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Resident tutorial57

Surat Tanprawate, MD, FRCPT


Division of Neurology, Chiangmai University
Neurology you should know
1. Symptomatology approach
2. Disease based learning
3. Skills learning-
1. History taking, Physical exam
2. Thinking skills: summarisation, problem lists,
discussion
Symptomatology approach

Cognitive function and behavioural change

Level of consciousness: coma, delirium

Content of conscious: dementia, other higher cognitive


disorder (dysphasia, acalculia etc)

Neuropsychiatric problems

Cranial nerve function

visual loss, diplopia, dysarthria, hearing loss, vertigo,


dysphagia
Symptomatology approach

Motor system

weakness

movement disorder

gait disorder

ataxia

Sensory system

numbness

pain, and headache

Autonomic function

bowel bladder involvement,


dysautonomia

Episodic disorder

transient loss of
consciousness

episodic neurological signs/


symptoms
Cognitive dysfunction
- coma

A middle aged woman

She presented with sudden alteration of consciousness

PE: conscious: coma

pupils: 3 mm SRTL

no motor response

vertical eye movement

dolls eye-negative
case
case
The question of alter level of
conscious state

Coma mimicker: lock-in syndrome

Localize lesion

Caused of coma state

Evaluated brain death


Arousal and awareness, the two components of consciousness in coma,
vegetative state, minimally conscious state, and locked-in syndrome.
Lancet Neurol 2004; 3: 53746
11
Alteration of consciousness
Level of consciousness
Stupor and coma
Content of
consciousness
Behavioural state
Structural
Non-structural
-Metabolic
-Toxic
Symmetrical Asymmetrical
C P O M R
(1)
(2)
(3)
Localise lesion and identify
the cause
Behavioral state Denition Lesion Comment
Locked-in
syndrome
Alert and aware,
quadriplegic with lower CN
palsy
Bilateral anterior
pontine
Similar state:severe
polyneuropathy
MG, NM blocking
agent
Persistent
vegetative state
Absent cognitive function
but retain vegetative
component
Extensive cortical grey
and subcortical white
matter with relative
preservation of brain
stem
Synonyms include
apallic syndrome,
coma vigil, cerebral
cortical death
Abulia Severe apathy, patient
neither speak nor moves
spontaneously
Bilateral frontal medial Severe case
resemble akinetic
mutism, but patient is
alert and aware
Catatonia Mute, and mark decrease
motor activity
Usually psychiatric May be mimicked by
frontal lobe
dysfunction and drug
Pseudocoma Feigned coma
Behavioural state that may mimic coma
Locked in
syndrome
Localisation of the structural
lesions

C: state of consciousness

P: pupillary size and response to light

O: ocular movement, nystagmus, and ocular reex

M: motor response

R: respiratory pattern
Hippus Greek hippos meaning horse

Hippus, also known as pupillary athetosis, is
spasmodic, rhythmic, but irregular dilating and
contracting pupillary movements between the
sphincter and dilator muscles
Unilateral/bilateral miosis,
retained light reaction
Bilateral unresponsive large pupils
Pupils remain xed in mid-position
Bilateral xed mid-position pupils
Hypothalamic/
diencephalon
Upper midbrain
Central midbrain
Lower brainstem/
medulla
Rostro-caudal brainstem compression secondary to
an expanding supratentorial process
O: Ocular movement

Resting position

Eye deviation

Spontaneous eye movement: nystagmus, ocular


bobbing, ocular dipping

Reex ocular movement: VOR, OCR


J of Neurol and Psychi 1988;51:725-727
mnemonic used to remember the FAST direction of
nystagmus is COWS

COWS: Cold Opposite, Warm Same.

Cold water = FAST phase of nystagmus to the side
Opposite from the cold water lled ear

Warm water = FAST phase of nystagmus to the
Same side as the warm water lled ear
M: Motor response

Resting position

Eyes and head are deviated to the one side opposite


hemiparesis

Decerebrate and decorticate

Adventitious movements

Tonic clonic

myoclonus

Purposeful movement
Posture in coma

Decerebrate rigidity

bilateral upper and


lower limb extensor
posture, usually the
consequence of
bilateral mid-brain
lesions

Decerebrate cat

Decorticate posture

bilateral exion of the


upper limbs and
extension of the lower
limbs, usually the
consequence of an
diencephalic
lesion(late)
R: Respiratory pattern

Cheyne- stoke respiration

Central neurogenic hyperventilation

Apneustic breathing

Cluster breathing

Ataxic respiration
Localisation from respiratory
patterns

Cheyne Stokes - crescendo-decrescendo


breathing - intact brainstem

Central Neurogenic hyperventilation - lower


midbrain/upper pons

Apneustic - lower pontine lesion

Biot breathing/Ataxic breathing - Medullary lesion


Localisation schematic
Cause of coma/alter mental status

Structural

Non-structural

Exogenous:

drugs

toxin (lead, thallium, cyanide, methanol, CO)

Endogenous

metabolic (Na, glucose, Ca, lactic), hypoxemia,


hypercapnia, hypothyroid

Toxin from organ failure: uraemia, hepatic


encephalopathy
Point of concern
Structure mimic toxic-metabolic
SAH, Sinus vein thrombosis, Chronic
subdural hemorrhage,
Diffuse multifocal disorder; vasculitis,
demyelinating

Toxic-metabolic mimic structural
barbiturate, lead poisoning,
hypoglycaemia, hepatic encephalopathy,
hyponatremia
Non convulsive status epilepticus

Fixed stare, repetitive blinking and chewing or


swallowingsmall myoclonic twisting of face and
extremities

Circumstance

Prolong post ictal state

Acute and uctuating of confusion or stupor

Stupor with myoclonus

Episodic partial complex sign

Acute catatonia
Intoxication

Can occur with sympatholytic (clonidine)

Anti-cholonergics (TCA, phenothiazine, anti-


parkinson, OTC

Cholinergic (organophosphate)

Serotonin syndrome (MAOI)

Anion gap acidosis poisonings (ethylene glycol,


salicylates, toluene, paraldehyde, uremia, DKA)
Cognitive dysfunction
- dementia
The memory
Episodic memory & semantic memory
Long term memory: a wide dispersed networks
The cascade of brain areas through which visual information is rst
processed perceptually and then for the purpose of memory
Amnestic and dementia syndrome
!
Amnestic syndrome
Profound loss of the episodic memory
!
Dementia
Acquired and persistent compromise in multiple
cognitive, domains that are severe enough to
interfere with every day functioning
!
Delirium or acute confusional state(ACS)
Prominent decits or uctuations in attention
processing
Gad
e
Amnesia - Causes and localizations
Amnestic
syndrome
= loss of episodic memory
anterograde loss
variable retrograde loss
Normal or relatively spared:

intelligence
working memory
conditioning
priming
Classic case: HM (Scoville &Milner, 1957)
Bilateral removal of mesial temporal
lobes
@openneurons
A man with short term
memory loss
Gade
Alzheimers disease: Topography of neuropathological
changes
Neurobrillary
tangles
Van Hoesen & Solodkin, Ann.N.Y.Acad.Sci. 1994,747:12-35
Herpes simplex
encephalitis

Clinical symptoms

fever

memory loss

alteration of consciousness

neurological decit

Investigation:

Brain imaging: fronto-temporal


lobe involvement

CSF: increase cell, relatively


normal sugar
Wernicke-Korsakoff syndrome
After 2 days treatment with thiamine
* Confusion
* Eye symptoms
- gaze paralysis
- nystagmus
* Gait ataxia
Neuropathological lesions:
Lesions along the neural axis,
particularly close to the ventricle walls
Victor, Adams & Collins, 1971, 1989
Chronic phase:
Korsakoffs disease
(amnesic syndrome)
Transient Global
Amnesia

Hours to day

Temporary version of amnestic syndrome

Causes

Idiopathic

Associated with CPS, Migraine, TIA of


hippocampus, Drug intoxication, Alcohol
blackout, Minor head injury
Dementia diagnosis: The DSM IV
criteria
!
Cognitive problems
!
Memory +
!
Aphasia, Apraxia, Agnosia, Disturbance of
executive function
!
Impairment in occupational or social functioning
Dementia
Reversibel dementia
- Drug
- Syphilis
- Hypothyroid
- Vitamin deciency
- Organ failure
Irreversible dementia
Stable
Progressive
- Vascular
- Post traumatic
- Post encephalitis
- etc
Neurodegenerative Non-neurodegenerative
- CJD
- ADC
- Vascular
Alzheimers
disease
Non-Alzheimers
disease
- Parkinsons disease dementia
- DLB
- Parkinson plus syndrome
- Genetic (Wilson, Huntington)
Alzheimers disease (AD)

AD is a common neurodegenerative disease characterised


by memory impairment plus one or more additional
cognitive disturbance (dementia)

Gradual decline in 3 key symptom domains

Cognition (MMSE, MOCA, ADAS-Cog)

Behaviour and personality

Activities of daily living (ADL)

Prevalence

Age > 65 years : 10%

Age > 85 years : 30%


Staging and diagnosis of MCI and Alzheimers disease
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Pathophysiology

Depletion of acetylcholine (ACh): especially in moderate to severe disease stages


Aim of dementia
management
1. Cure disease
2. Prevent disease or delay onset
3. Slow progression of disease
4. Treat primary symptoms eg memory
5. Treat secondary symptoms eg
depression, hallucinations
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Pathophysiology

Depletion of acetylcholine (ACh): especially in moderate to severe disease stages


APP A"
Neuronal
cell death
#-secretase
"-secretase
Ach
deciency
Secretase modulators
Immunotherapy
amyloid binders
anti-inammation
anti-oxidants
neuroprotection
inammation
oxidative stress
excitotoxicity
Acethylcholine
esterase inhibitor
AD modifying and symptomatic strategies
Neurotransmitters deficiency

Acetylcholine esterase inhibitor


(AchEI)

Donepezil(Aricept),
Rivastigmine(Exelon),
Galantamine(Reminyl)
Pharmacologic treatment

Acetylcholine esterase inhibitor (AchEI)

Donepezil(Aricept),
Rivastigmine(Exelon),
Galantamine(Reminyl)

Symptomatic treatment

drug to control psychological


symptoms
Memantine
NMDA receptor antagonist
Beta amyloid
Dysfunction of Glutamate
reuptake pump
Dysfunction of glutamate
synthetase enzyme
NMDA antagonists: slow intracellular Ca
accumulation and delay nerve damage
Memantine

Approved for use of moderate-severe AD

Use in combination with AchE inhibitor

Mild benets in cognition and clinicians global


assessment of change

Not efcacious in mild AD

No effect on survival time


Psychological and Behavioral
symptoms in dementia

BPSD (Behavioral and Psychological


Symptoms of Dementia)

Apathy, agitation, anxiety, irritability,


aberrant motor behavior, dysinhibition,
delusion, hallucination, euphoria
BPSD
Pharmacologic treatment
Other dementia

Vascular dementia

Normal pressure hydrocephalus (NPH)

Hypothyroidism

AID Dementia

Wernicke-Kosakoff amnestic syndrome

Other neurodegenerative dementia (PDD, FTD, DLB)


66
History
Normal pressure
hydrocephalus (NPH)
First described 40
years ago by
neurosurgeon Solomon
Hakim
Treatable syndrome
Dementia
Gait apraxia
Urinary urgency and
incontinence
The New England Journal of Medicine in 1965
10/3/57
67
NPH : clinical condition or syndrome
characterized by
triad of symptoms
Motor disturbances
Incontinence of urine
Mental change
Ventriculomegaly and normal CSF pressure
10/3/57
68
The difference between NPH [normal
pressure hydrocephalus and other treatable
dementias is that this is a surgically treated
dementia.
CSF shunt if the hydrocephalus is communicating
Endoscopic third ventriculostomy if hydrocephalus
is obstructive
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Diagnosis
Most patients start as possible NPH
Differential diagnosis of symptoms is important,
because theyre among the most common
symptoms of elderly
Gait :peripheral neuropathy, cervical or lumbar stenosis
and myelopathy, parkinsonism, or arthritis
Incontinence:prostate for men or stress incontinence
for women
Dementia : Alzeimer,s disease, frontotemporal
dementia, vascular dementia, or parkinsonism
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70
Diagnosis
Starts either with symptom, CT or MRI showing
enlarged ventricle, or both
Symptom triad
Does not need to be present in its entirety
Most experts believe gait impairment is required
If gait is normal, then look for other causes first
Neuroimaging
In the elderly, ventriculomegaly is sometimes hard to
distinguish from normal ageing, and periventricular T2
changes are ubiquitous
10/3/57
71
Diagnostic : CSF- Removal Approach
2 approaches in use in the United States

Large volume lumbar puncture (LP)

Continuous CSF drainage via spinal
catheter
10/3/57
Dementia in hypothyroidism
Patients with the AIDS dementia complex
present with a variable, yet characteristic,
constellation of abnormalities in cognitive,
motor, and behavioral function. Perhaps
the salient aspects of the disorder are the
slowing and loss of precision in both
mentation and motor control . These
patients often lose interest in their work as
well as in their social and recreational
activities. (Price et al., 1988)
HIV-associated Neurocognitive Disorders
(HAND)

HIV-1-Associated Dementia (HIV-D)

AIDS Dementia Complex (ADC)



HIV-associated Cognitive/Motor Complex
HIV-associated Mild Neurocognitive Disorder

Asymptomatic Neurocognitive Impairment

HIV-Associated Mild Cognitive/Motor Disorder
HIV-D

Essential features

disabling cognitive impairment accompanying by


motor dysfunction, and behavioural change

HIV dementia symptoms are more associated


with motor slowing and loss of executive control
than with language and memory disturbance.

Subcortical dementia
Janssen et al. Neurology 1991. 41:778-785
White-matter abnormalities on CT and MRI
Left: CT scan showing ventricular enlargement and white-matter
hypodensity.
Right: FLAIR MRI showing both cortical and central atrophy,
and characteristic conuent signal abnormalities deep within the
white matter.
Operational denition of HIV-D and clinical
features of use for diagnosis

HIV-1 seropositivity

History of acquired and commonly progressive cognitive-behavioural decline,


with apathy, memory loss, and slowed mental processing

Neurological examination: diffuse and symmetrical CNS signs, including slowed


eye and limb movements, apraxia, hyperreexia, hypertonia, and release signs

Neuropsychological assessment: impairment in at least two domains, including


frontal lobe, psychomotor speed, and non-verbal memory

CSF analysis: exclusion of neurosyphilis, TB, and cryptococcal meningitis

CT and MRI: diffuse cerebral atrophy with symmetrical deep white-matter


hyperintensities.

Exclusion criteria: major psychiatric disorder, intoxication or other cause for


dementia; metabolic impairmenteg, hypoxia, sepsis, uraemia; active CNS
opportunistic processes
Janssen RS, et al. Neurology 1991; 41: 77885.
HIV-D CMV encephalitis PML
Features
Memory disturbance,
mental slowing, gait
disturbance
Delirium, seizures,
brainstem sign
Focal neurological signs
Course Several months Days to weeks Weeks to months
MRI
Diffuse atrophy,
symmetrical deep white
matter, diffuse intensities
Normal or
periventriculitis
Scattered, asymmetrical
subcortical white matter
lesions
CSF
Non-diagnostic immune
activation less marked
in patients treated with
HAART
PCR+ for CMV 90%
PCR+ for JC/BK virus
60%
Differentiation of HIV-D from opportunistic infection
Pre- vs Post HAART era

Natural history change from 6 months (mean) to 44 months to death

Altered pattern of neuropsychological decits in such patients, with


tendency for more cortical type

Hypermetabolism location on PET scan

Pre-HAART: basal ganglia

HAART: mesial temporal lobe

CSF biomarker: beta-2 microglobulin and HIV viral load are not
strongly correlated with ADC severity
Navia B, et al. Ann Neurol 1986, 19:517 524.
Dore GJ, et al. AIDS 2003, 17:15391545.
Cysique L, et al. XIVth International AIDS Conference. Spain 2002.
Treatment of HIV-D

Objective: to maximally suppress HIV replication in CNS

PI containing regimen can reverse neurocognitive


decits
Sacktor N et al. J Neurovirol 2000; 6: 84-88