EPILEPSY

1. EPILEPSY Review of new treatments and Recommendations

2. 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.

3. 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

4. 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

5. 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

6. Differential Diagnosis of Paroxysmal Events (Nonepileptic) • Syncope • Migraine • Movement disorders • TIA • Sleep disorders • TGA • Various psychogenic causes

8. Evaluation of the first seizure in adults

9. 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

10. 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.

11. 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.

12. 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.

13. 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.

14. 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)

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

16. Initial Work-UpPrimary Objectives • Did the event result from a correctable systemic process • Is the patient at risk for future episodes

17. 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)

18. 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

19. 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

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

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

22. 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

24. Second Generation AED’S • Topiramate (Topomax – 1996) • Oxcarbazepine (Trileptal – 2000) • Lamotrigine (Lamictal – 1994) • Gabapentin (Neurotin – 1993) • Levetiracetam (Keppra – 1999)

25. 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)

26. Second Generation AED’S • With the exception of Felbamate second generation AED’S have advantages over first generation agents.

27. Second Generation AED’S • Generally lower side effect rates • Little or no need for serum monitoring • Once or twice daily dosing • Fewer drug interactions

28. Second Generation AED’S • There is no significant difference in efficacy with the second generation agents • Higher cost associated with the new agents

29. Second Generation AED’S • Monotherapy is well established for Lamotrigine and Oxcarbazepine • The other agents are undergoing and many have completed monotherapy trials.

30. 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

31. 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.

32. 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

33. AED’S in General Enzyme inducing Drugs • Phenytoin • Carbamazepine • Phenobarbital • Felbamate • Topiramate • Oxcarbazepine

34. 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

35. 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

36. Pregnancy Considerations • The possibility of prenatal diagnosis of malformations can be considered with AFP levels and ultrasonography

38. 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

39. Cost • Keppra 750mg #60 -$190.00 • Trileptal 600mg #60 - $211.00 • Zonisamide 100mg #90 - $184.00 • Lyrica 300mg #90 – 180.00

40. 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

41. 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.

42. 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.