Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

Roelineke J Lunsing,Paul E Sijens,Tom J De Koning,Kim Strating

doi:10.1007/s00330-016-4454-8

Roelineke J Lunsing, Paul E Sijens + Show 2 more

Open Access

https://doi.org/10.1007/s00330-016-4454-8

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Abstract

ObjectivesMagnetic 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.MethodsMultivoxel 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.ResultsMRS 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.ConclusionMRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children.Key points• 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.

Highlights

Mitochondrial disorders represent a clinically, biochemically, and genetically heterogeneous group of diseases associated with dysfunction of the oxidative phosphorylation system (OXPHOS) [1]
Magnetic resonance spectroscopy (MRS)-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children
MRS lactate and lactate/Cr are increased in children with mitochondrial disease

Summary

Introduction

Mitochondrial disorders represent a clinically, biochemically, and genetically heterogeneous group of diseases associated with dysfunction of the oxidative phosphorylation system (OXPHOS) [1]. Correct diagnosis of an OXPHOS disorder is important for prognosis, genetic counseling, and supportive management of associated impairments [3]. In mitochondrial disorders the process of adenosine triphosphate (ATP) production is disrupted. Low ATP results in an upregulation of glycolysis, leading to an overproduction of pyruvate, and this excess pyruvate is either transaminated to alanine or reduced to form lactate [4]. Venous lactate acidosis/lactic acidosis or elevated lactate is generally considered as a clinically relevant indicator for mitochondrial disease, but can be falsely positive or negative. Cerebrospinal fluid lactate (CSF) may be elevated, even in the presence of normal venous

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