4-aminopyridine improves cerebellar tremor in a patient with multiple sclerosis

The reversible potassium channel blocker 4-aminopyridine (4-AP) effectively improves gait performance in patients with multiple sclerosis (MS). Moreover, 4-AP alleviates cerebellar gait disorders by reducing the magnitude of gait variability. Here, we report on a novel effect of 4-AP that efficiently reduced cerebellar tremor in a patient with multiple sclerosis. A 44 years old woman with a progredient form of MS was treated with 5mg of 4-AP t.i.d. The Expanded Disability Status Scale (EDSS) was 6.5 with the leading symptoms of gait disturbance and cerebellar intention and holding tremor. Gait performance and tremor were measured using a pressure-sensitive carpet system (GaitRite®) and a surface EMG with 3D 1g-accelerometer (Noraxon®). Under treatment with 4-AP gait velocity increased from 0.35 m/s to 0.84 m/s 62h after initial treatment. Temporal gait variability decreased from 8.4% to 3.1% coefficient of variation. Root mean square (RMS) of acceleration decreased under 4-AP from 10.89 m/s2 to 2.23 m/s2 (left hand) and 4.23 m/s2 to 0.90 m/s2 (right hand). The patient reported a reduction of subjective daily impairment from 8 to 4 on a Visual Analog Scale (VAS). Here, we describe for the first time a patient with MS whose cerebellar tremor substantially decreased under the treatment with 4-AP. In an animal model, 4-AP was shown to reduce the excitability of neurons in ponto-cerebellar circles, which were attributed to generate tremor in mice. This might explain the positive effect of 4-AP on cerebellar tremor in our patient. The current case report gives first evidence, for the integration of tremor as an relevant parameter in future trials on 4-AP and its sustained release form Dalfampridine® in the symptomatic treatment of MS patients.

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