4-Aminopyridine and cerebellar gait: a retrospective case series

Abstract

Dear Sirs, Patients with cerebellar ataxia typically walk with a broadened base of support, decreased step length, and increased gait fluctuations [5]. Temporal and spatial gait variability in patients with degenerative cerebellar disorders depends on the actual walking speed and is increased in particular during fast and slow walking [9]. The latter is a critical parameter, since increased variability is associated with a higher risk of falls [3]. The symptomatic treatment of cerebellar gait disorders is mainly based on physiotherapeutic interventions. Coordinative training leads to short-term [6] and long-term [4] improvements in motor performance. So far, there has been no pharmacotherapeutic option for the treatment of patients with cerebellar gait disorders. 4-Aminopyridine (4-AP) was recently approved for the symptomatic treatment of gait impairment in multiple sclerosis [2]. Further, 4-AP has been shown to suppress downbeat nystagmus (DBN) in cerebellar patients [7] and to reduce the frequency and intensity of attacks in episodic ataxia type 2 (EA2) [10]. We recently reported on two patients with cerebellar ataxia caused by mutations of the calcium-channel gene CACNA 1A. 4-AP improved temporal gait variability and the subjective fall risk scale (falls efficacy scale FES-I) in both patients [8]. On the basis of these findings we retrospectively analyzed temporal and spatial gait parameters in patients with different cerebellar disorders under therapy with 4-AP. Thirty-one patients with different cerebellar disorders (sixteen with DBN, eight with sporadic adult-onset ataxia (SAOA), two with cerebellar stroke (CS), three with CACNA 1A mutation, two with multisystem atrophy (MSA-c); mean age 61 years; 11 females; clinical data in Supplemental Table 2) were treated with 5 mg 4-AP t.i.d. Gait analysis was performed using a 6.7 m pressure-sensitive carpet (GaitRITE , CIR System, Havertown, USA) with a sampling rate of 120 Hz. Under treatment, the mean preferred gait velocity increased (p \ 0.05, Table 1), whereas the mean gait velocity during slow and fast walking remained unaffected. The mean cadence at preferred speed was slightly increased (p \ 0.05). A repeated measures ANOVA revealed that the treatment with 4-AP leads to a significant decrease of the coefficient of variation (CV) of stride time under all speed Electronic supplementary material The online version of this article (doi:10.1007/s00415-012-6595-2) contains supplementary material, which is available to authorized users.