title: Resistance to valproic acid as predictor of treatment resistance in genetic generalized epilepsies.
abstract: This study aimed at defining clinical predictors of drug resistance in adults with genetic generalized epilepsy (GGE) who were treated with a broad spectrum of antiepileptic drugs. Of a cohort of 137 unselected adult GGE patients with long-term follow up, clinical and demographic data, putative prognostic factors (e.g., psychiatric comorbidities, electroencephalography [EEG]), treatment response, and data indicative of social status were collected. Fifty-eight patients had seizures within the past year. Thirty-three patients met the definition of "drug-resistant epilepsy" according to the International League Against Epilepsy (ILAE) definition. Psychiatric comorbidities, age at first diagnosis, and absences were associated with worse seizure control, whereas focal changes in EEG remained without prognostic impact. Resistance to valproic acid was the most important prognostic factor for refractory seizures. Resistance to valproic acid had a specificity of 100% to identify patients with drug resistance and correlated strongly with bad social outcome and seizure burden. Conversely, 21.2% of all patients with refractory seizures according to the ILAE definition later became seizure free (mainly with valproic acid). Our data suggest that "drug resistant GGE" must not be declared unless patients were adequately treated with valproic acid, and advocate resistance to valproic acid as a new clinical biomarker for drug-resistant GGE. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
authors.affiliation: Department of Neurology, University Hospital of Odense, Odense, Denmark.
authors.forename: Joanna
authors.initials: J
authors.lastname: Gesche
authors.affiliation: Department of Neurology, University Hospital of Odense, Odense, Denmark.
authors.forename: Marina
authors.initials: M
authors.lastname: Khanevski
authors.affiliation: Department of Neurology, University Hospital of Odense, Odense, Denmark.
authors.forename: Carl
authors.initials: C
authors.lastname: Solberg
authors.affiliation: Department of Neurology, University Hospital of Odense, Odense, Denmark.|Department for Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Christoph Patrick
authors.initials: CP
authors.lastname: Beier
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D015331:Cohort Studies; D003700:Delta Rhythm / Q000187:drug effects / Q000502:physiology; D003710:Demography; D000069279:Drug Resistant Epilepsy / Q000175:diagnosis*; D004569:Electroencephalography; D004829:Epilepsy, Generalized / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D018709:Statistics, Nonparametric; D014635:Valproic Acid / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid
keywords: Drug resistance; Genetic generalized epilepsy; Juvenile absence epilepsy; Juvenile myoclonic epilepsy; Valproic acid