Objectives: Prospective cohort study to characterize the clinical features and course of spinal muscular atrophy type I (SMA-I).Methods: Patients were enrolled at 3 study sites and followed for up to 36 months with serial clinical, motor function, laboratory, and electrophysiologic outcome assessments. Intervention was determined by published standard of care guidelines. Palliative care options were offered.

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Objective: To characterize the natural history of spinal muscular atrophy type 2 and type 3 (SMA 2/3) beyond 1 year and to report data on clinical and biological outcomes for use in trial planning. Methods:We conducted a prospective observational cohort study of 79 children and young adults with SMA 2/3 who participated in evaluations for up to 48 months. Clinically, we evaluated motor and pulmonary function, quality of life, and muscle strength. We also measured SMN2 copy number, hematologic and biochemical profiles, muscle mass by dual x-ray absorptiometry (DXA), and the compound motor action potential (CMAP) in a hand muscle. Data were analyzed for associations between clinical and biological/laboratory characteristics cross-sectionally, and for change over time in outcomes using all available data. Results:In cross-sectional analyses, certain biological measures (specifically, CMAP, DXA fatfree mass index, and SMN2 copy number) and muscle strength measures were associated with motor function. Motor and pulmonary function declined over time, particularly at time points beyond 12 months of follow-up. Conclusion:

Objective: To determine the most critical symptoms in a national myotonic dystrophy type 1 (DM1) population and to identify the modifying factors that have the greatest effect on the severity of these symptoms. Methods:We performed a cross-sectional study of 278 adult patients with DM1 from the national registry of patients with DM1 between April and August 2010. We assessed the prevalence and relative significance of 221 critical DM1 symptoms and 14 disease themes. These symptoms and themes were chosen for evaluation based on prior interviews with patients with DM1. Responses were categorized by age, CTG repeat length, gender, and duration of symptoms.Results: Participants with DM1 provided symptom rating survey responses to address the relative frequency and importance of each DM1 symptom. The symptomatic themes with the highest prevalence in DM1 were problems with hands or arms (93.5%), fatigue (90.8%), myotonia (90.3%), and impaired sleep or daytime sleepiness (87.9%). Participants identified fatigue and limitations in mobility as the symptomatic themes that have the greatest effect on their lives. We found an association between age and the average prevalence of all themes (p Ͻ 0.01) and between CTG repeat length and the average effect of all symptomatic themes on participant lives (p Ͻ 0.01). Conclusions:There are a wide range of symptoms that significantly affect the lives of patients with DM1. These symptoms, some previously underrecognized, have varying levels of importance in the DM1 population and are nonlinearly dependent on patient age and CTG repeat length. Neurology Myotonic dystrophy type 1 (DM1) is a multisystem disorder caused by an unstable trinucleotide repeat expansion on chromosome 19q13.3 in the DMPK gene.1-3 The core features of DM1 are myotonia, weakness, and early-onset cataracts (Ͻ50 years of age). Along with these core features, patients commonly report symptoms related to cognition, gastrointestinal function, sleep, fatigue, mood, ability to swallow, vision, social relations, and physical function. 4 The effect of each symptom on health-related quality of life is unknown. Furthermore, given the multisystem manifestations of DM1, we hypothesize that there are additional underrecognized symptoms that are important to patients and have a critical effect on their health status.

The Six-Minute Walk Test (6MWT) can be safely performed in ambulatory patients with spinal muscular atrophy (SMA), correlates with established outcome measures, and is sensitive to fatigue-related changes. The 6MWT is a promising candidate outcome measure for clinical trials in ambulatory subjects with SMA.