Therapy-refractory symptomatic focal epilepsy with methylmalonic aciduria: Case report on positive effect of rufinamide

Aims: Regarding epilepsy and its therapeutic options in children with methylmalonic aciduria there are only case reports (1–3). Rufinamide (RUF) itself is an „orphan drug“ licensed for add-on therapy in patients with Lennox-Gastaut-Syndrome.

Case report:: 3.5 year-old boy: birth after uneventful pregnancy on date; normal early psychomotor development until 11th month. First metabolic crisis in the course of a viral infection and diagnosis of methylmalonic aciduria. Restitutio ad integrum. With 2.5 years after measles-mumps-rubella vaccination second metabolic crisis with vast metabolic stroke in the area of the left hemisphere. In MRI/T2W symmetrical signal intensity in putamen and nucleus caudatus together with atrophy of the left brain parenchyma. Consecutively the patient developed a right-sided hemi pareses (leg > arm), aphasia together with a pharmacoresistant epilepsy with up to 20 atonic drop attacks/d and a electroencephalographic Status epilepticus. Therefore together with the registration for a video-EEG-intensive-monitoring an add-on therapy with rufinamide was started to the existing anticonvulsive drugs valproic acid and oxcarbamazepine.

Results: A few days after starting therapy with rufinamide notable reduction in seizure frequency. Since two weeks after obtaining the final dose of 28mg/kg/d the patient has remained seizure free for six month, the electroencephalographic Status epilepticus has disappeared and the boy starts to show some progress in his psychomotor development. Valproic acid treatment could be stopped, oxcarbamazepine and is to be gradually discontinued.

Discussion: Differing to the treatment indication a therapy with rufinamide was started in a pharmacoresistant epilepsy with numerous atonic drop attacks before a neurosurgical option. The therapy showed a very good effect, similar to ethosuximide in drop attacks with negative epileptic myoclonus. The few studies regarding rufinamide suggest a possible therapeutic effect in drop attacks of different aetiology, with possibly less effect in symptomatic focal epilepsy. For further valuation more case reports and multicenter-studies are important under observance of the limited treatment indication, to gain knowledge of possible further mechanism of action of rufinamide.

Literature: [1] Guevara-Campos J, González-de-Guevara L, Medina-Atopo M. Methylmalonic aciduria associated with myoclonic convulsions, psychomotor retardation and hypsarrhythmia; Rev Neurol. 2003 Apr; 36(8):735–7. [2] Aikoh H, Sasaki M, Sugai K, Yoshida H, Sakuragawa N. Effective immunoglobulin therapy for brief tonic seizures in methylmalonic acidemia. Brain Dev. 1997 Nov;19(7):502–5. [3] Ye J, Li CJ, Liu JH. A clinical analysis of methylmalonic academia in adolescents. Zhonghua Nei Ke Za Zhi. 2008 Oct;47(10):823–5