Modulation of the Association Between Corticospinal Tract Damage and Outcome After Stroke by White Matter Hyperintensities

 I could see ABSOLUTELY NOTHING in here that will help survivors recover! Useless.

Modulation of the Association Between Corticospinal Tract Damage and Outcome After Stroke by White Matter Hyperintensities

Jennifer K. Ferris, MSc, PhD https://orcid.org/0000-0003-3624-6996, Bethany P. Lo, BSc, Giuseppe Barisano, MD, PhD https://orcid.org/0000-0001-5598-1369, Amy Brodtmann, MBBS, PhD, FRACP https://orcid.org/0000-0001-9466-2862, Cathrin M. Buetefisch, MD, PhD, Adriana B. Conforto, Miranda R. Donnelly, MS https://orcid.org/0000-0002-1983-3008, … Show All … , and Sook-Lei Liew, PhD, OTR/L, FAOTA https://orcid.org/0000-0001-5935-4215Authors Info & Affiliations

May 28, 2024 issue

102 (10)

https://doi.org/10.1212/WNL.0000000000209387

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• • Abstract
  • Introduction
  • Methods
  • Results
  • Discussion
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  • Study Funding
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  • Publication History
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Abstract

Background and Objectives

Motor outcomes after stroke relate to corticospinal tract (CST) damage. The brain leverages surviving neural pathways to compensate for CST damage and mediate motor recovery. Thus, concurrent age-related damage from white matter hyperintensities (WMHs) might affect neurologic capacity for recovery after CST injury. The role of WMHs in post-stroke motor outcomes is unclear. In this study, we evaluated whether WMHs modulate the relationship between CST damage and post-stroke motor outcomes.

Methods

We used data from the multisite ENIGMA Stroke Recovery Working Group with T1 and T2/fluid-attenuated inversion recovery imaging. CST damage was indexed with weighted CST lesion load (CST-LL). WMH volumes were extracted with Freesurfer's SAMSEG. Mixed-effects beta-regression models were fit to test the impact of CST-LL, WMH volume, and their interaction on motor impairment, controlling for age, days after stroke, and stroke volume.

Results

A total of 223 individuals were included. WMH volume related to motor impairment above and beyond CST-LL (β = 0.178, 95% CI 0.025–0.331, p = 0.022). Relationships varied by WMH severity (mild vs moderate-severe). In individuals with mild WMHs, motor impairment related to CST-LL (β = 0.888, 95% CI 0.604–1.172, p < 0.001) with a CST-LL × WMH interaction (β = −0.211, 95% CI −0.340 to −0.026, p = 0.026). In individuals with moderate-severe WMHs, motor impairment related to WMH volume (β = 0.299, 95% CI 0.008–0.590, p = 0.044), but did not significantly relate to CST-LL or a CST-LL × WMH interaction.

Discussion

WMHs relate to motor outcomes after stroke and modify relationships between motor impairment and CST damage. WMH-related damage may be under-recognized in stroke research as a factor contributing to variability in motor outcomes. Our findings emphasize the importance of brain structural reserve in motor outcomes after brain injury.

Introduction

Upper extremity motor impairment is one of the most common consequences of stroke¹ and typically results in long-term disability.² The degree of damage to the corticospinal tract (CST) relates strongly to motor impairment after stroke,^3,4 indicating a primary insult to the motor system. However, motor recovery after stroke is variable even after accounting for CST damage.⁵ Recovery after stroke is likely mediated by compensation of surviving neural substrate.⁶ This suggests that the integrity of structures beyond the CST might be prognostic of motor recovery^7,8 because overall brain health may be important in explaining why 2 individuals with similar stroke lesions can experience very different trajectories of recovery.⁹

White matter hyperintensities (WMHs) of presumed vascular origin are the most common form of age-related cerebrovascular damage.¹⁰ They are present in more than half of people older than 60 years.¹¹ Individuals with WMHs are more likely to experience a stroke¹² in part because of common cardiometabolic risk factors between WMHs and stroke.¹³ There is growing evidence that WMHs can also affect functional outcomes after stroke.¹⁴ The relationship between WMHs and post-stroke cognitive impairment has been well established¹⁴; however, there have been few investigations of the specific impact of WMHs on motor outcomes after stroke. WMHs modulate relationships between stroke lesion volume and overall functional outcome.^15,16 Motor outcomes after stroke may similarly be modulated by concurrent WMHs because of the widespread impacts of WMHs on cerebral networks,^17,18 which may create preexisting damage in compensatory pathways and, therefore, decrease the brain's capacity for motor recovery.

We tested whether the relationship between post-stroke motor impairment and CST damage is affected by concurrent WMH damage, controlling for age, time after stroke, and stroke lesion volume. We hypothesized that the relationship between motor impairment and CST damage would be attenuated in individuals with higher WMH volumes, indicating a greater influence of concurrent WMHs on motor outcomes after stroke.

 

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