Domain-Specific Outcomes for Stroke Clinical Trials

Abstract

Global outcome measures that are widely used in stroke clinical trials, such as the modified Rankin Scale (mRS), lack sufficient detail to detect changes within specific domains (e.g. sensory, motor, visual, linguistic, or cognitive function). Yet such data are vital for understanding stroke recovery and its mechanisms. Post-stroke deficits in specific domains differ in their rate and degree of recovery, and in their effects on overall independence and quality of life. For example, even in a patient with complete recovery of strength, persistent deficits in the non-motor domains such as language and cognition may make a return to independent living impossible. In such cases, global measures based solely on the patient’s degree of independence would overlook a complete recovery in the motor domain. Capturing these important aspects of recovery demands a domain-specific approach. If stroke outcomes trials are to incorporate finer-grained recovery metrics -- which can require substantial time, effort, and expertise to implement -- efficiency must be a priority. In this paper we discuss how commonly collected clinical data from the NIHSS can guide the judicious selection of relevant recovery domains for more detailed testing. Our overarching goal is to make the implementation of domain-specific testing more feasible for large scale clinical trials on stroke recovery.

Association of Modified Rankin Scale With Recovery Phenotypes in Patients With Upper Extremity Weakness After Stroke

“…It will be essential that we develop disability measures that have greater levels of granularity and that capture improvements across different modalities: motor, language, cognitive. 6 For feasibility in clinical settings, item-response theory and computer adaptive testing could be used to optimize data collection. Progress in stroke recovery requires the optimal selection and deployment of outcome measures that reflect neurologic and functional status and are meaningful to patients and caregivers.…”

The relevance of rich club regions for functional outcome post-stroke is enhanced in women

“…Essentially, the combination of this ascertained real-world value and the ease of its collection has motivated the widespread reliance on the mRS as primary, FDA- 36 and NINDS-endorsed 37 endpoint in the majority of acute stroke treatment trials. 38,39,40…”

“…In addition, it will be promising to continue exploring the specifics of rich club lesion links to acute and chronic impairments in individual domains, such as sensory, motor, visual, cognitive, their combination (e.g., cognitive and motor impairments 46 ) and domain-specific recovery trajectories. 38 In an ideal scenario, various behavioral domains would be evaluated in the same stroke sample to allow for direct comparisons. Are lesions in rich club regions linked to differing domains with equal or varying strength?…”

Lesions in putative language and attention regions are linked to more severe strokes in patients with higher white matter hyperintensity burden

“…Specific symptoms post-stroke, such as aphasia and neglect, may thus not have been represented well enough in the mRS to have a comparable effect to the NIHSS analyses (as the NIHSS might be more sensitive to these deficits). 48 Secondly, the process of neurorecovery may, like instantaneous language and attention performances, precisely rely on the integrity of large-scale networks connected through WM tracts and thus be negatively affected by WMHs.…”