4-Aminopyridine improves downbeat nystagmus, smooth pursuit, and VOR gain

Abstract

Downbeat nystagmus (DBN), the most frequent form of acquired persisting fixation nystagmus, is hypothesized to occur when physiologic, inhibitory cerebellar input to the vestibular nuclei is inhibited. Bilateral cerebellar lesions affecting the vestibulocerebellum or bilateral paramedian brainstem lesions could induce such inhibition.1 GABAergic, glutaminergic, or cholinergic drugs have been used to manage DBN with moderate success.2 3,4-Diaminopyridine (3,4-DAP) was shown recently to effectively suppress DBN.3 In animal experiments, the related 4-aminopyridine (4-AP) increased the excitability of Purkinje cells (PCs).4 Both agents seem to influence DBN by increasing the physiologic, inhibitory influence of the vestibulocerebellum on the vestibular nuclei.3 4-AP penetrates the blood–brain barrier better than 3,4-DAP but has not yet been tested for management of ocular motor disorders. To evaluate how aminopyridines affect DBN and to test whether 4-AP is also effective, we measured DBN, smooth pursuit, gaze holding, and the gain of the vestibular ocular reflex (VOR) with the search coil technique in one patient. A 65-year-old pharmacist had blurred vision for 7 years that increased during lateral gaze. Neurologic examination was normal, except for DBN during fixation, impaired smooth pursuit, and postural imbalance. DBN increased during lateral and downward gaze and convergence. Brain MRI and blood chemistry (including vitamin B12 and Mg2+ …