Transition from downbeat to upbeat nystagmus caused by 4-aminopyridine

Abstract

Since 2003, aminopyridines have been used to treat downbeat nystagmus (DBN) [1] and more recently to treat episodic ataxia type 2 (EA2) [2] and cerebellar gait disorders [3]. Therefore, aminopyridines have become a treatment option as symptomatic therapy for different cerebellar disorders (for ref. see [4]). Here we report on a case of idiopathic DBN that exhibited a transition from persistent DBN to transient upbeat nystagmus (UBN) during medication with sustained-release 4-aminopyridine (fampridine, Fampyra). A 68-year-old woman presented in with permanent dizziness, unsteadiness of gait, spontaneous vertical oscillopsia and blurred vision. The symptoms started about 1 year prior to examination at our center. Neurological examination revealed a DBN during fixation, which increased on lateral gaze. In addition, a gaze-evoked nystagmus, saccadic smooth pursuit particularly in downward direction, reduced optokinetic nystagmus and impaired visual fixation suppression of the vestibulo ocular reflex (VOR) were found. Thus, a DBN syndrome was diagnosed. The patient had no family history of neurodegenerative disease. Brain MRI showed supratentorial microangiopathic lesions and no cerebellar atrophy or infratentorial lesions. Blood chemistry was normal. As in most cases [5], the etiology remained unclear. Eye movements were measured in an upright position by a 30-second eye movement recording carried out with 3-D video-oculography (EyeSeeCam ) according to prior work (Resolution = 0.02 , Accuracy = 0.6 , Sampling rate = 120 Hz, Range ±20 in horizontal and vertical direction) [6]. Data were analyzed off-line using Matlab version R2011b (The Mathworks, Natick, MA, USA) to analyse the slow-phase velocity (SPV) of DBN. Slow-phase velocity of DBN was evaluated in primary position with fixed straight position of head in a frame at three different times (before medication, 180 min after the first administration and after 2 weeks of treatment). Tests were performed in darkness. Due to the dependence of DBN of daytime [7], all tests were performed until noon. Patients were seated upright while recording in the following order: (1) calibration primary position and 8.5 right, left, up and down, (2) gaze straight ahead with fixation. Targets were video-projected at eye level onto a wall with white projector screen paint located 180 cm in front of the patient [6]. After giving her written consent, the patient was treated with a test dose of fampridine, the sustained-release of 4-aminopyridine (Fampyra) 10 mg orally. Then she was treated for a period of 2 weeks with 10 mg twice daily. Before treatment, she exhibited a linear vertical nystagmus with a slow upward phase velocity (SPV ± SD) during fixation straight ahead of 1.04 /s ± 0.60. One hundred and eighty minutes after ingestion of the first dose of 10 mg of Fampyra she had a transition from a DBN to an UBN with a mean SPV of -1.40 /s ± 0.70 (Fig 1). After the first administration the patient already did not notice any symptoms. After a treatment period of 2 weeks with Fampyra 10 mg twice daily, the patient had no nystagmus at all in the video-oculography and no subjective symptoms, i.e., she responded very well to this treatment. Downbeat nystagmus is the most frequent form of acquired persisting fixation nystagmus [8, 9]. It is most often caused by bilaterally impaired function of the K. Feil (&) J. Claasen S. Bardins J. Teufel M. Habs R. Kalla M. Strupp Department of Neurology and German Center for Vertigo and Balance Disorders, University Hospital Munich, Campus Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany e-mail: katharina.feil@med.uni-muenchen.de