Early Subacute White Matter Hyperintensities and Recovery of Language After Stroke

So you did absolutely useless research? Describe a way to identify a problem, BUT DID NOTHING TO SOLVE IT! I'd fire everyone involved in this!

Early Subacute White Matter Hyperintensities and Recovery of Language After Stroke

Veronika Vadinova https://orcid.org/0000-0001-7176-1008 veronika.vadinov@gmail.com, Aleksi J. Sihvonen, […], and Sonia L. E. Brownsett+6View all authors and affiliations

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https://doi.org/10.1177/15459683231168384

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• • Abstract
  • Introduction
  • Methods
  • Results
  • Discussion
  • Conclusion
  • Acknowledgments
  • Declaration of Conflicting Interests
  • Funding
  • ORCID iDs
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Abstract

Background

White matter hyperintensities (WMH) are considered to contribute to diminished brain reserve, negatively impacting on stroke recovery. While WMH identified in the chronic phase after stroke have been associated with post-stroke aphasia, the contribution of premorbid WMH to the early recovery of language across production and comprehension has not been investigated.

Objective

To investigate the relationship between premorbid WMH severity and longitudinal comprehension and production outcomes in aphasia, after controlling for stroke lesion variables.(Wrong objective; the mentors and senior researchers need to be flogged for this crapola.)

Methods

Longitudinal behavioral data from individuals with a left-hemisphere stroke were included at the early subacute (n = 37) and chronic (n = 28) stage. Spoken language comprehension and production abilities were assessed at both timepoints using word and sentence-level tasks. Magnetic resonance imaging (MRI) was performed at the early subacute stage to derive stroke lesion variables (volume and proportion damage to critical regions) and WMH severity rating.

Results

The presence of severe WMH explained an additional 18% and 25% variance in early subacute (t = −3.00, p = .004) and chronic (t = −3.60, P = .001) language comprehension abilities respectively, after controlling for stroke lesion variables. WMH did not predict additional variance of language production scores.

Conclusions

Subacute clinical MRI can be used to improve prognoses of recovery of aphasia after stroke. We demonstrate that severe early subacute WMH add to the prediction of impaired longitudinal language recovery in comprehension, but not production. This emphasizes the need to consider different domains of language when investigating novel neurobiological predictors of aphasia recovery.

Introduction

Poststroke aphasia affects approximately 25 million individuals worldwide,¹ with multiple neurological, demographic, and health-related factors contributing to recovery.^2,3 While some studies have succeeded in predicting almost half of the variability in post-stroke aphasia outcomes by considering the contribution of different lesion characteriscs,⁴ recovery among individuals with aphasia (IWA) remains highly variable and unpredictable.^5,6 Clinicians need reliable predictors⁷ of residual aphasia, beside lesion characteristic, to allow them to deliver meaningful prognoses to patients and caregivers.³ In some stroke survivors, the quantifiable premorbid integrity of the brain, “brain reserve” in the presence of neural pathology, may increase susceptibility to more severe impairments, or to diminished recovery potential.⁸ Such measures of “brain reserve” may therefore improve prediction of functional outcomes after stroke.^3,9

Small vessel disease (SVD) is a common cerebrovascular pathology associated with aging and cerebrovascular risk factors¹⁰ that is typically detected in midlife and found in the majority of people over 60 years.¹¹ After stroke, premorbid SVD burden has been shown to be associated with poorer outcomes^12,13 and therefore purported as a possible index of diminished “brain reserve.”^14,15 White matter hyperintensities (WMH), the most commonly assessed radiological marker of SVD burden,¹⁰ is most frequently assessed using the Fazekas scale¹⁶; which differentiates between WMH severity (mild, moderate, severe) within both periventricular white matter hyperintensities (PVWMH) and deep white matter hyperintensities (DWMH). WMH are considered to be a radiological manifestation of progressive white matter integrity loss^17,18 and have been associated with poor cognitive skills,^19,20 including language.^21,22 Given that WMH burden likely reflects the disintegration of white matter pathways, assumed to contribute to effectiveness of neuroplastic recovery processes reliant on these pathways, markers of WMH severity could be considered a surrogate measure of premorbid “brain reserve.”⁹ Therefore, measures of early WMH severity may explain some of the variability observed across many cognitive domains and skills after stroke, including language.

Whilst a detrimental role of WMH burden on language has been suggested in both elderly individuals^21,22 and people with aphasia,^23-25 this evidence is either limited to WMH assessed within the chronic stage of recovery,^3,24-26 or limited by temporal inconsistencies in WMH and behavioral assessments.²³ WMH represent a dynamic pathology that progresses over time,²⁷ usually leading to an increase in WMH severity²⁸ but has been shown to reduce in severity in a smaller portion of patients.²⁹ As a result of the evolving nature of WMH lesions, the timing of WMH assessment must be taken into consideration when used as an explanatory variable in stroke. To this end, premorbid WMH burden is likely to be most accurately assessed on neuroimaging acquired within the early stages after stroke, reflecting the individual premorbid “brain reserve” available for optimal recovery.³⁰

To date, 4 studies have identified an association between language (overall aphasia severity, naming and fluency) and chronic WMH burden.^3,24-26 Whilst Wilmskoetter et al²⁵ did not find a direct relationship between overall severity of aphasia and chronic WMH burden, they did show that PVWMH severity (using Fazekas scale) mediated a relationship between the number of long-ranging white matter fibers and overall aphasia severity. Basilakos et al²⁴ also found a relationship between chronic WMH severity (again using the Fazekas scale) and the rate of decline in language abilities in chronic aphasia. Most recently, Johnson et al³ demonstrated, in a large sample of patients, that chronic WMH severity (using the Fazekas scale) contributed to language outcomes, together with many other predictors. When considering naming skills alone, Varkanitsa et al²⁶ found no association between naming scores and WMH in the chronic post-stroke stage, however they did find a negative association between participants’ response to naming therapy and both total chronic Fazekas WMH, and DWMH scores. Finally, Wright et al²³ demonstrated that both subacute WMH, as assessed by the Cardiovascular Health Study scale,³¹ and brain atrophy, calculated as a ratio of brain volume to cerebrospinal fluid volume, were associated with chronic naming and fluency deficits. Whilst Wright et al²³ is the only study to date to have investigated the contributions of subacute WMH to aphasia outcomes, an important limitation of this study was the heterogenous timing of the neuroimaging (early subacute stage) and behavioral (range 3-157 months post onset) data acquisition. These inconsistencies in the timing of behavioral assessment have prevented researchers from disentangling the effects of premorbid WMH on early compared to chronic recovery processes.

The neural networks underpinning the language skills required for effective communication are likely more extensive than the networks required to support single-word production tasks, potentially making language more susceptible to the anatomically diffuse effects of WMH than identified in studies investigating single word level production only.^23,26 Moreover, comprehension skills may be particularly vulnerable to the adverse effects of WMH burden given the frequently identified association of language comprehension after stroke with both a range of cognitive abilities,^32,33 and the upregulation of domain-general cognitive neural networks.³⁴ Given that WMH can compromise multiple domains of cognitive processing,^20,35 language comprehension skills may be more vulnerable than other aspects of language, to the adverse effects of WMH burden. A global measure of aphasia severity that incorporates several aspects and domains of language, as used in two previous studies,^3,24 may be insufficient to identify any differential contributions across language domains. To this end more research is required to investigate the potential role of premorbid WMH across both production and comprehension, using a range of levels of language processing including single word, sentence and discourse level tasks.

To this end, we aimed to examine the contribution of WMH assessed at an early subacute stage (subsequently referred to as “early subacute WMH”), a surrogate measure of premorbid brain reserve, to post-stroke aphasia outcomes. Specifically, we examined the extent to which language comprehension and production skills are differentially impacted by early subacute WMH burden at two different phases of recovery (early subacute and chronic). Given that stroke lesion volume and anatomy have been shown to be a reasonably reliable predictor of aphasia,^4,36,37 we investigated if WMH burden could explain any additional variance, over and above stroke lesion volume and distribution, within the language network.