Alex Mitchell

Leicester MRCPsych Part II 2008

 Five 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 changes
Medical history=>
Medical Diseases that were psychiatric

Leprosy 18th Century

Porphyrias
Thyrotoxicosis
Syphilis 19th Century

Epilepsy
20th Century
Alzheimer’s disease
Huntington’s disease

? Schizophrenia 21st Century

? depression
Conditions with a Diagnostic Test Conditions that NEARLY have a Conditions that have little chance of
diagnostic test a diagnostic test

Fragile X Autism ADHD

Lesch-Nyhan Syndrome Anorexia Nervosa School Refusal

Sydenham’s chorea Panic Attacks Separation Anxiety

Illicit Drug Intoxication ??Melancholic Depression Mild Depression

Alcohol Intoxication or Harmful Use Gilles de la Tourette Generalised Anxiety Disorder

Huntington’s Chorea Drug Withdrawal Personality Disorders

Narcolepsy Alcohol Withdrawal Acute Stress Reaction

Sleep Apnoea Alcohol Dependency Adjustment Disorder

Delirium (often) Maternity Blues Hypochondriasis

Non-degenerative dementia Post-natal depression Somatization Disorder

Kluver Bucy Syndrome Post-partum psychosis Bulimia Nervosa

Wilson’s Disease Degenerative Dementias Malingering

Carbon Monoxide Poisoning Factitious Disorder

Misc. Poisoning Syndromes Suicidality

Hydrocephalus

Neurosyphilis

Neurological Disorders? Organic Psychiatric Disorders? Functional Psychiatric Disorders?

 Toxins

NUS Head Injury Neurological Disease

CJD

Alzheimer’s Disease
Tourette’s

Brief Reactive Psychosis

Schizophrenia

Psychosis Persistent Delusional Disorder

Huntington’s
Mood Organic Psychosis

Stroke

Unipolar Depression
Bipolar Affective Disorder
HIV/AIDs Adjustment Disorder
Anxiety Disorders
Post-Partum Affective Disorders
Organic Affective Disorders
Delirium
Cognition Dementia Alcohol
CNS Tumours Organic Amnesic Syndrome

Systemic MND Parkinson’s

Multiple Sclerosis Epilepsy
 Registration

Retrograde Anterograde
Past Recent New Future
Memory
Storage Storage Storage Storage
Retrieval
Retention

Implicit Declarative
Learning of Skills & Automatic Behaviours Learning of Information

Working Memory Short-term Memory Long-term Memory

Retention over Seconds Retention over Minutes Retention over days

Motor Conditioning Priming

Semantic Memory Episodic Memory

Visuospatial Verbal
Database of information Narrative Account
 MUS => The Elephant in the Room?
% C ases Accounted for by MU S from H ospital C linics (n=550)
Nimnuan et al (2001) J Psychosom Res Medically Unexplained Symptoms
70 An Epidemiological Study in Seven Specialities 66
62
58
60
53 52

50 45
41
40 37

30

20
10
0

Gynaeacology
Neurology
Rheumatology

Gastroenterology
Cardiology
Dental

Chest

Total
 Localisation and Neuropsychiatry

Audience:
Name any psychiatric presentations attributable to specific regional effects
 Background
Brain – Behaviour Relationships

1. Based on area affected

2. Based on cause
Primer of Basic Neuroanatomy
 Anatomical – Behaviour Relationships

DSPFC
Medial Frontal/
Cingulate

Orbito-frontal
What Makes a Diagnosis Correct?
Alzheimer Tests - Correlation with Cognition
Neuropsychiatry and Regional Syndromes 1

Frontal Lobe Syndrome

Pre-Central Gyrus Poorly Localized
(Primary Motor) Contralateral Hemiplegia
Disinhibition
Motor Association Gyrus Ipsilateral Head / Eye Turning
(Premotor) Aggression

Paracentral Gyrus Incontinence & Gait

Perseveration

Broca's Area Expressive Aphasia Primitive Reflexes

Frontal Mid Gyrus Saccadic Gaze

Dorsolateral Prefrontal Cortex Executive Function

Orbitofrontal Social Judgement & Empathy

Neuropsychiatry and Regional Syndromes 2

Post-Central Gyrus
Higher Sensory Loss

Optic Radiation Lower Homonymous Quadrantopia

Non-Dominant Hemisphere Dominant Hemisphere

Anosognosia Finger / Body Agnosia

Agraphia
Geographical Agnosia
Acalculia
Apraxia
Alexia

L / R Disorientation
Neuropsychiatry and Regional Syndromes 3

Posterior Parieto-Temporal Wernicke's Dysphasia

Küver-Bucy Syndrome

Medial Temporal Lobe Episodic Memory

Hyperorality

Inferior Lateral Cortex (Left) Semantic Memory Hypersexuality

(Right) Faces

Hyperphagia
Insula Cortical Deafness / Amusia
Metamorphosis

Optic Radiation Upper Homonymous Quadrantopia

Irritative Lesion Forced Thinking, Deja Vu, Hallucinations

Neuropsychiatry and Regional Syndromes 4

Cortex Homonymous Hemianopia

Pole
Macular / Central Hemianopia

Occipito-Temporal
Prosopagnosia

Association Cortex Pallinopsia

Alexia without Agraphia

Irritative Lesion Hallucinations

 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

Tympanic Membrane

Hearing

Cochlea
Cochlear Nerve
Superior Olivary Nucleus
Lateral Leminiscus
Inferior Colliculus
Inferior Brachium
Medial Geniculate Body

Comprehension

Primary Auditory Cortex

Wernicke’s Area
Auditory Association Cortex
Angular Gyrus

Direct Response Indirect Response

Cerebral Cortex
Arcuate Fasiculus
Cortical Association Areas
Corpus Callosum
Corpus Callosum
Cerebellum
Output Basal Ganglia

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 Cognitive Dementia Psychosis
(all types) Deficits

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 disease
Fronto-temporal Dementia
Huntington’s Chorea
Multiple Sclerosis
Vascular Dementia - SPECT
Head Injury
Parkinson’s Dementia
Cerebral Tumour - Metastases
Alcohol – Wernicke Korsakoffs
 Neuropsychiatry and Aetiology:
Lessons for the organic vs functional debate?

I: Post-Stroke Depression
II: Parkinson’s Psychosis

Audience:
What is the cause of post-stroke depression?
Aetiology of Post-Stroke Depression

• Post-Stroke Depression
How Common Is It
Is the presentation unique?
Link with disability => Organic of functional?
What is the onset and duration
What Mechanism, anatomical, biochemical, neuropeptide?
Any special treatments?
Depression & 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)
 Critical
Risk Factors Anatomical Precipitants

Lesion Degenerative Change

Lipids &Diet Smoking

Cardiovascular Anomaly
Hypertension Exercise Anterior Frontal lobe

Trauma
Comorbidity Social Medial Temporal lobe

Basal Ganglia

Neurobiological
Markers
Neurological Final Common Neurophysiology
Impairment
Pathway
Neurotransmitters

Functional
Neuroendocrinology
Disability
Neuromodulators

Handicap Pre-Existing Vulnerability

(Quality of Life)
Social Support
Vicious Circle Post-Stroke
Depression Life Events

Coping Style
Treatment of Post-Stroke Depression

Special Issues Individual Studies

• Ischaemic vs Haemorrhagic • Placebo Controlled

Stroke Lipsey (1984) n = 34
SSRIs Reding et al (1986) n= 27
Andersen et al (1994) n=66
• Influence on rehabilitation Grade et al (1998) n = 21
NA vs Serotonin
• Head-to-Head
• Influence on Mortality Lauritzen et al (1994) n = 20
Antidepressants Dam et al (1996) n =52
Olanzapine and risperidone Robinson et al (2000) n = 56
(Pettenati – XXXV SIN) Jorge et al (2003) n=104
Jorge et al (2003) Am J Psychiatry
N=104; 9 year follow up
Nortriptyline, fluoxetine, placebo (RCT
• Parkinson’s Psychosis

One syndrome or many?

How often?
Vulnerability factors?
Explanation?
Psychosis in PD – Why So Common?
Drug Induced Psychosis
• anticholinergics

• amantadine

• selegiline

• dopamine agonists

• COMT inhibitors

• levodopa
 Diagnosis and Neuropsychiatry

I: Alzheimer’s disease
II: Lewy Body disease
The Dementias – Clinical Series
Diagnostic criteria & dementia prevalence
 How to Assess Accuracy of a Diagnosis?

I: Audience
Theory of Diagnostic Tests

Number
of Population
Individuals

Cognitive Score
Theory of Diagnostic Tests
Point of Partial Rarity?

Number
of Cognitive Impairment
Individuals

Dementia

True
True -ve
-ve

True
True +ve
+ve

False
False -ve
-ve False
False +ve
+ve

Optimum Cut-off value Cognitive Score

Simple Measures of Accuracy

Dementia Dementia
PRESENT ABSENT

Test +ve True +ve False +ve PPV

Test -ve False -Ve True -Ve NPV

Sensitivity Specificity Prevalence

Memory Complaints
 Memory Complaints in the Community
50

45

40

35

30

25

20

15

10

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Bassett SS, Folstein MF.Memory complain, memory performance, and psychiatric diagnosis: a community study. J Geraitr Psychiatry Neurol 1993(6) 105-111
SMC 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?”
St. John & Montgomery, J Geriatr Psychiatr Neurol 2003 (n=1751)

Dementia MCI Dementia

Present Absent

Yes 33 55 312 10%

No 24 39 1151 95%

61% (se) 58.5% (se) 79% (Sp) Prevalence =

10%

clinician =>
Accuracy of Diagnostic Tests – Exp Clinical
ALZHEIMER’S ALZHEIMER’S
PRESENT ABSENT

Test +ve 750 90 840 Total +ve

PPV 90%

Test -ve 60 100 160 Total _ve

NPV 64%

810 190 1000

True n= 2188, Sensitivity Specificity Prevalence

GS = pathology
93% 55% 81%
Mayeux et al (1998)
 Recognition Rate of Dementia by Severity

100 97%

90

80
73%
71%
70 66%

60

50 46%

40
33%
30

20

10

0
Severe Severe Moderate Moderate Mild Mild
Dementia Dementia Dementia Dementia dementia dementia
(CI) (Dementia) (CI) (Dementia) (CI) (dementia)
 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 =>
 0
5
10
15
20
25
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Distribution of MMSE Scores

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108 Controls
54 with dementia

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Accuracy of MMSE (n=10,400 x 20 >22)

Dementia Dementia
Present Absent

MMSE 2192 1005 68% (PPV)

Yes

MMSE 669 6534 90% (NPV)

No
76% (se) 86% (Sp) Prevalence = 10%

ceiling =>
 Diagnosis and Neuropsychiatry

II: Lewy Body disease

How do you make a diagnosis of LBD?

Criteria for Lewy Body Dementia

• Lewy Body Dementia vs

Parkinson’s Dementia

• Lewy Body Dementia vs

Alzheimer Dementia

• Lewy Body Dementia vs

Vascular Dementia

• Lewy Body Dementia vs

Delirium
Lewy Body vs Alzheimer Dementia
 Prognosis and Neuropsychiatry

I: MCI
II: Delirium
• Mild Cognitive Impairment

A Discrete entity?
Treatment?

Features?