Progressive microvascular failure in acute ischemic stroke: A systematic review, meta-analysis, and time-course analysis.

This systematic review, meta-analysis, and novel time course analysis examines microvascular failure in the treatment of acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) and/or thrombolytic administration for stroke management. A systematic review and meta-analysis following PRIMSA-2020 guidelines was conducted along with a novel curve-of-best fit analysis to elucidate the time-course of microvascular failure. Scopus and PubMed were searched using relevant keywords to identify studies that examine recanalization and reperfusion assessment of AIS patients following large vessel occlusion. Meta-analysis was conducted using a random-effects model. Curve-of-best-fit analysis of microvascular failure rate was performed with a negative exponential model. Twenty-seven studies with 1151 patients were included. Fourteen studies evaluated patients within a standard stroke onset-to-treatment time window (≤6 hours after last known normal) and thirteen studies had an extended time window (>6 hours). Our analysis yields a 22% event rate of microvascular failure following successful recanalization (95% CI: 16-30%). A negative exponential curve modeled a microvascular failure rate asymptote of 28.5% for standard time window studies, with no convergence of the model for extended time window studies. Progressive microvascular failure is a phenomenon that is increasingly identified in clinical studies of AIS patients undergoing revascularization treatment.

Mechanical thrombectomy after acute ischemic stroke in patients with left ventricular assist devices: A nationwide analysis.

INTRODUCTION: Left ventricular assist devices (LVADs) are an established, durable, and life-saving treatment option for patients with advanced heart failure. However, large vessel occlusions (LVOs) remain one of its most devastating embolic complications. Mechanical thrombectomy (MT) is safe and effective in the management of LVOs in the general population, but LVO trials largely excluded patients on mechanical circulatory support, and large-scale analyses of outcomes following these interventions in the LVAD population are lacking. METHODS: Using the National Inpatient Sample, we identified all adult patients hospitalized with acute ischemic stroke (AIS) from 2005 to 2018. Regression models adjusting for patient demographics, hospital factors, and clinical severity were used to compare outcomes following MT in patients with and without LVAD. Subgroup analyses were also performed in LVAD patients experiencing stroke in the post-operative setting and stroke in the setting of pre-existing devices. RESULTS: Of the 1,633,234 AIS hospitalizations identified, 794 occurred in patients with LVADs. Around 61% were post-operative. Post-stroke in-hospital mortality was higher among patients with LVADs (23.3% vs 7.23%, P < 0.001). Among those receiving MT, mortality was also higher in the LVAD population (31.0% vs 14.1%, P = 0.009), though this was largely driven by the post-operative LVAD subgroup. In multivariable analysis, only post-operative LVAD patients experienced greater odds of in-hospital death after MT (adjusted odds ratio (aOR): 8.66, confidence interval (CI):1.46-51.3); patients with pre-existing LVADs demonstrated no difference in post-MT mortality (aOR: 1.06; 95% CI: 0.29-3.91) or in odds of discharge home after MT (aOR 0.63, CI: 0.17-2.32). CONCLUSION: Our data suggest MT is not a futile treatment approach in patients with pre-existing LVADs and may result in similar rates of good outcomes. Additional research is needed to evaluate the long-term benefits of endovascular therapy after stroke in patients on LVAD support.

Delayed-Onset Cranial Nerve Palsy After Transvenous Embolization of Indirect Carotid Cavernous Fistulas.

BACKGROUND: Carotid cavernous fistulas (CCF) often present with diplopia secondary to cranial nerve palsy (CNP). Immediate development of postoperative CNP has been described in the literature. This study described delayed-onset of CNP after complete and reconfirmed obliteration of the CCF and resolution of initial CNP. METHODS: A retrospective analysis was performed on patients with indirect CCF between 1987 and 2006 at 4 academic endovascular centers. Details of the endovascular procedures, embolic agents used, and complications were studied. Partial or complete obliteration was determined. Immediate and delayed cranial nerve palsies were independently assessed. RESULTS: A total of 267 patients with symptomatic indirect CCF underwent transvenous endovascular treatment. Four patients (1.5%) developed delayed abducens nerve (VI) palsy after complete resolution of presenting symptoms after embolization. Delayed presentation ranged between 3 and 13 months after complete resolution of initial double vision and cranial nerve palsies. Transvenous coil embolization through the inferior petrosal sinus was performed in all 4 affected patients. All had follow-up angiography confirming durable closure of their CCF. MRI did not show new mass lesions or abnormal soft tissue enhancement. In all 4 patients, their abducens nerve (VI) palsy remained. CONCLUSIONS: Delayed CNP can develop despite complete endovascular obliteration of the CCF. The cause of delayed CNP is not yet determined, but may represent fibrosis and ischemia. Long-term follow-up is needed even after complete neurological and radiological recovery is attained in the immediate perioperative period.

Stroke and mechanical thrombectomy in patients with COVID-19: technical observations and patient characteristics.

BACKGROUND: COVID-19 infections have been shown to be associated with a range of thromboembolic disease. OBJECTIVE: To describe our endovascular experience in a consecutive series of patients with COVID-19 who presented with large vessel occlusions, and to describe unique findings in this population. METHODS: Mechanical thrombectomy was performed on five consecutive patients with COVID-19 with large vessel occlusions. A retrospective study of these patients was performed. Patient demographics, laboratory values, mechanical thrombectomy technique, and clinical and angiographic outcomes were reviewed. RESULTS: Four patients with COVID-19 presented with anterior circulation occlusions and one patient with COVID-19 presented with both anterior and posterior circulation occlusions. All patients had coagulation abnormalities. Mean patient age was 52.8 years. Three patients presented with an intracranial internal carotid artery occlusion. Two patients presented with an intracranial occlusion and a tandem thrombus in the carotid bulb. One patient presented with an occlusion in both the internal carotid and basilar arteries. Clot fragmentation and distal emboli to a new vascular territory were seen in two of five (40%) patients, and downstream emboli were seen in all five (100%) patients. Patient clinical outcome was generally poor in this series of patients with COVID-19 large vessel occlusion. CONCLUSION: Our series of patients with COVID-19 demonstrated coagulation abnormalities, and compared with our previous experience with mechanical thrombectomy in large vessel occlusion, this group of patients were younger, had tandem or multiple territory occlusions, a large clot burden, and a propensity for clot fragmentation. These patients present unique challenges that make successful revascularization difficult.

Curative treatment for low-grade arteriovenous malformations.

BACKGROUND: Spetzler-Martin (SM) grade I-II (low-grade) arteriovenous malformations (AVMs) are often considered safe for microsurgery or radiosurgery. The adjunctive use of preoperative embolization to reduce surgical risk in these AVMs remains controversial. OBJECTIVE: To assess the safety of combined treatment of grade I-II AVMs with preoperative embolization followed by surgical resection or radiosurgery, and determine the long-term functional outcomes. METHODS: With institutional review board approval, a retrospective analysis was carried out on patients with ruptured and unruptured SM I-II AVMs between 2002 and 2017. Details of the endovascular procedures, including number of arteries supplying the AVM, number of branches embolized, embolic agent(s) used, and complications were studied. Baseline clinical and imaging characteristics were compared. Functional status using the modified Rankin Scale (mRS) before and after endovascular and microsurgical treatments was compared. RESULTS: 258 SM I-II AVMs (36% SM I, 64% SM II) were identified in patients with a mean age of 38 ± 17 years. 48% presented with hemorrhage, 21% with seizure, 16% with headache, 10% with no symptoms, and 5% with clinical deficits. 90 patients (68%) in the unruptured group and 74 patients (59%) in the ruptured group underwent presurgical embolization (p = 0.0013). The mean number of arteries supplying the AVM was 1.44 and 1.41 in the unruptured and ruptured groups, respectively (p = 0.75). The mean number of arteries embolized was 2.51 in the unruptured group and 1.82 in the ruptured group (p = 0.003). n-Butyl cyanoacrylate and Onyx were the two most commonly used embolic agents. Four complications were seen in four patients (4/164 patients embolized): two peri-/postprocedural hemorrhage, one dissection, and one infarct. All patients undergoing surgery had a complete cure on postoperative angiography. Patients were followed up for a mean of 55 months. Good long-term outcomes (mRS score ≤ 2) were seen in 92.5% of patients with unruptured AVMs and 88.0% of those with ruptured AVMs. Permanent neurological morbidity occurred in 1.2%. CONCLUSIONS: Curative treatment of SM I-II AVMs can be performed using endovascular embolization with microsurgical resection or radiosurgery in selected cases, with very low morbidity and high cure rates. Compared with other published series, these outcomes suggest that preoperative embolization is a safe and effective adjunct to definitive surgical treatment. Long-term follow-up showed that patients with low-grade AVMs undergoing surgical resection or radiosurgery have good functional outcomes.

Cerebral Vasospasm after Open Fenestration of an Arachnoid Cyst in a 4-Year-Old Boy: Case Report and Review of the Literature.

Cerebral vasospasm is associated with significant morbidity, and most commonly occurs following subarachnoid hemorrhage. Rarely, vasospasm can follow tumor resection and traumatic brain injury. We present the first reported case of a young child who developed diffuse vasospasm following open fenestration of an arachnoid cyst and was promptly treated, with full recovery of neurologic function. Although vasopasm after arachnoid cyst fenestration is rare, it can be included in the differential for a new focal neurologic deficit.

Functional Outcomes and Delayed Cerebral Ischemia Following Nonperimesencephalic Angiogram-Negative Subarachnoid Hemorrhage Similar to Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The angiogram-negative subarachnoid hemorrhage (SAH) literature includes patients with perimesencephalic hemorrhage, which is recognized to have a much better outcome than aneurysmal SAH. OBJECTIVE: To evaluate the clinical outcomes of Nonperimesencephalic Angiogram-Negative SAH (NPAN-SAH). METHODS: A prospective, spontaneous SAH database of 1311 patients that accrued between April 2006 and December 2014 was screened. All patients with NPAN-SAH and 2 consecutive negative cerebral angiograms were included. RESULTS: We identified 191 (11%) from a total of 1311 patients with spontaneous SAH. Amongst angiogram-negative patients, 83 (4.9%) were adjudicated to have NPAN-SAH. Patient characteristics were similar across the groups, except NPAN-SAH patients were more likely to be men and had higher rates of diabetes. In a multivariable logistic regression model, NPAN-SAH patients were less likely to develop vasospasm, after adjusting for Fisher grade, sex, and diabetes (odds ratio [OR]: 0.197, 95% confidence interval [CI; 0.07-0.55], P = .002). In another adjusted model accounting for Hunt and Hess clinical grade, NPAN-SAH patients were also less likely to develop vasospasm (OR: 0.2, 95% CI [0.07-0.57], P = .002). We found no statistical significance between 2 groups for rebleed, developing hydrocephalus, seizures, or delayed cerebral ischemia. NPAN-SAH patients were equally associated with poor functional outcome (modified Rankin scale ≥3; OR: 1.16, 95% CI [0.615-2.20], P = .6420), and death (OR: 1.22, 95% CI [0.362-4.132], P = .7455) compared to aneurysmal SAH. CONCLUSION: Although the risk of vasospasm may be lower, patients with NPAN-SAH are equally associated with delayed cerebral ischemia, poor outcome, and death as compared to patients with aneurysmal SAH. Furthers studies may be necessary to further clarify these findings.

Imaging of Subdural Hematomas.

The imaging of subdural hematoma has evolved significantly. Computed tomography and MRI have supplanted other procedures and rendered most obsolete for the evaluation of intracranial pathology because of ease of use, tremendous soft tissue resolution, safety, and availability. Noncontrast computed tomography has become the accepted standard of care for the initial evaluation of patients with suspected subdural hematoma because of widespread availability, rapid acquisition time, and noninvasive nature. MRI offers important features in determining potential secondary causes of subdural hematoma, such as dural-based neoplasms.

Analysis of Hemorrhage Volumes After Angiogram-Negative Subarachnoid Hemorrhage.

BACKGROUND: Antiplatelet medication use is associated with worsened outcome after angiogram-negative subarachnoid hemorrhage (SAH). It has been hypothesized that these worsened outcomes may be the result of an association between antiplatelet medication use and increased hemorrhage volumes after angiogram-negative SAH. To test this hypothesis, we performed volumetric analysis of computed tomography (CT)-defined hemorrhage after angiogram-negative SAH. METHODS: This was a retrospective analysis of patients presenting with nontraumatic, angiogram-negative SAH in the Columbia University Subarachnoid Hemorrhage Outcomes database between 2000 and 2013. SAH volumes on admission head CT scans were measured using the MIPAV software package, version 7.20 in a semiautomated fashion. RESULTS: A total of 108 presenting CT scans from patients with angiogram-negative SAH were analyzed. The mean hemorrhage volume was 14.3 mL in the patients with a history of antiplatelet medication use, compared with 6.8 mL in those with no history of antiplatelet use. This difference was found to be significant (P = 0.0029). CONCLUSIONS: Antiplatelet medication use is associated with increased SAH volumes in patients with angiogram-negative SAH. Increased hemorrhage volumes may contribute to poor outcomes in this patient population. Prospective studies are warranted to confirm this association.

Arteriovenous malformations and headache.

Brain arteriovenous malformations (AVM) are complex vascular lesions commonly associated with chronic headache. An occipital location appears to increase the risk of concurrent migraine-like headaches in AVM patients. We have experienced great success in treating these headaches through a multidisciplinary approach to eradicate cerebral AVM. However, the specific clinical characteristics of AVM-associated headaches and the most effective treatment strategies for these patients remain unclear. Here, we provide a comprehensive review of the literature on AVM-associated headaches. We detail the history, classification, epidemiology, presentation, pathophysiology, treatment options, and outcomes for this poorly described condition. Additionally, we illustrate our approach to the management of patients with occipital AVM and associated intractable headaches.

Reassessing the Role of Intra-Arterial Drug Delivery for Glioblastoma Multiforme Treatment.

Effective treatment for glioblastoma (GBM) will likely require targeted delivery of several specific pharmacological agents simultaneously. Intra-arterial (IA) delivery is one technique for targeting the tumor site with multiple agents. Although IA chemotherapy for glioblastoma (GBM) has been attempted since the 1950s, the predicted benefits remain unproven in clinical practice. This review focuses on innovative approaches to IA drug delivery in treating GBM. Guided by novel in vitro and in vivo optical measurements, newer pharmacokinetic models promise to better define the complex relationship between background cerebral blood flow and drug injection parameters. Advanced optical technologies and tracers, unique nanoparticles designs, new cellular targets, and rational drug formulations are continuously modifying the therapeutic landscape for GBM. Personalized treatment approaches are emerging; however, such tailored approaches will largely depend on effective drug delivery techniques and on the ability to simultaneously deliver multidrug regimens. These new paradigms for tumor-selective drug delivery herald dramatic improvements in the effectiveness of IA chemotherapy for GBM. Therefore, within this context of so-called "precision medicine," the role of IA delivery for GBM is thoroughly reassessed.

Late onset aneurysm development following radiosurgical obliteration of a cerebellopontine angle meningioma.

The development of de novo intracranial aneurysms following stereotactic radiosurgery for intracranial pathology is a rare complication secondary to vascular injury. Typically, these aneurysms develop within the first few years after radiation surgery. We present the first case of an aneurysm developing 10 years after radiosurgery for a cerebellopontine angle meningioma. This case highlights the importance of careful long-term follow-up of patients who undergo radiosurgery for lesions abutting major vessels and/or who suffer post-radiation complications.

Number and location of draining veins in pediatric arteriovenous malformations: association with hemorrhage.

OBJECT: The significance of draining vein anatomy is poorly defined in pediatric arteriovenous malformations (AVMs). In adult cohorts, the presence of fewer veins has been shown to lead to an increased rate of hemorrhage, but this phenomenon has not yet been studied in pediatric AVMs. This report analyzes the impact of draining vein anatomy on presentation and outcome in a large series of pediatric AVMs. METHODS: Eighty-five pediatric patients with AVMs were treated at the Columbia University Medical Center between 1991 and 2012. Charts were retrospectively reviewed for patient characteristics, clinical course, neurological outcome, and AVM angioarchitectural features identified on the angiogram performed at presentation. Univariate analyses were performed using chi-square test and ANOVA when appropriate; multivariate analysis was performed using logistic regression. RESULTS: Four patients were excluded due to incomplete records. Twenty-seven patients had 2 or 3 draining veins; 12 (44.4%) of these patients suffered from hemorrhage prior to surgery. Fifty-four patients had 1 draining vein; 39 (72.2%) of these 54 suffered from hemorrhage. Independent predictors of hemorrhage included the presence of a single draining vein (p = 0.04) and deep venous drainage (p = 0.02). Good outcome (modified Rankin Scale [mRS] score < 3) on discharge was found to be associated with higher admission Glasgow Coma Scale (GCS) scores (p = 0.0001, OR 0.638, 95% CI 0.40-0.93). Poor outcome (mRS score > 2) on discharge was found to be associated with deep venous drainage (p = 0.04, OR 4.68, 95% CI 1.1-19.98). A higher admission GCS score was associated with a lower discharge mRS score (p = 0.0003, OR 0.6, 95% CI 0.46-0.79), and the presence of a single draining vein was associated with a lower mRS score on long-term follow-up (p = 0.04, OR 0.18, 95% CI 0.032-0.99). CONCLUSIONS: The authors' data suggest that the presence of a single draining vein or deep venous drainage plays a role in hemorrhage risk and ultimate outcome in pediatric AVMs. Small AVMs with a single or deep draining vein may have the highest risk of hemorrhage.

The role of antiplatelet medications in angiogram-negative subarachnoid hemorrhage.

BACKGROUND: The use of antiplatelet medications has greatly expanded and this has been associated with an increased rate of complications after aneurysmal subarachnoid hemorrhage (SAH). The influence of antiplatelet medications on outcomes after non-aneurysmal SAH is unknown. OBJECTIVE: To analyze the frequency and impact on outcome of antiplatelet medication use among patients with angiogram-negative SAH. METHODS: An analysis of patients within the Columbia University SAH Outcomes Project database was performed. All patients who underwent catheter cerebral angiography after presenting with nontraumatic SAH between 1996 and 2013 were included. Outcomes were assessed by using the modified Rankin Scale. RESULTS: A total of 1351 patients underwent catheter angiography for evaluation of SAH. Of these, 173 (13%) were designated angiogram-negative. The fraction of patients presenting with angiogram-negative SAH as well as the frequency of antiplatelet use among these patients significantly increased during the study period. Antiplatelet use was more commonly associated with angiogram-negative SAH than with angiogram-positive SAH (27% vs 14%, P = .001). At 14 days after presentation, poor outcome was significantly more frequent among patients who took antiplatelet agents than among those who did not (38% vs 20%, P = .017). This effect was also seen after multivariate analysis (odds ratio, 2.58; P = .034), although no difference was observed by 12 months (P > .05). CONCLUSION: Antiplatelet medication use is associated with poor early, but not late, outcomes after angiogram-negative SAH. Corresponding increased rates of antiplatelet medication use and angiogram-negative SAH may be related. Additional studies are needed to confirm this association.

Late onset aneurysm development following radiosurgical obliteration of a cerebellopontine angle meningioma.

The development of de novo intracranial aneurysms following stereotactic radiosurgery for intracranial pathology is a rare complication secondary to vascular injury. Typically, these aneurysms develop within the first few years after radiation surgery. We present the first case of an aneurysm developing 10 years after radiosurgery for a cerebellopontine angle meningioma. This case highlights the importance of careful long-term follow-up of patients who undergo radiosurgery for lesions abutting major vessels and/or who suffer post-radiation complications.

Role of embolization for cerebral arteriovenous malformations.

Cerebral arteriovenous malformations (AVMs) are complex high-flow lesions that can result in devastating neurological injury when they hemorrhage. Embolization is a critical component in the management of many patients with cerebral AVMs. Embolization may be used as an independent curative therapy or more commonly in an adjuvant fashion prior to either micro- or radiosurgery. Although the treatment-related morbidity and mortality for AVMs--including that due to microsurgery, embolization, and radiosurgery--can be substantial, its natural history offers little solace. Fortunately, care by a multidisciplinary team experienced in the comprehensive management of AVMs can offer excellent results in most cases.

Spinal arteriovenous malformation associated with Schimmelpenning syndrome.

The authors report the presentation and management of a 13-year-old girl with Schimmelpenning syndrome, a rare neurocutaneous syndrome; this patient suffered hemorrhage of a spinal arteriovenous malformation. This is the first case of a spinal arteriovenous malformation reported in association with Schimmelpenning syndrome. Neurosurgeons should be aware of this rare phacomatosis as well as of the various neurological disorders associated with this diagnosis. The threshold for imaging the neuraxis in these patients should be low.