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Multiple Lesions Are More Frequent Than Previously Thought in Acute Ischemic Stroke

Key findings

  • This study investigated the frequency and distribution of multiple ischemic lesions and their associations with clinical factors and stroke outcomes by profiling MR images for 2,466 patients at an unprecedented level of detail
  • Multiple lesions (located either within one vascular territory or multiple vascular territories) occurred in 1,241 patients (50%), and 87% of them occurred in a single vascular territory
  • Cardioembolic and large artery occlusion etiologies were significantly more common in patients with multiple lesions, but every stroke etiology occurred in both single- and multiple-lesion stroke
  • In the case of posterior circulation stroke, but not anterior circulation stroke, a given lesion volume was linked to higher stroke severity in patients with multiple lesions than those with single lesions
  • Patients with single lesions and those with multiple lesions did not significantly differ in their three-month post-stroke functional outcome

The most recent MRI-focused studies have concluded that multiple ischemic lesions occur in 10% to 30% of patients with acute ischemic stroke.

However, after analyzing a large MRI dataset with unprecedented detail, researchers at Massachusetts General Hospital reported a frequency of 50%. Anna K. Bonkhoff, MD, research fellow in the Department of Neurology, Natalia S. Rost, MD, MPH, chief of the Stroke Division, and colleagues also determined that in patients with posterior circulation stroke, multiple lesions were linked to greater stroke severity independent of the individual lesion volume, although not poorer three-month functional outcomes. They published their findings in Frontiers in Neuroscience.


The data source for this study was the international MRI–Genetics Interface Exploration study, which aimed to facilitate genetic analysis of patients with acute ischemic stroke by creating a large dataset of clinical data and well-characterized MRI scans.

This analysis included 2,466 patients (39% female, mean age 63) with lesions visible on diffusion-weighted imaging. Two neuroradiologists manually reviewed all scans using a structured reporting tool to capture detailed information on whether the lesions were single or multiple, their location(s), and other characteristics.

Multiple-lesion stroke was defined as either multiple lesions in any vascular territory (anterior, middle or posterior cerebral artery, cerebellum, or brainstem) or distinct lesions in more than one territory. In many previous studies, "multiple lesions" had to occur in multiple vascular territories.

Frequency and Location of Multiple Lesions

1,241 patients (50%) exhibited multiple ischemic lesions. Of those, 87% had all their lesions within one vascular territory, and 13% had lesions in multiple territories.

When each vascular territory was considered separately, the frequency of multiple lesions was approximately 50% in all but one: multiple lesions within the brainstem were four times less likely than single lesions (19% vs. 81%).

Multiple Lesions and Patient Characteristics

Patients with multiple lesions were significantly more likely than those with single lesions to:

  • Have a diagnosis of atrial fibrillation—17% vs. 12% (P=0.005)
  • Be nonsmokers—50% vs. 43% (P=0.002)
  • Be diagnosed with cardioembolic stroke—18% vs. 14% (P=0.008)
  • Be diagnosed with large artery occlusion stroke—30% vs. 16% (P<0.001)

However, differences in stroke etiology were not absolute, as every stroke etiology occurred in both single- and multiple-lesion stroke.

Multiple Lesions and Stroke Severity

Data about lesion volume and acute stroke severity were available for a subset of 1,011 patients (48% with multiple lesions). Patients with multiple lesions presented with both significantly higher stroke severity (mean NIHSS score 6.3 vs. 4.6; P<0.001) and greater lesion volume (mean 7.7 vs. 1.7 mL; P=0.001).

In regression analysis, they found:

  • Entire cohort—The effects of lesion volume were comparable between patients with single and multiple lesions
  • Patients with anterior circulation strokes—Same result as for the entire cohort
  • Patients with posterior circulation strokes—A given lesion volume was linked to higher stroke severity in patients with multiple lesions than those with single lesions

Multiple Lesions and Outcomes

Information about three-month functional outcomes was available for 747 of the patients (53% with multiple lesions). In regression analysis of that cohort, there was a positive relationship between lesion volume and unfavorable functional outcomes. Still, that effect did not differ between the single- and multiple-lesion groups.

Among patients with posterior circulation stroke, lesion volume was not significantly associated with unfavorable functional outcomes for patients with either single or multiple lesions.

Therapeutic Relevance

The high frequency of multiple lesions in this study underscores their clinical importance. Many patients could benefit from optimizing preventive regimens and acute treatments.

It should be worthwhile to reevaluate the more atypical constellations of stroke etiology, such as small artery occlusion in patients with multiple lesions. A better understanding of what causes multiple versus single lesions may improve secondary prevention strategies.

of patients with acute ischemic stroke had multiple lesions

of patients with multiple ischemic lesions had lesions in a single vascular territory

greater rate of single lesions than multiple lesions in the brainstem

Learn more about the Stroke Service at Mass General

Learn more about the Department of Neurology

Related topics


Anna K. Bonkhoff, MD, and Natalia S. Rost, MD, MPH, of the Kistler Stroke Research Center, and colleagues found considerable sex differences in the lesion patterns that underlie the severity of acute ischemic stroke. Further investigation may lead to sex-specific approaches to stroke management.


Robert Regenhardt, MD, PhD, and Natalia S. Rost, MD, MPH, of the Department of Neurology, and colleagues found that among patients with large vessel occlusion stroke, ischemic lesions identified by MRI after endovascular thrombectomy were associated with both acute stroke severity and 90-day functional outcome.