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From the Department of Clinical Neurosciences (Drs. Ellis, Simmons, Bland, Dawson, Williams, and Leigh), Institute of Psychiatry, and Guy’s, King’s and St. Thomas’ School of Medicine; Neuroimaging Department (Drs. Simmons, Dawson, and Williams), Maudsley Hospital; and Division of Medical Physics (D.K. Jones and Dr. Horsfield), University of Leicester, Leicester Royal Infirmary, London, UK.
Address correspondence and reprint requests to Dr. Cathy M. Ellis, Department of Clinical Neurosciences, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
BACKGROUND: A number of neurophysiologic and neuroimaging techniques have been evaluated in the research setting to assess upper motor neuron (UMN) damage in ALS. Changes in tissue structure in the CNS modify the diffusional behavior of water molecules, which can be detected by diffusion tensor MRI.
OBJECTIVES: To explore the hypothesis that degeneration of the motor fibers in ALS would be reflected by changes in the diffusion characteristics of the white matter fibers in the posterior limb of the internal capsule and that these changes could be detected by diffusion tensor MRI.
METHODS: We studied 22 patients with El Escorial definite, probable, or possible ALS—11 with limb onset (mean age 54.5 ± 10.7 years) and 11 with bulbar onset (mean age 49.6 ± 11.7 years)—and compared them with 20 healthy, age-matched controls (mean age 46.0 ± 12.6 years). We assessed central motor conduction time (CMCT), threshold to stimulation, and silent period using transcranial magnetic stimulation. Diffusion tensor MRI was performed using a 1.5-T GE Signa system (Milwaukee, WI) fitted with Advanced NMR hardware and software capable of producing echo planar MR images. Data were acquired from seven coronal slices centered to include the posterior limb of the internal capsule. Maps of the mean diffusivity, fractional anisotropy, and T2-weighted signal intensity were generated.
RESULTS: There were no differences between the subject groups on measures of CMCT, threshold to stimulation, and silent period. However, the CMCT correlated with clinical measures of UMN involvement. We found a significant increase in the mean diffusivity and reduction in fractional anisotropy along the corticospinal tracts between the three subject groups, most marked in the bulbar-onset group. The fractional anisotropy correlated with measures of disease severity and UMN involvement, whereas the mean diffusivity correlated with disease duration.
CONCLUSION: The results support the use of diffusion tensor MRI in detecting pathology of the corticospinal tracts in ALS.
Key words: Amyotrophic lateral sclerosis—Diffusion tensor MRI.
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