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Patients with MELAS with negative myopathology for characteristic ragged-red fibers
Yuanyuan Lu1, Jianwen Deng1, Yuying Zhao2
1Department of Neurology, Peking University First Hospital, Beijing, China.
Background:
Muscle pathology usually contributes to mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS), even in patients without prominent muscle symptoms. We report a series of patients with MELAS without significant myopathic changes.
Methods:
Twelve patients without ragged-red fibers (RRFs) on muscle pathology (RRF-negative group) and 99 patients with MELAS and RRFs and/or cytochrome c oxidase (COX)-deficient fibers (control RRF-positive group) were recruited. We analyzed clinical features, neuroimaging and pathological findings, gene mutation data, immunofluorescence assay of key respiratory chain subunits of complexes I and IV and mitochondrial DNA (mtDNA) mutation load in biopsied muscle samples.
Results:
None of the RRF-negative patients had RRF or COX-negative fibers, but four patients had strongly succinate dehydrogenase-stained vessels (SSVs). There was a lower proportion of m.3243A>G and higher proportion of mitochondria-encoded ND gene mutations in RRF-negative than RRF-positive patients. The proportion of aphasia was relatively higher, while complex I and IV subunit abundance in muscle and mutation load were lower in RRF-negative than in RRF-positive patients.
Conclusion:
RRF-negative patients had a similar disease course, clinical symptoms, and neuroimaging results to RRF-positive patients with MELAS. SSV is a valuable diagnostic indicator for MELAS. For highly suspected MELAS yet without positive myopathological findings, combined immunofluorescence and genetic studies should be used to achieve final diagnosis.
Insights
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS) can occur without muscle pathology. Strongly succinate dehydrogenase-stained vessels (SSVs) aid diagnosis in these cases, alongside immunofluorescence and genetic testing.
Area of Science:
- Neurology
- Mitochondrial Diseases
- Genetics
Background:
- Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS) typically involves muscle pathology.
- However, MELAS can present without significant myopathic changes in some patients.
Purpose of the Study:
- To investigate clinical and pathological features of MELAS patients lacking ragged-red fibers (RRFs).
- To identify diagnostic markers for RRF-negative MELAS.
Main Methods:
- Compared 12 RRF-negative MELAS patients with 99 RRF-positive controls.
- Analyzed clinical data, neuroimaging, muscle pathology (RRFs, COX, SDH staining), immunofluorescence for respiratory chain subunits, and mitochondrial DNA (mtDNA) mutation load.
Main Results:
- RRF-negative patients lacked RRFs and COX-deficient fibers but showed strongly succinate dehydrogenase-stained vessels (SSVs).
- RRF-negative group had lower m.3243A>G mutation proportion, higher mitochondria-encoded ND gene mutations, higher aphasia proportion, and lower complex I/IV subunit abundance and mtDNA mutation load.
- Disease course, symptoms, and neuroimaging were similar between RRF-negative and RRF-positive groups.
Conclusions:
- MELAS can occur without RRFs, presenting similar clinical courses to RRF-positive cases.
- SSV is a valuable diagnostic indicator for MELAS.
- Immunofluorescence and genetic studies are crucial for diagnosing suspected MELAS without positive myopathology.
