Cortical thickness in ALS: Towards a marker for upper motor neuron involvement

Renée Walhout, Henk Jan Westeneng, Esther Verstraete, Jeroen Hendrikse, Jan H. Veldink, Martijn P. Van Den Heuvel, Leonard H. Van Den Berg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)


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<sup>-13</sup>) 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<sup>-3</sup>). 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.

Original languageEnglish
Pages (from-to)288-294
Number of pages7
JournalJournal of Neurology, Neurosurgery and Psychiatry
Issue number3
Publication statusPublished - 1 Mar 2015


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