Neurology Flashcards
What type of inheritance is tuberous sclerosis?
Autosomal Dominant (~70% de novo)
TSC1(hamartin) and TSC2 (tuberin)
Neurological follow up of patient with TS?
MRI 1-3 years
Routine EEG in asymptomatic infants with TSC every 6 weeks until age 12 months and 3 monthly to aged 2.
Routine EEG in other patients
How do you diagnose TS?
2 Major or
1 major and 2 minor
Major:
- Hypomelanotic macules
- Angiofibromas
- Ungal fibroma
- Shagreen patch
- ocular
- Multiple retinal hamartomas
- Multiple cortical tubers or radial migration lines
- Subendymal nodules
- Subependymal giant cell astrocystoma
- Cardiac rhabdomyoma
- Angiomyoliomas
Minor:
- Confetti skin lesions
- Dental enamel pits >3
- Intraoral fibromas >2
- Retinal achromatic patch
- multiple renal cysts
- Non-renal hamartomas
- Sclerotic bone lesions
What can be used to slow growth of subependymal giant cell astrocystomas in TS?
mTOR inhibitors (Everolimus)
What is the TSC gene in tuberous sclerosis responsible for?
Suppresses MTOR function, therefore in TS over activation leads to overgrowth, abnormal differentiation, increased protein translation and growth of tumours.
What anti-epileptic medication is used to treat seizures in TS?
Vigabactrin
What type of inheritance is seen in neurofibromatosis?
Autosomal dominant inheritance
NF1 - 17q11.2
How large do cafe au lait macule need to be to diagnose NF1?
Prepubertal >5mm
Post-pubertal >15mm
Diagnostic criteria for NF1?
Someone who does not have a parent diagnosed with NF1
* If two or more of the following are present:
* Six or more café au lait macules
* >5mm (prepubertal)
* >15mm (pubertal)
* Axillary or inguinal freckling (Crowe sign)
* Two or more neurofibromas of any type or one plexiform neurofibroma
* Optic glioma
* Two or more iris hamartomas (Lisch nodules)
* Distinctive osseous lesion such as sphenoid dysplasia, anterolateral bowing of
the tibia, or pseudoarthrosis of a long bone
* A heterozygous pathogenic NF1 variant with a variant allele fraction of 50%
in apparently normal tissue such as WBCs
* A child of a parent who meets the diagnostic criteria specified above
merits a diagnosis of NF1 if one or more the above criteria are present.
What treatment is available for plexiform neurofibromas in NF1?
MEK Inhibitors (trametinib, selumetinib)
What malignant tumour is associated with NF1?
Malignant peripheral nerve sheath tumour
What are the skeletal abnormalities seen in children with NF1?
Sphenoid dysplasia
Bowing of long bones +/- pseudoarthrosis
What is the gene mutation involved in sturge weber syndrome?
Somatic mutation of GNAQ on chromosome 9q21 - sporadic
What is the ophthalmological complication in Sturge Weber Syndrome?
Glaucoma (choroidal angioma)
What is the cranial complication seen in Sturge Weber Syndrome?
Leptomeningeal angiomata
What is the gene mutation in ataxia telangiectasia?
ATM
What Ig deficiency do children with ataxia telangiectasia have?
IgA
What migraine medication should be avoided in sturge weber syndrome and why?
Triptans - abnormal vasculature can increase risk of stroke
Where is the defect in smooth muscle atrophy?
Anterior horn cell
What is the gene mutation for SMA?
Homozygous deletion of exon 7 of the SMN1 gene = decreased production of survival motor neuron protein –> motor degeneration and muscle atrophy
Autosomal recessive
What is the carrier frequency of SMA?
1:50
6 month old
Hypotonic frog leg posture, poor head control, paucity of anti gravity movements, weak cry and cough, tongue fasciculation’s, bright alert face, areflexic with feeding difficulties and paradoxical respirations?
SMA1
What does a bell-shaped chest on chest xray suggest?
Neuromuscular disorder eg. SMA
What is the treatment for SMA?
AAV9 vector gene therapy Zolgensma (introduces SMN1 gene into patients cells)
Antisense oligonucleotide therapy such as Nusinersen (spinraza) and risdiplam - modulation of low functioning SMN2 gene
What is the best predictor for prognosis in SMA?
Number of SMN2 copies, more copies = better prognosis
What determines whether you will be affected by Duchenne or Becker muscular dystrophy?
If mutation is an out of frame mutation you will have Duchenne if you have an in frame mutation you will have Beckers.
What type of inheritance is seen in Duchenne muscular dystrophy and Becker muscular dystrophy?
X-linked recessive inheritance
Some children with turners syndrome or girls with skewed X lionisation can be affected also
What are the signs of Duchenne muscular dystrophy?
Aged 3-5
Mild delay in gross motor milestones
Frequent falls
Difficulty keeping up with peers or climbing stairs
Toe walking
Specific learning difficulties
CK >5000
What are the signs of Beckers muscular dystrophy?
Present in teen years
Walk beyond 16 years
Muscle cramps and pains
Raised CK<5000
How do you test for Duchenne muscular dystrophy and what is the treatment?
Dystrophin MLPA
If negative dystrophin sequence usually done as part of a gene panel
Steroids (prednisone, deflazacort)
Ensure had MMR and varicella as can’t have these once on steroids.
Sick day management
What is the first line agent for absence seizures?
Ethosuximide
Absence seizures show 3Hz generalised spike waves on EEG provoked by hyperventilation
Why is sodium valproate avoided in children under two years with seizures?
Risk of metabolic condition - lead to hyper ammonia and also cause liver failure
What is the gene involved in benign familial neonatal seizures?
KCNQ2 and KCNQ3 - potassium channel
Autosomal dominance
Present with repetitive clonic seizures onset day 2-3 that usually resolve within weeks-months
What does hypsarrhythmia indicate on EEG?
Infantile spasms
What is the treatment of infantile spasms?
Steroids first line
Vigabactrin (mTOR inhibitor) for children with tuberous sclerosis.
Previously ACTH injections were used.
What sort of seizures are seen in Lennox Gastaut Syndrome?
Multiple seizure types including atypical absence, tonic, atonic and myoclonic with long periods of non-convulsive status.
Frequent drop attacks
EEG - Slow spike and wave pattern
Treatment for Lennox-Gastaut Syndrome
Sodium valproate
Benzodiazepine
Ketogenic diet
Corpus Callostomy and vagal nerve stimulation for refractory
Genetic epilepsy with febrile seizures + is related to which main gene mutation?
SCN1A
Children have febrile seizures beyond 6 years old.
If you have a child less then 12 months who has had multiple prolonged febrile seizures that present hemiclonic what should you consider?
Dravet syndrome
EEG - Slows generalised poly spikes
Stiripentol is the most effective treatment
Focal sensori-motor seizures from sleep that initially involves the face and tongue with gagging and facial twitching followed by generalised T/C seizure.
Self limited epilepsy with centrotemporal spikes (Benign rolandic epilepsy)
Centro-temporal spikes seen on EEG
Early morning myoclonus - difficulty eating breakfast in the morning due to tremor of hand. What could this indicate?
Juvenile myoclonic epilepsy
EEG - Photic induced burst of generalised polyspike 4-6Hz
What epileptic condition would you think about in a child with acquired epileptic aphasia?
Landau-Kleffner Syndrome - lose the ability to recognise voice, sound, speech. Regression in language and associated with seizures with marked behavioural disturbance.
What is the classical finding on EEG in Landau-Kleffner Syndrome?
Continuous status epilepticus of sleep
If Tics are impacting one QOL what medication can be used?
Clonidine
What other conditions can tics be associated with?
Tourettes, OCD, ADHD
In someone who has HLA-B*1502 what does this predispose them to?
Stevens johnson syndrome with carbamazepine
Which anti-seizure medication has the highest risk of Stevens Johnson syndrome?
Lamotrigine
Which anti-seizure medication can cause hypospadias in the foetus?
Topiramate
Which anti-seizure medications are renal excreted?
Gabapentin
Levetiracetam
Vigabactrin
Topiramate
Which anti-seizure medications are metabolised in the liver?
Lamotrigine
Sodium valproate
Carbamazepine
Which anti-epileptic medication should not be used in generalised epilepsy?
Carbamazepine - can worsen
Which anti-seizure medication can cause weight loss?
Topiramate
Which anti-seizure medication can cause psychosis?
Levetiracetam
