Transcript Status Epilepticus was defined by the International Classification of

Management of Epilepsy
Robert L. Macdonald M.D., Ph.D.
Department of Neurology
Vanderbilt University Medical Center
Nashville, TN
Epidemiology of Seizures and Epilepsy
Seizures
Incidence: approximately 80/100,000 per year
Lifetime prevalence: 9%
(1/3 benign febrile convulsions)
Epilepsy
Chronic recurring, unprovoked seizures
Incidence: approximately 45/100,000 per year
Point prevalence: 0.5-1%
Seizure Classification
Partial seizures (focal or local origin)
Simple partial seizures with:
motor signs
somatosensory or special sensory symptoms
autonomic symptoms or signs
psychic symptoms (disturbance of higher cerebral
function)
Complex partial seizures with:
Impaired consciousness
Presence and nature of aura (simple partial origin)
Automatisms and other motor activity
Secondary generalized seizures
Seizure Classification
Primary generalized seizures (bilateral origin)
Absence
Myoclonic
Atonic
Tonic
Tonic-clonic
Epilepsy Syndromes
Partial epilepsies
Idiopathic
Symptomatic
Cryptogenic
Generalized epilepsies
Idiopathic
Symptomatic
Cryptogenic
Undetermined epilepsies
Special syndromes
Age Dependent Etiologies of Epilepsies
Infancy and childhood
Birth injury
Inborn error of metabolism
Congenital malformation
Childhood and adolescence
Idiopathic/genetic syndrome
CNS infection
Age Dependent Etiologies of Epilepsies
Adolescence and young adult
Head trauma
Drug intoxication and withdrawal*
Older adult
Stroke
Brain tumor
Acute metabolic disturbances*
*causes of acute symptomatic seizures, not epilepsy
Questions Raised by a First Seizure
Seizure or not?
Focal or generalized onset?
Evidence of CNS dysfunction?
Metabolic or other precipitant?
Seizure type? Syndrome type?
Studies?
Start an AED?
Seizure Precipitants
Metabolic and Electrolyte Imbalance
Low (occ high) blood glucose, Na, Ca, Mg
Stimulant/other proconvulsant intoxication
IV drug use, cocaine, ephedrine, herbal remedies
Sedative/medication reduction
Sleep deprivation, stress
Hormonal variations
Infection
Evaluation of a First Seizure
History, physical exam
Blood tests: CBC, electrolytes, glucose, Ca, Mg,
hepatic and renal function
Lumbar puncture only if meningitis or
encephalitis suspected and potential for brain
herniation is ruled out
Blood or urine screen for drugs
Electroencephalogram if indicated
CT or MR brain scan if indicated
Medical Treatment of First Seizure
Whether to treat first seizure is controversial.
16-62% will recur within 5 years.
Relapse rate is reduced by antiepileptic drug
treatment.
Abnormal imaging, abnormal EEG or family
history increase relapse risk.
Quality of life issues are important.
Was the seizure “precipitated”?
Medical Treatment of Epilepsy
Treat with an antiepileptic drug (AED)
following a first seizure if the patient has a
high likelihood of developing epilepsy to
prevent seizure recurrence.
Treat with an AED if the patient has
recurrent, unprovoked seizures (epilepsy).
Choosing an AED
Seizure type
Epilepsy syndrome
Pharmacokinetic profile
Interactions/other medical conditions
Efficacy
Expected adverse effects
Useful as monotherapy - simplifies treatment
and reduces adverse effects
Cost
Spectrum of seizure efficacy for
classical AEDs
AED
Partial/ GAE
GTC
JME
Phenytoin
++
-
-
Carbamazepine
++
-
-
Valproate
++
++
++
Primidone
+
-
-
Phenobarbital
+
-
-
Clonazepam
+
+
+
Methsuximide
+
+
+
Ethosuximide
-
++
-
Monotherapy treatment of new onset
epilepsy with new AEDs
AED
Partial\mixed
Absence
Gabapentin
+
-
Lamotrigine
+
+
Topiramate
+
-
Tiagabine
-
-
Levetiracetam
-
-
Oxcarbazepine
+
-
Zonisamide
-
Neurology 62:1252, 2004
Choosing an AED
Partial onset seizures
phenytoin*
gabapentin
carbamazepine*
phenobarbital
valproate
primidone
lamotrigine
felbamate**
oxcarbazepine
topiramate
levetiracetam
tiagabine
zonisamide
* considered by many as drugs of choice
**associated with aplastic anemia and hepatic failure
Choosing an AED
Generalized onset seizures
Absence:
valproate* = ethosuximide
Myoclonic:
valproate, clonazepam
Tonic-clonic:
valproate = phenytoin, carbamazepine
*
the risk of valproate-induced hepatic failure must be carefully weighed in
young children
Preconception counseling and
teratogenicity
Preconception information should be offered to all
females with childbearing potential.
If changes in AED medication are to be made, they
should be completed before conception.
If AED treatment is needed, a single agent is
preferred.
The risk of fetal malformation is increased in women
receiving treatment for epilepsy compared with the
general population (3% with carbamazepine or
lamotrigine, 7% with valproate sodium, and 15% with
two or more AEDs).
Preconception counseling and
teratogenicity
Most major malformations occur at an early stage in
pregnancy, often before the woman knows she is
pregnant.
Women with epilepsy who are planning a pregnancy
should take folic acid 5 mg/day in the preconception
period and throughout the pregnancy; vitamin K should
be used in the last month of pregnancy in women on
enzyme-inducing AEDs.
The use of phenytoin, valproate, carbamazepine,
lamotrigine, and phenobarbital has been associated
with an increased risk of major malformations and
minor morphological anomalies .
Preconception counseling and
teratogenicity
Although valproate may the most suitable drug for
some women, the risks and benefits should be
carefully considered and discussed with the patient.
It is not known whether vigabatrin, gabapentin,
levetiracetam, topiramate, oxcarbazepine, pregabalin,
and tiagabine are associated with a risk of fetal
abnormalities in humans; gabapentin, pregabalin, and
tiagabine are not associated with fetal abnormalities
in animal studies.
Contraception and AEDs
There are no contraindications to the use of
nonhormonal methods of contraception in women with
epilepsy.
For women on nonenzyme-inducing AEDs (valproate
sodium, benzodiazepines, vigabatrin, gabapentin,
tiagabine, levetiracetam, pregabalin), all current
contraceptive methods are suitable.
Hormonal forms of contraception are affected by
enzyme-inducing AEDs (phenytoin, barbiturates,
carbamazepine, oxcarbazepine, topiramate [>200
mg/day], and lamotrigine); women taking these forms
of contraception should be counseled on their risks
and benefits.
AED Interactions
Drugs that induce metabolism of other drugs:
carbamazepine, phenytoin, phenobarbital
Drugs that inhibit metabolism of other drugs:
valproate, felbamate
Drugs that are highly protein bound: valproate,
phenytoin, tiagabine
Other drugs may alter metabolism or protein
binding of antiepileptic drugs
Dose Initiation and Monitoring
Discuss likely and unlikely but important
adverse effects.
Discuss likelihood of success.
Discuss recording/reporting seizures (seizure
calendar), adverse effects, potential
precipitants.
Obtain appropriate “baseline” laboratory tests
CBC, platelets, LFTs
Initiate therapy with an appropriate dose.
Monitor AED levels when appropriate.
AED Serum Concentrations
In general AED serum concentrations can be
used as a guide for evaluating the efficacy of
medication therapy for epilepsy. Serum
concentrations are useful when optimizing AED
therapy, assessing compliance, or teasing out
drug-drug interactions. They should be used to
monitor pharmacodynamic and pharmacokinetic
interactions.
AED Serum Concentrations
Serum concentrations are also useful when
documenting positive or negative outcomes
associated with AED therapy. Most often
individual patients define their own
“therapeutic range” for AEDs. The new AEDs
have potential serum ranges where patients in
clinical trials had optimal seizure control and
minimal side-effects from the medication. For
the new AEDs there is no clearly defined
“therapeutic range.”
Non-Drug Treatment/Lifestyle
Modifications
Adequate sleep
Avoidance of alcohol, stimulants, etc.
Avoidance of non-precipitants
Stress reduction — specific techniques
Adequate diet
Exercise
Discontinuing AEDs
Seizure free 2 years implies overall >60%
chance of successful withdrawal in some
epilepsy syndromes
Favorable factors
Control achieved easily on one drug at low dose
No previous unsuccessful attempts at withdrawal
Normal neurologic status and EEG?
Primarily generalized seizures except JME
“Benign” syndrome
Consider relative risks/benefits (driving,
pregnancy)
Evaluation After Seizure Recurrence
Progressive pathology?
Avoidable precipitant?
If on an AED
Problem with compliance or pharmacokinetic factor?
Increase dose?
Change medication?
If on multiple AEDs
Convert to monotherapy from polytherapy?
Eliminate sedative drugs first
Withdraw antiepileptic drugs slowly over several months
If not on AED
Start therapy?
Treatment of refractory epilepsy with
new AEDs
AED
Partial Partial Primary Symp Ped
Adj
Mono Gen
Gen Partial
Gabapentin
+
-
-
-
+
Lamotrigine
+
+
-
+
+
Topiramate
+
+
+(GTC) +
+
Tiagabine
+
-
-
-
-
Levetiracetam
+
-
-
-
-
Oxcarbazepine
+
+
-
-
+
Zonisamide
+
-
-
-
Neurology 62:1261, 2004
AED Alternatives: Ketogenic Diet
Anti-seizure effect of ketosis, acidosis
Low carbohydrate, low protein, high fat after
fasting to initiate ketosis
Main experience with children, especially with
multiple seizure types
Long-term effects unknown
AED Alternatives: Vagal Nerve
Stimulator
Intermittent programmed electrical stim of L
vagus
Option of patient-triggered stimulation (auras)
Adverse effects related to local stimulus
(hoarseness, throat discomfort, dyspnea)
Mechanism unknown
Clinical trials show 26% effective
FDA says useful for partial onset seizures
AED Alternatives: Surgery
Epilepsy syndrome not responsive to medical
management
Unacceptable seizure control despite maximum
tolerated doses of 2-3 appropriate drugs as
monotherapy
Epilepsy syndrome amenable to surgical
treatment
Evaluation for Surgery
History and Exam: consistency, localization of
seizure onset and progression
MRI: 1.5 mm coronal cuts with sequences
sensitive to gray-white differentiation and to
gliosis
Other neuroimaging options: PET, ictal SPEC
EEG: ictal and interictal, special electrodes
Neuropsychological battery and WADA test
Psychosocial evaluation
Surgical Treatment
Potentially curative
Resection of epileptogenic region (“focus”) without
causing significant new neurologic deficit
Palliative
Partial resection of epileptogenic region
Disconnection procedure to prevent seizure spread
— corpus callosotomy
Vagal nerve stimulation
Epilepsy Surgery Outcomes
Temporal
Extra
Temporal
Lesional
HemisphX
Callosotomy
Seizure Free
68
45
66
45
8
Improved
23
35
22
35
61
9
20
12
20
31
100
100
100
100
100
Not improved
Total