Epilepsy and Sleep Flashcards
Gene most commonly associated with generalized epilepsy with febrile seizures plus (GEFS+)
SCN1A (same gene as Dravet)
Other genes associated include other Na channel subunits like SCN1B and SCN2A) and GABA_A receptor subunits (GABRD and GABRG2).
Treatment for Rasmussen’s syndrome refractory to medical management
Hemispherectomy
What medication is frequently used for JME but may worsen myoclonic seizures?
Lamotrigine
At what age does the typical PDR form?
8-10 years
In addition to slowing and other nonspecific EEG abnormalities, what finding can be associated with HSV encephalitis?
Periodic lateralized epileptiform discharges (PLEDs)
(These can also be seen with other destructive processes like stroke and tumor)
Epilepsy syndrome with focal motor, sensory, or autonomic symptoms, primarily seen in face +/- arms,are classically primarily nocturnal?
EEG finding?
Benign epilepsy with centrotemporal spikes.
EEG: centrotemporal spikes
Prognosis for BECTS
Good - usually normal development (although a/w things like ADHD), seizures typically resolve in teenage years
(Benign epilepsy with centro-temporal spikes (BECTS), aka Benign Rolandoc Epilepsy)
ASM with zero-order kinetics within/slighty above its therapeutic window?
Phenytoin (hepatic enzymes that metabolize become saturated)
Idiosyncratic reactions to phenytoin (3)
- SJS
- Aplastic anemia
- Hepatic failure
Effects of chronic phenytoin that can be seen on imaging?
Cerebellar atrophy
Formula for phenytoin load
(Goal - current level) * wt_kg * vol_distribution
(Vol_distribution often taken to be 0.8.
(Goal is typically about 20 in status, goal is 10-20 overall)
Neurologic side effects of chronic phenytoin (4)
- Ataxia with cerebellar atrophy
- Nystagmus and diplopia
- Dysarthria
- Peripheral neuropathy
Superficial side effects of phenytoin (3)
- Gingival hyperplasia
- Coarse facial features
- Hirsuitism
Hematologic side effect of phenytoin (2)
- Aplastic anemia (rare, idiosyncratic)
- Thrombocytopenia
Nutritional effects of phenytoin (2)
- Folate deficiency
- VItamin D deficiency -> osteoporosis
Hematologic side effect of VPA?
Thrombocytopenia
In addition to liver injury, what other solid organ toxicity can VPA have?
Pancreatitis
Serious idiosyncratic reactions to carbamazepine (3)
- SJS
- Aplastic anemia
- Leukopenia
What pharmacokinetic feature of carbamazepine requires slow uptitration?
Autoinduction of its own metabolism
(This is not seen with oxcarb)
How is carbamazepine eliminated?
Hepatic metabolism -> renal excretion of metabolites (so can be problematic in either liver or kidney failure)
What metabolic difference between carbamazepine and oxcarbazepine can allow oxcarabzepine to have less toxicity?
CBZ is metabolized to 10,11-CBZ epoxide, which leads to many side effects.
OXC is not.
How is topiramate eliminated?
Renally
Acute idiosyncratic effect of topiramate?
Acute angle closure glaucoma
Specific mechanism of lacosamide
Enhancing slow inactivation of Na channels
In addition to Na channels, what enzyme can lacosamide affect?
CRMP-2 (involved in neuronal differentiation and axonal guidance - the effects of this are unclear)
Target of rufinamide
Modulation of Na channels (leads to prolonged inactive state)
Aicardi’s syndrome features (3)
- Infantile spasms
- Chorioretinal lacunae (other eye problems too)
- Agenesis of the corpus callosum
Inheritence of Aicardi’s syndrome
X-linked DOMINANT (so seen in girls)
(Fatal in boys)
Other name for Doose’s sydrome
Myoclonic-astatic epilepsy
(Astatic; loss of tone)
EEG findings in myoclonic-astatic epilepsy (Doose’s syndrome)
- 2-3 Hz irregular spike-and-wave
- Rhythmic parietal theta activity (4-7 Hz)
Prognosis in myoclonic-astatic epilepsy (Doose’s syndrome)
Good in many cases, but in some cases associated with intractible seizures and developmental delay
Other name for Ohtahara’s syndrome
Associated EEG pattern?
Early infantile epileptic encephalopathy
EEG: burst auppression
Devestating epilepsy syndrome with seizures in early infancy (1 days - 3 months onset)
Ohtahara’s syndrome aka early infantile epileptic encephalopathy
Syndrome of brief myoclonic seizures beginning between 4 months and 3 years.
Prognosis?
Benign myoclonic epilepsy of infancy (BMEI)
Prognosis is good- usually seizures resolve in a year
Otherwise healthy newborns develop frequent seizures associated with apnea in first week of life.
Prognosis?
Benign neonatal seizures (“fifth day fits)
Prognosis is good - resolution by 4-6 weeks, normal development
Genes linked to benign neonatal seizures (“fifth day fits”)
VGKC - KCNQ2 and KCNQ3
Other name for Panayiotopoulos syndrome
Early-onset childhood occipital epilepsy (a idiopathic occipital epilepsy)
Seizures with tonic eye deviation and vomiting
Panayiotopoulos syndrome (aka early-onset childhood occipital epilepsy)
EEG finding in Panayiotopoulos syndrome (aka early-onset childhood occipital epilepsy)
Occipital spikes in 1-3 Hz bursts only with eyes closed or darkness
Prognosis of Panayiotopoulos syndrome
Good - resolution within several years
Other name for Landau-Kleffner syndrome
Acquired epileptic aphasia
Prognosis in Landau-Kleffner sydrome aka acquired epileptic aphasia
Mixed - some recover language, some do not. Generally seizures can be controlled with medication
Syndrome of mixed seizure types with lnew language dysfunction
Landau-Kleffner syndrome aka acquired epileptic aphasia
Syndrome of episodes of hypermotor behaviors (e.g. thrashing, jerking) that occurin in non-REM sleep
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)
Newer name: sleep-related hypermotor seizures (SHE)
Genes linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) aka sleep-related hypermotor seizures (SHE)
Nicotinic acetylcholine receptor subunits - CNRNA4 and CHRNB2
Classic ASM used for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) aka sleep-related hypermotor seizures (SHE)
Carbamazepine
(Other Na channel blockers used as well)
Typical age of onset of ESES
Peak 4-5 years, typically seen 1-12 years
EEG finding in ESES
Slow spike-waves during in non-REM sleep.
In “figure of 4” movement in seizures originating in SMA, how does it lateralize?
Extended arm is contralateral to seizure focus
(Makes sense to me - attention is contralateral seizure)
Localization of seizure beginning with unilateral dystonia hand/arm posturing
Temporal lobe contralateral to dystonic arm (possibly due to effects on the pasal ganglia)
Name for seizures with uncontrollable episodes of laughter.
Classic localization?
Classic associated finding?
Gelastic seizures
Hypothalamus (although can be elsewhere)
A/w hypothalamic hamartomas
Genetic syndrome with stimulus-sensitive myoclonus followed by seizures, then ataxia and cognitive decline.
Genetic mutation?
Unverricht-Lundborg syndromea.k.a. Baltic myoclonis epilepsy (a progressive myoclonic epilepsy).
Mutation: EPM1 (cystatin B, involved with apoptosis).
What are some progressive myoclonic epilepsies? (5)
- Unverricht-Lundborg syndrome
- Lafora body disease
- MERRF
- Sialidosis
- Neuronal ceroid lipofuscinosis
Progressive myoclonic epilepsy with a cherry red macula
Genetic cause?
Sialidosis
Type 1 (milder, adolescent onset): alpha-neuraminidase
Type 2 (more severe, infant onset): N-acetyl neuraminidase
Progressive myoclonic epilepsy with multiple occipital lobe seizures as well as multiple other seizure types and neurological decline?
Genetic cause?
Lafora body disease (PAS-posiive polyglucosan infclusion bodies)
EPM2A mutation, AR (laforin, ribosomal protein, mechanism unclear)
Antibody associated with Rasmussen encephalitis
AMPA receptor, GluR3 subunit (although not a specific finding
What is a typical REM latency?
90 minutes
EEG features of N1 sleep (5)
- Roving eye movements.
- Slowing
- Attenuation of PDR
- Vertex sharp waves
- POSTS (positive occipital sharp transients of sleep)
EEG features of N2 sleep (2)
- K complexes
- Sleep spindle
EEG feature of N3 sleep (1)
Delta >20%
Apnea-hypopnea index in mild, moderate, and severe OSA
Mild: 5-15/hr
Moderate: 15-30/hr
Severe: >30/hr
Which stage of sleep do sleep terrors occur in?
N3 / slow wave sleep (as do sleepwalking and confusional arousals)
Which stage of sleep does sleepwalking occur in?
N3 / slow wave sleep (as do sleep terorrs and confusional arousals)
What phase of sleep has higher risk of obstructive respiratory events?
REM sleep (accessory respiratory muscle are atonic)
Dayslong episodes of excessive sleepiness/sleep time associated with irritability and impulsivity?
Kleine-Levin syndrome (aka recurrent hypersomnia)
Brain region that is site of pathology in narcolepsy with cataplexy
Lateral hypothalamus (hypocretin neurons)
What CSF abnormality is seen in narcolepsy with cataplexy?
Low hypocretin
(It is normal in narcolepsy without cataplexy)
What antidepressant is least likely to cause RLS?
Buproprion (doesn’t have serotonergic activity)
