Inflammatory myopathies with mitochondrial pathology and protein aggregates

J Neurol Sci. 2009 Mar 15;278(1-2):25-9. doi: 10.1016/j.jns.2008.11.010. Epub 2008 Dec 20.


Objectives: To compare the clinical course and muscle biopsy features of polymyositis with mitochondrial pathology (PM-Mito) to inclusion body myositis (IBM) and steroid-responsive inflammatory myopathies (polymyositis).

Methods: We compared clinical, laboratory and myopathologic features in a retrospective study of patients with PM-Mito (23), IBM (26) and polymyositis (12).

Results: Selective weakness in the quadriceps or finger flexors was common in PM-Mito (62%) and IBM (87%). Weakness progressed more slowly in PM-Mito than in IBM. PM-Mito patients with more rapidly progressive weakness had more cytochrome oxidase negative muscle fibers. There was no history of benefit from corticosteroid treatment in any PM-Mito or IBM patients. B-cell foci were absent in IBM and PM-Mito. LC3, an autophagy marker, and alphaB-crystallin were common in aggregates in PM-Mito and IBM, but not polymyositis. SMI-31 and TDP-43 positive aggregates were common in IBM but not in PM-Mito or polymyositis. beta-amyloid showed no differences in aggregates among the three groups.

Conclusions: PM-Mito and IBM may be part of the same disease spectrum. PM-Mito has more slowly progressive weakness than IBM and rarely has TDP-43 or SMI-31 staining aggregates in muscle fibers. The most frequent proteins in aggregates in both PM-Mito and IBM are LC3, an autophagy marker, and alphaB-crystallin. Alterations in autophagic degradation pathways may be a common pathogenic mechanism in PM-Mito and IBM. In pathologically typical polymyositis, staining for mitochondrial enzyme activity, aggregates and B-cells helps to distinguish PM-Mito from inflammatory myopathy syndromes that are more likely to respond to corticosteroid treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Autophagy
  • B-Lymphocytes / pathology
  • Biopsy
  • Crystallins / metabolism
  • Disease Progression
  • Electron Transport Complex IV / metabolism
  • Humans
  • Inclusion Bodies / pathology
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria, Muscle / pathology*
  • Muscle Weakness
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Myositis / drug therapy
  • Myositis / pathology*
  • Myositis / physiopathology*
  • Retrospective Studies


  • Adrenal Cortex Hormones
  • Crystallins
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • Electron Transport Complex IV