Acute Encephalopathy in Children From Muzaffarpur, Bihar, India, and the Potential Role of Ambient Heat Stress-Induced Mitochondrial Dysfunction

Background: Periodic outbreaks of acute encephalopathy in children have been reported from Muzaffarpur, Bihar, India. No infectious cause has been identified for this. This study presents the clinical and metabolic profile of children hospitalized with acute encephalopathy and the potential role of ambient heat stress. Methods: This cross-sectional study included children (<15 years) with acute encephalopathy admitted from April 4, 2019, to July 4, 2019. The clinical and laboratory investigations included infections, metabolic abnormalities, and muscle tissue analysis. The children who had metabolic derangements but no infectious cause were labeled as acute metabolic encephalopathy. The descriptive analysis summarized the clinical, laboratory, and histopathology findings, and their association with the ambient heat parameters was explored. Results: Out of the 450 children hospitalized (median age, four years), 94 (20.9%) died. Children had early morning onset (89%), seizures (99%), fever (82%), hypoglycemia at admission (64%), raised aminotransferases (60%), and high blood urea (66%). Blood lactate (50%), lactate dehydrogenase (84%), pyruvate (100%), ammonia (32%), and creatinine phosphokinase (69%) were raised. Viral marker tests were negative. The patients had abnormal metabolic markers like decreased blood-free carnitine, elevated blood acylcarnitines, and elevated urinary lactate, oxalate, maleate, adipate, and fatty acid metabolites. Blood carnitine and acylcarnitine levels normalized in 75% of the patients treated with carnitine and coenzyme-Q. Muscle tissues showed megamitochondria on electron microscopy and reduced respiratory enzyme complex-I activity. A significant correlation between the number of admissions and ambient heat indices was observed. Conclusions: The findings suggest secondary mitochondrial dysfunction as a possible mechanism for acute encephalopathy in children from Muzaffarpur, Bihar, and ambient heat stress as a possible risk factor.