Loss of Myofilaments in Gastrointestinal Smooth Muscle: A Novel Pathological Finding in MELAS-Associated Chronic...

Chronic intestinal pseudo-obstruction (CIPO) occurs in up to 40% of patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). While enteric nervous system abnormalities have been documented, 15%-38% of CIPO cases show normal histology, suggesting alternative pathogenic mechanisms. We aimed to investigate smooth muscle pathology in MELAS-associated CIPO.

Comprehensive pathological examination including light and electron microscopy was performed on autopsy material from a 52-year-old male with MELAS (m.3243A > G mutation) and recurrent intestinal obstruction symptoms. Gastrointestinal tissue from the entire digestive tract was analyzed and compared with age-matched control tissue.

Histological examination revealed widespread vacuolization and pallor of gastrointestinal smooth muscle throughout the digestive tract (esophagus, stomach, duodenum, and colon). Electron microscopy demonstrated abundant abnormal mitochondria in smooth muscle cells and, notably, marked loss of myofilaments in the colonic muscle. The ultrastructural preservation was limited by postmortem changes (autolysis, occurring approximately 4 h after death) and the re-embedding technique from formalin-fixed paraffin-embedded tissue; however, the striking difference was evident compared to age-matched controls. Similar abnormalities were observed in the Auerbach plexus.

This represents the first report of myofilament loss in MELAS-associated CIPO, suggesting that mitochondrial dysfunction may directly impair smooth muscle contractile apparatus beyond previously described neuronal abnormalities. These findings provide novel insights into CIPO pathogenesis and may inform therapeutic strategies emphasizing early enteral nutrition interventions that bypass affected gastrointestinal segments.