Abstracts

Rationale: Rufinamide was recently approved for adjunctive therapy of seizures associated with Lennox Gastaut syndrome (LGS) based on its efficacy in reducing the frequency of tonic-atonic and atypical absence seizures. However, the European experience showed possible efficacy for other seizure types, including focal and generalized seizures. Methods: We report 4 cases of patients with generalized or mixed epilepsy syndromes on a variety of pre-existing antiepileptic drugs who experienced an exacerbation of their seizure frequency and/or severity after the addition of rufinamide. Results: Patient 1: 12 year old boy with childhood absence epilepsy intractable to several medications. Rufinamide was added to lamotrigine and titrated to 400 mg BID. He experienced slight increase in seizure frequency, but a significant worsening of seizure duration and severity. His seizure duration increased from 10-15 seconds up to 30 seconds and he developed increased head bobbing and sometimes head drops toward the end of his seizures, with return to baseline duration and severity after discontinuation of Rufinamide. Patient 2: 4 year old girl with perinatal brain injury, right hemiparesis and developmental delay had up to 15 myoclonic, tonic and atonic seizures per day. Rufinamide was added to topiramate, and titrated up to 400 mg BID. She experienced a significant increase in seizure frequency and duration, which returned to baseline after discontinuation of rufinamide. Patient 3: 36 year old female with symptomatic generalized epilepsy not entirely consistent with LGS, remote atonic-tonic seizures and very frequent myoclonic seizures refractory to numerous AEDs. Rufinamide was added to lamotrigine, phenobarbital, and levetiracetam. She had minimal initial improvement, but after titrating to 3200 mg total per day, she had multiple daily episodes of prolonged myoclonic seizures, which persisted until the rufinamide was partially tapered. Patient 4: This is a 3.5 year old boy with a history of successfully treated infantile spasms with ACTH at 6 months, who progressed into LGS with frequent atonic seizures. Rufinamide was added to levetiracetam, clonazepam, valproic acid and vigabatrin. His atonic seizures increased by 15 to 20 seizures a day compared to baseline on a dose of 200mg BID. In addition, he developed bicycling-like seizures and convulsive seizures. The seizures returned to baseline after decrease and discontinuation of rufinamide. Conclusions: Rufinamide has been demonstrated to be effective for seizures associated with LGS, but its efficacy and safety profile for seizures associated with other generalized epilepsy syndromes is not well established. This report reveals that some patients with generalized epilepsy syndromes including LGS may experience a paradoxical increase in seizure frequency and severity which is reversible with reduction or discontinuation of the AED. Further systematic investigation is necessary to confirm this observation.