Patients with MELAS with negative myopathology for characteristic ragged-red fibers

Abstract

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.

Keywords: Diagnosis; MELAS; Mitochondrial DNA; Ragged-red fibers; Strongly succinate dehydrogenase-stained vessels.