Neurology Flashcards
Following a TIA, in what timeframe is the greatest risk of a stroke occurring
Within the first 48 hours
How rapidly should complete work-up and initiation of secondary prevention be completed following a TIA
Within 24 hours
What urgent work up is required in patients with TIA
Diagnostic confirmation by a stroke specialist
ECG +/- cardiac monitoring ?AF
Brain imaging (CT or MRI at minimum)
- if anterior circulation symptoms are present, carotid imaging (USS, CTA or MRA) also indicated
Which TIA patients required immediate hospital referral
Those with:
- ongoing focal neurological symptoms
- > 1 TIA in the past 7 days
- Presence of atrial fibrillation
- Patient treated with anticoagulation (needs exclusion of haemorrhage)
- ABCD2 score >3
Risk stratification score for TIA
ABCD2: Age >60 = 1 BP >140/90 =1 Clinical features: - Unilateral weakness = 2 - Speech disturbance without weakness = 1 - Other symptoms = 0 Duration of symptoms: - <10min = 0 - 10-59 min = 1 - >60 min = 2 Diabetes history = 1
Score 0-3 = low risk
4-5 points = moderate
6+ = high risk
Clinical features of lacunar/subcortical stroke syndromes
PURE motor hemipareses OR PURE sensory loss affecting contralateral face, arm and leg equally
- note that face may not be affected if infarct is beneath the mid pons
NO associated dysphagia, visual inattention or visual field loss
Clinical features of ACA stroke
Leg weakness > arm weakness
Personality change
Occulomotor palsy (eye deviated down and out)
Urinary incontinence
Clinical features of MCA stroke
Arm weakness > leg weakness Dysphasia Dyspraxias Agnosia (unable to recognise things e.g. faces, objects, places Hemi-neglect Poor two-point discrimination Dysgraphaesthesia
Clinical features of PCA stroke
Cortical blindness - contralateral homonymous hemianopia with normal fundoscopy and light reflex
(Can also have subcortical signs which will confuse picture)
What is Gerstmann’s syndrome
Syndrome due to infarct in the dominant parietal lobe. Clinical features RAAF pneumonic: Right-left confusion Agraphia Acalculia Finger agnosia
Clinical features of vertebrobasilar territory ischaemia
BILATERAL weakness or sensory disturbance
Diplopia
Vertigo
+/- nausea, vomiting, inability to stand
Differences between migraines in children v adults
Children:
- tend to be shorter duration (<4h)
- photophobia/phonophobia often don’t develop until >12y
- usually bilateral (though younger kids have difficulty describing this)
- tend not to be associated with mental health
- triptans have no clear evidence for <12y, but are safe from >6y
Indications for imaging paediatric headaches (7)
- abnormal neuro exam
- change in character or pattern of pre-existing headaches
- new-onset severe headaches
- seizures or other signs of neurological dysfucntion
- history of neurocutaneous syndrome (e.g. neurofibromatoisis, tuberous sclerosis, Sturge-Weber syndrome)
- age <6y
- headache location exclusively occipital
Risk of a second seizure after a first unprovoked epileptic seizure
40%
Causes of provoked seizures
Acute neurological insult (stroke, trauma, infection, inflammation)
Biochemical (hypo/hyper - glycaemia, natraemia, calcaemia, hypomagnesaemia, hypoxia, acid-base disturbance)
Alcohol or other drug intoxication OR withdrawal
Pregnancy (eclampsia
Diagnosis of epilepsy
Implies demonstrated tendency for recurrent unprovoked seizures
- often made after 2 unprovoked seizures >24h apart
OR
- after one seizure if EEG or neuroimaging indicates a structural basis for seizure tendence
Features of generalised tonic clonic seizures
Initial phase of stiffening and few second LOC (often causes fall and forced scream AKA ictal cry)
Followed by all limbs jerking for up to 2 mins
Cyanosis, tongue-biting, urinary incontinence are common
Post-ictal stertor (heavy breathing/snoring), confusion, amnesia typically for several minutes
Clinical features of generalised absence seizures
Frequent (>daily) brief (<30 second) episodes of behavioural arrest without motor features and immediate recovery (no post-ictal phase)
Clinical features of myoclonic seizures
Single jerks of muscles, usually generalised
No post-ictal period
Occur during wakefulness, but otherwise are similar to hypnic jerks
Clinical features of focal seizures
Myriad of presentations but show high degree of sterotypy in an individual
Can be associated with impairment of consciousness (e.g. temporal lobe epilepsy) - typically these type tend to be less frequent, more prolonged than absence seizures and with post-ictal phase
Can evolve into secondary generalisation
Differential diagnoses of ?epileptic seizures
Cardiac syncope: - arrhythmias, bradycardia, heart block, tachycardia - aortic stenosis - cardiomyopathy Non-cardiac syncope - vasovagal - postural hypotension Migraine Narcolepsy-cataplexy Tremors Tics Movement disorders Pscyhiatric/psychological: - pseudoseizures - hyperventilation - panic attacks - disassociative reactions
Triggers for epileptic seizures
Sleep deprivation Overuse of alcohol Fever Intercurrent illness Severe sustained stress (combination of above)
Despite if trigger is identified or not, if first presentation, need work up for epilepsy syndrome
Investigations to consider in first presentation of seizure
- CBE, CRP ?infection
- BGL!
- LFT, EUC, CMP
- blood alcohol or urine drug screen (if indicated)
CT/MRI if:
- trauma
- focal onset of seizure
- diseases that could lead to seizures (e.g. cancer)
- fever, meningism or neurological signs
- EEG!! - for all of them
Preferred neuroimaging for workup of seizures and why
MRI more sensitive than CT for small/subtle lesions. Can also better demonstrate the temporal lobe than a CT
How to get maximal yield from an EEG after first seizure presentation
Best performed within 24h of all acute cases
If initial EEG non-diagnostic, sleep deprivation EEG should be obtained
Indicated for the diagnosis of epilepsy syndromes, NOT for prognosis
Features of childhood absence epilepsy
- Begins 3-12y (peaks at 6y)
- Frequent episodes (>20/day)
- Abrupt onset without warning, rapid offset with resumption of previous activities
- brief impairment of awareness (<20 seconds)
- adversely affect school performance
- can be triggered by stress, fatigue, hyperventilation
Can be accompanied with GCTC (which tend to occur later in adolescence)
60% will resolve by mid-adolescence
Prognosis of childhood absence epilepsy
60% will resolve by mid adolesence
Paediatric idiopathic generalised epilepsy syndromes
Childhood absence epilepsy
Juvenile absence epilepsy
Juvenile myoclonic epilepsy
Triggers of childhood absence epilepsy episodes
Stress
Fatigue
Hyperventilation
How does juvenile absence epilepsy differ from childhood absence epilepsy?
Later age of onset (10-20y)
Less frequent episodes (e.g. 1/week)
Less severe impairment of awareness may occur
Other seizure types more common
Clinical features of juvenile myoclonic epilepsy
Onset 8-20y
Isolated myoclonic seizures, especially after awakening
Other seizure types are common (80% GTCT, 30% absence seizures)
Triggered by sleep deprivation, fatigue, alcohol use
Seizure types associated with juvenile myoclonic epilpesy
80% GTCS
30% absence seizures
Triggers for juvenile myoclonic epileptic seizures
Sleep deprivation
Fatigue
Alcohol use
Treatment of juvenile myoclonic epilepsy
Typically respond well to low doses of valproate or levetiracetam
Other AEDs can control GTCs but can worse then absence or myoclonic seizures
Prognosis of juvenile myoclonic epilepsy
Usually require lifelong treatment
General management of idiopathic generalised epilepsies in children
Valproate is first line (but ensure adequate contraception in child-bearing age)
Lamotrigine second line, especially in combination with valproate
Definition of symptomatic epiepsy
Epilepsy occurring in the setting of a known or suspected abnormality of the CNS
Clinical features of West syndrome
Epileptic syndrome developing around 6 months
Often mistaken for infantile colic
Clusters of (often subtle) epileptic spasms, developmental arrest or regression
Treatment of West Syndrome
Oral corticosteroids
Should be commenced ASAP
Prognosis of West syndrome
20% will evolve to Lennox-Gastaut syndrome
Clinical features of Lennox-Gastaut syndrome
- Begins between 1-8y
- Generally TONIC seizures (but may also have atonic drop attacks, atypical absence seizures, GTCS and/or myoclonic seizures)
Commonly associated with intellectual disability, cognition may have been normal prior to development of the syndrome
Treatment of Lennox-Gastaut syndrome
Difficult to treat
Most effective treatment is often combination of valproate and lamotrigine
Cause of Lennox-Gastaut syndrome
Symptomatic epilepsy Multiple aetiologies including - cortical malformations - tuberous sclerosis - trauma
Idiopathic partial epilepsies of childhood
Benign epilepsy with centro-temporal spikes (BECS, AKA Rolandic epilepsy, or benign focal epilepsy of childhood)
Benign occipital epilepsies of childhood
Most common childhood epilepsy syndrome
Benign epilepsy with centro-temporal spikes
Clinical features of benign epilepsy with centro-temporal spikes
Begins at 3-13y, stops by 16y
Nocturnal seizures, occurring shortly after falling asleep, or just before waking
Often experience aura of perioral or gum paraesthesia before:
- speech arrest
- drooling
- tonic OR clonic involvement of upper limb or face
- gurgling or grunting noises (generally if progresses to secondary GTCS)
Prognosis of benign epilepsy with centro-temporal spikes/ benign Rolandic epilepsy
Excellent prognosis, even with frequent seizures
Treatment of benign epilepsy with centro-temporal spikes
No treatment required for first few seizures
- CBZ or valproate should be considered if seizures are frequent
Time of onset of benign occipital epilepsy of childhod
Onset between 3-14y, usually resolve by mid teens
Two distinct syndromes:
Early onset = panayiotopoulous syndrome
Late onset = Gastaut syndrome
Clinical features of Early onset benign occipital epilepsy of childhood (Panayiotopoulous Syndrome)
Rare, prolonged nocturnal attacks with eye deviation, vomiting and autonomic features
Clinical features of later onset benign occipital epilepsy of childhood (Gastaut syndrome)
Frequent, brief episodes of elementary visual auras, prominent headache and transient visual impairment
Investigation of benign occipital epilepsy of childhood
EEG - abnormal activity is brought out by eye closure
MRI is indicated as symptomatic occipital epilepsy can present very similarly
Clinical features of temporal lobe epilepsy
Aurus (olfactory or gusstatory hallucinations, perceptual phenomena e.g. deja vu)
Seizure itself:
- staring spell with psychomotor arrest and loss of awareness
- Automatisms involving perioral region or upper limbs
- lasts 30s to few minutes
-Followed by a postictal phase of confusion, drowsiness and headache
How does temporal lobe epilepsy differ from absence seizures (clinically)
Temporal lobe epilepsy has an associated aura, longer duration, and postictal changes
Treatment of temporal lobe epilepsy
Is the most common form of refractory epilepsy in children and in adults
Often requires >1 AED
Surgery can be considered (anterior temporal lobectomy) as most common structural cause is hippocampal sclerosis
General first line AED for generalised seizures
Valproate
If not tolerated, change to lamotrigine or topiramate
General first line AED for partial seizures
Carbamazepine (controlled release formulation is preferred)
Treatment duration of epilepsy
Highly variable depending on particular syndrome and individual, generally a MINIMUM of 2 years complete seizure control
Common adverse effects of all AEDs
Somnoloence, cognitive impairment, ataxia, other neurotoxic adverse effects
All are dose-dependent (which vary a lot between individuals) and resolve rapidly on discontinuation
Enzyme inducing anti-epileptic medications
Phenytoin
Carbamazepine
Topiramate (weak inducer)
Oxcarbazepine (weak inducer)
Non enzyme-inducing anti-epileptic drugs
Clonazepam Valproate Lamotrigine Gabapentin Levetiracetam Pregabalin
Typical dose of phenytoin for seizure control
200-400mg once daily
Typical dose of carbamazepine for seizure controll
200-600mg BD
Typical dose of topiramate for seizure control
50-200mg BD
Typical dose of oxcarbazepine for seizure control
300-900mg BD (approx 1.5x less potent than CBZ)
Typical dose of clonazepam for seizure control
0.5-2mg BD
Typical dose of valpraote for seizure control
400-1000mg BD
Typical dose of lamotrigine for seizure control
50-200mg BD
Note lower dose requiredment (approx half) if also on valproate
Typical dose of gabapentin for seizure control
300-800mg RDS
Typical dose of levetiracetam for seizure control
500-1500mg BD
Typical dose of pregabalin for seizure control
75-300mg BD
Adverse effects of phenytoin
Hirsutism, acne, coarse facies
Gum hypertrophy
Rash/SJS
(Cosmetic side effects limit use)
Adverse effects of carbamazepine
Hyponatraemia
Rash/SJS
Adverse effects of topirmate
Anorexia & weight loss Word-finding difficulty Nephrolithiasis Oligohidrosis Metabolic acidosis Depression
Adverse effects of oxcarbazepine
Hyponatraemia (more so than with carbamazepine)
Adverse effects of clonazepam
Sedation
Ataxia
Which benzodiazepine is used for seizure control
Clonazepam
Adverse effects of valproate
Weight gain
Tremor
Alopecia
Adverse effects of lamotrigine
Rash/SJS (risk reduced with slow titration to target dose over 8 weeks)
Adverse effects of gabapentin
Weight gain
Adverse effects of levetiracetam
Agitation
Depression
Adverse effects of pregabalin
Weight gain
When should genetic testing be performed prior to AED commencement
Asian patients should all have HLA testing prior to commencing carbamazepine, as patients with HLA-B*1502 allele have a higher risk of SJS
When is therapeutic drug monitoring indicated for antiepileptics
Monitoring efficacy of AEDs is clinical, not pharmocological.
TDM may be useful in cases when adherence is questioned OR when altered pharmacokinetics is expected:
- pregnancy
- drug-drug interactions
- hepatic or renal impairment
Which is the only AED that effective controls absence seizures and myoclonic jerks
Valproate
Which AEDs can exacerbate absence and myoclonic seizures (or cause them to emerge)
Carbamazepine
Phenytoin
Restrictions to driving in patients with epilepsy
Generally, patients with stable epilepsy on AEDs, and patients after a first epileptic seizure will be judged fit to return to driving after being seizure free for 6 months
Ideally, provide DLA with a concise medical report allowing them to make the decision about a person’s driving
Epilepsy and contraception
ENZYME-INDUCING AEDs reduce the efficacy of COCP by increasing clearance of oestrogen AND progesterone components
Increasing to high dose oestrogen unlikely to prevent ovulation
Strategies for effective contraception on enzyme-inducing AEDs:
- double dose (of both oestrogen AND progesterone)
- continuous use of active pills
- alternative contraceptive methods
- changing AEDs
Risk of AEDs in pregnancy
Double the risk of congenital malformations (to 6%) compared to pregnancies not exposed to AEDs
Only agent with a specific higher risk is valproate at a daily dose >1100mg
preconceptional folate supplementation is recommended (not proven) to mitigate risk
AED dose in pregnancy
Requirements usually increase after the first trimester
- especially for lamotrigine and levetiracetam
- therapeutic drug monitoring can be extremely useful
Epilepsy and bone halth
Evidence that long-term use of AEDs is associated with reduced BMD, thus general preventative measures should be taken
- optimise physical activity
- optimise dietary calcium intake
- correct vitamin D deficiency
- smoking cessation
Factors that influence seizures during pregnancy in epileptic women
Metabolic changes Pregnancy symptoms (vomiting, malaise, sleep deprivation) Pharmacokinetic changes (reduced absorption and protein binding, change to volume of distribution, metabolism and excretion of drugs)
Anti-epileptic drugs that have the most significant pharmacokinetic changes during pregnancy
Lamotrigine
Oxcarbazepine
Predictors of seizure control in pregnancy
- significantly more likely if have had a seizure in the 12 months (particularly 1 month) prior to conception
- AED polytherapy
- Oxcarbazepine or lamotrigine monotherapy
Valproate monotherapy has the lowest risk in terms of treatment
Most likely timing of seizures in pregnancy
Focal seizures: 2nd-3rd month, and 6th month of pregnancy
Generalised: 3rd month of pregnancy
Risks to pregnancy of having a seizure during pregnancy
SGA
Low birthweight babies
Pre-term delivery
Risk of AEDs to foetus/child
Teratogenicity
- especially valproate >1.1g daily dose
- lowest risk in lamotrigine
- probably increased with AED polytherapy, therefore aim to avoid polytherapy in the 1st trimester
- recommend pre-conception folic acid supplementation 400microg/day
Reduced cognition
- increased in AED polytherapy
- most associated with valproate exposure (esp >1.1g) - language impairment, 7-10 IQ point loss, verbal and memory abilities
- evidence of benefit with preconception folate
What are OBSTETRIC risks of antiepileptic drugs in pregnancy
No conclusive evidence of higher risks of obstetric complications in women on AEDs
Suggested management of pregnant women with epilepsy
Aim for monotherapy prior to conception (lamotrigine if possible)
Take baseline pre-pregnancy lamotrigine levels, and regular monitoring and dose adjustments during pregnancy to maintain pre-pregnancy levels
Beware risk of toxicity in immediate post-partum period due to rapid reduction in metabolism
Definition of multiple sclerosis
A MULTIFOCAL central nervous system disease characterised by inflammatory demyelinating lesions affecting both white and grey matter, thought to be medited by autoreactive T cells
Epidemiology of MS
More common the further south (most common in Tasmania 1/1000), progressively less common further north
F:M = 3:1
Mean age of symptom onset and diagnosis in mid 30s
Risk factors associated with MS
Family history Place of residence in pre-adult years (temperate regions higher risk than tropical) Later age of exposure to EBV (seronegative individuals very low risk) Smoking Dairy and saturated fat consumption Stress Lack of omega 3s Inadequate sun exposure Low vitamin D
Natural history of MS
Clinically isolated syndrome (1st demyelinating event occurs in 85%)
Most commonly develops into relapsing remitting MS
40-45% will transition after 10y to Secondary progressive MS
15-20% will have primary progressive MS from the onset
Multiple sclerosis clinically isolated syndrome presentations
First demyelinating event, occurs in 85% of MS patients
Episode of neurological disturbance evolving over days or weeks
- motor or sensory deficits (46%)
- Clinically isolated optic neuritis (21%)
- brainstem syndrome (10%)
- multifocal abnormalities (23%)
Pattern of disease in relapsing remitting MS
Most common pattern of disease in MS
- Complete resolution or mild residual symptoms or signs between attacks
- Relapses occur erratically approx every 2y in untreated patients
- fatigue in isolation is not a relapse, but termed psuedorelapse
Pattern of disease in secondary progressive MS
40-45% of patients will transition after 10 years of relapsing remitting MS (80% lifetime risk)
Occasional plateaus and temporary minor improvements may be observed, trend progressively increasing disability
Pattern of disease in primary progressive MS
15-20% will have this pattern Progressive from onset NO relapses or remissions Most commonly: slowly progressive spastic paraparesis (cerebellar or hemiplegic syndromes next most common) Does not respond to current treatments
Common sites of disease in MS
Optic nerve Cerebellum Spinal cord (usually multifocal and asymmetric) - pyramidal tracts or spinothalamic tract and posterior columns Brainstem Bowel/bladder upper motor neurons
Signs and symptoms of MS involving the optic nerve
(Optic neuritis) Pain on eye movements Blurred vision Reduced monocular acuity Colour desaturation
Signs and symptoms of MS involving the cerebellum
Unsteadiness
Limb or gait ataxia
horizontal or torsional gaze evoked nystagmus
Signs and symptoms of MS involving the spinal cord
Usually multifocal and asymmetric
- Involving the pyramidal tracts:
- upper or lower limb weakness in pyramidal distribution - Spinothalamic tract and posteriod columns
- unilateral or bilateral numbness or paraesthesias
- L’hermitte’s phenomemon (short electric shock-like sensation on neck movement)
What is L’hermitte’s phenomenon
Short electric shock-like sensations on neck movement
Associated with spinothalamic MS
Signs and symptoms of MS involving the brainstem
(Internuclear ophthalmoplegia)
- blurred or double vision
- affected eye shows impaired adduction, whereas contralateral eye abducts but with nystagmus
Signs and symptoms of MS involving the upper motor neurons of bowel and bladder
Constipation
Urinary frequency
Urge incotinence
Erectile dysfunction
Diagnosis of MS
Clinical diagnosis supported by:
- MRI (demyelinating lesions of multiple ages)
- CSF findings (oligoclonal bands and raised IgG index)
- evoked potential studies
Only certain diagnosis is through brain biopsy. Though this is not done in practice.
Differential diagnoses of MS
Other demyelinating conditions:
- neuromyelitis optica
- acute disseminated encephalomyelitis
Others:
- migraine
- neoplasms
- nutritional deficiencies (B12 or copper)
- compressive lesions of spinal cord
- Infections (syphilis, HIV)
- Amyotrophic lateral sclerosis
- Steroid sensitive relapsing disorders (e.g. SLE, neurosarcoidosis)
- recurrent infarcts
- paraneoplastic syndromes
- psychiatric disease/functional symptoms
Management of acute MS relapse
If relapse significantly impacting quality of life:
- IV methylprednisolone 1g/day for 3 days
If steroid unresponsive with severe relapse -> Plasma exchange
Long-term management of MS
Disease modifying treatments are useful for patients with clinically isolated syndromes, and those with relapsing remitting MS, but only on PBS for RRMS
Monitor response by suppression of relapses, and suppression of new lesions on repeat MRI after 6 months
Options on PBS:
- Interferon B
- Glatiramer acetate
- natalizumab
- Fingolimod
- mitoxantrone
- cyclophosphamide
Common troublesome symptoms of MS
Spasticity Paroxysmal neuralgias, paraesthesias Fatigue Intention tremor Urinary urgency Erectile dysfunction
Good prognostic features of MS
Optic neuritis or isolated SENSORY symptoms as the clinically isolated syndrome
Initial relapsing remitting course
Long interval to second relapse
No disability after 57
Normal initial MRI
Younger age at onset
Complete recovery from the first neurological episode
Poor prognostic features in MS
Efferent systems affected in the clinically isolated syndrome, or “multifocal” ICS
High relapse rate in the first 2-5y
Substantial disability at 5y
Abnormal initial MRI with large lesion load
Effect of pregnancy on MS
Pregnancy reduces disease activity, especially in 3rd trimester
High risk of relapse in the first 3 months post partum (however breastfeeding offers some protection)
Only disease modifying treatment suitable is glatiramer (B1), and antalizumab (C), others are classed D - decision of when to stop treatment prior to pregnancy is highly individualised
What biochemical markers should be obtained in a patient with suspected MS
Vitamin D.
Hypovitaminosis D is more common in patients with MS and is a common trigger for relapse
Primary prevention of MS in susceptible individuals
I.e. close family members of someone with MS
- Vitamin D supplementation 5000IU daily (for adults, or equivalent for children)
Eligibility criteria for commencing a PBS subsidised disease modifying agent for multiple sclerosis
Must be clinically diagnosed with MS via MRI OR be contraindicated to have an MRI
+ AT LEAST TWO relapses in the previous 2 years prior to commencing PBS subsidised therapy
+ be ambulatory
Typical features of an essential tremor
Bilateral, largely symmetrical
Postural or kinetic (usually not present at rest, occurs immediately on new posture)
Usually involves hands and forearms - can spread to neck and voice
Tends to have family history
Typically improves with alcohol
Typical features of a Parkinsonian tremor
Typically purely at rest, + with postural component emerging after latent period following adoption of a new posture Low frequency (coarse tremor) Improves with activity
