Research and Advances in Epilepsy Preeti Puntambekar, MD, PHD Epileptologist Northeast regional epilepsy group
Epilepsy History Hippocrateson the sacred disease Galen Avicenna Middle ages Renaissance Paracelcus Images German Epilepsy Museum Tissot Jackson
History of Epilepsy Medical Treatment
First generation anti-epileptic medications Valproate (Depakote) Benzodiazepines Diazepam (Valium, Diastat), Midazolam (Versed) Neuronal Synapse
Second generation anti-epileptic medications Levetiracetam (Keppra) Oxcarbazepine (Trileptal) Zonisamide (Zonegran) Pregabalin (Lyrica)
Newer anti-epileptic medications Perampanel (Fycompa) -2012 Clobazam (Onfi) -2011 Ezogabine (Potiga) -2011 Vigabatrin (Sabril) -2009 Rufinamide (Banzel) -2008 Lacosamide (Vimpat) -2008
What do we expect from newer antiepileptic medications?
Indication Mechanism of action Analog of Levetiracetam (Keppra) Efficacy SE 10-26%
Indication Mechanism of action 3 rd generation carbamazepine Efficacy SE 30-40%
Indication Mechanism of action Efficacy Side Effects 19-33% (black box warning)
Future advances in Medical Treatment of Epilepsy Research
Epidiolex Indication: Yes 5
Mechanism of action Efficacy- Side Effects Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S (2017) Cannabidiol in Dravet Syndrome Study Group.Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. May 25;376(21):2011-2020
Dravet syndrome Yes complex-associated Tuberous sclerosis Yes
Epilepsy Research Pipeline
http://www.epilepsy.com/clinical_trials http://www.epilepsy.com/accelerating-new-therapies/newtherapies-pipeline https://www.centerwatch.com/clinicaltrials/listings/condition/62/epilepsy
Acute Seizures or Status Epilepticus - Treatment Overview Prehospital Treatment Emergent Initial Therapy Urgent Control Therapy Seizures Stop Treatment of Refractory Status Epilepticus
Status Epilepticus - Prehospital Studies Leppick et al., JAMA 1983 Treiman et al., NEJM 1998 Silbergleit et al., NEJM 2012
Future advances in Medical Treatment of Epilepsy Intranasal Midazolam Mechanism of action Haut SR, Seinfeld S, Pellock J (2016) Benzodiazepine use in seizure emergencies: A systematic review. Epilepsy Behav.Oct;63:109-117
Future advances in Medical Treatment of Epilepsy Intranasal Midazolam
Advances in Medical Treatment of Epilepsy
Alternatives to Medical Treatment Devices History of Epilepsy surgical treatment Surgery
Devices FDA approves SenTiva Device and Next-Generation VNS Therapy Programming System for epilepsy therapy October 2017
Devices-RNS (Neuropace) First of a kind device to provide targeted responsive stimulation for epilepsy Acute and sustained efficacy in adults with partial onset seizures Provides another treatment option for adults with medically intractable partial onset seizures Neuropace launches Next Gen RNS System with long-lasting 8-year battery life - June 2018
RNS (Neuropace) Neurostimulator and Leads Programmer Patient Data Management System (PDMS) Remote Monitor
Detection settings specific to that activity are programmed Responsive stimulation - Stimulation is enabled using standard settings Detection and stimulation is adjusted as needed RNS (Neuropace)
RNS (Neuropace) In clinical trials, adults treated with the RNS System experienced significant, long-term seizure reduction and compelling quality of life improvements. 1 Some individuals also showed benefit in memory and language. 2 Long term seizure reduction The chart shows seizure reduction over time for patients treated with the RNS System. By year three, patients reported 60% seizure reduction. 1 This continued to improve, with 72% median seizure reduction by year seven. 4 1 Bergey GK, et al. Neurology, 2015 2 Loring DW, et al. Epilepsia, 2015 3 Heck, et al. Epilepsia, 2014 4 Morrell et. al American Epilepsy Society 2016 Data at 7 years were presented at the 2016 American Epilepsy Society meeting and are from a more recent data cut-off than those published by Bergey et al. As a result, more patients had completed 7 years of post-implant follow-up. Data are from open label study. 73% median seizure reduction at year 8
Future Advances in devices as treatment for epilepsy lateralization of mesial temporal lobe seizures 5 weeks anti-epileptic medication one month
Future Advances in devices as treatment for epilepsy quality of life domains - seizure worry, cognition, mental health, and physical health. improvements in mood no adverse cognitive effects improvements in naming improvements in verbal memory
Surgical treatment of Epilepsy
Surgical treatment of Epilepsy
Magnetic resonance-guided Laser interstitial thermotherapy (LiTT) Minimally invasive
Visualase Hoppe C, Witt JA, Helmstaedter C, Gasser T, Vatter H, Elger CE (2017) Laser interstitial thermotherapy (LiTT) in epilepsy surgery. Seizure. May;48:45-52.
Research and Advances in Epilepsy
Conclusion