The TriAGe + score for vertigo or dizziness: A validation study in a university hospital emergency department in Hong Kong.

OBJECTIVE: Patients with dizziness commonly present to Emergency Departments (ED) and 6% of these patients will be diagnosed with acute stroke. The TriAGe+ score comprises of eight clinical parameters and stratifies patients into four risk groups. The Japanese authors reported that the tool performed well, so our aim was to validate this diagnostic tool in our ED in Hong Kong. MATERIALS AND METHODS: A single-center retrospective observational study was conducted in the ED of our university hospital in Hong Kong. The primary outcome was the diagnosis of an acute cerebrovascular event. Receiver operator characteristic (ROC) analysis was performed to determine the best cut-off score. Secondary outcomes included univariable and multivariable analyses of stroke predictors. RESULTS: 455 patients aged 18 years or above with dizziness or vertigo at ED triage were recruited between 19 July and 30 September 2021. The overall prevalence of stroke was 11.9%. The median TriAGe+ score was 7 (IQR = 4-9). The AUC was 0.9. At a cut-off >5, sensitivity was 96.4% (95%CI: 87.3-99.5) and the negative likelihood ratio was 0.09 (95%CI: 0.02-0.3). At a cut-off >10, specificity was 99.8% (95%CI: 98.6-100.0), and the positive likelihood ratio was 237.6 (95%CI: 33.1-1704). On multivariable analyses, atrial fibrillation, blood pressure, gender, dizziness (not vertigo) and no history of dizziness, vertigo or labyrinth/vestibular disease were found to be positively associated with stroke outcomes significantly. CONCLUSION: The TriAGe+ score is an efficient stroke prediction score for patients presenting to the ED with dizziness.

Autonomic Dysfunction Predicts Clinical Outcomes After Acute Ischemic Stroke: A Prospective Observational Study.

BACKGROUND AND PURPOSE: Central autonomic dysfunction increases stroke morbidity and mortality. We aimed to investigate whether poststroke autonomic dysfunction graded by Ewing battery can predict clinical outcome. METHODS: In this prospective observational study, we assessed autonomic function of ischemic stroke patients within 7 days from symptom onset by Ewing battery. On the basis of the magnitude of autonomic dysfunction, we stratified patients into significant (definite, severe, or atypical) or minor (normal or early) autonomic function impairment groups and correlated the impairment with the 3-month modified Rankin Scale score (good outcome: modified Rankin Scale score 0≈2; poor outcome: modified Rankin Scale score 3≈6). RESULTS: Among the 150 patients enrolled (mean age, 66.4±9.9 years; 70.7% males), minor autonomic dysfunction was identified in 36 patients (24.0%), and significant autonomic dysfunction was identified in 114 patients (76.0%) based on Ewing battery. In 3 months, a poor functional outcome was found in 32.5% of significant group patients compared with 13.9% in the minor group (P=0.031). Crude odds ratios of the magnitude of autonomic dysfunction and 3-month unfavorable functional outcome after acute ischemic stroke were 2.979 (95% confidence interval, 1.071-8.284; P=0.036). After adjusting for confounding variables with statistical significance between the 2 functional outcome subgroups identified in univariate analysis (including sex and National Institutes of Health Stroke Scale score on admission), the magnitude of autonomic dysfunction still independently predicted an unfavorable outcome, with an odds ratio of 3.263 (95% confidence interval, 1.141-9.335; P=0.027). CONCLUSIONS: Autonomic dysfunction gauged by Ewing battery predicts poor functional outcome after acute ischemic stroke.

Mapping the contribution and strategic distribution patterns of neuroimaging features of small vessel disease in poststroke cognitive impairment.

OBJECTIVES: Individual neuroimaging features of small vessel disease (SVD) have been reported to influence poststroke cognition. This study aimed to investigate the joint contribution and strategic distribution patterns of multiple types of SVD imaging features in poststroke cognitive impairment. METHODS: We studied 145 first-ever ischaemic stroke patients with MRI and Montreal Cognitive Assessment (MoCA) examined at baseline. The local burdens of acute ischaemic lesion (AIL), white matter hyperintensity, lacune, enlarged perivascular space and cross-sectional atrophy were quantified and entered into support vector regression (SVR) models to associate with the global and domain scores of MoCA. The SVR models were optimised with feature selection through 10-fold cross-validations. The contribution of SVD features to MoCA scores was measured by the prediction accuracy in the corresponding SVR model after optimisation. RESULTS: The combination of the neuroimaging features of SVD contributed much more to the MoCA deficits on top of AILs compared with individual SVD features, and the cognitive impact of different individual SVD features was generally similar. As identified by the optimal SVR models, the important SVD-affected regions were mainly located in the basal ganglia and white matter around it, although the specific regions varied for MoCA and its domains. CONCLUSIONS: Multiple types of SVD neuroimaging features jointly had a significant impact on global and domain cognitive functionings after stroke on top of AILs. The map of strategic cognitive-relevant regions of SVD features may help clinicians to understand their complementary impact on poststroke cognition.

Converting MMSE to MoCA and MoCA 5-minute protocol in an educationally heterogeneous sample with stroke or transient ischemic attack.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is psychometrically superior over the Mini-mental State Examination (MMSE) for cognitive screening in stroke or transient ischemic attack (TIA). It is free for clinical and research use. The objective of this study is to convert scores from the MMSE to MoCA and MoCA-5-minute protocol (MoCA-5 min) and to examine the ability of the converted scores in detecting cognitive impairment after stroke or TIA. METHODS: A total of 904 patients were randomly divided into training (n = 623) and validation (n = 281) samples matched for demography and cognition. MMSE scores were converted to MoCA and MoCA-5 min using (1) equipercentile method with log-linear smoothing and (2) Poisson regression adjusting for age and education. Receiver operating characteristics curve analysis was used to examine the ability of the converted scores in differentiating patients with cognitive impairment. RESULTS: The mean education was 5.8 (SD = 4.6; ranged 0-20) years. The entire spectrum of MMSE scores was converted to MoCA and MoCA-5 min using equipercentile method. Relationship between MMSE and MoCA scores was confounded by age and education, and a conversion equation with adjustment for age and education was derived. In the validation sample, the converted scores differentiated cognitively impaired patients with area under receiver operating characteristics curve 0.826 to 0.859. CONCLUSION: We provided 2 methods to convert scores from the MMSE to MoCA and MoCA-5 min based on a large sample of patients with stroke or TIA having a wide range of education and cognitive levels. The converted scores differentiated patients with cognitive impairment after stroke or TIA with high accuracy.

Impact of Side Branches on the Computation of Fractional Flow in Intracranial Arterial Stenosis Using the Computational Fluid Dynamics Method.

BACKGROUND: Computational fluid dynamics (CFD) allows noninvasive fractional flow (FF) computation in intracranial arterial stenosis. Removal of small artery branches is necessary in CFD simulation. The consequent effects on FF value needs to be judged. METHODS: An idealized vascular model was built with 70% focal luminal stenosis. A branch with one third or one half of the radius of the parent vessel was added at a distance of 5, 10, 15 and 20 mm to the lesion. With pressure and flow rate applied as inlet and outlet boundary conditions, CFD simulations were performed. Flow distribution at bifurcations followed Murray's law. By including or removing side branches, five patient-specific intracranial artery models were simulated. Transient simulation was performed on a patient-specific model, with a larger branch for validation. Branching effect was considered trivial if the FF difference between paired models (branches included or removed) was within 5%. RESULTS: Compared with the control model without a branch, in all idealized models the relative differences of FF was within 2%. In five pairs of cerebral arteries (branches included/removed), FFs were 0.876 and 0.877, 0.853 and 0.858, 0.874 and 0.869, 0.865 and 0.858, 0.952 and 0.948. The relative difference in each pair was less than 1%. In transient model, the relative difference of FF was 3.5%. CONCLUSION: The impact of removing side branches with radius less than 50% of the parent vessel on FF measurement accuracy is negligible in static CFD simulations, and minor in transient CFD simulation.

Sex Differences Do Not Exist in Outcomes among Stroke Patients with Intracranial Atherosclerosis in China: Subgroup Analysis from the Chinese Intracranial Atherosclerosis Study.

BACKGROUND: To date, sex difference in outcomes among patients with intracranial atherosclerosis (ICAS) has rarely been discussed in China as well as in the world. This study aimed to estimate the sex difference in outcomes among patients with ICAS in Chinese cerebral ischemia patients. METHODS: We analyzed 1,335 men and women with ICAS who were enrolled in the Chinese Intracranial Atherosclerosis study. They were followed-up for ischemic stroke recurrence, any cause of death, cerebral vascular events (including transient ischemic attack, ischemic and hemorrhagic stroke), combined end points (including cerebral vascular events, angina or myocardial infarction, pulmonary embolism, peripheral vascular events), and unfavorable outcome (modified Rankin scale score of 3-6) at 1 year. RESULTS: During the follow-up period, 59 (13.44%) combined end points were documented in women and 107 (11.94%) in men. Of the combined end points, 47 were recurrent ischemic stroke events (14 in women and 33 in men), and 51 other causes of deaths (24 in women and 27 in men). There were 349 unfavorable end points (117 in women and 232 in men). The cumulative probability of death was higher in women, but after adjusting for age, diabetes mellitus, hypertension, family history of stroke, current smoker, heavy drinking, hyperhomocysteinemia, and heart disease, there was no significant difference. There was also a lack of difference in 1-year ischemic stroke recurrence, cerebral vascular events, combined end points, and unfavorable outcome between women and men at 1 year. CONCLUSIONS: These results suggest no sex difference in outcome among patients with ICAS in Chinese cerebral ischemia patients.

Impact of collaterals on the efficacy and safety of endovascular treatment in acute ischaemic stroke: a systematic review and meta-analysis.

OBJECTIVE: We aimed to investigate the role of pretreatment collateral status in predicting the efficacy and safety of endovascular treatment (EVT) in acute ischaemic stroke due to cervical and/or cerebral arterial occlusions. METHODS: Relevant full-text articles published since 1 January 2000, investigating correlations between collateral status and any efficacy or safety outcome in patients undergoing EVT in cohort or case-control studies, or randomised clinical trials, were retrieved by PubMed and manual search. Two authors extracted data from eligible studies and assessed study quality. Risk ratios (RR) were pooled for good versus poor collaterals for outcomes based on a random-effects model. Sensitivity and subgroup analyses were conducted. RESULTS: In total, 35 (3542 participants) and 23 (2652 participants) studies were included in qualitative review and quantitative meta-analysis, respectively. Overall, good pretreatment collaterals increased the rate of favourable functional outcome at 3 months (RR=1.98, 95% CI 1.64 to 2.38; p<0.001), and reduced the risks of periprocedural symptomatic intracranial haemorrhage (RR=0.59, 95% CI 0.43 to 0.81; p=0.001) and 3-month mortality (RR=0.49, 95% CI 0.38 to 0.63; p<0.001), as compared with poor collaterals, in patients with acute ischaemic stroke under EVT. No individual study could alter the estimate of overall effect of collateral status, but there were moderate to significant heterogeneities between subgroups of studies with different modes of EVT, different arterial occlusions and different collateral grading methods. CONCLUSIONS: Good pretreatment collateral status is associated with higher rates of favourable functional outcome, and lower rates of symptomatic intracranial haemorrhage and mortality, in patients with acute ischaemic stroke receiving endovascular therapies.

Impact of Collateral Status on Successful Revascularization in Endovascular Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: Pre-treatment collateral status may be associated with the rates of successful revascularization in acute ischemic stroke patients receiving endovascular treatment (EVT). We conducted a systematic review and meta-analysis to synthesize relevant evidence currently available. METHODS: Relevant full-text articles published in English since January 1, 2000, reporting associations between collateral status and successful reperfusion and/or recanalization in acute ischemic stroke patients receiving EVT in cohort or case-control studies, or randomized clinical trials, were retrieved through search of PubMed. Study selection, data extraction and study quality assessment were carried out by 2 investigators. Risk ratios (RR) were pooled for good vs. poor collaterals for the outcomes of successful reperfusion and recanalization, based on random-effects models. Subgroup analyses were conducted to explore for potential factors that might interfere with the effects of pre-treatment collateral status on reperfusion by EVT. RESULTS: In total, 27 studies (2,366 subjects) were included in qualitative analysis, among which 24 studies (2,239 subjects) were quantitatively analyzed. Overall, good pre-treatment collaterals significantly increased the rate of both successful reperfusion (RR 1.28, 95% CI 1.17-1.40; p < 0.001) and recanalization (RR 1.23, 95% CI 1.06-1.42; p = 0.006), as compared with poor collaterals. Subgroup analyses revealed that the effects of collateral status on successful reperfusion by EVT might be different between populations with different ethnicities. CONCLUSIONS: Good pre-treatment collaterals may enhance the rates of successful reperfusion and recanalization in EVT for acute ischemic stroke. This may partly explain the favorable effects of good pre-treatment collaterals on clinical outcomes of stroke patients receiving EVT. Thus, it would be valuable to assess the collateral status prior to EVT in acute ischemic stroke. But studies are needed to further verify if the positive effects of good collaterals on revascularization by EVT are restricted to certain subgroups of patients.

Diminished Signal Intensities Distal to Intracranial Arterial Stenosis on Time-of-Flight MR Angiography Might Indicate Delayed Cerebral Perfusion.

BACKGROUND: Intracranial arterial stenosis (ICAS) is a predominant cause of ischemic stroke in Asia. Changes in the signal intensities (SIs) across ICAS lesions on time-of-flight magnetic resonance angiography (TOF-MRA) have been indicated to partially reflect the hemodynamic significance of the lesions, which we aimed to verify by correlating it with cerebral perfusion features provided by CT perfusion (CTP) imaging. METHODS: Ischemic stroke or transient ischemic attack patients with unilateral symptomatic stenosis (≥50%) of intracranial internal carotid artery or middle cerebral artery (MCA) were included in this study. Change of SIs across an ICAS lesion on TOF-MRA was calculated by the distal and proximal SI ratio (SIR). Cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) within the MCA territory of ipsilateral and contralateral hemispheres were evaluated on the CTP images at the basal ganglia level. Relative CBV, CBF and MTT were defined as ratios of the values obtained from ipsilateral and contralateral hemispheres. The relationships between SIR and CTP parameters were analyzed. RESULTS: Fifty subjects (74% male, mean age 62) were recruited. Overall, the mean SIR was 0.77 ± 0.17. SIR of ICAS was significantly, linearly and negatively correlated with ipsilateral CBV (r = -0.335, p = 0.017), ipsilateral MTT (r = -0.301, p = 0.034), and ipsilateral/contralateral MTT ratio (r = -0.443, p = 0.001). CONCLUSIONS: Diminished SIs distal to ICAS on TOF-MRA might be associated with delayed ipsilateral cerebral perfusion. Changes of the SIs across ICAS lesions on TOF-MRA may be a simple marker to reflect cerebral perfusion changes in patients with symptomatic ICAS.

Delayed-onset dementia after stroke or transient ischemic attack.

INTRODUCTION: Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. METHODS: Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. RESULTS: Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. DISCUSSION: Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group.

Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese Intracranial Atherosclerosis (CICAS) Study.

BACKGROUND AND PURPOSE: We aimed to establish the prevalence, characteristics, and outcomes of intracranial atherosclerosis (ICAS) in China by a large, prospective, multicenter study. METHODS: We evaluated 2864 consecutive patients who experienced an acute cerebral ischemia<7 days after symptom onset in 22 Chinese hospitals. All patients underwent magnetic resonance angiography, with measurement of diameter of the main intracranial arteries. ICAS was defined as ≥50% diameter reduction on magnetic resonance angiography. RESULTS: The prevalence of ICAS was 46.6% (1335 patients, including 261 patients with coexisting extracranial carotid stenosis). Patients with ICAS had more severe stroke at admission and stayed longer in hospitals compared with those without intracranial stenosis (median National Institutes of Health Stroke Scale score, 3 versus 5; median length of stay, 14 versus 16 days; both P<0.0001). After 12 months, recurrent stroke occurred in 3.27% of patients with no stenosis, in 3.82% for those with 50% to 69% stenosis, in 5.16% for those with 70% to 99% stenosis, and in 7.27% for those with total occlusion. Cox proportional hazards regression analyses showed that the degree of arterial stenosis, age, family history of stroke, history of cerebral ischemia or heart disease, complete circle of Willis, and National Institutes of Health Stroke Scale score at admission were independent predictors for recurrent stroke at 1 year. The highest rate of recurrence was observed in patients with occlusion with the presence of ≥3 additional risk factors. CONCLUSIONS: ICAS is the most common vascular lesion in patients with cerebrovascular disease in China. Recurrent stroke rate in our study was lower compared with those of previous clinical trials but remains unacceptably high in a subgroup of patients with severe stenosis.

Chronic post-COVID neuropsychiatric symptoms persisting beyond one year from infection: a case-control study and network analysis.

Our study aims to delineate the phenotypes of chronic neuropsychiatric symptoms among adult subjects recovering from their first COVID that occurred more than one year ago. We also aim to explore the clinical and socioeconomic risk factors of having a high loading of chronic neuropsychiatric symptoms. We recruited a post-COVID group who suffered from their first pre-Omicron COVID more than a year ago, and a control group who had never had COVID. The subjects completed app-based questionnaires on demographic, socioeconomic and health status, a COVID symptoms checklist, mental and sleep health measures, and neurocognitive tests. The post-COVID group has a statistically significantly higher level of fatigue compared to the control group (p < 0.001). Among the post-COVID group, the lack of any COVID vaccination before the first COVID and a higher level of material deprivation before the COVID pandemic predicts a higher load of chronic post-COVID neuropsychiatric symptoms. Partial correlation network analysis suggests that the chronic post-COVID neuropsychiatric symptoms can be clustered into two major (cognitive complaints -fatigue and anxiety-depression) and one minor (headache-dizziness) cluster. A higher level of material deprivation predicts a higher number of symptoms in both major clusters, but the lack of any COVID vaccination before the first COVID only predicts a higher number of symptoms in the cognitive complaints-fatigue cluster. Our result suggests heterogeneity among chronic post-COVID neuropsychiatric symptoms, which are associated with the complex interplay of biological and socioeconomic factors.

Prognostic value of inflammatory mediators in 1-year outcome of acute ischemic stroke with middle cerebral artery stenosis.

BACKGROUND AND PURPOSE: Inflammation exists in inception, progression, and reperfusion of acute ischemic stroke. Insightful understanding of correlation in inflammatory mediators and stroke severity with intracranial artery stenosis may improve rational stroke therapy. METHODS: We prospectively recruited 977 patients with acute noncardioembolic ischemic stroke with MCA stenosis by MRA as none to mild (<50%), moderate (50-69%), severe (70-99%), or occlusive (100%). The peripheral levels of WBC, homocysteine (HCY), and high sensitivity C-reactive protein (hs-CRP) were recorded. All patients were assessed of 1-year outcome by mRS as favorable (0-2) or poor (3-6). RESULTS: The levels of WBC, HCY, and hs-CRP had no significant differences in patients with categorized MCA stenosis (all P > 0.05). Higher levels of WBC, HCY, and hs-CRP were found in patients with 1-year poor outcome (all P < 0.05), but only hs-CRP is an independent predictor (OR 1.06, 95% CI 1.027-1.093, P = 0.0003). The combination of any two of increased hs-CRP (>3 mg/L), WBC (>6.91 × 10(9)/L), and HCY (>15 µ mol/L) had higher power in predicting 1-year poor outcome than the single elevated mediator. CONCLUSIONS: Elevated hs-CRP independently predicts 1-year poor outcome in acute stroke. The combination of increased hs-CRP, WBC, or HCY had a stronger predictive value in poor outcome than individual elevated mediator.

Intra-arterial revascularisation therapy for acute ischaemic stroke: initial experience in a Hong Kong hospital.

OBJECTIVES: To assess the outcome of acute ischaemic stroke patients who received intra-arterial therapy in our unit. DESIGN: Case series. SETTING: A tertiary hospital in Hong Kong. PATIENTS: Patients with ischaemic stroke due to large artery occlusion treated within 6 hours from symptom onset between January 2007 and May 2011. INTERVENTION: Acute intra-arterial revascularisation therapy. MAIN OUTCOME MEASURES: Primary outcome was functional independence (modified Rankin Scale score of ≤ 2) at 3 months. Secondary outcome was rate of recanalisation. Safety outcomes were symptomatic intracranial haemorrhage and 3-month mortality. RESULTS: Twenty-one patients with a mean age of 67 years fulfilled the inclusion criteria. Their mean National Institutes of Health Stroke Scale score was 18. The mean onset-to-puncture time was 212 minutes. Nine received intra-arterial tissue plasminogen activator alone, 11 had an adjunctive mechanical thrombectomy, and one received balloon angioplasty without tissue plasminogen activator. At the end of the procedure, thrombolysis grade 2a or better was attained in 18 (86%) of the patients, and 8 (38%) achieved functional independence at 3 months. Rates of symptomatic intracranial haemorrhage and 3-month mortality were 10% and 24%, respectively. CONCLUSION: In this setting, intra-arterial revascularisation therapy appeared safe and efficacious for this selected group of ischaemic stroke patients with large artery occlusions. Experience gained from this pilot study may help improve clinical outcomes of such patients.

Is stroke thrombolysis safe and efficacious in Hong Kong?

OBJECTIVE: To investigate the safety and efficacy of stroke thrombolysis in a local hospital. DESIGN: Historical cohort study. SETTING: A tertiary hospital in Hong Kong. PATIENTS: The outcome of acute ischaemic stroke patients treated with intravenous tissue plasminogen activator between October 2008 and May 2011 was compared to those admitted during the same period who were thrombolysis-eligible, but treated conservatively due to unavailability of the thrombolysis service after-hours. INTERVENTIONS: Intravenous tissue plasminogen activator. MAIN OUTCOME MEASURES: Primary outcome was functional independence (modified Rankin Scale score of 2 or below) at 3 months. Safety outcomes were symptomatic intracranial haemorrhage and 3-month mortality. Secondary outcomes were hospital length of stay, direct home discharge, and nursing home discharge. RESULTS: A total of 48 thrombolysis and 63 non-thrombolysis patients were identified. Fifty-two percent of the thrombolysis group achieved functional independence compared to 24% of non-thrombolysis group (P=0.003), without significant increase in mortality (15% vs 13%, P=0.51) or symptomatic intracranial haemorrhage (4% vs 2%, P=0.58). Twenty-nine percent of the thrombolysis group patients were discharged home directly, versus 6% of non-thrombolysis group (P<0.001). Mean length of stay was shorter for the thrombolysis group (25 vs 35 days; P=0.034). A similar percentage from each group was discharged to nursing homes. CONCLUSION: Implementation of the stroke thrombolysis service in Hong Kong appeared safe and efficacious. Patients who received thrombolysis had better outcomes compared to non-thrombolysis cohort. Further studies are needed to investigate the economics of stroke thrombolysis in Hong Kong, which may help to improve funding for provision of this service.

Faecal microbiome-based machine learning for multi-class disease diagnosis.

Systemic characterisation of the human faecal microbiome provides the opportunity to develop non-invasive approaches in the diagnosis of a major human disease. However, shared microbial signatures across different diseases make accurate diagnosis challenging in single-disease models. Herein, we present a machine-learning multi-class model using faecal metagenomic dataset of 2,320 individuals with nine well-characterised phenotypes, including colorectal cancer, colorectal adenomas, Crohn's disease, ulcerative colitis, irritable bowel syndrome, obesity, cardiovascular disease, post-acute COVID-19 syndrome and healthy individuals. Our processed data covers 325 microbial species derived from 14.3 terabytes of sequence. The trained model achieves an area under the receiver operating characteristic curve (AUROC) of 0.90 to 0.99 (Interquartile range, IQR, 0.91-0.94) in predicting different diseases in the independent test set, with a sensitivity of 0.81 to 0.95 (IQR, 0.87-0.93) at a specificity of 0.76 to 0.98 (IQR 0.83-0.95). Metagenomic analysis from public datasets of 1,597 samples across different populations observes comparable predictions with AUROC of 0.69 to 0.91 (IQR 0.79-0.87). Correlation of the top 50 microbial species with disease phenotypes identifies 363 significant associations (FDR < 0.05). This microbiome-based multi-disease model has potential clinical application in disease diagnostics and treatment response monitoring and warrants further exploration.

Ethnic influences on neurovascular coupling: a pilot study in whites and Asians.

BACKGROUND AND PURPOSE: An ethnic extraintracranial difference in atherosclerosis has been well reported, whereas the potential mechanism remains unclear. We aimed to investigate neurovascular coupling in healthy whites and Asians. METHODS: Twenty volunteers of each ethnicity were recruited to perform a functional transcranial Doppler examination with standardized checkerboard patterns as visual stimulation (3 x 4, 6 x 8, and 12 x 16 checks subtending a visual field section of 18 degrees x 24 degrees , flicker rate 1 Hz). Hemodynamic responses in both posterior cerebral arteries were evaluated with a control system approach. RESULTS: The rate time, that is, the initial speed of flow velocity adaptation, was significantly lower in Asians leading to an approximately 2-second delayed hemodynamic adaptation. The other hemodynamic parameters and the dependency of hemodynamic responses in regard to the complexity degree of the stimulus were similar between groups. CONCLUSIONS: The constellation suggests a greater initial mismatch between functionally increased metabolic demand of neurons and adjusted cerebral blood flow in Asians.

Intracranial Atherosclerosis Coexisting With White Matter Hyperintensities May Predict Unfavorable Functional Outcome in Patients With Acute Cerebral Ischemia.

Background and Purpose: This study aimed to assess the effect of baseline white matter hyperintensities (WMH) on 1-year stroke recurrence and the functional outcome for patients with intracranial atherosclerosis (ICAS). Methods: We analyzed 2,076 patients who were enrolled in the Chinese IntraCranial AtheroSclerosis (CICAS) study. ICAS and WMH were diagnosed by baseline magnetic resonance angiography. The primary outcomes were stroke recurrence and unfavorable functional outcome (modified Rankin Scale score 3-6) at 1 year. Results: Of the 2,076 patients included in this study, 1,370 (65.99%) were men, and the mean age was 61.70 years. In total, 224 (10.79%) patients had no WMH and no ICAS, 922 (44.41%) patients had WMH and no ICAS, 157 (7.56%) patients had ICAS and no WMH, and 773 (37.24%) had both WMH and ICAS. During the follow-up period, 87 patients had a recurrent stroke and 333 had unfavorable outcomes at 1 year. Compared to WMH (-) ICAS (-) group, the adjusted odd ratios and 95% confidence interval for unfavorable functional outcome were 0.791 (0.470-1.332; p = 0.3779) in the WMH (+) ICAS (-) group, 1.920 (1.024-3.600; p = 0.0421) in the WMH (-) ICAS (+) group, and 2.046 (1.230-3.403; p = 0.0058) in the WMH (+) ICAS (+) group. There was no significant difference in stroke recurrence risk among the four groups. Conclusion: ICAS coexisting with WMH may predict an unfavorable functional outcome at 1 year, but not stroke recurrence.

Herb-drug interaction of gastrodiae rhizoma on carbamazepine: A pharmacokinetic study in rats.

OBJECTIVE: Gastrodiae Rhizoma (GR), is a traditional Chinese Medicine that has been used for neurological disorders, including epilepsy. Epilepsy patients may be treated with adjunctive therapy of GR with antiepileptic drugs (AEDs). In particular, carbamazepine (CBZ) is of high potential to interact with concurrent treatment of Chinese Medicine. This study was to investigate the herb-drug interactions of GR and CBZ, an AED, through pharmacokinetic approach in rats. METHODS: We adopted a high-performance liquid chromatography (HPLC) system to quantify the plasma level of CBZ and its metabolite (carbamazepine-10, 11-epoxide, CBZE). The method was validated as per instructions under United States Food and Drug Administration (USFDA) guidance. For the herb-drug interaction study, rats were randomly divided into four different treatment groups: single-dose CBZ treatment, single-dose CBZ/GR treatment, 2-week course of CBZ treatment and 2-week course of CBZ/GR treatment. RESULTS: Our results demonstrated the auto-induction of CBZ metabolization when comparing single-dose with 2-week course of CBZ treatment. Pharmacokinetic interactions were noted in concomitant use of GR with CBZ by comparing two single-dose treatments (CBZ versus CBZ/GR). Our data showed that GR increased the mean residence time (MRT0-t) and the time taken to reach the maximum concentration (Tmax) of CBZ in single-dose of CBZ/GR treatment. The maximum drug concentration (Cmax) of CBZ was reduced in single-dose CBZ/GR treatment. When comparing the 2-week course of CBZ treatment with the 2-week course of CBZ/GR treatment, the MRT0-t and half-life of CBZ were increased. The AUC0-t, the Cmax and the half-life of CBZE were increased. CONCLUSION: CBZ/GR treatment may reduce the auto-induction of CBZ over 2 weeks. While the reduction of auto-induction could enhance the therapeutic effects of CBZ, it could also lead to an increase in neurological side effects and non-neurological adverse effects. Our results provided preclinical evidence of herb-drug interaction, which may have implications for epilepsy patients treated with GR.

Hemodynamic Significance of Middle Cerebral Artery Stenosis Associated With the Severity of Ipsilateral White Matter Changes.

Background: Previous studies conflicted in the association between intracranial atherosclerotic stenosis (ICAS) and the severity of white matter changes (WMC). Aims: We aimed to investigate the relationships between the severity of luminal stenosis and the hemodynamic significance of middle cerebral artery (MCA) stenosis, and the severity of ipsilateral WMC. Methods: In this cross-sectional study, patients with a recent ischemic stroke or transient ischemic attack and a 50-99% MCA-M1 stenosis in the Chinese Intracranial Atherosclerosis study cohort were analyzed. The post- to pre-stenotic signal intensity ratio (SIR) was obtained in time-of-flight MR angiography (MRA) to represent the hemodynamic significance of MCA-M1 stenosis, with a lower SIR indicating a hemodynamically more severe lesion. The severity of ipsilesional WMC was assessed by an age-related WMC (ARWMC) scale in T2-weighted fluid attenuated inversion recovery MR imaging. The relationships between the degree of MCA-M1 stenosis, SIR, and ipsilesional ARWMC scale were analyzed. The MCA-M1 lesion with a higher percentage of stenosis was chosen for analyses in patients with bilateral MCA-M1 stenoses. Results: Among 180 subjects (mean age, 64 years), a lower SIR of MCA-M1 stenosis (Spearman correlation coefficient, -0.543; p < 0.001), but not the degree of stenosis (p = 0.93), was significantly linearly correlated with a higher ipsilateral ARWMC. Multivariate ordinal logistic regression identified older age (OR = 1.037; 95% CI, 1.008-1.066; p = 0.011) and lower SIR (OR = 0.010; 95% CI, 0.002-0.058; p < 0.001) as independent predictors for more severe ipsilateral WMC. Conclusion: Patients with hemodynamically more severe ICAS are more likely to have more severe ipsilateral WMC. Longitudinal studies with sequential imaging exams may further reveal the impact of hemodynamic significance of ICAS on the development and progression of WMC.