Hip Displacement in Spinal Muscular Atrophy: The Influences of Genetic Severity, Functional Level, and Disease-modifying Treatments.

PURPOSE: Hip displacement (HD) is common in spinal muscular atrophy (SMA), but neither genetic severity nor gross motor function level have been investigated as risk factors. Although disease-modifying agents (DMA) have improved function and overall health, their effects on the prevention of HD are unknown. The purpose of this study was to determine risk factors for HD development in SMA. METHODS: Retrospective cohort. Children with SMA presenting between January 2005 and August 2021, at least 1 hip radiograph, and a minimum 2-year follow-up were included. The primary outcome measure was the prevalence of HD (migration percentage ≥40%). Secondary outcomes included SMA type (I/II/III), survival motor neuron 2 copy number, Hammersmith Functional Motor Scale (HFMS, out of 66), ambulatory status (Functional Mobility Scale at 50 m), clinically relevant scoliosis (>40 degrees and/or surgery), and DMA treatment (>1-year duration, nusinersen/risdiplam/onasemnogene abeparvovec) as risk factors. Univariate and multivariate logistic regression analyses were performed. RESULTS: Eighty-two patients (52% female) with SMA type I (n=32, 39%), II (n=36, 44%), and III (n=14, 17%) met the inclusion criteria, with a final follow-up of 4.5 (SD: 2.7) years. Age at first hip radiograph was 3.4 (SD: 2.9) years. The prevalence of HD was 75.6%, with a mean age of onset of 4.6 (SD: 2.7) years. When stratified by SMA type, the prevalence/age of onset (mean, years) was 84%/3.1 (SD: 1.7), 80%/5.8 (SD: 2.3), and 36%/9.0 (SD: 4.3), respectively. HFMS score >23 was protective against HD by receiver operating characteristic analysis ( P =0.008). Significant risk factors by univariate analysis were SMA type I ( P =0.002) and II ( P =0.002), HFMS ≤23 ( P =0.01), nonambulatory status (Functional Mobility Scale at 50 m = 1, P =0.001), clinically relevant scoliosis ( P =0.01), and DMA treatment ( P =0.01). By multivariate analysis, only SMA type II ( P =0.04) and scoliosis ( P =0.04) were independent risk factors. CONCLUSIONS: The prevalence of HD in SMA is highly linked to disease severity. Identified risk factors can be used in the development of surveillance programs for early detection of HD in SMA, allowing for timely management. LEVEL OF EVIDENCE: Level III.

A Mixed-Method Study Exploring Patient-Experienced and Caregiver-Reported Benefits and Side Effects of Corticosteroid Use in Duchenne Muscular Dystrophy.

BACKGROUND: Corticosteroids are recommended to all people with Duchenne as standard of care; patient experience data is important to guide corticosteroid decision making and as a comparator for new treatment options. OBJECTIVE: This study assesses patient and caregiver-reported benefits and side effects from corticosteroids to treat Duchenne muscular dystrophy, their importance, and satisfaction. METHODS: Using one-on-one interviews (n = 28) and an online survey (n = 236), parents and adults with Duchenne reported corticosteroid benefits and side effects rated as both experienced and important. RESULTS: Benefits to breathing, heart function, arm strength, slowing progression of weakness, and getting around were rated as particularly important, regardless of ambulatory status. Important side effects included increased fracture risk, unwanted weight gain, and diabetes/prediabetes. Parents rated behavior issues and adults rated delayed puberty as having high importance. Being ambulatory was independently associated with reporting more net benefit (p = 0.02). For side effects, parent scores were significantly higher than adult score (p = 0.02). Corticosteroid type was not significant. Participants were, overall, satisfied with corticosteroids (means ranging from 6.2 to 7.7 on a scale of 0-10), with no significant differences based on corticosteroid type. CONCLUSIONS: Overall, most participants were satisfied with the use of corticosteroids. While a range of side effects were rated as important and relatively common, individuals using corticosteroids and their caregivers indicate that benefits outweigh the side effects. Qualitative data indicate that high acceptability is influenced by lack of treatment alternatives. Patient experience data on use of corticosteroids in Duchenne may be relevant to drug development, regulatory assessment of new treatments, and to families making decisions about corticosteroid use.

Critical Airway Stenosis in an Adolescent Male With Pompe Disease and Thoracic Lordosis: A Case Report.

An adolescent male with late-onset Pompe disease (glycogen storage disease type II) presented with a history of restrictive airway disease and a near-cardiorespiratory arrest during anesthesia for a liver biopsy initially thought to be due to bronchospasm. During a subsequent posterior spinal fusion procedure, he suffered cardiorespiratory arrest resulting in the procedure being aborted. Bronchoscopy performed shortly after resuscitation revealed an undiagnosed narrowing of the distal trachea and bronchi. This is the first description of a patient with late-onset Pompe disease with undiagnosed critical tracheal stenosis due to the progression of thoracic lordosis, which was ultimately relieved by posterior spinal fusion.

Design and testing of a functional arm orthosis in patients with neuromuscular diseases.

The objective of this study was to determine the utility of a passive gravity-balanced arm orthosis, the Wilmington robotic exoskeleton (WREX), for patients with neuromuscular diseases. The WREX, a four-degrees-of-freedom functional orthosis, is energized by rubber bands to eliminate gravity and is attached to the wheelchair. The development and clinical testing of WREX is described in this report. Seventeen patients (14 boys and 3 girls) with muscular disabilities participated in the study. Ages ranged from 4 to 20 years. Criteria for inclusion included a weakened arm, use of a wheelchair, the ability to grasp and release objects, and the ability to provide feedback on device use. Testing consisted of administering the Jebsen test of hand function without WREX and then testing again after approximately two weeks of wearing the WREX orthosis. The timed results of each task within the test then were compared. Specific tasks related to vertical movement required less time to perform with the WREX. A large number of subjects were able to perform the Jebsen tasks with the WREX, where they were unable to perform the task without the WREX. Patients can benefit from WREX because it increases their performance in daily living activities and makes many tasks possible. The range-of-motion in the patients' arms increased considerably, while the time required to complete some of the Jebsen test tasks decreased. Most patients were very receptive to WREX, although a few were ambivalent.

T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy.

OBJECTIVE: To determine the clinical consequences of the PMP22 point mutation, T118M, which has been previously considered to either cause an autosomal recessive form of Charcot-Marie-Tooth (CMT) disease or be a benign polymorphism. METHODS: We analyzed patients from five separate kindreds and characterized their peripheral nerve function by clinical and electrophysiological methods. RESULTS: All heterozygous patients had clinical and/or electrophysiological features of a neuropathy similar to hereditary neuropathy with liability to pressure palsies (HNPPs). The homozygous patient had a severe axonal neuropathy without features of demyelination. INTERPRETATION: These findings suggest that T118M PMP22 retains some normal PMP22 activity, allowing the formation of compact myelin and normal nerve conduction velocities in the homozygous state. Taken together, these findings suggest that T118M is a pathogenic mutation causing a dominantly inherited form of CMT by a partial loss of PMP22 function.