BackgroundPatients with downbeat nystagmus syndrome suffer from oscillopsia, which leads to an unstable visual perception and therefore impaired visual acuity. The aim of this study was to use real-time computer-based visual feedback to compensate for the destabilizing slow phase eye movements.MethodsThe patients were sitting in front of a computer screen with the head fixed on a chin rest. The eye movements were recorded by an eye tracking system (EyeSeeCam®). We tested the visual acuity with a fixed Landolt C (static) and during real-time feedback driven condition (dynamic) in gaze straight ahead and (20°) sideward gaze. In the dynamic condition, the Landolt C moved according to the slow phase eye velocity of the downbeat nystagmus. The Shapiro-Wilk test was used to test for normal distribution and one-way ANOVA for comparison.ResultsTen patients with downbeat nystagmus were included in the study. Median age was 76 years and the median duration of symptoms was 6.3 years (SD +/- 3.1y). The mean slow phase velocity was moderate during gaze straight ahead (1.44°/s, SD +/- 1.18°/s) and increased significantly in sideward gaze (mean left 3.36°/s; right 3.58°/s). In gaze straight ahead, we found no difference between the static and feedback driven condition. In sideward gaze, visual acuity improved in five out of ten subjects during the feedback-driven condition (p = 0.043).ConclusionsThis study provides proof of concept that non-invasive real-time computer-based visual feedback compensates for the SPV in DBN. Therefore, real-time visual feedback may be a promising aid for patients suffering from oscillopsia and impaired text reading on screen. Recent technological advances in the area of virtual reality displays might soon render this approach feasible in fully mobile settings.

Objective:The therapeutic effects of 4-aminopyridine (4AP) were investigated in a randomized, double-blind, crossover trial in 10 subjects with familial episodic ataxia with nystagmus.Methods: After randomization, placebo or 4AP (5 mg 3 times daily) was administered for 2 3-month-long treatment periods separated by a 1-month-long washout period. The primary outcome measure was the number of ataxia attacks per month; the secondary outcome measures were the attack duration and patient-reported quality of life (Vestibular Disorders Activities of Daily Living Scale [VDADL]). Nonparametric tests and a random-effects model were used for statistical analysis. Results:The diagnosis of episodic ataxia type 2 (EA2) was genetically confirmed in 7 subjects.Patients receiving placebo had a median monthly attack frequency of 6.50, whereas patients taking 4AP had a frequency of 1.65 (p ϭ 0.03). Median monthly attack duration decreased from 13.65 hours with placebo to 4.45 hours with 4AP (p ϭ 0.08). The VDADL score decreased from 6.00 to 1.50 (p ϭ 0.02). 4AP was well-tolerated.Conclusions: This controlled trial on EA2 and familial episodic ataxia with nystagmus demonstrated that 4AP decreases attack frequency and improves quality of life. Level of evidence:This crossover study provides Class II evidence that 4AP decreases attack frequency and improves the patient-reported quality of life in patients with episodic ataxia and related familial ataxias. Neurology Episodic ataxia type 2 (EA2) is a rare autosomal dominant hereditary disorder caused by heterozygous mutations of the gene CACNA1A on chromosome 19p13.1 The carbonic anhydrase inhibitor acetazolamide has been the drug of first choice for the preventive treatment of episodic ataxia (EA) and especially EA2 (doses of 250 -1,000 mg/day), 2,3 because of the serendipitous discovery of its dramatic impact. 4 Its efficacy, however, has never been proven in a randomized controlled trial. 5,6 Acetazolamide effectively prevents or attenuates the attacks in approximately 50%-75% of all patients with EA2. 7 Clinical experience, however, shows that many patients stop this treatment in the long run because they develop adverse effects or are no longer responsive. 5,6 Furthermore, the adverse effects of acetazolamide (such as nephrocalcinosis, hyperhidrosis, paresthesia, muscle stiffening with easy fatigability, and gastrointestinal disturbances) limit its usage. 6 In view of the need to identify an alternative treatment option to acetazolamide and on the basis of pilot studies in subjects with downbeat nystagmus 8 and EA 9 as well as findings from animal studies, 10,11 we conducted a prospective randomized, doubleblind, placebo-controlled crossover study of 4AP in familial EA with nystagmus (the majority

No abstract

Among patients admitted with out-of-hospital SE, CSE is mostly recognized while NCSE is frequently missed especially in patients with increasing age and no seizure history. This calls for heightened awareness for out-of-hospital NCSE in such patients, as missed NCSE is associated with lack of treatment and less recovery to functional baseline in survivors independent of established outcome predictors.

On the basis of reports by patients with downbeat nystagmus (DBN) that their symptoms were worse during the morning but better during the daytime, we investigated whether the intensity of DBN changes during the daytime. DBN was measured at 9 am, 11 am, and 1 pm. The mean peak slow phase velocity (MPSPV) of DBN was determined in different eye positions, with and without fixation, as well as in three different body positions: sitting upright, lying supine with the nose up, and lying prone with the nose down. Twelve patients with DBN either due to cerebellar degeneration or of idiopathic etiology were examined. The major findings of this study were as follows. First, the intensity of DBN significantly decreased during the daytime. When measured in the sitting upright position and primary eye position, MPSPV decreased from 4.32 deg/sec (+/-SEM 1.02) at 9 am to 2.12 deg/sec (+/- 0.5) at 11 am (P < 0.01) and stayed constant around 1.93 deg/sec (+/- 0.57) at 1 pm (P < 0.01 from 9 am to 1 pm) and 2.08 deg/sec (+/- 0.75) at 3 pm (P < 0.01 from 9 am to 3 pm). Second, this change did not depend on fixation during the measurements. Third, this effect was not influenced by the eye position during the measurements (upward, downward, or straight ahead). Our data show that the intensity of DBN decreases during the daytime. This decrease correlates with the symptoms of the patients. This change during daytime did not depend on visual fixation. Another possible mechanism is the modulation of DBN by head position relative to gravity, that is, by otolith input. This should be evaluated in further studies.

Based on these results, 10-mg doses of 4-AP lead to a more pronounced decrease of the SPV of downbeat nystagmus than do equivalent doses of 3,4-DAP.

We investigated the effects of dalfampridine, the sustained-release form of 4-aminopyridine, on slow phase velocity (SPV) and visual acuity (VA) in patients with downbeat nystagmus (DBN) and the side effects of the drug. In this proof-of-principle observational study, ten patients received dalfampridine 10 mg bid for 2 weeks. Recordings were conducted at baseline, 180 min after first administration, after 2 weeks of treatment and after 4 weeks of wash-out. Mean SPV decreased from a baseline of 2.12 deg/s ± 1.72 (mean ± SD) to 0.51 deg/s ± 1.00 180 min after first administration of dalfampridine 10 mg and to 0.89 deg/s ± 0.75 after 2 weeks of treatment with dalfampridine (p < 0.05; post hoc both: p < 0.05). After a wash-out period of 1 week, mean SPV increased to 2.30 deg/s ± 1.6 (p < 0.05; post hoc both: p < 0.05). The VA significantly improved during treatment with dalfampridine. Also, 50 % of patients did not report any side effects. The most common reported side effects were abdominal discomfort and dizziness. Dalfampridine is an effective treatment for DBN in terms of SPV. It was well-tolerated in all patients.

This study provides Class II evidence that for patients with DBN 2 hours of rest in the upright position decreases nystagmus more than 2 hours of rest in the supine or prone positions (relative improvement 79% upright, 33% supine, and 38% prone: p < 0.05).