Neurometabolic Alterations in Motor Neuron Disease: Insights from Magnetic Resonance Spectroscopy

Magnetic resonance spectroscopy (MRS) has contributed important academic insights in motor neuron diseases (MNDs), particularly in amyotrophic lateral sclerosis (ALS). Over the past three decades momentous methodological advances took place, including the emergence of high-field magnetic resonance imaging (MRI) platforms, multi-voxel techniques, whole-brain protocols, novel head-coil designs, and a multitude of open-source imaging suites. Technological advances in MRS are complemented by important conceptual developments in MND, such as the recognition of the importance of extra-motor brain regions, multi-timepoint longitudinal study designs, assessment of asymptomatic mutation carriers, description of genotype-associated signatures, and the gradual characterisation of non-ALS MND phenotypes. We have conducted a systematic review of published MRS studies in MND to identify important emerging research trends, key lessons from pioneering studies, and stereotyped shortcomings. We also sought to highlight notable gaps in the current literature so that research priorities for future studies can be outlined. While MRS remains relatively underutilised in MND compared to other structural, diffusivity and functional imaging modalities, our review suggests that MRS can not only advance our academic understanding of MND biology, but has a multitude of practical benefits for clinical and pharmaceutical trial applications.