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Updated: Aug 24, 2026

Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes
08:56

Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes

Published on: October 10, 2025

Cerebral lactic acidosis correlates with neurological impairment in MELAS

P Kaufmann1, D C Shungu, M C Sano

  • 1Department of Neurology, Columbia University, New York, NY 10032, USA.

Neurology
|April 28, 2004
PubMed
Abstract

Insights

Chronic cerebral lactic acidosis, a brain spectroscopic signature of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), is linked to increased neurologic impairment in patients with MELAS.

Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited disorder.
  • Cerebral lactic acidosis is a known hallmark of MELAS, but its direct correlation with disease severity requires further elucidation.

Purpose of the Study:

  • To investigate the association between chronic cerebral lactic acidosis and the clinical spectrum of MELAS.
  • To evaluate the utility of magnetic resonance spectroscopy (MRS) in quantifying cerebral lactate levels in MELAS patients.

Main Methods:

  • Studied 91 individuals with MELAS (A3243G mutation) and 15 with myoclonus epilepsy and ragged red fibers (MERRF) (A8344G mutation).
  • Classified subjects into four groups: paternal controls, asymptomatic, oligosymptomatic, and symptomatic MELAS/MERRF patients.
  • Utilized neurologic examination, neuropsychological testing, MRS for lactate measurement, and leukocyte DNA analysis.

Main Results:

  • Significantly elevated ventricular lactate levels were observed in symptomatic and oligosymptomatic MELAS subjects compared to controls and asymptomatic individuals.
  • A strong positive correlation was found between the degree of neurologic and neuropsychological impairment and cerebral lactic acidosis, as measured by ventricular MRS lactate.

Conclusions:

  • High ventricular lactate levels, indicative of cerebral lactic acidosis, serve as a spectroscopic marker for MELAS.
  • Increased cerebral lactic acidosis is directly associated with greater neurologic severity in MELAS patients.

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