Abstract
Four patients with clinically and genetically defined MELAS were examined using quantitative
localized proton magnetic resonance spectroscopy of the brain. Acute and chronic lesions
were located in the occipital lobe and mostly characterized by strongly elevated concentrations
of lactate (Lac) and glucose (Glc) as well as severely reduced concentrations of total
N-acetylaspartyl compounds (tNAA, neuroaxonal markers), glutamate (Glu), and total
creatine. These findings indicate a high degree of nonoxidative glycolysis reflecting
either impaired oxidative energy metabolism or the use of anerobic metabolism by infiltrating
macrophages as well as damage or loss of viable neuroaxonal tissue. In contrast, glial
cell populations, in particular astrocytes, seem to remain unaffected as evidenced
by unchanged concentrations of myo-nositol (glial marker). In addition, all patients
including one who never experienced a stroke-like episode showed elevated Lac and
Glc as well as reduced tNAA and Glu in tissues appearing normal on MRI. These disturbances
were stronger in cortical gray matter and cerebellum than in white matter and indicate
that neuroaxonal damage is not restricted to structural lesions. The steady presence
of Lac is consistent with a reduced capacity of the mitochondrial oxidative energy
metabolism resulting from impaired respiratory chain function.
Key words
MELAS - Proton MRS - Brain metabolites - Brain lactate - Energy metabolism - Neuroaxonal
damage
