Thrombectomy Outcomes in Acute Basilar Artery Occlusions Due to Intracranial Atherosclerotic Disease.

BACKGROUND AND OBJECTIVES: Intracranial atherosclerotic disease (ICAD) large vessel occlusion (LVO) is responsible for up to 30% of LVO. In this study, we aimed to determine the likelihood of favorable functional outcomes (modified Rankin Scale 0-3) in acute ICAD-LVO basilar occlusion compared with embolic basilar occlusion. METHODS: This is an analysis of the Posterior Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intraprocedural Predictors for Mechanical Thrombectomy Registry in which patients with acute basilar artery occlusions from 8 comprehensive stroke centers were included from 2015 to 2021. Patients were dichotomized into with (ICAD-LVO) or without underlying ICAD (embolic). Descriptive statistics for each group and multivariate logistic analysis were performed on the primary outcome. RESULTS: Three hundred forty-six patients were included. There were 215 patients with embolic (62%) and 131 patients with ICAD-LVO (38%). Baseline demographics were equivalent between the 2 groups except for sex (male 47% vs 67%; P < .001), history of stroke (12% vs 25%; P = .002), and atrial fibrillation (31% vs 17%; P = .003). At 90 days, patients in the ICAD-LVO cohort were less likely to achieve favorable functional outcomes (odds ratio [OR] 0.41, 95% CI 0.22-0.72; P = .003) after adjusting for potentially confounding factors. In addition, ICAD-LVO strokes were less likely to achieve thrombolysis in cerebral infarction ≥2b (OR 0.29, 95% CI 0.14-0.57; P < .001). ICAD-LVO lesions were more likely to require stent placement (OR 14.94, 95% CI 4.91-45.49; P < .001). Subgroup analysis demonstrated favorable functional outcomes in patients who underwent stenting and angioplasty compared with failed recanalization cohort (OR 4.96, 95% CI 1.68-14.64; P < .004). CONCLUSION: Patients with acute basilar ICAD-LVO have higher morbidity and mortality compared with patients with embolic source. Lower rates of successful recanalization in the ICAD-LVO cohort support this finding. Our subgroup analysis demonstrates that stenting should be considered in patients with recanalization failure. Rates of symptomatic intracranial hemorrhage were similar between the ICAD-LVO and embolic cohorts.

MR Imaging-based Biomarker Development in Hemorrhagic Stroke Patients Including Brain Iron Quantification, Diffusion Tensor Imaging, and Phenomenon of Ultra-early Erythrolysis.

This review article discusses the role of MR imaging-based biomarkers in understanding and managing hemorrhagic strokes, focusing on intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage. ICH is a severe type of stroke with high mortality and morbidity rates, primarily caused by the rupture of small blood vessels in the brain, resulting in hematoma formation. MR imaging-based biomarkers, including brain iron quantification, ultra-early erythrolysis detection, and diffusion tensor imaging, offer valuable insights for hemorrhagic stroke management. These biomarkers could improve early diagnosis, risk stratification, treatment monitoring, and patient outcomes in the future, revolutionizing our approach to hemorrhagic strokes.

Early and late basilar artery thrombectomy time window outcomes.

Importance: Stroke-to-recanalization time is a strong predictor of outcomes in anterior circulation large-vessel occlusion (LVO). The authors aimed to evaluate functional outcomes in early (<6 h) vs. late (6-24 h) time windows for thrombectomy-treated basilar artery occlusions. Methods: Patients were derived from the Posterior Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intra-procedural Predictors of Mechanical Thrombectomy (PC-SEARCH) Registry and retrospectively analyzed early and late basilar artery thrombectomy time windows cohorts. Patients were dichotomized based on the last known well and correlated to 90-day functional outcomes (mRS 0-3). A multiple logistic regression analysis was performed. Results: A total of 405 patients were included in this study: 216 and 189 patients in the early and late time windows, respectively. Baseline demographic, stroke, radiographic, and intraprocedural characteristics were similar between the groups. A total of 99 (46%) and 79 (42%) patients in the early and late time windows, respectively, achieved favorable functional outcomes at 90 days (p = 0.41), and multiple logistic regression analysis did not reveal differences between cohorts (OR: 0.74; 95% CI: 0.46-1.19; p = 0.22). Symptomatic hemorrhage (7% vs. 5%; p = 0.69) and neurological complications (8% vs. 9%; p = 0.83) were similar between the groups; however, hospital complications were more common in the early time window cohort (22% vs. 13%; p = 0.01). Conclusion: The early and late thrombectomy time windows can achieve similar rates of 90-day favorable functional outcomes. However, timely thrombectomy influences the likelihood of achieving excellent functional outcomes (mRS ≤ 2) within the early time window.

Predictors of outcome and symptomatic intracranial hemorrhage in acute basilar artery occlusions: Analysis of the PC-SEARCH thrombectomy registry.

INTRODUCTION: Recent randomized controlled trials demonstrated superiority of mechanical thrombectomy compared to medical therapy in acute basilar artery occlusions, however, little data is available to guide clinicians in functional prognosis and risk stratification. PATIENTS AND METHODS: Data from the retrospectively established PC-SEARCH Thrombectomy registry, which included patients with basilar artery occlusion from eight sites from January 2015 to December 2021, was interrogated. Outcomes were dichotomized into 90-day favorable (mRS ⩽ 3) and unfavorable (mRS > 3). Multivariate logistic regression analysis was performed with respect to the outcome groups and were adjusted for potential confounding baseline characteristics. RESULTS: Four-hundred-forty-four patients were included in this analysis. Mean age was 66 [SD 15], with 56% male, and comprised of 76% Caucasian. Patients presented with an initial median NIHSS of 18 and 199 patients (44.8%) achieved favorable 90-day functional outcomes. Independent predictors of favorable outcomes included younger age, pc-ASPECTS > 8 (OR 2.30 p < 0.001), and TICI ⩾ 2b (OR 7.56 p < 0.001). Unfavorable outcomes were associated with increasing number of passes (OR 1.29 p = 0.004) and sICH (OR 4.19 p = 0.015). IA-tPA was an independent risk factor for sICH (OR 7.15 p = 0.002) without improving favorable functional outcomes. CONCLUSION AND DISCUSSION: PC-ASPECTS > 8, successful recanalization (TICI ⩾ 2b), first-pass recanalization, and younger age are independent predictors of favorable 90-day functional outcome in thrombectomy treated patients with acute basilar artery occlusion. Conversely, sICH were independent predictors of unfavorable outcomes. IA-tPA and unsuccessful recanalization are independently associated with sICH.

Attenuation of ventriculomegaly and iron overload after intraventricular hemorrhage by membrane attack complex inhibition.

OBJECTIVE: The pathophysiology of posthemorrhagic hydrocephalus (PHH) is not well understood, but recent data suggest blood components play a significant role. This study aimed to understand the timing of membrane attack complex (MAC) activation after intraventricular hemorrhage (IVH) and the effect of MAC inhibition on PHH development. METHODS: This study was composed of four parts. First, 24 young adult male rats underwent stereotactic intraventricular injection of autologous blood or saline and MRI on day 1, 3, or 7 after hemorrhage. Second, 18 rats underwent intraventricular injection of saline, autologous blood with aurin tricarboxylic acid (ATA) in vehicle, or autologous blood with vehicle and underwent serial MRI studies on days 1 and 3 after hemorrhage. Third, 12 rats underwent intraventricular injections as above and MRI 2 hours after hemorrhage. Finally, 24 rats underwent the intraventricular injections as above, as well as serial MRI studies on days 1, 7, 14, and 28 after hemorrhage. The MR images were used to calculate ventricular volume and iron deposition. Open field testing was performed to assess functional outcomes. Outcomes on day 28 were reported as a ratio to the animal's baseline values and normalized via log-transformation. Statistical analysis included the Shapiro-Wilk tests for normality and t-tests and 1-way analysis of variance for 2 and 3 groups of continuous variables, respectively. RESULTS: MAC was found within the hematoma 1 day after hemorrhage and persisted until day 7. Administration of ATA resulted in similar intraventricular hematoma volumes compared to vehicle 2 hours after hemorrhage. At 1 and 3 days after hemorrhage, ATA administration resulted in significantly smaller ventricular volumes and less hemolysis within the hematoma than in the vehicle animals. Administration of ATA also resulted in significantly smaller ventriculomegaly and less iron deposition in the periventricular area than in the vehicle rats 28 days after hemorrhage. Functionally, ATA rats were significantly faster, traveled longer distances, and spent less time resting than vehicle rats at 28 days. CONCLUSIONS: MAC was activated early and persisted within the hematoma until day 7 after IVH. MAC inhibition attenuated hemolysis in the clot and ventriculomegaly acutely after IVH. One month after hemorrhage, MAC inhibition attenuated ventriculomegaly and iron accumulation and improved functional outcomes.

Patients with progression of spinal metastases who present to the clinic have better outcomes compared to those who present to the emergency department.

BACKGROUND: As cancer therapies have improved, spinal metastases are increasingly common. Resulting complications have a significant impact on patient's quality of life. Optimal methods of surveillance and avoidance of neurologic deficits are understudied. This study compares the clinical course of patients who initially presented to the emergency department (ED) versus a multidisciplinary spine oncology clinic and who underwent stereotactic body radiation therapy (SBRT) secondary to progression/presentation of metastatic spine disease. METHODS: We performed a retrospective analysis of a prospectively maintained database of adult oncologic patients who underwent spinal SBRT at a single hospital from 2010 to 2021. Descriptive statistics and survival analyses were performed. RESULTS: We identified 498 spinal radiographic treatment sites in 390 patients. Of these patients, 118 (30.3%) presented to the ED. Patients presenting to the ED compared to the clinic had significantly more severe spinal compression (52.5% vs. 11.7%; p < 0.0001), severe pain (28.8% vs. 10.3%; p < 0.0001), weakness (24.5% vs. 4.5%; p < 0.0001), and difficulty walking (24.5% vs. 4.5%; p < 0.0001). Patients who presented to the ED compared to the clinic were significantly more likely to have surgical intervention followed by SBRT (55.4% vs. 15.3%; p < 0.0001) compared to SBRT alone. Patients who presented to the ED compared to the clinic had a significantly quicker interval to distant spine progression (5.1 ± 6.5 vs. 9.1 ± 10.2 months; p = 0.004), systemic progression (5.1 ± 7.2 vs. 9.2 ± 10.7 months; p < 0.0001), and worse overall survival (9.3 ± 10.0 vs. 14.3 ± 13.7 months; p = 0.002). CONCLUSION: The establishment of multidisciplinary spine oncology clinics is an opportunity to potentially allow for earlier, more data-driven treatment of their spinal metastatic disease.

Comparing Functional Outcomes and Safety Profiles of First-Line Aspiration Thrombectomy Versus Stentriever for Acute Basilar Artery Occlusion: Propensity Analysis of the PC-SEARCH Thrombectomy Registry.

BACKGROUND: Aspiration catheters (ASPs) and stentriever thrombectomy devices have comparable safety and efficacy in anterior circulation ischemic strokes. However, there is lack of high-quality comparative data in acute basilar artery occlusions. Our objective is to compare the outcomes and safety of ASPs and stentriever devices in acute basilar artery occlusions. METHODS: This is an analysis of the retrospectively established PC-SEARCH Thrombectomy (Posterior-Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intraprocedural Predictors for Mechanical Thrombectomy) registry. Patients were dichotomized based on their first-line thrombectomy device (ASP and stentriever) and associated with their 90-day functional outcomes, intraprocedural metrics, and safety measures. Propensity analysis based on unequal baseline characteristics was performed. Consecutive patients with acute basilar artery occlusions who received mechanical thrombectomy were included from January 2015 to December 2021. Patients received either first-line contact aspiration or stentriever mechanical thrombectomy. Primary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale score of 0 to 3 and symptomatic intracranial hemorrhage, respectively. Secondary outcomes included puncture-recanalization times, first-pass recanalization rates, crossovers to other thrombectomy device, and neurological/hospital complications. RESULTS: Five hundred eighteen patients were included in the registry, and a total of 383 patients were included (mean [SD] age, 65.5 [15] years; 228 [59%] men) in this analysis. Of these, 219 patients were first-line ASP while 164 patients received first-line stentriever devices. Median premorbid modified Rankin Scale was zero and median presenting National Institutes of Health Stroke Scale was 17 (interquartile range, 8-26). The proportion of favorable functional outcome was similar between the 2 techniques before (47.3% versus 42.5%; odds ratio, 1.22 [95% CI, 0.78-1.89]; P=0.38) and after propensity matching (odds ratio, 1.46 [95% CI, 0.85-2.49]; P=0.17). In our propensity-matched cohorts, puncture-recanalization times (18 versus 52 minutes; P<0.01) favored first-line ASP; however, first-pass recanalization rates (43.5% versus 44.5%; P=0.90) were similar between groups. First-line ASP was associated with higher rates of crossover (22% versus 6%; P<0.01), whereas stentriever was associated with higher rates of symptomatic intracranial hemorrhage (9.8% versus 3.4%; P=0.04). CONCLUSIONS: First-line ASP and stentriever methods demonstrated similar functional outcome and recanalization rates. Stentriever methods were associated with higher rates of symptomatic intracranial hemorrhage, whereas ASPs were associated with higher rates of crossover to alternative technique in patients with acute basilar occlusions.

Local Control in Patients with Metastatic Renal Cell Carcinoma to the Spine: The Experience of an Institution with a Multidisciplinary Spine Oncology Program.

BACKGROUND: The outcomes for patients with metastatic renal cell carcinoma (RCC) to the spine who underwent stereotactic body radiotherapy (SBRT) through a multidisciplinary spine oncology program are not well described. We sought to describe the clinical course and local control rates at 1 and 2 years for these patients. METHODS: A retrospective analysis of a prospectively maintained database of adult oncologic patients receiving SBRT to the spine through a multidisciplinary spine oncology program at a single institution from 2010 to 2021 was performed. Patients with a pathologic diagnosis of RCC were included. RESULTS: A total of 75 spinal sites were treated in 60 patients. Of the 60 patients, 75.0% were men, and the mean patient age was 59.2 ± 11.3 years. At 1 year after treatment, 6 of the 60 patients were lost to follow-up. Of the remaining 54 patients, 18 were censored by death and 7 treatment sites showed local recurrence, for 37 of 44 treatment sites with local control (87.8%). At 2 years, 1 additional local recurrence had developed, 15 patients were censored by death, and no additional patients had been lost to follow-up, resulting in 28 of 36 treatment sites with local control (83.2%). None of the patients who had undergone repeat SBRT had local recurrence at 1 or 2 years. For those with local recurrence, the average time from treatment to progression was 6.6 ± 6.5 months. CONCLUSIONS: In this cohort, one of the largest reported studies of spine SBRT for metastatic RCC, local control was high at 1 and 2 years. Our findings support the role of coordinated, algorithmic treatment for these patients.

Characteristics of activation of monocyte-derived macrophages versus microglia after mouse experimental intracerebral hemorrhage.

Both monocyte-derived macrophages (MDMs) and brain resident microglia participate in hematoma resolution after intracerebral hemorrhage (ICH). Here, we utilized a transgenic mouse line with enhanced green fluorescent protein (EGFP) labeled microglia (Tmem119-EGFP mice) combined with a F4/80 immunohistochemistry (a pan-macrophage marker) to visualize changes in MDMs and microglia after ICH. A murine model of ICH was used in which autologous blood was stereotactically injected into the right basal ganglia. The autologous blood was co-injected with CD47 blocking antibodies to enhance phagocytosis or clodronate liposomes for phagocyte depletion. In addition, Tmem119-EGFP mice were injected with the blood components peroxiredoxin 2 (Prx2) or thrombin. MDMs entered the brain and formed a peri-hematoma cell layer by day 3 after ICH and giant phagocytes engulfed red blood cells were found. CD47 blocking antibody increased the number of MDMs around and inside the hematoma and extended MDM phagocytic activity to day 7. Both MDMs and microglia could be diminished by clodronate liposomes. Intracerebral injection of Prx2 but not thrombin attracted MDMs into brain parenchyma. In conclusion, MDMs play an important role in phagocytosis after ICH which can be enhanced by CD47 blocking antibody, suggesting the modulation of MDMs after ICH could be a future therapeutic target.

Iron-Induced Hydrocephalus: the Role of Choroid Plexus Stromal Macrophages.

Evidence indicates that erythrocyte-derived iron and inflammation both play a role in intraventricular hemorrhage-induced brain injury including hydrocephalus. Many immune-associated cells, primarily stromal macrophages, reside at the choroid plexus where they are involved in inflammatory responses and antigen presentation. However, whether intraventricular iron impacts those stromal cells is unknown. The aim of this study was to evaluate the relationship between choroid plexus stromal macrophages and iron-induced hydrocephalus in rats and the impact of minocycline and clodronate liposomes on those changes. Aged (18-month-old) and young (3-month-old) male Fischer 344 rats were used to study choroid plexus stromal macrophages. Rats underwent intraventricular iron injection to induce hydrocephalus and treated with either minocycline, a microglia/macrophage inhibitor, or clodronate liposomes, a macrophage depleting agent. Ventricular volume was measured using magnetic resonance imaging, and stromal macrophages were quantified by immunofluorescence staining. We found that stromal macrophages accounted for about 10% of the total choroid plexus cells with more in aged rats. In both aged and young rats, intraventricular iron injection resulted in hydrocephalus and increased stromal macrophage number. Minocycline or clodronate liposomes ameliorated iron-induced hydrocephalus and the increase in stromal macrophages. In conclusion, stromal macrophages account for ~10% of all choroid plexus cells, with more in aged rats. Treatments targeting macrophages (minocycline and clodronate liposomes) are associated with reduced iron-induced hydrocephalus.

Neuroendovascular Procedures in Patients with Ehlers-Danlos Type IV: Multicenter Case Series and Systematic Review.

BACKGROUND: Ehlers-Danlos type IV or vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited disorder characterized by profound vascular fragility resulting from defective production of type III procollagen. Cerebrovascular diseases including spontaneous dissections, cerebral aneurysms, and cavernous carotid fistulae are common. Endovascular therapies in this patient population are known to be higher risk, although many studies (before 2000) involved older techniques and equipment. The purpose of this study is to investigate the safety and efficacy of modern neuroendovascular techniques in the treatment of cerebrovascular diseases in patients with vEDS. METHODS: We combined a multi-institutional retrospective case series at 3 quaternary-care centers with a systematic literature review of individual case reports and case series spanning 2000-2021 to evaluate the safety and efficacy of neuroendovascular procedure in patients with vEDS with cerebrovascular diseases. RESULTS: Fifty-nine patients who underwent 66 neuroendovascular procedures were evaluated. Most of the patients had direct cavernous carotid fistulas (DCCF). Neuroendovascular procedures had a 94% success rate, with a complication rate of 30% and a mortality of 7.5%. CONCLUSIONS: Neuroendovascular procedures can be performed with a high rate of success in the treatment of cerebrovascular diseases in patients with vEDS, although special care is required because complication rates and mortality are high. Access site and procedure-related vascular injuries remain a significant hurdle in treating vEDS with cerebrovascular diseases, even with modern techniques.

Bone metastasis from glioblastoma: a systematic review.

INTRODUCTION: Glioblastoma (GBM) is a devastating disease with poor overall survival. Despite the common occurrence of GBM among primary brain tumors, metastatic disease is rare. Our goal was to perform a systematic literature review on GBM with osseous metastases and understand the rate of metastasis to the vertebral column as compared to the remainder of the skeleton, and how this histology would fit into our current paradigm of treatment for bone metastases. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant literature search was performed using the PubMed database from 1952 to 2021. Search terms included "GBM", "glioblastoma", "high-grade glioma", "bone metastasis", and "bone metastases". RESULTS: Of 659 studies initially identified, 67 articles were included in the current review. From these 67 articles, a total of 92 distinct patient case presentations of metastatic glioblastoma to bone were identified. Of these cases, 58 (63%) involved the vertebral column while the remainder involved lesions within the skull, sternum, rib cage, and appendicular skeleton. CONCLUSION: Metastatic dissemination of GBM to bone occurs. While the true incidence is unknown, workup for metastatic disease, especially involving the spinal column, is warranted in symptomatic patients. Lastly, management of patients with GBM vertebral column metastases can follow the International Spine Oncology Consortium two-step multidisciplinary algorithm for the management of spinal metastases.