EPILEPSY

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EPILEPSY

• Review of new treatments and Recommendations

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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.

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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

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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

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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

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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
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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

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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.

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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.

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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.

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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.

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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)

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Hospitalization

• First seizure with a prolonged post-ictal state
  or unusual features
• Status Epilepticus
• An associated systemic illness
• History of significant head trauma

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Initial Work-UpPrimary Objectives

• Did the event result from a correctable systemic
  process
• Is the patient at risk for future episodes

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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)

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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

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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

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High Risk Patients

• A history of serious brain injury
• Lesion on CT or MRI that could promote recurrent
  seizures
• Focal neurologic exam
• Mental retardation

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High Risk Patients

• Partial seizure as the first seizure
• An abnormal EEG
• Absence, myoclonic, and atonic seizures are more
  likely to recur

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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 AEDS

• Topiramate (Topomax 1996)
• Oxcarbazepine (Trileptal 2000)
• Lamotrigine (Lamictal 1994)
• Gabapentin (Neurotin 1993)
• Levetiracetam (Keppra 1999)

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Second Generation AEDS

• Tiagabine (Gabitril 1997)
• Zonisamide (Zonegran 2000)
• Pregabalin (Lyrica - 2005)
• Felbamate (Felbatol-1993)
• Vigabatrin (Sabril 2005-2006 Available in
  Canada and Europe)

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Second Generation AEDS

• With the exception of Felbamate second generation
  AEDS have advantages over first generation
  agents.

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Second Generation AEDS

• Generally lower side effect rates
• Little or no need for serum monitoring
• Once or twice daily dosing
• Fewer drug interactions

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Second Generation AEDS

• There is no significant difference in efficacy
  with the second generation agents
• Higher cost associated with the new agents

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Second Generation AEDS

• Monotherapy is well established for Lamotrigine
  and Oxcarbazepine
• The other agents are undergoing and many have
  completed monotherapy trials.

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AEDS 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

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AED Special Considerations
BCPs

• Expected contraception failure rate .7 per
  100 women years using BCPS.
• Women taking enzyme inducing AEDS it is 3.1 per
  100.

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AED Special Considerations BCPs

• This occurs with all the first generation agents
  with the exception of valproate.
• Felbamate,Topiramate, Oxcarbazepine induce enzyme
  activity and therefore decrease efficacy of BCPS
• Women on AEDS that induce enzymes should be on a
  BCP with at least 50 mcg of the estrogen
  component

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AEDS in General Enzyme inducing
Drugs

• Phenytoin
• Carbamazepine
• Phenobarbital
• Felbamate
• Topiramate
• Oxcarbazepine

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Pregnancy Considerations

• Consider withdraw of AEDS if patient is a good
  candidate
• Use monotherapy where appropriate
• Folate 1-4 mg per day in all women on AEDS

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Pregnancy Considerations

• The risk of fetal malformations are increased in
  pregnant women on AEDS
• Seizures during pregnancy can induce miscarriage
• Seizures during pregnancy can be deleterious to
  the mother or fetus

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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

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Cost

• Keppra 750mg 60 -190.00
• Trileptal 600mg 60 - 211.00
• Zonisamide 100mg 90 - 184.00
• Lyrica 300mg 90 180.00

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AEDS 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

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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.

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Conclusions

• Use folic acid, calcium and Vitamin D
  supplementation in patients on the first
  generation AEDS and probably the second
  generation ones as well.

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