Prevalence, Trajectory, and Factors Associated With Patient-Reported Nonmotor Outcomes After Stroke: A Systematic Review and Meta-Analysis.

Importance: The evidence on nonmotor outcomes after acute ischemic stroke and intracerebral hemorrhage (ICH) is limited and domain-specific. The prevalence, natural history, and factors associated with nonmotor outcomes across multiple domains are unclear. Objective: To synthesize the published data and to identify the prevalence, natural history, and factors associated with multidomain nonmotor outcome burden in patients with stroke. Data Sources: A search of PubMed, MEDLINE, EMBASE, and PsycINFO databases between January 1999 to June 2023 was supplemented by search of bibliographies of the key articles. Study Selection: The analysis included prospective cohort studies that reported nonmotor outcomes across 10 domains: anxiety, depression, fatigue, sleep disturbance, social participation, pain, bladder dysfunction, bowel dysfunction (constipation and fecal incontinence), and sexual dysfunction assessed by patient-reported scales. Data Extraction and Synthesis: Two reviewers independently assessed studies, extracting baseline data, nonmotor prevalence, and follow-up information. Pooled prevalence of nonmotor outcomes was estimated using random-effects models. Meta-regression models were used to analyze natural history and factors associated with nonmotor outcomes. Subgroup analysis was used to assess prevalence by symptom description within each nonmotor domain. Publication bias and study quality were assessed using funnel plots and the Newcastle-Ottawa scale. Results: A total of 279 prospective cohort studies met the inclusion criteria (117 440 participants with stroke; median [IQR] age, 65 [59-70] years; 209 of 279 studies with more male than female participants) with a nonmotor outcome follow-up period ranging from 30 days to 10 years after stroke. The most prevalent adverse nonmotor outcomes by pooled prevalence were sleep disturbance (59.9%; 95% CI, 53.9%-63.9%), sexual dysfunction (59.8%; 95% CI, 50.0%-69.5%), constipation (58.2%; 95% CI, 53.9%-62.6%), reduced social participation (56.5%; 95% CI, 52.1%-60.8%), bladder dysfunction (45.9%; 95% CI, 38.0%-53.8%), and fatigue (45.2%; 95% CI, 40.7%-49.5%). Meta-regression analysis showed no significant improvement over time for most nonmotor outcomes, except pain (coefficient = -11.0%; P = .05) and sexual dysfunction (coefficient = -24.1%; P < .001). The heterogeneity ranged between 52% and 98% across all studies. The common factors associated with adverse nonmotor outcomes were female sex, studies with mixed stroke cohort (ischemic stroke or ICH), and older age. Conclusions and Relevance: Patient-reported nonmotor outcomes were common after stroke. Sexual dysfunction, sleep disturbance, constipation, reduced social participation, bladder dysfunction, and fatigue were most prevalent. These adverse outcomes often persisted over time, especially in women, older adults, and those in studies with mixed stroke cohorts.