Myofibrillar disorganization characterizes myopathy of camptocormia in Parkinson’s disease

摘要

Camptocormia is a highly disabling syndrome that occurs in various diseases but is particularly associated with Parkinson’s disease (PD). Although first described nearly 200 years ago, the morphological changes associated with camptocormia are still under debate and the pathophysiology is unknown. We analyzed paraspinal muscle biopsies of 14 PD patients with camptocormia and compared the findings to sex-matched postmortem controls of comparable age to exclude biopsy site-specific changes. Camptocormia in PD showed a consistent lesion pattern composed of myopathic changes with type-1 fiber hypertrophy, loss of type-2 fibers, loss of oxidative enzyme activity, and acid phosphatase reactivity of lesions. Ultrastructurally, myofibrillar disorganization and Z-band streaming up to electron-dense patches/plaques were seen in the lesions. No aberrant protein aggregation, signs of myositis or mitochondriopathy were found, but the mitochondrial content of paraspinal muscles in patients and controls was markedly higher than known from limb biopsies. Additionally, we were able to demonstrate a link between the severity of the clinical syndrome and the degree of the myopathic changes. Because of the consistent lesion pattern, we propose criteria for the diagnosis of camptocormia in PD from muscle biopsies. The morphological changes show obvious parallels to the muscle pathology of experimental tenotomy reported in the 1970s, which depend on an intact innervation and do not occur after interruption of the myotactic reflexes. A dysregulation of the proprioception could be part of the pathogenesis of camptocormia in Parkinson’s disease, particularly in view of the clinical symptoms of rigidity and loss of muscle strength.