A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias.

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 = 0.03). Median monthly attack duration decreased from 13.65 hours with placebo to 4.45 hours with 4AP (p = 0.08). The VDADL score decreased from 6.00 to 1.50 (p = 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.

[Clinical characteristics, progression and risk factors of geographic atrophy]. / Klinische Merkmale, Progression und Risikofaktoren bei geographischer Atrophie.

Geographic atrophy (GA) as the late stage manifestation of age-related macular degeneration (AMD) is a progressive disease process afflicting the retinal pigment epithelium, choriocapillaris and the outer neurosensory retina. GA represents a complex, multifactorial disease governed by the interdependence of genetic, endogenous and exogenous factors. Diagnosis and monitoring of GA progression is largely based on various retinal imaging modalities. After the breakthrough in the treatment of wet AMD GA represents a large clinical challenge. Recent studies have contributed to a better understanding of the pathophysiological pathways, natural history and predictive markers for progression.

Vestibular paroxysmia: diagnostic features and medical treatment.

BACKGROUND: Vestibular paroxysmia (VP), which is attributed to neurovascular cross-compression (NVCC), leads to vertiginous spells. Although VP was described more than 30 years ago by Jannetta and colleagues, we still need more reliable data on its diagnostic features and the efficacy of medical treatment. METHODS: A follow-up study of 32 patients with recurrent short spells of vertigo and with diagnosis of VP by published criteria was performed using medical records and patient consultation (mean follow-up time 31.3 months). RESULTS: In 28% of patients the attacks occurred exclusively when at rest, whereas in 22% they were regularly precipitated by a certain action, most frequently a head turn (60%). The most common accompanying symptom was unsteadiness of stance or gait (75%). Constructive interference in steady state magnetic resonance imaging (n = 23) demonstrated at least one site of NVCC in all but one patient. Caloric testing disclosed a mild increase in vestibular deficit over time, and a hyperventilation-induced nystagmus was found in 70% of the tested patients (n = 23). The majority of patients were treated with carbamazepine (mean dose 568 mg/d) or oxcarbazepine (mean dose 870 mg/d). Treatment led to a significant reduction in the attack frequency to 10% of baseline (95% CI 6.69-14.96%), in attack intensity to 15% (95% CI 11.57-19.63%), and a reduction in attack duration to 11% (95% CI 6.72-17.40), after adjusting for time effects. CONCLUSION: 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.