Neurology Flashcards
Carbamazepine side effects
SJS (esp HLA-B15:02 Han Chinese)
Agranulocytosis, transient leukopenia, aplastic anaemia
Hepatitis
Tics
Ataxia, dizziness
Headache, drowsiness
Cannot be used in absence or myoclonic epilepsy
Decreases OCP and warfarin
Induces cytochrome P450 (decreases effectiveness others meds)
Clobazam side effects
Apnoea Drowsiness, sedation Ataxia Drooling Paroxysmal hyperactivity
Lamotrigine side effects
Rash 3-5% SJS (inc risk with valproate) 1:100 - need to monitor serum levels Hepatitis Nausea and vomiting Headache Ataxia, dizziness Diplopia
Recommended if AED needed in pregnancy
Dose decreased when use with carbamazepine and phenytoin
Requires very slow titration of dose
Phenytoin side effects
Hirsutism Ataxia Gum hyperplasia Nausea Nystagmus Peripheral neuropathy Glove and stocking red hand syndrome Teratogenic Inhibits absorption folate - megaloblastic anaemia Induces cytochrome P450
Sodium valproate side effects
Vomiting Anorexia Liver toxicity Pancreatitis Retention o weight Oedema Alopecia Teratogenecity, tremors Enzyme inhibition
Hyperammonemia Menstrual irregularities Low WCC and platelets Teratogenic = neural tube defects 1-5% Avoid <2yrs due to mental retardation, fatal hepatotoxicity
Septo-optic dysplasia (de Morsier syndrome) features?
Optic nerve hypoplasia, optic chiasm hypoplasia, absent septum pallucidum, pituitary stalk hypoplasia
Antibiotic causing carbamazepine toxicity?
Erythromycin
Causes of positive Gower’s sign?
DMD, BMD, juvenile dermatomyositis, myotonic dystrophy, Pompe disease (glycogen storage disease type II).
Seizures on EEG precipitated by eye closure indicates what syndrome?
Gastaut syndrome (late onset childhood occipital epilepsy)
- can be mistaken for migraine but has EEG changes similar to Panayiotopoulos syndrome
- Unlike Panayiotopoulos syndrome, seizures occur during the day and EEG changes are activated by eye closure.
Levetiracetam side effects
- Behavioural side effects: agitation, anxiety, aggression or emotional lability are the most common side effect of
- Older children: low mood and the risk of suicidal ideation
- Headache, fatigue
Side effects of topiramate?
- Kidney stones, metabolic acidosis
- Language impairment
- Cognitive, somnolence, word-finding difficulties
- Anorexia and weight loss
- Teratogen
- Rare glaucoma risk
4–6/sec irregular spike and wave pattern, which is enhanced by photic stimulation
Juvenile myoclonic epilepsy
Tx: life-long sodium valproate
Describe the interactions between carbamazepine and lamotrigine
- Lamotrigine may increase the concentration of carbamazepine, increasing the adverse CNS effects of carbamazepine
- Carbamazepine may decrease the concentration of lamotrigine and decrease its efficacy
Describe the mode of inheritance for myotonic dystrophy
Autosomal dominant
CTG triplet repeat expansion leads to anticipation with subsequent generations
What is paramyotonia, and what is it associated with?
- Temperature related myotonia, aggravated by cold weather
- Common scenario = patient out into cold wind, cannot open their eyes, difficulty swimming in cold water
- Alleviated by warm temperatures
- Associated with myotonia congenita
Describe chronic inflammatory demyelinating polyneuropathy (CIDP)
- Acquired disorder of peripheral nerves and nerve roots
- Usually symmetrical glove and stocking, motor > sensory, both proximal and distal muscles
- Globally diminished or absent reflexes
- Cranial nerve and bulbar involvement occur in a minority.
Winging of the scapula is caused by damage to which nerve?
Long thoracic nerve, which supplies the serratus anterior. Originates from C5,6,7 cervical nerve roots.
Visual field deficit caused by surgery for hippocampal sclerosis?
Contralateral homonymous superior quadrantanopia
What are the cardiac complications of DMD?
Early diastolic dysfunction and focal fibrosis proceed to dilated cardiomyopathy, complicated by heart failure and arrhythmia in most patients.
Describe the different hearing tests
- Auditory brainstem response (ABR) testing - neonate
- Kendall-toy test >2.5y - speech discrimination test
- Visual reinforcement audiometry, not ear specific, 6m-2.5y
- Tympanometry - does not assess hearing but checks compliance of tympanic membranes and ear ossicles
What medications are associated with benign intracranial hypertension?
Possible drugs causing BIH are: tetracyclines; sulfonamides; nitrofurantoin; nalidixic acid; cytarabine; cyclosporine; phenytoin; mesalamine; corticosteroid therapy and withdrawal
What are the key features and mechanism of transmission of Friedreich’s ataxia?
- The combination of spinocerebellar degeneration (slurred speech, unsteady gait) with peripheral neuropathy gives the distinctive features of Friedreich’s ataxia: extensor plantar responses with absent lower limb deep tendon reflexes.
- Autosomal recessive inheritance, expansion of GAA repeat
Which cranial nerve has the longest course?
4, trochlear
Describe Mobius syndrome
- Congenital palsy of the abducens (VI) and facial (VII) nerves (close to each other, originate at the pons, infarcts at this level can affect both nerves)
- Results in a lack of facial expression and weakness on eye abduction
- There is occasionally associated syndactyly, supernumerary digits and micrognathia.
Which antiepileptic drug has the highest risk of SJS?
- Lamotrigine > carbamazepine > phenytoin
- Increased risk HLA B*1502 Han Chinese (carbamazepine)
Which medications should not be used in basilar or hemiplegic migraines?
- Theorised to be due to vasoconstrictive effects on dilated extracranial arteries and thus could be potentiated by ergotamine or triptans.
Side effects of vigabatrin?
- Visual field constriction from peripheral retinal atrophy, optic neuritis, vision loss (rods > cones, therefore night vision mostly affected) - irreversible
- Long half life
- Weight gain, lethargy
What is Canavan disease?
- AR leukoencephalopathy seen in infancy/early childhood
- Developmental delay from 3-6 months of age then neurodevelopmental regression
- Acquired macrocephaly, spasticity, seizures and optic atrophy
- Deficiency of aspartoacylase, leading to excessive excretion of N-acetylaspartic acid
- MRI demonstrates megalencephaly and diffuse leukodystrophy without sparing of the subcortical U-fibres
- Usually die 1st decade of life
What is a Dandy Walker malformation?
- Brain malformation with hypoplasia of the cerebellum, particularly the cerebellar vermis and often marked enlargement of the posterior fossa, cyst
- Associated with encephalocele
- Children usually present within the first year with hydrocephalus, “sun downing”, irritability and sleepiness
- Macrocephaly
- Mild-severe ID, develop delay
Which nerves lie in the cavernous sinus?
3-6
List the order of the cranial nerves
O: olfactory nerve (CN I) O: optic nerve (CN II) O: oculomotor nerve (CN III) T: trochlear nerve (CN IV) T: trigeminal nerve(CN V) A: abducens nerve (CN VI) F: facial nerve (CN VII) V: vestibulocochlear (or auditory) nerve (CN VIII) G: glossopharyngeal nerve (CN IX) V: vagus nerve (CN X) S: spinal accessory nerve (CN XI) H: hypoglossal nerve (CN XII)
Which nerve injuries can lead to a foot drop?
Injury at the level of the L5 nerve root, sciatic nerve or common peroneal nerve may result in foot drop
Which nerve is affected when you have a winged scapula?
Long thoracic nerve (innervates serratus anterior)
What does the accessory nerve innervate?
Accessory nerve = CN XI - innervates the sternocleidomastoid and trapezius muscles.
Which nerves provide taste to posterior 1/3rd of tongue, and the rest of the tongue?
- Posterior 1/3rd = glossopharyngeal nerve
- Anterior 2/3rd = facial nerve
What is Miller-Dieker syndrome?
- 15% of cases of Lissencephaly have Miller-Dieker syndrome
- Lissencephaly
- Facial dysmorphism (prominent forehead, bitemporal hollowing, anteverted nostrils, a prominent upper lip, and micrognathia)
- Chromosome deletions of 17p13.3
Discuss lissencephaly
- MRI: absence of cerebral sulci, maldeveloped sylvian fissures (lateral sulci/fissures), enlarged ventricles
- Neuronal migration disorder due to defective neuronal migration during the 12-24th weeks of gestation
- Lack of development of gyri and sulci. There are absent cerebral convolutions and rudimentary sylvian fissure.
- Agyria = lack of gyri, pachygyria = thickened cortex
- Microcephaly, microphthalmia
- Severe developmental delay, failure to thrive and seizures
Discuss lateral medullary syndrome
- Due to blockage of posterior inferior cerebellar artery (PICA) - supplies the lateral medulla and cerebellum
- Vertigo, ataxia, ipsilateral dysmetria, cranial nerve palsies (often IX, X) and loss of pain and temperature on the contralateral side (crossing of the spinothalamic tracts).
Describe neuronal ceroid lipofuscinosis
- Batten’s disease, deficiency in the TPP1 enzyme
- The first sign is a delay in receptive language followed by increasing language difficulties
- Difficult to manage epilepsy
- EEG: photoparoxysmal response at low flash frequencies - Progressive motor impairment, eventually becoming wheelchair bound, and progressive visual and cognitive impairment
Mutation in KCNQ2 is associated with?
- Benign familial neonatal epilepsy (BFNE), AD, FHx+ve
- Seizures usually present within the first few days of life (fifth day fits) and are brief but frequent
- Repetitive clonic seizures, no impact on development
- Usually resolve within 15 weeks
- EEG: interictal usually normal
- Rarely have severe outcome: KCNQ2 epileptic encephalopathy
Discuss Ohtahara syndrome
- Early infantile epileptic encephalopathy
- Focal or generalised tonic seizures
- Frequent intractable seizures, onset 1-3m
- SevereDD
- Evolves to West or Lennox Gastaut syndrome
- Causes: structural, metabolic, genetic
- EEG: burst suppression, may progress to hypsarrhythmia
Discuss West syndrome
- Infantile spasms, 3-12m age, epileptic encephalopathy
- GDD +/- regression
- May have normal neuro exam + head size
- Sudden flexion/ext of proximal/truncal muscles, head nodding, occur on wakening, last 1-2 seconds, clusters
- Causes: structural (HIE, lissencephaly, tuberous sclerosis), chromosomal (T21), genetic, metabolic (rare)
- EEG: hypsarrhythmia, highly disorganised, slow waves with multifocal polyspikes. May initially only be in sleep
- Tx: vigabatrin (TS), corticosteroids
- 80% intractable epilepsy, 80% intellectual impairment
- Can evolve into Lennox-Gastaut
Discuss Dravet syndrome
- 1st year of life
- Prolonged febrile seizures, seizures post vaccine, GTC but often hemifocal
- From age 1-4yr: myoclonic, absences, clusters GTC
- Usually intractable
- Developmental arrest, ID, ataxia, pyramidal signs
- 75% abnormality in SCN1A (Na channel gene), 30-50% have family history
- EEG: initially normal, then generalised spike and wave, slowing. Photic stimulation + sleep deprivation
- Tx: valproate and clobazam - often drug resistant
- Carbamazepine + phenytoin contraindicated as are sodium channel agents
Discuss childhood absence epilepsy
- Genetic/idiopathic generalised epilepsy
- Age 2-12y, may have prev febrile convulsions
- Otherwise well child, normal neuro exam
- May have ADHD/learning difficulties
- Frequent per day, ~10sec, impaired awareness, no aura, no post-ictal, can have blinking/mouthing, ends abruptly
- Onset >10y likely to become juvenile absence (associated with GTCS)
- EEG: 3Hz spike and wave, inducible with hyperventilation
- Tx: ethosuximide, valproate, lamotrigine
- Atypical absence has diff EEG pattern
- 75% outgrow seizures, 25% develop GTCS or JME
Discuss Lennox Gastaut syndrome
- Epileptic encephalopathy with onset 1-7 years
- 70% have a structural brain abnormality, rest genetic
- Multiple intractable seizure types including tonic (esp in sleep - trunk or arms elevating), atonic, and atypical absence seizures
- May have drop attacks - issues with care
- Cognitive and behavioural impairment
- EEG: slow-spike wave occurring at 2.5Hz
- Tx: valproate and clobazam, lamotrigine, benzodiazepine, ketogenic diet
- Carbamazepine and vigabatrin make symptoms worse
Discuss childhood epilepsy with centrotemporal spikes
- BECTS or Rolandic epilepsy
- Self-limiting, 4-10 years, usually resolved by 13y
- Focal brief hemifacial seizures (lip, mouth, chewing, hypersalivation), aphasia, clonic movements face +/- unilateral limb
- Usually <5min, <10 seizures total
- Seizures usually occur from sleep (75%) or evening/early morning
- Often +ve FHx
- Normal neuro exam, behaviour, development
- 20% generalise, >20% of childhood epilepsy
- EEG: high amplitude centrotemporal spikes or sharp + slow waves in sleep
- Tx: carbamazepine (only if recurrent), often no treatment
- Annual EEG - when changes resolve, so does epilepsy
Discuss Landau-Kleffner syndrome
- Subacute progressive aphasia with previously normal language development
- Peak 5-7yrs
- Difficulties with verbal response, verbal audtiory agnosia
- Often misdiagnoised mutism, regression, autism
- Seizures and EEG may resolve but language impairment remains >80%
- Can have behavioural, psych issues
- May have focal or absence seizures, often nocturnal
- EEG: continuous temporal spike and wave, status in sleep
- Tx: valproate +/- clobazam, trial steroids, may need methylphenidate for behaviour
Discuss myoclonic epilepsy
- Mean onset 2-5y
- Brief, sudden, generalised jerks
- 50% have GTCS, 30% have FHx
- Normal exam/development
- EEG: fast spike complexes >2.5Hz
- Tx: valproate, lamotrigine, levetiracetam
- > 50% seizure-free after several years
- Carbamazepine exacerbates seizures
Discuss temporal lobe seizures
- Onset 1st decade-adult
- With or without aura, can have normal awareness: anxiety olfactory, auditory, fear, hallucinations, de-ja vu
- Focal with change in awareness: automatisms common 50-75% - lip-smacking, chewing, swallowing, picking/pulling at clothes, behavioural arrest
- Post-ictal several minutes, may recall aura
- Causes: mesial temporal sclerosis, post encephalitis, AVM, infarct. Need MRI
- EEG: anterior temporal lobe sharp wave or spike, multifocal spikes common. May have normal interictal EEG
- Tx: carbamazepine or valproate, lamotrigine. Surgery if intractable
Discuss juvenile myoclonic epilepsy
- Onset >8y, peak 12-16y
- 5% evolve into this from childhood absence epilepsy
- Myoclonus usually distal, upon waking e.g. knocking over cereal, dropping hairbrush
- Associated GTCS 90% with occ. absences 10-30% (less impaired awareness)
- EEG: 4-6Hz polyspike-wave bursts evoked by photo stimulation
- Lifelong seizures, normal neuro exam + development
- Tx: valproate, lamotrigine
What is the frequency, risks factors, and cause of SUDEP?
- 1:5000 per year, ? due to seizure-induced hypoventilation and cardiac arrest
- Refractory epilepsy
- GTCS frequency
- Poor medication compliance
- Young age
- Early age of seizure onset
- Underlying neurological disability
Ethosuximide mechanism and side effects
GI esp nausea Rash, can lead to SJS Blood dyscrasia Itching Headache, fatigue Works by blocking T-type calcium channels
What are examples of excitatory and inhibitory neurotransmitters?
- Glutamate - excitatory
- GABA, glycine - inhibitory
3Hz spike and wave on EEG is characteristic of?
Childhood absence epilepsy, inc with hyperventilation
Continuous temporal spike and wave on EEG is characteristic of?
Landau-Kleffner, may have continuous status in sleep
Discuss genetic epilepsy with febrile seizures plus
- Febrile seizures until ~age 11, focal and GTCS in adolescence, rather than remission
- Can have absence, myoclonic, akinetic, focal
- AD, incomplete penetrance
- Can progress into Dravet if develop other seizure types
- Associated with SCN1A mutation in 75%
Discuss early onset childhood occipital syndrome
- Panayiotopoulos syndrome
- Associated with vomiting, retching, autonomic symptoms
- Often initially end up in ICU with concerns for encephalopathy
- Seizures usually nocturnal and prolonged (last more than five minutes). Up to 50% of seizures last more than 30 minutes consistently
Which MHC can increase the risk of Steven Johnson syndrome in carbamazepine?
HLA-B 1502
Han Chinese
Treatment of childhood absence epilepsy?
Ethosuximide
2nd: valproate, lamotrigine
Treatment of juvenile myoclonic epilepsy?
Valproate
2nd: lamotrigine, leviteracetam
Treatment of BECTS?
Often no treatment required
Carbamazepine
2nd: lamotrigine
Treatment of infantile spasms?
ACTH/prednisolone - 2 weeks then taper
Vigabatrin in tuberous sclerosis
2nd: ketogenic diet
Treatment of Dravet syndrome?
Valproate and clobazam
2nd: levetiracetam, ketogenic diet, stiripentol
Treatment of Lennox Gastaut syndrome?
Valproate and clobazam
2nd: rufinamide, ketogenic diet
What is the recurrence risk after a first unprovoked seizure?
42% (88% within first 2 years)
Abnormal EEG in idiopathic epilepsy has 2 x risk recurrence than if normal EEG
What are predictive factors for pharmacoresistance in epilepsy?
- Symptomatic/cryptogenic epilepsy with MRI lesion
- Onset <1y age
- High no. seizures prior to medications
- Failure of 1st and 2nd AED
- EEG abnormal - focal discharge or generalised slowing
Treatment for generalised or unclassified epilepsy?
Valproate
- Not for females of child-bearing potential
- Avoid in <2yo if undiagnosed or metabolic
4-6Hz polyspike-wave bursts evoked by photo stimulation
Juvenile myoclonic epilepsy
Discuss frontal lobe epilepsy
- Clusters or motor seizures, often nocturnal, bizzare and complex motor activity, vocalisation. Clue: stereotyped for each patient, can be mistaken for night terrors
- Brief <30sec, sudden onset
- Minimal post-ictal confusion
- CHRNA4, may be AD
Which antiepileptics are associated with depression and psychosis?
Vigabatrin
Levetiracetam
What is the rate of SJS in lamotrigine use in children?
1:100 (1:1000 for adults)
Neural tube defects are associated with which AEDs?
Valproate and carbamazepine
Require high dose folic acid (5mg OD)
Discuss fetal valproate syndrome
- Neural tube defects
- Cleft lip/palate, epicanthic folds, upturned nose and small mouth, long philtrum
- Arachnodactyly, radius/limb defects
- Develop delay, autism risk
Which AED is safest in pregnancy?
Lamotrigine
Discuss fetal hydantoin syndrome
- Teratogenic effects of phenytoin on fetus
- Affects 1/3rd infants
- Microcephaly, IUGR, lim defects
- Heart defects, cleft palate
- Develop delay, ID
Which AED would you use in liver disease
Levetiracetam (renally excreted) - could also use gabapentin but less effective as AED
Which antiepileptics are inducers of CYP450?
Phenytoin
Phenobarb
Carbamazepine
Which AED have low renal clearance?
Phenytoin, carbamazepine, sodium valproate, diazepam, lamotrigine (levetiracetam, gabapentin, topiramate high)
What drug can you use for refractory seizures in tuberous sclerosis?
Everolimus
Discuss depolarisation and hyperpolarization of neurons
- Glutamate - excitatory neurotransmitter binds to neuron and allows influx of Na and Ca through channels and outflux of K. Net result is increased + charge and depolarisation of the neuron
- This triggers action potential
- GABA - inhibitory neurotransmitter binds to neuro and allows influx of Cl, leading to a net - charge and hyperpolarization of the neuron
Which AEDs block voltage-gated Na+ channels?
- Carbamazepine
- Valproate (also inhibits GABA transaminase)
- Topiramate (also inhibits glutamate + voltage-gated Ca channels)
- Phenytoin
- Lamotrigine (also inhibits glutamate)
Which AEDs are calcium channel blockers?
- Ethosuximide
- Gabapentin
- Levetiracetam (also inhibits glutamate release, but unknown mechanism action)
Adverse effects of gabapentin?
Sedation and ataxia
What is the mechanism of action of vigabatrin?
Inhibits GABA transaminase, enhancing effect of inhibitory neurons
Discuss subacute combined degeneration of the cord
- Due to B12 deficiency (vegan, loss terminal ileum, pernicious anaemia), vit E deficiency
- Degeneration of posterior and lateral columns spinal cord
- Gradual onset weakness, tingling, numbness in arms and legs
- Upgoing plantars, spasticity, dec vibration and touch sensation
- Prolonged deficiency causes irreversible damage
When do the palmer grasp and moro reflexes disappear by?
4 months
When does the asymmetric tonic neck reflex resolve by?
4 months
When does the rooting reflex stop by?
3-4 months
When does the galant reflex disappear by (stroking spine)?
2 months
When does the stepping reflex disappear?
5-6 months
When does the Babinski reflex normalise in infants?
About 1 year
When should you develop handedness?
Around 3y age
What is the difference between Erb’s palsy and Klumpke paralysis?
- Erb’s: C5-C6 - arm is flaccid, adducted, int. rotates, elbow ext and wrist flexed, loss of biceps reflex
- Klumpke: C7-T1, paralysed hand (intrinsic hand muscles), flexed claw hand and supination of forearm. May have ipsilateral Horner’s,
What percentage of children with autism have intellectual disability?
- 50%
- Receptive language delayed more than expressive language
- Increased risk seizures and macrocephaly
Which antiepileptic is a CYP450 inhibitor?
Valproate (so increases levels of other drugs)
Discuss the use of CBD oil in epilepsy
- Effective in reducing seizures in Dravet and Lennox-Gastaut syndrome
- Can lead to raised transaminases
- Causes increased levels of clobazam
Discuss purine nucleoside phosphorylase (PNP) deficiency
- AR, immunodeficiency
- Autoimmunity, especially autoimmune haemolytic anemia, is also frequently present
- Recurrent bacterial, viral, and opportunistic infections and failure to thrive
- 2/3 also present with neurological symptoms eg ataxia
- Low serum uric acid associated with T cell deficiency is highly suggestive of PNP deficiency.
When does neural tube formation and closure occur?
Between 3-7 weeks gestation
When does neuronal migration and corpus callosum formation occur, and what can errors lead to?
- 12-19w
- Lissencephaly, pachygyria, agenesis of corpus callosum
When does myelination occur?
From 24w to early childhood, errors cause dysmyelination
When do cortical structures develop?
From 22w until postnatally, errors cause cortical dysplasia
What are risk factors for neural tube defects?
- Lack of folate
- Maternal anticonvulsants: valproate, carbemazepine
- Previous child with spina bifida/ FHx
- Malnutrition
- Maternal obesity or diabetes
- Inc AFP on antenatal screening
- Folate: 400ug or 5mg (high risk)
Discuss spina bifida oculta
- Common, 5% population, asymptomatic
- Midline defect of vertebral bodies without protrusion of spinal cord or meninges
- Dysraphism: cutaneous manifestations - haemangioma, pit, sinus, hairy patch. May be associated with lipoma, tethered cord
- Usually L5-S1
Discuss meningocele
- Meninges herniates through defect in vertebral arches or sacrum
- Spinal cord usually unaffected
- May have tethering or syringomyelia
- If thin skin or leaking - risk meningitis
- Tx: surgery
Discuss myelomeningocele
- Most severe form spina bifida
- Herniation of meninges, nerve roots, spinal cord
- If 1 affected child, 4% inc risk, if 2 children 10% risk
- Motor and sensory deficits below lesions, sphincter disturbance, bladder/bowel incontinence
- May have associated arnold chiari malformation (downward displacement cerebellar tonsils through foramen magnum), may have aqueductal stenosis or hydrocephalus
- Tx: surgical repair +/- shunt, catheterisation, ortho, tx associated seizures, enema/suppositories
- Inc mortality with renal dysfunction
Discuss encephalocele
- Protrusion cerebral tissue through midline cranial defect in frontal occipital region
- Inc risk aqueductal stenosis, Chiari malformation, Dandy walker malformation (abn cerebellum/4th ventricle)