Andrew J. Skalsky

Prevention and Management of Limb Contractures in Neuromuscular Diseases

Limb contractures are a common impairment in neuromuscular diseases. They contribute to increased disability from decreased motor performance, mobility limitations, reduced functional range of motion, loss of function for activities of daily living, and increased pain. The pathogenesis of contractures is multifactorial. Myopathic conditions are associated with more severe limb contractures compared with neuropathic disorders. Although the evidence supporting the efficacy of multiple interventions to improve range of motion in neuromuscular diseases in a sustained manner is lacking, there are generally accepted principles with regard to splinting, bracing, stretching, and surgery that help minimize the impact or disability from contractures.

The natural history of cardiac and pulmonary function decline in patients with duchenne muscular dystrophy

Study Design. Retrospective review of scoliosis progression, pulmonary and cardiac function in a series of patients with Duchenne Muscular Dystrophy (DMD). Objective. To determine whether operative treatment of scoliosis decreases the rate of pulmonary function loss in patients with DMD. Summary of Background Data. It is generally accepted that surgical intervention should be undertaken in DMD scoliosis once curve sizes reach 35° to allow intervention before critical respiratory decline has occurred. There are conflicting reports, however, regarding the effect of scoliosis stabilization on the rate of pulmonary function decline when compared to nonoperative cohorts. Methods. We reviewed spinal radiographs, echocardiograms, and spirometry, hospital, and operative records of all patients seen at our tertiary referral center from July 1, 1992 to June 1, 2007. Data were recorded to Microsoft Excel (Microsoft, Redmond, WA) and analyzed with SAS (SAS Institute, Cary, NC) and R statistical processing software (www.r-project.org). Results. The percent predicted forced vital capacity (PPFVC) decreased 5% per year before operation. The mean PPFVC was 54% (SD = 21%) before operation with a mean postoperative PPFVC of 43% (SD = 14%). Surgical treatment was associated with a 12% decline in PPFVC independent of other treatment variables. PPFVC after operation declined at a rate of 1% per year and while this rate was lower, it was not significantly different than the rate of decline present before operation (P = 0.18). Cardiac function as measured by left ventricular fractional shortening declined at a rate of 1% per year with most individuals exhibiting a left ventricular fractional shortening rate of more than 30 before operation. Conclusion. Operative treatment of scoliosis in DMD using the Luque Galveston method was associated with a reduction of forced vital capacity related to operation. The rate of pulmonary function decline after operation was not significantly reduced when compared with the rate of preoperative forced vital capacity decline.

Assessment of regional body composition with dual-energy X-ray absorptiometry in Duchenne muscular dystrophy: correlation of regional lean mass and quantitative strength.

The purpose of this study was to assess regional body composition and its correlation with regional strength in Duchenne muscular dystrophy (DMD) subjects and able‐bodied controls. Regional dual‐energy X‐ray absorptiometry (DEXA) measurements and isometric strength were obtained for 23 DMD subjects and 23 control subjects. DMD subjects showed a decreased regional lean mass (P < 0.001). The correlation between regional strength and regional lean mass was stronger for controls than for DMD subjects. DMD subjects had decreased regional lean mass, increased regional fat mass, and decreased strength. Muscle Nerve 39: 647–651, 2009

A population-based study of dystrophin mutations in Canada.

INTRODUCTION We carried out a population-based study of dystrophin mutations in patients followed by members of the Canadian Paediatric Neuromuscular Group (CPNG) over a ten-year period. OBJECTIVES We aimed to describe the changes in diagnostic testing for dystrophinopathy and to determine the frequency of dystrophin mutations from 2000 to 2009. METHODS De-identified data containing the clinical phenotypes, diagnostic methods, and mutational reports from dystrophinopathy patients followed by CPNG centres from January 2000 to December 2009 were analyzed using descriptive statistics. RESULTS 773 patients had a confirmed diagnosis of dystrophinopathy based on genetic testing (97%), muscle biopsy (2%), or family history (1%). 573 (74%) had complete deletion/duplication analysis of all 79 exons or whole gene sequencing, resulting in 366 (64%) deletions, 64 (11%) duplications, and 143 (25%) point mutations. The percentage of patients who were diagnosed using currently accepted genetic testing methods varied across Canada, with a mean of 63% (SD 23). 246 (43%) mutations involved exons 45 to 53. The top ten deletions (n=147, 26%) were exons 45-47, 45-48, 45, 45-50, 45-55, 51, 45-49, 45-52, 49-50, and 46-47. 169 (29%) mutations involved exons 2 to 20. The most common duplications (n=29, 5.1%) were exons 2, 2-7, 2-17, 3-7, 8-11, 10, 10-11, and 12. CONCLUSION This is the most comprehensive report of dystrophin mutations in Canada. Consensus guidelines regarding the diagnostic approach to dystrophinopathy will hopefully reduce the geographical variation in mutation detection rates in the coming decade.

The relationship between regional body composition and quantitative strength in facioscapulohumeral muscular dystrophy (FSHD)

This study determines in facioscapulohumeral muscular dystrophy (FSHD) and able-bodied controls (1) the regional body composition and (2) the correlation between regional lean tissue mass and the corresponding regional strength. This is a cross-sectional, criterion standard, case-control study at a university based neuromuscular disease clinic. A dual-energy X-ray absorptiometry (DEXA) scanner was used to obtain regional body composition measurements in 14 FSHD and anthropometrically matched control pairs. A dynamometer determined peak isometric strength for the elbow and knee. Compared to controls, FSHD subjects showed increased regional fat tissue mass (p < 0.001-0.017), decreased regional lean tissue mass (p < 0.001-0.010), and decreased strength (p < 0.001-0.020). There was a correlation between quantitative strength and lean tissue mass for both FSHD and controls (r = 0.791-0.906; p < 0.001). FSHD subjects have higher regional fat tissue mass and lower regional lean tissue mass despite similar BMI and anthropometrics. Regional lean tissue mass correlates with strength.

Shunted Hydrocephalus Has a Significant Impact on Quality of Life in Children With Spina Bifida

To determine which clinical (health status) and nonclinical (demographic) factors may affect perceptions of quality of life in children with spina bifida and their parents.

Regional and Whole-Body Dual-Energy X-Ray Absorptiometry to Guide Treatment and Monitor Disease Progression in Neuromuscular Disease

Dual-energy x-ray absorptiometry (DEXA) is a safe, noninvasive, inexpensive tool for managing patients with neuromuscular diseases. Regional and whole-body DEXA can be used to guide clinical treatments, such as determining body composition to guide nutritional recommendations, as well as to monitor disease progression by assessing regional and whole-body lean tissue mass. DEXA can also be used as an outcome measure for clinical trials.

Evaluation of Phrenic Nerve and Diaphragm Function with Peripheral Nerve Stimulation and M-Mode Ultrasonography in Potential Pediatric Phrenic Nerve or Diaphragm Pacing Candidates

Assessing phrenic nerve function in the setting of diaphragmatic paralysis in diaphragm pacing candidates can be challenging. Traditional imaging modalities and electrodiagnostic evaluations are technically difficult. Either modality alone is not a direct measure of the function of the phrenic nerve and diaphragm unit. In this article, the authors present their method for evaluating phrenic nerve function and the resulting diaphragm function. Stimulating the phrenic nerve with transcutaneous stimulation and directly observing the resulting movement of the hemidiaphragm with M-mode ultrasonography provides quantitative data for predicting the success of advancing technologies such as phrenic nerve pacing and diaphragm pacing.

An instrumented glove for improving spasticity assessment

An instrumented glove worn by caregivers that can augment subjective assessments of spasticity with an objective, repeatable metric with reduced inter- and intra-rater variability and improved resolution over existing standards is highly desirable. We present the design and preliminary results of such a system using commercial, off the shelf (COTS) components. The glove includes spatially-resolved, force-dependent resistive sensor elements and an inertial measurement unit. We developed a mock patient that is equipped with a mechanism to adjust the arm stiffness, a load-cell and a potentiometer to measure the work done to move the arm. The mock patient provides ground truth to validate the proposed concept. We report the power measured by the sensors in the mock patient to move the arm and the power estimated by the glove in moving the arm and show Pearson correlation coefficient of 0.64. We observe that raw sensor data and instrumentation errors contributed to significant outliers in these experiments. Initial assessments by clinician show promise of the proposed approach to improve spasticity assessment. Future work includes improvements to instrumentation and further clinical evaluations.

Common Complications of Pediatric Neuromuscular Disorders

Children with pediatric neuromuscular disorders experience common complications, primarily due to immobility and weakness. Musculoskeletal complications include hip dysplasia with associated hip subluxation or dislocation, neuromuscular scoliosis, and osteoporosis and resulting fractures. Constipation, gastroesophageal reflux, and obesity and malnutrition are commonly experienced gastrointestinal complications. Disordered sleep also is frequently observed, which affects both patients and caregivers.