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Brain Advance Access originally published online on November 7, 2003
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Brain, Vol. 127, No. 2, 340-350, 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh041

Diffusion tensor MRI of early upper motor neuron involvement in amyotrophic lateral sclerosis

Miriam Sach, Gerhard Winkler, Volkmar Glauche, Joachim Liepert, Bernhard Heimbach, Martin A. Koch, Christian Büchel and Cornelius Weiller

Department of Neurology, Neuroimage Nord, University Hospital Hamburg, Eppendorf, Germany

Correspondence to: Miriam Sach, MD, Klinik und Poliklinik für Neurologie, UKE, Martinistrasse 52, 20246 Hamburg, Germany E-mail: sach{at}uke.uni-hamburg.de

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative system disorder affecting both upper and lower motor neurons. Despite supportive electrophysiological investigations, the involvement of the upper motor neuron is often difficult to assess at an early stage of disease. Diffusion tensor MRI provides an estimate of the orientation of fibre bundles in white matter on the basis of the diffusion characteristics of water. Diffusivity is generally higher in directions along fibre tracts than perpendicular to them. This degree of directionality of diffusion can be measured as fractional anisotropy. Changes in tissue structure due to degeneration of the corticospinal fibres can lead to a modification of the degree of directionality which can be detected by diffusion tensor MRI. We investigated 15 patients with ALS, six of whom had no clinical signs of upper motor neuron involvement at the time of MRI investigation, but developed pyramidal tract symptoms later in the course of their disease. These patients met the El Escorial criteria as their disease progressed. We found a decrease in fractional anisotropy in the corticospinal tract, corpus callosum and thalamus in all 15 ALS patients, including the patients without clinical signs of upper motor neuron lesion, compared with healthy controls. Regression analysis showed a negative correlation between fractional anisotropy and central motor conduction time obtained by transcranial magnetic stimulation, allowing spatial differentiation between the degenerated corticospinal tract fibres that supply the upper and lower extremities. Thus, diffusion tensor MRI can be used to assess upper motor neuron involvement in ALS patients before clinical symptoms of corticospinal tract lesion become apparent, and it may therefore contribute to earlier diagnosis of motor neuron disease.

Key Words: diffusion tensor MRI; amyotrophic lateral sclerosis; upper motor neuron; corticospinal tract; transcranial magnetic stimulation

Abbreviations: ALS = amyotrophic lateral sclerosis; CMCT = central motor conduction time; DTI = diffusion tensor imaging; EPI = echoplanar imaging; LMN = lower motor neuron; MEP = motor evoked potential; MNI = Montreal Neurological Institute; ROI = region of interest; STEAM = stimulated echo acquisition mode; TMS = transcranial magnetic stimulation; SNR = signal-to-noise ratio; UMN = upper motor neuron

Received March 22, 2003. Revised August 18, 2003. Accepted September 23, 2003.


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