4-Aminopyridine improves gait variability and reduces fall risk in patients with cerebellar gait disorders

Aims: The fall risk of patients with cerebellar disorders is markedly increased. These falls cause immobility due to serious injuries or a fear of falling. Therefore, reducing the fall risk is the major goal in symptomatic treatment of cerebellar gait disorders. We examined the effect of the potassium channel blocker 4-aminopyridine (4-AP) on the gait performance of patients with different cerebellar syndromes. Patients and Methods: 31 patients with different cerebellar gait disorders (16 downbeat nystagmus, 8 sporadic adult-onset ataxia, 3 CACNA 1A mutation, 2 cerebellar stroke, 2 multisystem atrophy) received 4-Aminopyridine as an individual treatment attempt. Gait performance was measured using a sensor carpet system (GaitRITE®). Further, subjective ambulatory functions were acquired using a FES-I- and ABC-score. Results: The coefficient of variation of stride time decreased under the therapy with 4-AP from 7.8±2.4% to 3.6±2.0% (p<0.001). Subjective ambulatory function and fall risk also improved significantly. A high coefficient of variation of stride time before treatment predicted the improvement of objective gait parameters and the reduction of the subjective fall risks (p<0.001). Conclusion: This retrospective study indicates an improvement of gait under a therapy with 4-AP in patients with different cerebellar disorders. Drug treatment also reduced the subjective risk of falls, which has an important impact on the quality of life of the patients. Temporal gait variability at baseline has a predictive value for the improvement of gait and fall risk under treatment. 4-AP has been shown to improve disturbed Purkinje cell function in animals which might be a promising approach for symptomatic treatment of cerebellar syndromes in humans.

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