AGENDA

Seminar

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Amnesia Causing Entities

Transient Amnesia Syndromes

Persistent Amnesic Disorders

OADBACKGROUND

PresenterDr. Anusa A M

Second year MD PG 28th August 2013

Hon. Chairperson

Dr. KUMANAN MD DPM, Professor

Dr. Amudha MD, DCh, Assistant Professor

Prepared by Prof. Rooban T,

Oral & Maxillofacial Pathologist

What’s Common ?

Finding Nemo

Ghajini

Bourne Identity 50 First dates

Organic Amnesic Disorders

Agenda

Memory – Basics

Amnesia

Organic Amnesia

Persistent

Transient

DSM4 vs DSM 5

References

Memory

Memory – Long term memory

HM or Henry Molaison Gustav

“It’s a funny thing—you just live and learn. I ’m living, and you’re learning.” 

Cognitive Disorders – DSM IV TR

Overlap features

Core feature of Amnesic Disorder

Memory impairment that is NOT due

to dementia or delirium and

represents a decline from a

previously attained functional level.

Memory impairment is likely to be

restricted to specific kinds of

memory

Amnesic Disorders

“An abnormal mental state in which

memory and learning are affected out of

all proportion to other cognitive

functions in an otherwise alert and

responsive patient”

Victor et al., 1971

Amnesic Disorders

Severe memory impairment or deficit, irrespective of the cause

Till 1980s Later

Amnesia is a memory impairment that occurs in the absence of other substantial cognitive impairments, and is restricted to specific disorders - amnesic or amnestic disorders

Based on proximal cause of impairment

Amnesic disorders

Organic / biological instances

Brain disorders, tumors, Strokes, Temporal lobe surgery, ECT,

Infection, metabolic, trauma, TGA

Functional / Psychogenic

Substance induced

Organic Amnesic Disorders

SYSTEMIC MEDICALCONDITIONS

Thiamine deficiency(Korsakoff's

syndrome)Hypoglycemia

PRIMARY BRAIN CONDITIONS

Seizures Head trauma - closed and

penetrating Cerebral tumors (especially

thalamic and temporal lobe) Cerebrovascular diseases Surgical procedures on the

brain Encephalitis due to herpes

simplex Hypoxia Electroconvulsive therapy Multiple sclerosis

Medial Temporal

Diancephalic

Retrograde

AnterogradeEncoding

Site TimeProcess

Declarative

Non-declarative

Transient

Chronic Retrieval

Storage

Content Duration

OAD

OAD characterized by

Severe impairment of recent or short term memory - inability to learn new material

Impaired remote or long term memory - inability to recall previously learnt material

No impairment of immediate memory - immediate retention and recall.

OAD – ICD 10 Diagnostic Criteria Recent /remote memory impaired

Antero/retrograde amnesia.

No impairment of Immediate & recall attention, Consciousness Global intellectual functioning.

Historical or objective evidence of brain disease injury

OAD – ICD 10 Diagnostic CriteriaAssociated features

Confabulations

Emotional changes Apathy Lack of initiative

Lack of insight

DSM 4 criteria

Part of - “Delirium, Dementia and Amnestic &other Cognitive disorders”

Include Due to General Medicine

Condition Substance induced Persisting Amnestic

disorders Amnestic - NOS

OAD - Where ?

Any part of the brain Cortex Hypothalamus Hippocampus Thalamus Reticular formation Amygdala Septum

OAD – Where?

Differential Diagnosis

Dementia

Depressive disorder

Malingering Memory loss

Dissociative amnesia

Amnesia – Substance use

What is Korsakoff’s Syndrome - KSMemory disorder due to thiamine

deficiency

It affects 1-2% of the population

Causes: Chronic alcoholism Severe malnutrition Medical conditions

KS – Site of damage

First phase: Wernicke’s encephalopathy Damage in lower parts of the brain

▪ Thalamus▪ Mamillary bodies

Second phase: Korsakoff syndrome Damage to areas

▪ Anterior Thalamus▪ Mamillary body▪ Mamillothalamic tract

KS - Symptoms

First phase: Wernicke’s encephalopathy

1. Confusion2. Ocular Motor Movement defects3. Ataxia

Second phase: Korsakoff syndrome

1. Amnesia2. Confabulation

Diagnosis

Difficult to differentiate - alcohol intoxication or withdrawal

Missed -clinical examination in 80% of cases Clinical assessment:

▪ Mental status change▪ Ocular motor movement abnormality▪ Physical assessment for ataxia

Thiamine blood measurement▪ Measure thiamine level directly from the whole blood▪ Measure the activity of transketolase from erythrocytes

Brain imaging (MRI)

KS The Basal Forebrain:

nuclei of tha basal forebrain

nucleus basalis of Meynert.

The Cerebral Cortex:

Widening of the sulci

↑ size of ventricles - cortical atrophy.

Damage to the frontal cortex.

Thiamine (Vitamin B1)

Yeast, cereal grains, beans, nuts,

and meat

DDA - 1 mg of thiamine/day

30 mg thiamine in store

Half-life of 9 – 18 days

Signs of encephalopathy - brain

thiamine stores < 20% of normal

levels

Pathology

Thiamine function: conversion of glucose to

ATP

Thiamine→ Thiamine-pyrophosphate

Thiamine-pyrophosphate: A cofactor for

enzymes involved in glucose metabolism:

• Transketolase

• Pyruvate dehydrogenase

• α-ketoglutarate dehydrogenase

Overview of

Intracellular

Pathway

Adapted from: Lough, M.E. (2012). Wernicke’s encephalopathy: expanding the diagnostic tool box. Neuropsychol Rev, 22(2), 181-94.

Transketolase

Adapted from: Martin, P.R., Singleton, C.K., and Sturmhofel, S.H. (2004). The Role of Thiamine Deficiency in Alcoholic Brain Disease. NIAAA.

Pyruvate Dehydrogenase & α-Ketoglutarate Dehydrogenase

Adapted from: Martin, P.R., Singleton, C.K., and Sturmhofel, S.H. (2004). The Role of Thiamine Deficiency in Alcoholic Brain Disease. NIAAA.

Thiamine Deficiency & Brain

• Thalamus-major relay for (sensory and motor input)• Mamillary Body-helps processes memories• Cerebellum-movement coordination•Peripheral Nerves-transmission of nerve impulses

Korsakoff Syndrome

Memory problems

Anterograde

Retrograde

Confabulations:

Falsification of memory

Clear consciousness

Confabulations

Falsification of memory – clear consciousness Embrassement Fantastic nature

Unaware

Most often – Autobiographic memory

Management

Thiamine

Replacement

T2 weighted MRI of patient 4: coronal sections show (especially in the top right—black arrow —and bottom left) involvement of the right sided MS/ndbB complex as well as bilateral lesions of the rectus gyrus together with the clip artefact.

Böttger S et al. J Neurol Neurosurg Psychiatry 1998;65:93-102

©1998 by BMJ Publishing Group Ltd

Rupture of Ant. Comm. Artery

Herpes encephalitis25-year-old woman with herpes simplex virus encephalitis and HIV infection and history of sudden general convulsion and consciousness disorder while talking to friends.A–E, Sequential axial T1-weighted MR image (TR/TE, 435/12) (A), FLAIR image (8,000/105; inversion time, 2,300 (B), diffusion-weighted image (DWI) (4,500/105.2; b = 1,000 s/mm2) (C), apparent diffusion coefficient (ADC) map (D), and contrast-enhanced T1-weighted image (435/12) (E) immediately after onset of neurologic symptoms show T1- and T2-prolonged lesions (arrow, A and B) at left hippocampus and amygdala, left inferior frontal lobe, and insula. High signal intensity (arrow, C) on DWIwith low ADC (arrow, D) also are evident. Abnormal gyral enhancement (arrowheads, E) along left medial temporal lobe occurred after gadopentetate dimeglumine ministration.F–J, Axial T1-weighted MR image (435/12) (F), FLAIR image (8,000/105; inversion time, 2,300 milliseconds (G), DWI (4,500/105.2; b = 1,000 s/mm2) (H), ADC map (I), and contrast-enhanced T1-weighted image (435/12) (J) on day 11 after onset of neurologic symptoms show expansion of affected regions (arrowheads, G–I) in inferior aspect of both frontal lobes, right hippocampus, and amygdala on FLAIR and DWI images and area of T1 shortening (arrows, F) along cortex.K–O, Axial T1-weighted image (528/12 (K), FLAIR image (9,000/108; inversion time, 2,300 milliseconds (L), DWI (4,500/130; b = 1,000 s/mm2) (M), ADC map (N), and contrast-enhanced T1-weighted image (528/12) (O) 34 days after onset of neurologic symptoms show further development of cortical T1 shortening (arrowheads, K), persistence of high signal intensity and atrophic change (arrowheads, L), and disappearance of high signal intensity on DWI and low ADC (N)

Seizure disorder

Post –Ictal Amnesia

Non purposive wandering

Earlier Autobiographical memory loss

Random in involvement

EEG abnormalities

Transient Amnesic Syndromes

In a variety of neuropsychiatric disorders

As a normal phenomenon starting in midlife

TAS

Some short-lived amnesia Transient global amnesia (TGA). Temporal lobe epilepsy/ Transient epileptic

amnesia Transient cerebral ischemia Migraine, Alcohol intoxication (“blackouts”) Drugs (eg, benzodiazepines, barbiturates,

ketamine15) and head injury. Concussion - temporary retrograde and

anterograde

TGA - OVERVIEW

Benign disorder

Characterized by anterograde and/or retrograde amnesia

Remain oriented to person

No other focal neurologic deficit

Permanent inability to recall TGA episode

TGA - OVERVIEW

First described by Bender 1956

TGA coined by Fisher and Adams 1964

Annual incidence 8.6 to 10.0 per 100,000 and up to 32 per 100,000 if > 50 years

Usually occur in healthy, middle-aged or elderly patients

Typically no major vascular risk factors

TGA - Diagnostic Criteria

FEATURES PRESENT:

Anterograde amnesia& also retrograde amnesia

Resolves within 24 hours

Witnessed event

FEATURES ABSENT

Aphasia or apraxia

Clouding of consciousness

Loss of personal identity

Epileptic features

Focal neurologic deficits

Recent hx head trauma

Seizure in preceding 2

years

Precipitating Events

Emotional stress

Physical exertion

Medical procedures

Valsalva maneuvers

Sexual intercourse

Immersion in cold water

Chronic headaches/migraines

TGA - Pathogenesis

Controversial

Transient decrease in blood flow to

temporal lobes (seen on SPECT)

Epileptic discharge in the hippocampus

Spreading depression of cortical activity –

short-lasting wave of depolarization –

responsible for auras & migraines

TGA - Differential Diagnosis

Brain tumor

Stroke

Intracerebral/subarachnoid bleed

Complex partial seizure

Migraine

Toxins/drugs

Acute coronary syndrome

Hepatic encephalopathy

TGA – work up

EKG, CBC, electrolytes, urine toxicology screen, PT/PTT, cardiac enzymes, liver enzymes, noncontrast head CT

Also consider brain MRI/MRA, EEG, holter monitor, and TTE.

Imaging

Imaging

ECT & Amnestic Disorder

Recent memory – Retrograde amnesia

Permanent

Anterograde Amnesia – Retention defect – related to strength & duration of electrical stimulation/ seizures Less after U/L Non dominant ECT

Post-traumatic Amnesia

Open/ closed injuries of brain

Reflects the intensity of damage to brain

Duration - prognostic factor

Injury characteristics

Mild TBI Moderate TBI Severe TBI

Loss of consciousness

<30 min 30 min – 24 hrs

> 24 hrs

Posttraumatic amnesia

< 24 hrs 24 hrs – 7 days > 7 days

Disorientation /confusion – Glasgow coma scale

13 – 15 (not below 13 at 30 minutes)

9 - 12 3 - 8

Alcoholic “Black outs”

Period of Acute intoxications

Prolonged alcohol abuse

Types Fragmentary En-bloc

Drugs Causing Amnesia

Benzodiazepine  Midazolam  Flunitrazepam  Propofol  Scopolamine 

Domoic Acid

Diagnostic Work Flow

Tests for intellectual functions

Is Memory (?) loss Useful

11 Million Bits/Sec of raw data - unconscious mind from all senses

40 bits/sec – conscious

Human retina - brain - 10 million bits/sec

PPT slide - 40 words < 10 sec to read - 1000 bits/sec

So What ?

May 23rd 2013 DSM 5 was released

What DSM5 Says ?

What’s the change?

DSM 4

Delerium, Dementia and Amnestic disorders

DSM 5

Neurocognitive disorders (NCD) Delerium Major/Minor NCD

▪ Alzheimer's associated ▪ Frontotemporal NCD▪ NCD – Lewy Bodies▪ Vascular associated▪ Traumatic Brain injury▪ HIV infection▪ Prion disease▪ Parkinson’s ▪ Huntington’s▪ Another medical conditions▪ Multiple Etiologies▪ Unspecified etiologies

What change?

Primary deficit is in cognitive function

Acquired

Section Unique - Pathology/etiology known

“AMNESTIC DISORDER” IS REPLACED AS

MAJOR/Mild NCD – DUE TO ANOTHER

MEDICAL CONDITION

NCD – due to other medical condition

Structural lesions

Brain tumors

Subdural hematoma

Hydrocephalus

NCD – due to other medical condition

Infectious diseases

Neuro-syphilis

Crytococcosis

NCD – due to other medical condition

Other neurological

Epilepsy

Multiple sclerosis

References

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3. Levenson JL. Psychiatric Issues in Neurology, Part 4: Amnestic Syndromes and Conversion Disorder. Primary Psychiatry. 2008;15(3):39-42

4. Shimamura, AP, Organic Amnesia, from L. R. Squire (Ed.), Encyclopedia of Learning and Memory, 1992, pp. 30-35, Macmillan: New York

5. Noguchi T et al., CT and MRI Findings of Human Herpesvirus 6–Associated Encephalopathy: Comparison With Findings of Herpes Simplex Virus Encephalitis. AJR 2010;194:754-60

6. Kopelman MD. Disorders of memory. Brain 2002;125:2152-1907. Caixeta L, Ghini BG, Peres JFP. Neuroimaging and Other amnestic disorders.

Neuroimaging for clinicians - combining reseacrh and practice. www.intechopen.com

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20.8.2013, from http://www.dana.org/brainhealth/detail.aspx?id=471612. Budson AE, Price BH. Memory Dysfunction. New England Journal of

Medicine 2005;352:692-9913. Fujiwara, E., Brand, M., Kracht, L., Kessler, J., Diebel, A., Netz, J.,

Markowitsch, H.J. (2008). Functional retrograde amnesia: a multiple case study. Cortex, 44, 29-45.

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transient global amnesia. Neurology 2005;64:1170-7418. Sarazin M et al., Amnestic syndrome of the medial temporal type identifies

prodromal AD: A longitudinal study. Neurology 2007;69:1859-67

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21. DSM-522. DSM-423. ICD1024. Oxford Textbook of psychiatry, 2nd Edition25. Comprehensive textbook of psychiatry, 9th Edition26. Lishman's neuropsyhciatry

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