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

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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?