Objectives:
The aim of this study was to assess the Dutch nationwide incidence of myelin oligodendrocyte glycoprotein (MOG)-IgG-associated acquired demyelinating syndromes (ADS) and to describe the ...clinical and serological characteristics of these patients.
Methods:
All serum samples for routine diagnostics from February 2014 to December 2017 were sent to the single central reference laboratory for the full-length MOG-IgG cell-based assay (CBA) in the Netherlands. Clinical data from patients known in our National ADS centre were available.
Results:
A total of 1414 samples of 1277 patients were received; of these, 92 patients (7%) were MOG-IgG-seropositive. The mean incidence was 0.16/100,000 people, with higher seropositivity in children (0.31/100,000) than in adults (0.13/100,000). In MOG-IgG-positive patients at the National ADS centre (61/92, 66%), the most common presenting phenotype is acute disseminated encephalomyelitis (ADEM, 56%) in children and optic neuritis (ON, 44%) in adults. Relapsing disease occurred in 9/34 (26%) children and 11/27 (41%) adults during median follow-up of 27.5 months. Patients were tested MOG-IgG-positive >200 months after the initial attack, suggesting an extended time to first relapse (TTFR). Longitudinal analysis of MOG-IgG (25/61, 41%) showed that 67% of the monophasic patients remain seropositive and 60% in relapsing patients. Majority of seronegative patients had no relapses (89%).
Conclusion:
This nationwide study shows that the overall incidence of MOG-IgG-seropositive disorders is 0.16 per 100,000 people. The distribution over the clinical phenotypes differs between adults and children. Seropositivity can be maintained over years even without clinical activity, while seronegative patients generally had no relapses.
Muscle hypertrophy and muscle weakness are well known in Duchenne muscular dystrophy. Decreased muscle force can have secondary effects on skeletal growth and development such as facial and dental ...morphology changes. In this study, we quantified temporal muscle thickness, circumference, and eccentricity of the skull and the head on T1-weighted magnetic resonance imaging (MRI) scans of the head of 15 Duchenne muscular dystrophy patients and 15 controls. Average temporal muscle thickness was significantly increased in patients (12.9 ± 5.2 mm) compared to controls (6.8 ± 1.4 mm) (P < .0001), whereas the shape of the skull was significantly rounder compared to controls. Temporal muscle thickness and skull eccentricity were significantly negatively correlated in patients, and positively in controls. Hypertrophy of the temporal muscles and changes in skull eccentricity appear to occur early in the course of Duchenne muscular dystrophy. Further studies in younger patients are needed to confirm a causal relationship.
Learning and behavioral problems are common in Duchenne muscular dystrophy (DMD) patients. In normal brain, various dystrophin isoforms are expressed, but little is known about their function. ...Cortical atrophy and disordered architecture have been reported in post mortem and CT scan studies. Since MRI is currently the most advanced technique to provide detailed morphological information of the brain, we performed structural MRI in 35 boys with DMD and 22 healthy age-matched controls (age 8–18 years). Three-dimensional T1-weighted scans were obtained for quantitative volume measurements. Diffusion tensor images (DTI) were obtained as a measure of structural integrity of the white matter. Localization of volumetric differences was assessed with voxel-based morphometry analysis. A cognitive profile of the boys was evaluated and found to be representative of the Dutch DMD population. Total brain volume was significantly smaller in DMD both before and after correcting for intracranial volume. Grey matter volume was also smaller in DMD and we found no focal differences in grey matter, suggesting an overall deficiency in neuronal cell bodies. The white matter volume in DMD was similar to controls. Throughout the white matter tracts, DTI showed lower fractional anisotropy (FA) in DMD indicating lower directionality of the neuronal fiber tracts. DTI also showed higher mean diffusivity (MD) in DMD. Lower FA and higher MD indicate reduced fiber density, increased membrane permeability and/or increased structural disorganization. These correspond with altered white matter integrity. In summary, our findings show that both the grey matter and white matter are affected in DMD, with a reduction in volume in the grey matter and altered integrity of the white matter. Future analyses will correlate these morphological abnormalities to cognitive function and behavioral problems.
Abstract Hypertrophy is an adaptive response of muscle. This is a well-known phenomenon of the calve muscles in Duchenne muscular dystrophy (DMD), but less well studied in other dystrophic muscles. ...In DMD chewing and biting are important motor skills that can be affected by the disease. Decreased bite force can be observed in patients from the age of eight years on. Imbalance of muscle strength influences growth and development in the orofacial region and resulting in anatomical variations, like dental malocclusion. In an ongoing MRI study on brain morphology in boys with DMD we observed marked hypertrophy of the temporal muscles. This prompted us to study these muscles in more detail and to investigate the consequences for skull morphology. MR images of 15 boys with DMD (age 12.4 ± 2.7 y) and 15 healthy age-matched boys (age 12.4 ± 1.7 y) were compared. Regions of interest of the head, skull and temporal muscles were manually drawn on transversal T1w images and averaged for 10 slices. Analysis on temporal muscle size, head size and eccentricity (roundness) of the skull was performed. All DMD boys had temporal muscle hypertrophy. The cross-sectional size of the temporal muscles was significantly larger in DMD ( p < 0.0001) compared with controls, with on averaging doubling in size. The head circumference was not different between the two groups. There was a significantly different eccentricity of the skull between DMD and healthy boys ( p = 0.03). The differences in skull morphology in DMD appeared to be more prominent in older boys. Muscle hypertrophy in DMD is not restricted to larger skeletal muscles. Hypertrophy of the temporal muscles and possibly of other orofacial muscles indicates early involvement of these muscles in DMD and probably contributes to the changes in skull morphology.
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