MRI-defined Acute Ischemic Brain Lesions Can Predict Long-term Outcome After Endovascular Thrombectomy for LVO Stroke

Endovascular thrombectomy (EVT) has revolutionized the management of large vessel occlusion (LVO) stroke, but more than half of the patients treated are functionally disabled or die within 90 days.

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Robert William Regenhardt, MD, PhD, a neurointerventionalist and instructor at Massachusetts General Hospital, Anna K. Bonkhoff, MD, neurology research fellow, Natalia S. Rost, MD, MPH, chief of the Stroke Division in the Department of Neurology, and colleagues used structural and functional MRI to better understand how lesion location affects acute stroke severity and long-term outcomes. They published their findings in Neurology.

Methods

Mass General maintains a prospective database on patients who undergo EVT. The researchers retrospectively studied 151 patients with LVO stroke who were treated with EVT and underwent post-procedure MRI between January 2011 and September 2019.

56% experienced unfavorable long-term functional outcomes, defined as a modified Rankin Scale (mRS) score >2 at 90 days after stroke. The researchers used MRI data to analyze lesion topography.

Region-specific Factors

The regions in the cortex most relevant to unfavorable 90-day outcomes were:

• Bilateral precentral gyri of the frontal lobes—involved in primary motor function
• Bilateral postcentral gyri of the parietal lobes—involved in primary somatosensory function
• Bilateral insular cortex—a somewhat surprising result, perhaps attributable to altered consciousness/emotions and autonomic dysregulation
• Opercular cortex—recently linked to depressive symptoms after stroke

Important subcortical regions were:

• Left putamen—involved in motor control and language
• Left caudate nucleus—associated with cognitive and language problems when infarcted in isolation; extensive infarcts can result in movement abnormalities and neuropsychiatric symptoms
• Left-hemispheric white matter tracts, particularly the corticospinal tract, which is involved in voluntary motor control

Compartment-specific Factors

The researchers then compared the overall effects of lesions in the cortex, subcortex, and white matter tracts on outcomes. There were divergent results:

• Acute stroke severity—Lesions affecting subcortical nuclei were the most relevant
• 90-day mRS score—Lesions affecting white matter tracts had the greatest influence

Functional Connectivity

Lesion network mapping estimates how local stroke lesions affect whole-brain functional networks. This technique derives the burden of indirect lesion effects (functional disconnection).

Mapping showed that across all patients:

• Acute ischemic lesions were most positively connected to insular, opercular, and pre- and post-central regions of the cortex, mostly as part of the sensorimotor network; in other words, the lesions were most functionally disconnected from these brain regions
• Acute ischemic lesions were most negatively connected to posterior and medial frontal regions of the cortex
• Patients who had reperfusion <50% after EVT had especially pronounced lesion connectivity in both the positive and negative directions; in particular, pre- and post-central regions in the right hemisphere were more positively connected to damaged tissue
• Whole-brain lesion connectivity correlated positively with 90-day mRS scores (r=0.32; P=0.00005)

Thus, higher lesion connectivity in the absence of good reperfusion after EVT predicted worse functional outcomes. Even stroke lesions that don't directly affect cortical motor areas seem to interfere with their physiological function through disconnection and thus may promote further deterioration in function.

Relevance to Patient Care

Improved prognostication in the acute setting would:

• Identify patients with large infarct volumes who could undergo EVT because the stroke spared highly relevant regions
• Allow better planning for rehabilitation
• Guide goals-of-care discussions with patients and their families

A better understanding of highly relevant brain regions in LVO stroke should also facilitate the development of targeted agents for neuroprotection or neural repair. For instance, this work suggests a key role for white matter neuroprotection, which has been understudied because of limitations in animal models.

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