Ozkan, Hatice; (2024) Prevalence and predictors of non-motor outcomes after stroke. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Adverse non-motor outcomes are common after stroke, imposing a major long-term symptom burden for patients and caregivers. Despite increasing understanding of some individual non-motor outcomes post-stroke, comprehensive reporting of their prevalence across multiple health domains, and the factors influencing them, remain limited; consequently, effective management remains challenging. The program of research described in this PhD theses had seven key aims: 1. To undertake a comprehensive systematic review and meta-analysis of non-motor outcomes documented in historical publications over the past two decades, across multiple health domains (anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, pain, bowel dysfunction, bladder dysfunction, and sexual dysfunction) after acute stroke (an ischaemic stroke (IS) or ICH) 2. To design and conduct original research to assess the prevalence of patient-reported non-motor outcomes across multiple non-motor outcome domains (anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, pain, bowel control, bladder control, mood problems, communication problems, memory problems, activities of daily living, and social relationships) within an ethnically diverse stroke population in North and Central London (NCL) at 30-days and 6-months post-stroke called the stroke investigation group in NCL (SIGNAL) 3. To investigate how and whether adverse prevalence of non-motor outcomes is associated with sociodemographic (i.e. age, sex, ethnic origin, etc.), and clinical factors (i.e. stroke type, past medical history, stroke severity, etc.) of patients with cerebral ischaemic stroke or ICH 4. To evaluate the correlations between individual non-motor outcome domains 5. To investigate the prevalence and factors associated with non-motor outcomes 6-months after revascularisation with intravenous thrombolysis, endovascular thrombectomy, or both for acute ischaemic stroke 6. To identify the prevalence and association between specific brain imaging characteristics in ICH, such as location, volume, and total cerebral small vessel disease burden (cSVD), and the prevalence of adverse non-motor outcomes 7. To identify the impact of the United Kingdom (UK) SARS-CoV-2 virus-2019 (COVID-19) pandemic on non-motor outcomes 30-days after stroke The comprehensive systematic review and meta-analysis (Chapter 2) included 279 prospective cohort studies (comprising 117 440 participants with stroke, median age 65 years old) with a non-motor outcome follow-up period ranging from 30-days to 10 years after stroke. Across 10-domains the pooled prevalence of non-motor outcomes ranges between 7% to 59.9%. The most prevalent adverse non-motor outcomes were: sleep disturbance 59.9% (95% Cl, 53.9 – 63.9), sexual dysfunction 59.8% (95% Cl 50.0 – 69.5), constipation 58.2% (95% Cl 53.8 –62.6), reduced social participation 56.5% (95% Cl 52.1 – 60.8); bladder dysfunction 45.9% (95% Cl 38.0 – 53.8); and fatigue 45·1% (95% Cl 40.7 – 49.5). Meta-regression analysis showed no significant improvement over time for most non-motor outcomes, except pain (coefficient=↓11.0%, p=0.052) and sexual dysfunction (coefficient=↓24.1%, p<0.001). The heterogeneity ranged between I2 52% to 98% across all studies. The common predictors of adverse non-motor outcomes were female sex, studies with mixed stroke cohort (ischaemic stroke or ICH), and older age. The SIGNAL study (Chapter 3) is a multiborough observational, prospective, population-based study of acute ischaemic stroke and ICH in North Central London (NCL). All patients presenting to the University College London Hyperacute Stroke Unit (HASU) with acute ischaemic stroke and/or ICH with a routine non-motor outcome (anxiety, depression, fatigue, sleep disturbance, social participation, pain, bowel dysfunction, bladder dysfunction, communication problems, verbal memory and thinking, activities of daily living, mood problems, and social relationships) follow-up between 2017 to 2020 were eligible for inclusion in the SIGNAL. The non-motor outcome follow-up was performed using 3 patient-reported outcome measures at around 30 days (via telephone/Skype) follow-up 1 (FU1), and at around 6 months (at the outpatient stroke clinic, patient’s home or via telephone/Skype) follow-up 2 (FU2). The 30-day study (Chapter 4) investigated the prevalence, multiple patterns, correlations, and factors associated with non-motor outcomes after stroke. The results showed (N= 605) 16%-57% prevalence of adverse non-motor outcomes. The common adverse non-motor outcomes included: anxiety, fatigue, bladder dysfunction, reduced social participation, and pain. Factors associated with multiple non-motor outcomes included ICH, National Institutes of Health Stroke Scale (NIHSS) severity, and previous stroke or transient ischaemic attack (TIA). Adverse outcomes rates in multiple domains were: ⩾ 1: 89%, ⩾ 2: 66.3%, ⩾ 3: 45.8%, and significant correlations were found between bowel-bladder (κ = 0.908), social-bladder (κ = 0.844), and anxiety-fatigue (κ = 0.613). The 6-month study (Chapter 5) described the prevalence, determined factors, and described correlations of adverse non-motor outcomes across 13 domains. The results suggest that at 6-month post-stroke (N= 3080), adverse non-motor outcomes ranged from 23% to 57%, with fatigue, reduced social participation, sleep disturbance, and constipation impacting 44%-57% of patients with stroke. Consistent factors associated with adverse outcomes included ICH, NIHSS severity, and previous stroke/TIA. Adverse non-motor outcomes rates in multiple domains were: ≥1: 75%, ≥2: 51%, ≥3: 49%, ≥4: 40%, ≥5: 26% and moderate correlations were found between fatigue-sleep (k=0·72), memory-ADL/IADL (k=0·68), communication-ADL/IADL (k=0·70). The first sub-study (Chapter 6) investigates the prevalence, mRS score distribution, and factors associated with 6-month adverse non-motor outcomes after revascularisation with intravenous thrombolysis (IVT), endovascular thrombectomy (EVT), or both for acute ischaemic stroke. The study included 642 patients (age 73 years and 43.5% female) revascularised with IVT, EVT, or both. The median mRS score at 6-months was 1 (range 0-3) indicating a good clinical outcome. Despite this, the prevalence of adverse non-motor outcomes remained high with a range of 26% to 53% across 13 domains. Particularly, among those with an excellent mRS score (0-1), the prevalence of adverse non-motor outcomes ranges between 17% to 51%. Fatigue (51%), sleep disturbances (49%), and bowel dysfunction (39%) were the most prevalent. Age, stroke severity, and no early supported discharge (ESD) plan are significantly associated with adverse outcomes across multiple domains. The ICH study (Chapter 7) investigates the prevalence and imaging factors associated with adverse non-motor outcomes after spontaneous ICH. The results show that (N= 319) fatigue 201 (63%), sleep disturbance 163 (51%), constipation 153 (48%), and reduced social relationships 150 (47%) were the most common adverse non-motor outcomes 6-months post ICH. In the adjusted analysis, large ICH volume (>30 ml) with 10 out of the 13 non-motor outcomes. A total SVD burden >2 showed significant associations with 7 out of the 13 non-motor outcomes. Similarly, CAA showed a significant association with 6 out of the 13 non-motor outcomes. Lastly, the COVID-19 study (Chapter 8) evaluates the impact of the UK COVID-19 pandemic on non-motor outcomes after acute stroke. The results show (N= 205) showed an increased prevalence of adverse non-motor outcomes in patients with stroke. Anxiety, fatigue, depression, and sleep disturbance were the most common adverse outcomes during the COVID-19 pandemic. Factors such as admission to the stroke unit during the pandemic, no early support plan, Modified Rankin Scale (mRS) score of 4-5 at discharge, and no GP contact 30 days post-stroke were significantly associated with adverse non-motor outcomes.

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