Frontiers in Neuroscience (Aug 2022)

Deep profiling of multiple ischemic lesions in a large, multi-center cohort: Frequency, spatial distribution, and associations to clinical characteristics

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

DOI
https://doi.org/10.3389/fnins.2022.994458
Journal volume & issue
Vol. 16

Abstract

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Background purposeA substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort.Materials and methodsAnalyses relied upon imaging and clinical data from the international MRI-GENIE study. Imaging data comprised both Fluid-attenuated inversion recovery (FLAIR) for white matter hyperintensity (WMH) burden estimation and diffusion-weighted imaging (DWI) sequences for the assessment of acute stroke lesions. The initial step featured the systematic evaluation of occurrences of MAL within one and several vascular supply territories. Associations between MAL and important imaging and clinical characteristics were subsequently determined. The interaction effect between single and multiple lesion status and lesion volume was estimated by means of Bayesian hierarchical regression modeling for both stroke severity and functional outcome.ResultsWe analyzed 2,466 patients (age = 63.4 ± 14.8, 39% women), 49.7% of which presented with a single lesion. Another 37.4% experienced MAL in a single vascular territory, while 12.9% featured lesions in multiple vascular territories. Within most territories, MAL occurred as frequently as single lesions (ratio ∼1:1). Only the brainstem region comprised fewer patients with MAL (ratio 1:4). Patients with MAL presented with a significantly higher lesion volume and acute NIHSS (7.7 vs. 1.7 ml and 4 vs. 3, pFDR < 0.001). In contrast, patients with a single lesion were characterized by a significantly higher WMH burden (6.1 vs. 5.3 ml, pFDR = 0.048). Functional outcome did not differ significantly between patients with single versus multiple lesions. Bayesian analyses suggested that the association between lesion volume and stroke severity between single and multiple lesions was the same in case of anterior circulation stroke. In case of posterior circulation stroke, lesion volume was linked to a higher NIHSS only among those with MAL.ConclusionMultiple 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 total DWI lesion volume and a lower WMH lesion volume. In posterior circulation stroke, lesion volume was linked to a higher stroke severity in multiple lesions only.

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