Cerebral lactic acidosis correlates with neurological impairment in MELAS

Objective: To evaluate the role of chronic cerebral lactic acidosis in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes ( MELAS). Methods: The authors studied 91 individuals from 34 families with MELAS and the A3243G point mutation and 15 individuals from two families with myoclonus epilepsy and ragged red fibers ( MERRF) and the A8344G mutation. Subjects were divided into four groups. Paternal relatives were studied as controls ( Group 1). The maternally related subjects were divided clinically into three groups: asymptomatic ( no clinical evidence of neurologic disease) ( Group 2), oligosymptomatic ( neurologic symptoms but without the full clinical picture of MELAS or MERRF) ( Group 3), and symptomatic ( fulfilling MELAS or MERRF criteria) ( Group 4). The authors performed a standardized neurologic examination, neuropsychological testing, MRS, and leukocyte DNA analysis in all subjects. Results: The symptomatic and oligosymptomatic MELAS subjects had significantly higher ventricular lactate than the other groups. There was a significant correlation between degree of neuropsychological and neurologic impairment and cerebral lactic acidosis as estimated by ventricular MRS lactate levels. Conclusions: High levels of ventricular lactate, the brain spectroscopic signature of MELAS, are associated with more severe neurologic impairment.