25 years of neuroimaging in amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease for which a precise cause has not yet been identified. Standard CT or MRI evaluation does not demonstrate gross structural nervous system changes in ALS, so conventional neuroimaging techniques have provided little insight into the pathophysiology of this disease. Advanced neuroimaging techniques—such as structural MRI, diffusion tensor imaging and proton magnetic resonance spectroscopy—allow evaluation of alterations of the nervous system in ALS. These alterations include focal loss of grey and white matter and reductions in white matter tract integrity, as well as changes in neural networks and in the chemistry, metabolism and receptor distribution in the brain. Given their potential for investigation of both brain structure and function, advanced neuroimaging methods offer important opportunities to improve diagnosis, guide prognosis, and direct future treatment strategies in ALS. In this article, we review the contributions made by various advanced neuroimaging techniques to our understanding of the impact of ALS on different brain regions, and the potential role of such measures in biomarker development.

Recent Advances and the Future of Stem Cell Therapies in Amyotrophic Lateral Sclerosis

“…It is likely that the microenvironment is already compromised at the time symptoms develop and even more so when ALS is diagnosed; therefore, improving the time to diagnosis as a means to achieve earlier institution of therapy is essential in order to confer the best possible opportunity for MN rescue. The development of more robust biomarkers, including electrodiagnostic testing, transcranial magnetic stimulation, and advanced imaging techniques will complement advances in stem cell therapy by allowing earlier detection of disease, as well as more detailed assessments of therapeutic benefits [125,126].…”

Detecting neuronal dysfunction of hand motor cortex in ALS: A MRSI study

“…However, sensitivity and specificity of this strategy for ALS diagnosis is relatively limited (sensitivity: 50-70%; specificity: 40-90%) (Turner and Modo 2010). Reduction of the NAA/Cr ratio was only mild to moderate (Foerster et al 2013) and there was considerable overlap in metabolite ratios of PMC between ALS patients and normal controls (Ellis et al 1998;Kalra et al 2006b). Such overlapping is probably a combined result of the physical feature of cerebral cortex and limitation of MRS scanning.…”

“…Specifically, the location and volume of the region of interest (ROI) varies from study to study, making it difficult to reconcile results from different groups. Besides, the relationship between neuroimaging findings and clinical measures is also inconsistent (Foerster et al 2013). Hand motor cortex (HMC), a landmark for PMC (Yousry et al 1997), has been constantly used for identification of PMC in these studies.…”

Genetics of Amyotrophic Lateral Sclerosis

“…5 In patients with ALS, signal intensity changes on proton attenuation, T2-weighted, and FLAIR sequences may be seen anywhere along the cerebrospinal tract, from the centrum semiovale to the brain stem. 2,5 Typical changes in the brain are often best appreciated on coronal imaging and appear as areas of bilateral symmetric increased signal intensity. 8 The frequency of cerebrospinal tract lesions in patients with ALS ranges widely across studies (from 15-76%), with combination imaging approaching a sensitivity above 60%.…”

“…While the disease may chronically persist in such form, it usually progresses to the generalized muscle weakness of typical ALS. 1,2 Patients with ALS are more often male and typically present in late middle age. ALS is often rapidly progressive, and most patients die within 3-5 years of onset; however considerable variability exists.…”