Background: Natural history data are essential for trial design in Duchenne (DMD) and Becker muscular dystrophy (BMD), but recruitment for observational studies can be challenging. Objective: We reviewed reasons why patients or caregivers declined participation, and compared characteristics of participants and non-participants to assess possible selection bias in four observational studies, three on DMD and one on BMD. Methods: Three pediatric DMD studies focused on cross-sectional cognitive function and brain MRI (DMDbrain, n = 35 and DMDperfusion, n = 12), and on longitudinal upper extremity function and muscle MRI (DMDarm, n = 22). One adult BMD study assessed longitudinal functioning (n = 36). Considerations for non-participation were retrospectively reviewed from screening logs. Age, travel-time, DMD gene mutations and age at loss of ambulation (DMDarm and BMD study only), of participants and non-participants were derived from the Dutch Dystrophinopathy Database and compared using nonparametric tests (p < 0.05). Results: The perceived burden of the protocol (38.2%), use of MRI (30.4%), and travel-time to the study site (19.1%) were the most frequently reported considerations for non-participation. Only few patients reported lack of personal gain (0.0– 5.9%). Overall, participating patients were representative for the studied sub-populations, except for a younger age of DMDarm study participants and a complete lack of participants with a mutation beyond exon 63. Conclusion: Optimizing patient involvement in protocol design, improving MRI experiences, and integrating research into clinics are important factors to decrease burden and facilitate participation. Nationwide registries are essential to compare participants and non-participants and ensure representative observational research. Specific effort is needed to include patients with distal mutations in cognitive studies.
It may be difficult for clinicians to estimate the prognosis of pediatric acute transverse myelitis (ATM). The aim of this study was to define prognostic factors for relapsing disease and poor outcome in pediatric ATM.This prospective cohort study included 49 children, 18 boys and 31 girls (median age 13.1 years, IQR 6.5-16.2) with a first episode of ATM. Factors associated with relapsing disease and poor outcome (Expanded Disability Status Scale (EDSS) ≥ 4) were assessed during a median follow-up of 37 months (IQR 18-75).In total, 14 patients (29%) experienced ≥ 1 relapse(s) and nine patients (18%) had a poor outcome. Factors at onset associated with relapsing disease included higher age (16.1 vs. 11.6 years, p = 0.002), longer time to maximum severity of symptoms (5.5 vs. 3 days, p = 0.01), lower maximum EDSS score (4.0 vs. 6.5, p = 0.003), short lesion on spinal MRI (64 vs. 21%, p = 0.006), abnormalities on brain MRI (93 vs. 44%, p = 0.002) and presence of oligoclonal bands in cerebrospinal fluid (67 vs. 14%, p = 0.004). The only factor associated with poor outcome was presence of a spinal cord lesion on MRI without cervical involvement (56 vs. 14%, p = 0.02).Pediatric ATM patients presenting with clinical, radiological and laboratory features associated with multiple sclerosis (MS) are at risk for relapsing disease. In absence of these known MS risk factors at onset of disease these patients are at low risk for relapses. Only a minority of pediatric ATM patients in this cohort have a poor outcome.
Duchenne muscular dystrophy (DMD) is a progressive muscle disease. No curative therapy is currently available, but in recent decades standards of care have improved. These improvements include the use of corticosteroids and mechanical ventilation.To present a detailed population based report of the DMD disease course in The Netherlands (1980-2006) and evaluate the effect of changes in care by comparing it with an historical Dutch DMD cohort (1961-1974).Information about DMD patients was gathered through the Dutch Dystrophinopathy Database using a standardized questionnaire and information from treating physicians.The study population involved 336 DMD patients (70% of the estimated prevalence), of whom 285 were still alive. Mean age at disease milestones was: diagnosis 4.3 years, wheelchair dependence 9.7 years, scoliosis surgery 14 years, cardiomyopathy (fractional shortening <27%) 15 years, mechanical ventilation 17 years and death 19 years. Within our cohort, corticosteroid use was associated with an increased age of wheelchair dependence from 9.8 to 11.6 years (p < 0.001). When comparing the recent cohort to the historical cohort, mean survival improved from 17 to 27 years (p < 0.001).The current study gives detailed information about the disease course of DMD patients, provides evidence for the positive effect of steroid treatment and mechanical ventilation and supports the use of patient registries as a valuable resource for evaluating improvements in care.
N-glycosylation of the immunoglobulin Fc moiety influences its biological activity by, for example, modulating the interaction with Fc receptors. Changes in IgG glycosylation have been found to be associated with various inflammatory diseases. Here we evaluated for the first time IgG Fc N-glycosylation changes in well-defined antibody-mediated autoimmune diseases, that is, the neurological disorders Lambert-Eaton myasthenic syndrome and myasthenia gravis, with antibodies to muscle nicotinic acetylcholine receptors or muscle-specific kinase. IgGs were purified from serum or plasma by protein A affinity chromatography and digested with trypsin. Glycopeptides were purified and analyzed by MALDI-FTICR-MS. Glycoform distributions of both IgG1 and IgG2 were determined for 229 patients and 56 controls. We observed an overall age and sex dependency of IgG Fc N-glycosylation, which was in accordance with literature. All three disease groups showed lower levels of IgG2 galactosylation compared to controls. In addition, LEMS patients showed lower IgG1 galactosylation. Notably, the galactosylation differences were not paralleled by a difference in IgG sialylation. Moreover, the level of IgG core-fucosylation and bisecting N-acetylglucosamine were evaluated. The control and disease groups revealed similar levels of IgG Fc core-fucosylation. Interestingly, LEMS patients below 50 years showed elevated levels of bisecting N-acetylglucosamine on IgG1 and IgG2, demonstrating for the first time the link of changes in the level of bisecting N-acetylglucosamine with disease.
Some patients with myasthenia gravis (MG) have autoantibodies to muscle specific kinase (MuSK) instead of the acetylcholine receptor (AChR). Anti-AChR antibodies may be transferred across the placenta causing a self-limiting neonatal myasthenic syndrome. We describe an infant with a similar disorder whose mother had MuSK MG.
### Case report.
In September 1994, the mother noticed unilateral ptosis and a feeling of generalized fatigue at age 13. Over the next months, she developed severe oculobulbar weakness, dyspnea, and weakness of the neck. Symptoms were fluctuating and unresponsive to acetylcholinesterase inhibitors. No antibodies to the AChR were found. In 1995, a normal thymus was removed. High doses of prednisone had little effect. In 1997, plasmapheresis induced a partial remission and this became her regular therapy for several years. In 2004 anti-MuSK antibodies were found. She had two first trimester miscarriages while using pyridostigmine and prednisone in September and December 2004. In May 2005, she became pregnant using only prednisone 20 mg on alternating days. This pregnancy was uneventful without large fluctuations of her myasthenic symptoms.
In February 2006, at 38 + 1 week of gestation, she unaidedly delivered a boy in head position. Apgar score was 10 after 1 and 5 minutes. Birthweight was 3,190 g (P25). Physical examination was unremarkable. After 8 hours, however, drinking became difficult. After 16 hours, he showed mild generalized hypotonia with diminished facial expression …
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
