Volumetric analysis reveals corticospinal tract degeneration and extramotor involvement in ALS

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 remain s unclear. Methods: The authors used automated image analysis to quantify v olumes of cerebral gray and white matter in 16 patients with ALS (eight lim b 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 H-1-MRS in the subcortical white matter in the motor cortex region in the patients with bulbar-onset ALS. To determine wh ether this resulted from axonal degeneration, they also compared gray and w hite matter volumes in the patients with limb- and bulbar-onset ALS. Result s: There were no differences in the total brain volumes of gray or white ma tter for the three subject groups (p > 0.23). Comparison of the total ALS g roup and controls revealed localized deficits in gray matter volume centere d on Brodmann areas 8, 9, and 10 bilaterally. Comparison of the patients wi th limb- and bulbar-onset ALS revealed deficits in the white matter volume in the bulbar-onset group, extending bilaterally from the precentral gyros into the internal capsule and brainstem, consistent with the course of the corticospinal tract. There was no loss in gray matter volume in the precent ral gyri, Conclusions: The loss of gray matter in the frontal regions (tota l ALS group) provides further support that ALS is a multisystem disorder. I n addition, there is in vivo evidence of axonal degeneration in the subcort ical white matter in the motor region in patients with bulbar-onset ALS. Th is is consistent with a "dying back" process affecting cortical motoneurons in bulbar-onset ALS.