Resident Tutorial 57-Part 1

8/10/2019 Resident Tutorial 57-Part 1

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Resident tutorial57

Surat Tanprawate, MD, FRCPTDivision of Neurology, Chiangmai University


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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


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Symptomatology approach Cognitive function and behavioural change

Level of consciousness: coma, delirium

Content of conscious: dementia, other higher cognitivedisorder (dysphasia, acalculia etc)

Neuropsychiatric problems

Cranial nerve function

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


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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 ofconsciousness

episodic neurological signs/

symptoms


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Cognitive dysfunction- coma


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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


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case


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The question of alter level of

conscious state Coma mimicker: lock-in syndrome

Localize lesion

Caused of coma state

Evaluated brain death


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Arousal and awareness, the two components of consciousness in coma,vegetative state, minimally conscious state, and locked-in syndrome.

Lancet Neurol 2004; 3: 53746


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Alteration of consciousness

Level of consciousness

Stupor and coma

Content ofconsciousness

Behavioural state

StructuralNon-structural

-Metabolic-Toxic

Symmetrical Asymmetrical

C P O M R

(1)

(2)

(3)Localise lesion and identify

the cause


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Behavioural state that may mimic coma


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Locked insyndrome


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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


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Hippus Greek hippos meaning horse

Hippus, also known as pupillary athetosis, isspasmodic, rhythmic, but irregular dilating andcontracting pupillary movements between the

sphincter and dilator muscles


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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 toan expanding supratentorial process


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O: Ocular movement

Resting position

Eye deviation

Spontaneous eye movement: nystagmus, ocularbobbing, ocular dipping

Reex ocular movement: VOR, OCR


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J of Neurol and Psychi 1988;51:725-727


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mnemonic used to remember the FAST direction ofnystagmus is COWS

COWS: Cold Opposite, Warm Same.

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

Warm water = FAST phase of nystagmus to theSame side as the warm water lled ear


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M: Motor response Resting position

Eyes and head are deviated to the one side oppositehemiparesis

Decerebrate and decorticate

Adventitious movements

Tonic clonic

myoclonus

Purposeful movement


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Posture in coma Decerebrate rigidity

bilateral upper andlower limb extensorposture, usually theconsequence ofbilateral mid-brain

lesions Decerebrate cat

Decorticate posture

bilateral exion of the

upper limbs andextension of the lowerlimbs, usually theconsequence of an

diencephaliclesion(late)


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R: Respiratory pattern

Cheyne- stoke respiration

Central neurogenic hyperventilation

Apneustic breathing

Cluster breathing

Ataxic respiration


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Localisation from respiratory

patterns Cheyne Stokes - crescendo-decrescendo

breathing - intact brainstem

Central Neurogenic hyperventilation - lowermidbrain/upper pons

Apneustic - lower pontine lesion

Biot breathing/Ataxic breathing - Medullary lesion


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Localisation schematic


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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, hepaticencephalopathy


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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


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Non convulsive status epilepticus

Fixed stare, repetitive blinking and chewing orswallowingsmall myoclonic twisting of face andextremities

Circumstance

Prolong post ictal state

Acute and uctuating of confusion or stupor

Stupor with myoclonus

Episodic partial complex sign

Acute catatonia


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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)


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Cognitive dysfunction- dementia


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The memory

Episodic memory & semantic memory


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Long term memory: a wide dispersed networks

The cascade of brain areas through which visual information is rstprocessed perceptually and then for the purpose of memory


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Amnestic and dementia syndrome

!

Amnestic syndromeProfound loss of the episodic memory

! Dementia

Acquired and persistent compromise in multiplecognitive, domains that are severe enough tointerfere with every day functioning! Delirium or acute confusional state(ACS)

Prominent decits or uctuations in attentionprocessing


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Ga

Amnesia - Causes and localizations


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Amnesticsyndrome

= 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 temporallobes


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@openneurons


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A man with short termmemory loss


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Gade

Alzheimers disease: Topography of neuropathologicalchanges

Neurobrillarytangles

Van Hoesen & Solodkin, Ann.N.Y.Acad.Sci. 1994,747:12-35


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Herpes simplexencephalitis

Clinical symptoms fever

memory loss

alteration of consciousness neurological decit

Investigation:

Brain imaging: fronto-temporallobe involvement CSF: increase cell, relatively

normal sugar


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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)


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Transient GlobalAmnesia

Hours to day Temporary version of amnestic syndrome

Causes Idiopathic Associated with CPS, Migraine, TIA of

hippocampus, Drug intoxication, Alcoholblackout, Minor head injury

D i di i Th DSM IV


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Dementia diagnosis: The DSM IVcriteria

! Cognitive problems

! Memory +

! Aphasia, Apraxia, Agnosia, Disturbance ofexecutive function

!

Impairment in occupational or social functioning


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Dementia

Reversibel dementia

- Drug- Syphilis- Hypothyroid- Vitamin deciency- Organ failure

Irreversible dementia

Stable Progressive- Vascular- Post traumatic- Post encephalitis- etc

NeurodegenerativeNon-neurodegenerative

- CJD- ADC- Vascular

Alzheimers

disease

Non-Alzheimersdisease

- Parkinsons disease dementia- DLB- Parkinson plus syndrome- Genetic (Wilson, Huntington)


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Alzheimers disease (AD)

AD is a common neurodegenerative disease characterisedby memory impairment plus one or more additionalcognitive 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%


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Staging and diagnosis of MCI and Alzheimers disease

P th h i l g


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Pathophysiology

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


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Aim of dementiamanagement

1. Cure disease

2. Prevent disease or delay onset

3. Slow progression of disease

4. Treat primary symptoms eg memory

5. Treat secondary symptoms egdepression, hallucinations

Pathophysiology


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Pathophysiology

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


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APP A"Neuronalcell death

# -secretase

" -secretaseAchdeciency

Secretase modulators

Immunotherapyamyloid binders

anti-inammation

anti-oxidants neuroprotection

inammation oxidative stress

excitotoxicity

Acethylcholineesterase inhibitor

AD modifying and symptomatic strategies

N i d fi i


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Neurotransmitters deficiency

Acetylcholine esterase inhibitor(AchEI)

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


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Pharmacologic treatment

Acetylcholine esterase inhibitor (AchEI) Donepezil(Aricept),

Rivastigmine(Exelon),Galantamine(Reminyl)

Symptomatic treatment

drug to control psychologicalsymptoms


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Memantine NMDA receptor antagonist

Beta amyloid

Dysfunction of Glutamatereuptake pump

Dysfunction of glutamatesynthetase enzyme


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NMDA antagonists: slow intracellular Caaccumulation and delay nerve damage


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Memantine Approved for use of moderate-severe AD

Use in combination with AchE inhibitor

Mild benets in cognition and clinicians globalassessment of change

Not efcacious in mild AD

No effect on survival time


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Psychological and Behavioralsymptoms in dementia

BPSD (Behavioral and PsychologicalSymptoms of Dementia)

Apathy, agitation, anxiety, irritability,aberrant motor behavior, dysinhibition,delusion, hallucination, euphoria


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BPSD Pharmacologic treatment


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Other dementia Vascular dementia

Normal pressure hydrocephalus (NPH)

Hypothyroidism

AID Dementia

Wernicke-Kosakoff amnestic syndrome

Other neurodegenerative dementia (PDD, FTD, DLB)


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History

Normal pressurehydrocephalus (NPH)

First described 40years ago byneurosurgeon SolomonHakim

Treatable syndrome Dementia Gait apraxia

Urinary urgency andincontinence

The New England Journal of Medicine in 1965

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NPH : clinical condition or syndromecharacterized by

triad of symptoms Motor disturbances Incontinence of urine Mental change

Ventriculomegaly and normal CSF pressure

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The difference between NPH [normalpressure hydrocephalus and other treatabledementias is that this is a surgically treateddementia.

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 commonsymptoms of elderly

Gait :peripheral neuropathy, cervical or lumbar stenosisand 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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Diagnosis

Starts either with symptom, CT or MRI showingenlarged 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 todistinguish from normal ageing, and periventricular T2changes are ubiquitous

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Diagnostic : CSF- Removal Approach

2 approaches in use in the United States

Large volume lumbar puncture (LP)

Continuous CSF drainage via spinalcatheter

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Dementia in hypothyroidism


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Dementia in hypothyroidism


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Patients with the AIDS dementia complexpresent with a variable, yet characteristic,constellation of abnormalities in cognitive,motor, and behavioral function. Perhaps

the salient aspects of the disorder are theslowing and loss of precision in bothmentation and motor control . Thesepatients often lose interest in their work aswell as in their social and recreationalactivities. (Price et al., 1988)

HIV-associated Neurocognitive Disorders


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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


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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 controlthan with language and memory disturbance.

Subcortical dementia

Janssen et al. Neurology 1991. 41:778-785


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White-matter abnormalities on CT and MRI

Left: CT scan showing ventricular enlargement and white-matterhypodensity.

Right: FLAIR MRI showing both cortical and central atrophy,and characteristic conuent signal abnormalities deep within thewhite matter.

Operational denition of HIV-D and clinical


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

Neuropsychological assessment : impairment in at least two domains, includingfrontal 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 fordementia; metabolic impairmenteg, hypoxia, sepsis, uraemia; active CNSopportunistic processes

Janssen RS, et al. Neurology 1991; 41: 77885.

Differentiation of HIV-D from opportunistic infection


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P P HAART


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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, withtendency 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 notstrongly 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.


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Treatment of HIV-D

Objective: to maximally suppress HIV replication in CNS

PI containing regimen can reverse neurocognitivedecits

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Resident Tutorial 57-Part 1