Epilepsy/Sleep Flashcards
phenytoin and albumin
phenytoin loves to bind to albumin (~90%), and only unbound PHT is pharmacologically active. but some drugs can rip phenytoin apart from albumin, setting more free and causing toxicity
phenytoin metabolism
CYP P450
fluconazole and TMP also use this pathway and can increase levels of phenytoin
risk factors to develop first febrile seizure
close relative with febrile seizures
developmental delay
NICU stay for > 30 days
going to daycare
risk of recurrent febrile seizures
family history of febrile seizure
younger onset of age (<18 months)
lower peak temperature
shorter duration of fever prior to seizure
NO difference in recurrence between simple and complex…weird
progressive myoclonic epilepsies (5)
Unverricht-Lundborg syndrome, Lafora body disease, MERFF, sialidosis, and NCL
Unverricht-Lundborg (Baltic myoclonic epilepsy) - inheritance, mutation, presentation?
AR
EPM1 mutation encoding for cystatin B
present between late childhood/adolescence with stimulus-sensitive myoclonus that worsens, eventually other seizure types with neurocognitive decline.
MRI normal. EEG gen spike-waves/polyspikes
MERFF
migraines, short stature, ataxia, cognitive impairment, deafness, epilepsy, elevated lactate
generalized proximal weakness –> muscle biopsy shows ragged red fibers
sialidosis - inheritance, mutation,labs,2 types
AR, NEU1 mutation
dx: high urinary sialyl oligosaccharides and lysosomal enzyme deficiency in leukocytes/fibroblasts
Type 1: a-neuraminidase deficiency
teens/adults with action myoclonus, progressive ataxia, GTCs, vision loss. CHERRY RED SPOT!
Type 2: N-acetyl neuroaminidase and B galactosialidase
babies-young adults - myoclonus, coarse facial features, corneal clouding
Lafora body disease (inheritance, sx, EEG, dx)
AR, EPM2A mutation encoding laforin
present in adolescence - various seizure types including occipital sz with transient blindness/hallucinations
occipital epis and gen bursts on EEG
Lafora bodies are PAS + inclusion bodies in neurons, heart, and sweat glands
Dx: skin biopsy
Rasmussen’s encephalitis - antibody, path findings
GluR3 subunit of AMPA glutamate receptor antibody
path shows perivascular cuffs of lymphocytes + monocytes, glial nodules in gray and white matter. spongy tissue degeneration
AED pharmacokinetics in elderly
lower gastric acidity –> weakly basic drugs less easily absorbed and weakly acidic drugs more easily absorbed
gastric emptying is slowed
volume of distribution of hydrophilic and lipophilic drugs smaller
hepatic metabolism decreases, renal excretion decreased
what does IV flumazenil do
reverse benzo overdose
work up for adults with 1st unprovoked seizure
same as kiddos…MRI brain and EEG!
dont need labs, tox, LP unless concerns
when is highest risk for repeat seizure after first unprovoked one?
2 years after sz
EEG pattern of 1 Hz generalized periodic pattern consistent with what dx?
CJD
K complex and sleep spindles features of what stage of sleep
N2
first REM sleep period occurs how long after sleep onset
90 minutes
when do normal people get K complexes and spindles
K complexes - 5 months old
sleep spindles - 2 months, but look like adult sleep spindles by 2 years
apnea-hypopnea index - mild, mod, severe?
0-5 per hour is allowed
5-15 - mild
15-30 - moderate
>30 - severe
apnea with no respiratory effort
central sleep apnea
cause of central sleep apnea in adults
comorbid heart failure -
treat underlying condition and CPAP
what stage of sleep do non-REM parasomnias occur in (i.e. sleep walking, night terrors) and what part of night do they occur
slow wave sleep (n3)
first third of night when SWS most common
what part of night do nightmares occur
last third of night
which stage of sleep has greater heart rate variability
REM sleep
absence of heart rate variability suggests dysautonomia
do dreams occur only in REM?
nope, mostly, but can be in non-REM too
recurrent hypersomnia in a teen with mood changes, lasting days-weeks but normal in between episodes
Kleine-Levin syndrome
dx of narcolepsy by sleep study (2 things)
- mean sleep latency <8 minutes
- REM sleep within 15 minutes of sleep onset during 2+ of four nap trials
treatment for cataplexy
gamma-hydroxybutyrate
TCAs or SSRIs also used
narcolepsy with cataplexy - CSF testing
low hypocretin levels in CSF (due to loss of hypocretin neurons in lateral hypothalamus)
will be normal in narcolepsy without cataplexy
advanced sleep phase syndrome
me - want to go to bed at 9 pm and when i go to bed early and wake up early i feel refreshed
delayed sleep phase syndrome
charles - wants to go to bed at midnight and wake up at 10 am, then he feels refreshed
what brain structure regulates our circadian rhythms
suprachiasmatic nucleus in anterior hypothalamus
conditions associated with restless leg syndrome
folate deficiency, chronic renal failure, neuropathy, myelopathy, MS, diabetes, amyloidosis, cancer, peripheral vascular disease, rheumatoid arthritis, hypothyroid
antidepressants (EXCEPT bupropion) will worsen RLS sx
pathophys of RLS
altered dopaminergic transmission
DA agonists (pramipexole and ropinirole) used to treat
also gabapentin, pregabalin, opioids
phenytoin pharmacokinetics
zero order kinetics
constant set amount eliminated over time, not constant proportion
metabolism is NOT proportionate to the concentration of the drug
autosomal dominant nocturnal frontal lobe epilepsy - genetics
autosomal dominant
ENFL1 gene, affects CHRNA4 gene which is important for nicotinic AChRs
where to stim with DBS for refractory epilepsy
anterior nucleus of thalamus (papez circuit)
RLS treatment
ropinirole or pramipexole
DAR AGONISTS
how to treat hypoventilation due to neuromuscular dz
bi-level ST mode (spontaneously timed mode helps patients who may not be able to trigger the vent)
othahara syndrome vs early myoclonic encephalopathy
othahara has burst suppression during wake and sleep
early myoclonic epileptic encephalopathy - burst suppression during sleep + myoclonic seizures
FIRDA assoc with what?
increased ICP
