Neuroimaging Endpoints in Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative, clinically heterogeneous syndrome pathologically overlapping with frontotemporal dementia. To date, therapeutic trials in animal models have not been able to predict treatment response in humans, and the revised ALS Functional Rating Scale, which is based on coarse disability measures, remains the gold-standard measure of disease progression. Advances in neuroimaging have enabled mapping of functional, structural, and molecular aspects of ALS pathology, and these objective measures may be uniquely sensitive to the detection of propagation of pathology in vivo. Abnormalities are detectable before clinical symptoms develop, offering the potential for neuroprotective intervention in familial cases. Although promising neuroimaging biomarker candidates for diagnosis, prognosis, and disease progression have emerged, these have been from the study of necessarily select patient cohorts identified in specialized referral centers. Further multicenter research is now needed to establish their validity as therapeutic outcome measures.Electronic supplementary materialThe online version of this article (doi:10.1007/s13311-016-0484-9) contains supplementary material, which is available to authorized users.

Cortical influences drive amyotrophic lateral sclerosis

“…Also diffusion tensor imaging (DTI) findings of reduced white matter integrity in the frontal, temporal and parietal lobes and, often early in the corpus callosum, suggest widespread white matter involvement may underlie both cognitive and other functional changes in ALS 63. These changes are independent of spinal cord pathology.…”

An Appraisal of Novel Biomarkers for Evaluating and Monitoring Neurologic Diseases: Editorial Introduction

“…Advances in imaging have led to an increased ability to discern structural changes that make quantitative imaging a powerful outcome measure [3][4][5]. In ALS, quantitative magnetic resonance imaging (MRI) technology can show abnormalities prior to the development of symptoms, and clear changes occur as the disease progresses [4].…”

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

“…Menke et al 8 have recently reported imaging abnormalities even before clinical symptoms, offering the potential for neuroprotective intervention, particularly in familial cases. Current literature points to DTI technique as the most promising candidate for imaging biomarker in ALS, able to elucidate the brain phenotype of ALS and also detect white matter tract changes in extramotor regions 8,10 .The results of Chaves et al 11 using a 1.5 Tesla MR equipment reinforce the clinical use of fractional anisotropy (FA) to detect extra-motor brain abnormalities in ALS patients. Despite this further multicenter validation with larger cohorts of patients remains mandatory prior to the integration of this technique into the clinical routine as biomarker able to contribute in standard clinical decision-making algorithms.…”

“…Menke et al 8 have recently reported imaging abnormalities even before clinical symptoms, offering the potential for neuroprotective intervention, particularly in familial cases. Current literature points to DTI technique as the most promising candidate for imaging biomarker in ALS, able to elucidate the brain phenotype of ALS and also detect white matter tract changes in extramotor regions 8,10 .…”

“…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 .…”