Cerebellar tract alterations in PLS and ALS

Abstract

The cerebellum shows neuropathological change in a number of neurodegenerative conditions where clinical involvement is not the primary feature, including amyotrophic lateral sclerosis (ALS). Whether these changes are associated with disruption to the direct cerebellar tract pathways to the motor cortex and spinal cord in ALS is uncertain. Diffusion tensor imaging was used to examine the integrity of two primary cerebellar pathways, the dentato-rubro-thalamo-cortical (DRTC) and spino-cerebellar (SC) tracts. ALS patients with an upper motor neuron (UMN)-predominant phenotype (n = 9), were matched to a group with the UMN-only condition primary lateral sclerosis (PLS, n = 10) and healthy controls (n = 17). Significant alterations across diffusion metrics in the DRTC proximal to the motor cortex were found in both patient groups. PLS patients were found to have an independent diffusion abnormality in the cerebellar region of the DRTC and SC tracts. Disruption to primary cerebellar tracts in PLS is therefore postulated, adding to other markers of its divergent pathogenesis from ALS.

Keywords:

• Amyotrophic lateral sclerosis
• primary lateral sclerosis
• diffusion tensor imaging
• cerebellum

Acknowledgments

The authors thank all the study participants for their efforts and enthusiasm for clinical research.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

The Oxford MND Centre (MRT, KT) receives funding from the Motor Neurone Disease Association. ST is funded by the Australian National Health and Medical Research Council CJ Martin Early Career Fellowship (APP1121859). MCK was supported by the Australian National Health and Medical Research Council Program Grant (Forefront #1037746). MRT is funded by the Medical Research Council and Motor Neurone Disease Association Lady Edith Wolfson Senior Clinical Fellowship (MR/K01014X/1).