Epilepsy Flashcards
what are 3 ways to classify seizure?
where/onset, awareness, and motor/nonmotor
what are some causes of nonepileptic seizures?
alcohol withdrawals, fevers, psychological trauma
IPSP and EPSP summation not action potential directly; usually thalamocortical
Paroxysomal Depolarization
Focal cortical dysplasia
Focal area of abnormal neuronal organization and development
Most common cause of medically refractory epilepsy in kids and 2nd in adults
Seen as blurring of the grey–white matter junction and hyperintense signal on FLAIR imaging
Potential causes: mostly unknown, maybe genetics or in utero infection
Tuberous sclerosis complex
Loss of TSC1 (codes for hamartin) or TSC2 (tuberin) genes. Inherited or spontaneous
Affects mTOR pathway
Multisystem hamartomas (including cortical tubers
Dravet’s Syndrome
SCN1A mutated; codes for a voltage-gated Na+ channel on GABAergic neurons
Angelman syndrome
UBE3A deleted or mutated on maternal copy of chromosome 15. Codes for ubiquitin protein ligase E3A Seizures, ataxia, severe intellectual disability and developmental delay, nonverbal, inappropriate laughter
Rett syndrome
MECP2 mutation on X chromosome
Codes for methyl CpG binding protein 2 (MeCP2); involved in interpreting DNA methylation, synaptic maintenance
Predominantly in females
developmental regression, ataxia, seizures, stereotyped handwringing/loss of hand purposeful movement, difficulty with speech
What are some infections that cause epilepsy?
Neurocysticercosis
Cerebral malaria
Viral encephalitis
Tuberculosis
HIV
Zika virus
Chronic brain inflammation leading to intractable seizures, progressive hemiparesis, and cognitive loss
Rasmussens syndrome
metabolic epilepsy caused by changes in
GLUT1 and mitochondria
What are pharmokinetics of ASM?
Well absorbed orally
Cross the blood brain barrier readily
Most are metabolized in the liver (many by CYP2C9, CYP2C19, or CYP3A4) and excreted by the kidney - exceptions: gabapentin, vigabatrin
Which ASMs inhibit VG Na channels?
Phenytoin, Carbamazepine, Lamotrigine, VPA, Topiramate
What are ADRs of VG Na targeting ASMs?
affect heart
Phenytoin
used for focal seizures, if given IV use fosphyentoin (Cerebryx), nonsedative
What are some drug interactions of phenytoin?
Induces CYP450, CYP2C19
“Broad spectrum inducer”
Can induce its own metabolism! Highly binds to plasma proteins
which drugs affect phenytoin
eslicarbazepine, oxacarbazepine, topiramate
ADRs of phenytoin (PHENYTOIN)
CytochromeP-450 inducer
Hirsutism
Enlargedgums(gingival hyperplasia)
Nystagmus
Yellow-browningofskin(melisma, freckle-like spots)
Teratogenicity
Osteopenia
Impairedfolate absorption
Neuropathy
Carbamazepine
focal seizures and bipolar disorder
induces CYP3As
Carbamazepine
What are some ADRs of Carbamazepine
exacerbate myclonic or absence seizures, osteopenia, blurred vision, blood disease, hyponatremia
Lamotrigine
for focal and general seizures, including absence. Also good for bipolar
What are ADRs lamotrigine?
SJS, dizziness, hemophagolytic lymphohistocytosis (uncontrolled immune response)
VPA
for focal seizures and general. Good for myoclonic and bipolar. Is a broad INHIBITOR
What are some ADRs of VPA?
GI, sedates, bad neurodevelopment, pancreatitis, hepatotoxic
Topiramate
monotherapy for focal and general seizure
Whats MOA and interactions of Topiramate?
blocks VG Na channels, antagonize AMPA, enhance GABAa. May increase phenytoin
ADRs of Topiramate
sedation glaucoma, decreasing levels in pregnancy
What are ASMs that inhibit Ca channels?
Gabapentin, Pregabalin, Ethosuxide
Ethosuximide
ABSENCE SEIZURES by inhibiting T-tyoe Ca
Levetiracetam
does general tonic clonic seizures in adults and focal in kids by binds to synaptic vesicle protein, SV2A; don’t give to someone with behavior probs
ASMs that block GluRs
Perampanel -AMPA and Felbamate - NMDA
Perampanel
focal in age 4 and up, and general in greater than 12
Perampanel drug interactions
Extensively metabolized by the liver
Not recommended for patients with severe hepatic (or renal) impairment
Also interacts with alcohol and levonorgestrel oral contraceptives
ADRs of Perampanel
weight gain, aggression
Felbamate
rarely used because only for very severe because causes liver failure/aplastic anemia.
ASMs that increase inhibition
Tiagabine, Vigabatrin, BZs, Phenobarbital
Tiagabine
focal seizures, inhibits GABA uptake through GAT-1
Vigabatrin
An irreversible inhibitor of GABA T which is that degrading enzyme of GABA. Used in infants, TSC
ADRs of Vigabatrin
dizziness, weight gain
In infants: MRI abnormalities
Long-term tx associated with irreversible peripheral visual field defects in 30-50% of patients and Higher in males. Decreases serum phenytoin
Phenobarbital
for really resistant status epilepticus, a barbituate, and 1st line in NEONATES. Induces CYP450s.
ADRs of phenobarbital
sedation, tolerance, cardio/respi depression, cleft palate
BZ for Myoclonic, atonic, focal and general t/c seizures. Admin I/V or rectally to stop status epilepticus and nasally for cluster seizures
Diazepam (also Lorazepam)
BZ Used for absence seizures; adjunctive for other types of seizures
One of the more potent ASMs. SJS potential ADR
Clonazepam
All … are rescue drugs
BZs
Cannabidiol trx ASM
Epidiolex
Toxicities of ASMs
Osteomalacia, osteoporosis (Carbamazepine, barbiturates, phenytoin, valproic acid)
Altered connective tissue metabolism or growth (phenytoin, phenobarbital)
Polycystic ovarian syndrome (valproic acid)
Neurologic
Neuropathy (phenytoin, carbamazepine)
Cerebellar degeneration (phenytoin)
Sexual dysfunction (phenytoin, carbamazepine, phenobarbital)
How does ASMs affect pregnancy?
Several anti-seizure drugs → ↑ metabolism of hormonal contraceptives → contraceptive failure
(Phenytoin,phenobarbital,carbamazepine, topiramate,clobazam)
Pregnancy planning is vital; many anti-seizure drugs are teratogenic
Patients considering pregnancy should be on high doses of folic acid prior to conception
Syncope vs seizure
syncope - confusion for less than 30 sec, eyes upward lateral deviation, flaccid.
seizure - confusion for greater than 2 min, tongue bite, stiff
how to diagnose nonepileptic seizures
need EEG at time of occurrence, which looks for sharp waves
What’s 2 important characteristics of nonepileptic seizures
eyes closed tight for >40 sec, and assymetrical movements
when do seizures usually occur after alcohol withdrawal
6 to 48 hours later
TRUE or FALSE: you should use MRI for epilepsy
false because over 50% epileptic people have normal MRI
whens onset absence epilepsy, results, and treatment
4-10yrs, see 3Hz spikes and hyperventilation during seize, give ethosuximide
Onset age: 12-18 years old
Seizures: myoclonic jerks (morning), GTC, some have absence
Exam: neurologically normal, photosensitive
Juvenile Myoclonic
most common epilepsy in adults, deja vu, staring seizures, can be focal to bilateral tonic clonic
temporal lobe epilepsy which you can also treat with lobectomy if mesial temporal sclerosis
Etiology often brain insults, malformations of cortical development such as TSC; or genetic
Age: by 4 yrs old
Seizures: multiple types tonic, tonic-clonic, atonic, FASS, FAIS, FTBTC, atypical absence
Exam: often diffuse neurologic impairment (cerebral palsy and intellectual disability); epileptic encephalopathy
Prognosis: Drug resistant
Lennox Gastaut Syndrome which you treat with clobazam and vagus nerve stimulation
ADR carbamazepine
hyponatremia, SJS
ADR ethosuximide
GI effects, leukopenia
ADR Phenobarbital
somnolence
ADR Phenytoin
hirsutism, gingival hyperplasia
ADR VPA
tremor, weight gain, hair loss, GI
ADR pregabalin
weight gain
ADR Topiramate
change verbal fluency, memory, weight loss
ADR Vigabatrin
permanent peripheral vision loss
ADR clobazam
drooling
ADR Perampanel
irritability
which ASM decrease warfarin
carbamazepine, phenobarbital, phenytoin, elisacarbazepine
which ASM increase warfarin
felbamate, VPA
what drugs (besides warfarin) can ASM decrease
protease inhibitors and immunosuppressants
Neurology unit
Specialized personnel
Designed to evaluate, diagnose, and treat unprovoked seizures. Guidelines for use:
Treatment failure of 1 year
Failure of 2-3 AEDs
Epilepsy Monitoring Unit
