Is magnetic resonance imaging a plausible biomarker for upper motor neuron degeneration in amyotrophic lateral sclerosis/primary lateral sclerosis or merely a useful paraclinical tool to exclude mimic syndromes? A critical review of imaging applicability in clinical routine

Abstract

<jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons in the cerebral cortex, brainstem, and spinal cord, brain regions in which conventional magnetic resonance imaging is often uninformative. Although the mean time from symptom onset to diagnosis is estimated to be about one year, the current criteria only prescribe magnetic resonance imaging to exclude "ALS mimic syndromes". Extensive application of non-conventional magnetic resonance imaging (MRI) to the study of ALS has improved our understanding of the in vivo pathological mechanisms involved in the disease. These modern imaging techniques have recently been added to the list of potential ALS biomarkers to aid in both diagnosis and monitoring of disease progression. This article provides a comprehensive review of the clinical applicability of the neuroimaging progress that has been made over the past two decades towards establishing suitable diagnostic tools for upper motor neuron (UMN) degeneration in ALS.</jats:p>

And what about Gaba Magnetic Resonance Spectroscopy as an Indirect Tool to Evaluate Riluzole Efficacy in Amyotrophic Lateral Sclerosis?

“…MRS studies have confirmed the finely tuned balancing act between glutamate and GABA in the human brain both biochemically, as the huge majority of GABA is metabolized from glutamate, and functionally, with regard to the strict control of the inhibitory/excitability balance in healthy [6,12]. However, it has been reported that MRS gives a less accurate reflection of glutaminergic actions than GABAergic activity [10,11]. All these contentions led us to hypothesize that GABA MRS may represent an indirect promising tool to evaluate riluzole efficacy with timely detailed description of the dynamics of changes in GABA levels due to druginduced effects on extracellular glutamate uptake.…”

“…Intriguingly, it has been found that riluzole significantly enhances glutamate uptake in a dose-dependent manner increasing the affinity of glutamate for the transporters including EAAC1 [9]. Magnetic Resonance Spectroscopy (MRS) is a powerful methodology that allows to quantify neurotransmitter concentrations in discrete regions of the human brain non-invasively in vivo [4,10]. Over recent years there has been a particular interest in using this technique to detect biologically relevant alterations in GABA concentrations [10,11].…”

“…Magnetic Resonance Spectroscopy (MRS) is a powerful methodology that allows to quantify neurotransmitter concentrations in discrete regions of the human brain non-invasively in vivo [4,10]. Over recent years there has been a particular interest in using this technique to detect biologically relevant alterations in GABA concentrations [10,11]. High field strengths have improved signal-to-noise with a better separation of metabolic peaks, such as glutamate and GABA, which play an important role in the ALS pathogenesis [6,11,12].…”

Revealing the microstructural brain damage in amyotrophic lateral sclerosis: the relentless pursuit to approach an imaging biomarker

“…A plausible biomarker for upper motor neuron degeneration in ALS is becoming tangible after recent advances in high-throughput MRI techniques, through which one can believe that we are going to the forefront of a breakthrough able to translate research findings into reliable clinical tests that will support the practice of personalized medicine 8,9,10 .…”

Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile

“…Therefore, there is currently great interest in developing biomarkers of cognitive and extra-motor systems damage in ALS. In this regard, new neuroimaging techniques are postulated as potential tools to obtain accurate data and measure early activity in non-motor structures 4 . Diffusion tensor imaging (DTI) is a technique of magnetic resonance imaging (MRI) used to characterize the architecture of the white matter, based on the orientation properties of diffusion of water molecules in the brain 5 .…”