White matter pathology in ALS and lower motor neuron ALS variants: a diffusion tensor imaging study using tract-based spatial statistics

J Neurol. 2012 Sep;259(9):1848-59. doi: 10.1007/s00415-012-6420-y. Epub 2012 Feb 21.


The aim of this work was to investigate white-matter microstructural changes within and outside the corticospinal tract in classical amyotrophic lateral sclerosis (ALS) and in lower motor neuron (LMN) ALS variants by means of diffusion tensor imaging (DTI). We investigated 22 ALS patients and 21 age-matched controls utilizing a whole-brain approach with a 1.5-T scanner for DTI. The patient group was comprised of 15 classical ALS- and seven LMN ALS-variant patients (progressive muscular atrophy, flail arm and flail leg syndrome). Disease severity was measured by the revised version of the functional rating scale. White matter fractional anisotropy (FA) was assessed using tract-based spatial statistics (TBSS) and a region of interest (ROI) approach. We found significant FA reductions in motor and extra-motor cerebral fiber tracts in classical ALS and in the LMN ALS-variant patients compared to controls. The voxel-based TBSS results were confirmed by the ROI findings. The white matter damage correlated with the disease severity in the patient group and was found in a similar distribution, but to a lesser extent, among the LMN ALS-variant subgroup. ALS and LMN ALS variants are multisystem degenerations. DTI shows the potential to determine an earlier diagnosis, particularly in LMN ALS variants. The statistically identical findings of white matter lesions in classical ALS and LMN variants as ascertained by DTI further underline that these variants should be regarded as part of the ALS spectrum.

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / pathology*
  • Analysis of Variance
  • Anisotropy
  • Brain / pathology*
  • Brain Mapping
  • Diffusion Tensor Imaging*
  • Disability Evaluation
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Linear Models
  • Male
  • Middle Aged
  • Motor Neurons / pathology*
  • Nerve Fibers, Myelinated / pathology*