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MELAS with the mitochondrial DNA 3243 point mutation: a neuropathological study
C Tanahashi1, A Nakayama, M Yoshida
1Department of Pathology, Nagoya University School of Medicine, Japan.
Abstract:
We performed a neuropathological examination of the central nervous system from seven autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Five of the seven cases were confirmed to have the mitochondrial DNA (mtDNA) 3243 point mutation. In addition to the changes reported previously, diffuse atrophy of the cerebral and cerebellar cortices, diffuse gliosis of cerebral and cerebellar white matter, and cactus formation of Purkinje cells were observed. Electron microscopy revealed accumulation of mitochondria in the cactus formations. These lesions are common in MELAS with the mtDNA 3243 point mutation, but cannot be explained solely by mitochondrial angiopathy, and suggest that intrinsic mitochondrial malfunction contributes to neuronal damage in MELAS pathology. Moreover, the pathological changes observed in the cerebellum suggest that cerebellar function should be evaluated more carefully at the clinical level.
Insights
Neuropathological examination of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) revealed neuronal damage beyond mitochondrial angiopathy. Intrinsic mitochondrial dysfunction is implicated in MELAS pathology, highlighting the cerebellum
Area of Science:
- Neuropathology
- Mitochondrial Diseases
- Neuroscience
Background:
- Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a complex multisystem disorder.
- The 3243 point mutation in mitochondrial DNA (mtDNA) is a common genetic cause of MELAS.
Purpose of the Study:
- To investigate the neuropathological changes in the central nervous system of patients with MELAS.
- To determine the contribution of intrinsic mitochondrial malfunction to neuronal damage in MELAS.
Main Methods:
- Neuropathological examination of the central nervous system from seven autopsied MELAS patients.
- Confirmation of the mtDNA 3243 point mutation in five cases.
- Histological and electron microscopic analysis of brain tissue.
Main Results:
- Observed diffuse atrophy of cerebral and cerebellar cortices and white matter gliosis.
- Identified cactus formation of Purkinje cells with accumulated mitochondria via electron microscopy.
- Lesions suggest neuronal damage is not solely due to mitochondrial angiopathy.
Conclusions:
- Intrinsic mitochondrial malfunction significantly contributes to neuronal damage in MELAS.
- Pathological findings in the cerebellum indicate a need for careful clinical evaluation of cerebellar function in MELAS patients.