Peripheral Peripheral NeuropathyNeuropathy

Peripheral NervePeripheral Nerve

MyelinMyelin : Current cannot flow: Current cannot flow AxonAxon : Not nerves left: Not nerves left

Types of nerve fibersTypes of nerve fibers DiameterDiameter ConductionConduction Function Function

micronsmicrons Velocity m/sVelocity m/s

AA alpha 1-20alpha 1-20 70-11070-110 Motor, ProprioceptionMotor, Proprioception

beta 5-10beta 5-10 30-6030-60 TouchTouch

gama 3-6gama 3-6 20-3020-30 Fusimotor, spindlesFusimotor, spindles

delta 2-5delta 2-5 20-30 20-30 Sharp painSharp pain

BB <3 <3 5-155-15 Autonomic, pregangl.Autonomic, pregangl.

CC <1.3 <1.30.5-20.5-2 Slow painSlow painNon myelinatedNon myelinated

The Peripheral Nervous SystemThe Peripheral Nervous System MotorMotor: weakness, : weakness,

atrophyatrophy Sensory lossSensory loss

Large Fibers (position)Large Fibers (position) Small fiber (pain)Small fiber (pain)

Reflex lossReflex loss Autonomic symptomsAutonomic symptoms

(redness, dizziness, ED)(redness, dizziness, ED)

DefinitionsDefinitions NeuropathyNeuropathyPathological process affecting a Pathological process affecting a peripheral nerve/speripheral nerve/s

MononeuropathyMononeuropathyA single nerve affectedA single nerve affected

Mononeuritis multiplexMononeuritis multiplex Multiple mononeuropathy or Multifocal neuropathyMultiple mononeuropathy or Multifocal neuropathy

Polyneuropathy Diffuse symmetrical disease usually beginning peripherally Acute/Chronic Static/Prog Relapsing/Recovering Motor Sensory

Sensrimotor(Mixed) AutonomicDemyelinating Axonal

Radiculopathy Nerve root disease

Mechanisms of damageMechanisms of damage Demyelination Demyelination Myelin sheath disrupted

GBS Post Diphtheric HSMN

Axonal degeneration Axonal degeneration Axon damage

Toxic neuropathies

Wallerian degenerationWallerian degeneration Nerve section CompressionCompression Focal demyelination

Entrapment-Carpel tunnel syndrome

InfarctionInfarction Arteritis

Polyarteritis nodosa Churg-Strauss synd. DM

InfiltrationInfiltration Infiltration

Leprosy Sarcoidosis

ClassificationClassificationEXAMINATION FINDINGSEXAMINATION FINDINGS

Purely Motor or Sensory or Purely Motor or Sensory or Sensorimotor?Sensorimotor?

Proximal or distal? Symmetric or Proximal or distal? Symmetric or asymmetric?asymmetric?

Multifocal, generalized, regional?Multifocal, generalized, regional? Upper limbs, lower limbs, neck, trunk?Upper limbs, lower limbs, neck, trunk?

TIMINGTIMING Acute or chronic?Acute or chronic?

ASSOCIATED FINDINGSPainful or painless?

Hereditary or sporadic?

ELECTRODIAGNOSISAxonal or demyelinating?

LABORATORYParaprotein present? Type?

Antibody against nerve?CSF protein level?

HISTOLOGYInflammatory Cells

EpidemiologyEpidemiology

Prevalence Prevalence ~ 2.4%~ 2.4% ~ 8% in people older than 55 years~ 8% in people older than 55 years

DM is most common causeDM is most common cause

EpidemiologyEpidemiology

Other common systemic causesOther common systemic causes Metabolic disordersMetabolic disorders Infectious agentsInfectious agents VasculitisVasculitis ToxinsToxins DrugsDrugs AutoimmunityAutoimmunity InheritedInherited

DiagnosisDiagnosis

Most important details to determineMost important details to determine DistributionDistribution DurationDuration Course Course

DiagnosisDiagnosis

Clinical manifestations vary widelyClinical manifestations vary widely Altered sensationAltered sensation PainPain Muscle weakness or atrophyMuscle weakness or atrophy Autonomic symptomsAutonomic symptoms

Laboratory Screening for Laboratory Screening for “Treatable” Neuropathy?“Treatable” Neuropathy?

B12B12 Not truly length-dependentNot truly length-dependent

DiabetesDiabetes This type of neuropathy This type of neuropathy generally a late findinggenerally a late finding

ANA, chronic disease ANA, chronic disease screenscreen

Screen for connective tissue Screen for connective tissue diseases (late finding)diseases (late finding)

TSHTSH If positive, have you proven If positive, have you proven anything?anything?

ESRESR If onset is recentIf onset is recent

HIVHIV Risk FactorsRisk Factors

Review medicationsReview medications Big questionBig question

DiagnosisDiagnosis

Electro diagnostic studiesElectro diagnostic studies Sensitive, specific, validatedSensitive, specific, validated Extension of neurologic examExtension of neurologic exam

Nerve conduction studies (NCS)Nerve conduction studies (NCS) Needle electromyography (EMG)Needle electromyography (EMG)

DiagnosisDiagnosis

Establish distributionEstablish distribution MononeuropathyMononeuropathy Mononeuropathy multiplexMononeuropathy multiplex PolyneuropathyPolyneuropathy

Determine primary pathologyDetermine primary pathology Demyelinating Demyelinating AxonalAxonal

MononeuropathyMononeuropathy

Focal lesion involving a single nerveFocal lesion involving a single nerve Electro diagnostic studies indispensibleElectro diagnostic studies indispensible

Localize site of injuryLocalize site of injury Determine severity of lesionDetermine severity of lesion

MononeuropathyMononeuropathy

CausesCauses EntrapmentEntrapment

Carpal tunnel syndrome is most commonCarpal tunnel syndrome is most common Foot dropFoot drop

Focal compressionFocal compression TraumaTrauma

Mononeuropathy Mononeuropathy MultiplexMultiplex

Separate/noncontiguous involvementSeparate/noncontiguous involvement SimultaneouslySimultaneously SeriallySerially

PatternPattern RandomRandom MultifocalMultifocal

Frequently evolves quicklyFrequently evolves quickly

Mononeuropathy Mononeuropathy MultiplexMultiplex

Urgent assessment for vasculitisUrgent assessment for vasculitis Polyarteritis nodosaPolyarteritis nodosa Churg-Strauss diseaseChurg-Strauss disease Connective tissue diseasesConnective tissue diseases

Rheumatoid arthritisRheumatoid arthritis Sjogren’s syndromeSjogren’s syndrome

PolyneuropathyPolyneuropathy

Most commonly distal symmetricalMost commonly distal symmetrical Fiber effect is length-dependentFiber effect is length-dependent Toes and soles affected firstToes and soles affected first AssociationsAssociations

Systemic diseasesSystemic diseases Metabolic disordersMetabolic disorders Exogenous toxinsExogenous toxins

PolyneuropathyPolyneuropathy

Diabetes is prototypeDiabetes is prototype Chronic, sensory and motorChronic, sensory and motor Commonest in developed worldCommonest in developed world Alcoholism is the second most commonAlcoholism is the second most common

PolyneuropathyPolyneuropathy

Early symptoms Early symptoms Sensory abnormalitiesSensory abnormalities

NumbnessNumbness BurningBurning ParesthesiasParesthesias Dysesthesias Dysesthesias

Distally predominantDistally predominant SymmetricalSymmetrical

PolyneuropathyPolyneuropathy

Evolution is centripetalEvolution is centripetal Symptoms spread up legsSymptoms spread up legs

Sensory lossSensory loss DysesthesiasDysesthesias

Ankles jerks are depressedAnkles jerks are depressed Patients have trouble walking on their heelsPatients have trouble walking on their heels Foot plantar flexion remains strongFoot plantar flexion remains strong

PolyneuropathyPolyneuropathy

Symptoms noticed in fingertipsSymptoms noticed in fingertips NumbnessNumbness Dysesthesias Dysesthesias

Advanced picture is easily recognizableAdvanced picture is easily recognizable Stocking-glove sensory lossStocking-glove sensory loss Distal muscle wasting and weaknessDistal muscle wasting and weakness Absent tendon reflexesAbsent tendon reflexes

PolyneuropathyPolyneuropathy

Sub classificationSub classification Historical features are indispensible Historical features are indispensible

Other medical conditionsOther medical conditions Symptoms of systemic diseaseSymptoms of systemic disease Recent viral or other infectious diseasesRecent viral or other infectious diseases Recent vaccinationsRecent vaccinations Institution of new medicationsInstitution of new medications

PolyneuropathyPolyneuropathy

Exposure to toxinsExposure to toxins AlcoholAlcohol Heavy metalsHeavy metals Organic solventsOrganic solvents

Family historyFamily historyDuration and clinical course are helpfulDuration and clinical course are helpful

Acute = days to weeksAcute = days to weeks Chronic = months to yearsChronic = months to years

Laboratory InvestigationsLaboratory Investigations

CBCCBC SUGARSUGAR TFTsTFTs

ESRESR CRPCRP

UREAUREA

B12B12 Methylmalonic acidMethylmalonic acid HomocysteineHomocysteine

FolateFolate

TreatmentTreatment

GeneralGeneral Subtype specificSubtype specific

Diabetes mellitusDiabetes mellitus Renal insufficiencyRenal insufficiency HypothyroidismHypothyroidism Vitamin B12 deficiencyVitamin B12 deficiency Systemic vasculitisSystemic vasculitis

TreatmentTreatment

GeneralGeneral PainPain

Antiepileptic drugsAntiepileptic drugs AntidepressantsAntidepressants Tramadol Tramadol

TreatmentTreatment

Preventative and palliativePreventative and palliative Weight reductionWeight reduction Assiduous foot careAssiduous foot care Good shoesGood shoes Ankle-foot orthoses as neededAnkle-foot orthoses as needed

Several organizations provide Several organizations provide supportsupport

Chronic Length Dependent Chronic Length Dependent NeuropathyNeuropathy

Begins in toes or feetBegins in toes or feet Stocking distributionStocking distribution

Progresses rostrallyProgresses rostrally Tops and bottoms of Tops and bottoms of

feetfeet

Weakness begins in Weakness begins in ankles when ankles when sensation reaches sensation reaches calvescalves

Sometimes diagnosable, Never treatable?Sometimes diagnosable, Never treatable?

Phenotype CIDPPhenotype CIDP

Small DifferentialSmall Differential

Phenotype-MADSAM Phenotype-MADSAM NeuropathyNeuropathy Key DDx: Key DDx:

Brachial plexopathiesBrachial plexopathies Vasculitis Vasculitis

mononeuropathy mononeuropathy multiplexmultiplex

Compression Compression neuropathiesneuropathies

HNPP (genetic testing)HNPP (genetic testing)

Multifocal Motor Multifocal Motor Neuropathy (MMN)Neuropathy (MMN) Almost always in Almost always in

hands and wrists hands and wrists Pattern of weakness is Pattern of weakness is

in the distribution of in the distribution of individual peripheral individual peripheral nervesnerves i.e. severe involvement in i.e. severe involvement in

ulnar distribution sparing ulnar distribution sparing medianmedian

Lack of atrophy in Lack of atrophy in weak musclesweak muscles

No pathological No pathological reflexesreflexes

UncertaintyUncertainty

Many cases are not easily definable Many cases are not easily definable because of multiplicity of patternsbecause of multiplicity of patterns

Cases that are not clearly untreatable are Cases that are not clearly untreatable are possibly treatablepossibly treatable