MRS can provide important insights into the regional chemical pathology of the brain and how this chemical pathology changes in response to drug therapy. As an index of neuronal integrity, NAA holds promise as a biomarker of degeneration and a surrogate marker of therapeutic efficacy in ALS. NAA changes in the brain parallel the spatial distribution of pathologic changes and modest associations are present with clinical parameters.
However, to date, the finding of reduced motor cortex NAA lacks discriminatory power to distinguish individual ALS patients from healthy controls because of significant overlap between the two groups. Furthermore, longitudinal changes in NAA over the very short term are variable and relatively small and challenge the precision of the method. The increasing use of higher field magnets should substantially help in this regard. Measurement of other metabolites (e.g. glutamate) using high field techniques could supplement NAA imaging; this could increase the potential of MRS as a diagnostic instrument and as a tool to better understand pathogenesis. Additionally, technical developments are necessary to decrease scan times so that more patients can tolerate the procedure.
Further studies are required to delineate the temporal and spatial profile of the NAA response to effective drugs, to validate these responses as surrogates of clinical efficacy, and to improve the precision of the measurement. Such data will be critical in the development of NAA as a surrogate marker of therapeutic efficacy in ALS.
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