Distal myopathy with rimmed vacuoles (DMRV) is a major entity of distal myopathy. It is an autosomal recessive disorder and is due to mutations in the GNE gene that regulates the synthesis of sialic ...acid. Although reported predominantly from Japan, cases have been reported from other parts of the world. We report the first genetically proven case of DMRV from India in a 23-year-old male with gradual onset, progressive distal weakness of both lower limbs with features of inflammation in muscle biopsy.
To study the histological features on muscle biopsy and correlate them with clinical features, other laboratory data in adult patients to make a diagnosis of dermatomyositis (DM), applying the ...European Neuromuscular center (ENMC) criteria.
Adult patients who fulfilled clinical, laboratory, and muscle biopsy findings according to ENMC criteria for DM during the period 2010-2013 were included in the study. Cryostat sections of muscle biopsy were reviewed with emphasis on Perifascicular atrophy (PFA), perivascular/endomysial inflammation. Muscular dystrophies and metabolic myopathies were excluded by appropriate immunohistochemistry and special stains.
The diagnosis of adult DM was made in 45 patients out of 170 clinically suspected idiopathic inflammatory myopathies. These included 33 definite, 4 probable, 7 possible sine dermatitis, and 1 amyopathic DM. All patients with definite DM had typical rash and proximal muscle weakness and muscle biopsy showed PFA with or without inflammation. Thirteen patients had quadriparesis, neck muscle weakness, dysphagia/dysphonia at presentation. Patients with probable DM had rash and showed perivascular/endomysial inflammation with no PFA. Possible DM sine dermatitis showed PFA with perivascular/endomysial infiltrates. One patient of amyopathic DM had typical heliotrope rash and characteristic skin biopsy.
Histological features are important for the diagnosis of DM. Relying on PFA for diagnosis of definite DM underestimates the true frequency of DM.
...the three patients in this report suggest that malignant cell infiltration of the peripheral nerve may be the presenting feature of lymphoreticular malignancy and should be included in the ...diagnostic algorithm of peripheral neuropathy.
Multiple sclerosis typically has onset in young adults and new disease activity diminishes with age. Most clinical trials of disease-modifying therapies for multiple sclerosis have not enrolled ...individuals older than 55 years. Observational studies suggest that risk of return of disease activity after discontinuation of a disease-modifying therapies is greatest in younger patients with recent relapses or MRI activity. We aimed to determine whether risk of disease recurrence in older patients with no recent disease activity who discontinue disease-modifying therapy is increased compared to those who remain on disease-modifying therapy.
DISCOMS was a multicentre, randomised, controlled, rater-blinded, phase 4, non-inferiority trial. Individuals with multiple sclerosis of any subtype, 55 years or older, with no relapse within the past 5 years or new MRI lesion in the past 3 years while continuously taking an approved disease-modifying therapy were enrolled at 19 multiple sclerosis centres in the USA. Participants were randomly assigned (1:1 by site) with an interactive response technology system to either continue or discontinue disease-modifying therapy. Relapse assessors and MRI readers were masked to patient assignment; patients and treating investigators were not masked. The primary outcome was percentage of individuals with a new disease event, defined as a multiple sclerosis relapse or a new or expanding T2 brain MRI lesion, over 2 years. We assessed whether discontinuation of disease-modifying therapy was non-inferior to continuation using a non-inferiority, intention-to-treat analysis of all randomly assigned patients, with a predefined non-inferiority margin of 8%. This trial is registered at ClinicalTrials.gov, NCT03073603, and is completed.
259 participants were enrolled between May 22, 2017, and Feb 3, 2020; 128 (49%) were assigned to the continue group and 131 (51%) to the discontinue group. Five participants were lost to follow-up (continue n=1, discontinue n=4). Six (4·7%) of 128 participants in the continue group and 16 (12·2%) of 131 in the discontinue group had a relapse or a new or expanding brain MRI lesion within 2 years. The difference in event rates was 7·5 percentage points (95% CI 0·6–15·0). Similar numbers of participants had adverse events (109 85% of 128 vs 104 79% of 131) and serious adverse events (20 16% vs 18 14%), but more adverse events (422 vs 347) and serious adverse events (40 vs 30) occurred in the discontinue group. The most common adverse events were upper respiratory infections (20 events in 19 15% participants in the continue group and 37 events in 30 23% participants in the discontinue group). Three participants in the continue group and four in the discontinue group had treatment-related adverse events, of which one in each group was a serious adverse event (multiple sclerosis relapse requiring admission to hospital). One participant in the continue group and two in the discontinue group died; no deaths were deemed to be related to treatment.
We were unable to reject the null hypothesis and could not conclude whether disease-modifying therapy discontinuation is non-inferior to continuation in patients older than 55 years with multiple sclerosis and no recent relapse or new MRI activity. Discontinuation of disease-modifying therapy might be a reasonable option in patients older than 55 years who have stable multiple sclerosis, but might be associated with a small increased risk of new MRI activity.
Patient-Centered Outcomes Research Institute and the National Multiple Sclerosis Society.
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