Transcript EPILEPSY - Oklahoma State University–Stillwater

EPILEPSY
Review of new treatments and
Recommendations
OBJECTIVES
To understand the work-up of new onset
seizures.
Understand the differential diagnosis of
Paroxysmal events
Be familiar with the new medications
used to treat epilepsy and special
considerations in there use.
Glossary
Seizure - An alteration in behavior
sensation or awareness caused by an
abnormal neuronal discharge of the
brain
Epilepsy – The recurring tendency to
have seizures having excluded an
underlying reversible etiology
Epidemiology
Prevalence .5-1.0% of the population
Each year 300,000 people seek medical
care for new onset seizures.
50% are subsequently diagnosed with
epilepsy
More than 2 million Americans have
active epilepsy of which 17% are under
the age of 18
Differential Diagnosis of
Paroxysmal Events
Paroxysmal symptoms may be either
epileptic or nonepileptic (physiological
or psychogenic)
The interview and exam is aimed at
narrowing the possibilities
Seizures in many individuals are
provoked, this is not epilepsy
Differential Diagnosis of
Paroxysmal Events
(Nonepileptic)
Syncope
Migraine
Movement disorders
TIA
Sleep disorders
TGA
Various psychogenic causes
Epilepsy 20005.gif
Evaluation of the first
seizure in adults
History
Was the event a seizure?
Are there witnesses
What were the circumstances under
which the event occurred
Is there an obvious provoking cause
Tongue biting, incontinence, post – ictal
state, muscle soreness
History
Medication history
Past Medical history – Risk factors for
epileptic seizures include a history of
head injury, stroke, alcohol and drug
abuse
Family history – Absence and myoclonic
seizures may be inherited.
Physical and Neurologic
Examination
The purpose of the neurologic exam
initially is to look for focal features
Screen acutely for musculoskeletal
trauma (fractures etc.)
Remember the possibility of aspiration
Pneumonia etc.
Diagnostic Studies
Neuroimaging – Brain MRI is the preferred
modality.
CT brain is done in the emergency setting to
rule out acute pathology but should be
followed up by MRI if no contraindication
PET and SPECT imaging and functional
imaging are not used in the initial evaluation.
Diagnostic Studies
Lab studies – CBC, serum glucose,
Calcium, Magnesium, renal function
studies and drug and toxicology
screens.
Lumbar puncture – done if an infectious
process is suspected. This may be
misleading if the seizure was prolonged.
Diagnostic Studies
EEG
This study is helpful if positive
A normal EEG does not rule out
epilepsy
The study is more sensitive if the patient
sleeps during the record (sleep
deprived)
Hospitalization
First seizure with a prolonged post-ictal
state or unusual features
Status Epilepticus
An associated systemic illness
History of significant head trauma
Initial Work-Up
Primary Objectives
Did the event result from a correctable
systemic process
Is the patient at risk for future episodes
Single Unprovoked
Seizures
Common affecting 4% of the population
by age 80
30%-40% of patients with a first seizure
will have a second unprovoked seizure
( epilepsy)
Single Unprovoked
Seizures
Risk factors for seizure recurrence
include a history of neurologic insult,
focal lesions on MRI, epileptiform EEG,
and family history of epilepsy
Adult patients with these risk factors
have a 60%-70% of recurrence
Antiepileptic Drug
Therapy
AED therapy is not necessary if a first
seizure provoked by factors that resolve
AED therapy may be indicated if there is
a permeate injury to the brain
(stroke,tumor)
In general AED therapy is started if
there is a high risk of recurrent seizures
High Risk Patients
A history of serious brain injury
Lesion on CT or MRI that could promote
recurrent seizures
Focal neurologic exam
Mental retardation
High Risk Patients
Partial seizure as the first seizure
An abnormal EEG
Absence, myoclonic, and atonic
seizures are more likely to recur
Choosing an AED
Treatment should start with one drug
titrated to the appropriate levels
Monitor response and side effects
Combination therapy should be
attempted only if two adequate
monotherapy trials have occurred
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Second Generation
AED’S
Topiramate (Topomax – 1996)
Oxcarbazepine (Trileptal – 2000)
Lamotrigine (Lamictal – 1994)
Gabapentin (Neurotin – 1993)
Levetiracetam (Keppra – 1999)
Second Generation
AED’S
Tiagabine (Gabitril – 1997)
Zonisamide (Zonegran – 2000)
Pregabalin (Lyrica - 2005)
Felbamate (Felbatol-1993)
Vigabatrin (Sabril 2005-2006
Available in Canada and Europe)
Second Generation
AED’S
With the exception of Felbamate second
generation AED’S have advantages
over first generation agents.
Second Generation
AED’S
Generally lower side effect rates
Little or no need for serum monitoring
Once or twice daily dosing
Fewer drug interactions
Second Generation
AED’S
There is no significant difference in
efficacy with the second generation
agents
Higher cost associated with the new
agents
Second Generation
AED’S
Monotherapy is well established for
Lamotrigine and Oxcarbazepine
The other agents are undergoing and
many have completed monotherapy
trials.
AED’S In General
The most important factor in
determining success of drug therapy is
the duration of the epilepsy
The patient needs to know that AED
treatment is a commitment and noncompliance can be dangerous
AED Special
Considerations
BCP’s
Expected contraception failure rate
.7 per 100 women years using BCP’S.
Women taking enzyme inducing AED’S
it is 3.1 per 100.
AED Special
Considerations
BCP’s
This occurs with all the first generation
agents with the exception of valproate.
Felbamate,Topiramate, Oxcarbazepine
induce enzyme activity and therefore
decrease efficacy of BCP’S
Women on AED’S that induce enzymes
should be on a BCP with at least 50
mcg of the estrogen component
AED’S in General
Enzyme inducing Drugs
Phenytoin
Carbamazepine
Phenobarbital
Felbamate
Topiramate
Oxcarbazepine
Pregnancy
Considerations
Consider withdraw of AED’S if patient is
a good candidate
Use monotherapy where appropriate
Folate 1-4 mg per day in all women on
AED’S
Pregnancy
Considerations
The risk of fetal malformations are
increased in pregnant women on AED’S
Seizures during pregnancy can induce
miscarriage
Seizures during pregnancy can be
deleterious to the mother or fetus
Pregnancy
Considerations
The possibility of prenatal diagnosis of
malformations can be considered with
AFP levels and ultrasonography
Epi_cont.gif
Cost
Felbamate 600mg #180 - $376.00
Neurotin 400mg #90 – $132.00/74.00
Lamictal 150mg #60 –$208.00
Topamax 200mg #60 – $223.00
Gabitril 32mg #60 – $152.00
Cost
Keppra 750mg #60 -$190.00
Trileptal 600mg #60 - $211.00
Zonisamide 100mg #90 - $184.00
Lyrica 300mg #90 – 180.00
AED’S in General
Calcium and vitamin D supplements
should be used in patients on enzyme
inducing drugs
Generics should not be used if at all
possible unless it is the same generic or
the patient has a very easy to control
seizure problem
Conclusions
The work up of a first seizure is
straightforward in most instances but
relies on a good History and
consideration of the differential
diagnosis.
New medications approved for epilepsy
are effective and have a lower side
effect profile.
Conclusions
Use folic acid, calcium and Vitamin D
supplementation in patients on the first
generation AED’S and probably the
second generation ones as well.