封入体筋炎

OBJECTIVE: Idiopathic inflammatory myopathies (IIM) are a heterogenous group of conditions with substantial morbidity but population-based epidemiology is lacking. We aimed to provide a contemporary epidemiological assessment of IIM. METHODS: Population-based study using the Clinical Practice Research Datalink (CPRD) Aurum primary care database with linkage to hospital episode data. All patients (aged >2 years) from England registered between 1 March 2002 and 31 March 2021 were included. Incidence was estimated for three main IIM subtypes: dermatomyositis (DM), inclusion body myositis (IBM) and other IIM. Incidence rate ratios using Poisson models were compared across subgroups. RESULTS: We identified n=1590 DM, n=432 IBM and n=2083 other IIM incident cases. Incidence of DM was 0.79 (95% CI 0.75 to 0.83), IBM 0.50 (95% CI 0.46 to 0.55) and other IIM 1.03 (95% CI 0.99 to 1.08) per 100 000 person-years.Females had a higher incidence of DM (adjusted incidence rate ratio (aIRR) 1.84, 95% CI 1.66 to 2.04) and other IIM (aIRR 1.09, 95% CI 1.00 to 1.19), but a lower incidence of IBM (aIRR 0.73, 95% CI 0.60 to 0.89), compared with males. South Asian, black, other and unknown ethnic groups had a higher incidence of DM and other IIM compared with those of white ethnicity, particularly individuals of black ethnicity for other IIM (aIRR 2.80, 95% CI 2.32 to 3.37).Point prevalence at study end was 0.015% for DM, 0.005% for IBM and 0.016% for other IIM. CONCLUSION: There are major demographic differences in IIM incidence, notably by sex and ethnicity. Resource planning should account for these marked differences.

BACKGROUND: Dorsal arachnoid web (DAW) is a rare spinal pathology involving a thickened band of arachnoid tissue that compresses the thoracic spinal cord, potentially causing myelopathy. Patients with DAW who present with pain or neurological complaints should be evaluated thoroughly to determine the most likely cause of symptoms, particularly in the context of clinical presentations that overlap with other neurological or pain syndromes. CASE REPORT: A 76-year-old man with a history of inclusion body myositis and prior middle cerebral artery stroke presented with left-sided pain and weakness. Although DAW was noted on imaging, further evaluation indicated that the patient's pain symptoms were due to central pain syndrome secondary to his previous stroke, given the correlation between symptom localization and stroke territory. He was managed successfully with pregabalin and amitriptyline without the need for surgical intervention. CONCLUSION: In patients with overlapping neurological and pain syndromes, accurate diagnosis is essential to determining the best choice of treatment.

OBJECTIVES: Inclusion body myositis (IBM) is the most common idiopathic inflammatory myopathy after age 50, causing progressive weakness of quadriceps and finger flexors. With no effective disease-modifying therapies, accessible non-pharmacological strategies are needed. Exercise is safe, may slow disease progression and improve strength. However, most studies focus on lower limb strengthening, despite hand strength being vital to independence. Our study analysed the acceptability, tolerability and efficacy of an at-home TheraPutty® hand exercise intervention on grip strength and function in adults with IBM. METHODS: In this 12-week, single-arm pilot study, thirteen participants underwent baseline, 6-week, and 12-week assessments of grip/pinch strength (hand-held dynamometry), dexterity (Nine-Hole Peg Test, Box and Block Test), and function (IBM Functional Rating Scale, Duruöz Hand Index). Use of intention-to-treat and per-protocol approaches assessed the effect of adherence on strength outcomes. Adherence (≥75% sessions), acceptability, and tolerability were assessed through weekly diaries and an end-of-study questionnaire. RESULTS: Nine participants (69%) achieved ≥75% adherence. Intention-to-treat analysis showed no significant changes in grip or pinch strength, although Box and Block performance improved significantly bilaterally. In the per-protocol analysis, significant improvements were observed in non-dominant 2-point and bilateral 3-point pinch strength. Fatigue, pain, and difficulty using even the lowest resistance TheraPutty® limited adherence. Overall, participants rated the programme as moderately acceptable (mean 3.5/5) and tolerable (3.4/5). CONCLUSIONS: A home-based TheraPutty® programme is feasible and generally acceptable in IBM, with potential signals of benefit among adherent participants. Future larger, longer-term studies should refine treatment protocols to reduce fatigue and optimise efficacy.

Valosin-containing protein (VCP) pathogenic variants cause a multisystem proteinopathy characterized by myopathy, Paget disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS). We evaluated 82 affected individuals, 14 presymptomatic carriers, and 36 unaffected first-degree relatives from 48 families to identify sensitive measures for disease monitoring. Mean age of onset was ∼42 years for myopathy, Paget disease, or ALS, and 53 years for dementia. Functional assessments included the Inclusion Body Myositis Functional Rating Scale (IBMFRS), ALSFRS-R, Fatigue Severity Scale (FSS), and six-minute walk test (6MWT). Affected individuals demonstrated progressive functional decline, with IBMFRS decreasing 1.9% annually, FSS increasing 4.4%, and 6MWT decreasing 6% annually when modeled against disease duration. Women declined more rapidly on IBMFRS but showed slower ambulatory and fatigue progression. Potential genotype-specific effects were observed, with earlier onset and shorter survival in p.Arg155Cys compared to later onset in p.Arg155His. Strong correlations among IBMFRS, FSS, and 6MWT indicate these as accessible endpoints for longitudinal monitoring and clinical trials. Rapid decline with ALS and dementia necessitates multidisciplinary support, while longer survival after myopathy or Paget onset offers a window for preventive and supportive interventions.

Mutations in the valosin-containing protein (VCP) gene lead to a hereditary type of inclusion body myositis (hIBM), in which sarcoplasmic and myonuclear inclusions with TAR DNA-binding protein 43 (TDP-43) pathology and mitochondrial abnormalities are observed in histological analysis. Pathophysiological conditions in the cell cause the protein quality control system to depend on the autophagy-lysosome pathway (ALP) for degradation of accumulated misfolded proteins and mitochondrial turnover. BCL2-associated athanogene 3 (BAG3) protein has a role in initiating the ALP. Our aim was to ameliorate disease processes resulting from mitochondrial abnormalities and misfolded protein aggregation by upregulating the ALP through overexpression of human BAG3 (hBAG3). The VCP-A232E mouse, a model for hIBM, received AAVrh74.tMCK.hBAG3 systemically at 3 months of age, and outcome measures, including functional, histological, and molecular studies, were assessed 9 months post-gene delivery. hBAG3 treatment improved treadmill running distance and rotarod duration, reduced the number of TDP-43-positive aggregates, and decreased the number of fibers showing abnormalities in mitochondrial enzyme histochemistry, compared with the untreated cohort. Moreover, hBAG3 gene therapy resulted in improvements in mitophagy and mitochondrial homeostasis observed as increased levels in mitophagy markers Parkin and Bnip3, mitochondria biogenesis marker Pgc1α and mitochondrial DNA-encoded subunits of complex IV, Cox1 and Cox3. In addition, the LC-II/I ratio increased, indicating increased autophagic flux. Our study presents evidence that the strategy of supporting the ALP system by overexpressing BAG3 has potential therapeutic use for myodegenerative conditions associated with abnormal protein aggregates and mitochondrial turnover.