Challenges to Widespread Implementation of Stroke Thrombectomy.

Endovascular treatment (EVT) for acute ischemic stroke is one of the most efficacious and effective treatments in medicine, yet globally, its implementation remains limited. Patterns of EVT underutilization exist in virtually any health care system and range from a complete lack of access to selective undertreatment of certain patient subgroups. In this review, we outline different patterns of EVT underutilization and possible causes. We discuss common challenges and bottlenecks that are encountered by physicians, patients, and other stakeholders when trying to establish and expand EVT services in different scenarios and possible pathways to overcome these challenges. Lastly, we discuss the importance of implementation research studies, strategic partnerships, and advocacy efforts to mitigate EVT underutilization.

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.

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.

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.

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.

Chronic Kidney Disease and Outcome Following Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) is present in 20% to 35% of acute ischemic stroke patients and may increase the risk of poor functional outcome or death. We aimed to determine whether CKD was associated with worse outcome in stroke patients treated with endovascular thrombectomy (EVT). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Consecutive EVT patients were identified from a prospective registry and dichotomized into patients with and without CKD, defined as an eGFR of less than 60 mL/min/1.73m2. The primary outcome was 3-month mortality following EVT. Secondary outcomes included symptomatic intracerebral hemorrhage (defined by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study), early neurological recovery (defined as change in National Institutes of Health Stroke Scale [NIHSS] score of ≥8 at 24 hours or an NIHSS of 0-1 at 24 hours) and functional independence (defined as a modified Rankin Scale [mRS] score of 0, 1 or 2) at 3 months. RESULTS: 378 EVT patients (223 men; mean ± SD age 65 ± 15 years) were included. The median (IQR) admission eGFR was 71 (58-89) mL/min/1.73 m² and 117 (31%) patients had CKD. Multiple logistic regression adjusted for potential confounders demonstrated that CKD was a significant predictor of lower rates of functional independence (OR = .54, 95% CI, .31 to .90, P = .02), higher mRS scores (common OR = 1.78, 95% CI, 1.14 to 2.81, P = .01), and increased mortality (OR = 2.19, 95% CI, 1.16 to 4.12, P = .01). There was no association between CKD and early neurological recovery (OR = .92, 95% CI, .55 to 1.49, P = .71) or symptomatic intracerebral hemorrhage (OR = 1.18, 95% CI, .38 to 3.69, P = .77). CONCLUSIONS: CKD was a significant predictor of worse functional outcome and mortality in stroke patients treated with EVT. The presence of CKD should not preclude patients from proceeding to EVT, but may help with prognostication and improve shared decision-making between patients, families and physicians.

Contrast-Associated Acute Kidney Injury in Endovascular Thrombectomy Patients With and Without Baseline Renal Impairment.

Background and Purpose- In ischemic stroke, baseline renal impairment is present in 20 to 35% of patients and may increase the risk of contrast-associated acute kidney injury (CA-AKI). We aimed to determine whether endovascular thrombectomy (EVT) patients with baseline renal impairment are at increased risk of CA-AKI. Methods- Consecutive EVT patients were identified from a prospective database. Patients were stratified by estimated glomerular filtration rate. The primary outcome was CA-AKI assessed at 24 to 72 hours following EVT, defined as an increase in serum creatinine of ≥26.5 µmol/L or 1.5× baseline serum creatinine. Secondary outcomes included requirement for renal replacement therapy and 3-month mortality. Results- Three hundred thirty-three EVT patients (201 men; mean±SD age 63.9±15.8 years) were included. The mean±SD iohexol contrast volume used in diagnostic and EVT imaging was 236±77 mL per patient. CA-AKI occurred in 11 (3.3%) patients; none required renal replacement therapy, but 4 of 11 (36.4%) had died by 3 months. Propensity score-adjusted logistic regression showed that estimated glomerular filtration rate <30 mL/(min·1.73 m2) was a significant predictor of CA-AKI (odds ratio, 19.93; 95% CI, 2.33-170.74; P=0.006). The dose of contrast was not associated with an increased risk of CA-AKI (P>0.05). Multiple logistic regression adjusted for potential confounders demonstrated that CA-AKI was independently associated with increased mortality (odds ratio, 4.68; 95% CI, 1.05-20.97; P=0.04). Conclusions- There is utility in obtaining baseline creatinine levels to identify patients at risk of CA-AKI and to establish a diagnosis of CA-AKI in patients with subsequent creatinine rises. However, contrast-requiring diagnostic imaging and EVT should not be delayed by waiting for the results of baseline renal function.

Automated Measurement of Cerebral Atrophy and Outcome in Endovascular Thrombectomy.

Background and Purpose- Methods of identifying ischemic stroke patients with a greater probability of poor outcome following endovascular thrombectomy (EVT) might improve shared treatment decision-making between patients, families, and physicians. We used an objective, automated method to measure cerebral atrophy and investigated whether this was associated with outcome in EVT patients. Methods- Consecutive EVT patients from a single-center registry were studied. CT brain scans were segmented with a combination of a validated U-Net and Hounsfield unit thresholding. Intracranial cerebrospinal fluid (CSF) volume was used as a marker of cerebral atrophy and calculated as a proportion of total intracranial volume. The primary outcome was functional independence, defined as a 3-month modified Rankin Scale score of 0 to 2. Results- Three-hundred sixty EVT patients were included. Functional independence was achieved in 204 (56.7%) patients. The mean±SD CSF volume was 9.0±4.7% of total intracranial volume. Multivariable regression demonstrated that increasing CSF volume was associated with reduced functional independence (OR=0.65 per 5% increase in CSF volume; 95% CI, 0.48-0.89; P=0.007) and higher 3-month modified Rankin Scale scores (common OR, 1.59 per 5% increase in CSF volume; 95% CI, 1.05-2.41; P=0.03). Conclusions- Cerebral atrophy determined by automated measurement of intracranial CSF volume is associated with functional outcome in patients undergoing EVT. If validated in future studies, this simple, objective, and automated imaging marker could potentially be incorporated into decision-support tools to improve shared treatment decision-making.

Psychiatric comorbidity in psychogenic nonepileptic seizures compared with epilepsy.

OBJECTIVES: Psychogenic nonepileptic seizures (PNESs) are closely linked with psychological distress, but their etiology is not well-understood. We reviewed psychiatric comorbidity in PNESs and epileptic seizures (ESs) with an aim to assist understanding, diagnosis, and management of PNESs. METHODS: A search of Web of Science, MEDLINE (PubMed), PsycINFO, and Scopus identified 32 relevant studies on the prevalence of psychiatric comorbidity in PNESs. We used meta-analysis to compare psychiatric comorbidity between PNESs and ESs. RESULTS: Samples with PNESs had high rates of psychiatric comorbidity overall (53-100%), notably including posttraumatic stress disorder (PTSD), depression, and personality and anxiety disorders. Compared with ESs, samples with PNESs had more psychiatric comorbidity overall (RR: 1.30, 95% CI: 1.14-1.48, p<0.0001) with significantly elevated risks found for PTSD, personality disorder, and anxiety but not depression. CONCLUSIONS: Psychiatric disorders are more common in PNESs than ESs. Because of methodological limitations of available studies, causality cannot be established; prospective longitudinal designs are required.

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.

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.

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.

Days Alive and Out of Hospital as an Outcome Measure in Patients Receiving Hyperacute Stroke Intervention.

BACKGROUND: Patient outcome after stroke is frequently assessed with clinical scales such as the modified Rankin Scale score (mRS). Days alive and out of hospital at 90 days (DAOH-90), which measures survival, time spent in hospital or rehabilitation settings, readmission and institutionalization, is an objective outcome measure that can be obtained from large administrative data sets without the need for patient contact. We aimed to assess the comparability of DAOH with mRS and its relationship with other prognostic variables after acute stroke reperfusion therapy. METHODS AND RESULTS: Consecutive patients with ischemic stroke treated with intravenous thrombolysis or endovascular thrombectomy were analyzed. DAOH-90 was calculated from a national minimum data set, a mandatory nationwide administrative database. mRS score at day 90 (mRS-90) was assessed with in-person or telephone interviews. The study included 1278 patients with ischemic stroke (714 male, median age 70 [59-79], median National Institutes of Health Stroke Scale score 14 [9-20]). Median DAOH-90 was 71 [29-84] and median mRS-90 score was 3 [2-5]. DAOH-90 was correlated with admission National Institutes of Health Stroke Scale score (Spearman rho -0.44, P<0.001) and Alberta Stroke Program Early CT [Computed Tomography] Score (Spearman rho 0.24, P<0.001). There was a strong association between mRS-90 and DAOH-90 (Spearman rho correlation -0.79, P<0.001). Area under receiver operating curve for predicting mRS score >0 was 0.86 (95% CI, 0.84-0.88), mRS score >1 was 0.88 (95% CI, 0.86-0.90) and mRS score >2 was 0.90 (95% CI, 0.89-0.92). CONCLUSIONS: In patients with stroke treated with reperfusion therapies, DAOH-90 shows reasonable comparability to the more established outcome measure of mRS-90. DAOH-90 can be readily obtained from administrative databases and therefore has the potential to be used in large-scale clinical trials and comparative effectiveness studies.

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.

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.