Current Therapy for Epilepsy J. Layne Moore, MD, MPH Professor Neurology Wright State University Boonshoft School of Medicine

Epilepsy A disease known from antiquity A disease known from antiquity Initially thought to be from the attack of a spirit or demon Initially thought to be from the attack of a spirit or demon The name epilepsy is derived from the Greek word for “to attack” So a person does not “seizure” they are seized. The name epilepsy is derived from the Greek word for “to attack” So a person does not “seizure” they are seized.

Rationale of Bloodletting Bloodletting goes back 3000 years to the Egyptians. Bloodletting goes back 3000 years to the Egyptians. To appreciate the rationale for bloodletting one must first understand the paradigm of disease 2300 years ago in the time of Hippocrates ( circa 460–370 BC). To appreciate the rationale for bloodletting one must first understand the paradigm of disease 2300 years ago in the time of Hippocrates ( circa 460–370 BC). Hippocrates believed that existence was represented by the four basic elements—earth, air, fire, and water—which in humans were related to the four basic humors: blood, phlegm, black bile, yellow bile.. Hippocrates believed that existence was represented by the four basic elements—earth, air, fire, and water—which in humans were related to the four basic humors: blood, phlegm, black bile, yellow bile..

Humorism

Humorism

Ohio Hospital for epileptics at Gallipolis Ohio

The commission consulted the foremost neurologists and alienists, at home and abroad, especially those experienced in the treatment of epilepsy, and submitted plans for the construction of 36 buildings for the segregation of epileptics in classified colonies, after the method of the Bielefeld Colony in Germany, as the best adapted for the welfare and treatment of those affected with epilepsy. The commission consulted the foremost neurologists and alienists, at home and abroad, especially those experienced in the treatment of epilepsy, and submitted plans for the construction of 36 buildings for the segregation of epileptics in classified colonies, after the method of the Bielefeld Colony in Germany, as the best adapted for the welfare and treatment of those affected with epilepsy.

The Ohio Hospital for Epileptics In 1892 the General Assembly passed an act changing the name of the institution from " The Asylum for Epileptics and Epileptic Insane " to " The Ohio Hospital for Epileptics." In 1892 the General Assembly passed an act changing the name of the institution from " The Asylum for Epileptics and Epileptic Insane " to " The Ohio Hospital for Epileptics."

allipolis_Epileptic_Hospital allipolis_Epileptic_Hospital

Hans Berger

Science to problem

Wilder Penfield

PBPHTCBZ VPA FBM GBP LTG FOS TPM TGB 3 rd Generation “ 2nd Generation ” OCBZ LVT ZNS Antiepileptic Drug (AED) Therapy

Newer AEDs

Rufinamide developed in 2004 by Novartis and manufactured by Eisai. Approved for marketing developed in 2004 by Novartis and manufactured by Eisai. Approved for marketing Approved as adjunct therapy for LGS Approved as adjunct therapy for LGS MOA uncertain perhaps sodium channels MOA uncertain perhaps sodium channels

Lacosamide Approved in 2008 Approved in 2008 Voltage-gated sodium channels Voltage-gated sodium channels UCB UCB Approved for adjunct therapy for partial onset Approved for adjunct therapy for partial onset

Ezogabine A potassium channel A potassium channel Therefore unique Therefore unique Effective in many animal models of epilepsy Effective in many animal models of epilepsy Studies underway in neuropathic pain, tinnitus and migraine Studies underway in neuropathic pain, tinnitus and migraine TID dosing TID dosing

Perampanel acts as a selective noncompetitive antagonist of AMPA receptors. acts as a selective noncompetitive antagonist of AMPA receptors. Being studied in Parkinson’s disease Being studied in Parkinson’s disease Half-life 105 hours Half-life 105 hours 95% protein bound 95% protein bound

Brivaracetam Approval may be early 2015 Approval may be early 2015 it is around 10 times more potent for some models of epilepsy than Levetiracetam it is around 10 times more potent for some models of epilepsy than Levetiracetam

VNS Approved for partial epilepsy 1997 Approved for partial epilepsy 1997 Approved for depression 2005 Approved for depression 2005

Responsive Neurostimulator Device The RNS System utilizes a neurostimulator implanted in the skull with one or two leads implanted in the brain at focal points of seizures The RNS System utilizes a neurostimulator implanted in the skull with one or two leads implanted in the brain at focal points of seizures

Quality of Life Side-effects Side-effects Mood Mood Anxiety Anxiety Stigma Stigma Isolation Isolation

Genetics Severe childhood epilepsies: Large international study pinpoints synapse genes with major roles September 25, 2014 Children's Hospital of Philadelphia An international research team has identified gene mutations causing severe, difficult-to-treat forms of childhood epilepsy. Many of the mutations disrupt functioning in the synapse, the junction at which nerve cells intercommunicate. An international research team has identified gene mutations causing severe, difficult-to-treat forms of childhood epilepsy. Many of the mutations disrupt functioning in the synapse, the junction at which nerve cells intercommunicate.

What’s New at WSU/PHP? Looking at new medicines (Brivaracetam) for the treatment of in hospital non-convulsive status epilepticus Looking at new medicines (Brivaracetam) for the treatment of in hospital non-convulsive status epilepticus Assessment of stigma experienced by our epilepsy patients in clinic Assessment of stigma experienced by our epilepsy patients in clinic

What’s Next? Science Science Hope Hope