Control-matched octo/nonagenarian outcomes in acute basilar artery occlusions treated with mechanical thrombectomy-analysis of the PC-SEARCH thrombectomy registry.

INTRODUCTION: Age is often used as a predictor in determining outcomes in large vessel occlusions treated with mechanical thrombectomy. However, limited data exist for octo/nonagenarian outcomes compared to younger individuals in acute basilar artery occlusions treated with thrombectomy. METHODS: Patient data were obtained from the PC-SEARCH Thrombectomy Registry which consists of 444 acute basilar artery occlusions treated with mechanical thrombectomy. Individuals were dichotomized based on age (>80 and ≤80 years old). Primary outcome was defined as modified Rankin Scale of 0-3 at 90 days. Logistic and multivariate regression, as well as control-matched analysis, were performed. RESULTS: There were 373 and 71 patients in the younger and older cohorts, respectively. Gender, ethnicity, smoking status, atrial fibrillation, and coronary artery disease were noted to be significantly different between cohorts. At 90 days, 178 (47.7%) and 23 (32.4%) patients achieved primary outcome at 90 days (p = 0.02), however, after controlling for potentially confounding factors this association lost significance (OR 0.50 95% CI 0.24-1.05; p = 0.07). There were 84 patients included in the control matched analysis and demonstrated no significant differences on multivariate analysis between cohorts (OR 0.68 95% CI 0.25-1.84; p = 0.45). INTERPRETATION: Octa/nonagenarians presenting with an acute basilar artery occlusion treated with mechanical thrombectomy can achieve acceptable rates of favorable functional outcomes compared to younger individuals with similar baseline demographic and stroke characteristics.

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.

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.

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.

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.

Acute T2*-Weighted Magnetic Resonance Imaging Detectable Cerebral Thrombosis in a Rat Model of Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is associated with a high incidence of morbidity and mortality, particularly within the first 72 h after aneurysm rupture. We recently found ultra-early cerebral thrombosis, detectable on T2* magnetic resonance imaging (MRI), in a mouse SAH model at 4 h after onset. The current study examined whether such changes also occur in rat at 24 h after SAH, the vessels involved, whether the degree of thrombosis varied with SAH severity and brain injury, and if it differed between male and female rats. Adult Sprague Dawley rats were subjected to an endovascular perforation SAH model or sham surgery and underwent T2 and T2* MRI 24 h later. Following SAH, increased numbers of T2* hypointense vessels were detected on MRI. The number of such vessels correlated with SAH severity, as assessed by MRI-based grading of bleeding. Histologically, thrombotic vessels were found on hematoxylin and eosin staining, had a single layer of smooth muscle cells on alpha-smooth muscle actin immunostaining, and had laminin 2α/fibrinogen double labeling, suggesting venule thrombosis underlies the T2*-positive vessels on MRI. Capillary thrombosis was also detected which may follow the venous thrombosis. In both male and female rats, the number of T2*-positive thrombotic vessels correlated with T2 lesion volume and neurological function, and the number of such vessels was significantly greater in female rats. In summary, this study identified cerebral venous thrombosis 24 h following SAH in rats that could be detected with T2* MRI imaging and may contribute to SAH-induced brain injury.

Mechanical Thrombectomy Improves Outcome for Large Vessel Occlusion Stroke after Cardiac Surgery.

BACKGROUND: Stroke is a feared complication of cardiac surgery. Modern clot-retrieval techniques provide effective treatment for large vessel occlusion (LVO) strokes. The purpose of this study was to 1) report the incidence of LVO stroke after cardiac surgery at a large academic center, and 2) describe outcomes of postoperative LVO strokes. METHODS: All patients experiencing stroke within 30 days after undergoing cardiac surgery at a single center in 2014-2018 were reviewed. LVOs were identified through review of imaging and medical records, and their characteristics and clinical courses were examined. RESULTS: Over the study period, 7,112 cardiac surgeries, including endovascular procedures, were performed. Acute ischemic stroke within 30 days after surgery was noted in 163 patients (2.3%). Among those with a stroke, 51/163 (31.3%) had a CTA or MRA, and 15/163 (9.2%) presented with LVO stroke. For all stroke patients, the median time from surgery to stroke was 2 days (interquartile range, IQR, 0-6 days), and for patients with LVO, the median time from surgery to stroke was 4 days (IQR 0-6 days). The overall rate of postoperative LVO was 0.2% (95% CI 0.1-0.4%), though only 6/15 received thrombectomy. LVO patients receiving thrombectomy were significantly more likely to return to independent living compared to those managed medically (n = 4/6, 66.6% for mechanical thrombectomy vs. n = 0/9, 0% for medical management, P = .01). Of the 9 patients who did not get thrombectomy, 6 may currently be candidates for thrombectomy given new expanded treatment windows. CONCLUSIONS: The rate of LVO after cardiac surgery is low, though substantially elevated above the general population, and the majority do not receive thrombectomy currently. Patients receiving thrombectomy had improved neurologic outcomes compared to patients managed medically. Optimized postoperative care may increase the rate of LVO recognition, and cardiac surgery patients and their caregivers should be aware of this effective therapy.

Analysis of the effect of intraoperative neuromonitoring during resection of benign nerve sheath tumors on gross-total resection and neurological complications.

OBJECTIVE: The aim of this study was to examine the role of intraoperative neuromonitoring (IONM) during resection of benign peripheral nerve sheath tumors in achieving gross-total resection (GTR) and in reducing postoperative neurological complications. METHODS: Data from consecutive adult patients who underwent resection of a benign peripheral nerve sheath tumor at 7 participating institutions were combined. Propensity score matching was used to balance covariates. The primary outcomes of interest were the association between IONM and GTR and the association of IONM and the development of a permanent postoperative neurological complication. The secondary outcomes of interest were the association between IONM and GTR and the association between IONM and the development of a permanent postoperative neurological complication in the subgroup of patients with tumors involving a motor or mixed nerve. Univariate and multivariate logistic regression were then performed on the propensity score-matched samples to assess the ability of the independent variables to predict the outcomes of interest. RESULTS: A total of 337 patients who underwent resection of benign nerve sheath tumors were included. In multivariate analysis, the use of IONM (OR 0.460, 95% CI 0.199-0.978; p = 0.047) was a significant negative predictor of GTR, whereas none of the variables, including IONM, were associated with the occurrence of a permanent postoperative neurological complication. Within the subgroup of motor/mixed nerve tumors, in the multivariate analysis, IONM (OR 0.263, 95% CI 0.096-0.723; p = 0.010) was a significant negative predictor of a GTR, whereas IONM (OR 3.800, 95% CI 1.925-7.502; p < 0.001) was a significant positive predictor of a permanent postoperative motor deficit. CONCLUSIONS: Overall, 12% of the cohort had a permanent neurological complication, with new or worsened paresthesias most common, followed by pain and then weakness. The authors found that formal IONM was associated with a reduced likelihood of GTR and had no association with neurological complications. The authors believe that these data argue against IONM being considered standard of care but do not believe that these data should be used to universally argue against IONM during resection of benign nerve sheath tumors.

Intra-hematomal White Matter Tracts Act As a Scaffold for Macrophage Infiltration After Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a stroke subtype with high mortality and severe morbidity. Hemorrhages frequently develop within the white matter, but whether white matter fibers within the hematoma survive after ICH has not been well studied. The current study examines whether white matter fibers persist in the hematoma after ICH, fibers that might be impacted by evacuation, and their relationship to macrophage infiltration in a porcine model. Male piglets had 2.5 ml blood with or without CD47 blocking antibody injected into the right frontal lobe. Brains were harvested from 3 days to 2 months after ICH for brain histology. White matter fibers were detected within the hematoma 3 and 7 days after hemorrhage by brain histology and myelin basic protein immunohistochemistry. White matter still remained in the hematoma cavity at 2 months after ICH. Macrophage scavenger receptor-1 positive macrophages/microglia and heme oxygenase-1 positive cells infiltrated into the hematoma along the intra-hematomal white matter fibers at 3 and 7 days after ICH. Treatment with CD47 blocking antibody enhanced the infiltration of these cells. In conclusion, white matter fibers exist within the hematoma after ICH and macrophages/microglia may use such fibers as a scaffold to infiltrate into the hematoma and aid in hematoma clearance.

Drivers of variation in 90-day episode payments after mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: Although mechanical thrombectomy for acute ischemic stroke from a large vessel occlusion is now the standard of care, little is known about cost variations in stroke patients following thrombectomy and factors that influence these variations. METHODS: We evaluated claims data for 2016 to 2018 for thrombectomy-performing hospitals within Michigan through a registry that includes detailed episode payment information for both Medicare and privately insured patients. We aimed to analyze price-standardized and risk-adjusted 90-day episode payments in patients who underwent thrombectomy. Hospitals were grouped into three payment terciles for comparison. Statistical analysis was carried out using unpaired t-test, Chi-square, and ANOVA tests. RESULTS: 1076 thrombectomy cases treated at 16 centers were analyzed. The average 90-day episode payment by hospital ranged from $53 046 to $81,767, with a mean of $65 357. A $20 467 difference (35.1%) existed between the high and low payment hospital terciles (P<0.0001), highlighting a significant payment variation across hospital terciles. The primary drivers of payment variation were related to post-discharge care which accounted for 38% of the payment variation (P=0.0058, inter-tercile range $11,977-$19,703) and readmissions accounting for 26% (P=0.016, inter-tercile range $3,315-$7,992). This was followed by professional payments representing 20% of the variation (P<0.0001, inter-tercile range $7525-$9,922), while index hospitalization payment was responsible for only 16% of the 90-day episode payment variation (P=0.10, inter-tercile range $35,432-$41,099). CONCLUSIONS: There is a wide variation in 90-day episode payments for patients undergoing mechanical thrombectomy across centers. The main drivers of payment variation are related to differences in post-discharge care and readmissions.

Using a Mobile Application for Evaluation of Procedural Learning in Neurosurgery.

BACKGROUND: Feedback is a major component of any educational process. Competency assessment and feedback are essential tools for teaching surgical skills. Most current systems of assessment within neurosurgical residency programs use evaluations aggregated over a period of time, which lead to significant bias, rather than case-specific feedback. We describe the use of a mobile device application called SIMPL (System for Improving and Measuring Procedural Learning) to allow for immediate surgical competency assessment and improve the quality of feedback after every operative experience. METHODS: We retrospectively assessed our use of this program and neurosurgery residents' response to the program. Institutional review board approval was not required, and no patients were involved in the study. This application has already been implemented within general surgery programs with promising results. We document its implementation in a neurosurgery program and the output of the program for residents and program directors. RESULTS: This is the first documentation of such an application within a neurosurgical residency program. In a 6-month period at a single institution, around 300 evaluations were completed by residents and faculty, with a >80% response rate within both groups. Furthermore, these evaluations were companied by a 60% dictation rate from faculty, which contains verbal feedback that is available to residents for playback at any time. CONCLUSIONS: The telephone-based SIMPL application allows for assessment of surgical competency and remains quick and easy to use, giving it the potential to improve individual neurosurgical training experiences across the United States.

The Presence and Persistence of Unrealistic Expectations in Patients Undergoing Nerve Surgery.

BACKGROUND: Unrealistic expectations of the outcomes of peripheral nerve surgery reduce patient satisfaction. Most clinicians can recall patients with unrealistic expectations despite verbal preoperative education. OBJECTIVE: To assess patients' baseline level of understanding regarding nerve surgery and appropriate expectations. Additionally, we tested the effect of a written, preoperative educational handout on the patients' retention of knowledge. METHODS: This cross-sectional survey recruited patients scheduled to undergo peripheral nerve surgery at a single institution in 2016 to 2017. During the preoperative visit, a specialized nurse practitioner reviewed perioperative protocols, risks and benefits of the surgery, and postoperative care. Patients immediately completed a survey to assess their preoperative understanding of the verbally reviewed information. During the same visit, an additional written handout was given to patients in a randomized fashion. At their first postoperative visit, all patients completed the survey again. RESULTS: A total of 60 patients (mean age 52 yr) were enrolled of which 62% were male. Immediately following verbal instruction, 31% of patients had erroneous (unrealistic) expectations regarding pain, 30% had erroneous expectations regarding postoperative motor outcome, and 41% had erroneous expectations regarding the timing of postoperative recovery. There was no significant difference between patients who received the written handout vs those who did not, on retesting in the postoperative period. CONCLUSION: Patients undergoing peripheral nerve procedures demonstrated a high baseline level of unrealistic expectations despite standard in-person verbal counseling by specialty providers. A written handout did not have clear benefit in the retention of preoperative surgical teaching. Further investigation into more effective preoperative patient counseling is needed.

Refractory Orthostatic Hypotension Caused by a Recurrent Hemangioblastoma: Case Report and Review of the Literature.

Refractory orthostatic hypotension (OH) has been described following surgery for posterior fossa tumors. We present the case of a patient with refractory OH following attempted surgical resection. We also reviewed the available literature to describe pathophysiologic mechanisms for this rare entity. A 58-year-old female was found to have a hemangioblastoma at the cervicomedullary junction following workup for dysphagia and coordination difficulties. She underwent successful suboccipital craniotomy and gross total resection. However, the patient's symptoms returned several years later and a magnetic resonance imaging (MRI) showed tumor recurrence. A surgical resection was attempted but could not be performed due to significant scarring. Following discharge, she returned to our care with severe syncopal episodes, refractory OH, and an inability to ambulate. Aggressive medical therapy resulted in a gradual improvement in her ability to ambulate and a reduction in her orthostatic episodes. Unfortunately she died due to sepsis from aspiration pneumonia several months later. A survey of the literature yielded a total of 10 reports (14 patients) with refractory OH as a result of tumors in the cervicomedullary region. Five of fourteen patients died from complications related to OH and brainstem compression while the remainder had some improvement and were discharged. Refractory OH can rarely be a presenting sign of a tumor in the cervicomedullary junction or can manifest following surgical resection of tumors in this region. Recognition of OH and the institution of medical therapy (sodium and fluid replacement) and pharmacotherapy may curb the significant morbidity associated with this condition.