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Updated: Jan 26, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Autopsied case with MERRF/MELAS overlap syndrome accompanied by stroke-like episodes localized to the precentral
Hiroaki Miyahara1, Shinjiro Matsumoto2, Kenji Mokuno2
1Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan.
Abstract:
We present an autopsied case with A8344G-mutated myoclonus epilepsy with ragged red fibers (MERRF)/mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) overlap syndrome accompanied by stroke-like episodes localized to the precentral gyrus. A 16-year-old Japanese woman suddenly experienced repetitive consciousness disturbances with increased serum lactate and creatine kinase levels. Magnetic resonance imaging showed abnormal intensity of bilateral precentral gyrus. She was clinically diagnosed as having a mitochondrial disorder and the A8344G mutation was detected in mitochondrial DNA. At 17 years of age, she died from congestive heart failure secondary to a third episode of lactic acidosis. Neuropatho-logically, multifocal laminar necrosis, which is responsible for stroke-like episodes in MELAS, was seen in the frontal cortex including the precentral gyrus, but there was no neuronal loss and gliosis in the basal ganglia, cerebellum, and brainstem, which were compatible with MERRF. Hypertrophy of the vascular smooth muscle and choroidal epithelium were seen, and were strongly visualized by an anti-mitochondrial antibody. Skeletal muscles showed uneven muscular diameters, increased central nuclei, and ragged red fibers (RRFs). Decreased cytochrome c oxidase (COX) activity and strongly succinate dehydrogenase (SDH)-reactive blood vessels were also noted. Stroke-like episodes in MERRF/MELAS overlap syndrome are thought to be rare in the frontal cortex including the precentral gyrus. Only two cases of MERRF/MELAS overlap syndrome with A8344G mutation, including this case, have shown stroke-like episodes in the frontal lobes. Other than the A8344G mutation and frontal lobe involvement, they had a high degree of similarity in terms of presence of RRFs, gastrointestinal dysfunction, and lack of typical MERRF neuropathology. In conclusion, this is an important case describing the clinical spectrum associated with A8344G-mutated MERRF/MELAS overlap syndrome.
Insights
This study details a rare case of A8344G-mutated myoclonus epilepsy with ragged red fibers/mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes overlap syndrome. The patient experienced stroke-like episodes in the precentral gyrus, a rare frontal lobe manifestation.
Area of Science:
- Neurology
- Mitochondrial Genetics
- Pathology
Background:
- Mitochondrial disorders, including MERRF and MELAS, are complex genetic conditions affecting multiple organ systems.
- The A8344G mutation in mitochondrial DNA is a common cause of MERRF and can be associated with MELAS.
- Overlap syndromes present unique clinical and pathological challenges.
Observation:
- An autopsied case of a 16-year-old female with A8344G-mutated MERRF/MELAS overlap syndrome presenting with stroke-like episodes localized to the precentral gyrus.
- Neuropathological findings included multifocal laminar necrosis in the frontal cortex, consistent with MELAS, and ragged red fibers in skeletal muscle, characteristic of MERRF.
- Vascular smooth muscle and choroidal epithelium hypertrophy were noted, with decreased cytochrome c oxidase activity and increased succinate dehydrogenase reactivity in blood vessels.
Findings:
- Stroke-like episodes in the precentral gyrus are a rare manifestation of MERRF/MELAS overlap syndrome with the A8344G mutation.
- This case, along with one other, highlights frontal lobe involvement in A8344G-mutated MERRF/MELAS overlap syndrome.
- Key similarities among these cases include ragged red fibers, gastrointestinal dysfunction, and atypical MERRF neuropathology.
Implications:
- This case expands the understanding of the clinical and pathological spectrum of A8344G-mutated MERRF/MELAS overlap syndrome.
- It underscores the importance of considering mitochondrial disorders in patients with unexplained neurological events, particularly stroke-like episodes.
- Further research into genotype-phenotype correlations in mitochondrial diseases is warranted.
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