Increase of mitochondria in vasa nervorum of cases with mitochondrial myopathy, Kearns‐Sayre syndrome, progressive externaI ophthalmoplegia and MEWS *

Previous studies on patients with mitochondrial myopathy, encephalopathy. lactic acidosis, and stroke‐like episodes (MELAS) revealed accumulations of mitochondria in endothelial cells. smooth muscle cells of pial arterioles, and small intracerebral arteries up to 250μm in diameter; in pericytes of capillaries, endothelial cells, and smooth muscle cells of small blood vessels in skeletal muscle; and according to preliminary results also in endothelial and smooth muscle cells of capillaries and arterioles in sural nerves. These mitochondria do not show the prominent paracrystalline inclusions which are seen in striated muscle fibres and led to the identification of this group of disorders. To corroborate our preliminary findings in peripheral nerves, additional cases have been evaluated morphometrically by electron microscopy including cases in which rnitochondrial DNA (mtDNA) mutations have been identified. In fact, an increase of the mean number and an enlargement of the mean cross‐sectional area of mitochondria was noted in endothelial and smooth muscle cells of endoneurial and epineurial arterioles, and in endothelial cells and in pericytes of capillaries in sural nerves of the 20 cases with mitochondrial disorders studied. This increase was statistically significant compared to the control group. However, due to heteroplasmia, which is a common feature in mitochondrial disorders, and because of the limited number of measurable blood vessels and cases, no significant differences could be detected between the various types of mitochondrial diseases which were characterized by dflerent point mutations or deletions of mtDNA. Our findings suggest that the mitochondria play a significant role in the pathogenesis not only of myopathic and encephalopathic symptoms, but also in the pathogenesis of peripheral neuropathy which appears to be regularly associated with mitochondrial disorders.

[1]  I. Nonaka,et al.  Single muscle fiber analysis of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS) , 1994, Annals of neurology.

[2]  M. Malgat,et al.  MERRF family with 8344 mutation in tRNA (lys). Evidence of a mitochondrial vasculopathy in muscle biopsies , 1993, Neuromuscular Disorders.

[3]  R. Myers,et al.  Spatial Distribution of Nerve Injury after Occlusion of Individual Major Vessels in Rat Sciatic Nerves , 1993, Journal of neuropathology and experimental neurology.

[4]  J. Schröder.  Neuropathy Associated with Mitochondrial Disorders , 1993, Brain pathology.

[5]  R. Sakuta,et al.  Increased mitochondrial DNA in blood vessels and ragged‐red fibers in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS) , 1993, Annals of neurology.

[6]  H. Tritschler,et al.  Mitochondrial DNA alterations as a source of human disorders , 1993, Neurology.

[7]  A. Harding,et al.  A molecular genetic study of focal histochemical defects in mitochondrial encephalomyopathies. , 1992, Brain : a journal of neurology.

[8]  Y. Goto,et al.  Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS) , 1992, Neurology.

[9]  H. Tashiro,et al.  MELAS of infantile onset: mitochondrial angiopathy or cytopathy? , 1991, Journal of the Neurological Sciences.

[10]  S. Dimauro,et al.  Detection of "deleted" mitochondrial genomes in cytochrome-c oxidase-deficient muscle fibers of a patient with Kearns-Sayre syndrome. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Sakuta,et al.  Vascular involvement in mitochondrial myopathy , 1989, Annals of neurology.

[12]  S. Dimauro,et al.  Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. , 1989, The New England journal of medicine.

[13]  K. Wessel,et al.  Mitochondrial myopathies with necrotizing encephalopathy of the Leigh type. , 1988, Pathology, research and practice.

[14]  N. Bresolin,et al.  Peripheral neuropathy in mitochondrial disease , 1987, Journal of the Neurological Sciences.

[15]  A. Bellavance,et al.  Neuropathy and mitochondrial myopathy , 1980, Annals of neurology.

[16]  S. Dimauro,et al.  Mitochondrial diseases. , 1989, Neurologic clinics.