Deep profiling of multiple ischemic lesions in a large, multi-center cohort: Frequency, spatial distribution, and associations to clinical characteristics
Authors: Bonkhoff Anna K. , Ullberg Teresa , Bretzner Martin , Hong Sungmin , Schirmer Markus D. , Regenhardt Robert W. , Donahue Kathleen L. , Nardin Marco J. , Dalca Adrian V. , Giese Anne-Katrin , Etherton Mark R. , Hancock Brandon L. , Mocking Steven J. T. , McIntosh Elissa C. , Attia John , Cole John W. , Donatti Amanda , Griessenauer Christoph J. , Heitsch Laura , Holmegaard Lukas , Jood Katarina , Jimenez-Conde Jordi , Kittner Steven J. , Lemmens Robin , Levi Christopher R. , McDonough Caitrin W. , Meschia James F. , Phuah Chia-Ling , Ropele Stefan , Rosand Jonathan , Roquer Jaume , Rundek Tatjana , Sacco Ralph L. , Schmidt Reinhold , Sharma Pankaj , Slowik Agnieszka , Sousa Alessandro , Stanne Tara M. , Strbian Daniel , Tatlisumak Turgut , Thijs Vincent , Vagal Achala , Woo Daniel , Zand Ramin , McArdle Patrick F. , Worrall Bradford B. , Jern Christina , Lindgren Arne G. , Maguire Jane , Wu Ona , Frid Petrea , Rost Natalia S. , Wasselius Johan 
Published: July 2022

Background

A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). However, the spatial distribution and clinical implications of such MAL are incompletely understood.

Methods

Analyses relied upon imaging and clinical data of patients with AIS from the international MRI-GENIE study. Initially, we systematically evaluated the occurrences of MAL within (i) one and, (ii) several vascular supply territories. Associations between the presence of MAL and important characteristics, such as DWI lesion volume, NIHSS-based acute stroke severity, and long-term functional outcome were subsequently determined. The interaction effect between single and multiple lesion status and DWI lesion volume was estimated by means of Bayesian regression modeling for stroke severity and functional outcome.

Results

We analyzed 2,466 patients [age: 63.4±14.8, 39% women], 49.7% of which presented with single lesions. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in several territories. Within most territories (anterior, middle, and posterior cerebral artery, cerebellar), multiple lesions occurred as frequently as single lesions (ratio ∼1:1). Only the brainstem region comprised fewer patients with multiple lesions (ratio ∼1:4). Patients with MAL presented with a significantly higher DWI lesion volume and acute NIHSS (7.7ml vs. 1.7ml and 4 vs. 3,pFDR≤0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1ml versus 5.3ml,pFDR=0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between DWI lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In the case of posterior circulation stroke, DWI lesion volume was linked to a higher acute NIHSS only among those with multiple lesions.

Conclusions

Multiple lesions, especially those within one vascular territory, occurred more frequently than previously reported. Overall, multiple lesions were distinctly linked to a higher acute stroke severity, a higher DWI lesion volume and lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.