The Role of Circadian Rhythms in Stroke: A Narrative Review.

Stroke, a debilitating condition often leading to long-term disability, poses a substantial global concern and formidable challenge. The increasing incidence of stroke has drawn the attention of medical researchers and neurologists worldwide. Circadian rhythms have emerged as pivotal factors influencing stroke's onset, pathogenesis, treatment, and outcomes. To gain deeper insights into stroke, it is imperative to explore the intricate connection between circadian rhythms and stroke, spanning from molecular mechanisms to pathophysiological processes. Despite existing studies linking circadian rhythm to stroke onset, there remains a paucity of comprehensive reviews exploring its role in pathogenesis, treatment, and prognosis. This review undertakes a narrative analysis of studies investigating the relationship between circadian variation and stroke onset. It delves into the roles of various physiological factors, including blood pressure, coagulation profiles, blood cells, catecholamines, cortisol, and the timing of antihypertensive medication, which contribute to variations in circadian-related stroke risk. At a molecular level, the review elucidates the involvement of melatonin, circadian genes, and glial cells in the pathophysiology. Furthermore, it provides insights into the diverse factors influencing stroke treatment and outcomes within the context of circadian variation. The review underscores the importance of considering circadian rhythms when determining the timing of stroke interventions, emphasizing the necessity for personalized stroke management strategies that incorporate circadian rhythms. It offers valuable insights into potential molecular targets and highlights areas that require further exploration to enhance our understanding of the underlying pathophysiology. In comparison to the published literature, this manuscript distinguishes itself through its coverage of circadian rhythms' impact on stroke across the entire clinical spectrum. It presents a unique synthesis of epidemiological, clinical, molecular, and cellular evidence, underscoring their collective significance.

Sex Alters the Effect of Perfusion Deficits on Functional Outcome in Patients with Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

INTRODUCTION: The discourse surrounding differences in cerebral hemodynamics and clinical outcomes among male and female patients treated with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) remains unresolved. We aimed to elucidate these differences by employing computed tomography perfusion (CTP) imaging before MT and examining the influence of perfusion deficits on the 90-day functional outcome. METHODS: This single-center retrospective analysis involved patients with anterior circulation AIS treated with MT at the Comprehensive Stroke Center, University Hospital, Krakow, from January 2019 to July 2023. We compared male and female patients in terms of baseline characteristics, CTP deficits, hypoperfusion intensity ratio (HIR, defined as T10max/T6max), and complications. The endpoints included the 90-day excellent functional outcome, defined as modified Rankin Score <2, and the 90-day mortality rate. RESULTS: We included 794 patients, of whom 408 were female (51.4%). Female patients had a smaller early infarct volume (median [interquartile range]: 7 mL [0-24.8] vs. 10 mL [0-33], p = 0.004), smaller penumbra volume (77.5 mL [46-117] vs. 99.5 mL [59.8-140], p < 0.001), lower HIR (0.34 [0.16-0.5] vs. 0.37 [0.2-9.53], p = 0.043) and were less likely to achieve an excellent functional outcome (55.6% vs. 66.1%, p = 0.003). For every 10 mL increase in early infarct volume, the odds for achieving an excellent outcome were lower in females (odds ratio [OR]: 0.82 [95% confidence interval: 0.73-0.92]) compared to males (OR: 0.96 [0.88-1.04]), whereas the risk of death was higher for females (OR: 1.25 [1.13-1.39] than for males (OR: 1.05 [0.98-1.14]). DISCUSSION: Despite more favorable cerebral hemodynamic profile, female AIS patients have worse outcomes than their male counterparts. This effect seems to be independently mediated by the more pronounced impact of early infarct volume on the prognosis in female patients. These findings underscore the possible explanatory power arising from sex-specific interpretation of early infarct volume in clinical practice.

The benefit of optimizing recanalization during mechanical thrombectomy in patients with acute ischemic stroke depends on preprocedural tissue-level collateralization.

PURPOSE: Thrombolysis in Cerebral Infarction (TICI) 3 represents the optimal angiographic outcome following mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Although it is known to yield better outcomes than TICI 2b, the influence of preprocedural cerebral hemodynamics on the clinical advantage of TICI 3 over TICI 2b remains unexplored. METHODS: This single-center retrospective analysis involved patients with anterior circulation AIS who underwent successful recanalization during MT at the Comprehensive Stroke Center, University Hospital, Krakow between January 2019 and July 2023. We assessed the benefit of achieving TICI 2c/3 over TICI 2b on the basis of preprocedural computed perfusion imaging results, primarily focusing on early infarct volume (EIV) and tissue-level collaterals indicated by hypoperfusion intensity ratio (HIR). Good functional outcome (GFO) was defined as a modified Rankin Score < 3 on day 90. RESULTS: The study comprised 612 patients, of whom 467 (76.3%) achieved TICI 2c/3. GFO was more frequent in the TICI 2c/3 group (54.5% vs 69.4%, p < 0.001). There was interaction between the recanalization status and both HIR (Pi = 0.042) and EIV (Pi = 0.012) in predicting GFO, with disproportionately higher impact of HIR and EIV in TICI 2b group. The benefit from TICI 2c/3 over TICI 2b was insignificant among patients with good collaterals, defined by HIR < 0.3 (odds ratio:1.36 [0.58-3.18], p = 0.483). CONCLUSION: TICI 2c/3 improves patient functional outcomes compared to TICI 2b regardless of EIV. However, such angiographic improvement may be clinically futile in patients with good tissue-level collateralization. Our findings suggest that preprocedural HIR should be considered when optimization of recanalization is considered during MT.

Relationships between obesity and functional outcome after ischemic stroke: a Mendelian randomization study.

BACKGROUND AND OBJECTIVES: Most previous studies suggested obesity deteriorates the functional outcome after ischemic stroke. But there are researches claiming that obesity is associated with lower mortality, recurrence, and readmission rates, which is known as the obesity paradox. Our current research aimed to investigate the correlation between genetically obesity and the post-stroke outcome with the Mendelian randomization (MR) method. METHODS: The UK Biobank and the GIANT consortium provided instrumental variables for body mass index (BMI, 806,834 individuals) and waist-to-hip ratio (WHR, 697,734 individuals). Data of functional outcome after ischemic stroke were obtained from the Genetics of Ischemic Stroke Functional Outcome network (6012 individuals). Inverse-variance weighted approach was utilized as the primary analyses. Sensitivity analyses involved the utilization of different MR methods. The heterogeneity among genetic variants was assessed by I2 and Q value statistics. RESULTS: In univariable analysis, there was a significant connection between genetic susceptibility to WHR and worse functional outcome (modified Rankin Scale 3) after ischemic stroke (OR [95%CI] = 1.47 [1.07, 2.02], P = 0.016). Genetic liability to BMI and was not associated with post-stroke functional outcome (all P > 0.05). The overall patterns between genetic liability to WHR and functional outcome post-ischemic outcome no longer existed in the multivariable MR analysis after adjusting for BMI (OR [95%CI] = 1.26[0.76,1.67], P = 0.56). CONCLUSION: The current MR study provided evidence that WHR was correlated to unfavorable outcome post-ischemic stroke. Exploring interventions against obesity may potentially improve recovery after ischemic stroke.

Do stroke services still show sex differences? A multicenter study.

BACKGROUND: The issue of sex differences in stroke has gained concern in the past few years. However, multicenter studies are still required in this field. This study explores sex variation in a large number of patients and compares stroke characteristics among women in different age groups and across different countries. METHODS: This multicenter retrospective cross-sectional study aimed to compare sexes regarding risk factors, stroke severity, quality of services, and stroke outcome. Moreover, conventional risk factors in women according to age groups and among different countries were studied. RESULTS: Eighteen thousand six hundred fifty-nine patients from 9 countries spanning 4 continents were studied. The number of women was significantly lower than men, with older age, more prevalence of AF, hypertension, and dyslipidemia. Ischemic stroke was more severe in women, with worse outcomes among women (p: < 0.0001), although the time to treatment was shorter. Bridging that was more frequent in women (p:0.002). Analyzing only women: ischemic stroke was more frequent among the older, while hemorrhage and TIA prevailed in the younger and stroke of undetermined etiology. Comparison between countries showed differences in age, risk factors, type of stroke, and management. CONCLUSION: We observed sex differences in risk factors, stroke severity, and outcome in our population. However, access to revascularization was in favor of women.

Location-Specific Hematoma Volume Cutoff and Clinical Outcomes in Intracerebral Hemorrhage.

BACKGROUND: Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the heterogeneity of ICH outcomes based on their location, where a small strategic ICH could be debilitating, thus confounding therapeutic effects. We aimed to determine the ideal hematoma volume cutoff for different ICH locations in predicting ICH outcomes. METHODS: We retrospectively analyzed consecutive ICH patients enrolled in the University of Hong Kong prospective stroke registry from January 2011 to December 2018. Patients with premorbid modified Rankin Scale score >2 or who underwent neurosurgical intervention were excluded. ICH volume cutoff, sensitivity, and specificity in predicting respective 6-month neurological outcomes (good [modified Rankin Scale score 0-2], poor [modified Rankin Scale score 4-6], and mortality) for specific ICH locations were determined using receiver operating characteristic curves. Separate multivariate logistic regression models were also conducted for each location-specific volume cutoff to determine whether these cutoffs were independently associated with respective outcomes. RESULTS: Among 533 ICHs, the volume cutoff for good outcome according to ICH location was 40.5 mL for lobar, 32.5 mL for putamen/external capsule, 5.5 mL for internal capsule/globus pallidus, 6.5 mL for thalamus, 17 mL for cerebellum, and 3 mL for brainstem. ICH smaller than the cutoff for all supratentorial sites had higher odds of good outcomes (all P<0.05). Volumes exceeding 48 mL for lobar, 41 mL for putamen/external capsule, 6 mL for internal capsule/globus pallidus, 9.5 mL for thalamus, 22 mL for cerebellum, and 7.5 mL for brainstem were at greater risk of poor outcomes (all P<0.05). Mortality risks were significantly higher for volumes that exceeded 89.5 mL for lobar, 42 mL for putamen/external capsule, and 21 mL for internal capsule/globus pallidus (all P<0.001). All receiver operating characteristic models for location-specific cutoffs had good discriminant values (area under the curve >0.8), except in predicting good outcome for cerebellum. CONCLUSIONS: ICH outcomes differed with location-specific hematoma size. Location-specific volume cutoff should be considered in patient selection for ICH trials.

Crossed Cerebellar Diaschisis Worsens the Clinical Presentation in Acute Large Vessel Occlusion.

INTRODUCTION: Initial NIHSS in anterior large vessel occlusion (LVO) correlates partially with the hypoperfusion volume. We aimed at assessing the contribution of crossed cerebellar diaschisis (CCD) from the hypoperfused territory on LVO initial clinical deficit. METHODS: CCD was retrospectively identified by brain CT perfusion imaging (CTP) in patients with anterior LVO treated by mechanical thrombectomy from January 2017 to July 2021. CCD was defined by CTP parameter alteration in the contralateral cerebellar hemisphere to the LVO. NIHSS, clinical/perfusion variables, and CCD were included in regression models to assess their interrelationships. RESULTS: 206 patients were included. CCD was present in 90 patients (69%). NIHSS scores were higher on admission and at stroke discharge among patients with CCD (17.90 ± 6.1 vs. 11.4 ± 8.4, p < 0.001; 9.6 ± 7.7 vs. 6.6 ± 7.9, p = 0.049; respectively). Patients with a CCD had higher stroke volumes (118.2 ± 60.3 vs. 69.3 ± 59.7, p < 0.001) and lower rate of known atrial fibrillation (22% vs. 41%, p = 0.021). On multivariable logistic regression, CCD independently worsened the initial NIHSS (OR 4.85 [2.37-7.33]; p < 0.001). CONCLUSION: CCD is found in 69% of LVO on admission CTP, correlates with stroke volumes, and independently worsens initial NIHSS.

Association of Incomplete Neurovascular Imaging After Emergency Department Encounters for Transient Ischemic Attack and Odds of Subsequent Stroke: A National Medicare Analysis.

BACKGROUND. Multisociety guidelines recommend urgent brain and neurovascular imaging for patients with transient ischemic attack (TIA), to identify and treat modifiable stroke risk factors. Prior research suggests that most patients with TIA who present to the emergency department (ED) do not receive prompt neurovascular imaging. OBJECTIVE. The purpose of this study was to evaluate the association between incomplete neurovascular imaging workup during ED encounters for TIA and the odds of subsequent stroke. METHODS. This retrospective study obtained data from the Medicare Standard Analytical Files for calendar years 2016 and 2017; these files contain 100% samples of claims for Medicare beneficiaries. Information was extracted using ICD 10th revision (ICD-10) and CPT codes. Those patients who were discharged from an ED encounter with a TIA diagnosis and who underwent brain CT or brain MRI during or within 2 days of the encounter were identified. Patients were considered to have complete neurovascular imaging if they underwent cross-sectional vascular imaging of both the brain (brain CTA or brain MRA) and neck (neck CTA, neck MRA, or carotid ultrasound) during or within 2 days of the encounter. The association between incomplete neurovascular imaging and a new stroke diagnosis within the subsequent 90 days was tested by multivariable logistic regression analysis. RESULTS. The sample included 111,417 patients (47,370 men, 64,047 women; 26.0% older than 84 years) who had TIA ED encounters. A total of 37.3% of patients (41,592) had an incomplete neurovascular imaging workup. A new stroke diagnosis within 90 days of the TIA ED encounter occurred in 4.4% (3040/69,825) of patients with complete neurovascular imaging versus 7.0% (2898/41,592) of patients with incomplete neurovascular imaging. Incomplete neurovascular imaging was associated with increased likelihood of stroke within 90 days (OR, 1.30 [95% CI, 1.23-1.38]) after adjustment for patient characteristics (age, sex, race and ethnicity, high-risk comorbidities, median county household income) and hospital characteristics (region, rurality, number of beds, major teaching hospital designation). CONCLUSION. TIA ED encounters with incomplete neurovascular imaging were associated with higher odds of subsequent stroke occurring within 90 days. CLINICAL IMPACT. Increased access to urgent neurovascular imaging for patients with TIA may represent a target that could facilitate detection and treatment of modifiable stroke risk factors.

Assessing the influence of migraine on ischemic penumbra and on the prognosis of ischemic stroke: A prospective cohort study.

INTRODUCTION: There is controversy as to whether migraine affects the behavior of ischemic penumbra during the acute phase of an ischemic stroke, thereby accelerating the formation of cerebral infarction. OBJECTIVES: To assess whether migraine modifies the existence and volume of the divergence between the areas of diffusion and perfusion in the stroke (the penumbra) and whether migraine implies a poorer prognosis after the stroke. METHODS: This was a prospective cohort study. We included hospitalized patients with ischemic stroke within 72 h of symptom onset (convenience sampling). A semi-structured questionnaire, the National Institute of Health Stroke Scale, and the modified Rankin Scale (mRS) were used. Patients underwent magnetic resonance imaging (MRI) of the brain with diffusion and with perfusion. Patients were assessed by telephone 3 months after the stroke to determine the prognosis. Scores of > 2 on the mRS were considered to have a poor prognosis. RESULTS: A total of 221 patients were included, 131/221 (59%) of whom were male, and with a mean (SD) age of 68.2 (13.8) years. Ischemic penumbra analysis was performed in 118 patients. There was no association between migraine and the absence of ischemic penumbra (16/63 [25%] vs. 12/55 [22%]; odds ratio 1.22, 95% confidence interval 0.52-2.87; p = 0.64). There was no difference in stroke volume between those with and without migraine (median [interquartile range] 1.0 [0.4-7.9] vs. 1.8 [0.3-9.4] cm3 ; p = 0.99). Migraine was not associated with the stroke prognosis after multivariable analysis. CONCLUSION: Migraine is not associated with the absence of ischemic penumbra, the volume of the ischemic penumbra, or the stroke prognosis.

Impact of white matter hypodensities on outcome after intracerebral hemorrhage.

OBJECTIVES: White matter hypodensities (WMH), a surrogate of small vessel disease, associate with cognitive decline and stroke risk. The impact of WMH on functional outcome after intracerebral hemorrhage (ICH) has differed between studies. We aimed to examine factors associated with the severity of WMH in ICH, and whether there is an independent association between the extent of WMH and outcome. MATERIALS AND METHODS: This was a prospective study of consented patients with non-traumatic primary ICH, admitted to the Helsinki University Hospital between May 2014 and December 2018. To evaluate the extent of the WMH, modified van Swieten score of the side contralateral to the ICH was obtained. Patients were grouped into 3 categories of the scores. We performed univariate and multivariable analyses to find out factors associated with the severity of WMH, and whether WMH associate with functional outcome and mortality up to 12 months, adjusted for the known major outcome predictors. RESULTS: In our cohort of 417 ICH patients, WMH severity associated with older age, female sex, admission National Institutes of Health Stroke Scale (NIHSS) points, and signs of previous ischemic stroke on CT. We found an independent association between WMH severity and poor functional outcome at 3 months (OR 1.72, 95% CI 1.27-2.33), and 1 year (OR 2.16, 95% CI 1.57-2.95), and mortality at 1 year (OR 1.91, 95% CI 1.29-2.85). CONCLUSIONS: In our ICH patients, vascular comorbidities and older age associated with the presence of WMH, which, in turn, strongly associated with poor functional outcome.

Association of underlying untreated cardiovascular risk factors with mortality and functional outcome in ischaemic stroke patients.

OBJECTIVES: The study aimed to determine the prevalence of untreated pharmacologically modifiable cardiovascular risk factors (PMRF) among patients with ischaemic stroke and the association with in-hospital mortality and functional outcome. METHODS: We analysed the data from ischaemic stroke cases admitted to Sarawak General Hospital between June 2013 and June 2021. We matched the underlying PMRFs with prior medications and categorised them as treated, untreated, or no PMRF. We calculated the prevalence and assessed the association between untreated PMRFs and in-hospital mortality or favourable functional outcome (FFO) at discharge, which was adjusted for age, sex, and other covariates in multivariable models. RESULTS: We included 1963 patients [65.4% male, 59.8 (SD 13.4) years]; 43.8% who had at least one untreated PMRF had triple the odds of in-hospital mortality [adjusted OR (aOR) 2.86, (95%CI 1.44, 5.70)], whereas 30.2% who had all PMRFs treated showed no significant association. Untreated hypertension [aOR 2.19 (95%CI 1.21, 3.98)], treated [aOR 3.02 (95%CI 1.32, 6.92)], and untreated atrial fibrillation [aOR 1.89 (95%CI 1.18, 3.03)] were significantly associated with more in-hospital death, whereas treated prior stroke was associated with fewer in-hospital death [aOR 0.31 (95%CI 0.11, 0.84)]. Treated diabetes [aOR 0.66 (95%CI 0.49, 0.88)] and untreated prior stroke [aOR 0.53 (95%CI 0.33, 0.83)] were associated with fewer FFO. CONCLUSION: The high prevalence of untreated underlying PMRFs was significantly associated with poorer outcomes among Malaysian patients with ischaemic stroke in Sarawak. Efforts are needed to promote early screening and treatment of cardiovascular risk factors to reduce the burdens and improve stroke outcomes in this region.

The Study of the Association of Polymorphisms in LSP1, GPNMB, PDPN, TAGLN, TSPO, and TUBB6 Genes with the Risk and Outcome of Ischemic Stroke in the Russian Population.

To date, there has been great progress in understanding the genetic basis of ischemic stroke (IS); however, several aspects of the condition remain underexplored, including the influence of genetic factors on post-stroke outcomes and the identification of causative loci. We proposed that an analysis of the results obtained from animal models of brain ischemia could be helpful. To this end, we developed a bioinformatic approach for exploring single-nucleotide polymorphisms (SNPs) in human orthologs of rat genes expressed differentially after induced brain ischemia. Using this approach, we identified and analyzed 11 SNPs from 6 genes in 553 Russian individuals (331 patients with IS and 222 controls). We assessed the association of SNPs with the risk of IS and IS outcomes. We found that the SNPs rs858239 (GPNMB), rs907611 (LSP1), and rs494356 (TAGLN) were associated with different parameters of IS functional outcomes. In addition, the SNP rs1261025 (PDPN) was associated significantly with IS itself (p = 0.0188, recessive model). All these associations were demonstrated for the first time. Analysis of the literature suggests that they should be characterized as being inflammation related. This supports the pivotal role of inflammation in both the incidence of stroke and post-stroke outcomes. We believe the findings reported here will help with stroke prognosis in the future.

The prognostic value of the Charlson comorbidity index in aged patients with intracerebral hemorrhage.

BACKGROUND: Comorbidities are common in aged intracerebral hemorrhage patients. The purpose of this study was to assess whether the Charlson Comorbidity Index (CCI) was associated with in-hospital death and short-term functional outcome in elderly patients (age ≥ 70) with intracerebral hemorrhage (ICH). METHODS: This was a retrospective cohort of aged ICH patients (≥70 years old) admitted within 24 hours of ICH onset. The CCI was derived using hospital discharge ICD-9 CM codes and patient history obtained from standardized case report forms. Multivariable logistic regression was used to determine the independent effect of the CCI score on clinical outcomes. RESULTS: In this cohort of 248 aged ICH patients, comorbid conditions were common, with CCI scores ranging from 2 to 12. Logistic regression showed that the CCI score was independently predictive of 1-month functional outcome (OR = 1.642, P < 0.001) and in-hospital death (OR = 1.480, P = 0.003). Neither ICH volume nor the presence of IVH was an independent predictive factor for 1-month functional outcome or in-hospital mortality (P < 0.05). CONCLUSION: Comorbid medical conditions as assessed by the CCI independently influence short-term outcomes in aged ICH patients. The characteristics of the hematoma itself, such as ICH volume and the presence of IVH, seem to have a reduced effect on it.

Clinical and laboratory features in patients with positive syphilis serology presenting with acute ischemic stroke or transient ischemic attack: a prospective cohort study.

BACKGROUND: Neurosyphilis (NS) can lead to acute ischemic stroke (AIS) or transient ischemic attack (TIA). We compared the clinical characteristics and laboratory features among AIS and TIA patients who were syphilis-seronegative (control group) or had latent syphilis (LS) or NS to evaluate their stroke outcome. METHODS: This prospective cohort study was conducted on patients who had recently suffered AIS or TIA. After serological syphilis screening, clinical and laboratory data were collected, and brain imaging and spinal tap (serologically syphilis-positive patients only) were performed. Stroke outcome was re-evaluated approximately three months later. RESULTS: The 344 enrolled patients were divided into three groups: control group (83.7%), LS (13.1%), and NS (3.2%). A multivariate analysis revealed: 1) age of ≥ 70 years, generalized brain atrophy via imaging, and alopecia (adjusted odds ratio [AOR] = 2.635, 2.415, and 13.264, respectively) were significantly associated with LS vs controls; 2) age of ≥ 70 years (AOR = 14.633) was significantly associated with NS vs controls; and 3) the proportion of patients with dysarthria was significantly lower (AOR = 0.154) in the NS group than in the LS group. Regarding the NS patient cerebrospinal fluid (CSF) profile, only 2/11 cases had positive CSF-Venereal Disease Research Laboratory (VDRL) test results; the other nine cases were diagnosed from elevated white blood cell counts or protein levels combined with positive CSF fluorescent treponemal antibody absorption (FTA-ABS) test results. Regarding disability, the initial modified Rankin scale (mRS) score was lower in the control group than in the NS group (p = 0.022). At 3 months post-stroke, the mRS score had significantly decreased in the control (p < 0.001) and LS (p = 0.001) groups. Regarding activities of daily living, the 3-month Barthel Index (BI) score was significantly higher in control patients than in LS (p = 0.030) or NS (p = 0.002) patients. Additionally, the 3-month BI score was significantly increased in the control (p < 0.001) and LS (p = 0.001) groups. CONCLUSIONS: Because syphilis was detected in many AIS and TIA patients, especially those aged ≥ 70 years, routine serological syphilis screening may be warranted in this population. Patients with syphilitic infection had worse stroke outcomes compared with NS patients.

National Institutes of Health Stroke Scale Correlates Well with Initial Intracerebral Hemorrhage Volume.

OBJECTIVES: The US Centers for Medicare and Medicaid Services (CMS) currently publicly reports hospital-quality, risk-adjusted mortality measure for ischemic stroke but not intracerebral hemorrhage (ICH). The NIHSS, which is captured in CMS administrative claims data, is a candidate metric for use in ICH risk adjustment and has been shown to predict clinical outcome with accuracy similar to the ICH Score. Correlation between early NIHSS and initial ICH volume would further support use of the NIHSS for ICH risk adjustment. MATERIALS AND METHODS: Among 372 ICH patients enrolled in a large multicenter trial (FAST-MAG), the relation between early NIHSS and early ICH volume was assessed with correlation and linear trend analysis. RESULTS: Overall, there was strong correlation between NIHSS and ICH volume, r = 0.77 (p < 0.001), and for every 10cc increase in ICH the NIHSS increased by 4.5 points. Correlation coefficients were comparable in all subgroups, but magnitude of NIHSS increase with ICH unit volume increase was greater with left than right hemispheric ICH, with presence rather than absence of IVH, with imaging done within the first hour than second hour after last known well, with men than women, and with younger than older patients. CONCLUSION: Early NIHSS neurologic deficit severity values correlate strongly with initial ICH hematoma volume. As with ischemic stroke, lesion volume increases produce greater NIHSS change in the left than right hemisphere, reflecting greater NIHSS sensitivity to left hemisphere function. These findings provide further support for the use of NIHSS in risk-adjusted mortality measures for intracerebral hemorrhage.

Association between nocturnal oxygen desaturation and ischaemic stroke outcomes.

CLINICAL RATIONALE FOR THE STUDY: This study aimed to assess the association between nocturnal hypoxemia and early acute ischaemic stroke (AIS) outcomes in patients without oxygen supplementation. MATERIAL AND METHODS: One hundred and six AIS patients consecutively admitted to the stroke unit were included in this study. Baseline demographic and medical data and arterial blood saturation (SpO2) measurements during night-sleep (from 10pm to 6am) were examined for their association with stroke outcomes, including the National Institutes of Health Stroke Scale (NIHSS) score on the 7th day or differences between the NIHSS score on the 1st day and the 7th day after stroke onset. Measurements of SpO2 were made using a pulse oximeter of the Spacelabs Medical Inc. (USA) monitoring system, and the number of apnoea episodes and their duration were recorded by ECG Holter with respiration monitoring (CardioMem®, Getamed, GE). RESULTS: The study showed that age (Spearman's r = 0.207, p = 0.033) and parameters attributable to anaemia (RBC r = -0.205, p = 0.035, Hb r = -0.225, p = 0.02 and HCT r = -0.196, p = 0.044), atrial fibrillation and ischaemic changes in both brain hemispheres (p = 0.023 and 0.01, respectively) were correlated with the study outcomes. In terms of saturation parameters, we demonstrated that the 'total desaturation burden' (i.e. [100% minus actual measured SpO2%] x apnoea duration) and multiple apnoeas of longer than 20 seconds were correlated with worse functional outcomes. Measures of shorter desaturation episodes (i.e. SpO2 oxygen desaturation index (ODI) at 3% and 4%, and time-weighted desaturations below the determined thresholds (SpO2 from 95% to 85%) demonstrated non-significant associations with the study outcomes. CONCLUSIONS AND CLINICAL IMPLICATIONS: This study demonstrated that long-lasting desaturation episodes during the night, depicted by the 'total desaturation burden', were correlated with worse functional outcomes in AIS, while measures of shorter desaturation episodes were not correlated. In future clinical trials, indications for oxygen supplementation should include the methodology of personalised medicine and introduce individual approaches based on specially formulated, novel multifactorial algorithms.

Aging Immune System in Acute Ischemic Stroke: A Transcriptomic Analysis.

[Figure: see text].

Missense Variants in Hypoxia-Induced VEGFA/VEGFR2 Signaling Predict the Outcome of Large Artery Atherosclerotic Stroke.

Collateral density variations are a major determinant of stroke outcome. Here, we explored the association of missense variants in hypoxia-induced VEGFA/VEGFR2 signaling and stroke outcome. We recruited 683 large artery atherosclerotic (LAA) stroke patients as the training set from Nanjing Stroke Registry Program between August 2013 and January 2016. To validate the findings from the training set, we recruited an additional 333 LAA stroke patients between February 2016 and January 2017 as the validation set. Genotyping of target SNPs (rs11549465 [HIF-1α], rs11549467 [HIF-1α], rs1870377 [VEGFR2], and rs2305948 [VEGFR2]) was conducted using a SNPscan method. Unfavorable outcome was defined as a modified Rankin Scale (mRS) score > 2 at three months after index event. In the training set, the AA genotype of rs1870377 led to a decreased risk of unfavorable outcomes in the recessive model (AA vs. TA + TT, OR 0.60, 95% CI 0.38-0.95, P = 0.031). This was confirmed in the validation set (OR 0.43, 95% CI 0.21-0.86, P = 0.017) and the combined set (OR 0.54, 95% CI 0.36-0.79, P = 0.002). We also found that A allele was a protective factor for stroke outcome in both validation set and combined set (OR 0.70, 95% CI 0.49-0.99, P = 0.044 and OR 0.77, 95% CI 0.63-0.94, P = 0.012, respectively). In silico analysis indicated that the rs1870377 variant led to structural alterations in VEGFR2 that may influence its activity. Our findings demonstrate that the rs1870377 in the hypoxia-induced VEGFA/VEGFR2 axis predicts the 3-month outcome of patients with LAA stroke.

Insights in the pathophysiology of haemorrhagic strokes in a sub-Sahara African country, an epidemiological and MRI study.

OBJECTIVE: Intra-cerebral Haemorrhage (ICH) seems more prevalent in sub-Saharan Africa (SSA) than in High-Income Countries (HIC) with poorer clinical outcome. Higher impact of hypertension and/or amyloid angiopathy could account for this disproportion. Here, we sought to (i) retrospectively compare ICH clinical and imaging patterns in Belgium and Guinea and in a subsequent cohort (ii) prospectively compare brain MRI characteristics to seek evidence for a different proportion of amyloid angiopathy patterns. METHODS: Ninety one consecutive patients admitted for spontaneous ICH at Brussels Erasme-ULB Hospital and at Conakry Ignace Deen-UGANC were retrospectively compared in terms of ICH volume estimated with the ABC/2 method, clinical characteristics and modified ranking (mRS) score at 30 days. mRS was dichotomised as good outcomes (≤3) and poor outcomes (>3). A prospective cohort of 30 consecutive patients with ICH admitted at CHU Conakry Ignace Deen-UGANC was prospectively included to undergo brain MRI. Results of the Guinean MRI were compared to 30 patients randomly selected from Brussels' initial cohort. Paired Student's t-test and Mann-Whitney u-test were used for group comparisons. RESULTS: Age of ICH onset was higher in Belgium (68 ± 17 years vs. 56 ± 14 years, P < 0.01) while ICH volume and 30-day mortality rate were higher in Guinea (20 ml vs. 11 ml, P < 0.01 and mortality 33% vs. 10 %, P < 0.01). ICH burden in survivors in Conakry and Brussels showed respectively good outcomes in 56.7% and 60.4% (P = 0.09) and poor outcomes in 10.3% vs. 29.6% (P < 0.001). MRI analysis of the prospective cohort failed to disclose significant differences regarding brain MRI characteristics. CONCLUSIONS: Intra-cerebral Haemorrhage affected patients 15 years younger in Guinea with larger haematoma volumes and higher mortality than in Belgium. MRI findings did not show more prevalent amyloid angiopathy pathology suggesting that better primary prevention of hypertension could positively impact ICH epidemiology in Guinea.

OBJECTIF: L'hémorragie intracérébrale (HIC) semble plus répandue en Afrique subsaharienne (ASS) que dans les pays à revenu élevé (PRE), avec des résultats cliniques moins bons. Un impact plus élevé de l'hypertension et/ou de l'angiopathie amyloïde pourrait expliquer cette disproportion. Ici, nous avons cherché à (i) comparer rétrospectivement les schémas cliniques et d'imagerie de l'HIC en Belgique et en Guinée et dans une cohorte subséquente (ii) comparer de manière prospective les caractéristiques de l'IRM cérébrale pour rechercher des preuves d'une proportion différente des profils d'angiopathie amyloïde. MÉTHODES: 91 patients consécutifs admis pour HIC spontanée à l'hôpital Erasme-ULB de Bruxelles et à Ignace Deen-UGANC de Conakry ont été rétrospectivement comparés en termes de volume d'HIC estimé avec la méthode ABC/2, les caractéristiques cliniques et le score de classement modifié (mRS) à 30 jours. Le mRS a été dichotomisé en bons résultats (≤3) et mauvais résultats (>3). Une cohorte prospective de 30 patients consécutifs atteints d'HIC admis au CHU Ignace Deen-UGANC de Conakry a été incluse de manière prospective pour subir une IRM cérébrale. Les résultats de l'IRM guinéenne ont été comparés à ceux de 30 patients sélectionnés aléatoirement dans la cohorte initiale de Bruxelles. Le test t de Student apparié et le test u de Mann-Whitney ont été utilisés pour les comparaisons de groupe. RÉSULTATS: L'âge d'apparition de l'HIC était plus élevé en Belgique (68 ± 17 ans vs 56 ± 14 ans, P < 0,01) tandis que le volume de l'HIC et le taux de mortalité à 30 jours étaient plus élevés en Guinée (20 ml vs 11 ml, P < 0,01 et mortalité 33% vs 10%, P <0,01). La charge de l'HIC chez les survivants à Conakry et à Bruxelles a montré respectivement de bons résultats dans 56,7% et 60,4% (P = 0,09) et de mauvais résultats dans 10,3% vs 29,6% (P < 0,001). L'analyse IRM de la cohorte prospective n'a pas permis de révéler de différences significatives concernant les caractéristiques de l'IRM cérébrale. CONCLUSIONS: L'HIC a touché des patients 15 ans plus jeunes en Guinée avec des volumes d'hématomes plus importants et une mortalité plus élevée qu'en Belgique. Les résultats de l'IRM n'ont pas montré de pathologie angiopathique amyloïde plus répandue, ce qui suggère qu'une meilleure prévention primaire de l'hypertension pourrait avoir un impact positif sur l'épidémiologie de l'HIC en Guinée.

The Association between Substance Use Disorders and Long-Term Outcome of Stroke: Results from a Population-Based Study of Stroke among 450,229 Urban Citizens.

INTRODUCTION: Little is known regarding long-term stroke outcomes in patients with substance use disorder (SUD). Based on anecdotal data, some individuals use illicit drugs, particularly opioids, in an attempt to reduce stroke mortality, disability, or recurrence. This study is aimed to assess the effect of SUD on stroke outcomes. METHODS: Patients were recruited from the Mashhad Stroke Incidence Study, a population-based study of stroke in Iran. For a period of 1 year, all patients with first-ever stroke (FES) were recruited and then followed up for the next 5 years. Disability and functional dependency were defined using modified Rankin Scale (>2) and Barthel Index (<60), respectively. We compared the cumulative rates of mortality in follow-up points using the log-rank test. We used multivariable logistic, Cox regression and competing risk models to assess adjusted hazard ratio (aHR) with 95% confidence interval (CI) of stroke disability, functional dependency, mortality, and recurrence among those with a history of SUD. RESULTS: 595 FES patients (mean age of 64.6 ± 14.8 years) were recruited in this study. Eighty-one (13.6%) were current substance users, including opium (n = 68), naswar (n = 5, 6.1%), hashish (n = 1), heroin (n = 1), and (n = 7) others. The frequency of vascular risk factors was similar between the SUD and non-SUD groups, except for a higher rate of cigarette smoking in the SUD group (p < 0.001). After adjusting for various sociodemographic variables, vascular risk factors, and the severity of stroke at admission, SUD increased the 3-month (aHR: 1.60, CI: 1.01-2.49), 1-year (aHR: 1.73, CI: 1.20-2.65), and 5-year (aHR: 1.72, CI: 1.23-2.35) poststroke mortality risk. We did not observe a significant change in the risk of stroke recurrence, disability, and functional dependency in those with a history of SUD. CONCLUSION: SUD increased the hazard ratio of stroke mortality with no effect on the disability rate. The public should be advised about the potential harm of substance abuse.