This follow-up proves the usefulness of the diagnostic criteria, especially constructive interference in steady state magnetic resonance imaging, and the therapeutic efficacy of medical treatment.

Study queStion

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

Combined cSLO and SD-OCT imaging provides unprecedented insight into dynamic microstructural changes of GA enlargement that may help to better understand the pathogenesis of the disease. Quantitative progression data indicate local factors may exist that drive progression in junctional areas (ClinicalTrials.gov number, NCT00393692).