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Differential corticospinal tract degeneration in homozygous 'D90A' SOD-1 ALS and sporadic ALS.
J Neurol Neurosurg Psychiatry. 2011 Aug; 82(8):843-9.JN

Abstract

BACKGROUND

The homogeneous genotype and stereotyped phenotype of a unique familial form of amyotrophic lateral sclerosis (ALS) (patients homozygous for aspartate-to-alanine mutations in codon 90 (homD90A) superoxide dismutase 1) provides an ideal model for studying genotype/phenotype interactions and pathological features compared with heterogeneous apparently sporadic ALS. The authors aimed to use diffusion tensor tractography to quantify and compare changes in the intracerebral corticospinal tracts of patients with both forms of ALS, building on previous work using whole-brain voxelwise group analysis.

METHOD

21 sporadic ALS patients, seven homD90A patients and 20 healthy controls underwent 1.5 T diffusion tensor MRI. Patients were assessed using 'upper motor neuron burden,' El Escorial and ALSFR-R scales. The intracranial corticospinal tract was assessed using diffusion tensor tractography measures of fractional anisotropy (FA), mean diffusivity, and radial and axial diffusivity obtained from its entire length.

RESULTS

Corticospinal tract FA was reduced in sporadic ALS patients compared with both homD90A ALS patients and controls. The diffusion measures in sporadic ALS patients were consistent with anterograde (Wallerian) degeneration of the corticospinal tracts. In sporadic ALS, corticospinal tract FA was related to clinical measures. Despite a similar degree of clinical upper motor neuron dysfunction and disability in homD90A ALS patients compared with sporadic ALS, there were no abnormalities in corticospinal tract diffusion measures compared with controls.

CONCLUSIONS

Diffusion tensor tractography has shown axonal degeneration within the intracerebral portion of the corticospinal tract in sporadic ALS patients, but not those with a homogeneous form of familial ALS. This suggests significant genotypic influences on the phenotype of ALS and may provide clues to slower progression of disease in homD90A patients.

Authors+Show Affiliations

Department of Clinical Neuroscience, King’s College London, Institute of Psychiatry, London, UKNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21515558

Citation

Blain, C R V., et al. "Differential Corticospinal Tract Degeneration in Homozygous 'D90A' SOD-1 ALS and Sporadic ALS." Journal of Neurology, Neurosurgery, and Psychiatry, vol. 82, no. 8, 2011, pp. 843-9.
Blain CR, Brunton S, Williams VC, et al. Differential corticospinal tract degeneration in homozygous 'D90A' SOD-1 ALS and sporadic ALS. J Neurol Neurosurg Psychiatry. 2011;82(8):843-9.
Blain, C. R., Brunton, S., Williams, V. C., Leemans, A., Turner, M. R., Andersen, P. M., Catani, M., Stanton, B. R., Ganesalingham, J., Jones, D. K., Williams, S. C., Leigh, P. N., & Simmons, A. (2011). Differential corticospinal tract degeneration in homozygous 'D90A' SOD-1 ALS and sporadic ALS. Journal of Neurology, Neurosurgery, and Psychiatry, 82(8), 843-9. https://doi.org/10.1136/jnnp.2010.236018
Blain CR, et al. Differential Corticospinal Tract Degeneration in Homozygous 'D90A' SOD-1 ALS and Sporadic ALS. J Neurol Neurosurg Psychiatry. 2011;82(8):843-9. PubMed PMID: 21515558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential corticospinal tract degeneration in homozygous 'D90A' SOD-1 ALS and sporadic ALS. AU - Blain,C R V, AU - Brunton,S, AU - Williams,V C, AU - Leemans,A, AU - Turner,M R, AU - Andersen,P M, AU - Catani,M, AU - Stanton,B R, AU - Ganesalingham,J, AU - Jones,D K, AU - Williams,S C R, AU - Leigh,P N, AU - Simmons,A, Y1 - 2011/04/21/ PY - 2011/4/26/entrez PY - 2011/4/26/pubmed PY - 2011/10/5/medline SP - 843 EP - 9 JF - Journal of neurology, neurosurgery, and psychiatry JO - J. Neurol. Neurosurg. Psychiatry VL - 82 IS - 8 N2 - BACKGROUND: The homogeneous genotype and stereotyped phenotype of a unique familial form of amyotrophic lateral sclerosis (ALS) (patients homozygous for aspartate-to-alanine mutations in codon 90 (homD90A) superoxide dismutase 1) provides an ideal model for studying genotype/phenotype interactions and pathological features compared with heterogeneous apparently sporadic ALS. The authors aimed to use diffusion tensor tractography to quantify and compare changes in the intracerebral corticospinal tracts of patients with both forms of ALS, building on previous work using whole-brain voxelwise group analysis. METHOD: 21 sporadic ALS patients, seven homD90A patients and 20 healthy controls underwent 1.5 T diffusion tensor MRI. Patients were assessed using 'upper motor neuron burden,' El Escorial and ALSFR-R scales. The intracranial corticospinal tract was assessed using diffusion tensor tractography measures of fractional anisotropy (FA), mean diffusivity, and radial and axial diffusivity obtained from its entire length. RESULTS: Corticospinal tract FA was reduced in sporadic ALS patients compared with both homD90A ALS patients and controls. The diffusion measures in sporadic ALS patients were consistent with anterograde (Wallerian) degeneration of the corticospinal tracts. In sporadic ALS, corticospinal tract FA was related to clinical measures. Despite a similar degree of clinical upper motor neuron dysfunction and disability in homD90A ALS patients compared with sporadic ALS, there were no abnormalities in corticospinal tract diffusion measures compared with controls. CONCLUSIONS: Diffusion tensor tractography has shown axonal degeneration within the intracerebral portion of the corticospinal tract in sporadic ALS patients, but not those with a homogeneous form of familial ALS. This suggests significant genotypic influences on the phenotype of ALS and may provide clues to slower progression of disease in homD90A patients. SN - 1468-330X UR - https://www.unboundmedicine.com/medline/citation/21515558/Differential_corticospinal_tract_degeneration_in_homozygous_'D90A'_SOD_1_ALS_and_sporadic_ALS_ L2 - http://jnnp.bmj.com/cgi/pmidlookup?view=long&pmid=21515558 DB - PRIME DP - Unbound Medicine ER -