Predictors of post stroke cognitive impairment: VITATOPS cognition substudy.

INTRODUCTION: Post stroke cognitive impairment (PSCI) is a common complication of ischemic stroke. PSCI can involve different depending on clinical and stroke related characteristics. The aim of this study is to determine the factors associated with impairments in specific cognitive domains. METHODS: The Vitamins to Prevent Stroke (VITATOPS) trial is a large, multinational randomised controlled trial. In this substudy, consecutive patients admitted for ischaemic stroke or transient ischaemic attack (TIA) at a tertiary hospital in Singapore were included. PSCI was defined as impairment of any of the six cognitive subgroups - visuoconstruction, attention, verbal memory, language, visual memory and visuomotor function - that were assessed annually for up to five years. Univariate and multivariate Cox proportional hazard models were used to determine factors associated with impairments in each of these cognitive domains. RESULTS: A total of 736 patients were included in this study, of which 173 (23.5 %) developed cognitive impairment. Out of the six cognitive domains, the greatest proportion of patients had an impairment in visuoconstruction (26.4 %) followed by attention (19.8 %), verbal memory (18.3 %), language (17.5 %), visual memory (17.3 %) and visuomotor function (14.8 %). Patients with posterior circulation cerebral infarction (POCI) as the index stroke subtype had higher rates of cognitive impairment. Further subgroup analyses show that Indian race and advanced age were predictive of language impairment, whilst fewer years of education and POCI were predictive of verbal memory impairment. POCI was predictive of visual memory impairment, and advanced age and POCI were predictive of visuomotor function impairment. CONCLUSION: We identified visuoconstruction and attention domains to be the most affected in our Asian cohort of PSCI. Advanced age, lower levels of education, posterior circulation strokes and concomitant comorbidities such as peripheral artery disease are independent predictors of PSCI.

Endovascular coiling versus neurosurgical clipping in the management of aneurysmal subarachnoid haemorrhage in the elderly: a multicenter cohort study.

The comparability of endovascular coiling over neurosurgical clipping has not been firmly established in elderly patients with aneurysmal subarachnoid haemorrhage (aSAH). Data were obtained from all patients with aSAH aged ≥60 across three tertiary hospitals in Singapore from 2014 to 2019. Outcome measures included modified Rankin Scale (mRS) score at 3 and at 6 months, and in-hospital mortality. Of the 134 patients analyzed, 84 (62.7%) underwent coiling and 50 (37.3%) underwent clipping. The endovascular group showed a higher incidence of good mRS score 0-2 at 3 months (OR = 2.45 [95%CI:1.16-5.20];p = 0.018), and a lower incidence of in-hospital mortality (OR = 0.31 [95%CI:0.10-0.91];p = 0.026). There were no significant difference between the two treatment groups in terms of good mRS score at 6 months (OR = 1.98 [95%CI:0.97-4.04];p = 0.060). There were no significant differences in the incidence of complications, such as aneurysm rebleed, delayed hydrocephalus, delayed ischemic neurological deficit and venous thromboembolism between the two treatment groups. However, fewer patients in the coiling group developed large infarcts requiring decompressive craniectomy (OR = 0.32 [95%CI:0.12-0.90];p = 0.025). Age, admission WFNS score I-III, and coiling were independent predictors of good functional outcomes at 3 months. Only age and admission WFNS score I-III remained significant predictors of good functional outcomes at 6 months. Endovascular coiling, compared with neurosurgical clipping, is associated with significantly better short term outcomes in carefully selected elderly patients with aSAH. Maximal intervention is recommended for aSAH in the young elderly age group and those with favorable WFNS scores.

Anti-NMDAR encephalitis in Southeast Asia - A single-centre, longitudinal study.

AIMS: To describe the clinical features and outcomes of anti-NMDA receptor encephalitis (ANMDARE) in Southeast Asian (SEA) patients. METHOD: SEA patients diagnosed and treated for ANMDARE at Singapore General Hospital between January 2010 and June 2020 were included in this observational study, in which their clinical features and outcomes were retrospectively analysed. RESULTS: We studied 20 patients: 11 Chinese, 3 Tagalogs, 2 Malays, 2 Indians, 1 Eurasian and 1 Javanese. Their median age was 28 years. 15 were females, amongst whom teratomas were demonstrated in 13 (12 ovarian, 1 mediastinal). Delirium and seizures were the two commonest events leading to their presentation at our facility. 1 male had biliary neuroendocrine tumour. Comparison between genders revealed a strong male predilection for early seizures and insomnia; females were four times likelier than males to develop movement disorders or have underlying neoplasms. Patients with dysautonomia required longer ICU stay beyond 14 days, but their outcomes at 1 year did not differ. When reviewed at 1 year, none had clinical relapses, and outcomes were favourable (mRS 0-2) in nearly two-thirds. CONCLUSIONS: SEA patients with ANMDARE frequently present with delirium and seizures. Underlying neoplasms are very common in females. Differences in clinical characteristics may exist between the two genders. Recognition of these can facilitate diagnosis, and permit earlier initiation of appropriate treatment strategies, and thus improve outcomes of SEA patients.

Plasma Soluble ST2 Levels Are Higher in Neurodegenerative Disorders and Associated with Poorer Cognition.

BACKGROUND: Suppressor of tumorgenicity 2 (ST2) is highly expressed in brain tissue and is a receptor for interleukin 33 (IL-33). ST2 exists in two forms, a transmembrane receptor (ST2L) and a soluble decoy receptor (sST2). IL-33 binds to ST2L, triggering downstream signaling pathways involved in amyloid plaque clearance. Conversely, sST2 binds competitively to IL-33, attenuating its neuroprotective effects. High sST2 levels have been reported in mild cognitive impairment (MCI) and Alzheimer's disease (AD), suggesting that the IL-33/ST2 signaling pathway may be implicated in neurodegenerative diseases. OBJECTIVE: To investigate plasma sST2 levels in controls and patients with MCI, AD, frontotemporal dementia (FTD), and Parkinson's disease (PD). METHODS: Plasma sST2 levels were measured using ELISA in 397 subjects (91 HC, 46 MCI, 38 AD, 28 FTD, and 194 PD). Cerebrospinal fluid (CSF) levels of sST2 were measured in 22 subjects. Relationship between sST2 and clinical outcomes were analyzed. RESULTS: Plasma sST2 levels were increased across all disease groups compared to controls, with highest levels seen in FTD followed by AD and PD. Dementia patients with higher sST2 had lower cross-sectional cognitive scores in Frontal Assessment Battery and Digit Span Backward. At baseline, PD-MCI patients had higher sST2, associated with worse attention. In the longitudinal PD cohort, higher sST2 significantly associated with decline in global cognition and visuospatial domains. Plasma sST2 levels correlated with CSF sST2 levels. CONCLUSION: Plasma sST2 is raised across neurodegenerative diseases and is associated with poorer cognition. Higher baseline sST2 is a potential biomarker of disease severity in neurodegeneration.

Prehospital technologies for early stroke detection - A review.

The rate of neural circuitry loss in a typical large vessel occlusion well emphasizes that 'Time is Brain'. Every untreated minute in a large vessel ischaemic stroke results in loss of 1.9 million neurons and 13.8 billion synapses. As such, it is essential to optimize the flow-limiting steps in delivering the current standard of care. The current diagnostic model involves recognition of symptoms by patients, followed by access to Emergency Medical Services and subsequent physical examination and neuroimaging in the Emergency Department. With more than 50% of stroke patients using Emergency Medical Services as the first point of care contact, it can be deduced that the outcome of the 'stroke chain of survival' can be improved by addressing the bottleneck of prehospital stroke diagnosis. Here we present a review of the existing technologies.

Bridging thrombolysis improves survival rates at 90 days compared with direct mechanical thrombectomy alone in acute ischemic stroke due to basilar artery occlusion: a systematic review and meta-analysis of 1096 patients.

BACKGROUND: Mechanical thrombectomy (MT) is an effective treatment for patients with acute ischemic stroke (AIS) from basilar artery occlusion (BAO). OBJECTIVE: To compare the clinical outcomes of MT, with and without bridging intravenous thrombolysis (IVT), in acute BAO through a systematic review and meta-analysis of the current literature. METHODS: Systematic searches of Medline, EMBASE, and Cochrane Central were undertaken on August 1, 2022. Good functional outcome defined as 90-day modified Rankin Scale score 0-2 was the primary outcome measure. Secondary outcome measures were 90-day mortality, successful post-thrombectomy recanalization (modified Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracranial hemorrhage (sICH), and subarachnoid hemorrhage (SAH). RESULTS: Three studies reporting 1096 patients with BAO AIS were included in the meta-analysis. No significant differences in good functional outcome were detected between the two groups (RR=1.28 (95% CI 0.86 to 1.92); p=0.117). However, specifically patients with large artery atherosclerosis (LAA) benefited from bridging IVT (OR=2.52 (95% CI 1.51 to 4.22); p<0.001) with better functional outcomes. There was a significantly lower 90-day mortality rate for patients who underwent bridging IVT compared with MT alone (RR=0.70 (95% CI 0.62 to 0.80); p=0.008). No significant differences were detected in rates of post-treatment recanalization (RR=1.01 (95% CI 0.35 to 2.91); p=0.954), sICH (RR=0.96 (95% CI 0.66 to 1.42); p=0.724), and SAH (RR=0.93 (95% CI 0.31 to 2.83); p=0.563). CONCLUSIONS: In patients with AIS due to BAO, bridging IVT was associated with lower mortality rates at 90 days, compared with direct MT. There were no improved functional outcomes or increased sICH or SAH between both arms, However, patients with LAA benefited from bridging IVT, with better functional outcomes.

The initial experience with the Embotrap III stent-retriever in a real world setting.

MATERIALS AND METHODS: We performed a retrospective review of our prospectively maintained database to identify all patients treated with the Embotrap 3 stent-retriever between January 2021 and January 2022. We recorded the baseline demographics, NIHSS, ASPECT score and clot characteristics, first pass and final eTICI scores, complications and 90 day mRS. RESULTS: One hundred and ten patients met the inclusion criteria, average age 69 ± 14 years, 50% were male (n = 55). The median NIHSS at presentation was 18 (range 3-30) and 58.2% received IV tPA prior to MT. The median ASPECT score on plain CT was 8 with average clot length 20.2 ± 14.8 mm (n = 93). The first pass effect (FPE) was seen in 41.8% of cases with modified FPE seen in 59.1%. A 24-hour CT scan (n = 97) showed median ASPECTs of 7. 43.8% of patients achieve mRS ≤ 2 at 90-day mRS (n = 64). CONCLUSION: The Embotrap 3 stent-retriever has a high rate of FPE and final recanalization in this real world cohort of patients.

Effect of Sex on Outcomes of Mechanical Thrombectomy in Basilar Artery Occlusion: A Multicentre Cohort Study.

INTRODUCTION: Identifying differences in outcome of basilar artery occlusion (BAO) between males and females may be useful in aiding clinical management. Recent studies have demonstrated widespread underrepresentation of women in acute stroke clinical trials. This international multicentre study aimed to determine sex differences in outcome after mechanical thrombectomy (MT) for patients with acute BAO. METHODS: We performed a retrospective analysis of consecutive patients with BAO who had undergone MT in seven stroke centres across five countries (Singapore, Taiwan, United Kingdom, Sweden, and Germany), between 2015 and 2020. Primary outcome was a favourable functional outcome measured by a modified Ranking Scale (mRS) of 0-3 at 90 days. Secondary outcomes were mRS 0-3 upon discharge, mortality, symptomatic intracranial haemorrhage (sICH) and subarachnoid haemorrhage (SAH). RESULTS: Among the 322 patients who underwent MT, 206 (64.0%) patients were male and 116 (36.0%) were female. Females were older than males (mean ± SD 70.9 ± 14.3 years vs. 65.6 ± 133.6 years; p = 0.001) and had higher rates of atrial fibrillation (38.9% vs. 24.2%; p = 0.012). Time from groin puncture to reperfusion was shorter in females than males (mean ± SD 57.2 ± 37.2 min vs. 71.1 ± 50.9 min; p = 0.021). Despite these differences, primary and secondary outcome measures were similar in females and males, with comparable rates of favourable 90-day mRS scores (mean ± SD 46 ± 39.7 vs. 71 ± 34.5; OR = 1.20; 95% confidence interval [CI] = 0.59-2.43; p = 0.611), favourable discharge mRS scores (mean ± SD 39 ± 31.6 vs. 43 ± 25.9; OR = 1.38; 95% CI = 0.69-2.78; p = 0.368) and in-hospital mortality (mean ± SD 30 ± 25.9 vs. 47 ± 22.8; OR = 1.15; 95% CI = 0.55-2.43; p = 0.710. Rates of complications such as sICH (mean ± SD 5 ± 4.3 vs. 9 ± 4.4; OR = 0.46; 95% CI = 0.08-2.66; p = 0.385) and SAH (mean ± SD 4 ± 3.4 vs. 5 ± 2.4; OR = 0.29; 95% CI = 0.03-3.09; p = 0.303) comparably low in both groups. CONCLUSION: Females achieved comparable functional outcomes compared with males after undergoing MT for BAO acute ischemic stroke.

Bridging Thrombolysis versus Direct Mechanical Thrombectomy in Stroke Due to Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT. METHODS: This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0-3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH). RESULTS: Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not as Comorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013). CONCLUSIONS: Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.

The road to achieving herd immunity: factors associated with Singapore residents' uptake and hesitancy of the COVID-19 vaccination.

OBJECTIVE: Achieving high vaccination rates is key to containing the coronavirus disease 2019 (COVID-19). This study evaluated the factors associated with uptake of the COVID-19 vaccine. METHODS: Six hundred and seventy-six respondents were surveyed online between May and June 2021. Data on demographics, perception of the COVID-19 pandemic, and vaccine willingness and hesitancy factors were collected. RESULTS: Approximately 54.6% of the respondents had received the COVID-19 vaccination. Age (p = 0.001), males (OR 1.7, 95% CI 1.1-2.6, p = 0.026), ethnicity (p = 0.004), occupation (p = 0.003)), working in healthcare (OR 6.1, 95% CI 2.8-13.2, p < 0.001), smoking (OR 3.3, 95% CI 1.3-8.8, p = 0.014), seeing vaccination as a social responsibility (OR 3.8, 95% CI 1.2-12.0, p = 0.022) and believing the vaccine is important to end the COVID-19 pandemic (OR 2.7, 95% CI 1.1-6.1, p = 0.020) were associated with greater vaccination uptake. CONCLUSION: Social responsibility and well-being of collective society are important values associated with vaccine uptake in an Asian society. Understanding factors behind vaccine uptake can help advise public health measures and strategies to achieve high levels of vaccination.

Hospital-based observational study of neurological disorders in patients recently vaccinated with COVID-19 mRNA vaccines.

PURPOSE: We describe the spectrum of acute neurological disorders among hospitalized patients who recently had COVID-19 mRNA vaccination. METHOD: We performed a prospective study at 7 acute hospitals in Singapore. Hospitalized patients who were referred for neurological complaints and had COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, in the last 6 weeks were classified into central nervous system (CNS) syndromes, cerebrovascular disorders, peripheral nervous system (PNS) disorders, autonomic nervous system (ANS) disorders and immunization stress-related responses (ISRR). RESULTS: From 30 December 2020 to 20 April 2021, 1,398,074 persons (median age 59 years, 54.5% males) received COVID-19 mRNA vaccine (86.7% BNT162b2, 13.3% mRNA-1273); 915,344(65.5%) completed 2 doses. Four hundred and fifty-seven(0.03%) patients were referred for neurological complaints [median age 67(20-97) years, 281(61.5%) males; 95.8% received BNT162b2 and 4.2% mRNA-1273], classified into 73(16.0%) CNS syndromes, 286(62.6%) cerebrovascular disorders, 59(12.9%) PNS disorders, 0 ANS disorders and 39(8.5%) ISRRs. Eleven of 27 patients with cranial mononeuropathy had Bell's palsy. Of 33 patients with seizures, only 4 were unprovoked and occurred within 2 weeks of vaccination. All strokes occurred among individuals with pre-existing cardiovascular risk factors. We recorded 2 cases of cerebral venous thrombosis; none were vaccine-induced thrombotic thrombocytopenia. Five had mild flares of immune-mediated diseases. CONCLUSION: Our observational study does not establish causality of the described disorders to vaccines. Though limited by the lack of baseline incidence data of several conditions, we observed no obvious signal of serious neurological morbidity associated with mRNA vaccination. The benefits of COVID-19 vaccination outweigh concerns over neurological adverse events.

Encephalitis as a neurological complication of COVID-19: A systematic review and meta-analysis of incidence, outcomes, and predictors.

BACKGROUND AND PURPOSE: Although COVID-19 predominantly affects the respiratory system, recent studies have reported the occurrence of neurological disorders such as stroke in relation to COVID-19 infection. Encephalitis is an inflammatory condition of the brain that has been described as a severe neurological complication of COVID-19. Despite a growing number of reported cases, encephalitis related to COVID-19 infection has not been adequately characterised. To address this gap, this systematic review and meta-analysis aims to describe the incidence, clinical course, and outcomes of patients who suffer from encephalitis as a complication of COVID-19. METHODS: All studies published between 1 November 2019 and 24 October 2020 that reported on patients who developed encephalitis as a complication of COVID-19 were included. Only cases with radiological and/or biochemical evidence of encephalitis were included. RESULTS: In this study, 610 studies were screened and 23 studies reporting findings from 129,008 patients, including 138 with encephalitis, were included. The average time from diagnosis of COVID-19 to onset of encephalitis was 14.5 days (range = 10.8-18.2 days). The average incidence of encephalitis as a complication of COVID-19 was 0.215% (95% confidence interval [CI] = 0.056%-0.441%). The average mortality rate of encephalitis in COVID-19 patients was 13.4% (95% CI = 3.8%-25.9%). These patients also had deranged clinical parameters, including raised serum inflammatory markers and cerebrospinal fluid pleocytosis. CONCLUSIONS: Although encephalitis is an uncommon complication of COVID-19, when present, it results in significant morbidity and mortality. Severely ill COVID-19 patients are at higher risk of suffering from encephalitis as a complication of the infection.

Stroke as a Neurological Complication of COVID-19: A Systematic Review and Meta-Analysis of Incidence, Outcomes and Predictors.

INTRODUCTION: COVID-19 is a multi-system infection which predominantly affects the respiratory system, but also causes systemic inflammation, endothelialitis and thrombosis. The consequences of this include renal dysfunction, hepatitis and stroke. In this systematic review, we aimed to evaluate the epidemiology, clinical course, and outcomes of patients who suffer from stroke as a complication of COVID-19. METHODS: We conducted a systematic review of all studies published between November 1, 2019 and July 8, 2020 which reported on patients who suffered from stroke as a complication of COVID-19. RESULTS: 326 studies were screened, and 30 studies reporting findings from 55,176 patients including 899 with stroke were included. The average age of patients who suffered from stroke as a complication of COVID-19 was 65.5 (Range: 40.4-76.4 years). The average incidence of stroke as a complication of COVID-19 was 1.74% (95% CI: 1.09% to 2.51%). The average mortality of stroke in COVID-19 patients was 31.76% (95% CI: 17.77% to 47.31%). These patients also had deranged clinical parameters including deranged coagulation profiles, liver function tests, and full blood counts. CONCLUSION: Although stroke is an uncommon complication of COVID-19, when present, it often results in significant morbidity and mortality. In COVID-19 patients, stroke was associated with older age, comorbidities, and severe illness.