Brain Structure, Connectivity, and Cognitive Changes Following Revascularization Surgery in Adult Moyamoya Disease

Abstract

BACKGROUND The effect of the combined direct/indirect revascularization surgery in Moyamoya disease has not been evaluated sufficiently with regard to cognitive function, brain microstructure, and connectivity. OBJECTIVE To investigate structural and functional changes following revascularization surgery in patients with moyamoya disease (MMD) through a combined analysis of brain morphology, microstructure, connectivity, and neurobehavioral data. METHODS Neurobehavioral and neuroimaging examinations were performed in 25 adults with MMD prior to and >12 mo after revascularization surgery. Cognitive function was investigated using the Wechsler Adult Intelligence Scale-III, Trail-Making Test, Wisconsin Card Sorting Test, Continuous Performance Test, Stroop test, and Wechsler Memory Scale. We assessed white matter integrity using diffusion tensor imaging, brain morphometry using magnetization-prepared rapid gradient-echo sequences, and brain connectivity using resting-state functional magnetic resonance imaging (MRI). RESULTS Cognitive examinations revealed significant changes in the full-scale intelligence quotient (IQ), performance IQ (PIQ), perceptual organization (PO), processing speed, and Stroop test scores after surgery (P < .05). Enlargement of the lateral ventricle, volume reductions in the corpus callosum and subcortical nuclei, and cortical thinning in the prefrontal cortex were also observed (P < .05). Fractional anisotropy in the white matter tracts, including the superior longitudinal fasciculus, increased 2 to 4 yr after surgery, relative to that observed in the presurgical state (P < .05). Resting-state brain connectivity was increased predominantly in the fronto-cerebellar circuit and was positively correlated with improvements in PIQ and PO (P < .05). CONCLUSION Revascularization surgery may improve processing speed and attention in adult patients with MMD. Further, multimodal MRI may be useful for detecting subtle postsurgical brain structural changes, reorganization of white matter tracts, and brain connectivity alterations.

Myelin and Axonal Damage in Normal-Appearing White Matter in Patients with Moyamoya Disease

“…As discussed above, the decrease in the MVF and the increase in the g-ratio might precede the decrease in the AVF and the decrease in the g-ratio. 7,25 Moreover, in patients with MMD, both the cortex and white matter are affected by chronic ischemia, [5][6][7]27,28 and while direct ischemic damage to white matter might result in more myelin damage than axonal damage, cortical damage must cause both myelin and axonal damage due to the decrease in axonal fibers radiating from the affected cortex. Thus, the presence of axonal damage might reflect more global damage than myelin damage in this disease population.…”

“…These results suggest that ischemic damage to myelin and axons in patients with MMD might be, at least partially, irreversible. 6,27 Postoperative improvements in microstructural integrity evaluated by diffusion MR imaging are reported in patients with MMD 28 and carotid artery stenosis, 31 but whether these observed changes are due to an increase in axon integrity, such as remyelination, or a decrease in interstitial fluid 32 remains unclear. Compared with diffusion MR imaging, which indirectly assesses the presence of myelin damage by evaluating increased water diffusion in the brain parenchyma, the MTsat method has the strength of being directly sensitive to myelin.…”

Contemporary and emerging magnetic resonance imaging methods for evaluation of moyamoya disease

“…microstructure in MMD that cannot be visibly assessed in so-called normal-appearing white matter. 24,30,31 Such changes have been correlated to clinical status, such as cognitive measures with frontal lobe white matter involvement; there is evidence that these imaging and clinical changes can improve after revascularization. 31…”

“…60 Recent evidence indicates that this reduced functional connectivity is associated with certain clinical features depending on the anatomical area of involvement and can improve after revascularization, both ipsilateral and contralateral to the bypass. 31,60 However, rsfMRI in the setting of MMD may lead to inaccurate results without appropriate expertise and corrections for temporal alterations of blood flow when assessing patterns of spontaneous brain activity; 23 rsfMRI requires hardware and software and specialized data processing and interpretation that is not universally available clinically.…”

“…3 VWI may be useful for lumen assessment in areas of artifact on 3D-TOF and segments of very high-grade stenosis. 31 In many cases, these VWI studies need confirmation with additional work to show reproducibility and validity in various patient populations if these findings are to be used to heavily influence clinical care. Readers should take into account spatial resolution and type of flow-suppression technique, as these technical factors can impact the appearance of vessel wall 12 and vessel wall enhance- ment.…”