Douglas Michael Sproule

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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(More)
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(More)
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.(More)
Body composition is sparsely described in spinal muscular atrophy (SMA). Body (BMI, mass/height in m(2)), fat-free (FFMI, lean mass/height in m(2)) and fat (FMI, fat mass/height in m(2)) mass indexes were estimated in 25 children (aged 5-18) with SMA (2 type I, 13 type II, 10 type III) using dual-energy radiograph absorptiometry and anthropometric data(More)
RATIONALE the diagnosis of non-epileptic spells (NES) in children can be challenging, even for experienced clinicians. Our objective was to describe the characteristics of such events. METHODS this was a retrospective study conducted from January 2004 to December 2006. Inclusion criteria were age >1 month and <18 years and the diagnosis of NES established(More)
OBJECTIVE To describe the natural history of clinical and laboratory features associated with the m.3243A>G mitochondrial DNA point mutation. Natural history data are needed to obtain prognostic information and for clinical trial planning. METHODS We included 85 matrilineal relatives from 35 families with at least 2 visits in this prospective cohort(More)
BACKGROUND Tissues with high energy demands, such as the heart, are susceptible to the effects of mitochondrial DNA point mutations. OBJECTIVE To investigate the frequency of Wolff-Parkinson-White (WPW) syndrome among a phenotypically and genotypically homogeneous cohort of patients with MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike(More)
Spinal muscular atrophy (SMA), a potentially devastating disease marked by progressive weakness and muscle atrophy resulting from the dysfunction and loss of motor neurons of the spinal cord, has emerged in recent years as an attractive target for therapeutic intervention. Caused by a homozygous mutation to the Survival of Motor Neurons 1 (SMN1) gene on(More)
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(More)
The relationship between body composition and function in spinal muscular atrophy (SMA) is poorly understood. 53 subjects with SMA were stratified by type and Hammersmith functional motor scale, expanded score into three cohorts: low-functioning non-ambulatory (type 2 with Hammersmith score < 12, n=19), high-functioning non-ambulatory (type 2 with(More)