1. © 2014 Direct One Communications, Inc. All rights reserved. 1 Treating the New-Onset Epilepsy Patient Ching Y. Tsao, MD Emory University Hospital, Atlanta, Georgia A REPORT FROM THE 67 TH ANNUAL MEETING OF THE AMERICAN EPILEPSY SOCIETY (AES 2013)

2. © 2014 Direct One Communications, Inc. All rights reserved. 2 What Is New-Onset Epilepsy? New-onset epilepsy: early stage of epilepsy; more than two seizures within a single year Newly diagnosed epilepsy: subtle seizures may have gone unrecognized for years prior to presentation Pohlmann-Eden B. Epilepsia. 2012;53:1277

3. © 2014 Direct One Communications, Inc. All rights reserved. 3 Factors Involved in Clinical Decisions Mulrow CD et al. Ann Intern Med. 1997;126:389

4. © 2014 Direct One Communications, Inc. All rights reserved. 4 Considerations When Choosing an AED Patient-specific variables: genetics, age, gender, comorbidities, other medications Antiepileptic drug (AED)-specific variables: efficacy for a particular type of seizures or syndromes, pharmacokinetics, adverse effects, teratogenicity, interaction potential Country-specific variables: availability of AEDs, cost, insurance coverage Glauser T et al. Epilepsia. 2006;47:1094

5. © 2014 Direct One Communications, Inc. All rights reserved. 5 New-Onset Epilepsy in Adults For treating partial-onset seizures: carbamazepine, phenytoin, levetiracetam, or zonisamide For treating generalized onset seizures: valproate or ethosuximide » Limited evidence » Recommendation based on one class I study for the treatment of absence seizures Glauser T et al. Epilepsia. 2013;54: 551

6. © 2014 Direct One Communications, Inc. All rights reserved. 6 Identifying New-Onset Epilepsy in Children First challenge is recognition of seizures versus nonepileptic paroxysms In one study, one-fourth of children were misdiagnosed as having seizures At the same time, the diagnosis of epilepsy was missed in one-third of the children. Hamiwka LD et al. Epilepsia. 2007;48:1062; Crompton DE, Berkovic SF. Lancet Neurol. 2009;8:370

7. © 2014 Direct One Communications, Inc. All rights reserved. 7 Treating New-Onset Epilepsy in Children Focal seizures: oxcarbazepine, carbamazepine, lamotrigine, or levetiracetam Primary generalized epilepsies: » Childhood and juvenile absence epilepsies: ethosuximide, valproate, or lamotrigine » Juvenile myoclonic epilepsy: clonazepam, lamotrigine, levetiracetam, topiramate, valproate, zonisamide Lennox-Gastaut syndrome (LGS): valproate, topiramate, lamotrigine, zonisamide, clobazam, rufinamide, or felbamate Mulrow CD et al. Ann Intern Med. 1997;126:389; Glauser T et al. Epilepsia. 2013;54:551; Scottish International Guidelines Network (http://www.sign.ac.uk/guidelines/fulltext/81/)

8. © 2014 Direct One Communications, Inc. All rights reserved. 8 Recommended Treatment of Childhood Focal Seizures Wheless JW et al. Epileptic Disord. 2007;9:353; Wheless JW et al. J Child Neurol. 2005;20:S1

9. © 2014 Direct One Communications, Inc. All rights reserved. 9 Treating New-Onset Epilepsy in Children Age-specific issues: » Valproate: risk of hepatotoxicity in children < 2 years of age » Topiramate: risk of appetite suppression » Phenobarbital: negative impact on cognition Sankar R. Neurology. 2004;63:S30

10. © 2014 Direct One Communications, Inc. All rights reserved. 10 New-Onset Epilepsy in the Elderly Incidence of epilepsy increases after age 50. Most cases of new-onset epilepsy in patients over age 65 (51%) are cryptogenic. Stroke (38%) and degenerative processes (12%) are also common etiologic or precipitating factors. 7%–21% of patients with Alzheimer’s disease have at least one unprovoked seizure. 43% of patients with stroke have recurrent seizures. » The risk increases with late onset of a first seizure after stroke, a hemorrhagic component, occipital location, or low Rankin score after initial seizure Hauser WA et al. Epilepsia. 1993;34:453; Amatniek JC et al. Epilepsia. 2006;47:867; Berges S et al. Eur Neurol. 2000;43:3

11. © 2014 Direct One Communications, Inc. All rights reserved. 11 New-Onset Epilepsy in the Elderly Hauser WA et al. Epilepsia. 1993;34:453 Age-specific incidence of epilepsy by gender in Rochester, Minnesota

12. © 2014 Direct One Communications, Inc. All rights reserved. 12 Treatment of New-Onset Epilepsy in the Elderly Therapeutic window is narrower in older adults » Risk of toxicity with AEDs at lower serum concentrations Seizure control comparable among gabapentin, lamotrigine, and carbamazepine in one study » A high rate of discontinuation of carbamazepine due to adverse effects was observed Data were obtained prior to the availability of levetiracetam Bergey GK. Neurology. 2004;63(suppl 4):S40; Cloyd J, in: Rowan AJ, Ramsay RE, eds. Seizures and Epilepsy in the Elderly. Boston: Butterworth-Heinemann, 1997;219; Rowan AJ et al. Neurology. 2005;64:1868

13. © 2014 Direct One Communications, Inc. All rights reserved. 13 The more seizures that occurred prior to initiation of AED therapy, the more difficult the epilepsy became to control. The number of AEDs previously attempted and that had failed may predict future response to AEDs. The addition of a second and a third AED increases the likelihood of seizure freedom only slightly. SANAD Trial: Prognosis for New-Onset Epilepsy Bonnett L et al. Lancet Neurol. 2012;11:331

14. © 2014 Direct One Communications, Inc. All rights reserved. 14 Cumulative Probability of Being Seizure Free Brodie MJ et al. Neurology. 2012;78:1548

15. © 2014 Direct One Communications, Inc. All rights reserved. 15 Two-thirds of patients with epilepsy are seizure free after the first year of treatment. More-favorable prognosis for seizure freedom: childhood absence epilepsy, benign rolandic epilepsy Less-favorable prognosis for seizure freedom: juvenile absence epilepsy, symptomatic generalized epilepsy, mesial temporal sclerosis Predictors of seizure freedom: number of seizures that have occurred, number of AEDs previous attempted Seizure Freedom: Prognosis for New-Onset Epilepsy