Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders.
OBJECTIVE
Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease.


METHODS
Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained.


RESULTS
MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate.


CONCLUSIONS
MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children.


CONCLUSIONS
• MRS-detected brain tissue lactate levels can be quantified. • MRS lactate and lactate/Cr are increased in children with mitochondrial disease. • CSF lactate is less suitable as marker of mitochondrial disease.
Department of Child Neurology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Roelineke J
RJ
Lunsing
Department of Child Neurology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Kim
K
Strating
Department of Pediatric Metabolic Diseases, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Tom J
TJ
de Koning
Department of Radiology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. p.e.sijens@umcg.nl.
Paul E
PE
Sijens
D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003401:Creatine / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019344:Lactic Acid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D028361:Mitochondrial Diseases / Q000378:metabolism*; D015203:Reproducibility of Results; D012189:Retrospective Studies
D015415:Biomarkers; D019344:Lactic Acid; D003401:Creatine
Cerebrospinal fluid; Lactate; MR spectroscopy; Magnetic resonance; Mitochondri