Dataset Information

Prospective cohort study of spinal muscular atrophy types 2 and 3.

ABSTRACT:

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 fat-free 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

The intermediate and mild phenotypes of SMA show slow functional declines when observation periods exceed 1 year. Whole body muscle mass, hand muscle compound motor action potentials, and muscle strength are associated with clinical measures of motor function. The data from this study will be useful for clinical trial planning and suggest that CMAP and DXA warrant further evaluation as potential biomarkers.

SUBMITTER: Kaufmann P

PROVIDER: S-EPMC3525313 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Publications

Prospective cohort study of spinal muscular atrophy types 2 and 3.

Kaufmann Petra P McDermott Michael P MP Darras Basil T BT Finkel Richard S RS Sproule Douglas M DM Kang Peter B PB Oskoui Maryam M Constantinescu Andrei A Gooch Clifton L CL Foley A Reghan AR Yang Michele L ML Tawil Rabi R Chung Wendy K WK Martens William B WB Montes Jacqueline J Battista Vanessa V O'Hagen Jessica J Dunaway Sally S Flickinger Jean J Quigley Janet J Riley Susan S Glanzman Allan M AM Benton Maryjane M Ryan Patricia A PA Punyanitya Mark M Montgomery Megan J MJ Marra Jonathan J Koo Benjamin B De Vivo Darryl C DC

Neurology 20121017 18

<h4>Objective</h4>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.<h4>Methods</h4>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, ...[more]

PMID: 23077013

Similar Datasets

Project description:BackgroundRespiratory complications are the most important cause of morbidity and mortality in spinal muscular atrophy (SMA). Respiratory muscle weakness results in impaired cough, recurrent respiratory tract infections and eventually can cause respiratory failure. We assessed longitudinal patterns of respiratory muscle strength in a national cohort of treatment-naïve children and adults with SMA, hypothesizing a continued decline throughout life.MethodsWe measured maximal expiratory and inspiratory pressure (PEmax and PImax), Sniff Nasal inspiratory pressure (SNIP), peak expiratory flow (PEF), and peak cough flow (PCF) in treatment-naïve patients with SMA. We used mixed-models to analyze natural history patterns.ResultsWe included 2172 measurements of respiratory muscle function from 80 treatment-naïve patients with SMA types 1c-3b. All outcomes were lower in the more severe phenotypes. Significant differences in PEF were present between SMA types from early ages onwards. PEF decline was linear (1-2%/year). PEF reached values below 80% during early childhood in types 1c-2, and during adolescence in type 3a. PEmax and PImax were severely lowered in most patients throughout life, with PEmax values abnormally low (i.e. < 80 cmH2O) in virtually all patients. The PEmax/PImax ratio was < 1 throughout life in all SMA types, indicating that expiratory muscles were most affected. All but SMA type 3b patients had a lowered PCF. Patients with types 2b and 3a had PCF levels between 160 and 270 L/min, those with type 2a around 160 L/min and patients with type 1c well below 160 L/min. Finally, SNIP was low in nearly all patients, most pronounced in more severely affected patients.ConclusionsThere are clear differences in respiratory muscle strength and its progressive decline between SMA types. We observed lower outcomes in more severe SMA types. Particularly PEF may be a suitable outcome measure for the follow-up of respiratory strength in patients with SMA. PEF declines in a rather linear pattern in all SMA types, with clear differences at baseline. These natural history data may serve as a reference for longer-term treatment efficacy assessments.

Dataset Information

Prospective cohort study of spinal muscular atrophy types 2 and 3.

Objective

Methods

Results

Conclusion

Publications

Prospective cohort study of spinal muscular atrophy types 2 and 3.

Similar Datasets

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