Download - MRCpsych - Neuropsychiatry (March08)
Leicester MRCPsych Part II 2008
Alex MitchellAlex Mitchell
Five Questions for AudienceFive Questions for Audience
• List a neurological disorder with a high rate of
(A) Depression (B) Psychosis (C) Cognitive Impairment (d) Anxiety
• List a psychiatric condition with an organic basis
• List 1 neurological & 1 psychiatric disorder that has a
diagnosis test available
• Name 1 form of neurological treatment that is curative
What is Neuropsychiatry?
Simple Definition: All Psychiatry + All Neurology
US Definition: Neurobiology of Psychiatry
UK Definition: Psychiatric Complications of Neurology
organic conditions=>
What is Organic Psychiatry?
Simple Definition: All Medical Disorders + Psychiatry
UK Definition: Neurobiology of Psychiatry
Future: Psychiatric Symptoms caused by demonstrable
brain changesMedical history=>
Medical Diseases that were psychiatricMedical Diseases that were psychiatric
LeprosyPorphyriasThyrotoxicosisSyphilis
Epilepsy
Alzheimer’s diseaseHuntington’s disease
? Schizophrenia? depression
21st Century
18th Century
19th Century
20th Century
Functional Psychiatric Disorders?Organic Psychiatric Disorders?Neurological Disorders?
Neurosyphilis
Hydrocephalus
SuicidalityMisc. Poisoning Syndromes
Factitious DisorderCarbon Monoxide Poisoning
MalingeringDegenerative DementiasWilson’s Disease
Bulimia NervosaPost-partum psychosisKluver Bucy Syndrome
Somatization DisorderPost-natal depressionNon-degenerative dementia
HypochondriasisMaternity BluesDelirium (often)
Adjustment DisorderAlcohol DependencySleep Apnoea
Acute Stress ReactionAlcohol WithdrawalNarcolepsy
Personality DisordersDrug WithdrawalHuntington’s Chorea
Generalised Anxiety DisorderGilles de la TouretteAlcohol Intoxication or Harmful Use
Mild Depression??Melancholic DepressionIllicit Drug Intoxication
Separation AnxietyPanic AttacksSydenham’s chorea
School RefusalAnorexia NervosaLesch-Nyhan Syndrome
ADHDAutismFragile X
Conditions that have little chance of a diagnostic test
Conditions that NEARLY have a diagnostic test
Conditions with a Diagnostic Test
MoodPsychosis
Cognition
Unipolar Depression
Bipolar Affective Disorder
Adjustment Disorder
Anxiety Disorders
Post-Partum Affective Disorders
Organic Affective Disorders
Brief Reactive Psychosis
Schizophrenia
Persistent Delusional Disorder
Organic Psychosis
Delirium
Dementia
Organic Amnesic Syndrome
Neurological Disease
Parkinson’sEpilepsyMultiple Sclerosis
Alzheimer’s Disease
Head Injury
Stroke
NUS
CNS Tumours
HIV/AIDs
Huntington’s
Tourette’s
CJD
Toxins
MND
Alcohol
Systemic
DeclarativeLearning of Information
ImplicitLearning of Skills & Automatic Behaviours
Motor Conditioning Priming
Working MemoryRetention over Seconds
Long-term MemoryRetention over days
Semantic MemoryDatabase of information
Episodic MemoryNarrative AccountVisuospatial
Memory
Registration
Retention
Retrieval
Short-term MemoryRetention over Minutes
Verbal
PastStorage
NewStorage
FutureStorage
Retrograde AnterogradeRecentStorage
MUS => The Elephant in the Room?MUS => The Elephant in the Room?% Cases Accounted for by MUS from Hospital Clinics (n=550)
3741
45
5358
6266
52
0
10
20
30
40
50
60
70
Den
tal
Che
st
Rhe
umat
olog
y
Car
diol
ogy
Gas
troe
nter
olog
y
Neu
rolo
gy
Gyn
aeac
olog
y
Tota
l
Nimnuan et al (2001) J Psychosom Res Medically Unexplained SymptomsAn Epidemiological Study in Seven Specialities
Localisation and Neuropsychiatry
Audience:
Name any psychiatric presentations attributable to specific regional effects
BackgroundBrain – Behaviour Relationships
1. Based on area affected
2. Based on cause
Primer of Basic NeuroanatomyPrimer of Basic Neuroanatomy
Anatomical – Behaviour Relationships
Orbito-frontal
DSPFCMedial Frontal/
Cingulate
What Makes a Diagnosis Correct?What Makes a Diagnosis Correct?
Alzheimer Tests - Correlation with CognitionAlzheimer Tests - Correlation with Cognition
Neuropsychiatry and Regional Syndromes 1Neuropsychiatry and Regional Syndromes 1
Pre-Central Gyrus(Primary Motor) Contralateral Hemiplegia
Motor Association Gyrus(Premotor)
Paracentral Gyrus
Ipsilateral Head / Eye Turning
Incontinence & Gait
Broca's Area Expressive Aphasia
Dorsolateral Prefrontal Cortex Executive Function
Orbitofrontal Social Judgement & Empathy
Frontal Mid Gyrus Saccadic Gaze
Disinhibition
Aggression
Perseveration
Primitive Reflexes
Frontal Lobe SyndromePoorly Localized
Neuropsychiatry and Regional Syndromes 2
Post-Central Gyrus
Optic Radiation
Higher Sensory Loss
Lower Homonymous Quadrantopia
Non-Dominant Hemisphere Dominant Hemisphere
Anosognosia
Geographical Agnosia
Apraxia
Finger / Body Agnosia
Agraphia
Acalculia
Alexia
L / R Disorientation
Neuropsychiatry and Regional Syndromes 3Neuropsychiatry and Regional Syndromes 3
Posterior Parieto-Temporal
Medial Temporal Lobe
Inferior Lateral Cortex
Insula
Irritative Lesion
Optic Radiation
Wernicke's Dysphasia
Episodic Memory
(Left) Semantic Memory(Right) Faces
Cortical Deafness / Amusia
Upper Homonymous Quadrantopia
Forced Thinking, Deja Vu, Hallucinations
Hyperorality
Hypersexuality
Hyperphagia
Metamorphosis
Küver-Bucy Syndrome
Neuropsychiatry and Regional Syndromes 4
Cortex Homonymous Hemianopia
PoleMacular / Central Hemianopia
Occipito-Temporal Prosopagnosia
Association Cortex Pallinopsia
Irritative Lesion Hallucinations
Alexia without Agraphia
Caveat
Audience:Why is it difficult to establish clinico-anatomical relationships?
What is the anatomical basis of hearing?
Audience:Why is it difficult to establish clinico-anatomical relationships?
Input
Hearing
Comprehension
Direct Response
Output
Cochlea
Cochlear Nerve
Superior Olivary Nucleus
Lateral Leminiscus
Inferior Colliculus
Inferior Brachium
Medial Geniculate Body
Primary Auditory Cortex
Wernicke’s Area
Auditory Association Cortex
Angular Gyrus
Indirect Response
Cerebral Cortex
Cortical Association Areas
Corpus Callosum
Cerebellum
Basal Ganglia
Tympanic Membrane
Arcuate Fasiculus
Corpus Callosum
Broca’s Area
Motor Cortex
Motor Association Cortex
Cranial Nerves V, VII and X
Muscles of articulation
Basics of Neuropsychiatry:Psychiatric Complications
Audience:What are examples of important neurological-psychiatric relationships?
CNS Disorder Depression (all types)
Cognitive Deficits
Dementia Psychosis
Alcohol 15% 80% 15% 5%
Epilepsy 20% Unknown rare 5%
Alzheimer’s disease 30% 100% 100% 30%
Head Injury 35% 3% Unknown 3%
HIV dementia 25% 40% 25% 6%
Huntington’s Disease 25% 40% Unknown 8%
Multiple Sclerosis 50% 50% 5% 10%
Parkinson’s Disease 50% 80% 30% 20%
Stroke 50% 50% 20% 5%
Subarachnoid Haemorrhage 20% 30% Unknown Unknown
Normal Control 10% 5% 2% 1%
Some Important Neuropsychiatric Conditions
Alzheimer’s diseaseAlzheimer’s disease
Fronto-temporal DementiaFronto-temporal Dementia
Huntington’s ChoreaHuntington’s Chorea
Multiple SclerosisMultiple Sclerosis
Vascular Dementia - SPECTVascular Dementia - SPECT
Head InjuryHead Injury
Parkinson’s DementiaParkinson’s Dementia
Cerebral Tumour - MetastasesCerebral Tumour - Metastases
Alcohol – Wernicke KorsakoffsAlcohol – Wernicke Korsakoffs
Neuropsychiatry and Aetiology:Lessons for the organic vs functional debate?
Audience:What is the cause of post-stroke depression?
I: Post-Stroke DepressionII: Parkinson’s Psychosis
• Post-Stroke DepressionHow Common Is ItIs the presentation unique?Link with disability => Organic of functional?What is the onset and durationWhat Mechanism, anatomical, biochemical, neuropeptide?Any special treatments?
Aetiology of Post-Stroke DepressionAetiology of Post-Stroke Depression
Depression & Stroke - CorrelatesDepression & Stroke - Correlates
Andersen et al (1995) n=285 - Major Depression– Cognitive impairment (p<0.001)– Social Dysfunction/Isolation (p<0.05)– Not Anatomical factors or Functional Disability– Female Gender (p<0.05)
Burvill et al (1997) n=191 - Major & Minor Depression– Functional disability (p<0.01)– Divorce (p<0.05)– Not Cognition
Sharpe et al (1994) n=60, 5yr follow up - Major Depression– Female Gender (p<0.05)– Functional Disability (p<0.05)– Large Cerebral Lesions (p<0.05)
Comorbidity
Hypertension
PostPost--StrokeStrokeDepressionDepression
Neuromodulators
Anterior Frontal lobe
Medial Temporal lobe
Basal Ganglia
Risk Factors Precipitants
Cardiovascular Anomaly
FunctionalDisability
Pre-Existing Vulnerability
Final Common Final Common PathwayPathway
Degenerative Change
Trauma
SmokingLipids &Diet
NeurobiologicalMarkers
NeurologicalImpairment Neurophysiology
Neurotransmitters
Neuroendocrinology
Handicap(Quality of Life)
CriticalCriticalAnatomicalAnatomical
LesionLesion
Social Support
Life Events
Coping Style
Exercise
Social
Vicious Circle
Treatment of Post-Stroke DepressionTreatment of Post-Stroke Depression
Special Issues
• Ischaemic vs Haemorrhagic StrokeSSRIs
• Influence on rehabilitationNA vs Serotonin
• Influence on MortalityAntidepressantsOlanzapine and risperidone(Pettenati – XXXV SIN)
Individual Studies
• Placebo ControlledLipsey (1984) n = 34Reding et al (1986) n= 27Andersen et al (1994) n=66Grade et al (1998) n = 21
• Head-to-HeadLauritzen et al (1994) n = 20Dam et al (1996) n =52Robinson et al (2000) n = 56Jorge et al (2003) n=104
Jorge et al (2003) Am J PsychiatryN=104; 9 year follow upNortriptyline, fluoxetine, placebo (RCT
• Parkinson’s Psychosis
One syndrome or many?How often?Vulnerability factors?Explanation?
Psychosis in PD – Why So Common?Psychosis in PD – Why So Common?
Drug Induced PsychosisDrug Induced Psychosis
• anticholinergics
• amantadine
• selegiline
• dopamine agonists
• COMT inhibitors
• levodopa
Diagnosis and Neuropsychiatry
I: Alzheimer’s diseaseII: Lewy Body disease
The Dementias – Clinical SeriesThe Dementias – Clinical Series
Diagnostic criteria & dementia prevalenceDiagnostic criteria & dementia prevalence
How to Assess Accuracy of a Diagnosis?
I: Audience
Theory of Diagnostic TestsTheory of Diagnostic Tests
PopulationNumber ofIndividuals
Cognitive Score
Theory of Diagnostic TestsTheory of Diagnostic Tests
Cognitive Impairment
Dementia
Number ofIndividuals
Optimum Cut-off value
False +veFalse +veFalse -veFalse -ve
True -veTrue -ve
True +veTrue +ve
Point of Partial Rarity?
Cognitive Score
PrevalenceSpecificitySensitivity
NPVTrue -VeFalse -VeTest -ve
PPVFalse +veTrue +veTest +ve
DementiaABSENT
DementiaPRESENT
Simple Measures of AccuracySimple Measures of Accuracy
Memory ComplaintsMemory Complaints
Memory Complaints in the CommunityMemory Complaints in the Community
0
5
10
15
20
25
30
35
40
45
50
No Diag
nosis
Anxiety
disord
ersCogn
itive d
isord
erAffe
ctive D
isord
ers
Schizo
phren
ia
Substance
Use
Adjustmen
t Diso
rders
Bassett SS, Folstein MF.Memory complain, memory performance, and psychiatric diagnosis: a community study. J Geraitr Psychiatry Neurol 1993(6) 105-111
SMC in wordsSMC in words
• 8 studies report the rate of SMC in dementia; 7 studies reported the rate of SMC; 4 compared the rate of SMC in dementia and MCI head-to-head.
• SMC were present in 42.8% of those with dementia and 38.2% of those with MCI compared with 17.4% in healthy elderly controls (relative risk 2.3).
• For dementia, sensitivity was 43.0% and specificity was 85.8%.
• For MCI sensitivity was 37.4% and specificity was 86.9%.
• In community studies with a low prevalence the positive and negative predictive values were 18.5% and 93.7% for dementia and 31.4% and 86.9% for MCI.
1Item: “Have You Had Memory Loss in the last year?”1Item: “Have You Had Memory Loss in the last year?”
58.5% (se)
39
55
MCI
Prevalence = 10%
79% (Sp)61% (se)
95%115124No
10%31233Yes
DementiaAbsent
DementiaPresent
St. John & Montgomery, J Geriatr Psychiatr Neurol 2003 (n=1751)
clinician =>
Accuracy of Diagnostic Tests – Exp ClinicalAccuracy of Diagnostic Tests – Exp Clinical
1000190810
160 Total _ve10060Test -ve
840 Total +ve90750Test +ve
ALZHEIMER’SABSENT
ALZHEIMER’SPRESENT
Sensitivity93%
PPV 90%
Specificity55%
NPV 64%
Prevalence81%
True n= 2188, GS = pathology
Mayeux et al (1998)
Recognition Rate of Dementia by Severity
97%
73% 71%
46%
66%
33%
0
10
20
30
40
50
60
70
80
90
100
SevereDementia
(CI)
SevereDementia
(Dementia)
ModerateDementia
(CI)
ModerateDementia
(Dementia)
Milddementia
(CI)
Milddementia
(dementia)
GP Testing by Actual MMSE Score (n=162)GP Testing by Actual MMSE Score (n=162)
Ganguli M et al. Detection and Management of Cognitive Impairment in Primary Care: The Steel Valley Seniors Survey. JAGS 52:1668–1675, 2004.
methdos =>
Distribution of MMSE ScoresDistribution of MMSE Scores
0
5
10
15
20
25
30Thir
tyTwen
try N
ineTwen
try E
ight
Twentry
Sev
e
Twentry
Six
Twentry
FiveTwen
try Four
Twentry
three
Twentry
TwoTwen
try O
ne
Nineteen
Twentry
Nine
108 Controls54 with dementia
Funabiki et al (2002) Geriatrics Gerontol Int.
Accuracy of MMSE (n=10,400 x 20 >22)Accuracy of MMSE (n=10,400 x 20 >22)
Prevalence = 10%86% (Sp)76% (se)
90% (NPV)6534669MMSE No
68% (PPV)10052192MMSE Yes
DementiaAbsent
DementiaPresent
ceiling =>
Diagnosis and Neuropsychiatry
II: Lewy Body disease
How do you make a diagnosis of LBD?
Criteria for Lewy Body DementiaCriteria for Lewy Body Dementia
• Lewy Body Dementia vsParkinson’s Dementia
• Lewy Body Dementia vsAlzheimer Dementia
• Lewy Body Dementia vsVascular Dementia
• Lewy Body Dementia vsDelirium
Lewy Body vs Alzheimer DementiaLewy Body vs Alzheimer Dementia
Prognosis and Neuropsychiatry
I: MCIII: Delirium
• Mild Cognitive Impairment
A Discrete entity?Treatment?
Features?