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From the Department of Neurology (Drs. Ellis, Simmons, Williams, and Leigh) and Clinical Age Research Unit (Dr. Suckling), Guy’s, Kings & St. Thomas’ School of Medicine and Dentistry, London; Department of Neuroimaging (Drs. Simmons and Williams), Maudsley Hospital, and Brain Image Analysis Unit (Drs. Amaro and Bullmore), Institute of Psychiatry, London; and the Department of Psychiatry (Dr. Bullmore), University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK.
Address correspondence and reprint requests to Dr. C.M. Ellis, Department of Clinical Neuroscience, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK; e-mail: c.ellis{at}iop.kcl.ac.uk
Background:— Pathologic changes in the motor cortex and corticospinal tracts in ALS may be reflected by abnormal signal intensities on conventional MRI. The sensitivity of these changes in detecting underlying pathology remains unclear.
Method:— The authors used automated image analysis to quantify volumes of cerebral gray and white matter in 16 patients with ALS (eight limb onset, eight bulbar onset) and eight normal controls. Previously they had demonstrated a reduction in N-acetyl aspartate/creatine + phosphocreatine (NAA/[Cr + PCr]) measured by 1H-MRS in the subcortical white matter in the motor cortex region in the patients with bulbar-onset ALS. To determine whether this resulted from axonal degeneration, they also compared gray and white matter volumes in the patients with limb- and bulbar-onset ALS.
Results:— There were no differences in the total brain volumes of gray or white matter for the three subject groups (p > 0.23). Comparison of the total ALS group and controls revealed localized deficits in gray matter volume centered on Brodmann areas 8, 9, and 10 bilaterally. Comparison of the patients with limb- and bulbar-onset ALS revealed deficits in the white matter volume in the bulbar-onset group, extending bilaterally from the precentral gyrus into the internal capsule and brainstem, consistent with the course of the corticospinal tract. There was no loss in gray matter volume in the precentral gyri.
Conclusions:— The loss of gray matter in the frontal regions (total ALS group) provides further support that ALS is a multisystem disorder. In addition, there is in vivo evidence of axonal degeneration in the subcortical white matter in the motor region in patients with bulbar-onset ALS. This is consistent with a "dying back" process affecting cortical motoneurons in bulbar-onset ALS.
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