Functional reorganization of motor cortex increases with greater axonal injury from CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-artery disease that clinically involves only the brain. Particularly early in the disease, patients can show substantial or complete recovery after individual strokes. Cortical functional reorganization may contribute to limiting disability with such ischemic injury. We sought to test whether the extent of any functional changes in the motor cortex increases with greater brain axonal injury from CADASIL. Functional MRI (fMRI) was used to characterize cortical activation during a simple hand-tapping task. Disease-associated pathology in subcortical white matter was assessed with the use of conventional fluid-attenuated inversion recovery (FLAIR) MRI and MR spectroscopic imaging for measurement of N-acetyl aspartate decreases, a relatively specific measure of axonal injury. There was evidence for variable but substantial hyperintense white matter signal in all of the patients with FLAIR imaging. With the use of fMRI, the brain regions activated during motor tasks were similar for the 9 CADASIL patients and 7 controls, except that most (6 of 9) patients showed primary motor cortex activation both ipsilateral and contralateral to the hand moved, a finding in only 1 of 7 healthy controls. Ipsilateral motor cortex activation increased (r=-0.77, P<0.05) and motor cortex activation lateralization index decreased (r=0.68, P<0.02) with greater white matter injury (as assessed from decreases in the relative N-acetyl aspartate concentration) in a region of interest including descending motor fibers of the corticospinal pathway. The extent of functional reorganization of motor cortex increases with increasing axonal injury, consistent with an adaptive role for these changes. Increased functional recruitment of cortex ipsilateral to the limb moved therefore may contribute to limiting motor impairment from the subcortical injury of CADASIL.