What’s New in Epilepsy Research? Evan Fertig, MD Epileptologist Director of Research Northeast Regional Epilepsy Group Outline Why is Epilepsy Research Important? What is a Clinical Trial? Epilepsy Medications under Study at NEREG New Surgical Approaches for Epilepsy 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 antiseizure medications with bad side effects, doing poorly in school 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 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! 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 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 Progress in Epilepsy Treatment Requires Teamwork between Patients Families agree and MDs to genetic testing (bloodwork) Todd’s Success with Diet treatment! • Dravet Mutation Found! Families with Dravet Mutation agree to participate in Diet Studies • Benefit Seen! 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 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 How do Neurons (Brain Cells) work? Ion Channel Sodium Channel: Excites! Potassium, Choride Channel: Rests! What causes Seizures? Brain Tumors, Scar tissue, etc. Ion Channel Problems Excessive firing SEIZURE How Do Seizure Medication Work? Block release Close Sodium Channels (CBZ) Open Chloride Channels (gabapentin) Excessive firing SEIZURE What are the Limits of Medical Therapy? Trial and Error Brain Side Effects Body Side Effects Seizure Control How do We Move Forward? Clinical Trials Basic Science FDA ApprovalMedication available for public Clinical Trials What is a clinical trial? Key terms (from Epilepsy Study Consortium) • Randomization and Control • Blinding • Placebo 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? What Are Some Promising New Medical Treatments under study at NEREG? Everyday Treatment Emergency Treatment • Lacosamide (Vimpat) • Intranasal Midazolam • Ezogabine (Potiga) • Intrabuccal Diazepam • Pregabalin (Lyrica) • Diet Therapies • IV Brivaracetam Potiga Potassium Channel Opener Partial Seizures Rare but serious side effects Bottom Line Potiga vs. Placebo in the Adjunctive Treatment of Subjects with Partial Onset Seizures (POS) Objective Requirement Study Procedure • How safe and effective is Potiga in adults with POS with poorly controlled seizures? • Age > 18, 1 AED (no VNS or KD), 3 or more sz per month • Visits to Hackensack office over 31 weeks. All medication, visits, and travel are provided for free + stipend Cognitive and Behavioral Effects of Lacosamide (Vimpat) for POS. PI- Marcelo Lancman, MD Objective Requirement Study Procedure • How does the new medicine Vimpat affect thinking (cognition) and mood (behavior)? • Age > 18, English, 2 or more sz per month • Visits to Hackensack office over 36 weeks. All medications, visits, and neuropsychological testing are provided for free plus stipend Effect of Lyrica on Anxiety in POS Objective Requirement Study Procedure • How safe and effective is Lyrica for Anxiety in Patients with poorly controlled POS? • Age > 18, 1-2 AEDs, not presently treated for anxiety • Visits to Hackensack office over 6 weeks. All medication, visits, travel free plus stipend Emergency Treatment Rectal Diastat • Clinically proven • Hard to give • Social Stigma • Can’t self administer Intranasal Midazolam Easy to give Preferred route Can be selfadministered or given by caretaker Under study Intranasal Midazolam (IM) Objective • How safe and effective IM for Seizure Clusters? Requirement • Age 14-22, Seizure Clusters Study Procedure • One visit to Hackensack Hospital for test dose then follow up visits. Travel and meds are free Intrabuccal Diazepam (Valium) Objective • How safe is Valium given in the mouth for seizure clusters? Requirement • Age > 2, epilepsy with a history of at least 1 grand mal seizure, to be admitted to EMU Study Procedure • IV line is placed, med is given after a seizure, blood is taken off the IV line several times What are the Limits of Surgical Therapy? What’s on the Horizon? When Do We Consider Resective 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? 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 How does Epilepsy surgery work? Brain Tumors, Scar tissue, etc. Excessive firing SEIZURE Epilepsy Surgery http://www.rch.unimelb.edu.au/cep/Media/brain/mri6.jpg http://www.fleni.org.ar/files/servicio_193_8 Rates of Surgical Success* Temporal Lobectomy 70-80% “Lesion” Resection 70-80% “Non-Lesional” Resection 30-50% Medical Management 5% * Absence of Disabling Seizures 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) Visualase •Laser Treatment •Evaluation is same as for epilepsy surgery No need for open brain operation Visualase Implant • Probe inserted in OR • Transferred to MRI Treatment • Laser Treatment • MRI monitors safety of Laser Rx real-time Follow up • Probe Removed • Patient can leave same day 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? NeuroPace Implant • Device under skull • Leads to seizure focus • Detects seizure • Electrical treatment Treatment delivered • MD reviews • Fine tunes Follow up treatment 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 Research at NEREG Jeff Politsky, MD • MEG • Tumor and Epilepsy • Critical Care EEG Olga LabanGrant, MD Lorna Myers, PhD • Women and Epilepsy • IV Brivaracetam and Seizures • Non-Epileptic Seizures • Spanish and Epilepsy Eric Segal, MD • Diet Therapies for Epilepsy • Sleep and Epilepsy • Dravet Syndrome 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 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 Please Contact Us for More Information! Director of Research Evan Fertig, MD Clinical Research Coordinator Munazza Malik, MD (201) 343-6676 munazza.malik@gmail.com Shweta Malhotra, TBA