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As part of a natural history study of giant axonal neuropathy, we hypothesized that the Friedreich Ataxia Rating Scale and the Gross Motor Function Measure would show a significant change over 6 months, reflecting subjects’ decline in motor function. The Friedreich Ataxia Rating Scale was performed on 11 subjects and the Gross Motor Function Measure was performed on 10 subjects twice with a six-month interval. A paired two-tailed t-test was used to assess the difference in each subject’s score. Significant changes were found over six months of 11.7 ± 11.0 (P = 0.006) for the Friedreich Ataxia Rating Scale and –10.0 ± 13.5 (P = 0.043) for the Gross Motor Function Measure, reflecting subjects’ decline in motor function on examination and by report. These standardized assessments of clinical function are the first to be validated in giant axonal neuropathy and will be used in an upcoming gene therapy clinical trial. [ABSTRACT FROM PUBLISHER]

Spinal muscular atrophy is an autosomal recessive neurodegenerative disease caused by homozygous mutation to the survival motor neuron 1 (SMN1) gene. Historically, spinal muscular atrophy has been considered to almost exclusively affect the function and survival of alpha motor neurons of the spinal cord and brainstem. With the development of animal models of spinal muscular atrophy, the presence of widespread systemic abnormalities affecting the brain, heart, and pancreas has been repeatedly noted among animals with diminished survival motor neuron protein expression. While these observations suggest similar possible effects in humans, reports of primary systemic disease manifestations among humans affected by spinal muscular atrophy are strikingly lacking. Here we report a case of a 29-year-old man with genetically confirmed spinal muscular atrophy type II who presented with new onset diabetes mellitus and diabetic ketoacidosis. [ABSTRACT FROM AUTHOR]

Weakness resulting from spinal muscular atrophy causes severe limitations in functional mobility. The early introduction of power mobility has potential to enhance development and mitigate disability. These outcomes are achieved by simulating normal skill acquisition and by promoting motor learning, visuospatial system development, self-exploration, cognition, and social development. There are few reports on early power mobility in spinal muscular atrophy, and it is typically not prescribed until school age. The authors evaluated 6 children under age 2 years with neuromuscular disease (5 spinal muscular atrophy, 1 congenital muscular dystrophy) for power mobility. Parents recorded the practice hours necessary to achieve independence using the Power Mobility Skills Checklist. Four children achieved independence in all items on the checklist by 7.9 months (range: 73-458 days). Introduction of early power mobility is feasible in spinal muscular atrophy patients under age 2 years and should be introduced in late infancy when children typically acquire locomotor skills. [ABSTRACT FROM AUTHOR]

Objectives: Spinal Muscular Atrophy (SMA) presents challenges in (i) monitoring disease activity and predicting progression, (ii) designing trials that allow rapid assessment of candidate therapies, and (iii) understanding molecular causes and consequences of the disease. Validated biomarkers of SMA motor and non-motor function would offer utility in addressing these challenges. Our objectives were (i) to discover additional markers from the Biomarkers for SMA (BforSMA) study using an immunoassay platform, and (ii) to validate the putative biomarkers in an independent cohort of SMA patients collected from a multi-site natural history study (NHS). Methods: BforSMA study plasma samples (N = 129) were analyzed by immunoassay to identify new analytes correlating to SMA motor function. These immunoassays included the strongest candidate biomarkers identified previously by chromatography. We selected 35 biomarkers to validate in an independent cohort SMA type 1, 2, and 3 samples (N = 158) from an SMA NHS. The putative biomarkers were tested for association to multiple motor scales and to pulmonary function, neurophysiology, strength, and quality of life measures. We implemented a Tobit model to predict SMA motor function scores. Results: 12 of the 35 putative SMA biomarkers were significantly associated (p<0.05) with motor function, with a 13th analyte being nearly significant. Several other analytes associated with non-motor SMA outcome measures. From these 35 biomarkers, 27 analytes were selected for inclusion in a commercial panel (SMA-MAP) for association with motor and other functional measures. Conclusions: Discovery and validation using independent cohorts yielded a set of SMA biomarkers significantly associated with motor function and other measures of SMA disease activity. A commercial SMA-MAP biomarker panel was generated for further testing in other SMA collections and interventional trials. Future work includes evaluating the panel in other neuromuscular diseases, for pharmacodynamic responsiveness to experimental SMA therapies, and for predicting functional changes over time in SMA patients. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy is a relatively stable chronic disease. Patients may gradually experience declines in muscle strength and motor function over time. However, functional progression is difficult to document, and the mechanism remains poorly understood. An 11-year-old girl was diagnosed at 19 months and took a few steps without assistance at 25 months. She was evaluated for 54 months in a prospective multicenter natural history study. Outcome measures were performed serially. From 6 to 7.5 years, motor function improved. From 7.5 to 11 years, motor function declined with increasing growth. Manual muscle testing scores minimally decreased. Motor unit number estimation studies gradually increased over 4.5 years. Compared to the published natural history of spinal muscular atrophy type III, our patient lost motor function over time. However, she walked with assistance 2 years longer than expected. Our report highlights possible precipitating factors that could affect the natural history of spinal muscular atrophy type III. [ABSTRACT FROM PUBLISHER]

Thigh muscle volume was assessed using magnetic resonance imaging in 16 subjects with spinal muscular atrophy. Scans were successful for 14 of 16 subjects (1 type 1, 6 type 2, and 7 type 3) as young as 5.7 years. Muscle volume with normal and abnormal signal was measured using blinded, semiautomated analysis of reconstructed data. Results were compared with segmental lean mass estimated by dual-energy X-ray absorptiometry and correlated with clinical and electrophysiological measures of disease severity. Muscle volume was reduced with abnormal signal quality. Test-retest reliability (r = .99) and correlation with dual-energy X-ray absorptiometry (r = .91) were excellent. Type 2 subjects had lower volume (3.5 ± 1.6 vs 6.3 ± 2.8 mL/cm height; P = .06) and higher percentage of muscle with abnormal signal (68% ± 20% vs 47% ± 27%; P = .14) than type 3. Reproducibility, tolerability, and strong correlation with clinical measures make magnetic resonance imaging a candidate biomarker for clinical research. [ABSTRACT FROM AUTHOR]