Inclusion body myositis : a nationwide study

The studies reported in this thesis aimed to survey the prevalence of inclusion body myositis (IBM), to describe its clinical features and course, to investigate whether the major histocompatibility complex predisposed subjects to IBM and autoimmune disorders (AID), to investigate the possible affliction of the neuromuscular junction (NMJ) and finally, to study whether the progression of IBM could be slowed down. On July 1st, 1999, the prevalence was estimated on at least 4.9.10-6 inhabitants in the Netherlands. The incidence rate increased since the 1980s. Time of onset was generally after the age of forty. Symptons at onset could be linked to weakness of the quadriceps muscles , the finger flexors or pharynbgeal muscles. Weakness showed a variable progression rate. Progression of weakness was faster when onset was over the age of 56. Ankylosis was common, but could be helpful in performing skilful movements. Ventral muscles were more frequently and severely affected than dorsal muscles, and girdle muscles were relatively spared, a specific pattern. Repetitive nerve stimulation studies showed normal compound muscle action potential patterns suggestive of normal NMJ transmission. In IBM patients a high frequency of AID was observed. Compared to controls, patients had a high frequency of HLA-antigens of the HLA-A1-B8-DR3-DR52-DQ2 complex. This high frequency could be related to IBM alone and not to the presence of AID. Lastly, in a randomized placebo controlled trial with methotrexate no important effect on weakness progression could be demonstrated.LEI Universiteit LeidenPathophysiologie van aanvalsgewijs en chronisch progressief verlopende aandoeningen van het centrale perifere zenuwstelse

Facioscapulohumeral muscular dystrophy: reproductive counseling, pregnancy, and delivery in a complex multigenetic disease

Reproductive counseling in facioscapulohumeral muscular dystrophy (FSHD) can be challenging due to the complexity of its underlying genetic mechanisms and due to incomplete penetrance of the disease. Full understanding of the genetic causes and potential inheritance patterns of both distinct FSHD types is essential: FSHD1 is an autosomal dominantly inherited repeat disorder, whereas FSHD2 is a digenic disorder. This has become even more relevant now that prenatal diagnosis and preimplantation genetic diagnosis options are available for FSHD1. Pregnancy and delivery outcomes in FSHD are usually favorable, but clinicians should be aware of the risks. We aim to provide clinicians with case-based strategies for reproductive counseling in FSHD, as well as recommendations for pregnancy and delivery.Genetics of disease, diagnosis and treatmen

Teaching NeuroImages: A protruding asymmetrical belly

Neurological Motor Disorder

Clinical reasoning: a 70-year-old man with walking difficulties

Neurological Motor Disorder

Clinical Reasoning: A 70-year-old man with walking difficulties

Neurological Motor Disorder

A 12-year follow-up in sporadic inclusion body myositis: an end stage with major disabilities

Sporadic inclusion body myositis is considered to be a slowly progressive myopathy. Long-term follow-up data are, however, not yet available. Follow-up data are important with a view to informing patients about their prognosis and selecting appropriate outcome measures for clinical trials. We performed a follow-up study of 64 patients with sporadic inclusion body myositis who participated in a national epidemiological study in the Netherlands. Case histories were recorded, and manual and quantitative muscle tests as well as laboratory tests were performed at baseline and 12 years (median) after the first out-patient visit. Date and cause of death were recorded for all deceased patients. Forty-six patients died during the follow-up period, two patients chose not to participate and one patient was lost to follow-up. The remaining 15 surviving patients had a mean disease duration of 20 years and were clinically evaluated at the second time point. The mean decline in strength was 3.5 and 5.4% per year according to the manual muscle testing and quantitative muscle testing, respectively. This decline was most pronounced in the lower legs, which were also the weakest extremities. Life expectancy was normal at 81 years, but activities of daily life were clearly restricted. At follow-up, all patients were found to be using a wheelchair, seven of them (47%) being completely wheelchair-bound. Disorders of the respiratory system were the most common cause of death. In three patients, euthanasia was requested and in another three, continuous deep sedation was applied. The fact that end-of-life care interventions were used in six patients (13%) reflects the severe disability and loss of quality of life at the end stage of this disease. Sporadic inclusion body myositis is a chronic progressive disorder, leading to major disabilities at the end stage of the disease due to extensive muscle weakness.Neurological Motor Disorder

Presence of the anti-Jo1 autoantibody excludes inclusion body myositis

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Magnetic resonance imaging of skeletal muscles in sporadic inclusion body myositis

Objective. To analyse whether MRI of upper and lower extremity muscles in a large patient group with sporadic IBM (sIBM) is of additional value in the diagnostic work-up of sIBM. Methods. Thirty-two sIBM patients were included. Magnetic resonance (MR) parameters evaluated in 68 muscles of upper and lower extremity were muscle atrophy, fatty infiltration and inflammation. These findings were correlated with disease duration, weakness and serum creatine kinase (sCK) levels. Results. Fatty infiltration was far more common than inflammation. Muscles most frequently infiltrated with fat were the flexor digitorum profundus (FDP), anterior muscles of the upper leg and all muscles of the lower leg, preferentially the medial part of the gastrocnemius. The rectus femoris was relatively spared compared with other quadriceps muscles as well as the adductors of the upper leg. Inflammation was common in general, but individually sparse, present in 78% of the patients with a median of two inflamed muscles per patient. A statistically significant correlation was found between the amount of fatty infiltration and disease severity, disease duration and sCK. Conclusion. We provide a detailed description of the MRI in sIBM and show a distinct pattern of muscle involvement. Relatively severe affliction of the medial compartment of the gastrocnemius, combined with relative sparing of the rectus femoris or involvement of the FDP can be indicative of sIBM. MRI can contribute to the diagnosis in selected patients with clear clinical suspicion, but lacking the mandatory set of muscle biopsy features.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

TREX1 mutations are not associated with sporadic inclusion body myositis

Background: Sporadic inclusion body myositis (sIBM) is the most frequent acquired myopathy above the age of fifty. The exact mechanism causing this disease is not known, but immune-mediated features are prominent and are probably to play a role in its pathogenesis. TREX1 gene mutations are associated with a large range of autoimmune diseases, such as systemic lupus erythematosus. We investigated whether mutations in the TREX1 gene were associated with sIBM. Methods: Fifty-four patients with sIBM were tested for TREX1 mutations by direct sequencing. Results: All 54 patients tested negative for pathogenic mutations in the TREX1 gene. One presumed non-pathogenic polymorphism was found in 42 out of 54 patients. Conclusion: TREX1 mutations do not play a role in the pathogenesis of sIBM.Pathophysiology of paroxysmal and chronic degenerative progressive disorder of the central and periferal nervous syste