Baseline characteristics and outcome of stroke patients after endovascular therapy according to previous symptomatic vascular disease and sex.

Aim: The aim of this study was to investigate baseline characteristics and outcome of patients after endovascular therapy (EVT) for acute large vessel occlusion (LVO) in relation to their history of symptomatic vascular disease and sex. Methods: Consecutive EVT-eligible patients with LVO in the anterior circulation admitted to our stroke center between 04/2015 and 04/2020 were included in this observational cohort study. All patients were treated according to a standardized acute ischaemic stroke (AIS) protocol. Baseline characteristics and successful reperfusion, recurrent/progressive in-hospital ischaemic stroke, symptomatic in-hospital intracranial hemorrhage, death at discharge and at 3 months, and functional outcome at 3 months were analyzed according to previous symptomatic vascular disease and sex. Results: 995 patients with LVO in the anterior circulation (49.4% women, median age 76 years, median admission NIHSS score 14) were included. Patients with multiple vs. no previous vascular events showed higher mortality at discharge (20% vs. 9.3%, age/sex - adjustedOR = 1.43, p = 0.030) and less independency at 3 months (28.8% vs. 48.8%, age/sex - adjustedOR = 0.72, p = 0.020). All patients and men alone with one or multiple vs. patients and men with no previous vascular events showed more recurrent/progressive in-hospital ischaemic strokes (19.9% vs. 6.4% in all patients, age/sex - adjustedOR = 1.76, p = 0.028) (16.7% vs. 5.8% in men, age-adjustedOR = 2.20, p = 0.035). Men vs. women showed more in-hospital symptomatic intracranial hemorrhage among patients with one or multiple vs. no previous vascular events (23.7% vs. 6.6% in men and 15.4% vs. 5.5% in women, OR = 2.32, p = 0.035/age - adjustedOR = 2.36, p = 0.035). Conclusions: Previous vascular events increased the risk of in-hospital complications and poorer outcome in the analyzed patients with EVT-eligible LVO-AIS. Our findings may support risk assessment in these stroke patients and could contribute to the design of future studies.

Intravenous thrombolysis in patients with recent intake of direct oral anticoagulants: A target trial analysis after the liberalization of institutional guidelines.

INTRODUCTION: This study aimed to report the safety and efficacy of off-label intravenous thrombolysis (IVT) with alteplase after sequentially liberalizing our institutional guidelines allowing IVT for patients under direct oral anticoagulants (DOACs) regardless of plasma levels, time of last intake, and without prior anticoagulation reversal therapy. PATIENTS AND METHODS: We utilized the target-trial methodology to emulate hypothetical criteria of a randomized controlled trial in our prospective stroke registry. Consecutive DOAC patients (06/2021-11/2023) otherwise qualifying for IVT were included. Safety and efficacy outcomes (symptomatic intracranial hemorrhage [ICH], any radiological ICH, major bleeding, 90-day mortality, 90-day good functional outcome [mRS 0-2 or return to baseline]) were assessed using inverse-probability-weighted regression-adjustment comparing patients with versus without IVT. RESULTS: Ninety eight patients fulfilled the target-trial criteria. IVT was given in 49/98 (50%) patients at a median of 178 (interquartile range 134-285) min after symptom onset with median DOAC plasma level of 77 ng/ml (15 patients had plasma levels > 100 ng/ml; 25/49 [51%] were treated within 12 h after last DOAC ingestion). Endovascular therapy was more frequent in patients without IVT (73% vs 33%). Symptomatic ICH occurred in 0/49 patients receiving IVT and 2/49 patients without IVT (adjusted difference -2.5%; 95% CI -5.9 to 0.8). The rates of any radiological ICH were comparable. Patients receiving IVT were more likely to have good functional outcomes. DISCUSSION AND CONCLUSION: After liberalizing our approach for IVT regardless of recent DOAC intake, we did not experience any safety concerns. The association of IVT with better functional outcomes warrants prospective randomized controlled trials.

Triple platelet inhibition in intracranial thrombectomy with additional acute cervical stent angioplasty due to tandem lesion: a retrospective single-center analysis.

BACKGROUND: Acute stroke treatment with intracranial thrombectomy and treatment of ipsilateral carotid artery stenosis/occlusion ("tandem lesion", TL) in one session is considered safe. However, the risk of stent restenosis after TL treatment is high, and antiplatelet therapy (APT) preventing restenosis must be well balanced to avoid intracranial hemorrhage. We investigated the safety and 90-day outcome of patients receiving TL treatment under triple-APT, focused on stent-patency and possible disadvantageous comorbidities. METHODS: Patients receiving TL treatment in the setting of acute stroke between 2013 and 2022 were analyzed regarding peri-/postprocedural safety and stent patency after 90 days. All patients received intravenous eptifibatide and acetylsalicylic acid and one of the three drugs prasugrel, clopidogrel, or ticagrelor. Duplex imaging was performed 24 h after treatment, at discharge and 90 days, and digital subtraction angiography was performed if restenosis was suspected. RESULTS: 176 patients were included. Periprocedural complications occurred in 2.3% of the patients at no periprocedural death, and in-hospital death in 13.6%. Discharge mRS score was maintained or improved at the 90-day follow-up in 86%, 4.54% had an in-stent restenosis requiring treatment at 90 days. No recorded comorbidity considered disadvantageous for stent patency showed statistical significance, the duration of the endovascular procedure had no significant effect on outcome. CONCLUSION: In our data, TL treatment with triple APT resulted in a low restenosis rate, low rates of sICH and a comparably high number of patients with favorable outcome. Aggressive APT in the initial phase may therefore have the potential to prevent recurrent stroke better than restrained platelet inhibition. Comorbidities did not influence stent patency.

Drug-Coated Balloons for Treatment of Internal Carotid Artery Restenosis After Stenting: A Single-Center Mid-Term Outcome Study.

PURPOSE: Endovascular and surgical treatments of stenosis of the extracranial internal carotid artery (ICA) are common procedures, yet both introduce a risk of restenosis due to endothelial hyperplasia. Drug-coated balloons (DCBs) are designed to decrease neointimal hyperplasia, however rarely used in the neurovascular setting. This study retrospectively analyzes mid-term results of DCB-treated in-stent restenosis (ISR) of the ICA. MATERIALS AND METHODS: The medical history, comorbidities, and periprocedural data of patients receiving DCB treatment for > 50% ISR of the ICA after carotid artery stenting were analyzed. Follow-up after DCB treatment was performed with Doppler ultrasound. Suspicious cases were checked with CT- or MR-angiography and-if there was agreement between the modalities-validated with digital subtraction angiography. Potential risk factors for restenosis and differences in outcomes after PTA with three types of DCB balloons were evaluated. RESULTS: DCB treatment was performed in 109 cases, 0.9% of which involved in-hospital major stroke; no minor strokes occurred. A total of 17 patients (15.6%) had recurrent ISR after DCB treatment, after a mean time of 30.2 months (7-85 months). Tobacco use was significantly associated with a higher incidence of recurrent ISR. CONCLUSION: DCB angioplasty for ISR is an effective treatment that may delay and decrease restenosis. Treating comorbidities and adopting lifestyle changes may additionally help prevent ISR.

Long-Term Effect of Mechanical Thrombectomy in Stroke Patients According to Advanced Imaging Characteristics.

PURPOSE: Data on long-term effect of mechanical thrombectomy (MT) in patients with large ischemic cores (≥ 70 ml) are scarce. Our study aimed to assess the long-term outcomes in MT-patients according to baseline advanced imaging parameters. METHODS: We performed a single-centre retrospective cohort study of stroke patients receiving MT between January 1, 2010 and December 31, 2018. We assessed baseline imaging to determine core and mismatch volumes and hypoperfusion intensity ratio (with low ratio reflecting good collateral status) using RAPID automated post-processing software. Main outcomes were cross-sectional long-term mortality, functional outcome and quality of life by May 2020. Analysis were stratified by the final reperfusion status. RESULTS: In total 519 patients were included of whom 288 (55.5%) have deceased at follow-up (median follow-up time 28 months, interquartile range 1-55). Successful reperfusion was associated with lower long-term mortality in patients with ischemic core volumes ≥ 70 ml (adjusted hazard ratio (aHR) 0.20; 95% confidence interval (95% CI) 0.10-0.44) and ≥ 100 ml (aHR 0.26; 95% CI 0.08-0.87). The effect of successful reperfusion on long-term mortality was significant only in the presence of relevant mismatch (aHR 0.17; 95% CI 0.01-0.44). Increasing reperfusion grade was associated with a higher rate of favorable outcomes (mRS 0-3) also in patients with ischemic core volume ≥ 70 ml (aOR 3.58, 95% CI 1.64-7.83). CONCLUSION: Our study demonstrated a sustainable benefit of better reperfusion status in patients with large ischemic core volumes. Our results suggest that patient deselection based on large ischemic cores alone is not advisable.

Transient ischemic attacks in patients with active and occult cancer.

Background and aim: Paraneoplastic coagulopathy can present as stroke and is associated with specific biomarker changes. Identifying paraneoplastic coagulopathy can help guide secondary prevention in stroke patients, and early cancer detection might improve outcomes. However, unlike ischemic stroke, it remains unclear whether paraneoplastic coagulopathy is associated with transient ischemic attacks (TIA). This study assessed the presence of cancer-related biomarkers in TIA patients and evaluated long-term mortality rates in patients with and without active cancer. Methods: Active cancer was retrospectively identified in consecutive TIA patients treated at a comprehensive stroke center between 2015 and 2019. An association between the presence of cancer and cancer-related biomarkers was assessed using multivariable logistic regression. Long-term mortality after TIA was analyzed using multivariable Cox regression. Results: Among 1436 TIA patients, 72 had active cancer (5%), of which 17 were occult (1.2%). Cancer-related TIA was associated with male gender (adjusted odds ratio [aOR] 2.29, 95% CI 1.12-4.68), history of smoking (aOR 2.77, 95% CI 1.34-5.7), elevated D-dimer (aOR 1.77, 95% CI 1.26-2.49), lactate dehydrogenase (aOR 1.003, 95% CI 1.00-1.005), lower leukocyte count (aOR 1.20, 95% CI 1.04-1.38), and lower hemoglobin (aOR 1.02, 95% CI 1.00-1.04). Long-term mortality was associated with both active cancer (adjusted hazard ratios [aHR] 2.47, 95% CI 1.58-3.88) and occult cancer (aHR 3.08, 95% CI 1.30-7.32). Conclusion: Cancer-related TIA is not uncommon. Biomarkers known to be associated with cancer-related stroke also seem to be present in TIA patients. Early identification would enable targeted treatment strategies and could improve outcomes in this patient population.

Management of covert brain infarction survey: A call to care for and trial this neglected population.

BACKGROUND: Covert brain infarction (CBI) is highly prevalent and linked with stroke risk factors, increased mortality, and morbidity. Evidence to guide management is sparse. We sought to gain information on current practice and attitudes toward CBI and to compare differences in management according to CBI phenotype. METHODS: We conducted a web-based, structured, international survey from November 2021 to February 2022 among neurologists and neuroradiologists. The survey captured respondents' baseline characteristics, general approach toward CBI and included two case scenarios designed to evaluate management decisions taken upon incidental detection of an embolic-phenotype and a small-vessel-disease phenotype. RESULTS: Of 627 respondents (38% vascular neurologists, 24% general neurologists, and 26% neuroradiologists), 362 (58%) had a partial, and 305 (49%) a complete response. Most respondents were university hospital senior faculty members experienced in stroke, mostly from Europe and Asia. Only 66 (18%) of respondents had established institutional written protocols to manage CBI. The majority indicated that they were uncertain regarding useful investigations and further management of CBI patients (median 67 on a slider 0-100, 95% CI 35-81). Almost all respondents (97%) indicated that they would assess vascular risk factors. Although most would investigate and treat similarly to ischemic stroke for both phenotypes, including initiating antithrombotic treatment, there was considerable diagnostic and therapeutic heterogeneity. Less than half of respondents (42%) would assess cognitive function or depression. CONCLUSIONS: There is a high degree of uncertainty and heterogeneity regarding management of two common types of CBI, even among experienced stroke physicians. Respondents were more proactive regarding the diagnostic and therapeutic management than the minimum recommended by current expert opinions. More data are required to guide management of CBI; meantime, more consistent approaches to identification and consistent application of current knowledge, that also consider cognition and mood, would be promising first steps to improve consistency of care.

Absence of susceptibility vessel sign and hyperdense vessel sign in patients with cancer-related stroke.

Background and aim: Identification of paraneoplastic hypercoagulability in stroke patients helps to guide investigations and prevent stroke recurrence. A previous study demonstrated an association between the absence of the susceptibility vessel sign (SVS) on brain MRI and active cancer in patients treated with mechanical thrombectomy. The present study aimed to confirm this finding and assess an association between the absence of the hyperdense vessel sign (HVS) on head CT and active cancer in all stroke patients. Methods: SVS and HVS status on baseline imaging were retrospectively assessed in all consecutive stroke patients treated at a comprehensive stroke center between 2015 and 2020. Active cancer, known at the time of stroke or diagnosed within 1 year after stroke (occult cancer), was identified. Adjusted odds ratios (aOR) and their 95% confidence interval (CI) for the association between the thrombus imaging characteristics and cancer were calculated using multivariable logistic regression. Results: Of the 2,256 patients with thrombus imaging characteristics available at baseline, 161 had an active cancer (7.1%), of which 36 were occult at the time of index stroke (1.6% of the total). The absence of SVS was associated with active cancer (aOR 3.14, 95% CI 1.45-6.80). No significance was reached for the subgroup of occult cancer (aOR 3.20, 95% CI 0.73-13.94). No association was found between the absence of HVS and active cancer (aOR 1.07, 95% CI 0.54-2.11). Conclusion: The absence of SVS but not HVS could help to identify paraneoplastic hypercoagulability in stroke patients with active cancer and guide patient care.

Absence of Susceptibility Vessel Sign in Patients With Malignancy-Related Acute Ischemic Stroke Treated With Mechanical Thrombectomy.

Background and Purpose: Clots rich in platelets and fibrin retrieved from patients with acute ischemic stroke (AIS) have been shown to be independently associated with the absence of the susceptibility vessel sign (SVS) on MRI and active malignancy. This study analyzed the association of SVS and the presence of active malignancy in patients with AIS who underwent mechanical thrombectomy (MT). Methods: This single-center, retrospective, and cross-sectional study included consecutive patients with AIS with admission MRI treated with MT between January 2010 and December 2018. SVS status was evaluated on susceptibility-weighted imaging. Adjusted odds ratios (aORs) were calculated to determine the association between absent SVS and the presence of active or occult malignancy. The performance of predictive models incorporating and excluding SVS status was compared using areas under the receiver operating characteristics curve (auROC). Results: Of 577 patients with AIS with assessable SVS status, 40 (6.9%) had a documented active malignancy and 72 (12.5%) showed no SVS. The absence of SVS was associated with active malignancy (aOR 4.85, 95% CI 1.94-12.11) or occult malignancy (aOR 11.42, 95% CI 2.36-55.20). The auROC of predictive models, including demographics and common malignancy biomarkers, was higher but not significant (0.85 vs. 0.81, p = 0.07) when SVS status was included. Conclusion: Absence of SVS on admission MRI of patients with AIS undergoing MT is associated with malignancy, regardless of whether known or occult. Therefore, the SVS might be helpful in detecting paraneoplastic coagulation disorders and occult malignancy in patients with AIS.

Endovascular Treatment of Intracranial Vein and Venous Sinus Thrombosis-A Systematic Review.

BACKGROUND: Cerebral venous sinus or vein thromboses (SVT) are treated with heparin followed by oral anticoagulation. Even after receiving the best medical treatment, numerous patients experience neurological deterioration, intracerebral hemorrhage or brain edema. Debate regarding whether endovascular treatment (EVT) is beneficial in such severe cases remains ongoing. This systematic review summarizes the current evidence supporting the use of EVT for SVT on the basis of case presentations, with a focus on patient selection, treatment strategies and the effects of the COVID-19 pandemic. METHODS: This systemic literature review included randomized controlled trials (RCTs) and retrospective observational data analyzing five or more patients. Follow-up information (modified Rankin scale (mRS)) was required to be provided (individual patient data). RESULTS: 21 records (n = 405 patients; 1 RCT, 20 observational studies) were identified. EVT was found to be feasible and safe in a highly selected patient cohort but was not associated with an increase in good functional outcomes (mRS 0-2) in RCT data. In observational data, good functional outcomes were frequently observed despite an anticipated poor prognosis. CONCLUSION: The current evidence does not support the routine incorporation of EVT in SVT treatment. However, in a patient cohort prone to poor prognosis, EVT might be a reasonable therapeutic option. Further studies determining the patients at risk, choice of methods and devices, and timing of treatment initiation are warranted.

Development of a Score for Prediction of Occult Malignancy in Stroke Patients (Occult-5 Score).

BACKGROUND AND PURPOSE: Malignancy associated acute ischemic stroke (AIS) requires specific diagnostic work-up, treatment and prevention to improve outcome. This study aimed to develop a biomarker-based score for prediction of occult malignancy in AIS patients. METHODS: Single-center cross-sectional study including consecutive AIS patients treated between July 2017 and November 2018. Patients with active malignancy at presentation, or diagnosed within 1 year thereafter and patients free of malignancy, were included and malignancy associated biomarkers were assessed. LASSO analyses of logistic regression were performed to determine biomarkers predictive of active malignancy. Predictors were derived from a predictive model for active malignancy. A comparison between known and unknown (=occult) malignancies when the index stroke occurred was used to eliminate variables not associated with occult malignancy. A predictive score (OCCULT-5 score) for occult malignancy was developed based on the remaining variables. RESULTS: From 1001 AIS patients, 61 (6%) presented an active malignancy. Thirty-nine (64%) were known and 22 (36%) occult. Five variables were included in the final OCCULT-5 score: age ≥ 77 years, embolic stroke of undetermined source, multi-territorial infarcts, D-dimer levels ≥ 820 µ/gL, and female sex. A score of ≥ 3 predicted an underlying occult malignancy with a sensitivity of 64%, specificity of 73%, positive likelihood ratio of 2.35 and a negative likelihood ratio of 0.50. CONCLUSIONS: The OCCULT-5 score might be useful to identify patients with occult malignancy. It may thus contribute to a more effective and timely treatment and thus lead to a positive impact on overall outcome.

Seasonal patterns and associations in the incidence of acute ischemic stroke requiring mechanical thrombectomy.

BACKGROUND: In order to identify risk periods with an increased demand in technical and human resources, we tried to determine patterns and associations in the incidence of acute ischemic stroke due to embolic large vessel occlusions (eLVO) requiring mechanical thrombectomy (MT). METHODS: We conducted a time series analysis over a 9-year period (2010-2018) based on observational data in order to detect seasonal patterns in the incidence of MT due to eLVO (n = 2628 patients). In a series of sequential negative binominal regression models, we aimed to detect further associations (e.g., temperature, atmospheric pressure, air pollution). RESULTS: There was a 6-month seasonal pattern in the incidence of MT due to eLVO (p = 0.024) peaking in March and September. Colder overall temperature was associated with an increase in MT due to eLVO (average marginal effect [AME], [95% CI]: -0.15 [-0.30-0.0001]; p = 0.05; per °C). A current increase in the average monthly temperature was associated with a higher incidence of MT due to eLVO (0.34 [0.11-0.56]; p = 0.003). Atmospheric pressure was positively correlated with MT due to eLVO (0.38 [0.13-0.64]; p = 0.003; per hectopascal [hPa]). We could detect no causal correlation between air pollutants and MT due to eLVO. CONCLUSIONS: Our data suggest a 6-month seasonal pattern in the incidence of MT due to eLVO peaking in spring and early autumn. This might be attributed to two different factors: (1) a current temperature rise (comparing the average monthly temperature in consecutive months) and (2) colder overall temperature. These results could help to identify risk periods requiring an adaptation in local infrastructure.

Functional Outcome and Safety of Intracranial Thrombectomy After Emergent Extracranial Stenting in Acute Ischemic Stroke Due to Tandem Occlusions.

Background and Purpose: Various endovascular approaches to treat acute ischemic stroke caused by extra- intracranial tandem occlusions (TO) exist: percutaneous transluminal angioplasty with or without emergent extracranial carotid stenting (ECS) due to high-grade stenosis preceded or followed by intracranial mechanical and/or aspiration thrombectomy (MT). Which treatment strategy to use is still a matter of debate. Methods: From our ongoing prospective stroke registry we retrospectively analyzed 1,071 patients with anterior circulation stroke getting endovascular treatment within 6 h of symptom onset. ECS prior to intracranial MT for TO (n = 222) was compared to MT as standard of care (control group; acute intracranial vessel occlusion without concomitant ipsilateral ICA-occlusion or high-grade stenosis [C; n = 849]). Good functional outcome (mRS ≤ 2 at 3 months), mortality rates, frequencies of symptomatic intracranial hemorrhage (sICH) and successful recanalization (Thrombolysis in Cerebral Infarction Score [TICI] 2b or 3) were assessed. In subgroup analyses we tried to detect possible influences of stroke etiology, dual inhibition of platelet aggregation (IPA; clopidogrel [CLO]: n = 83; ticagrelor [TIC]: n = 137; in combination with Aspirin) and intravenous thrombolysis (IVT). Results: Functional outcome was superior in TO (mRS 0-2: 44.6%) when compared with controls (36.0%; OR [95% CI]: 3.49 [1.59-7.67]; p = 0.002). There was no difference in all-cause mortality at 3 months (TO: 21.6%; C: 27.7%; 0.78 [0.47-1.29]; p = 0.324), in-hospital mortality (0.76 [0.45-1.30]; p = 0.324), sICH (TO: 3.2%; C: 5.0%; 0.70 [0.30-1.59]; p = 0.389), and TICI 2b/3 (TO: 89.1%; C: 88.3%; p = 0.813). In subgroup-analysis, TIC and CLO did not differ in functional outcome (TIC: 45.3%; CLO: 44.6%; 1.04 [0.51-2.09]; p = 0.920) and mortality rates (all-cause mortality: TIC: 23.4%; CLO: 16.9%; 0.75 [0.27-2.13]; p = 0.594). sICH was more frequent in TIC (n = 7 [5.1%]) vs. CLO (n = 0; p = 0.048). Conclusion: In our pre-selected cohort, ECS prior to intracranial MT in TO allowed for a good functional outcome that was superior compared to a control population. Mortality rates did not differ. Despite a dual IPA in TO, there was no increase in sICH. CLO and TIC for dual IPA did not differ in terms out outcome and mortality rates. A significant increase in sICH was observed after initial loading with TIC.

Hyperintense Vessels, Collateralization, and Functional Outcome in Patients With Stroke Receiving Endovascular Treatment.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery hyperintense vessels (FHV) are frequently observed on magnetic resonance imaging in acute stroke patients with proximal vessel occlusion. Whether FHV can serve as a surrogate for the collateral status and predict functional outcome of patients is still a matter of debate. METHODS: Acute ischemic stroke patients with M1-middle cerebral artery occlusion who received magnetic resonance imaging before endovascular treatment in 3 hospitals in Germany between January 2007 and June 2016 were eligible. Quantification of FHV was performed using an FHV-Alberta Stroke Program Early CT Score (ASPECTS) rating system. Functional outcome was evaluated with the modified Rankin Scale 3 months after stroke. Collateral status of patients was graded on baseline angiography using the American Society of Interventional and Therapeutic Neuroradiology grading system. Odds for good outcome (modified Rankin Scale score, 0-2) were determined using logistic regression analyses. RESULTS: Overall, 116 patients were analyzed (median age, 74; interquartile range [IQR], 64-79; median National Institutes of Health Stroke Scale, 14; IQR, 10-19). The median FHV-ASPECTS was 2 (IQR, 1-3). Good collateral status (American Society of Interventional and Therapeutic Neuroradiology grade 3-4) on angiography was more frequently observed in patients with FHV-ASPECTS ≤2 (83% versus 57%; P=0.025). Patients with an FHV-ASPECTS ≤2 had a better functional outcome after 3 months (median modified Rankin Scale score, 2; IQR, 0-5), compared with patients with an FHV-ASPECTS >2 (median modified Rankin Scale score, 4; IQR, 3-6; P=0.015). In multiple regression analyses, FHV-ASPECTS ≤2 was independently associated with good functional outcome (adjusted odds ratio, 5.3; 95% confidence interval, 1.5-18.2). CONCLUSIONS: Low FHV-ASPECTS is associated with both better collateral status and better 3-month functional outcome in acute stroke patients with M1 vessel occlusion.

Endovascular Thrombectomy in Acute Ischemic Stroke: Outcome in Referred Versus Directly Admitted Patients.

PURPOSE: Endovascular mechanical thrombectomy (mTE) in acute ischemic stroke due to large cerebral artery occlusion is effective and safe. The procedure is currently offered by specialized hospitals. Physicians from smaller hospitals need to refer patients to stroke centers. Secondary referrals involve delays for transportation. Little is known about effects of distant referrals on outcome and complications as compared to direct admittance. METHODS: To evaluate the effects of referral patterns on outcome and safety, we analyzed 941 patients with anterior circulation stroke receiving mTE between January 2010 and December 2015. Patients were divided into three groups: directly admitted patients (DAP), inner-city transfers (ICT) and long-distance referrals (LDR). We assessed (1) procedural parameters (2) frequency of good functional outcome (mRS ≤2 at 3 months) and (3) mortality rates. RESULTS: Referrals had a significantly longer imaging-to-groin time compared to DAP (median 150 min vs. 85 min, p <0.001), the same was true for LDR vs. ICT (median 157 min vs. 133.5 min, p <0.001). Time to recanalization was significantly longer for referrals compared to DAP (median 348 min vs. 260 min, p <0.001). There was no significant difference in the frequency of good functional outcome (DAP 39.5%, ICT 35.1%, LDR 37.0%; p =0.709), all-cause mortality at day 90 (DAP 31.5%, ICT 23.0%, LDR 27.0%; p =0.212) and the rate of symptomatic intracranial hemorrhage (p =0.834). CONCLUSION: Timing remains a critical factor in acute ischemic stroke treatment by endovascular means. Long distance referral to specialized neurovascular centers with high recanalization rates, however, does allow for a good functional outcome in a significant number of patients.

Mechanical Thrombectomy for M2 Occlusions: A Single-Centre Experience.

BACKGROUND: The recent success of several mechanical thrombectomy trials has resulted in a significant change in the management of patients presenting with stroke. However, questions still remain as to whether certain groups will benefit from mechanical thrombectomy. In particular, it is still uncertain whether mechanical thrombectomy should be performed in the M2 branches and, more generally, in the distal vasculature. METHODS: We retrospectively analysed our prospectively maintained database of all patients undergoing mechanical thrombectomy between January 2008 and August 2016. We collected demographic, radiological, procedural and outcome data. RESULTS: We identified 106 patients that met our inclusion criteria. The mean age of the patients was 68 ± 13.8 years, and there were 58 (54.7%) male patients. Associated medical conditions were common with hypertension seen in 71% of the patients. The average Alberta Stroke Program Early CT (ASPECT) score on admission was 8.5 ± 1.7. The mean National Institutes of Health Stroke Scale score was 11.8 ± 7.02. The mean duration of the procedure was 103 ± 3.4 min, and the average number of thrombectomy attempts required was 1.8 (range 1-8). Angiographically, Thrombolysis in Cerebral Infarction Scale (TICI) ≥2b was obtained in 90.5% of the patients. Five patients (4.7%) had symptomatic intracranial haemorrhage on follow-up. At 90-day follow-up, 54.6% of the patients had a modified Rankin Scale (mRS) score 0-2, and 71.5% had an mRS score ≤3. There were 15 deaths at 90 days (14.1%). CONCLUSION: Mechanical thrombectomy in patients with solitary M2 clots is technically possible and carries a high degree of success with a good safety profile. Patients with confirmed M2 occlusion should be considered for mechanical thrombectomy.

A Comparison of Mechanical Thrombectomy in the M1 and M2 Segments of the Middle Cerebral Artery: A Review of 585 Consecutive Patients.

BACKGROUND: Mechanical thrombectomy for anterior-circulation large-vessel occlusion has shown benefit; however, the question of whether this technique is safe and effective in the distal vasculature remains unanswered. We sought to compare the outcome data from mechanical thrombectomy of the M2 branches of the middle cerebral artery (MCA) with those of the M1 segment. METHODS: We performed a retrospective analysis of prospectively collected data of patients with acute ischaemic stroke undergoing mechanical thrombectomy of isolated M1 or M2 branches of the MCA between August 2008 and August 2016. RESULTS: We identified 585 patients, 479 with M1 occlusions and 106 with M2 occlusions. The average age was 72 ± 12.8 and 68 ± 13.8 years, respectively (p = 0.007). The baseline Alberta Stroke Program Early Computed Tomographic (ASPECT) score was similar in both cohorts, but patients with M1 occlusions presented with higher mean National Institutes of Health Stroke Scale (NIHSS) scores of 15.7 compared to 11.8 (p < 0.001). There was no significant difference in the average procedure time for each cohort; fewer thrombectomy attempts were required in the M2 cohort (2.3 vs. 1.8, p = 0.0004), but the overall time to recanalization was longer in the M2 cohort (353 vs. 399 min, p < 0.001). Similar rates of successful reperfusion (Thrombolysis in Ischaemic Stroke score [TICI] ≥2b 88.5 vs. 90.5%, p = 0.612) were seen, but food outcome (modified Rankin Scale ≤2) was lower in M1 occlusions (37.2 vs. 54.3%, p < 0.001). Rates of symptomatic intracranial haemorrhage were similar. CONCLUSION: Good clinical outcomes can be achieved for both groups with no significant differences in procedure length, final TICI recanalization rates or intracranial haemorrhage between the M1 and M2 cohorts.

Increased number of regulatory T cells (T-regs) in the peripheral blood of patients with Her-2/neu-positive early breast cancer.

BACKGROUND: Although progress has been made in establishing prognostic factors in breast cancer, there remains an urgent need for better prognostic and predictive scores for patients with early breast cancer. The important role of the immune system in controlling cancer progression is widely accepted. Regulatory T cells (T-regs) constitute a specialized T cell subset, which play an essential role in sustaining self-tolerance by negatively regulating immune responses. Increased frequencies of T-regs have been reported in the micromilieu of a variety of malignancies including breast cancer. However, little is known about the role of T-regs in the peripheral blood of cancer patients. METHODS: We analyzed T-reg numbers in the peripheral blood of 292 patients with newly diagnosed early breast cancer by flow cytometry (CD4(+)CD25(+)CD127(low) cells) prior to planned breast surgery. RESULTS: Absolute T-reg numbers/µl varied from 4 to 212/µl. No difference could be detected in T-reg numbers between nodal negative and nodal positive, well and poorly differentiated or small and locally advanced cancers. However, T-reg numbers of Her-2/neu-positive patients were higher than in samples from patients with hormone receptor positive, Her-2/neu-negative cancers. In contrast, numbers of T-regs were not increased in triple negative patients. In addition, T-reg numbers were higher in patients with invasive ductal carcinomas as compared to invasive lobular cancers. CONCLUSIONS: Increased numbers of circulating T-regs may contribute to the higher metastatic potential of Her-2/neu-positive cells. A potential role as a prognostic or predictive parameter is currently being analyzed in a larger cohort of patients with sufficient follow-up.

Multiple system atrophy: an update.

Multiple system atrophy (MSA) is a sporadic and rapidly progressive neurodegenerative disorder that presents with autonomic failure in combination with parkinsonism or cerebellar ataxia. Over the past 5 years, substantial progress has been achieved in understanding the pathogenesis of the disease. Important insights into the epidemiology and genetics of MSA have confirmed the key pathogenic role of alpha-synuclein. Advances in the early recognition of this disease have resulted in revised diagnostic criteria, including, for the first time, neuroimaging indices. Finally, novel therapeutic options targeting disease modification have been investigated in clinical trials. These include riluzole, recombinant human growth hormone, and minocycline. Although the trials did not find any positive effects on disease progression, they generated important trial expertise in MSA and were only possible because of the establishment of international networks.