Abstracts

Rationale: Juvenile myoclonic epilepsy (JME) is a form of genetic generalized epilepsy (GGE) which usually responds well to medication. However, 15-30% of JME patients are pharmacoresistant. Misdiagnosis of a progressive myoclonus epilepsy (PME) as JME may be one reason for pharmacoresistance. We aimed to identify phenotypic differences between pharmacoresistant and pharmacoresponsive JME patients and to clarify if misdiagnosis of JME may be a reason for missing seizure freedom. Methods: Medical reports of the Department of Neurology and Epilepsy Center, University Hospital Marburg, of the years 2004-2015, that included the search term “myoklon”, were automatically selected and manually evaluated regarding the presence of a JME diagnosis at any timepoint. The identified patients were evaluated regarding seizure outcome and pharmacoresistance. Patients were classified as seizure free if the duration of seizure freedom was higher than expected from the typical seizure frequency and the medication was not changed at last follow-up. Pharmacoresistance was classified according to ILAE criteria. Seizure freedom ≥1 year was considered as response. The pharmacoresistant patients underwent detailed phenotyping. Results: The keyword search resulted in 3329 medical reports of 1926 patients. Of these, 152 had been diagnosed with JME and 19 with PME. Most frequently, JME patients were last treated with valproate (48%), followed by levetiracetam (33%) and lamotrigin (30%). Valproate and levetiracetam were more efficacious that lamotrigine (seizure freedom>1 year with mono or add-on therapy 48%/39% vs. 13%). 82 patients (54%) were seizure free, 59 of these (39%) for >1 year which were classified as not pharmacoresistant (NPR). 67 patients (44%) were not seizure free, 24 of these (16%) were pharmacoresistant (PR). Three of these 24 had only had myoclonic seizures during the last year. Compliance issues led to seizure recurrence in further 17 patients (11%). PR patients had significantly more frequently dialeptic seizures as a prominent seizure type (17% vs. 0%; p=0.007),intellectual disability (13% vs. 4%; p=0.022) and impaired cognition (63% vs. 17%; p < 0.001), both medication-induced (33% vs. 9%; p=0.008), and not medication-induced (29% vs. 9%, p=0.033).The JME diagnosis was confirmed by re-phenotyping in 18 PR patients (75%). In 6 patients (25%), re-phenotyping revealed different diagnoses: 1 focal epilepsy with secondary bilateral synchrony, 2 focal epilepsies in addition to the JME, 1 epileptic encephalopathy, 1 epilepsy with eyelid myoclonia (Jeavons syndrome) and 1 medication-induced myoclonus in GGE. In 5 of these 6 patients the JME diagnosis had already been questioned independent of the study. Conclusions: In patients with pharmacoresistant JME different epilepsy syndromes should be excluded by detailed phenotyping. The misdiagnosis of PME as JME was not a relevant cause for pharmacoresistance in our cohort. Prominent dialeptic seizures and impaired cognition are associated with a higher risk of pharmacoresistance. Funding: None