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MELAS: clinical phenotype and morphological brain abnormalities

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Abstract

We describe the clinical and neuropathological findings of three unrelated autopsy cases of MELAS harboring the A3243G transition in the mitochondrial DNA (mtDNA). Using immunohistochemical techniques, we studied the expression of several subunits of the respiratory chain in various brain regions from the same cases. In all three cases there was a reduced immunocytochemical staining for mtDNA-encoded subunits of the respiratory chain, confirming the presence of a defective mitochondrial protein synthesis in this disease. Mitochondrial abnormalities were mostly confined to multiple areas of different size and shape, in agreement with the focal character of the brain pathology in MELAS, and were most prominent in the cerebral cortex, providing a morphological contribution to the explanation of the cognitive regression of the patients. Immunoreactivity for mtDNA-encoded subunits was reduced in the walls of many pial and intracerebral arterioles of different brain regions but there was no clear correlation between territories of affected vessels and distribution of the histological and immunohistochemical lesions. Cerebral focal lesions in MELAS might have a metabolic nature and several pathogenetic mechanisms might be involved in the genesis of stroke-like episodes when there is a local increased ATP demand.

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Acknowledgments

This work was supported by grant M.U.R.S.T. 60% to N.R., A.F. 2001.

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Authors and Affiliations

  1. U.O. di Neurologia con S.U., Azienda Ospedaliera "G. Rummo", Benevento, Italy

    M. Sparaco & M. Grauso

  2. Section of Clinical Neurology, Department of Neurological and Visual Sciences, Ospedale Policlinico "G. Rossi", University of Verona, Piazzale L.A. Scuro 10, 37134, Verona (VR), Italy

    A. Simonati, T. Cavallaro & N. Rizzuto

  3. U.O. di Neurologia, Ospedale "S. Bortolo", Vicenza, Italy

    L. Bartolomei

  4. U.O. di Anatomia Patologica, Ospedale "S. Maria del Carmine", Rovereto, Italy

    F. Piscioli & L. Morelli

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  1. M. Sparaco
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Sparaco, M., Simonati, A., Cavallaro, T. et al. MELAS: clinical phenotype and morphological brain abnormalities. Acta Neuropathol 106, 202–212 (2003). https://doi.org/10.1007/s00401-003-0716-z

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  • DOI: https://doi.org/10.1007/s00401-003-0716-z

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