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  • Review Article
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25 years of neuroimaging in amyotrophic lateral sclerosis

Nature Reviews Neurology volume 9, pages 513–524 (2013)Cite this article

Subjects

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.

Key Points

  • Advanced neuroimaging techniques noninvasively evaluate brain structure, chemistry, neural network connections, metabolism, and receptor distribution in neurodegenerative diseases

  • Nervous system changes in amyotrophic lateral sclerosis (ALS) involve the motor cortex, corticospinal tract, corpus callosum, frontal lobes, basal ganglia, thalamus, brainstem and cervical spinal cord

  • Neuroimaging in ALS provides evidence of neuronal loss, white matter tract disruption, alterations in neural networks, γ-aminobutyric acid system dysfunction, and changes in brain metabolism

  • Advanced neuroimaging techniques provide unique opportunities to more fully characterize and classify the different motor neuron disease subtypes

  • ALS is a heterogeneous disease, and neuroimaging studies generally include small numbers of patients with long disease duration, which could limit the generalizability of results

  • MRI and PET show promise for development of ALS biomarkers, although additional research is required to translate these technologies for clinical application

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Figure 1: Advanced imaging of the motor cortex in ALS.
Figure 2: Changes in functional connectivity directly related to white matter damage in ALS.
Figure 3: Diffusion tensor imaging in ALS.
Figure 4: Diagnostic accurary of diffusion tensor imaging for amyotrophic lateral sclerosis.

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Authors and Affiliations

  1. Department of Radiology, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, 48109, MI, USA

    Bradley R. Foerster & Robert C. Welsh

  2. Department of Neurology, University of Michigan, JDRF Center for the Study of Complications in Diabetes, 5017 BSRB, 109 Zina Pitcher Road, Ann Arbor, 48109-2200, MI, USA

    Eva L. Feldman

Authors
  1. Bradley R. Foerster
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  2. Robert C. Welsh
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  3. Eva L. Feldman
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Contributions

B. R. Foerster and R. C. Welsh researched data for the article, made substantial contributions to discussion of the content, and wrote the article. E. L. Feldman contributed to review and/or editing of the manuscript before submission.

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Correspondence to Bradley R. Foerster.

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Foerster, B., Welsh, R. & Feldman, E. 25 years of neuroimaging in amyotrophic lateral sclerosis. Nat Rev Neurol 9, 513–524 (2013). https://doi.org/10.1038/nrneurol.2013.153

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