvelocities, and F-wave latencies in the upper and lower ex-tremities are slow. Right femoral compound motor actionpotential amplitude is reduced, and both saphenous sen-sory responses are absent. Concentric needle EMG exam-ination showed acute denervation (i.e., fibrillations andpositive sharp waves) in the right quadriceps, thigh ad-ductors, iliopsoas, and L2–L4 paraspinous muscles. Thereare reduced (neurogenic) recruitment and long duration,large-amplitude polyphasic motor units.

REFERENCES:

1. Garland H. Diabetic amyotrophy. Br Med J 1955;2(4951):1287–1290.

2. Asbury AK. Proximal diabetic neuropathy. Ann Neurol1977;2(3):179–180.

3. Dyck PJ, Windebank AJ. Diabetic and nondiabetic lumbosacralradiculoplexus neuropathies: New insights into pathophysiol-ogy and treatment. Muscle Nerve 2002;25(4):477–491.

4. Kawagashira Y, Watanabe H, Oki Y, Iijima M, Koike H, HattoriH, Katsuno M, Tanaka F, Sobue G. Intravenous immunoglobu-lin therapy markedly ameliorates muscle weakness and severepain in proximal diabetic neuropathy. J Neurol Neurosurg Psy-chiatry 2007;78(8):899–901.

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ind BLBK284-Kaplan July 12, 2010 14:52 Trim: 246mm X 189mm Printer Name: Yet to Come

Index

Acute intermittent porphyria (AIP), diagnosis and treatment ofcase study on, 162diagnosis, 162, 164EMG/nerve conduction studies, 163, 165treatment, 164

Acute polyneuropathies, 162Akinetic mutism, 77Alcohol abuse. See Low-voltage fast beta patternAlpha coma

ancillary testing, 20clinical correlation, 20clinical evaluation, 20differential diagnosis, 20EEG recording, 21etiology, 20prognosis, 20treatment, 20

Alpha frequency patterns (AFPs), 20–21ALS. See Amyotrophic lateral sclerosis (ALS)Altered mental status, definition of, 1Amyotrophic lateral sclerosis (ALS), 122, 174

ancillary testing, 122clinical correlates, 122clinical evaluation, 122differential diagnosis, 122nerve conduction studies, 123prognosis, 122treatment, 122–3

Anesthetic agent, in SE, 61–2, 64, 66Anoxic coma, prognostic value of SSEP in

ancillary testing, 92clinical correlates, 92clinical evaluation, 92differential diagnosis, 92etiology, 92prognosis, 92–3

Antiepileptic drugs, 14Anti-epileptic drugs (AEDs), 30, 40

BIPLEDs and, 44and frontal lobe seizures, 52and occipital lobe seizures, 58parietal lobe partial seizures and, 56

in PLEDs, 40in simple partial status epilepticus, 66, 68temporal lobe seizures and, 54

Babinski reflexes, in hypoglycemia, 32Baclofen, 28Baclofen toxicity

ancillary testing, 28clinical correlation, 28clinical evaluation, 28differential diagnosis, 28EEG pattern, 29etiology, 28prognosis, 28treatment, 28

Benzodiazepine, 4, 28, 40, 44, 61–2, 66, 68, 82, 155Beta, diffuse and frontal fast activity

ancillary testing, 4clinical correlates, 4clinical evaluation, 4differential diagnosis, 4EEG pattern, 5etiology, 4medication effect and, 5prognosis, 4

Beta frequency bands, 5Bicuculline-insensitive GABA-B receptors, 28Bilateral independent PLEDs (BIPLEDs)

ancillary testing, 44clinical correlates, 44definition, 44differential diagnosis, 44EEG recording, 45etiology, 44frequency of discharges, 44prognosis, 44treatment, 44

Botulism, diagnosis and treatment ofcase study on, 166–8

Brachial plexopathyancillary testing, 128clinical correlates, 128

181

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182 Index

Brachial plexopathy (cont.)clinical evaluation, 128differential diagnosis, 128needle EMG examination, 129nerve conduction studies, 128prognosis, 128treatment, 128

Brainstem auditory evoked potentials (BAEPs), 94,97

in worsening hearing, 110–11Burst/suppression

ancillary testing, 26clinical correlate, 26clinical evaluation, 26differential diagnosis, 26EEG pattern, 27etiology, 26prognosis, 26treatment, 26

Catatonia, 73, 82, 84, 88, 91, 154ancillary testing, 90clinical correlates, 90clinical evaluation, 90differential diagnosis, 90EEG recording, 91etiology, 90

Closed head injury (CHI), 94Coma, 76, 82, 84, 88, 90, 152, 154

EEG of, 77–8Glasgow coma scale, 75

Comatose patients, 62, 64, 68, 70–71, 75, 97, 110Complex partial status epilepticus (CPSE), 64

of frontal region. See Complex partial status epilepticus,frontal

of temporal region. See Complex partial status epilepticus,temporal

Complex partial status epilepticus, frontalancillary testing, 62clinical correlates, 62clinical evaluation, 62differential diagnosis, 62EEG pattern, 63etiology, 62prognosis, 62treatment, 62

Complex partial status epilepticus, temporalancillary testing, 64clinical correlates, 64clinical evaluation, 64differential diagnosis, 64EEG pattern, 65etiology, 64prognosis, 64treatment, 64

Compound muscle action potential (CMAP), 166Confusion, definition of, 1

Consciousnessarousal, 76awareness, 76definition of, 76

Convulsive status epilepticus (CSE), 61Critical illness neuromyopathy

ancillary testing, 124clinical correlates, 124clinical evaluation, 124differential diagnosis, 124needle EMG, 125nerve conduction studies, 126prognosis, 124treatment, 124

Delirium, definition of, 1Delta, diffuse and slow activity

ancillary testing, 8clinical correlation, 8clinical evaluation, 8differential diagnosis, 8EEG pattern, 9–10etiology, 8prognosis, 8

Diabetic amyotrophy, diagnosis and treatment ofcase study on, 178–80

Distal symmetric peripheral neuropathy (DSPN). See HIV-relatedDSPN, diagnosis and treatment of

EEG, 2, 88, 90alpha coma, 21anoxic coma, 79baclofen toxicity, 29BIPLEDs, 44–5bursts of epileptiform activity with suppression periods, 27coma, 77–8diffuse alpha activity in comma, 21frontal intermittent delta activity, 13frontal lobe seizures, 52–3generalized suppression with no cortical activity, 25hypoglycemia, 33in LIS, 78, 83lithium toxicity, 31low-voltage fast beta pattern, 19medium- to high-voltage diffuse fast beta pattern, 5occipital blindness and seizures, 150occipital intermittent rhythmic delta activity, 15occipital lobe seizures, 59parietal lobe seizures, 57PLEDs, 40–41slow delta activity, 10spindle coma, 23temporal lobe seizures, 55theta activity, 5triphasic waves, 17for VS, 78, 84–5widespread arrhythmic delta pattern, 9

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Index 183

Electrocerebral inactivity, 25Electromyography (EMG), 114, 124, 130EMG. See Electromyography (EMG)Encephalopathy, definition of, 1Epilepsia partialis continua, 52, 62Epilepsy monitoring, 49EPs. See Evoked potentials (EPs)Evoked potentials (EPs), 97

brainstem auditory evoked potentials, 97role in coma prognosis, 78somatosensory evoked potentials, 97visual evoked potentials, 97in VS patients, 78, 84

Eye blink artifact, 7Eye deviation, 68–9Eye leads, 12–13Eye movement artifact, and FIRDA, 12–13

Femoral neuropathyancillary testing, 130clinical correlates, 130clinical evaluation, 130differential diagnosis, 130etiology, 130needle EMG examination, 131nerve conduction studies, 130–31treatment, 130

Focal arrhythmic (polymorphic) delta activityancillary testing, 36clinical correlates, 36clinical evaluation, 36definition, 36differential diagnosis, 36EEG pattern, 37etiology, 36

Frontal glioma with complex partial seizures, case study on,156–7

Frontal intermittent rhythmic delta activity(FIRDA)

ancillary testing, 12clinical correlates of, 12clinical evaluation, 12differential diagnosis, 12EEG pattern, 13in elderly patients, 12etiology, 12and eye movement artifact, 12–13prognosis, 12

Frontal lobe partial seizuresancillary testing, 52clinical correlates, 52clinical evaluation, 52differential diagnosis, 52EEG recording, 53etiology, 52prognosis, 52treatment, 52

Functional magnetic resonance imaging (fMRI), 76–7,82

comma, 78MCS, 77responses to language stimuli, study of, 79

Gait and posture testing, 114Generalized nonconvulsive status epilepticus (GNSE), 64, 70,

158clinical correlates, 70clinical evaluation, 70differential diagnosis, 70EEG recording, 71–2etiology, 70prognosis, 70treatment, 70

Generalized periodic epileptiform discharges (GPEDs), 46–7ancillary testing, 46clinical correlates, 46clinical evaluation, 46differential diagnosis, 46EEG recording, 47etiology, 46prognosis, 46treatment, 46

Glasgow coma scale, 20, 22, 26, 70, 75, 82, 84, 92, 94, 152GNSE. See Generalized nonconvulsive status epilepticus (GNSE)Guillain-Barre syndrome (GBS)

ancillary testing, 136clinical correlates, 136clinical evaluation, 136differential diagnosis, 136EMG/nerve conduction study, 137–8prognosis, 136treatment, 136

Head trauma, prognostic value of SSEP inancillary testing, 94clinical considerations, 94clinical correlates, 94clinical evaluation, 94differential diagnosis, 94prognosis, 94–5

HIV-related DSPN, diagnosis and treatment ofcase study on, 170

Hollow skull phenomenon, 78Hypoglycemia

ancillary testing, 32clinical correlates, 32clinical evaluation, 32differential diagnosis, 32EEG pattern, 33etiology, 32prognosis, 32treatment, 32

Index of global cortical function, determination of, 79

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184 Index

Limbic encephalopathyancillary testing, 34clinical correlates, 34clinical evaluation, 34differential diagnosis, 34EEG pattern, 35etiology, 34

Limbic status epilepticus from mycoplasma pneumonia, casestudy on, 154–5

LIS. See Locked-in syndrome (LIS)Lithium toxicity

ancillary testing, 30clinical correlates, 30clinical evaluation, 30differential diagnosis, 30EEG pattern in, 31etiology, 30prognosis, 30treatment, 30

Locked-in syndrome (LIS), 73, 75, 84, 88, 90, 152,154

ancillary testing, 82clinical correlates, 82clinical evaluation, 82definition of, 77differential diagnosis, 82EEG of, 78EEG recording, 83PET findings in, 78prognosis, 83treatment, 83

Long-latency auditory responses (N70), 78Lorazepam, 16, 28, 30, 46, 61, 64, 68, 70Low-voltage fast beta pattern

ancillary testing, 18clinical correlates, 18clinical evaluation, 18differential diagnosis, 18EEG recording, 19etiology, 18prognosis, 18

Low-voltage suppressed patternancillary testing, 24clinical correlation, 24clinical evaluation, 24differential diagnosis, 24EEG report with no cortical activity, 25etiology, 24prognosis, 24

Lumbar radiculopathyancillary testing, 134clinical correlates, 134clinical evaluation, 134differential diagnosis, 134EMG/nerve conduction study, 134–5prognosis, 134treatment, 134

Minimally conscious state (MCS), 73, 75–7ancillary testing, 88clinical correlates, 88clinical evaluation, 88definition of, 76differential diagnosis, 88EEG recordings, 89etiology, 88and fMRI findings, 76–7prognosis, 88treatment, 88–9

Multifocal motor neuropathy (MMN), diagnosis and treatmentof

case study on, 174–6Muscle artifact, 9, 57, 67Muscle testing, 113Myasthenia gravis (MG)

ancillary testing, 140clinical correlates, 140clinical evaluation, 140differential diagnosis, 140EMG/nerve conduction study, 140–41, 143–4etiology, 140treatment, 140

Myositisancillary testing, 142clinical correlates, 142clinical evaluation, 142differential diagnosis, 142prognosis, 142treatment, 143

NCSE. See Nonconvulsive status epilepticus (NCSE)Neuromuscular disorders, 113

clinical evaluation of, 116diagnosing of, 113–14in ICU patients, causes of, 115laboratory evaluation of, 117segmental weakness and sensory loss in, 119–20weakness in, 113

Neuromuscular junction dysfunction, 166. See also Botulism,diagnosis and treatment of

Neuropathic syndromes during HIV infection, 170Nonconvulsive status epilepticus (NCSE), 1, 16, 28, 30, 61, 70,

90, 158. See also Complex partial status epilepticus(CPSE)

Occipital blindness and seizures, case study on,150–51

Occipital epileptic activity, 68Occipital intermittent rhythmic delta activity (OIRDA)

ancillary testing, 14in children, 14clinical correlates, 14clinical evaluation, 14EEG pattern, 15etiology, 14

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Index 185

prognosis, 14treatment, 14

Occipital lobe simple partial seizuresancillary testing, 58clinical correlates, 58clinical evaluation, 58differential diagnosis, 58EEG recording in, 59etiology, 58prognosis, 58treatment, 58

Organ dysfunctionand diffuse slow theta activity, 6–7

Paralysis and respiratory failure in the ICU, causes of, 115Parietal lobe simple partial seizures

ancillary testing, 56clinical correlates, 56clinical evaluation, 56differential diagnosis, 56EEG pattern, 57etiology, 56prognosis, 56treatment, 56

Periodic discharges (PDs), 39Permanent VS, 77, 85Persistent vegetative state (PVS), 26, 73, 77, 85, 97Phenytoin, 61PLEDs. See Pseudoperiodic lateralized epileptiform discharges

(PLEDs)Positron emission tomography (PET), 34, 54, 56, 66, 83

LIS and, 78Posterior reversible encephalopathy syndrome (PRES), 150Potassium channel antibody-associated encephalopathy

(VGKC), case study on, 160–61Prolonged unresponsiveness, states of, 73, 76–7

behavioral characteristics in, 77electrophysiological findings, 77–8functional imaging, role of, 78–9prognosis using electrophysiology, 79

Pseudoperiodic lateralized epileptiform discharges (PLEDs)ancillary testing, 40clinical correlates, 40clinical evaluation, 40definition, 40differential diagnosis, 40EEG recording, 41etiology, 40frequency of discharges, 40prognosis, 40treatment, 40–41

Riluzole, 123

Secondary generalization, 68Segmental peripheral neurological disorders, evaluation of,

120

Seizures, 49complex partial, 52, 54, 56and EEG, 49–50frontal lobe seizures, 52–3in occipital lobes, 58–9parietal lobe seizures, 56–7partial seizures, 49and PLEDs, 39. See also Pseudoperiodic lateralized

epileptiform discharges (PLEDs)simple partial seizure, 54, 56temporal lobe seizures, 54–5

Sensory neuropathy/ganglionopathyancillary testing, 132clinical correlates, 132clinical evaluation, 132differential diagnosis, 132needle EMG examination, 133nerve conduction studies, 132prognosis, 132

Short-latency auditory evoked potentials, 77Simple partial status epilepticus, occipital

ancillary testing, 68clinical correlates, 68clinical evaluation, 68differential diagnosis, 68EEG recording, 69etiology, 68prognosis, 68treatment, 68

Simple partial status epilepticus, parietalancillary testing, 66clinical correlates, 66clinical evaluation, 66differential diagnosis, 66EEG recording, 67etiology, 66prognosis, 66treatment, 66

Somatosensory evoked potentials (SSEPs), 2, 8, 20, 22, 26, 46,78–9, 92, 97

after prolonged cardiac arrestclinical case study, 104responses above brachial plexus, absence of, 104–5

in asystolic cardiac arrestclinical case study, 102SSEP cortical responses, absence of, 102–3

in diffuse cortical anoxic injuryclinical case study, 100cortical and subcortical responses, absence of, 100–101

median and tibial nerve SSEP, after traumatic spinal cordinjury, 106–7

in midbrain lesionclinical case study, 98cortical responses, absence of, 98–9

Spindle beta patterns, in children, 4Spindle coma

ancillary testing, 22

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186 Index

Spindle coma (cont.)clinical correlation, 22clinical evaluation, 22differential diagnosis, 22EEG pattern, 23etiology, 22prognosis, 22treatment, 22

SSEPs. See Somatosensory evoked potentials (SSEPs)Static encephalopathies

and diffuse slow theta activity, 6–7Statin-induced myopathy

ancillary testing, 146clinical correlates, 146clinical evaluation, 146differential diagnosis, 146EMG/nerve conduction studies, 147–8prognosis, 146treatment, 146

Status epilepticus (SE), 49, 61. See also Nonconvulsive statusepilepticus (NCSE)

frontal lobe CPSE, 62–3generalized nonconvulsive status epilepticus, 70–72occipital lobe simple partial SE, 68–9parietal lobe simple partial SE, 66–7temporal lobe CPSE, 64–5

Temporal lobe partial seizuresancillary testing, 54clinical correlates, 54clinical evaluation, 54differential diagnosis, 54EEG pattern, 55etiology, 54prognosis, 54treatment, 54

Theta, diffuse slow activityancillary testing, 6clinical correlates, 6

clinical evaluation, 6differential diagnosis, 6EEG pattern, 7etiology, 6prognosis, 6

Thigh pain and leg weakness. See Diabetic amyotrophy,diagnosis and treatment of

Tonic–clonic seizure, 14Toxic encephalopathy. See Baclofen toxicityTriphasic waves (TWs), 16, 28, 44, 64, 70, 158

ancillary testing, 16baclofen overdose and, 28–9clinical correlates, 16clinical evaluation, 16differential diagnosis, 16EEG pattern, 17etiology, 16lithium toxicity and, 30–31prognosis, 16treatment, 16

TWs. See Triphasic waves (TWs)

Unresponsiveness, case study on states of, 152–3. See alsoLocked-in syndrome (LIS)

Valproate-induced hyperammonemia, case study on, 158–9Vegetative state (VS), 73, 75, 77, 82, 90, 152, 154

ancillary testing, 84clinical correlates, 84clinical evaluation, 84differential diagnosis, 84–5EEG of, 78EEG recording, 85etiology, 84prognosis, 85treatment, 85

Visual evoked potentials (VEPs), 97in worsening vision, 108–9

VS. See Vegetative state (VS)

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