Observational study of spinal muscular atrophy type 2 and 3: functional outcomes over 1 year.

OBJECTIVE: To characterize the short-term course of spinal muscular atrophy (SMA) in a genetically and clinically well-defined cohort of patients with SMA. DESIGN: A comprehensive multicenter, longitudinal, observational study. SETTING: The Pediatric Neuromuscular Clinical Research Network for SMA, a consortium of clinical investigators at 3 clinical sites. PARTICIPANTS: Sixty-five participants with SMA types 2 and 3, aged 20 months to 45 years, were prospectively evaluated. INTERVENTION: We collected demographic and medical history information and determined the SMN 2 copy number. MAIN OUTCOME MEASURES: Clinical outcomes included measures of motor function (Gross Motor Function Measure and expanded Hammersmith Functional Motor Scale), pulmonary function (forced vital capacity), and muscle strength (myometry). Participants were evaluated every 2 months for the initial 6 months and every 3 months for the subsequent 6 months. We evaluated change over 12 months for all clinical outcomes and examined potential correlates of change over time including age, sex, SMA type, ambulatory status, SMN2 copy number, medication use, and baseline function. RESULTS: There were no significant changes over 12 months in motor function, pulmonary function, and muscle strength measures. There was evidence of motor function gain in ambulatory patients, especially in those children younger than 5 years. Scoliosis surgery during the observation period led to a subsequent decline in motor function. CONCLUSIONS: Our results confirm previous clinical reports suggesting that SMA types 2 and 3 represent chronic phenotypes that have relatively stable clinical courses. We did not detect any measurable clinical disease progression in SMA types 2 and 3 over 12 months, suggesting that clinical trials will have to be designed to measure improvement rather than stabilization of disease progression.

The authorship lottery: an impediment to research collaboration?

Authorship of scientific publications holds great importance for basic and clinical researchers. Academic appointments and promotions, grant funding, and salary support depend to some extent on published recognition through authorship. Peer-recognition and personal satisfaction are additional incentives for authorship. Some current "rules" and conventions for assigning authorship are based on largely unwritten but widely-accepted arbitrary decisions. We hypothesize that the inherent uncertainties about assigning "credit where credit is due" serve as a disincentive for clinicians considering an academic career and may discourage or at least impede the collaborations essential to address most translational and clinical research issues. Surveys of the New England Journal of Medicine and the Annals of Neurology suggest that neurologists have been slow to adopt ways of sharing "credit" appropriately. We recommend that authorship of reports of the primary results of multicenter or multidisciplinary studies should be in the name of the group of investigators collaborating on the work. Given the availability of digital methods that could apportion credit quantitatively, academic leaders, including funding agencies and promotions committees, should consider challenging outmoded authorship conventions. Authorship is too important to be left to chance.

An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients.

PURPOSE: To develop and evaluate an expanded version of the Hammersmith Functional Motor Scale allowing for evaluation of ambulatory SMA patients. PROCEDURES: Thirty-eight patients with SMA type II or III were evaluated using the Gross Motor Function Measure and the Hammersmith Functional Motor Scale. Based on statistical and clinical criteria, we selected 13 Gross Motor Function Measure items to develop an expanded HFMS. The expanded Hammersmith Functional Motor Scale was validated by comparison with the Gross Motor Function Measure minus the 13 items (GMFM-75) and an assessment of clinical function. The reliability of the expanded Hammersmith Functional Motor Scale in 36 patients was established. FINDINGS: The expanded Hammersmith Functional Motor Scale was highly correlated with the GMFM-75 and the clinical function assessment (p=0.97, and p=0.90). The expanded Hammersmith Functional Motor Scale showed excellent test-retest reliability (International Coordinating Committee = 0.99). CONCLUSIONS: The expanded Hammersmith Functional Motor Scale allows assessment of high functioning SMA type II and III patients. Ease of administration and correlation with established motor function measures justify use in future SMA clinical trials.