Clinical Relevance of 'Cap' and 'Track' Development after Recent Small Subcortical Infarct

Yajun Cheng; Carmen Arteaga-Reyes; Una Clancy; Daniela Jaime Garcia; Maria Del C Valdés Hernández; Michael J Thrippleton; Michael S Stringer; Gordon W Blair; Stewart Wiseman; Francesca M Chappell; Junfang Zhang; Xiaodi Liu; Angela C C Jochems; Susana Muñoz Maniega; Eleni Sakka; Mark E Bastin; Rosalind Brown; Caroline M J Loos; Stephen D J Makin; Ming Liu; Bo Wu; Fergus N Doubal; Joanna M Wardlaw; MSS‐2, MSS‐3 and the INVESTIGATE‐SVDs Study Group

doi:10.1002/ana.27182

Clinical Relevance of 'Cap' and 'Track' Development after Recent Small Subcortical Infarct

Yajun Cheng, Carmen Arteaga-Reyes, Una Clancy, Daniela Jaime Garcia, Maria Del C Valdés Hernández, Michael J Thrippleton, Michael S Stringer, Gordon W Blair, Stewart Wiseman, Francesca M Chappell, Junfang Zhang, Xiaodi Liu, Angela C C Jochems, Susana Muñoz Maniega, Eleni Sakka, Mark E Bastin, Rosalind Brown, Caroline M J Loos, Stephen D J Makin, Ming LiuBo Wu, Fergus N Doubal, Joanna M Wardlaw^*, MSS‐2, MSS‐3 and the INVESTIGATE‐SVDs Study Group

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

OBJECTIVE: After a recent small subcortical infarct (RSSI), some patients develop perilesional or remote hyperintensities ('caps/tracks') to the index infarct on T2/FLAIR MRI. However, their clinical relevance remains unclear. We investigated the clinicoradiological correlates of 'caps/tracks', and their impact on long-term outcomes following RSSI.

METHODS: We identified participants with lacunar stroke and MRI-confirmed RSSI from 3 prospective studies. At baseline, we collected risk factors, RSSI characteristics, small vessel disease (SVD) features, and microstructural integrity on diffusion imaging. Over 1-year, we repeated MRI and recorded 'caps/tracks' blinded to other data. We evaluated predictors of 'caps/tracks', and their association with 1-year functional (modified Rankin Scale score ≥2), mobility (Timed Up-and-Go), cognitive outcomes (Montreal Cognitive Assessment [MoCA] score <26), and recurrent cerebrovascular events (stroke/transient ischemic attack/incident infarct) using multivariable regression.

RESULTS: Among 185 participants, 93 (50.3%) developed 'caps/tracks' first detected at median 198 days after stroke. 'Caps/tracks' were independently predicted by baseline factors: larger RSSI, RSSI located in white matter, higher SVD score, and higher mean diffusivity in normal-appearing white matter (odds ratio [OR] [95% confidence interval {CI}], 1.15 [1.07-1.25], 6.01 [2.80-13.57], 1.77 [1.31-2.44], 1.42 [1.01-2.03]). At 1 year, 'cap/track' formation was associated with worse functional outcome (OR: 3.17, 95% CI: 1.28-8.22), slower gait speed (β: 0.13, 95% CI: 0.01-0.25), and recurrent cerebrovascular events (hazard ratio [HR]: 2.05, 95% CI: 1.05-4.02), but not with cognitive impairment.

INTERPRETATION: 'Caps/tracks' after RSSI are associated with worse clinical outcomes, and may reflect vulnerability to progressive SVD-related injury. Reducing 'caps/tracks' may offer early efficacy markers in trials aiming to improve outcome after lacunar stroke. ANN NEUROL 2025.

Original language	English
Journal	Annals of Neurology
Early online date	17 Jan 2025
DOIs	https://doi.org/10.1002/ana.27182
Publication status	E-pub ahead of print - 17 Jan 2025

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Annals of Neurology - 2025 - Cheng - Clinical Relevance of Cap and Track Development after Recent Small SubcorticalFinal published version, 4.23 MBLicence: Creative Commons: Attribution (CC-BY)

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Cheng, Y., Arteaga-Reyes, C., Clancy, U., Garcia, D. J., Valdés Hernández, M. D. C., Thrippleton, M. J., Stringer, M. S., Blair, G. W., Wiseman, S., Chappell, F. M., Zhang, J., Liu, X., Jochems, A. C. C., Maniega, S. M., Sakka, E., Bastin, M. E., Brown, R., Loos, C. M. J., Makin, S. D. J., ... MSS‐2, MSS‐3 and the INVESTIGATE‐SVDs Study Group (2025). Clinical Relevance of 'Cap' and 'Track' Development after Recent Small Subcortical Infarct. Annals of Neurology. Advance online publication. https://doi.org/10.1002/ana.27182

@article{2302b14db2ff4c9195445627b8db2edf,

title = "Clinical Relevance of 'Cap' and 'Track' Development after Recent Small Subcortical Infarct",

abstract = "OBJECTIVE: After a recent small subcortical infarct (RSSI), some patients develop perilesional or remote hyperintensities ('caps/tracks') to the index infarct on T2/FLAIR MRI. However, their clinical relevance remains unclear. We investigated the clinicoradiological correlates of 'caps/tracks', and their impact on long-term outcomes following RSSI.METHODS: We identified participants with lacunar stroke and MRI-confirmed RSSI from 3 prospective studies. At baseline, we collected risk factors, RSSI characteristics, small vessel disease (SVD) features, and microstructural integrity on diffusion imaging. Over 1-year, we repeated MRI and recorded 'caps/tracks' blinded to other data. We evaluated predictors of 'caps/tracks', and their association with 1-year functional (modified Rankin Scale score ≥2), mobility (Timed Up-and-Go), cognitive outcomes (Montreal Cognitive Assessment [MoCA] score <26), and recurrent cerebrovascular events (stroke/transient ischemic attack/incident infarct) using multivariable regression.RESULTS: Among 185 participants, 93 (50.3%) developed 'caps/tracks' first detected at median 198 days after stroke. 'Caps/tracks' were independently predicted by baseline factors: larger RSSI, RSSI located in white matter, higher SVD score, and higher mean diffusivity in normal-appearing white matter (odds ratio [OR] [95% confidence interval {CI}], 1.15 [1.07-1.25], 6.01 [2.80-13.57], 1.77 [1.31-2.44], 1.42 [1.01-2.03]). At 1 year, 'cap/track' formation was associated with worse functional outcome (OR: 3.17, 95% CI: 1.28-8.22), slower gait speed (β: 0.13, 95% CI: 0.01-0.25), and recurrent cerebrovascular events (hazard ratio [HR]: 2.05, 95% CI: 1.05-4.02), but not with cognitive impairment.INTERPRETATION: 'Caps/tracks' after RSSI are associated with worse clinical outcomes, and may reflect vulnerability to progressive SVD-related injury. Reducing 'caps/tracks' may offer early efficacy markers in trials aiming to improve outcome after lacunar stroke. ANN NEUROL 2025.",

author = "Yajun Cheng and Carmen Arteaga-Reyes and Una Clancy and Garcia, {Daniela Jaime} and {Vald{\'e}s Hern{\'a}ndez}, {Maria Del C} and Thrippleton, {Michael J} and Stringer, {Michael S} and Blair, {Gordon W} and Stewart Wiseman and Chappell, {Francesca M} and Junfang Zhang and Xiaodi Liu and Jochems, {Angela C C} and Maniega, {Susana Mu{\~n}oz} and Eleni Sakka and Bastin, {Mark E} and Rosalind Brown and Loos, {Caroline M J} and Makin, {Stephen D J} and Ming Liu and Bo Wu and Doubal, {Fergus N} and Wardlaw, {Joanna M} and {MSS‐2, MSS‐3 and the INVESTIGATE‐SVDs Study Group}",

note = "{\textcopyright} 2025 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.",

year = "2025",

month = jan,

day = "17",

doi = "10.1002/ana.27182",

language = "English",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "Wiley",

}

Cheng, Y, Arteaga-Reyes, C , Clancy, U , Garcia, DJ , Valdés Hernández, MDC , Thrippleton, MJ , Stringer, MS, Blair, GW, Wiseman, S , Chappell, FM, Zhang, J, Liu, X, Jochems, ACC , Maniega, SM , Sakka, E , Bastin, ME , Brown, R, Loos, CMJ, Makin, SDJ, Liu, M, Wu, B, Doubal, FN , Wardlaw, JM & MSS‐2, MSS‐3 and the INVESTIGATE‐SVDs Study Group 2025, 'Clinical Relevance of 'Cap' and 'Track' Development after Recent Small Subcortical Infarct', Annals of Neurology. https://doi.org/10.1002/ana.27182

TY - JOUR

T1 - Clinical Relevance of 'Cap' and 'Track' Development after Recent Small Subcortical Infarct

AU - Cheng, Yajun

AU - Arteaga-Reyes, Carmen

AU - Clancy, Una

AU - Garcia, Daniela Jaime

AU - Valdés Hernández, Maria Del C

AU - Thrippleton, Michael J

AU - Stringer, Michael S

AU - Blair, Gordon W

AU - Wiseman, Stewart

AU - Chappell, Francesca M

AU - Zhang, Junfang

AU - Liu, Xiaodi

AU - Jochems, Angela C C

AU - Maniega, Susana Muñoz

AU - Sakka, Eleni

AU - Bastin, Mark E

AU - Brown, Rosalind

AU - Loos, Caroline M J

AU - Makin, Stephen D J

AU - Liu, Ming

AU - Wu, Bo

AU - Doubal, Fergus N

AU - Wardlaw, Joanna M

AU - MSS‐2, MSS‐3 and the INVESTIGATE‐SVDs Study Group

PY - 2025/1/17

Y1 - 2025/1/17

N2 - OBJECTIVE: After a recent small subcortical infarct (RSSI), some patients develop perilesional or remote hyperintensities ('caps/tracks') to the index infarct on T2/FLAIR MRI. However, their clinical relevance remains unclear. We investigated the clinicoradiological correlates of 'caps/tracks', and their impact on long-term outcomes following RSSI.METHODS: We identified participants with lacunar stroke and MRI-confirmed RSSI from 3 prospective studies. At baseline, we collected risk factors, RSSI characteristics, small vessel disease (SVD) features, and microstructural integrity on diffusion imaging. Over 1-year, we repeated MRI and recorded 'caps/tracks' blinded to other data. We evaluated predictors of 'caps/tracks', and their association with 1-year functional (modified Rankin Scale score ≥2), mobility (Timed Up-and-Go), cognitive outcomes (Montreal Cognitive Assessment [MoCA] score <26), and recurrent cerebrovascular events (stroke/transient ischemic attack/incident infarct) using multivariable regression.RESULTS: Among 185 participants, 93 (50.3%) developed 'caps/tracks' first detected at median 198 days after stroke. 'Caps/tracks' were independently predicted by baseline factors: larger RSSI, RSSI located in white matter, higher SVD score, and higher mean diffusivity in normal-appearing white matter (odds ratio [OR] [95% confidence interval {CI}], 1.15 [1.07-1.25], 6.01 [2.80-13.57], 1.77 [1.31-2.44], 1.42 [1.01-2.03]). At 1 year, 'cap/track' formation was associated with worse functional outcome (OR: 3.17, 95% CI: 1.28-8.22), slower gait speed (β: 0.13, 95% CI: 0.01-0.25), and recurrent cerebrovascular events (hazard ratio [HR]: 2.05, 95% CI: 1.05-4.02), but not with cognitive impairment.INTERPRETATION: 'Caps/tracks' after RSSI are associated with worse clinical outcomes, and may reflect vulnerability to progressive SVD-related injury. Reducing 'caps/tracks' may offer early efficacy markers in trials aiming to improve outcome after lacunar stroke. ANN NEUROL 2025.

AB - OBJECTIVE: After a recent small subcortical infarct (RSSI), some patients develop perilesional or remote hyperintensities ('caps/tracks') to the index infarct on T2/FLAIR MRI. However, their clinical relevance remains unclear. We investigated the clinicoradiological correlates of 'caps/tracks', and their impact on long-term outcomes following RSSI.METHODS: We identified participants with lacunar stroke and MRI-confirmed RSSI from 3 prospective studies. At baseline, we collected risk factors, RSSI characteristics, small vessel disease (SVD) features, and microstructural integrity on diffusion imaging. Over 1-year, we repeated MRI and recorded 'caps/tracks' blinded to other data. We evaluated predictors of 'caps/tracks', and their association with 1-year functional (modified Rankin Scale score ≥2), mobility (Timed Up-and-Go), cognitive outcomes (Montreal Cognitive Assessment [MoCA] score <26), and recurrent cerebrovascular events (stroke/transient ischemic attack/incident infarct) using multivariable regression.RESULTS: Among 185 participants, 93 (50.3%) developed 'caps/tracks' first detected at median 198 days after stroke. 'Caps/tracks' were independently predicted by baseline factors: larger RSSI, RSSI located in white matter, higher SVD score, and higher mean diffusivity in normal-appearing white matter (odds ratio [OR] [95% confidence interval {CI}], 1.15 [1.07-1.25], 6.01 [2.80-13.57], 1.77 [1.31-2.44], 1.42 [1.01-2.03]). At 1 year, 'cap/track' formation was associated with worse functional outcome (OR: 3.17, 95% CI: 1.28-8.22), slower gait speed (β: 0.13, 95% CI: 0.01-0.25), and recurrent cerebrovascular events (hazard ratio [HR]: 2.05, 95% CI: 1.05-4.02), but not with cognitive impairment.INTERPRETATION: 'Caps/tracks' after RSSI are associated with worse clinical outcomes, and may reflect vulnerability to progressive SVD-related injury. Reducing 'caps/tracks' may offer early efficacy markers in trials aiming to improve outcome after lacunar stroke. ANN NEUROL 2025.

U2 - 10.1002/ana.27182

DO - 10.1002/ana.27182

M3 - Article

C2 - 39821913

SN - 0364-5134

JO - Annals of Neurology

JF - Annals of Neurology

ER -

Clinical Relevance of 'Cap' and 'Track' Development after Recent Small Subcortical Infarct

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