A. LeBron Paige, M.D. Clinical Associate Professor Department of Neurology A. LeBron Paige, M.D. Clinical Associate Professor Department of Neurology Iowa EFA Seizure Smart Conference – 3/2/2013

 Epilepsy is a medical condition that produces seizures affecting a variety of mental and physical functions. When a person has two or more unprovoked seizures, they are considered to have epilepsy.  A seizure is the result of a strong sustained surge of electrical activity (discharges) that affects part or all of the brain.  Seizures can be brief or prolonged, typically less that 3 minutes, and can cause unusual movements, sensations, thinking, or can disturb many other body functions.  Seizures can be a subtle unresponsive staring (partial), a frighteningly dramatic convulsion (generalized), or in between.  Seizures can be caused by anything that can affect the brain, such as tumors, strokes, bleeding, infection, trauma, or unknown factors.  Treatments for epilepsy include medications, surgery, diet, electrical stimulators, and other emerging options.

Epilepsy Around the World  Epilepsy is one of the world’s oldest diseases.  Worldwide, million people are living with epilepsy  80% of all people with epilepsy live in the developing regions.  75% of affected people in these developing countries do not get the treatment they need (9 out of 10 in Africa).  The World Health Organization (WHO) estimates that 6-10 people per 1000 have active epilepsy in the developing world. (conservative)  Epilepsy accounts for 0.5% of the global burden of disease  The social stigma surrounding epilepsy worldwide is often more difficult to overcome than the seizures themselves

Epilepsy - US Incidence  200,000 new epilepsy cases diagnosed annually in the US o 50,000 new cases of Parkinson’s Disease in the US annually  67 new cases of epilepsy per 100,000 population each year o 62.6 individuals with lung cancer per 100,000 population per year  100 individuals with first convulsion per 100,000 population each year o 124 women with breast cancer per 100,000 population  50% of new onset epilepsy cases present w/ Generalized Sz  70% of these new cases have no apparent cause  Incidence is greater in Black and socially disadvantaged populations  Highest epilepsy incidence is in > 65 y/o & is increasing in recent years  Partial seizures predominate in patients >10 y/o

Childhood Epilepsy – US Incidence  120,000 children per year will experience their first seizure o 75,000 – 100,000 of these are < 5 y/o with febrile seizures  45,000 children will receive a diagnosis of epilepsy per year  Highest incidence found in 5y/o  Childhood epilepsy incidence has been trending down in recent years  Generalized seizures are the most common in patients < 10 y/o  Most children with seizures will not develop epilepsy  Most children with epilepsy will outgrow the condition  Most children with epilepsy are normal in every other respect

Alcohol Neonatal Other provoked Epilepsy Single Total Age Incidence Per 100,000 Patient Years

l 4):S6-S14. Complex 23% Other partial 7% Myoclonic 7% Unknown/ multiple 9% Simple partial 11% Other generalized 11% Absence 13% Complex partial 39% Myoclonic 2% Other generalized 4% Other partial 9% Simple partial 21% Tonic-clonic 25% Tonic-clonic 19% Children <15 YearsAdults Years

Idiopathic 65.5% Vascular 10.9% Congenital 8.0% Trauma 5.5% Neoplastic 4.1% Degenerative 3.5% Infectious 2.5 %

Epilepsy in the Elderly Stefan, H. Epilepsy in the Elderly, Acta Neurol Scand., 124: : ELDERLY (>65 y/o) 18 y/o < ADULTS < 65 y/o

Epilepsy Prevalence - US  million active epilepsy patients in the US (~1% of the population)  30,000 Iowans carry a diagnosis of epilepsy  1% of Americans aged birth to 20 y/o have a diagnosis of epilepsy  3% of Americans aged birth to 75 y/o have a diagnosis of epilepsy  10% of Americans aged birth to 80 y/o have had at least one seizure  There are more Americans living Epilepsy than MS, Cerebral Palsy, Muscular Dystrophy, Parkinson’s Disease, ALS, and Tourette’s syndrome combined.  Of all neurological Dz, only Migraine & Stroke is more prevalent than Epi  70% of people with epilepsy are controlled (> 5yr) on medications  Overall almost 10 % of new patients fail to gain control of seizures despite optimal medical management.

25.8% of children with mental retardation 13% of children with cerebral palsy 50% of children with both disabilities 10% of Alzheimer patients 22% of stroke patients 8.7% of children of mothers with epilepsy 2.4% of children of fathers with epilepsy 33% of people who have had a single, unprovoked seizure The basic underlying risk of developing epilepsy is about 1%, but individuals in certain populations are at higher risk.

Seizure Freedom by Seizure Type One year seizure free rates in patients treated with medications alone.

Epilepsy Mortality Cause of death among 3340 Epilepsy patients over 30 years Cause of Death Proportion of all Deaths Non-CNS Tumors23% CNS Tumors5% Heart Disease26% Stroke15% Epilepsy7% Trauma9% Respiratory Disease3% Pneumonia1% Other11%

Epilepsy Mortality - SUDEP  Sudden, Unexpected, Death in Epilepsy 1. Decedent has diagnosis of epilepsy 2. Death is Sudden 3. Death is Unexpected 4. Death is not the result of trauma 5. Death is not the result of drowning 6. No evidence that death was associated with status epilepticus 7. No structural or toxicological cause on post-mortem examination  Factors that increase the risk of SUDEP 1. Young adulthood (children at low risk) 2. Early epilepsy onset & long duration 3. Poorly controlled seizures 4. Poor medication compliance 5. Unsupervised sleep environment (prone position) 6. Generalized convulsion > Complex partial seizures >> myoclonic or absence 7. Epilepsy Surgical Candidates

16 SUDEP Incidence by Group

Information Sources  The Institute of Medicine (NAS), Epilepsy Across the Spectrum, 2012  The Epilepsy Foundation of America [  The World Health Organization (WHO) [  National Cancer Institute [  Neurological disorders: public health challenges, World Health Organization, 2006  Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: Epilepsia. 1993;34:  D. Hirtz, D. J. Thurman, K. Gwinn-Hardy, et al., How common are the ''common'' neurologic disorders? Neurology 2007;68;326.  Ficker, DM, Sudden Unexplained Death and Injury in Epilepsy, Epilepsia, (Supp1.2):S7-S12, 2000  Thomson, T., Sudden unexpected death in epilepsy: current knowledge & future directions. The Lancet Neurology, Sept  Stefan, H. Epilepsy in the Elderly, Acta Neurol Scand., 124: :  Trinka, E, et al., Cause-specific mortality among patients with epilepsy: Results from a 30-year cohort study, Epilepsia, ** (*):1–7, 2012

Epilepsy Discrimination  The Code of Hammurabi (1780 B.C.) established that a person with epilepsy could not marry, testify in court, and voided slave purchases  In both China and India, epilepsy is commonly viewed as a reason for prohibiting or annulling marriages.  In the United Kingdom, a law forbidding people with epilepsy to marry was repealed only in  In the United States, until 1956 it was illegal in 17 states for people with epilepsy to marry, and into the 1970s it was legal to deny them access to restaurants, theatres, rec centers and other public buildings.  1973 brought the first limited US laws to prohibit discrimination, but not until 1990 with the Americans with Disabilities Act was there uniform protection against discrimination.

PMD General Neurologist(s) Level-4 Epilepsy Center Spells are Likely Seizures Seizures are Refractory to two Medications Epilepsy Care Pathway Patient has “Spells” Level-4 Epilepsy Center Comprehensive Diagnostic Capability New & Experimental Medications Epilepsy Surgery Experience Implantable Stimulators Radiation treatment vs. Surgery Access to National Epilepsy Expertise National Association of Epilepsy Centers

22 Englot, DJ, et al., Epilepsy Surgery Trends in the United States , Neurology, 78;1200 (2012)