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Research paper
Structural MRI reveals cortical thinning in amyotrophic lateral sclerosis
  1. Esther Verstraete1,
  2. Jan H Veldink1,
  3. Jeroen Hendrikse2,
  4. H Jurgen Schelhaas3,
  5. Martijn P van den Heuvel4,
  6. Leonard H van den Berg1
  1. 1Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands
  2. 2Department of Radiology, University Medical Centre Utrecht, Utrecht, The Netherlands
  3. 3Department of Neurology and Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  4. 4Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands
  1. Correspondence to Professor L H van den Berg, Department of Neurology (HP G03.228), University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands; l.h.vandenberg{at}


Objectives Amyotrophic lateral sclerosis (ALS) is a fatal disease characterised by combined upper and lower motor neuron degeneration. An early and accurate diagnosis is important for patient care and might facilitate the search for a more effective therapy. MRI was used to study the whole cortical mantle, applying an unbiased surface based approach to identify a marker of upper motor neuron involvement in ALS.

Methods Surface based cortical morphology analyses were performed on structural, 3T MRI data of 45 patients with ALS and 25 matched healthy controls in a case control study design. These analyses consisted of measuring cortical thickness, surface area and volume. The effects of disease progression were examined by correlating cortical measures with progression rate and by longitudinal measures in 20 patients.

Results Cortical morphology analyses revealed specific thinning in the precentral gyrus, considered the primary motor cortex, in patients with ALS compared with controls (p=6.3×10−8). Surface area was reduced in the right inferior parietal region (p=0.049) and volume—the product of cortical thickness and surface area—was reduced in the right precentral gyrus (p=0.031). From these findings, it appears that cortical thickness is superior in detecting the degenerative effects of ALS. Relative cortical thinning in temporal regions was related to faster clinical progression (right inferior temporal gyrus: p=3.3×10−4).

Conclusions Cortical thinning of the primary motor cortex might be a diagnostic marker for upper motor neuron degeneration in ALS. Relative thinning in temporal regions was associated with a rapidly progressive disease course.

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  • MPH and LHB contributed equally to the manuscript.

  • Funding The current study was supported by the ‘Prinses Beatrix Fonds’ and the Netherlands ALS Foundation.

  • Competing interests None.

  • Ethics approval The study was approved by the medical ethics committee for research into humans of the University Medical Centre Utrecht.

  • Provenance and peer review Not commissioned; externally peer reviewed.