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.
Kaufmann
P
P
Department of Neurology, Columbia University, New York, NY 10032, USA.
Shungu
D C
DC
Sano
M C
MC
Jhung
S
S
Engelstad
K
K
Mitsis
E
E
Mao
X
X
Shanske
S
S
Hirano
M
M
DiMauro
S
S
De Vivo
D C
DC
D000140:Acidosis, Lactic / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose; D002552:Cerebral Ventricles / Q000378:metabolism*; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D006579:Heterozygote; D006801:Humans; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D017241:MELAS Syndrome / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D017243:MERRF Syndrome / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D017354:Point Mutation; D011237:Predictive Value of Tests; D012720:Severity of Illness Index
D001786:Blood Glucose; D019344:Lactic Acid