Epilepsy Flashcards
simple vs complex febrile seizures (gene)
simple >6 months and <5 yrs: generalized seizure <15 min, no more than 1 in 24 hrs
-peak: 18 months
complex “febrile plus”-SCN1A gene (sodium channel subunit) mutation
-can have afebrile GTCs
-FHx febrile seizures does not increase risk epilepsy
-Hx complex FS does not increase risk recurrent FS
-relationship with MTS?
Rasmussens
- progressive focal cortical atrophy (unilateral hemispheric atrophy)-inflammatory?
- progressive neurologic dysfunction: hemiparesis + cog delay
- epilepsia partialis continua
-Tx: IVIG; hemispherectomy; otherwise focal cortical atrophy spreads
-GLUR3? glutamate Ab
histo: perivascular cells; glial nodules; spongy degeneration
myoclonic epilpesy
progressive myoclonic epilepsy - PME - Lafora body, Unvcerricht Lundborg, MERRF, sialidosis, lipofuscinosis
Tx: Valproate acid
NO VPA if suspect mitochondiral mutation (POLG) - liver failure -POLG no myoclonus
-VPA liver enzyme inhibitor, ^^drugs/warfarin
*exacerbate myoclonus: phenytoin, gabapentin, carbamazepine, pregabalin, vigabatrin *
Unvvericht-Lundborg
Baltic myoclonic epilepsy
AR - EPM1 gene - cystatin B -
(protease inhibitor initiates apoptosis)
-action related myoclonus
-various seziure types
-ataxia, tremor, ID
Tx: VPA, onfi, KEppra
Lafora body
EPM2A encoding laforin protein
12-17 yrs
-Lafora bodies-skin biopsy - PAS+ intracell polyclucosan inclusion bodies - sweat gland duct cells
sialidosis
AR - NEU1
type 1 - no alpha-neuraminidase; presnt in adolescence/adults - ataxia, GTC, vision loss; normal cognition
-cherry red spot
type 2 - deficiency N acetyle neuraminidase, B galactosialidase; neonates to 20s; myoclonus, coarse faces, corneal clouding
Dx: urinary sialyl oligosaccharide; leukocyte lysosomal enzyme deficiency
PDR
alpha adult rhythm at 8-10 yrs (A for Adult for Alpha for Aight)
Absence
Peak 6 yrs, 70% girls
-provoked by hypoglycemia, hyperventilation
-staring few sec + eyelid/eyes/eyebrow movements
-CACNA1H calcium channel mutation (P/Q)
Or GABRG2
-Thalamus, T type calcium channels
Tx: ethosuxamide (inhibit T Ca); fewer attentional defects vs VPA but VPA can use
Exacerbate: lamotrigine, phenytoin, cabamazepine, gabapentin
-GABAb R activate T type Ca channels
GTCs + absence - Tx VPA, lamotrigine
enzyme inducing ASMs
primidine, PB, phenytoin, carbamazepine, oxcarbazepine
topiramate at doses >200 mg/d
-topiramate causes uric acid stones
-increase metabolic OCPs
-OCs containing estrogen could decrease the concentrations of some ASMs such as lamotrigine (LTG), through enhancing their metabolism by UGT1A4 (an enzyme responsible for the glucoronidation of some ASMs by ethinylestradiol)
SELECTS
Tx: Keppra; carbamazepine
childhood epilepsies age
6 months: focal onset seizure->West syndrome
3 yrs: focal onset->LGS
14 yrs: CAE (childhood absance)->JME
Phenytoin
-inhibits Na channels
zero order nonlinear kinetics at 10-15 ug/mL - small dose increases can cause toxicity
; mostly liver metabolism
enzyme inducer-lowers drug
-highly protein bound - check free phosphy levels
-TMP/SMX; fluconazoledisplaces PHT from albumin and increase free levels-> PHT toxicity
SE: gingival hyperplasia.
-DRESS, SJS
aplastic anemia, hepatic failure
-hirsutism, osteoporosis, coarse facial features
-peripheral neuropathy
-cerebellar atrophy (not cortical atrophy)
dosing IV bolus:
[target level 15 - current level XX] x [body weight x 0.8 L/kg volume distribution]
-worsen myoclonic + absence epilepsy
VPA
-inhibits Na + T type Ca; agonist at GABAa
enzyme inhibitor-raises drug levels; liver metabolized (increases half life LTG)
-not if mitochondrial disorder
-hepatotoxicity-in kids <6 on polytherapy
-secondary parkinsonism, weight gain, hair loss, PCOS
-loading dose = 20-25 mg/kg bolus
Lamotrigine
blocks Na channels, inhibits glutamate
-least cognitive side effects
-estrogen OCPs + pregnancy increase LTG clearance
therapeutic at >14; can get anxiety
vigabatran
inhibit GABA transaminise which breaks down GABA causing increased GABA
-exacerbates myoclonus
Spasm in TSC
Vis field defects
carbamazepine
blocks Na channels which prevents
AP firing in depolarized neurons
-oxidized to carbamazepine epoxide -active metabolite; causes side effects
-enzyme inducer; autoinduces which reaches max in 3-5 weeks->need gradual increase when levels decrease in 1-2 months
-VPA inhibits metabolism of 10,11 epoxide->levels increased and get toxicity even if normal carbamazepine levels
oxcarbazepine
Oxcarb: not autoinducer; can titrate faster
-no epoxide
-fast inactivation of VGSC
After OXC administration, a peak concentration of the parent drug is detectable in plasma, with a half-life of 1-2.5 hours, and also in the cerebrospinal fluid.This OXC peak concentration may produce an effect in brain before transformation to its active metabolite
Felbamate
FBM, reserving it for medically refractory epilepsy such as Lennox Gastaut syndrome
inhibits the cytochrome P-450 system thus resulting in significant interactions with other AEDs and in most instances increasing the levels of PHT, CBZ epoxide and VPA
hepatotoxic
eslicarbazepine
ESL is rapidly and extensively metabolized by hepatic esterases to eslicarbazepine. This active metabolite has a linear pharmacokinetic profile,
-a low binding to plasma proteins (<40%)
-half-life of 20-24 hours
- excreted by kidneys in an unchanged form or as glucuronide conjugates.
once a day and has a low potential for drug-drug interactions
ESL and OXC exert their effects through an identical metabolite, which is eslicarbazepine
-OXC affects fast inactivation of VGSC
-OXC is transformed to equal amounts of both stereoisomers-inactive and active
- ESL administration, the agent is rapidly converted to eslicarbazepine and is not even detectable in plasma
- ESL is mainly transformed to the active metabolite, less exposure to inactive metabolite
pregnancy and ASM
ASM clearance increases and plasma concentration decreases as pregnancy advance. This occurs especially for LTG, LEV and OXC [83, 91], which may be because of the strong enhancement of maternal glucuronidation and hydrolysis during pregnancy, through which the three ASMs are metabolized
-ESPECIALLY LTG
benzos
agonist at GABAa channels - open chloride channels causing hyper-polarization
-liver metabolism, renal excretion
intranasal midazolam contraindications: acute narrow-angle glaucoma
-if overdose->flumenazil
lacosamide
inhibits slow VG Na channel
-stabilizes hyperpolarized membranes
-inhibits CRMP2
SMA semiology
fencers posture - extended arm contralateral to seizing hemisphere (pointing/flexed arm ipsilateral to seizure)
Aicardi syndrome
X L dominant - girls
agenesis corpus callusum
infantile spasms
retinal blindness-chlorioretinal laucnae
EEG-burst suppression; asynchrony
