Article Text

Download PDFPDF
Research paper
Cortical thickness in ALS: towards a marker for upper motor neuron involvement
  1. Renée Walhout1,
  2. Henk-Jan Westeneng1,
  3. Esther Verstraete1,
  4. Jeroen Hendrikse2,
  5. Jan H Veldink1,
  6. Martijn P van den Heuvel3,
  7. Leonard H van den Berg1
  1. 1Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2Department of Radiology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
  3. 3Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
  1. Correspondence to Leonard H van den Berg, Department of Neurology, G03.228, University Medical Center Utrecht, PO Box 85500, Utrecht 3508 GA, The Netherlands L.H.vandenBerg{at}


Objective Examine whether cortical thinning is a disease-specific phenomenon across the spectrum of motor neuron diseases in relation to upper motor neuron (UMN) involvement.

Methods 153 patients (112 amyotrophic lateral sclerosis (ALS), 19 patients with a clinical UMN phenotype, 22 with a lower motor neuron (LMN) phenotype), 60 healthy controls and 43 patients with an ALS mimic disorder were included for a cross-sectional cortical thickness analysis. Thirty-nine patients with ALS underwent a follow-up scan. T1-weighted images of the brain were acquired using a 3 T scanner. The relation between cortical thickness and clinical measures, and the longitudinal changes were examined.

Results Cortical thickness of the precentral gyrus (PCG) was significantly reduced in ALS (p=1.71×10−13) but not in mimic disorders (p=0.37) or patients with an LMN phenotype (p=0.37), as compared to the group of healthy controls. Compared to patients with ALS, patients with a UMN phenotype showed an even lower PCG cortical thickness (p=1.97×10−3). Bulbar scores and arm functional scores showed a significant association with cortical thickness of corresponding body regions of the motor homunculus. Longitudinal analysis revealed a decrease of cortical thickness in the left temporal lobe of patients with ALS (parahippocampal region p=0.007 and fusiform cortex p=0.001).

Conclusions PCG cortical thinning was found to be specific for motor neuron disease with clinical UMN involvement. Normal levels of cortical thickness in mimic disorders or LMN phenotypes suggest that cortical thinning reflects pathological changes related to UMN involvement. Progressive cortical thinning in the temporal lobe suggests recruitment of non-motor areas, over time.

  • ALS
  • MRI

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.