What’s New in Epilepsy Research?

1. What’s New in Epilepsy Research? Evan Fertig, MD Epileptologist Director of Research Northeast Regional Epilepsy Group

2. Outline • Why is Epilepsy Research Important? • What is a Clinical Trial? • Epilepsy Medications under Study at NEREG • New Surgical Approaches for Epilepsy

3. Case #1: Why Epilepsy Research is Important • Todd age 15 • Grand mal seizures occur daily • Last MD told mom nothing else to do • He is on 2 anti-seizure medications with bad side effects, doing poorly in school

4. More about Todd… • One of his medication is carbamazepine which is a sodium channel blocker • Video-EEG: Seizures coming from multiple areas of his brain • MRI Brain: Normal

5. We learn that… • Seizures began 6 months with fever • Seizures occur more in the summer or with vigorous exercise (gym) • New genetic blood test sent: sodium channel mutation!

6. What’s Todd’s Diagnosis? Dravet Syndrome Caused by a genetic problem with a brain protein (sodium channel). This was not understood before! Symptoms: Bad febrile seizures, then multiple sz types, worsens with sodium channel blockers

7. And so what happened? Carbamazepine is stopped (the sodium channel blocker), Atkins Diet (like the ketogenic diet) started. Seizure free for 2 years No side effects, doing very well in school

8. Progress in Epilepsy Treatment Requires Teamwork between Patients and MDs

9. Key Points The better we understand the causes of epilepsy… The better our treatments will be! Clinical Research is the key but can’t happen without teamwork between patients, families, and MD’s

10. What is Epilepsy? A disorder of spontaneously occurring unprovoked seizures (more than 2) Seizures are electrical storms of brain cells that can cause many different symptoms

11. How do Neurons (Brain Cells) work? Ion Channel Sodium Channel: Excites! Potassium, Choride Channel: Rests!

12. What causes Seizures? Brain Tumors, Scar tissue, etc. Ion Channel Problems Excessive firing SEIZURE

13. How Do Seizure Medication Work? Block release Close Sodium Channels (CBZ) Open Chloride Channels (gabapentin) Excessive firing SEIZURE

14. What are the Limits of Medical Therapy? • Trial and Error • Brain Side Effects • Body Side Effects

15. Seizure Control

16. How do We Move Forward?

17. Clinical Trials • What is a clinical trial? • Key terms (from Epilepsy Study Consortium) • Randomization and Control • Blinding • Placebo

18. What Should I Know? • Previous safety record of study medication or device • Chance of getting it vs. placebo? • How long? What to expect at each visit? • Access to study agent after the trial?

19. What Are Some Promising New Medical Treatments under study at NEREG? • Everyday Treatment • Lacosamide (Vimpat) • Ezogabine (Potiga) • Pregabalin (Lyrica) • Diet Therapies • Emergency Treatment • Intranasal Midazolam • Intrabuccal Diazepam • IV Brivaracetam

20. Potiga • Potassium Channel Opener • Partial Seizures • Rare but serious side effects • Bottom Line

21. Potiga vs. Placebo in the Adjunctive Treatment of Subjects with Partial Onset Seizures (POS)

22. Cognitive and Behavioral Effects of Lacosamide (Vimpat) for POS. PI- Marcelo Lancman, MD

23. Effect of Lyrica on Anxiety in POS

24. Emergency Treatment • Rectal Diastat • Clinically proven • Hard to give • Social Stigma • Can’t self administer

25. Intranasal Midazolam • Easy to give • Preferred route • Can be self-administered or given by caretaker • Under study

26. Intranasal Midazolam (IM)

27. Intrabuccal Diazepam (Valium)

28. What are the Limits of Surgical Therapy?What’s on the Horizon?

29. When Do We ConsiderResective Epilepsy Surgery? • Partial Epilepsy • Treatment Resistant Epilepsy • Failure to become seizure free after > 2 adequate trials of 2 AEDs used appropriately • Intolerable adverse effects of AEDs?

30. Why? Rate of Seizure Freedom with continued trials of Sz med is low (5%) Potential for injury with uncontrolled epilepsy over a lifetime is high! Rate of Seizure Control with Resective Epilepsy Surgery is in comparison is high (30-80%) with a low complication rate Reduction or Elimination of Sz med is frequently possible

31. How does Epilepsy surgery work? Brain Tumors, Scar tissue, etc. Excessive firing SEIZURE

32. Epilepsy Surgery http://www.rch.unimelb.edu.au/cep/Media/brain/mri6.jpg http://www.fleni.org.ar/files/servicio_193_8

33. Rates of Surgical Success* * Absence of Disabling Seizures Temporal Lobectomy 70-80% “Lesion” Resection 70-80% “Non-Lesional” Resection 30-50% Medical Management 5%

34. What are the Limits of Surgical Therapy? Small risk: bleeding and infection Not effective for all seizures types Not effective if seizures are come from more than one location Not possible if seizures arise from critical brain tissue (hand area)

35. Visualase • Laser Treatment • Evaluation is same as • for epilepsy surgery • No need for open brain • operation

36. Visualase

37. Neuromodulatory Treatments • Device implanted to alter instead of destroy brain tissue • Range of treatment possible: Electrical, Cooling, local medications • Limit body/brain side effects • Improve brain function?

38. NeuroPace

39. What will Epilepsy Care Look Like in Future? • Personalized Medical Choices based on genetics • Truly Anti-epileptic therapy • Treatment directed right at the seizure focus

40. Research at NEREG

41. Conclusion In most cases, seizures can be well controlled with medications with minimal side effects The correct diagnosis to guide treatment is essential Epilepsy is more than just seizures, and the treatment may require a team approach

42. Conclusion • Some cases are more difficult to control, and treatment with diet therapy or surgery may be used, or clinical trials may be an option

43. Please Contact Us for More Information! • Director of ResearchEvan Fertig, MD • Clinical Research CoordinatorMunazzaMalik, MD(201) 343-6676munazza.malik@gmail.com • ShwetaMalhotra, TBA