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 populationEach 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

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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-UpPrimary 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 non-compliance can be dangerous

AED Special Considerations

BCP’sExpected 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’SWomen 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

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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.