A systematic review of randomized controlled trials of endovascular therapy for stroke on mortality and disability.

BACKGROUND: Endovascular treatment (EVT) has become standard of care for patients with anterior circulation large vessel occlusion (LVO) stroke, with indications having recently expanded to late time-window and large ischemic core patients. There is conflicting evidence on whether EVT reduces mortality or only disability. We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effect of EVT on mortality and severe disability. METHODS: We systematically searched PubMed, Web of Science, Scopus, and Embase on November 15, 2023, to identify phase 3 RCTs comparing EVT to best medical treatment (BMT) in patients with anterior circulation LVO stroke in a common effects meta-analysis. The primary outcome was mortality at 3 months. Secondary outcomes were moderately severe or severe disability (modified Rankin Scale (mRS) score 4-5) at 3 months. RESULTS: 18 studies comparing EVT to BMT were included, with a total of 4309 patients; 2159 that were treated with EVT, and 2150 treated with BMT. Mortality was significantly lower in the EVT group than in the BMT group (odds ratio (OR): 0.81, 95% CI: 0.70-0.94). Proportions of moderately severe or severe disability (OR: 0.55, 95% CI: 0.48-0.62) were also significantly lower in patients treated with EVT. CONCLUSIONS: This meta-analysis suggests that EVT reduces both mortality and moderately severe or severe disability in patients with anterior circulation LVO stroke.

Deep learning on pre-procedural computed tomography and clinical data predicts outcome following stroke thrombectomy.

BACKGROUND: Deep learning using clinical and imaging data may improve pre-treatment prognostication in ischemic stroke patients undergoing endovascular thrombectomy (EVT). METHODS: Deep learning models were trained and tested on baseline clinical and imaging (CT head and CT angiography) data to predict 3-month functional outcomes in stroke patients who underwent EVT. Classical machine learning models (logistic regression and random forest classifiers) were constructed to compare their performance with the deep learning models. An external validation dataset was used to validate the models. The MR PREDICTS prognostic tool was tested on the external validation set, and its performance was compared with the deep learning and classical machine learning models. RESULTS: A total of 975 patients (550 men; mean±SD age 67.5±15.1 years) were studied with 778 patients in the model development cohort and 197 in the external validation cohort. The deep learning model trained on baseline CT and clinical data, and the logistic regression model (clinical data alone) demonstrated the strongest discriminative abilities for 3-month functional outcome and were comparable (AUC 0.811 vs 0.817, Q=0.82). Both models exhibited superior prognostic performance than the other deep learning (CT head alone, CT head, and CT angiography) and MR PREDICTS models (all Q<0.05). CONCLUSIONS: The discriminative performance of deep learning for predicting functional independence was comparable to logistic regression. Future studies should focus on whether incorporating procedural and post-procedural data significantly improves model performance.

Ophthalmic artery stenosis on three-dimensional rotational angiography: Interrater agreement, prevalence, and risk factors.

BACKGROUND: There is emerging interest in ophthalmic artery (OA) stenosis angioplasty for the treatment of age-related macular degeneration. Three-dimensional rotational angiography (3DRA) could be used during conventional angiography to determine the presence and severity of OA stenosis. In patients who had undergone 3DRA of the internal carotid artery, we aimed to assess the interrater agreement, prevalence, and risk factors for OA stenosis. METHODS: Consecutive patients from two centers who had undergone conventional angiography with 3DRA of the internal carotid arteries were enrolled in this study. 3DRAs were independently double read for the presence of OA stenosis, as defined as narrowing of the proximal OA of at least 50% when compared to the more distal "normal" OA. Interrater agreement for the evaluation of OA stenosis was assessed with the Cohen's kappa coefficient. Univariate and multivariable logistic regression were used to identify potential predictors of OA stenosis. RESULTS: Three hundred and two patients (97 men; mean ± SD 57.6 ± 13.4 years) were included in the analysis. Cohen's kappa coefficient (95% CI) was 0.877 (0.798-0.956). OA stenosis was present in 45 patients (14.9%). Multiple logistic regression demonstrated that female sex (odds ratio [OR] = 2.70, 95% confidence interval [CI] 1.18-6.09, p = 0.02) and smoking (OR = 2.11, 95% CI 1.10-4.06, p = 0.03) were significant risk factors for OA stenosis. Age, hypertension, diabetes, coronary artery disease, and subarachnoid hemorrhage were not associated with OA stenosis. CONCLUSION: The evaluation of OA stenosis on 3DRA had excellent interrater agreement. OA stenosis was common and was associated with smoking and female sex.

Penumbral cooling in ischemic stroke with intraarterial, intravenous or active conductive head cooling: A thermal modeling study.

In ischemic stroke, selectively cooling the ischemic penumbra might lead to neuroprotection while avoiding systemic complications. Because penumbral tissue has reduced cerebral blood flow and in vivo brain temperature measurement remains challenging, the effect of different methods of therapeutic hypothermia on penumbral temperature are unknown. We used the COMSOL Multiphysics® software to model a range of cases of therapeutic hypothermia in ischemic stroke. Four ischemic stroke models were developed with ischemic core and/or penumbra volumes between 33-300 mL. Four experiments were performed on each model, including no cooling, and intraarterial, intravenous, and active conductive head cooling. The steady-state temperature of the non-ischemic brain, ischemic penumbra, and ischemic core without cooling was 37.3 °C, 37.5-37.8 °C, and 38.9-39.4 °C respectively. Intraarterial, intravenous and active conductive head cooling reduced non-ischemic brain temperature by 4.3 °C, 2.1 °C, and 0.7-0.8 °C respectively. Intraarterial, intravenous and head cooling reduced the temperature of the ischemic penumbra by 3.9-4.3 °C, 1.9-2.1 °C, and 1.2-3.4 °C respectively. Active conductive head cooling was the only method to selectively reduce penumbral temperature. Clinical studies that measure brain temperature in ischemic stroke patients undergoing therapeutic hypothermia are required to validate these hypothesis-generating findings.

Non-invasive Brain Temperature Measurement in Acute Ischemic Stroke.

Selective therapeutic hypothermia in the setting of mechanical thrombectomy (MT) is promising to further improve the outcomes of large vessel occlusion stroke. A significant limitation in applying hypothermia in this setting is the lack of real-time non-invasive brain temperature monitoring mechanism. Non-invasive brain temperature monitoring would provide important information regarding the brain temperature changes during cooling, and the factors that might influence any fluctuations. This review aims to provide appraisal of brain temperature changes during stroke, and the currently available non-invasive modalities of brain temperature measurement that have been developed and tested over the past 20 years. We cover modalities including magnetic resonance spectroscopy imaging (MRSI), radiometric thermometry, and microwave radiometry, and the evidence for their accuracy from human and animal studies. We also evaluate the feasibility of using these modalities in the acute stroke setting and potential ways for incorporating brain temperature monitoring in the stroke workflow.

Active conductive head cooling of normal and infarcted brain: A magnetic resonance spectroscopy imaging study.

Active conductive head cooling is a simple and non-invasive intervention that may slow infarct growth in ischemic stroke. We investigated the effect of active conductive head cooling on brain temperature using whole brain echo-planar spectroscopic imaging. A cooling cap (WElkins Temperature Regulation System, 2nd Gen) was used to administer cooling for 80 minutes to healthy volunteers and chronic stroke patients. Whole brain echo-planar spectroscopic imaging scans were obtained before and after cooling. Brain temperature was estimated using the Metabolite Imaging and Data Analysis System software package, which allows voxel-level temperature calculations using the chemical shift difference between metabolite (N-acetylaspartate, creatine, choline) and water resonances. Eleven participants (six healthy volunteers, five post-stroke) underwent 80 ± 5 minutes of cooling. The average temperature of the coolant was 1.3 ± 0.5°C below zero. Significant reductions in brain temperature (ΔT = -0.9 ± 0.7°C, P = 0.002), and to a lesser extent, rectal temperature (ΔT = -0.3 ± 0.1°C, P = 0.03) were observed. Exploratory analysis showed that the occipital lobes had the greatest reduction in temperature (ΔT = -1.5 ± 1.2°C, P = 0.002). Regions of infarction had similar temperature reductions to the contralateral normal brain. Future research could investigate the feasibility of head cooling as a potential neuroprotective strategy in patients being considered for acute stroke therapies.

Autoinflammatory syndromes in neurology: when our first line of defence misbehaves.

Autoinflammatory syndromes result from a defective innate immune system. They are characterised by unexplained fever and systemic inflammation involving the skin, muscle, joints, serosa and eyes, along with elevated acute phase reactants. Autoinflammatory syndromes are increasingly recognised as a cause of neurological disease with a diverse range of manifestations. Corticosteroids, colchicine and targeted therapies are effective if started early, and hence the importance of recognising these syndromes. Here, we review the neurological features of specific autoinflammatory syndromes and our approach (as adult neurologists) to their diagnosis.

Protocol for the MAnagement of Systolic blood pressure during Thrombectomy by Endovascular Route for acute ischemic STROKE randomized clinical trial: The MASTERSTROKE trial.

REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619001274167p. RATIONALE: Cerebral blood flow is blood pressure-dependent when cerebral autoregulation is impaired. Cerebral ischemia and anesthetic drugs impair cerebral autoregulation. In ischemic stroke patients treated with endovascular thrombectomy, induced hypertension is a plausible intervention to increase blood flow in the ischemic penumbra until reperfusion is achieved. This could potentially reduce final infarct size and improve functional recovery. AIM: To test if patients with large vessel occlusion stroke treated with endovascular thrombectomy will benefit from induced hypertension. DESIGN: Prospective, randomized, parallel group, open label, multicenter clinical trial with blinded assessment of outcomes. PROCEDURES: Patients with anterior circulation stroke treated with endovascular thrombectomy with general anesthesia within 6 h of symptom onset, and patients with 'wake up' stroke or presenting within 6 to 24 h with potentially salvageable tissue on computed tomography perfusion scanning, are included. Participants are randomized to a systolic blood pressure target of 140 mmHg or 170 mmHg from procedure initiation until recanalization. Methods to maintain the blood pressure are at the discretion of the procedural anesthesiologist. STUDY OUTCOMES: The primary efficacy outcome is improvement in disability measured by modified Rankin Scale score at 90 days. The primary safety outcome is all-cause mortality at 90 days. ANALYSIS: The Mann-Whitney U test will be used to test the ordinal shift in the seven-category modified Rankin Scale score. All-cause mortality will be estimated using the Kaplan-Meier method and compared using a log-rank test.

Adjunctive Intraarterial Thrombolysis in Endovascular Thrombectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the safety and efficacy of intra-arterial thrombolysis (IAT) as an adjunct to endovascular thrombectomy (EVT) in ischemic stroke, we performed a systematic review and meta-analysis of the literature. METHODS: Searches were performed using Medline, Embase, and Cochrane databases for studies that compared EVT to EVT with adjunctive IAT (EVT+IAT). Safety outcomes included symptomatic intracerebral hemorrhage (sICH) and mortality at three months. Efficacy outcomes included successful reperfusion (Thrombolysis in Cerebral Infarction score of 2b to 3), and functional independence, defined as a modified Rankin Scale score of 0 to 2 at three months. RESULTS: Five studies were identified that compared combined EVT+IAT (IA alteplase or urokinase) to EVT-only, and were included in the random effects meta-analysis. There were 1693 EVT patients, including 269 patients treated with combined EVT+IAT and 1424 patients receiving EVT-only. Pooled analysis did not demonstrate any differences between EVT+IAT and EVT-only in rates of sICH (OR: 0.61, 95% CI: 0.20-1.85; P=0.78), mortality (OR: 0.77, 95% CI: 0.54-1.10; P=0.15), or successful reperfusion (OR: 1.05, 95% CI: 0.52-2.15; P=0.89). There was a higher rate of functional independence in patients treated with EVT+IAT, although this was not statistically significant (OR: 1.34, 95% CI: 1.00-1.80; P=0.053). CONCLUSIONS: Adjunctive IAT appears to be safe. In specific situations, neurointerventionists may be justified in administering small doses of intraarterial alteplase or urokinase as rescue therapy during EVT.

Routine Use of Tenecteplase for Thrombolysis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand changed to routine off-label intravenous tenecteplase due to improved early recanalization in large vessel occlusion, inconsistent access to thrombectomy within stroke networks, and for consistency in treatment protocols between patients with and without large vessel occlusion. We report the feasibility and safety outcomes in tenecteplase-treated patients. METHODS: We performed a retrospective analysis of consecutive patients thrombolyzed with intravenous tenecteplase at 1 comprehensive and 2 regional stroke centers from July 14, 2018, to February 29, 2020. We report the baseline clinical characteristics, rates of symptomatic intracranial hemorrhage, and angioedema. These were then compared with patient outcomes with those treated with intravenous alteplase at 2 other comprehensive stroke centers. Multivariable mixed-effects logistic regression models were performed assessing the association of tenecteplase with symptomatic intracranial hemorrhage and independent outcome (modified Rankin Scale score, 0-2) at day 90. RESULTS: There were 165 patients treated with tenecteplase and 254 with alteplase. Age (75 versus 74 years), sex (56% versus 60% male), National Institutes of Health Stroke Scale scores (8 versus 10), median door-to-needle times (47 versus 48 minutes), or onset-to-needle time (129 versus 130 minutes) were similar between the groups. Symptomatic intracranial hemorrhage occurred in 3 (1.8% [95% CI, 0.4-5.3]) tenecteplase patients compared with 7 (2.7% [95% CI, 1.1-5.7]) alteplase patients (P=0.75). There were no differences between tenecteplase and alteplase in the rates of angioedema (4 [2.4%; 95% CI, 0.7-6.2] versus 1 [0.4%; 95% CI, 0.01-2.2], P=0.08) or 90-day functional independence (100 [61%] versus 140 [57%], P=0.47), respectively. In mixed-effects logistic regression models, there was no significant association between thrombolytic choice and symptomatic intracranial hemorrhage (odds ratio tenecteplase, 0.62 [95% CI, 0.14-2.80], P=0.53) or functional independence (odds ratio tenecteplase, 1.20 [95% CI, 0.74-1.95], P=0.46). CONCLUSIONS: Routine use of tenecteplase for stroke thrombolysis was feasible and had comparable safety profile and outcome to alteplase.

Intravenous Propofol Versus Volatile Anesthetics For Stroke Endovascular Thrombectomy.

BACKGROUND: The choice of anesthetic technique for ischemic stroke patients undergoing endovascular thrombectomy is controversial. Intravenous propofol and volatile inhalational general anesthetic agents have differing effects on cerebral hemodynamics, which may affect ischemic brain tissue and clinical outcome. We compared outcomes in patients undergoing endovascular thrombectomy with general anesthesia who were treated with propofol or volatile agents. METHODS: Consecutive endovascular thrombectomy patients treated using general anesthesia were identified from our prospective database. Baseline patient characteristics, anesthetic agent, and clinical outcomes were recorded. Functional independence at 3 months was defined as a modified Rankin Scale of 0 to 2. RESULTS: There were 313 patients (182 [58.1%] men; mean±SD age, 64.7±15.9 y; 257 [82%] anterior circulation), of whom 254 (81%) received volatile inhalational (desflurane or sevoflurane), and 59 (19%) received intravenous propofol general anesthesia. Patients with propofol anesthesia had more ischemic heart disease, higher baseline National Institutes of Health Stroke Scale scores, more basilar artery occlusion, and were less likely to be treated with intravenous thrombolysis. Multivariable logistic regression analysis showed that propofol anesthesia was associated with improved functional independence at 3 months (odds ratio=2.65; 95% confidence interval, 1.14-6.22; P=0.03) and a nonsignificant trend toward reduced 3-month mortality (odds ratio=0.37; 95% CI, 0.12-1.10; P=0.07). CONCLUSION: In stroke patients undergoing endovascular thrombectomy treated using general anesthesia, there may be a differential effect between intravenous propofol and volatile inhalational agents. These results should be considered hypothesis-generating and be tested in future randomized controlled trials.

General Anesthesia Versus Conscious Sedation in Endovascular Thrombectomy for Stroke: A Meta-analysis of 4 Randomized Controlled Trials.

BACKGROUND: In ischemic stroke patients, studies have suggested that clinical outcomes following endovascular thrombectomy are worse after general anesthesia (GA) compared with conscious sedation (CS). Most data are from observational trials, which are prone to measure and unmeasure confounding. We performed a systematic review and meta-analysis of thrombectomy trials where patients were randomized to GA or CS, and compared efficacy and safety outcomes. METHODS: The Medline, Embase, and Cochrane databases were searched for randomized controlled trials comparing GA to CS in endovascular thrombectomy. Efficacy outcomes included successful recanalization (Thrombolysis in Cerebral Infarction score of 2b to 3), and good functional outcome, defined as a modified Rankin Scale score of 0 to 2 at 3 months. Safety outcomes included intracerebral hemorrhage and 3-month mortality. RESULTS: Four studies were identified and included in the random effects meta-analysis. Patients treated with GA achieved a higher proportion of successful recanalization (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.26-3.62; P=0.005) and good functional outcome (OR: 1.71, 95% CI: 1.13-2.59; P=0.01). For every 7.9 patients receiving GA, one more achieved good functional outcome compared with those receiving CS. There were no significant differences in intracerebral hemorrhage (OR: 0.61, 95% CI: 0.20-1.85; P=0.38) or 3-month mortality (OR: 0.62, 95% CI: 0.33-1.17; P=0.14) between GA and CS patients. CONCLUSIONS: In centers with high quality, specialized neuroanesthesia care, GA treated thrombectomy patients had superior recanalization rates and better functional outcome at 3 months than patients receiving CS.

Systemic risk factors of dry eye disease subtypes: A New Zealand cross-sectional study.

PURPOSE: To evaluate systemic risk factors of dry eye disease, aqueous tear deficiency, and meibomian gland dysfunction. METHODS: Three hundred and seventy-two community residents (222 females, 150 males; mean ± SD age, 39 ± 22 years) were recruited in a cross-sectional study. Past medical history, dry eye symptomology, ocular surface characteristics, and tear film quality were evaluated for each participant within a single clinical session. The diagnosis of dry eye disease, aqueous tear deficiency, and meibomian gland dysfunction were based on the global consensus recommendations of the Tear Film and Ocular Surface Society's Dry Eye Workshop II (TFOS DEWS II) and International Workshop on Meibomian Gland Dysfunction. RESULTS: Overall, 109 (29%) participants fulfilled the TFOS DEWS II criteria for dry eye disease, 42 (11%) had aqueous tear deficiency, and 95 (26%) had meibomian gland dysfunction. Multivariate logistic regression analysis demonstrated that systemic rheumatologic disease and antidepressant medication were independently associated with aqueous tear deficiency (both p < 0.05). Significant risk factors for meibomian gland dysfunction included age, East Asian ethnicity, migraine headaches, thyroid disease, and oral contraceptive therapy (all p ≤ 0.01). CONCLUSIONS: Both etiological subtypes of dry eye disease were associated with a number of systemic risk factors. These findings would support routine systemic inquiry of dry eye disease and associated systemic conditions and medications, in order to facilitate opportunistic screening and timely inter-disciplinary referral where necessary.

Impact of Body Temperature Before and After Endovascular Thrombectomy for Large Vessel Occlusion Stroke.

Background and Purpose- In ischemic stroke, body temperature is associated with functional outcome. However, the relationship between temperature and outcome may differ in the intraischemic and postischemic phases of stroke. We aimed to determine whether body temperature before or after endovascular thrombectomy (EVT) for large vessel occlusion stroke is associated with clinical outcomes. Methods- Consecutive EVT patients were identified from a prospective registry. Temperature measurements within 24 hours of admission were stratified into pre-EVT (preprocedural and intraprocedural) and post-EVT measurements, which served as surrogates for the intraischemic and postischemic phases of large vessel occlusion stroke, respectively. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0, 1, or 2 at 3 months. Secondary outcomes included the ordinal shift of modified Rankin Scale scores at 3 months, symptomatic intracerebral hemorrhage, and mortality at 3 months. Results- Four hundred thirty-two participants were included (59% men, mean±SD age 65.6±15.7 years). Multivariable logistic regression demonstrated that higher median pre-EVT temperature (per 1°C increase) was an independent predictor of reduced functional independence (odds ratio [OR], 0.66 [95% CI, 0.46-0.94]; P=0.02), poorer modified Rankin Scale scores (common OR, 1.42 [95% CI, 1.08-1.85]; P=0.01), and increased mortality (OR, 1.65 [95% CI, 1.02-2.69]; P=0.04). Peak post-EVT temperature (per 1°C increase) was a significant predictor of elevated modified Rankin Scale scores (common OR, 1.39 [95% CI, 1.03-1.90]; P=0.03) and higher mortality (OR, 1.66 [95% CI, 1.04-2.67]; P=0.03). Conclusions- In patients with large vessel occlusion stroke treated with EVT, higher body temperatures during both the intraischemic and postischemic phases were associated with poorer clinical outcomes. Future research investigating the maintenance of normothermia or therapeutic hypothermia in patients needing to be transferred from primary to EVT-capable stroke centers could be considered.

Physician understanding, explainability, and trust in a hypothetical machine learning risk calculator.

OBJECTIVE: Implementation of machine learning (ML) may be limited by patients' right to "meaningful information about the logic involved" when ML influences healthcare decisions. Given the complexity of healthcare decisions, it is likely that ML outputs will need to be understood and trusted by physicians, and then explained to patients. We therefore investigated the association between physician understanding of ML outputs, their ability to explain these to patients, and their willingness to trust the ML outputs, using various ML explainability methods. MATERIALS AND METHODS: We designed a survey for physicians with a diagnostic dilemma that could be resolved by an ML risk calculator. Physicians were asked to rate their understanding, explainability, and trust in response to 3 different ML outputs. One ML output had no explanation of its logic (the control) and 2 ML outputs used different model-agnostic explainability methods. The relationships among understanding, explainability, and trust were assessed using Cochran-Mantel-Haenszel tests of association. RESULTS: The survey was sent to 1315 physicians, and 170 (13%) provided completed surveys. There were significant associations between physician understanding and explainability (P < .001), between physician understanding and trust (P < .001), and between explainability and trust (P < .001). ML outputs that used model-agnostic explainability methods were preferred by 88% of physicians when compared with the control condition; however, no particular ML explainability method had a greater influence on intended physician behavior. CONCLUSIONS: Physician understanding, explainability, and trust in ML risk calculators are related. Physicians preferred ML outputs accompanied by model-agnostic explanations but the explainability method did not alter intended physician behavior.

Vertebrobasilar Artery Calcification and Outcomes in Posterior Circulation Large Vessel Occlusion Thrombectomy.

Background and Purpose- Intracranial carotid artery calcification is associated with worse outcome in anterior circulation stroke patients who undergo endovascular thrombectomy. We investigated the association between vertebrobasilar artery calcification (VBAC) and outcome in patients undergoing endovascular thrombectomy for posterior circulation large vessel occlusion. Methods- Consecutive patients treated for posterior circulation large vessel occlusion from a prospective single-center registry were studied. VBAC was manually segmented on computed tomography brain scans. The associations between VBAC and VBAC volume, functional independence (90-day modified Rankin Scale score of 0-2), and 90-day mortality were assessed using propensity score-adjusted logistic regression. Results- Sixty-four posterior circulation large vessel occlusion patients were included. Twenty-five (39.1%) patients had VBAC, and of these, the median (interquartile range) VBAC volume was 19.8 (6.65-23.4) mm3. VBAC was associated with reduced functional independence (OR, 0.19 [95% CI, 0.04-0.78]; P=0.03) and increased mortality (OR, 9.44 [95% CI, 2.43-36.62]; P=0.005). Larger VBAC volumes were a significant predictor of reduced functional independence and increased mortality. Conclusions- VBAC is an independent predictor of outcome in patients undergoing endovascular thrombectomy for posterior circulation large vessel occlusion. Considering the presence of VBAC might improve prognostication and shared treatment decision-making between patients, families, and physicians.