N-of-1 Trials in Neurology: A Systematic Review.

BACKGROUND AND OBJECTIVES: To perform a systematic review of published N-of-1 trials (e.g., single patient crossover trials) in neurologic disorders, including an assessment of methodologic quality and reporting. METHODS: We searched PubMed, MEDLINE, and Embase from inception date to the December 1, 2019, for reports on N-of-1 trials in neurologic disorders. Basic trial information on design, disease, intervention, analysis, and treatment success was extracted. Strengths and weaknesses of the N-of-1 trials were assessed with the Consolidated Standards of Reporting Trials extension for N-of-1 trials (CENT) 2015 criteria checklist and the Jadad score as measures of quality and reporting. RESULTS: We retrieved 40 reports of N-of-1 trials in neurologic disorders (19 individual N-of-1 trials, 21 series of N-of-1 trials). Most N-of-1 trials were performed in neuromuscular and neurodegenerative/movement disorders. Unlike the majority of trials that studied the main symptom(s) of a chronic stable condition, 9 N-of-1 trials studied a stable chronic symptom of a progressive or acute neurologic disorder. Besides pharmacologic interventions, electric stimulation protocols and nutritional products were studied. A mean total CENT score of 20.88 (SD 9.10, range 0-43) and mean total Jadad score of 2.90 (SD 2.15, range 0-5) were found as methodologic measures of quality and reporting across all N-of-1 trials. DISCUSSION: N-of-1 trials have been reported in numerous neurologic disorders, not only in chronic stable disorders, but also in progressive or acute disorders with a stable symptom. This indicates the emerging therapeutic area of N-of-1 trials in neurology. Methodologic quality and reporting of N-of-1 trials were found to be suboptimal and can easily be improved in future trials by appropriately describing the methods of blinding and randomization and following CENT guidelines. Because most N-of-1 trials remain unreported in medical literature, this systematic review probably represents only the tip of the iceberg of conducted N-of-1 trials in neurologic disorders. In addition to conventional trial designs, N-of-1 trials can help to bridge the gap between research and clinical care by providing an alternative, personalized level 1 evidence base for suitable treatments.

High incidence of falls in patients with myotonic dystrophy type 1 and 2: A prospective study.

We aimed to examine the incidence as well as the circumstances and the consequences of falling in adult patients with myotonic dystrophy type 1 and 2 (DM1/DM2). We performed a prospective cohort study in 209 subjects, of which 102 had DM1, 42 had DM2 and 65 healthy controls. An assessment of their falls was carried out during 100 consecutive days. In addition, falls during the previous year were reported. The primary outcome measure was the number of self-reported falls per participant during these 100 days. The secondary outcome measures included self-reported causes, circumstances and consequences of the falls. Mean (SD) falls per participant in 100 days was seven- to eightfold higher in patients with DM1 (0.74 (0.14)) and DM2 (0.62 (0.20)) compared to the controls (0.09 (0.04); p < 0.001)). Sixteen percent of DM1 and 17% of DM2 patients fell at least twice. Two-thirds of the falls occurred inside. Fifty percent of falls resulted in an injury, including a head trauma in four patients. Compared to non-fallers, those patients who fell were older (DM1/DM2), had a lower DM1-Activ score (DM1), had more muscle weakness (DM1), and reported less confidence in balance (DM1). This study demonstrates a high incidence and clinical relevance of falling in patients with DM1 and DM2. Fall prevention strategies in both DM1 and DM2 should focus on adaptations of the home environment and the patient's interaction in this environment.