A Comparative Study of Hemorrhagic Conversion Patterns After Stroke Thrombolysis With Alteplase Versus Tenecteplase.

BACKGROUND AND PURPOSE: Tenecteplase is the thrombolytic drug of choice for acute ischemic stroke (AIS) as it has unique pharmacologic properties, along with results demonstrating its non-inferiority compared to alteplase. However, there are contradictory data concerning the risk of intracranial hemorrhage. The purpose of the study was to report the rate and patterns of symptomatic intracranial hemorrhage (sICH) in AIS patients after thrombolysis with tenecteplase compared to alteplase. METHODS: This is a retrospective cohort study with data collected 90 days before and after the change from alteplase to tenecteplase from 15 Texas stroke centers. The primary endpoint is the incidence of sICH according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) and European Cooperative Acute Stroke Study III (ECASS-3) criteria. The secondary endpoints are the radiographic pattern of hemorrhagic conversion according to the Heidelberg bleeding classification (HBC). RESULTS: A total of 431 patients were eligible for thrombolytic therapy. Half of the cohort received alteplase (n=216), and the other half received tenecteplase (n=215). The average age of the alteplase group was 62.94 years old (SD=15.12) and 64.45 years old (SD=14.51) for the tenecteplase group. Seven patients in the alteplase group (3.2%) and 14 (6.5%) in the tenecteplase group had sICH, with an odds ratio of 1.44 (95% CI 0.60-3.43; P=0.41). An increased National Institutes of Health Stroke Scale (NIHSS) score on arrival (1.06; 95% CI 1.0004-1.131; P=0.04) was a statistically significant predictor of sICH. Tenecteplase was associated with a statistically significant increase in HBC-3 (P=0.040) over alteplase. CONCLUSIONS: Compared with alteplase, our study revealed a higher rate of sICH with tenecteplase that was not statistically significant and a higher rate of HBC-3 hemorrhages that was statistically significant. The proposed mechanism of bleeding is hemorrhagic conversion in clinically silent infarcts and contusions underlying the lesions. Further studies are needed to confirm our findings and determine predictive risk factors.

Viz LVO versus Rapid LVO in detection of large vessel occlusion on CT angiography for acute stroke.

BACKGROUND: Endovascular thrombectomy improves outcomes and reduces mortality for large vessel occlusion (LVO) and is time-sensitive. Computer automation may aid in the early detection of LVOs, but false values may lead to alarm desensitization. We compared Viz LVO and Rapid LVO for automated LVO detection. METHODS: Data were retrospectively extracted from Rapid LVO and Viz LVO running concurrently from January 2022 to January 2023 on CT angiography (CTA) images compared with a radiologist interpretation. We calculated diagnostic accuracy measures and performed a McNemar test to look for a difference between the algorithms' errors. We collected demographic data, comorbidities, ejection fraction (EF), and imaging features and performed a multiple logistic regression to determine if any of these variables predicted the incorrect classification of LVO on CTA. RESULTS: 360 participants were included, with 47 large vessel occlusions. Viz LVO and Rapid LVO had a specificity of 0.96 and 0.85, a sensitivity of 0.87 and 0.87, a positive predictive value of 0.75 and 0.46, and a negative predictive value of 0.98 and 0.97, respectively. A McNemar test on correct and incorrect classifications showed a statistically significant difference between the two algorithms' errors (P=0.00000031). A multiple logistic regression showed that low EF (Viz P=0.00125, Rapid P=0.0286) and Modified Woodcock Score >1 (Viz P=0.000198, Rapid P=0.000000975) were significant predictors of incorrect classification. CONCLUSION: Rapid LVO produced a significantly larger number of false positive values that may contribute to alarm desensitization, leading to missed alarms or delayed responses. EF and intracranial atherosclerosis were significant predictors of incorrect predictions.

A Rare Case of Cerebral Vasospasm Secondary to Primary Intraventricular Hemorrhage With an Immediate Improvement in Neurological Status Following Intra-arterial Therapy.

Symptomatic vasospasm following aneurysmal subarachnoid hemorrhage (SAH) occurs in roughly 30% of cases. However, vasospasm after primary intraventricular hemorrhage (IVH) is rare and described in only a handful of case reports and small retrospective studies. We present a patient with primary IVH. A conventional cerebral angiogram ruled out vascular anomalies but demonstrated severe diffuse cerebral vasospasm. The patient was treated with intra-arterial vasodilators, resulting in an immediate and profound improvement in the patient's neurological examination. Several days later, the patient had another decline in neurological status that immediately resolved after treatment with intra-arterial therapy. To our knowledge, this is the first reported case of a profound and immediate improvement in neurological examination following intra-arterial vasodilator administration.

Integrated Stroke System Model Expands Availability of Endovascular Therapy While Maintaining Quality Outcomes.

BACKGROUND AND PURPOSE: The optimal endovascular stroke therapy (EVT) care delivery structure is unknown. Here, we present our experience in creating an integrated stroke system (ISS) to expand EVT availability throughout our region while maintaining hospital and physician quality standards. METHODS: We identified all consecutive patients with large vessel occlusion acute ischemic stroke treated with EVT from January 2014 to February 2019 in our health care system. In October 2017, we implemented the ISS, in which 3 additional hospitals (4 total) became EVT-performing hospitals (EPHs) and physicians were rotated between all centers. The cohort was divided by time into pre-ISS and post-ISS, and the primary outcome was time from stroke onset to EPH arrival. Secondary outcomes included hospital and procedural quality metrics. We performed an external validation using data from the Southeast Texas Regional Advisory Council. RESULTS: Among 513 patients with large vessel occlusion acute ischemic stroke treated with EVT, 58% were treated pre-ISS and 43% post-ISS. Over the study period, EVT procedural volume increased overall but remained relatively low at the 3 new EPHs (<70 EVT/y). After ISS, the proportion of patients who underwent interhospital transfer decreased (46% versus 37%; P<0.05). In adjusted quantile regression, ISS implementation resulted in a reduction of time from stroke onset to EPH arrival by 40 minutes (P<0.01) and onset to groin puncture by 29 minutes (P<0.05). Rates of postprocedural hemorrhage, modified Thrombolysis in Cerebral Infarction (TICI) 2b/3, and 90-day modified Rankin Scale were comparable at the higher and lower volume EPHs. The improvement in onset-to-arrival time was not reflective of overall improvement in secular trends in regional prehospital care. CONCLUSIONS: In our system, increasing EVT availability decreased time from stroke onset to EPH arrival. The ISS provides a framework to maintain quality in lower volume hospitals.

IAT-TiMeS: Intra-Arterial Thrombectomy Transfer Metric Study in Texas.

OBJECTIVE: We aim to report intra-arterial thrombectomy transfer metrics for ischemic stroke patients that were transferred to hub hospitals for possible intra-arterial thrombectomy in multiple geographic regions throughout the state of Texas and to identify potential barriers and delays in the intra-arterial thrombectomy transfer process. METHOD: We prospectively collected data from 8 participating Texas comprehensive stroke/thrombectomy capable centers from 7 major regions in the State of Texas. We collected baseline clinical and imaging data related to the pre-transfer evaluation, transfer metrics, and post-transfer clinical and imaging data. RESULTS: A total of 103 acute ischemic stroke patients suspected/confirmed to have large vessel occlusions between December 2016 to May 2019 that were transferred to hubs as possible intra-arterial thrombectomy candidates were enrolled. A total of 56 (54%) patients were sent from the spoke to the hub via ground ambulance with 47 (46%) patients traveling via air ambulance. The median spoke arrival to hub arrival time was 174 min, median spoke arrival to departure from spoke was 131 min, and median travel time was 39 min. The spoke arrival time to transfer initiation was 68 min. CT-perfusion obtained at the spoke and earlier initiation of transfer were statistically associated with shorter transfer times. CONCLUSION: Transfer of intra-arterial thrombectomy patients in Texas may take over 4 h from spoke arrival to hub arrival. This time may be shortened by earlier transfer initiation and acceptance.

Angiographic And Clinical Response Of Intracranial Atherosclerotic Disease Large Vessel Occlusion Stroke Undergoing Mechanical Thrombectomy.

OBJECTIVES: To identify whether intracranial atherosclerotic disease large vessel occlusion strokes differ compared to embolic large vessel occlusion strokes in angiographic response to mechanical thrombectomy and clinical course. METHODS: Retrospective analysis of acute ischemic stroke patients with large vessel occlusion, due to intracranial atherosclerotic disease or embolic etiology, who underwent mechanical thrombectomy in a primary stroke center from 11/2015 to 4/2018. We categorized patients into intracranial atherosclerotic disease or embolic large vessel occlusion based on the procedural findings. We compared pretreatment, procedural variables, and post-procedural outcomes. RESULTS: Ninety-five patients were included, 13 with intracranial atherosclerotic disease large vessel occlusion strokes and 82 with embolic large vessel occlusion strokes. Between the two groups, there was no statistically significant difference in angiographic success (100% for intracranial atherosclerotic disease and 89% for embolic large vessel occlusion strokes); first pass success (38% for intracranial atherosclerotic disease and 34% for embolic large vessel occlusion strokes); puncture-to-first-pass time; puncture-to-recanalization time (68 minutes for intracranial atherosclerotic disease and 62 minutes for embolic large vessel occlusion strokes); number of passes; or clinical outcomes. Intracranial angioplasty was performed in 6 (46%) of intracranial atherosclerotic disease large vessel occlusion patients, and in 5 (6%) of embolic large vessel occlusion patients (p < 0.0001). CONCLUSIONS: Similar angiographic success and procedural time metrics are achievable with intracranial atherosclerotic disease large vessel occlusion and embolic large vessel occlusion therapy. This occurred with more frequent intracranial angioplasty for intracranial atherosclerotic disease large vessel occlusion strokes.

Impact of Initial Imaging Protocol on Likelihood of Endovascular Stroke Therapy.

BACKGROUND AND PURPOSE: Noncontrast head CT and CT perfusion (CTP) are both used to screen for endovascular stroke therapy (EST), but the impact of imaging strategy on likelihood of EST is undetermined. Here, we examine the influence of CTP utilization on likelihood of EST in patients with large vessel occlusion (LVO). METHODS: We identified patients with acute ischemic stroke at 4 comprehensive stroke centers. All 4 hospitals had 24/7 CTP and EST capability and were covered by a single physician group (Neurology, NeuroIntervention, NeuroICU). All centers performed noncontrast head CT and CT angiography in the initial evaluation. One center also performed CTP routinely with high CTP utilization (CTP-H), and the others performed CTP optionally with lower utilization (CTP-L). Primary outcome was likelihood of EST. Multivariable logistic regression was used to determine whether facility type (CTP-H versus CTP-L) was associated with EST adjusting for age, prestroke mRS, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, LVO location, time window, and intravenous tPA (tissue-type plasminogen activator). RESULTS: Among 3107 patients with acute ischemic stroke, 715 had LVO, of which 403 (56%) presented to CTP-H and 312 (44%) presented to CTP-L. CTP utilization among LVO patients was greater at CTP-H centers (72% versus 18%, CTP-H versus CTP-L, P<0.01). In univariable analysis, EST rates for patients with LVO were similar between CTP-H versus CTP-L (46% versus 49%). In multivariable analysis, patients with LVO were less likely to undergo EST at CTP-H (odds ratio, 0.59 [0.41-0.85]). This finding was maintained in multiple patient subsets including late time window, anterior circulation LVO, and direct presentation patients. Ninety-day functional independence (odds ratio, 1.04 [0.70-1.54]) was not different, nor were rates of post-EST PH-2 hemorrhage (1% versus 1%). CONCLUSIONS: We identified an increased likelihood for undergoing EST in centers with lower CTP utilization, which was not associated with worse clinical outcomes or increased hemorrhage. These findings suggest under-treatment bias with routine CTP.

Development and validation of an interpretable deep learning framework for Alzheimer's disease classification.

Alzheimer's disease is the primary cause of dementia worldwide, with an increasing morbidity burden that may outstrip diagnosis and management capacity as the population ages. Current methods integrate patient history, neuropsychological testing and MRI to identify likely cases, yet effective practices remain variably applied and lacking in sensitivity and specificity. Here we report an interpretable deep learning strategy that delineates unique Alzheimer's disease signatures from multimodal inputs of MRI, age, gender, and Mini-Mental State Examination score. Our framework linked a fully convolutional network, which constructs high resolution maps of disease probability from local brain structure to a multilayer perceptron and generates precise, intuitive visualization of individual Alzheimer's disease risk en route to accurate diagnosis. The model was trained using clinically diagnosed Alzheimer's disease and cognitively normal subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset (n = 417) and validated on three independent cohorts: the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) (n = 382), the Framingham Heart Study (n = 102), and the National Alzheimer's Coordinating Center (NACC) (n = 582). Performance of the model that used the multimodal inputs was consistent across datasets, with mean area under curve values of 0.996, 0.974, 0.876 and 0.954 for the ADNI study, AIBL, Framingham Heart Study and NACC datasets, respectively. Moreover, our approach exceeded the diagnostic performance of a multi-institutional team of practicing neurologists (n = 11), and high-risk cerebral regions predicted by the model closely tracked post-mortem histopathological findings. This framework provides a clinically adaptable strategy for using routinely available imaging techniques such as MRI to generate nuanced neuroimaging signatures for Alzheimer's disease diagnosis, as well as a generalizable approach for linking deep learning to pathophysiological processes in human disease.

A Phase 2 Randomized, Sham-Controlled Trial of Internal Carotid Artery Infusion of Autologous Bone Marrow-Derived ALD-401 Cells in Patients With Recent Stable Ischemic Stroke (RECOVER-Stroke).

BACKGROUND: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow-derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy. METHODS: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications. RESULTS: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, -0.3 to 0.8; P=0.330). There were no significant differences between the groups on any of the secondary efficacy measures. CONCLUSIONS: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01273337.

Internal Maxillary Artery Preoperative Embolization Using n-Butyl Cyanoacrylate and Pushable Coils for Temporomandibular Joint Ankylosis Surgery.

BACKGROUND: Temporomandibular joint (TMJ) ankylosis causes disability through impaired digestion, mastication, speech, and appearance. Surgical treatment increases range of motion with resultant functional improvement. However, substantial perioperative blood loss can occur (up to 3 L) if the internal maxillary artery (IMAX) is injured as it traverses the ankylotic mass. Achieving hemostasis is difficult because of limited proximal IMAX access and poor visualization. Our aim is to investigate the technical feasibility and preliminary safety of preoperative IMAX embolization in patients undergoing TMJ ankylosis surgery. METHODS: Case series using chart reviews of 2 patients who underwent preoperative embolization before TMJ ankylosis surgery. RESULTS: Both patients were women (28 and 51 years old) who had severely restricted mouth opening. Embolization was performed using general anesthesia with nasal intubation on the same day of TMJ surgery. Both patients underwent bilateral IMAX embolization using pushable coils (Vortex, Boston Scientific) of distal IMAX followed by n-butyl-cyanoacrylate (Trufill, Cordis) embolization from coil mass up to proximal IMAX. There were no complications from the embolization procedures. Both patients had normal neurologic examination results. TMJ surgery occurred with minimal operative blood loss (≤300 mL for each surgery). Maximum postoperative mouth opening was 35 mm and 34 mm, respectively. One patient had a postoperative TMJ wound infection that was managed with antibiotics. CONCLUSIONS: Preoperative IMAX embolization before TMJ ankylosis surgery is technically feasible with encouraging preliminary safety. There were no complications from the embolization procedures and surgeries occurred with low volumes of blood loss.

Arteriovenous Malformations in the Pediatric Population: Review of the Existing Literature.

Arteriovenous malformations (AVMs) in the pediatric population are relatively rare but reportedly carry a higher rate of rupture than in adults. This could be due to the fact that most pediatric AVMs are only detected after rupture. We aimed to review the current literature regarding the natural history and the clinical outcome after multimodality AVM treatment in the pediatric population, as optimal management for pediatric AVMs remains controversial. A multidisciplinary approach using multimodality therapy if needed has been proved to be beneficial in approaching these lesions in all age groups. Microsurgical resection remains the gold standard for the treatment of all accessible pediatric AVMs. Embolization and radiosurgery should be considered as an adjunctive therapy. Embolization provides a useful adjunct therapy to microsurgery by preventing significant blood loss and to radiosurgery by decreasing the volume of the AVM. Radiosurgery has been described to provide an alternative treatment approach in certain circumstances either as a primary or adjuvant therapy.

Neurointerventional Stenting and Antiplatelet Function Testing: To Do or Not to Do?

BACKGROUND AND PURPOSE: Platelet function testing in neurointerventional (NI) procedures is still controversial. We compared the clinical outcomes between antiplatelet responders and nonresponders based on the results of the VerifyNow (VN) testing method. METHODS: This is a retrospective single-center analysis of all consecutive patients who underwent NI stenting procedures from January 2007 through July 2013 and had documented preprocedural aspirin (ASA) and clopidogrel VN assays. Patients were divided into two groups based on their responsiveness to antiplatelet. Baseline characteristics, good functional outcome measured by the modified Rankin Scale (mRS) at 90 days, combined procedural complication rate defined as postprocedural stroke, in-stent thrombosis, and intraoperative rupture were compared between the two groups. RESULTS: Our cohort included 37 patients: 26 were in the responder group (RG) and 11 were in the nonresponder group (NRG). Baseline characteristics were similar between the two groups. Even though the combined complication rate was similar between the two groups [NRG: 2/11 (18%) vs. RG: 2/26 (7%); p = 0.33], there was a trend for a higher rate of good functional outcome (90-day mRS: 0-2) in the RG (22/22, 100%) as compared to the NRG (8/10, 80%) (p = 0.0907). CONCLUSION: Overall, utilizing the VN antiplatelet function testing did not significantly change the clinical outcome after the NI procedures. Larger randomized trials are warranted to provide a better understanding of the utility of the antiplatelet testing in NI stenting procedures.

Flow diverters for intracranial aneurysms.

Flow diverters (pipeline embolization device, Silk flow diverter, and Surpass flow diverter) have been developed to treat intracranial aneurysms. These endovascular devices are placed within the parent artery rather than the aneurysm sac. They take advantage of altering hemodynamics at the aneurysm/parent vessel interface, resulting in gradual thrombosis of the aneurysm occurring over time. Subsequent inflammatory response, healing, and endothelial growth shrink the aneurysm and reconstruct the parent artery lumen while preserving perforators and side branches in most cases. Flow diverters have already allowed treatment of previously untreatable wide neck and giant aneurysms. There are risks with flow diverters including in-stent thrombosis, perianeurysmal edema, distant and delayed hemorrhages, and perforator occlusions. Comparative efficacy and safety against other therapies are being studied in ongoing trials. Antiplatelet therapy is mandatory with flow diverters, which has highlighted the need for better evidence for monitoring and tailoring antiplatelet therapy. In this paper we review the devices, their uses, associated complications, evidence base, and ongoing studies.

Acute antithrombotic treatment of ischemic stroke.

Antithrombotic medication is a cornerstone of acute ischemic stroke treatment and secondary prevention. The efficacy of thrombolysis with alteplase in acute stroke has been demonstrated in several clinical trials. This safe and costeffective therapy has transformed the practice of stroke care and has led to subsequent trials of other antithrombotic medications for treatment of ischemic stroke in the acute phase. These antithrombotics include thrombolytic, antiplatelet and anticoagulant agents. While, no other medication has yet demonstrated adequate efficacy, our current and evolving understanding of infarct expansion, ischemic penumbra, collateral circulation and the blood brain barrier is allowing testing of antithrombotic medications tailored to individual patient pathophysiology in clinical trials. This understanding accompanies developments in neuroimaging and organization of stroke care that allow for wide-spread recruitment in these trials. Alteplase remains the mainstay treatment of arterial acute ischemic stroke; however, anticoagulation is the standard therapy for cerebral venous sinus thrombosis. Antithrombotic use in acute stroke, arterial and venous, has demonstrated efficacy but leaves many questions unanswered. This patient population is a fertile ground for novel research, especially as it relates to; combination antithrombotic therapy, combination of pharmacological and mechanical thrombolysis, and the transition to secondary prevention. Here we review the current antithrombotics in the acute phase of ischemic stroke highlighting the evidence-base and areas of uncertainty.

Clotting factors to treat thrombolysis-related symptomatic intracranial hemorrhage in acute ischemic stroke.

BACKGROUND: Symptomatic intracranial hemorrhage (sICH) occurs uncommonly after ischemic stroke therapy with tissue plasminogen activator (tPA). Clotting factor administration may be a treatment option. OBJECTIVE: To determine if treatment with clotting factors (fresh frozen plasma [FFP] or cryoprecipitate) was associated with improved outcomes in sICH. METHODS: We conducted a retrospective cohort study within University of Texas at Houston Stroke registry involving consecutive patients from February 1, 2007, to June 30, 2011, with tPA-related sICH, including cases with subsequent intra-arterial therapy. Outcomes were Modified Rankin Scale (mRS) score at discharge, death, and hematoma expansion. RESULTS: Of 921 patients treated with tPA, 48 (5.2%) had sICH and 45 met criteria for the study. Nineteen patients received clotting factors (42.2%; 18 received FFP and 7 received cryoprecipitate), whereas 26 (57.8%) patients received conservative management without clotting factors. None of the patients treated with clotting factors and only 2 of those who did not receive clotting factors had a good outcome, mRS score of 2 or less. All the patients treated with clotting factors and most of those not treated were left bedridden or dead (mRS score 4-6), 19 (100%) versus 22 (85%). Mortality was 9 (47.4%) versus 9 (34.6%), respectively. There was no difference in hematoma expansion between the 2 groups. CONCLUSIONS: We found no evidence that treatment for sICH with clotting factors has a favorable effect on clinical or radiological outcomes. However, the sample was small because of the low frequency of sICH. New treatments are urgently needed for this uncommon yet serious condition.