Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke.

BACKGROUND: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood. METHODS: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications. RESULTS: Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p = 0.1; mRS 0-2: 47% vs 50%, p = 0.41) but higher mortality (26% vs 17%, p = 0.008). After PSM, there were no significant differences in outcomes between the two groups. CONCLUSION: Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates.

External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis.

OBJECTIVES: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. MATERIALS AND METHODS: The SI2NCAL2C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI2NCAL2C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. RESULTS: Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI2NCAL2C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year. CONCLUSIONS: The SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies.

Outcomes with General Anesthesia Compared to Conscious Sedation for Endovascular Treatment of Medium Vessel Occlusions: Results of an International Multicentric Study.

BACKGROUND: Optimal anesthetic strategy for the endovascular treatment of stroke is still under debate. Despite scarce data concerning anesthetic management for medium and distal vessel occlusions (MeVOs) some centers empirically support a general anesthesia (GA) strategy in these patients. METHODS: We conducted an international retrospective study of MeVO cases. A propensity score matching algorithm was used to mitigate potential differences across patients undergoing GA and conscious sedation (CS). Comparisons in clinical and safety outcomes were performed between the two study groups GA and CS. The favourable outcome was defined as a modified Rankin Scale (mRS) 0-2 at 90 days. Safety outcomes were 90-days mortality and symptomatic intracranial hemorrhage (sICH). Predictors of a favourable outcome and sICH were evaluated with backward logistic regression. RESULTS: After propensity score matching 668 patients were included in the CS and 264 patients in the GA group. In the matched cohort, either strategy CS or GA resulted in similar rates of good functional outcomes (50.1% vs. 48.4%), and successful recanalization (89.4% vs. 90.2%). The GA group had higher rates of 90-day mortality (22.6% vs. 16.5%, p < 0.041) and sICH (4.2% vs. 0.9%, p = 0.001) compared to the CS group. Backward logistic regression did not identify GA vs CS as a predictor of good functional outcome (OR for GA vs CS = 0.95 (0.67-1.35)), but GA remained a significant predictor of sICH (OR = 5.32, 95% CI 1.92-14.72). CONCLUSION: Anaesthetic strategy in MeVOs does not influence favorable outcomes or final successful recanalization rates, however, GA may be associated with an increased risk of sICH and mortality.

Use of the pRESET LITE thrombectomy device in combined approach for medium vessel occlusions: A multicenter evaluation.

PURPOSE: Our purpose was to assess the efficacy and safety of the pRESET LITE stent retriever (Phenox, Bochum, Germany), designed for medium vessel occlusion (MeVO) in acute ischemic stroke (AIS) patients with a primary MeVO. METHODS: We performed a retrospective analysis of the MAD MT Consortium, an integration of prospectively maintained databases at 37 academic institutions in Europe, North America, and Asia, of AIS patients who underwent mechanical thrombectomy with the pRESET LITE stent retriever for a primary MeVO. We subcategorized occlusions into proximal MeVOs (segments A1, M2, and P1) vs. distal MeVOs/DMVO (segments A2, M3-M4, and P2). We reviewed patient and procedural characteristics, as well as angiographic and clinical outcomes. RESULTS: Between September 2016 and December 2021, 227 patients were included (50% female, median age 78 [65-84] years), of whom 161 (71%) suffered proximal MeVO and 66 (29%) distal MeVO. Using a combined approach in 96% of cases, successful reperfusion of the target vessel (mTICI 2b/2c/3) was attained in 85% of proximal MeVO and 97% of DMVO, with a median of 2 passes (IQR: 1-3) overall. Periprocedural complications rate was 7%. Control CT at day 1 post-MT revealed a hemorrhagic transformation in 63 (39%) patients with proximal MeVO and 24 (36%) patients with DMVO, with ECASS-PH type hemorrhagic transformations occurring in 3 (1%) patients. After 3 months, 58% of all MeVO and 63% of DMVO patients demonstrated a favorable outcome (mRS 0-2). CONCLUSION: Mechanical thrombectomy using the pRESET LITE in a combined approach with an aspiration catheter appears effective for primary medium vessel occlusions across several centers and physicians.

Transcarotid Arterial Revascularization of Symptomatic Internal Carotid Artery Disease: A Systematic Review and Study-Level Meta-Analysis.

BACKGROUND: Transcarotid artery revascularization (TCAR) is an interventional therapy for symptomatic internal carotid artery disease. Currently, the utilization of TCAR is contentious due to limited evidence. In this study, we evaluate the safety and efficacy of TCAR in patients with symptomatic internal carotid artery disease compared with carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: A systematic review was conducted, spanning from January 2000 to February 2023, encompassing studies that used TCAR for the treatment of symptomatic internal carotid artery disease. The primary outcomes included a 30-day stroke or transient ischemic attack, myocardial infarction, and mortality. Secondary outcomes comprised cranial nerve injury and major bleeding. Pooled odds ratios (ORs) for each outcome were calculated to compare TCAR with CEA and CAS. Furthermore, subgroup analyses were performed based on age and degree of stenosis. In addition, a sensitivity analysis was conducted by excluding the vascular quality initiative registry population. RESULTS: A total of 7 studies involving 24 246 patients were analyzed. Within this patient cohort, 4771 individuals underwent TCAR, 12 350 underwent CEA, and 7125 patients underwent CAS. Compared with CAS, TCAR was associated with a similar rate of stroke or transient ischemic attack (OR, 0.77 [95% CI, 0.33-1.82]) and myocardial infarction (OR, 1.29 [95% CI, 0.83-2.01]) but lower mortality (OR, 0.42 [95% CI, 0.22-0.81]). Compared with CEA, TCAR was associated with a higher rate of stroke or transient ischemic attack (OR, 1.26 [95% CI, 1.03-1.54]) but similar rates of myocardial infarction (OR, 0.9 [95% CI, 0.64-1.38]) and mortality (OR, 1.35 [95% CI, 0.87-2.10]). CONCLUSIONS: Although CEA has traditionally been considered superior to stenting for symptomatic carotid stenosis, TCAR may have some advantages over CAS. Prospective randomized trials comparing the 3 modalities are needed.

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Incidence and clinical outcomes of perforations during mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke: A retrospective, multicenter, and multinational study.

BACKGROUND: Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO. METHODS: Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed. RESULTS: The incidence of vessel perforation was 4.8% (66/1373). Notably, our analysis indicates variations in perforation rates across different arterial segments: 8.9% in M3 segments, 4.3% in M2 segments, and 8.3% in A2 segments (p = 0.612). Patients with perforation had significantly worse outcomes, with lower rates of favorable angiographic outcomes (TICI 2c-3: 23% vs 58.9%, p < 0.001; TICI 2b-3: 56.5% vs 88.3%, p < 0.001). Functional outcomes were also worse in the perforation group (mRS 0-1 at 3 months: 22.7% vs 36.6%, p = 0.031; mRS 0-2 at 3 months: 28.8% vs 53.9%, p < 0.001). Mortality was higher in the perforation group (30.3% vs 16.8%, p = 0.008). CONCLUSION: This study reveals that while the occurrence of vessel perforation in MT for AIS due to MeVO is relatively rare, it is associated with poor functional outcomes and higher mortality. The findings highlight the need for increased caution and specialized training in performing MT for MeVO. Further prospective research is required for risk mitigation strategies.

First pass effect as an independent predictor of functional outcomes in medium vessel occlusions: An analysis of an international multicenter study.

INTRODUCTION: First pass effect (FPE), achievement of complete recanalization (mTICI 2c/3) with a single pass, is a significant predictor of favorable outcomes for endovascular treatment (EVT) in large vessel occlusion stroke (LVO). However, data concerning the impact on functional outcomes and predictors of FPE in medium vessel occlusions (MeVO) are scarce. PATIENTS AND METHODS: We conducted an international retrospective study on MeVO cases. Multivariable logistic modeling was used to establish independent predictors of FPE. Clinical and safety outcomes were compared between the two study groups (FPE vs non-FPE) using logistic regression models. Good outcome was defined as modified Rankin Scale 0-2 at 3 months. RESULTS: Eight hundred thirty-six patients with a final mTICI ⩾ 2b were included in this analysis. FPE was observed in 302 patients (36.1%). In multivariable analysis, hypertension (aOR 1.55, 95% CI 1.10-2.20) and lower baseline NIHSS score (aOR 0.95, 95% CI 0.93-0.97) were independently associated with an FPE. Good outcomes were more common in the FPE versus non-FPE group (72.8% vs 52.8%), and FPE was independently associated with favorable outcome (aOR 2.20, 95% CI 1.59-3.05). 90-day mortality and intracranial hemorrhage (ICH) were significantly lower in the FPE group, 0.43 (95% CI, 0.25-0.72) and 0.55 (95% CI, 0.39-0.77), respectively. CONCLUSION: Over 2/3 of patients with MeVOs and FPE in our cohort had a favorable outcome at 90 days. FPE is independently associated with favorable outcomes, it may reduce the risk of any intracranial hemorrhage, and 3-month mortality.

Endovascular therapy versus medical management for mild strokes due to medium and distal vessel occlusions.

BACKGROUND: Distal and medium vessel occlusion (DMVO) strokes account for up to 40% of all acute ischemic strokes, many of which have a low initial deficit severity. Increasingly, endovascular treatment (EVT) is considered for these patients. However, there is a paucity of data comparing potential safety and efficacy of EVT versus best medical management (BMT) in these patients, particularly when presenting with mild symptoms. METHODS: We retrospectively analyzed consecutive DMVO patients with NIHSS ≤6 who presented between January 2018 and December 2021 within 24 h from last seen well. We compared early and late clinical outcomes, as well as safety outcomes using multivariable linear and logistic regression analyses to determine whether EVT was independently associated with the outcomes of interest. RESULTS: We included 80 subjects that fulfilled our study criteria (n = 41 BMT and n = 39 EVT). On adjusted analyses, when comparing EVT and BMT groups, there was no statistical difference in the NIHSS at discharge (Coefficient = -0.6, 95%-CI = -3.45-2.26, p = 0.678) or in the modified Rankin scale (mRS) at discharge (Coefficient = 0.37, 95%-CI = -0.52-1.25, p = 0.408). Furthermore, there was no difference in the 3-month mRS defined as good (mRS 0-2) (OR = 0.56, 95%-CI = 0.17-1.83, p = 0.341) or excellent (mRS 0-1) (OR = 0.45, 95%-CI = 0.15-1.34, p = 0.152). Finally, there was no difference in the incidence of all-type parenchymal hemorrhage (OR = 0.9, 95%-CI = 0.22-3.62, p = 0.879). CONCLUSIONS: We found that among DMVO patients with low admission NIHSS treatment with EVT versus BMT was associated with similar outcomes. Larger prospective studies are required to confirm these findings.

Genetic ablation of Sarm1 attenuates expression and mislocalization of phosphorylated TDP-43 after mouse repetitive traumatic brain injury.

Traumatic brain injury (TBI), particularly when moderate-to-severe and repetitive, is a strong environmental risk factor for several progressive neurodegenerative disorders. Mislocalization and deposition of transactive response DNA binding protein 43 (TDP-43) has been reported in both TBI and TBI-associated neurodegenerative diseases. It has been hypothesized that axonal pathology, an early event after TBI, may promote TDP-43 dysregulation and serve as a trigger for neurodegenerative processes. We sought to determine whether blocking the prodegenerative Sarm1 (sterile alpha and TIR motif containing 1) axon death pathway attenuates TDP-43 pathology after TBI. We subjected 111 male Sarm1 wild type, hemizygous, and knockout mice to moderate-to-severe repetitive TBI (rTBI) using a previously established injury paradigm. We conducted serial neurological assessments followed by histological analyses (NeuN, MBP, Iba-1, GFAP, pTDP-43, and AT8) at 1 month after rTBI. Genetic ablation of the Sarm1 gene attenuated the expression and mislocalization of phosphorylated TDP-43 (pTDP-43) and accumulation of pTau. In addition, Sarm1 knockout mice had significantly improved cortical neuronal and axonal integrity, functional deficits, and improved overall survival after rTBI. In contrast, removal of one Sarm1 allele delayed, but did not prevent, neurological deficits and neuroaxonal loss. Nevertheless, Sarm1 haploinsufficient mice showed significantly less microgliosis, pTDP-43 pathology, and pTau accumulation when compared to wild type mice. These data indicate that the Sarm1-mediated prodegenerative pathway contributes to pathogenesis in rTBI including the pathological accumulation of pTDP-43. This suggests that anti-Sarm1 therapeutics are a viable approach for preserving neurological function after moderate-to-severe rTBI.

Delayed Diagnosis in Cerebral Venous Thrombosis: Associated Factors and Clinical Outcomes.

Background Identifying factors associated with delayed diagnosis of cerebral venous thrombosis (CVT) can inform future strategies for early detection. Methods and Results We conducted a retrospective cohort study including all participants from ACTION-CVT (Anticoagulation in the Treatment of Cerebral Venous Thrombosis) study who had dates of neurologic symptom onset and CVT diagnosis available. Delayed diagnosis was defined as CVT diagnosis occurring in the fourth (final) quartile of days from symptom onset. The primary study outcome was modified Rankin Scale score of ≤1 at 90 days; secondary outcomes included partial/complete CVT recanalization on last available imaging and modified Rankin Scale score of ≤2. Logistic regression analyses were used to identify independent variables associated with delayed diagnosis and to assess the association of delayed diagnosis and outcomes. A total of 935 patients were included in our study. Median time from symptom onset to diagnosis was 4 days (interquartile range, 1-10 days). Delayed CVT diagnosis (time to diagnosis >10 days) occurred in 212 patients (23%). Isolated headache (adjusted odds ratio [aOR], 2.36 [95% CI, 1.50-3.73]; P<0.001), older age (aOR by 1 year, 1.02 [95% CI, 1.004-1.03]; P=0.01), and papilledema (aOR, 2.00 [95% CI, 1.03-3.89]; P=0.04) were associated with diagnostic delay, whereas higher National Institutes of Health Stroke Scale score was inversely associated with diagnostic delay (aOR by 1 point, 0.95 [95% CI, 0.89-1.00]; P=0.049). Delayed diagnosis was not associated with modified Rankin Scale score of ≤1 at 90 days (aOR, 1.08 [95% CI, 0.60-1.96]; P=0.79). Conclusions In a large multicenter cohort, a quarter of included patients with CVT were diagnosed >10 days after symptom onset. Delayed CVT diagnosis was associated with the symptom of isolated headache and was not associated with adverse clinical outcomes.

Small vessel disease is associated with later onset of major adverse cardiovascular events after acute cervicocerebral artery dissection.

BACKGROUND: Cerebral small vessel disease (CSVD) is common among the elderly and has been associated with an increased risk of major adverse cardiac events (MACE) and increased risk of long-term disability. Little is known whether CSVD affects outcomes after cervicocerebral artery dissection (CAD), which predominantly affects younger patients. Specifically, there is a paucity as to whether CSVD increases the risk of MACE after CAD and whether this risk is different for early versus late events. METHODS: We retrospectively analyzed 140 consecutive patients with acute CAD. We determined CSVD on MRI using the STRIVE criteria and calculated the CSVD sum score based on the individual CSVD components. For statistical analysis the CSVD burden was dichotomized to mild (score 0-1) versus severe (score 2-4). The primary outcome of interest was the 6-month MACE risk. Secondary outcomes of interest were early versus late MACE, stroke at presentation, and good 90-day outcome (modified Rankin Scale score 0-2). RESULTS: There was no difference in overall MACE between subjects when stratified by CSVD burden (10.1% versus 9.8%, Log-rank P = 0.953). We found that patients with severe CSVD had significantly more late MACE as compared to mild CSVD (9.8% versus 1.1%, P = 0.024). There was no significant difference in the prevalence of stroke at the time of CAD diagnosis (50.6% versus 47.1%, P = 0.690) and the 90-day disability-free survival in subjects with mild versus severe CSVD (93.7% versus 91.7%, P = 0.729). CONCLUSION: Severe CSVD burden was associated with a significantly greater risk of late MACE. CSVD assessment in CAD patients may aid risk stratification and treatment optimization.

Repeated mild traumatic brain injury triggers pathology in asymptomatic C9ORF72 transgenic mice.

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative diseases that represent ends of the spectrum of a single disease. The most common genetic cause of FTD and ALS is a hexanucleotide repeat expansion in the C9orf72 gene. Although epidemiological data suggest that traumatic brain injury (TBI) represents a risk factor for FTD and ALS, its role in exacerbating disease onset and course remains unclear. To explore the interplay between traumatic brain injury and genetic risk in the induction of FTD/ALS pathology we combined a mild repetitive traumatic brain injury paradigm with an established bacterial artificial chromosome transgenic C9orf72 (C9BAC) mouse model without an overt motor phenotype or neurodegeneration. We assessed 8-10 week-old littermate C9BACtg/tg (n = 21), C9BACtg/- (n = 20) and non-transgenic (n = 21) mice of both sexes for the presence of behavioural deficits and cerebral histopathology at 12 months after repetitive TBI. Repetitive TBI did not affect body weight gain, general neurological deficit severity, nor survival over the 12-month observation period and there was no difference in rotarod performance, object recognition, social interaction and acoustic characteristics of ultrasonic vocalizations of C9BAC mice subjected to repetitive TBI versus sham injury. However, we found that repetitive TBI increased the time to the return of the righting reflex, reduced grip force, altered sociability behaviours and attenuated ultrasonic call emissions during social interactions in C9BAC mice. Strikingly, we found that repetitive TBI caused widespread microglial activation and reduced neuronal density that was associated with loss of histological markers of axonal and synaptic integrity as well as profound neuronal transactive response DNA binding protein 43 kDa mislocalization in the cerebral cortex of C9BAC mice at 12 months; this was not observed in non-transgenic repetitive TBI and C9BAC sham mice. Our data indicate that repetitive TBI can be an environmental risk factor that is sufficient to trigger FTD/ALS-associated neuropathology and behavioural deficits, but not paralysis, in mice carrying a C9orf72 hexanucleotide repeat expansion.

Stroke nurse navigator utilization reduces unplanned 30-day readmission in stroke patients treated with thrombolysis.

Background: Unplanned 30-day hospital readmissions following a stroke is a serious quality and safety issue in the United States. The transition period between the hospital discharge and ambulatory follow-up is viewed as a vulnerable period in which medication errors and loss of follow-up plans can potentially occur. We sought to determine whether unplanned 30-day readmission in stroke patients treated with thrombolysis can be reduced with the utilization of a stroke nurse navigator team during the transition period. Methods: We included 447 consecutive stroke patients treated with thrombolysis from an institutional stroke registry between January 2018 and December 2021. The control group consisted of 287 patients before the stroke nurse navigator team implementation between January 2018 and August 2020. The intervention group consisted of 160 patients after the implementation between September 2020 and December 2021. The stroke nurse navigator interventions included medication reviews, hospitalization course review, stroke education, and review of outpatient follow-ups within 3 days following the hospital discharge. Results: Overall, baseline patient characteristics (age, gender, index admission NIHSS, and pre-admission mRS), stroke risk factors, medication usage, and length of hospital stay were similar in control vs. intervention groups (P > 0.05). Differences included higher mechanical thrombectomy utilization (35.6 vs. 24.7%, P = 0.016), lower pre-admission oral anticoagulant use (1.3 vs. 5.6%, P = 0.025), and less frequent history of stroke/TIA (14.4 vs. 27.5%, P = 0.001) in the implementation group. Based on an unadjusted Kaplan-Meier analysis, 30-day unplanned readmission rates were lower during the implementation period (log-rank P = 0.029). After adjustment for pertinent confounders including age, gender, pre-admission mRS, oral anticoagulant use, and COVID-19 diagnosis, the nurse navigator implementation remained independently associated with lower hazards of unplanned 30-day readmission (adjusted HR 0.48, 95% CI 0.23-0.99, P = 0.046). Conclusion: The utilization of a stroke nurse navigator team reduced unplanned 30-day readmissions in stroke patients treated with thrombolysis. Further studies are warranted to determine the extent of the results of stroke patients not treated with thrombolysis and to better understand the relationship between resource utilization during the transition period from discharge and quality outcomes in stroke.

Outcomes of Telestroke Inter-Hospital Transfers Among Intervention and Non-Intervention Patients.

Background: Telestroke is an established telemedicine method of delivering emergency stroke care. However, not all neurological patients utilizing telestroke service require emergency interventions or transfer to a comprehensive stroke center. To develop an understanding of the appropriateness of inter-hospital neurological transfers utilizing the telemedicine, our study aimed to assess the differences in outcomes of inter-hospital transfers utilizing the service in relation to the need for neurological interventions. Methods: The pragmatic, retrospective analysis included 181 consecutive patients, who were emergently transferred from telestroke-affiliated regional medical centers between October 3, 2021, and May 3, 2022. In this exploratory study investigating the outcomes of telestroke-referred patients, patients receiving interventions were compared to those that did not following transfer to our tertiary center. Neurological interventions included mechanical thrombectomy (MT) and/or tissue plasminogen activator (tPA), craniectomy, electroencephalography (EEG), or external ventricular drain (EVD). Transfer mortality rate, discharge functional status defined by modified Rankin scale (mRS), neurological status defined by National Institutes of Health Stroke Scale (NIHSS), 30-day unpreventable readmission rate, 90-day clinical major adverse cardiovascular events (MACE), and 90-day mRS, and NIHSS were studied. We used χ2 or Fisher exact tests to evaluate the association between the intervention and categorical or dichotomous variables. Continuous or ordinal measures were compared using Wilcoxon rank-sum tests. All tests of statistical significance were considered to be significant at P < 0.05. Results: Among the 181 transferred patients, 114 (63%) received neuro-intervention and 67 (37%) did not. The death rate during the index admission was not statistically significant between the intervention and non-intervention groups (P = 0.196). The discharge NIHSS and mRS were worse in the intervention compared to the non-intervention (P < 0.05 each, respectively). The 90-day mortality and cardiovascular event rates were similar between intervention and non-intervention groups (P > 0.05 each, respectively). The 30-day readmission rates were also similar between the two groups (14% intervention vs. 13.4% non-intervention, P = 0.910). The 90-day mRS were not significantly different between intervention and non-intervention groups (median 3 (IQR: 1 - 6) vs. 2 (IQR: 0 - 6), P = 0.109). However, 90-day NIHSS was worse in the intervention compared to non-intervention group (median 2 (IQR: 0 - 11) vs. 0 (IQR: 0 - 3), P = 0.004). Conclusions: Telestroke is a valuable resource that expedites emergent neurological care via referral to a stroke center. However, not all transferred patients benefit from the transfer process. Future multicenter studies are warranted to study the effects or appropriateness of telestroke networks, and to better understand the patient characteristics, resources allocation, and transferring institutions to improve telestroke care.

Intravital Imaging of Fluorescent Protein Expression in Mice with a Closed-Skull Traumatic Brain Injury and Cranial Window Using a Two-Photon Microscope.

The goal of this protocol is to demonstrate how to longitudinally visualize the expression and localization of a protein of interest within specific cell types of an animal's brain, upon exposure to exogenous stimuli. Here, the administration of a closed-skull traumatic brain injury (TBI) and simultaneous implantation of a cranial window for subsequent longitudinal intravital imaging in mice is shown. Mice are intracranially injected with an adeno-associated virus (AAV) expressing enhanced green fluorescent protein (EGFP) under a neuronal specific promoter. After 2 to 4 weeks, the mice are subjected to a repetitive TBI using a weight drop device over the AAV injection location. Within the same surgical session, the mice are implanted with a metal headpost and then a glass cranial window over the TBI impacting site. The expression and cellular localization of EGFP is examined using a two-photon microscope in the same brain region exposed to trauma over the course of months.

Perioperative Acute Ischemic Stroke in Patients with Atrial Fibrillation.

OBJECTIVE: Anticoagulation therapy is commonly interrupted in patients with atrial fibrillation (AF) for elective procedures. However, the risk factors of acute ischemic stroke (AIS) during the periprocedural period remain uncertain. We performed a nationwide analysis to evaluate AIS risk factors in patients with AF undergoing elective surgical procedures. METHODS: Using the Nationwide Readmission Database, we included electively admitted adult patients with AF and procedural Diagnosis-Related Group codes from 2016 to 2019. Diagnoses were identified based on International Classification of Disease, 9th revision-Clinical Modification (ICD-10 CM) codes. We constructed a logistic regression model to identify risk factors and developed a new scoring system incorporating CHA2 DS2 VASc to estimate periprocedural AIS risk. RESULTS: Of the 1,045,293 patients with AF admitted for an elective procedure, the mean age was 71.5 years, 39.2% were women, and 0.70% had a perioperative AIS during the index admission or within 30 days of discharge. Active cancer (adjusted OR [aOR] = 1.58, 95% confidence interval [CI] = 1.42-1.76), renal failure (aOR = 1.14, 95% CI = 1.04-1.24), neurological surgery (aOR = 4.51, 95% CI = 3.84-5.30), cardiovascular surgery (aOR = 2.74, 95% CI = 2.52-2.97), and higher CHA2 DS2 VASc scores (aOR 1.25 per point, 95% CI 1.22-1.29) were significant risk factors for periprocedural AIS. The new scoring system (area under the receiver operating characteristic curve [AUC] = 0.68, 95% CI = 0.67 to 0.79) incorporating surgical type and cancer outperformed CHA2 DS2 VASc (AUC = 0.60, 95% CI = 0.60 to 0.61). INTERPRETATION: In patients with AF, periprocedural AIS risk increases with the CHA2 DS2 VASc score, active cancer, and cardiovascular or neurological surgeries. Studies are needed to devise better strategies to mitigate perioperative AIS risk in these patients. ANN NEUROL 2023;94:321-329.

Subsequent ischemic stroke and tobacco smoking: A secondary analysis of the POINT trial.

Background: The aim of this study was to determine the effect of smoking status on subsequent stroke risk in patients with minor ischemic stroke or TIA and to determine whether smoking modifies the effect of clopidogrel-based DAPT on subsequent stroke risk. Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which had a 90-day follow-up period. We used multivariable Cox regression and subgroup interaction analysis to determine the effect of smoking on the risk of subsequent ischemic stroke and major hemorrhage, respectively. Results: Data from 4877 participants enrolled in the POINT trial were analyzed. Among these, 1004 were current smokers and 3873 were non-smokers at the time of index event. Smoking was associated with a non-significant trend toward an increased risk of subsequent ischemic stroke during follow up (adjusted HR, 1.31 (95% CI, 0.97-1.78), p = 0.076). The effect of clopidogrel on ischemic stroke did not differ between non-smokers (HR, 0.74 (95% CI, 0.56-0.98), p = 0.03) and smokers (HR, 0.63 (95% CI, 0.37-1.05), p = 0.078), p for interaction = 0.572. Similarly, the effect of clopidogrel on major hemorrhage did not differ between non-smokers (hazard ratio, 1.67 (95% CI, 0.40-7.00), p = 0.481) and smokers (HR, 2.59 (95% CI, 1.08-6.21), p = 0.032), p for interaction = 0.613. Conclusions: In this post-hoc analysis of the POINT trial we found that the effect of clopidogrel on reducing subsequent ischemic stroke as well as risk of major hemorrhage did not depend on smoking status, indicating that smokers benefit to a similar degree from DAPT as non-smokers.

Clinical characteristics and risk factors for bilateral lateral geniculate body pathology: a systematic review of the literature.

BACKGROUND: Case presentation of acute onset bilateral painless vision loss caused by bilateral infarction of the lateral geniculate bodies (LGB) and a systematic review of the literature. METHODS: A descriptive case report is presented on a 17-year-old female diagnosed with acute pancreatitis who developed acute onset bilateral painless vision loss. A systematic literature review of cases with bilateral LGB lesions was conducted across three electronic databases (PubMed/PubMed Central/MEDLINE, Scopus, and ScienceDirect). The review was conducted in concordance with PRISMA guidelines and prospectively registered on PROSPERO (CRD42022362491). RESULTS: The reported 17-year-old female was found to have MRI findings consistent with bilateral hemorrhagic infarction of the LGB and Purtscher-like retinopathy. A systematic literature review of bilateral LGB infarction yielded 23 records for analysis. 19/23 (82.6%) of reported cases occurred in women. Bilateral vision loss was noted in all cases. The average reported age was 27 years old with a range from 2-50. Gastrointestinal pathology (e.g., pancreatitis, gastroenteritis) was present in 8/23 (34.7%) of cases. 8/23 (34.7%) cases had neuroimaging or pathological evidence of hemorrhagic transformation of the infarct. Most cases experienced partial recovery of visual loss; only one case (4.7%) had complete visual recovery. 9/23 (39.1%) cases were reported from the United States and 4/23 (17.3%) from India. CONCLUSIONS: Bilateral LGB lesion is a rare cause of vision loss, typically caused by systemic diseases and with female preponderance. Purported pathophysiology relates to increased vulnerability of the LGB to ischemic and metabolic stress.

Trends in Venous Thromboembolism Readmission Rates after Ischemic Stroke and Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Venous thromboembolism (VTE) is a life-threatening complication of stroke. We evaluated nationwide rates and risk factors for hospital readmissions with VTE after an intracerebral hemorrhage (ICH) or acute ischemic stroke (AIS) hospitalization. METHODS: Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included patients with a principal discharge diagnosis of ICH or AIS from 2016 to 2019. Patients who had VTE diagnosis or history of VTE during the index admission were excluded. We performed Cox regression models to determine factors associated with VTE readmission, compared rates between AIS and ICH and developed post-stroke VTE risk score. We estimated VTE readmission rates per day over a 90-day time window post-discharge using linear splines. RESULTS: Of the total 1,459,865 patients with stroke, readmission with VTE as the principal diagnosis within 90 days occurred in 0.26% (3,407/1,330,584) AIS and 0.65% (843/129,281) ICH patients. The rate of VTE readmission decreased within first 4-6 weeks (P<0.001). In AIS, cancer, obesity, higher National Institutes of Health Stroke Scale (NIHSS) score, longer hospital stay, home or rehabilitation disposition, and absence of atrial fibrillation were associated with VTE readmission. In ICH, longer hospital stay and rehabilitation disposition were associated with VTE readmission. The VTE rate was higher in ICH compared to AIS (adjusted hazard ratio 2.86, 95% confidence interval 1.93-4.25, P<0.001). CONCLUSIONS: After stroke, VTE readmission risk is highest within the first 4-6 weeks and nearly three-fold higher after ICH vs. AIS. VTE risk is linked to decreased mobility and hypercoagulability. Studies are needed to test short-term VTE prophylaxis beyond hospitalization in high-risk patients.