Abstracts

Rationale: KCNA2 epileptic encephalopathy is a recently described rare form of epilepsy. The KCNA2 gene encodes the voltage-dependent Kv1.2 potassium channel that plays a role in neuronal excitability and in neurotransmitter release. There are two clinical phenotypes depending on the functional repercussion of the mutation: gain of function and loss of function. Fampridine, a formulation of 4-aminopyridine, is a potassium channel blocker that may be useful to treat patients with gain of function mutations. Methods: We studied the effect of Fampridine in two patients (age 4 and 8 years) with the same gain of function mutation in KCNA2 (R297Q). Both presented a clinical picture consisting of drug-resistant epilepsy, psychomotor delay, and ataxia, with onset at birth in one case and at 7 months in the other. Both patients had frequent febrile seizures. Epileptic seizures were generalized in both patients: spasms, absences with atonic/myoclonic components, and generalized tonic-clonic. The electroencephalograms at the beginning were normal and later showed focal and generalized epileptiform activity. We investigated whether Fampridine improved the neurologic signs and symptoms, seizure control and electroencephalographic abnormalities. Both patients, have been treated with Fampridine for more than 12 months Results: After treatment with Fampridine a significant clinical improvement was observed in both patients including speech, gait and seizure frequency. Ataxia decreased significantly in both patients. A significant reduction of the total number of seizures was observed as to allow for dose reduction of antiepileptic drugs in both patients. Improvement in EEG background activity and reduction in epileptiform discharges was observed in one patient. There were no significant adverse effects with Fampridine. Conclusions: Our findings support the use of Fampridine, a potassium channel blocker, in patients with KCNA2 epileptic encephalopathy due to gain of function mutations. Fampridine may be especially effective for the treatment of gait ataxia and seizures. Funding: No funding was in support of this work.