Neurology Flashcards
What is essential tremor?
autosomal dominant tremor
affects both upper limbs
features of essential tremor
postural tremor : worse if arms outstretched. nothing on relaxed
improved by alcohol and rest
mc cause of titubation (head tremor)
management of essential tremor
1st line: propranolol
primidone sometimes
most common causes of dementia
1st: alzheimers
2nd: vascular and lewy body
assesment tools of dementia
delayed/difficult diagnosis
recommended assesment tool: 10-cs or 6CIT
non recommended but can do: AMTS, GPCOG, MMSE (24 or less/30 is dementia)
initial investigations in dementia
primary care: blood screen to exclude reversible causes eg hypothyroidism
fbc, u+e, lft, calcium, glucose , esr/crp, tft, vit b12, folate.
secondary care: neuroimaging - exclude subdural haematoma, normal pressure hydrocephalus.
Define Delirium
acute confusional state.
affects 30% of elderly admitted to hospital.
presdisposing factors to delirium
age>65
dementia background
significant injury eg hip fracture
polypharmacy
frailty/multimorbidity
precipitating factors for delirium
infection: uti
environmental change
severe pain
alcohol withdrawal
constipation
any significant cv, resp, neuro, endo condition
metabolic: hypercalcaemia, hypoglycaemia, hyperglycaemia, dehydration
features of delirium
memory disturbance (loss of short term>long term)
mood change
visual hallucination
disturbed sleep cycle
possibly agitated/withdrawn
poor attention
disoriented
how would you manage delirium?
tx underlying cause
change environment
haloperidol 0.5mg : 1st line sedative
possibly olanzapine
if parkinson patient, antipycotic worsen parkinsonism symptom - careful reduction of parkinson medication helpful.
if sx require urgent tx give atypical antipsychotic like quetiapine/clozapine
difference between delirium and dementia (favouring delirium)
acute onset
impaired conciousness
fluctuating symptoms - worse @ night, periods of normality
abnormal perception (illusions and hallucinations)
agitation, fear
delusions
depression vs dementia (favouring depression)
short history, rapid onset
patient worried about poor memory
reluctant taking tests, disappointed w/ results
MMSE: variable
global memory loss - dementia is recent memory loss
biological sx: wt loss, sleep disturbance
what is alzheimers?
progressive degenerative disease of the brain.
rf of alzheimers
increasing age
fhx of alzheimers
caucasian
downs syndrome
apoprotein E allele E4 - encodes a cholestrol transport protein
5% cases - inherited autosomal dominant trait. mutation in amyloid precursor protein (chr 21) , presenilin 1 (chr 14) and presenilin 2 (chr 1) genes - thought to cause inherited form
Pathological changes for alzheimers
macroscopic: widespread cerebral atrophy, particular involves cortex and hippocampus
microscopic: cortical plaques due to deposition of type A - beta - amyloid protein and intraneuronal neurofibrillary tangles caused by abnormal aggregation of tau protein
hyperphosphorylation of tau protein linked to AD
biochemical: deficit of acetylcholine from damage to an ascending forebrain projection
what are neurofibrillary tangles?
paired helical filaments made from tau protein.
in AD tau proteins excessively phosphorylated= impaired function
what is tau protein?
Alzhiemers
protein interacting with tubulin.
stabilises microtubules
promotes tubulin assembly into microtubules
how would you manage alzheimers? (non-pharmacological)
activities to promote wellbeing tailored to preference
group cognitive stimulation therapy - mild/moderate dementia
group reminiscence therapy , cognitive rehab
how would you manage alzheimers (pharmacological mx)
acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) - mild/moderate
memantine - nmda receptor antagonist. - 2nd line or monotherapy in severe alzheimers
moderate to severe: acetylcholineesterase inhibitor + memantine
moderate alzheimers intolerant of/contraindication of acetylcholinesterase inhibitors: memantine
how would you manage non cognitive symptoms in alzheimers?
NO to antidepressants for mild/moderate depression in patients with dementia
antipsycotics only for patient at risk of harming themselves or others/agitation/hallucination/delusions causing severe distress (increased risk of mortality)
which drug is contraindicated in alzheimers treatement in patients with bradycardia?
donepezil (Acetylcholine esterase inhibitor)
adverse effect: insomnia
causes of dementia
common : alzheimers,
lewy body (10-20%), cerebrovascular disease : multi-infarct dementia (10-20%)
rarer (5%) - huntingtons, CJD, picks disease (atrophy of frontal/temporal lobes), HIV (50% of AIDS pts)
important differentials for dementia
hypothyroid, addisons
b12/folate/thiamine def
syphilis
brain tumour
normal pressure hydrocephalus
subdural haematoma
depression
chronic drug use: alcohol, barbiturates
what is lewy body dementia?
20% of dementia cases.
lewy bodies (alpha-synuclein cytoplasmic inclusions) in substantia nigra, paralimbic and neocortical areas.
where would you find lewy bodies
substantia nigra
paralimbic
neocortical areas
what percentage of alzherimers patients have lewy bodies?
40%
features of lewy body dementia
parkinsonism
visual hallucination - delusion and non-visual hallucination too)
progressive cognitive impairement - BEFORE PARKINSONISM. - parkinsons is motor symptoms a yr before cognitive.
FLUCTUATING COGNITION COMPARED WITH DEMENTIA
HOW DOES LEWY BODY DEMENTIA COMPARE WITH ALZHEIMERS
IN LEWY BODY EARLY IMPAIREMENT IN ATTENTION AND EXECUTIVE FUNCTION RATHER THAN JUST MEMORY LOSS.
diagnosis of lewy body dementia
clinical
single-photon emission computed tomography (SPECT) / DaTscan.
isotope used: 123-I-FP-CIT - radioisotope.
what is the sensitivity and specifity of SPECT in diagnosing lewy body dementia
sensitivity: 90%
specificity: 100%
how would you manage lewy body dementia?
acetylcholinesterase inhibitors - donepezil, rivastigmine)
AVOID NEUROLEPTICS - pts could get irreversible parkinsonism.
what drug should lewy body dementia patients avoid?
NEUROLEPTICS - can develop irreversible parkinsonism.
causes of parkinsonisms
parkinson’s
drug-induced eg antipsychotics, metoclopramide
progressive supranuclear palsy - neurological condition causes issue with balance, movement,vision,speech, swallowing.
wilsons disease
post-encephalitis
toxins: carbon monoxide, MPTP
what is the first line anti-emetic ( used for parkinsons?
domperidone - doesnt cross blood brain barrier.
no extra-pyramidal side effects (movement disorder, parkinonism, tremor)
what is vascular dementia?
group of syndromes of cognitive impairement caused by different mechanisms causing ischaemia or haemorrhage secondary to cerebrovascular disease.
epidemiology of vascular dementia
17% of uk dementia.
prevalence following first stroke depends on location/size of infarct, interval after stroke, age. overall stroke doubles risk.
incidence increase with age
subtypes of vascular dementia
stroke related - multi-infarct or single-infarct dementia
subcortical - caused by small vessel disease
mixed - presence of both VD and Alzheimers
risk factors of Vascular dementia
hx of tia
AF
HTN
DM
SMOKING
OBESITY
CORONARY HEART DISEASE
HYPERLIPIDEMIA
FHX OF STROKE/CV
can vascular dementia be inherited?
rarely
if so CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
presentation of vascular dementia typically
several months/years of hx of a sudden or stepwise deterioration of cognitive function.
symptoms of vascular dementia
speed of progression and sx may vary :
seizures
gait disturbance
emotional disturbance
memory disturbance
attention and concentration difficulty
focal neurological abnormality: visual disturbance, sensory/motor sx.
how to make diagnosis of vascular dementia?
hx and physical exam
formal screen for cognitive impairement
medical review - exclude medication cause of cognitive decline
MRI - show infarcts and extensive white matter changes
criteria for diagnosing vascular dementia
NINDS-AIREN
presence of cognitive decline interfering with ADLs, not due to secondary effects of cv event. (clinical exam and neuropsychological testing)
cv disease - neurological signs/brain imaging
relationship between the above 2 disorders:
- fluctuating,stepwise deterioration of cognitive deficit
- abrupt deterioration of cognitive function
- onset of dementia within 3 months following recognised stroke
how would you manage vascular dementia?
symptomatic
non pharma:
cognitive stimulation programme
multisensory stimulation
music/art therapy, animal assisted therapy
address pain, avoid overcrowding, clear communication
pharma:
only with AChE inhibitor/memantine if have VD and Alzheimers,Parkinsons dementia or dementia w/ Lewy Bodies.
NO EVIDENCE OF ASPIRIN TREATING PTS WITH VD
no trails showed statins good to tx of vd
what is normal pressure hydrocephalus?
reversible cause of dementia. elderly
secondary to reduced CSF absorption at the arachnoid villi.
could be due to head injury, subarachnoid haemorrhage or meningitis.
classic triad of features seen in normal pressure hydrocephalus
urinary incontinence
dementia and bradyphrenia(slowness of thought)
gait abnormality - similar to parkinsons
sx typically develop over a few months
imaging for normal pressure hydrocephalus
MRI - ventriculomegaly in the absence of, or out of proportion to, sulcal enlargement
how would you manage normal pressure hydrocephalus?
ventriculoperitoneal shunting
potential complications of ventriculoperitoneal shunting treatment?
10% of patients
seizures
infection
intracerebral haemorrhages
what is parkinsons diseases
progressive
neurodegenerative
caused by degeneration of dopaminergic neurones in substantia nigra. reduction in dopaminergic output results in triad of features.
parkinson classic triad
bradykinesia - hypokinesia,short shuffling steps , reduced arm swing, difficulty initiating movement
tremor - at rest, 3-5 hz, worse when stressed/tired, voluntary movement improves. - PIN-ROLLING
rigidity - lead pipe. cogwheel: superimposed tremor
are parkinsons symtoms symmetrical or asymmetrical?
asymmetrical!!
epidemiology of parkinsons
twice as common in men
mean age of diagnosis: 65
other features of parkinsons
mask-like facies
flexed posture
micrographia - small writing
drooling of saliva
rem sleep behaviour disorder
fatigue
autonomic disfunction: postural hypotension
impaired olfaction
psychiatric: depression - 40% , dementia, psychosis, sleep disturbed
drug-induced parkinsonism features:
motor symptoms bilateral and rapid onset.
rigidity and rest tremor uncommon
how would you diagnosis parkinsons?
clinical.
if hard to differentiate between essential tremor and parkinsons consider : SPECT
single photon emission computed tomography
123 i - fp - cit
what colour stain is for lewy body?
brown - alpha synuclein
how would you manage parkinsons?
1st line: levodopa - if motor sx affect QoL
non-ergot derived dopamine agonist (ropinirole,rotigotine,apomorphine), levodopa, monoamine oxidase B inhibitor - if motor sx dont affect QoL
give an example of a monoamine oxidase b inhibitor and tell us how it works?
selegelline
inhibits breakdown of dopamine secreted by dopaminergic neurones
common adverse affects of levodopa
dry mouth
anorexia
palpitations
postural hypotension
psychosis
give an example of a catechol-o-methyl transferase inhibitor and how is works?
entacapone, tolcapone
comt is enzyme involved in dopamine breakdown, could use as adjunct in levodopa therapy.
esp with pts with established pd give with levodopa
give examples of antimuscarinics and tell us how they work
procyclidine, benzotropine, trihexyphenidyl (benzhexol)
block cholinergic receptors
treat drug-induced parkinsonism rather than idiopathic parkinsons disease
help tremor and rigidity
what class of drug is amantadine and what is its function?
antidyskinetic
most likely increases dopamine release and inhibits uptake at dopaminergic synapses
se: ataxia, slurred speech, confusion, dizziness, livedo reticularis (spasm of blood vessel near skin surface)
give examples of dopamine receptor agonists and potential side effects
bromocriptine, ropinirole, cabergoline, apomorphine
ergot derived : pulmonary,retroperitoneal and cardiac fibrosis. DO ECHO, ESR, CREATININE AND CXR BEFORE AND DURING TX.
INFORM PT POTENTIAL IMPULSE CONTROL DISORDER AND EXCESSIVE DAYTIME SOMNOLENCE(sleepy)
hallucination (more likely than levodopa in elder patients)
nasal congestion , postural hypotension.
what drug is nearly always combined with levodopa in PD tx and why?
decarboxylase inhibitor (carbidopa or benserazide)
prevents peripheral metabolism of levodopa to dopamine outside of brain so reduce side effects
what do you give if patient has sx despite optimal levodopa or developed dyskinesia?
add dopamine agonist, MAO-B inhibitor or COMT inhibitor as adjunct.
in parkinsons, what can cause acute akinesia or neuroleptic malignant syndrome?
medication not taken/absorbed - gastroenteritis
no drug holidays
causes of impulse control disorder
dopamine agonist therapy
hx of previous impulse behaviours
hx of alcohol consumption and/or smoking
patient develops excessive daytime sleepiness, he has pmh of parkinsons. how to treat?
do not drive.
adjust med to control symptoms.
give modafinil.
patient with parkinsons develops orthostatic hypotension. what to do?
medication review
midodrine (acts on peripheral alpha-adrenergic receptors to increase arterial resistance)
patient with parkinsons develops drooling of sailva. how to treat?
glycopyrronium bromide
things to know about prescribing levodopa
adverse affects due to difficulty achieving steady dose:
end of dose wearing off - sx worsen at end of dosage interval. decline in motor activity.
on-off phenomenon - large variation in motor performance. normal function in on period. weakness/restricted mobility in off.
dyskinesia at peak dose: dystonia (muscle contraction) , chorea(involuntary muscle movements) and athetosis(involuntary writhing movements)
rules for administering and stopping levodopa
dont acutely stop levodopa
if pt with PD cant take levodopa orally, give dopamine agonist patch as rescue medication to prevent ACUTE DYSTONIA (muscle contraction)
what is MND and types??
neuro condition of unknown cause
can present with both UMN,LMN signs.
amyotrophic lateral sclerosis
progressive muscular atrophy
bulbar palsy
primary lateral sclerosis
rarely presents before 40.
clues pointing towards MND diagnosis
asymmetric limb weakness - MC ALS
no sensory deficits
mixed umn and lmn signs
wasting of small hand muscles/ tibialis anterior
fasciculations
you might get vague sensory symptoms in early disease (limb pain) but never sensory signs
what muscles are spared in MND?
external ocular muscles - eyes are spared.
no cerebellar signs
abdominal reflexes preserved and sphincter dysfunction (late feature)
how would you diagnose MND?
clinical
nerve conduction study - normal motor conduction - help exclude neuropathy.
elelectromyography shows - reduced number of action potentials with increased amplitude.
MRI - excludes differentials of cervical cord compression and myelopathy
mnd type - presentation - ALS - AMYOTROPHIC LATERAL SCLEROSIS
50% pts
typically LMN signs in arms
UMN signs in legs
in familial cases, gene responsible lies on chr 21 and codes for superoxide dismutase
presentation of primary lateral sclerosis - MND
UMN signs only
presentation of MND - Progressive Muscular Atrophy
LMN signs only
affects distal muscles before proximal
carries best prognosis
presentation of progressive bulbar palsy - MND
palsy (paralysis) of the tongue, muscles of chewing/swallowing and facial muscles due to loss of function of brainstem motor nuclei
carries worst prognosis
how to manage MND?
riluzole - prevents stimulation of glutamate receptors . used in ALS mainly - prolongs life by about 3 months
respiratory care - non invasive ventilation (BIPAP) @ night. 7 months survival benefit
PEG tube - nutrition
prognosis of mnd
50% of patients die within 3 years
what is multiple sclerosis?
chronic cell-mediated autoimmune disorder characterised by demyelination in the CNS.
epidemiology of MS - multiple sclerosis
3 times more common in women
20-40
much more common at higher latitudes (5 times more common than in tropics.
genetics with multiple sclerosis
monozygotic twin concordance = 30%
dizygotic twin concordance = 2%
subtypes of multiple sclerosis
relapsing remitting - 85% mc - acute attacks (1-2mths) followed by remission periods
secondary progressive - relapsing remitting pts with deteriorating w/ neurological signs and symptoms between relapses. (65% pts develop within 15 yrs) - gait and bladder disorders seen too
primary progressive disease - 10% pts - progressive deterioration from onset. mc older ppl.
how would you investigate for multiple sclerosis?
YOU NEED TO SEE LESIONS DISSEMINATED IN TIME AND SPACE
MRI
CSF
VISUAL EVOKED POTENTIALS
when you do an MRI in someone with multiple sclerosis what will you see?
high signal t2 lesions
periventricular plaques
dawson fingers : seen in FLAIR images - hyperintense lesions perpendicular to corpus callosum
when you do a lumbar puncture in a multiple sclerosis pt , what would you see?
csf:
oligoclonal bands - not in serum
increased intrathecal synthesis of IgG
when you do visual evoked potentials in a multiple sclerosis pt, what would you see?
delayed, but well preserved waveform
how could you diagnose multiple sclerosis?
2 or more relapses
and either
objective clinical evidence of 2 or more lesions
or
objective clinical evidence of 1 lesion + reasonable historical evidence of previous relapse
visual features of multiple sclerosis
optic neuritis : MC
optic atrophy
UHTHOFF’S PHENOMENON - worsening of vision following body temp rise
internuclear opthalmoplegia
sensory features of multiple sclerosis
pins/needles
numbness
trigeminal neuralgia
lhermitte’s syndrome : paresthesia in limbs on neck flexion
motor features of multiple sclerosis
spastic weakness: mc legs
cerebellar features of multiple sclerosis
ataxia : more often in acute relapse than presenting symptom
tremor
general features (non specific) of Multiple Sclerosis
LETHARGY (85%)
urinary incontinence
sexual dysfunction
intellectual deterioration
is there a treatment for multiple sclerosis?
tx focused on reducing frequency and duration of relapse.
NO CURE
what drug would you give in an acute relapse of multiple sclerosis and for how long?
high dose steroids - oral/iv methylprednisolone - 5 DAYS
shortens length of acute relapse. but not degree of recovery
why would you give a disease modifying drug in multiple sclerosis , indications and examples?
reduce risk of relapse
indications:
relapse remitting disease + 2 relapses in past 2 yrs+ able to walk 100m unaided
secondary progressive + 2 relapses in lasat 2 yrs + able to walk 10m (aided/unaided)
natalizumab - iv - 1st line
ocrelizumab - iv
fingolimod - oral formulation
beta-interferon - subcut/intramuscular (not as effective as others)
qlatiramer acetate - subcut
MoA of natalizumab - MS 1st line DMD
recombinant monoclonal antibody - antagonises alpha 4 beta 1 integrin on surface of leucocytes.
inhibits migration of leucocytes across endothelium across blood brain barrier
strongest base for preventing relapse - 1st line
give IV
class of drug - ocrelizumab - MS tx
humanized anti-cd20 monoclonal antibody
high-efficacy drug - often 1st line like natalizumab
GIVE IV
what type of drug is fingolimod , MoA ? MS TX
sphingosine 1 phosphate receptor modulator
prevents lymphocytes from leaving lymph nodes
ORAL FORMULATION
what type of drug is glatiramer acetate? MS TX
immunomodulating drug - acts as a immune decoy
GIVE SUBCUT
older drug - less effective like beta interferon - monoclonal antibodies and s1p receptor modulators more effective.
if a MS pt experiences fatigue, how could you treat?
trial AMANTADINE - if anaemia, thyroid, depression
