Neurology Flashcards
Features of Juvenile Myoclonic Epilepsy
- Morning myoclonic jerks (often dropping things)
- +/- absence seizures
- Normal intelligence
- Family hx
- Onset 8-20yrs
- Generalised tonic-clonic seizures occurring just after waking or during sleep
- Increased seizures with sleep deprivation, stress, alcohol
Features of Absence seizures
- Short lapses in awareness (10-20sec)
- Absence of aura
- Amnesia during the episodes
- Abrupt onset and end
- Staring and behavioural arrest +/- flickering eyelids, eye rolling, mouth automaticisms
No post ictal period
EEG finding of 3Hz spike and wave is characteristic of what?
Absence seizures / Childhood absence epilepsy
Management of focal seizures
Carbamazepine
Which medication should be avoided in absence seizures and can worsen absence seizures
Carbamazepine
What genetic condition commonly causes infantile spasms (30%)
Tuberous sclerosis
Features of Lennox Gastaut Syndrome
- multiple seizure types
- intellectual disability
- EEG: “slow spike and wave”
What causes gelastic seizures (laughing seizures)
Hypothalamic hamartomas
Side effects of sodium valproate
Fat (weight gain)
Bald (hair loss)
Thrombocytopenia (dose related)
Pancreatitis
Incr Ammionia
Neural tube defects
What is vigabatrin used for and what is its main AEs
Used in West Syndrome (Infantile spasms)
AEs
- can cause irreversible visual field defects
- also causes weight gain
Side effects of carbamazepine?
- Severe leukopenia
- Hepatotoxicity
- SIADH and hyponatremia
- N, V, D
- Rash
- Diplopia
- Dizziness and drowsiness
Which AED is most teratogenic?
Sodium valproate
Hallmark EEG feature of Infantile spasms?
Hypsarrhythmia
Which anti-convulsant should be avoided in Chinese people with HLA-B1502 allele?
Carbamazepine and lamotrigine
Mutation found in Dravet syndrome
Loss of function mutation in SCN1A gene
Dravet syndrome often begins with febrile seizures which are more prolonged, more frequent, may be focal and come in clusters then develop afebrile seizures or various types
Features of Benign familial neonatal seizures
- Autosomal dominant, usually due to genes in KCNQ2 and KCNQ3 genes
- Onset ~ 2-4days old
- Usually remit ~ 2-15weeks of age
- Seizures consist of ocular deviation, tonic posturing, clonic jerks and motor automaticisms
- Interictal EEG usually normal
Approx 16% develop lateral epilepsy
Features of CNIII paralysis
Ptosis
Dilation of the pupil
Displacement of the eye down and out
Impaired adduction and elevation
Features of CNVI paralysis
Medial deviation of the eye
Inability to abduct beyond the midline
Difference between spasticity and rigidity
Spasticity is characterised by initial resistance and then sudden release (clasp-knife) and is due to UMN lesion. Velocity dependent
Rigidity is characterised by complete resistance to flexion and extension (lead-pipe) and may be due to lesion in basal ganglia
Which AED requires serial measurements of serum levels because of a narrow therapeutic index?
Phenytoin
Lamotrigine drug interactions?
- Topiramate may increase toxicity of sodium valproate.
- Topiramate concentration may be decreased by carbamazepine.
Inflammatory demyelination typically of the periventricular deep white matter with POSTERIOR-PREDOMINANT pattern?
Adrenoleukodystrophy (X-linked)
Bilateral symmetrical areas of periventricular deep white matter signal change around the atria and frontal horns forming a “BUTTERFLY PATTERN”?
Metachromatic leukodystrophy
Urine succinylacetone is present in which condition?
Tyrosinemia
What is the recurrence risk of myelomeningocoele in subsequent pregnancies?
2-3% if 1 affected child
10% if 2 affected children!
Difference between meningocele and myelomeningocoele
Meningocele is a herniation of the meninges (not the cord) through a defect in posterior vertebral arches
Less severe, less common
Myelomeningocoele is a herniation of nerve roots, spinal cord, meninges through a defect in the spinal cord. They cause a downward displacement of brainstem and cerebellar tonsils into the spinal column (Chiari II or ‘Arnold Chiari’ malformation) ->hydrocephalus
Which antenatal blood test could suggest an open neural tube defect (anencephaly or encephalocoele, myelomeningocoele) if elevated?
AFP
Causes of communicating hydrocephalus (impaired absorption)?
Meningitis
Subarachnoid haemorrhage
Congenital infections eg CMV, toxo, rubella
Anything that irritates the lining of the arachnoid granulations
Causes of non-communicating (obstructive) hydrocephalus
Congenital
- Dandy Walker malformation
- Congenital aqueductal stenosis
- X linked aqueduct stenosis (L1CAM mutation)
- Type 1 Chiari malformation
- Type 2 Chiari malformation
Acquired
- Brain tumours
- Intraventricular clots, abscesses
- Vein of Galen malformation
What is Chiari I malformation?
Downward displacement of cerebellar tonsils or vermis below the foramen magnum
What is Chiari II malformation (Arnold Chiari)?
Downward displacement of cerebellum AND 4th ventricle and lower medulla below the level of the foramen magnum. This blocks CSF outflow and 85% have hydrocephalus. Unlike type 1, surgical intervention usually required
What is polymicrogyria?
Multiple small gyri (folds) - cerebral cortex has an irregular, pebble like appearance. Can be focal or diffuse
What is lissencephaly?
Agyria
- Cerebral surface is smooth with lack of folds (gyri) and grooves (sulk)
Features of lissencephaly?
- Microcephaly
- Developmental delay
- Severe epilepsy
- Blindness
CT/MRI shows abnormally thick cortical ribbon
What is schizencephaly?
“split brain”
- unilateral or bilateral clefts within the cerebral hemisphere
What is holoprosencephaly?
- Failure of formation of 2 hemispheres
- often have facial anomalies: flat midface and nasal bridge, hypotelorism, medial cleft lip, single central incisor
- often have DI, hypopituitarism, epilepsy, vision impairment
Features of Erbs Palsy (C5,6 and sometimes 7)
“Waiters tip”
- Sagging shoulder
- Internally rotated arm
- Flexed wrist
- Absent biceps reflex
Can have phrenic nerve involvement -> unilateral diaphragm palsy, asymmetric chest expansion, hypoxia
Features of Klumpkes palsy (C8-T1)
“Claw hand”
- extension of MCP, flexion of DIP and PIPs
- Decreased sensation on ulnar side of hand
- Can experience Horner sydndrome (ptosis, miosis, anhydrous)
How does nusinursen (Spinraza) for SMA work?
It is an oligosense nucleotide which modifies splicing of SMN2 gene to increase production of SMN protein
How does onasemnogene (Zolgensma) for SMA work?
It is an SMN1 gene replacement delivered via an AAV9 viral envelope
Given once only IV
Differences between dystrophies and myopathies?
Dystrophies
- High CK (vs normal -mildly increased)
- abnormal extracellular proteins (vs intracellular proteins)
- progressive weakness (vs more stable weakness)
Management of muscular dystrophy
Steroids - prednisolone or deflazacort **many benefits
Plus allied health, orthotics etc
Cause of myotonic dystrophy?
Autosomally dominant inherited trinucleotide expansion of CTG of DMPK gene which encodes serine-threonine protein kinase
- Premutation: 37-50 repeats
- Mildly affected 50-150 repeats
- Classic disease 100-1000 repeats
Features of myotonic dystrophy
Hypotonia
Weakness
Wasting
Myotonia
Myopathic facies: long face, V shaped upper lip
Intellectual impairment
Cataracts
Low IgG
What causes juvenile myasthenia gravis
Antibodies bind to post-synaptic ACh receptor at the NMJ, blocking ACh (acetylcholine) from binding
AChR or MuSK antibodies probably originate in the thymus
Key features of myasthenia gravis
Fatiguable weakness
Ptosis
Ophthalmoplegia
CSF findings in Guillain Barre Syndrome
Very high protein
Low WBCs
(aka cytoalbuminologic dissociation)
Which inflammatory CNS condition may be associated with ovarian teratoma?
Anti-NMDA receptor encephalitis
Triplet repeat disorder of fraxatin (FXN) gene causing ataxia?
Friedrich’s Ataxia (AR inheritence)
Which neurologic condition is associated with increased sensitivity to ionising radiation?
Ataxia-Telangiectasia
Test and management of botulism
Test: stool Clostridium botulism (or C botulism toxin)
Management: ICU, anti-toxin
Clinical features of botulism
Constipation
Descending weakness (cranial nerves first)
Absent reflexes: pupils, gag, deep tendon
Dry mouth
Side effects of phenytoin
- Hirsutism
- Gum hypertrophy
- Ataxia and Nystagmus
- SJS
- Hepatic dysfunction (idiosyncratic hypersensitivity)
- Drowsiness
- Blood dyscrasias
- Macrocytosis (reduced folate absorption)
- p450 inducer- lots of drug interactions
Contraindications to sodium valproate?
Teen females (teratogenic)
Metabolic/ mitochondrial disorder (risk of severe hepatotoxicity)
Side effects of topiramate
- Kidney stones
- Metabolic acidosis
- Slowed cognition
- Acute angle-closure glaucoma
- Weight loss
- Reduced sweat/ heat intolerance
Orofacial seizures think..
Benign childhood epilepsy with centrotemporal spikes - wakes at night with focal seizure on one side of face, drooling, inability to speak but preserved awareness. May have secondary generalisation
First line treatment of childhood absence epilepsy?
Ethosuximide or sodium valproate
Remission rate of childhood and juvenile absence epilepsy?
CAE= 60%
JAE= lifelong but seizures can be controlled in 70-80%
Features of Self-limited epilepsy with autonomic seizures (SeLEAS) - previously Panayiotopoulos
Onset 3-6yrs
Focal seizures with autonomic features- VOMITING, pallor, flushing, abdominal pain, often head or eye deviation
Often only 1x seizure (25%) or remission within 1-2yrs
Which infection most commonly precedes Guillain Barre syndrome?
Campylobacter
(CMV, EBV, Mycoplasma)
Management of Guillain Barre Syndrome?
IVIG or plasma exchange
(NOT steroids- they have shown no benefit)
Eculizumab (complement blocker) being trialled
What are anti-GQ1b antibodies associated with?
Variants of Guillain barre syndrome: Miller Fisher syndrome, Bickerstaff brainstem encephalitis
3 features of Aicardi Syndrome?
Infantile spasms
Agenesis of corpus callosum
Chorioretinal lacunae (small holes in the retina)
It is X-linked dominant
What can happen if Na+ is corrected to quickly?
From low -> high: pontine demyelinosis
From high -> low: cerebral oedema
Diagnostic criteria for NF1?
2 or more if parent not diagnosed:
- 6+ cafe au lait macules >5mm (prepubertal)
- Axillary or inguinal freckling
- 2+ neurofibromas of any type or 1+ plexiform neurofibroma
- Optic pathway glioma
- 2+ Lisch Nodules
- Distinctive osseous lesion eg bowing of tibia, sphenoid dysplasia
- Heterozyogus pathogenic NF1 variant
Major features of tuberous sclerosis
- 3+ Hypomelanotic macules >5mm
- 3+ Angiofibromas
- 2+ ungal fibromas
- Shagreen patch
- Multiple retinal hamartomas
- Multiple cortical tubers and/or radial migration lines
- 2+ Subependymal nodules
- Subepnedeymal giant cell astrocytoma (SEGA)
- Cardiac rhabdomyoma
- Angiomyolioma
Lymphangioleiomyomatosis (LAM)
Mutation causing Sturge Weber syndrome
GNAQ gene
Acquired epileptic aphasia
Landau Kleffner syndrome
(onset 3-7yrs with language regression, ADHD like behaviour +/- focal motor seizures)
MOA of levetiracetam?
Binding to synaptic vesicle
protein 2A (SV2A)in the brain resulting in a change in neurotransmitter release
When do symptoms of Guillain Barre syndrome peak?
Usually ~7-10 days
Which infections commonly precede Guillain Barre syndrome?
Commonly have preceding infection 3-6 weeks earlier with campylobacter (30%), EBV, CMV, mycoplasma
Which antibodies are associated with neuromyelitis optica spectrum disease?
AQ-4 antibodies
(aggressive disease with high chance of release, blindness and wheelchair dependency at 5yrs)
How does MOG-antibody demyelinating disease present?
- ADEM (60%) or
- Optic neuritis (unilateral or bilateral) (37%)
- Transverse myelitis (13%) or
- Neuromyelitis optica spectrum disorder (50%)
Management of ADEM
High dose steroids (usually 5d Methylpred)
Cover with abx and acyclovir until infection excluded
If not responsive to steroids -> IVIG and PLEX
Management of Guillain Barre Syndrome?
IVIG
Plasma exchange
Steroids not effective
Weakness of which muscles causes trendelenburg gait?
Weakness of hip ABDUCTORS -> dropping of the pelvis to the contralateral side
Features of Aicardi syndrome?
X-linked dominant so females affected
Triad of:
agenesis of corpus callosum,
chorioretinal lacunae (often see coloboma)
seizures (incl infantile spasms)
