Management of Seizure
Disorders
Mark Kotlarewsky, MD FACP
Department of Medicine
Medstar Washington Hospital Center
Learning objectives
Understand the definition of seizure, epilepsy
Understand the types of treatment, both medical
and surgical
Understand notable side effects of common
antiepileptic drugs
Understand treatment and management of
epilepsy-related comorbidities
Management of antiepileptic drugs in women
Management of status epilepticus
Conflicts of interest
• None
Definitions
• seizure: abnormal, excessive, or
synchronous neuronal activity in the
cerebral cortex
•
1-2 min, altered consciousness is common,
confusion/fatigue after an episode, increased
HR, tonic-clonic movement, paresthesias,
aphasia
• epilepsy: two or more unprovoked
seizures
•
Seizure types
Partial
•
•
•
•
simple - does not impair awareness (eg. epileptic auras, jacksonian
march)
complex - impairs awareness by typically spreading to one or both
temporal lobes
secondarily generalized - when simple type spreads to involve both
hemispheres diffusely
Generalized
•
•
•
primary - tonic-clonic
absence - impairment of consciousness
myoclonic - muscle contractions in rapid succession without
consciousness impairment
Epilepsy types
• partial
•
temporal lobe - mesial temporal sclerosis
• generalized
•
juvenile myoclonic - morning myoclonus,
absence
Mesial temporal
sclerosis
Epilepsy-related
comorbidities
• psychiatric disorders - depression,
suicide, anxiety
• cognitive problems - visual/verbal
memory, attention
• osteoporosis, heart disease,
hypertension, stroke, obesity,
obstructive sleep apnea
• sudden death
•
•
•
•
•
•
•
•
Choosing an
antiepileptic drug
(AED)
effectiveness for seizure type
side effects
drug-drug interactions
comorbid conditions
age
gender
lifestyle, patient preferences
cost
Choosing an AED by
epilepsy type
•
•
•
•
partial - nearly all, particularly lamotrigine,
carbamazepine, oxcarbazepine, levetiracetam
generalized - lamotrigine, levetiracetam,
topiramate, zonisamide, NOT carbamazepine,
gabapentin, pregabalin as they can sometimes
exacerbate this type
absence - ethosuximide, valproate
atypical absence, myoclonic, atonic - valproate,
lamotrigine, levetiracetam
Initiating/adding
treatment
•
•
•
•
usually one drug, rather than two or more
2nd drug should have different mechanism,
different side effect profile
published therapeutic serum ranges should
not be used if patient is doing well clinically
(?)
unclear whether generic substitutions lead
to poorer control
Mechanisms
•
•
•
•
•
•
inhibitory transmission (benzodiazepines, clobazam,
phenobarbital, tiagabine, vigabatrin)
sodium channels (carbamazepine, lacosamide,
lamotrigine, oxcarbazepine, phenytoin, rufinamide)
calcium channels (ethosuximide)
potassium channels (ezogabine)
excitatory transmission (perampanel)
multiple mechanisms (felbamate, valproate, gabapentin,
levetiracetam, topiramate)
AED side effects
•
•
•
•
•
sedation, ataxia
folate deficiency
renal metabolism - gabapentin, levetiracetam,
pregabalin, topiramate, zonisamide
hepatic metabolism - carbamazepine, phenytoin,
valproate
elderly:
•
•
YES - gabapentin, lamotrigine, levetiracetam
NO - oxcarbazepine, phenytoin, carbamazepine
AED side effects
•
•
•
•
suicide - levetiracetam, topiramate, vigabatrin
Stevens Johnson Synrome, toxic epidermal necrolysis,
drug rash - phenytoin, carbamazepine (allele
screening hlab1502 in asians), oxacarbazepine,
primidone, phenobarbital, zonisamide, lamotrigine
osteoporosis - especially with: phenytoin,
carbamazepine, phenobarbital, primidone and valproate;
consider checking bone mineral density after five years
use with caution in patients with cardiac conduction
pathology: lacosamide, phenytoin, ezogabine
AED side effects
•
•
•
•
•
•
weight loss - zonisamide, felbamate, topiramate
weight gain - pregabalin, gabapentin, valproate
insomnia - felbamate, lamotrigine
nephrolithiasis - topiramate, zonisamide
valproic acid - exacerbates sx of polcystic
ovarian disease
carbamazepine - induces own metabolism
Oral contraceptives
• carbamazepine, phenytoin,
phenobarbital, primidone tend to
decrease contraceptive serum levels
(also felbamate, topiramate,
oxcarbazepine, rufinamide, clobazam,
perampanel)
• no interaction with levetiracetam,
valproate
• reduced lamotrigine concentrations,
which then go up during the week of
inactive tablets
Pregnancy
•
•
•
•
•
•
4-6% rate of teratogenicity, 2-3x general population
seizure control more important than teratogenicity
aim: monotherapy at lowest dose for control
avoid older AED’s: phenytoin, phenobarbital,
valproate; latter two associated with oral cleft,
cardiac, urinary tract, and neural tube defects, lower
IQ
topiramate: oral cleft, hypospadias
better: lamotrigine, carbamazepine, levetiracetam,
oxcarbazepine, gabapentin, but monitor levels
closely
Pregnancy
• induces AED metabolism, esp.
lamotrigine
• phenytoin, carbamazepine, primidone,
phenobarbital: hemorrhage in newborn
due to vitamin K deficiency
• folate: give 4mg starting 1-3 months
prior to conception if on
carbamazepine, valproic acid; standard
dose for others
Drug-drug
interactions
• phenytoin,
carbamazepine, primidone,
phenobarb, (oxcarbazepine,
topiramate)
• warfarin, OCP’s, anti-infectives, anticancer
• between AED’s (eg. carbamazepine
reduces lamotrigine levels, valproate
increases them)
• alcohol: 1-2 drinks in well-controlled
patient OK, highest risk of seizure 7-
Alternative tx
• vagal nerve stimulation, deep brain
stimulation of anterior nucleus of
thalamus, responsive neurostimulator
• epilepsy surgery - high rate of cure in
patients with known lesions (eg. tumor,
vascular malformation, mesial temporal
sclerosis)
• ketogenic/modified Atkins diet (hi fat,
low carb)
STATUS!
•
convulsive
•
•
•
•
continued seizure activity >30 min;
practically, initiate treatment within 5
min
lorazepam
fosphenytoin
intubate, sedate, additional AED
STATUS!
•
nonconvulsive
•
•
•
•
20% treated for convulsive status epilepticus,
develop EEG seizure
start management if altered mental status
more than 20min post cessation of convulsive
episode
sensitivity of EEG increases longer it is done
(95% at 48 hrs)
paradoxical improvement with low dose
benzodiazepines
Case #1
• 35 yom w h/o simple partial seizure,
failed levetiracetam due to side effects,
recently switched to carbamazepine,
presents c/o recurrent seizure
What to do?
1. switch to lamotrigine
2. add lamotrigine
3. switch to ethosuximide
4. switch back to levetiracetam
5. check carbamazepine level
Case #2
• 70yof w h/o osteoarthritis,1st degree AV
block, hepatic disease, deep venous
thrombosis on warfarin was diagnosed
with partial seizure disorder and started
on primidone; patient was lost to follow
up but showed up in the ED with
another DVT and a subtherapeutic INR
What to do?
1. switch to valproic acid
2. switch to gabapentin
3. continue primidone, low INR is due to
warfarin noncompliance
4. switch to lacosamide
5. switch to carbamazepine
Case #3
• 31yof w h/o nephrolithiasis, renal
insufficiency, and partial seizure
disorder taking valproic acid and OCP is
interested in having a child; aside from
stopping her OCP...
What do you
recommend?
1. folic acid and carbamazepine
2. folic acid and lamotrigine
3. phenytoin
4. folic acid and topiramate
5. folic acid and valproic acid
Case #4
• 21yom w h/o juvenile myoclonic
epilepsy presents to the ED with
uncontrolled seizure; after 15minutes of
observed tonic-clonic seizure, and 6mg
of IV lorazepam, the patient’s clinical
status does not improve
What to do next?
1. IV valproic acid, 30mg/kg at 3mg/kg/min
2. fosphenytoin 18 PE/kg at150PE/min
3. phenytoin 18mg/kg at 50mg/min
4. lorazepam 2mg
5. propofol 2-5 mg/kg bolus
Thank you!