Predictors of Extended Length of Stay Following Treatment of Unruptured Adult Cerebral Aneurysms: A Study of The National Inpatient Sample.

BACKGROUND: In an unprecedented era of soaring healthcare costs, payers and providers alike have started to place increased importance on measuring the quality of surgical procedures as a surrogate for operative success. One metric used is the length of hospital stay (LOS) during index admission. For the treatment of unruptured cerebral aneurysms, the determinants of extended length of stay are relatively unknown. The aim of this study was to identify the patient- and hospital-level factors associated with extended LOS following treatment for unruptured cerebral aneurysms. METHODS: The National Inpatient Sample years 2010 - 2014 was queried. Adults (≥18 years) with unruptured aneurysms undergoing either clipping or coiling were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Extended LOS was defined as greater than 75th percentile for the entire cohort (>5 days). Weighted patient demographics, comorbidities, complications, LOS, disposition and total cost were recorded. Multivariate logistic regression was used to determine the odds ratio for risk-adjusted extended LOS. The primary outcome was the degree which patient comorbidities or postoperative complications correlated with extended LOS. RESULTS: A total of 46,880 patients were identified for which 9,774 (20.8%) patients had extended LOS (Normal LOS: 37,106; Extended LOS: 9,774). Patients in the extended LOS cohort presented with a greater number of comorbidities compared to the normal LOS cohort. A greater proportion of the normal LOS cohort was coiled (Normal LOS: 63.0% vs. Extended LOS: 33.5%, P<0.001), while more patients in the extended LOS cohort were clipped (Normal LOS: 37.0% vs. Extended LOS: 66.5%, P<0.001). The overall complication rate was higher in the extended LOS cohort (Normal LOS: 7.3% vs. Extended LOS: 43.8%, P<0.001). On average, the extended LOS cohort incurred a total cost nearly twice as large (Normal LOS: $26,050 ± 13,430 vs. Extended LOS: $52,195 ± 37,252, P<0.001) and had more patients encounter non-routine discharges (Normal LOS: 8.5% vs. Extended LOS: 52.5%, P<0.001) compared to the normal LOS cohort. On weighted multivariate logistic regression, multiple patient-specific factors were associated with extended LOS. These included demographics, preadmission comorbidities, choice of procedure, and inpatient complications. The odds ratio for extended LOS was 5.14 (95% CI, 4.30 - 6.14) for patients with 1 complication and 19.58 (95% CI, 15.75 - 24.34) for patients with > 1 complication. CONCLUSIONS: Our study demonstrates that extended LOS after treatment of unruptured aneurysms is influenced by a number of patient-level factors including demographics, preadmission comorbidities, type of aneurysm treatment (open surgical versus endovascular), and, importantly, inpatient complications. A better understanding of these independent predictors of prolonged length of hospital stay may help to improve patient outcomes and decrease overall healthcare costs.

Macrovascular Lesions Underlying Spontaneous Intracerebral Hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is a morbid disease with a high case fatality rate. Prognosis, rehemorrhage rates, and acute, clinical decision making are greatly affected by the underlying etiology of hemorrhage. This review focuses on the evaluation, diagnosis, and management of structural, macrovascular lesions presenting with ICH, including ruptured aneurysms, brain arteriovenous malformations, cranial dural arteriovenous fistulas, and cerebral cavernous malformations.

A technical guide to robotic-assisted carotid angioplasty and stenting with the Corindus CorPath GRX system.

Robotic-assisted carotid artery angioplasty and stenting is becoming more popular due to its precision and radiation safety. In this video, we present a case using the CorPath GRX Robotic System (Corindus, a Seimens Healthineers Company, Waltham, Massachusetts, USA) with step-by-step procedure process and technical nuances (video 1). We demonstrate that cervical carotid angioplasty and stenting can be safely performed using the robotic system with efficiency and accuracy.

Use of a dedicated open transcarotid access system for neurovascular disease.

BACKGROUND: Transcarotid artery revascularization (TCAR) is an increasingly popular technique for the management of extracranial carotid stenosis. Its off-label use in the treatment of intracranial neurovascular disease is poorly described. Our objective is to describe the use of a dedicated open transcarotid access system for the treatment of neurovascular pathologies other than extracranial carotid stenosis. METHODS: We conducted a retrospective review of a prospectively maintained database of consecutive patients who underwent treatment of neurovascular disease at a single academic center using the ENROUTE Transcarotid Arterial Sheath. Demographics, procedural characteristics, and patient outcomes were reported. RESULTS: Twenty patients were included in the study between September 2017 and March 2023. The following pathologies were treated: intracranial atherosclerotic disease (ICAD, nine patients), complex cervico-petrous carotid disease (five patients), intracranial aneurysms (three patients), and large vessel occlusion-acute ischemic stroke (three patients). Eighteen of the 20 cases were performed with active carotid flow reversal. All cases were successfully completed. There were no access-related complications. One periprocedural complication was incurred: a microguidewire perforation during an exchange maneuver for the treatment of ICAD. CONCLUSION: An open transcarotid approach using a dedicated transcarotid system may offer a safe alternative access strategy for the endovascular treatment of complex neurovascular pathologies when a traditional transfemoral or transradial approach is contraindicated or failed.

Absence of CCL2 is sufficient to restore hippocampal neurogenesis following cranial irradiation.

Cranial irradiation for the treatment of brain tumors causes a delayed and progressive cognitive decline that is pronounced in young patients. Dysregulation of neural stem and progenitor cells is thought to contribute to these effects by altering early childhood brain development. Earlier work has shown that irradiation creates a chronic neuroinflammatory state that severely and selectively impairs postnatal and adult neurogenesis. Here we show that irradiation induces a transient non-classical cytokine response with selective upregulation of CCL2/monocyte chemoattractant protein-1 (MCP-1). Absence of CCL2 signaling in the hours after irradiation is alone sufficient to attenuate chronic microglia activation and allow the recovery of neurogenesis in the weeks following irradiation. This identifies CCL2 signaling as a potential clinical target for moderating the long-term defects in neural stem cell function following cranial radiation in children.

Robotic Diagnostic Cerebral Angiography: A Multicenter Experience of 113 Patients.

BACKGROUND: Neurointerventional robotic systems have potential to reduce occupational radiation, improve procedural precision, and allow for future remote teleoperation. A limited number of single institution case reports and series have been published outlining the safety and feasibility of robot-assisted diagnostic cerebral angiography. METHODS: This is a multicenter, retrospective case series of patients undergoing diagnostic cerebral angiography at three separate institutions - University of California, Davis (UCD); University of California, Los Angeles (UCLA); and University of California, San Francisco (UCSF). The equipment used was the CorPath GRX Robotic System (Corindus, Waltham, MA). RESULTS: A total of 113 cases were analyzed who underwent robot-assisted diagnostic cerebral angiography from September 28, 2020 to October 27, 2022. There were no significant complications related to use of the robotic system including stroke, arterial dissection, bleeding, or pseudoaneurysm formation at the access site. Using the robotic system, 88 of 113 (77.9%) cases were completed successfully without unplanned manual conversion. The principal causes for unplanned manual conversion included challenging anatomy, technical difficulty with the bedside robotic cassette, and hubbing out of the robotic system due to limited working length. For robotic operation, average fluoroscopy time was 13.2 min (interquartile range (IQR), 9.3 to 16.8 min) and average cumulative air kerma was 975.8 mGY (IQR, 350.8 to 1073.5 mGy). CONCLUSIONS: Robotic cerebral angiography with the CorPath GRX Robotic System is safe and easily learned by novice users without much prior manual experience. However, there are technical limitations such as a short working length and an inability to support 0.035" wires which may limit its widespread adoption in clinical practice.

Transcarotid artery revascularization (TCAR): a technical video.

Carotid revascularization is an important method of stroke prevention and includes carotid endarterectomy and transfemoral carotid angioplasty and stenting. More recently, a hybrid open-endovascular approach, termed transcarotid artery revascularization (TCAR), is garnering increased attention. Although fundamentally a 'stenting procedure', unlike transfemoral carotid angioplasty and stenting, TCAR allows for a proximal neuroprotection strategy based on flow reversal. In this technical video, we will review operative techniques and nuances of the TCAR procedure, with a particular focus on the neurovascular proceduralist looking to adopt this technique into routine clinical practice(video 1). neurintsurg;14/8/842/V1F1V1Video 1TCAR Technical Video.

Characterization of axon guidance cue sensitivity of human embryonic stem cell-derived dopaminergic neurons.

Dopaminergic neurons derived from human embryonic stem cells will be useful in future transplantation studies of Parkinson's disease patients. As newly generated neurons must integrate and reconnect with host cells, the ability of hESC-derived neurons to respond to axon guidance cues will be critical. Both Netrin-1 and Slit-2 guide rodent embryonic dopaminergic (DA) neurons in vitro and in vivo, but very little is known about the response of hESC-derived DA neurons to any axonal guidance cues. Here we examined the ability of Netrin-1 and Slit-2 to affect human ESC DA axons in vitro. hESC DA neurons mature over time in culture with the developmental profile of DA neurons in vivo, including expression of the DA neuron markers FoxA2, En-1 and Nurr-1, and receptors for both Netrin and Slit. hESC DA neurons respond to exogenous Netrin-1 and Slit-2, showing an increased responsiveness to Netrin-1 as the neurons mature in culture. These responses were maintained in the presence of pro-inflammatory cytokines that might be encountered in the diseased brain. These studies are the first to evaluate and confirm that suitably matured human ES-derived DA neurons can respond appropriately to axon guidance cues.

Wnt-mediated self-renewal of neural stem/progenitor cells.

In this work we have uncovered a role for Wnt signaling as an important regulator of stem cell self-renewal in the developing brain. We identified Wnt-responsive cells in the subventricular zone of the developing E14.5 mouse brain. Responding cell populations were enriched for self-renewing stem cells in primary culture, suggesting that Wnt signaling is a hallmark of self-renewing activity in vivo. We also tested whether Wnt signals directly influence neural stem cells. Using inhibitors of the Wnt pathway, we found that Wnt signaling is required for the efficient cloning and expansion of single-cell derived populations that are able to generate new stem cells as well as neurons, astrocytes, and oligodendrocytes. The addition of exogenous Wnt3a protein enhances clonal outgrowth, demonstrating not only a critical role for the Wnt pathway for the regulation of neurogenesis but also its use for the expansion of neural stem cells in cell culture and in tissue engineering.

Recurrent and Residual Aneurysms After Woven EndoBridge (WEB) Therapy: What's Next?

The prevalence of recurrent and residual aneurysms following Woven EndoBridge (WEB) treatment is not insignificant. The goal of this systematic review was to evaluate retreatment methods for such aneurysms and their outcomes. PubMed, Embase, and Scopus databases were systematically searched, and results were reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Original studies reporting on aneurysms that were retreated after WEB were included. Sixteen studies (n = 901 aneurysms), of which three were prospective, reported on retreated aneurysms following initial WEB treatment. Of those 901 aneurysms, on average 18.7 ± 11.5% were recurrent or residual at the last follow-up and 10.7 ± 11% required some form of retreatment. When compared to WEB-IT (WEB Intra-saccular Therapy) data, retreated aneurysms were more likely to be large in size (p < 0.0001) and more likely to have been initially treated with the WEB dual-layer configuration. The mean age of those with retreated aneurysms was 58 ± 5.7 years old, and the mean size of aneurysm dome was 11.1 ± 5.5 millimeters. Majority (34.1%) of the aneurysms were located at the basilar apex. Retreatment modalities included coiling (20%), stent-assisted coiling (38.7%), additional WEB device (13.3%), flow diversion (16%), and clipping (12%). Majority of retreated cases had favorable outcomes, with 96.4 ± 13.4% of the cases demonstrating technical success and 90.5 ± 18.2% having adequate occlusion at the last follow-up. Our systematic review suggests that retreatment of recurrent and residual aneurysms after initial WEB treatment is feasible. Future prospective studies would be helpful in validating these results.

Aneurysmal subarachnoid hemorrhage survivors show long-term deficits in spatial reference memory in a pilot study of a virtual water maze paradigm.

BACKGROUND: Limited data exists on the long-term effects of aneurysmal subarachnoid hemorrhage (SAH) on spatial memory. Herein, we used a computerized virtual water maze to evaluate the feasibility of spatial memory testing in pilot cohort of ten patients who survived previous SAH. METHODS: Ten SAH survivors (5.8 ± 5.1 years after initial hemorrhage) and 7 age-matched controls underwent testing in a virtual water maze computer program. Additional subgroup analyses were performed to evaluate spatial reference memory correlation for ventricular size on admission, placement of an external ventricular drain and placement of a shunt. RESULTS: With respect to the spatial memory acquisition phase, there was no significant difference of pathway length traveled to reach the platform between SAH survivors and control subjects. During the probe trial, control subjects spent significantly longer time in target quadrants compared to SAH survivors (F(3, 24) = 10.32, p = 0.0001; Target vs. Right: Mean percent difference 0.16 [0-0.32], p = 0.045; Target vs. Across: Mean percent difference 0.35 [0.19-0.51], p < 0.0001; Target vs. Left: Mean percent difference 0.21 [0.05-0.37], p = 0.0094). Furthermore, patients who initially presented with smaller ventricles performed worse that those patients who had ventriculomegaly and/or required surgical management of hydrocephalus. CONCLUSIONS: Our data demonstrate that SAH survivors have persistent spatial reference memory deficits years after the hemorrhage. Hydrocephalus at presentation and external ventricular drainage were not found to be associated with poor spatial memory outcomes in this pilot cohort. Therefore, other causes such as global cerebral edema or magnitude of initial ICP spike, need to be considered to be examined as root cause as well in subsequent studies. The protocol described in this manuscript is able to demonstrate a spatial reference memory deficit and can be used to study risk factors for spatial memory impairment on a larger scale.

Vessel wall MRI in ruptured cranial dural arteriovenous fistulas.

Intracranial high-resolution vessel wall MRI (VW-MRI) is an imaging paradigm that is useful in site-of-rupture identification in patients presenting with spontaneous subarachnoid hemorrhage and multiple intracranial aneurysms. Only a handful of case reports describe its potential utility in the evaluation of more complex brain vascular malformations. We report for the first time three patients with ruptured cranial dural arteriovenous fistulas (dAVFs) that were evaluated with high-resolution VW-MRI. The presumed site-of-rupture was identified based on contiguity of a venous ectasia with adjacent blood products and thick, concentric wall enhancement. This preliminary experience suggests a role for high-resolution VW-MRI in the evaluation of ruptured cranial dAVFs, in particular, site-of-rupture identification. It also supports an emerging hypothesis that all spontaneously ruptured, macrovascular lesions demonstrate avid vessel wall enhancement.

Thirty- and 90-Day Readmissions After Treatment of Traumatic Subdural Hematoma: National Trend Analysis.

OBJECTIVE: Subdural hematoma (SDH), a form of traumatic brain injury, is a common disease that requires extensive patient management and resource utilization; however, there remains a paucity of national studies examining the likelihood of readmission in this patient population. The aim of this study is to investigate differences in 30- and 90-day readmissions for treatment of traumatic SDH using a nationwide readmission database. METHODS: The Nationwide Readmission Database years 2013-2015 were queried. Patients with a diagnosis of traumatic SDH and a primary procedure code for incision of cerebral meninges for drainage were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Patients were grouped by no readmission (Non-R), readmission within 30 days (30-R), and readmission within 31-90 days (90-R). RESULTS: We identified a total of 14,355 patients, with 3106 (21.6%) patients encountering a readmission (30-R: n = 2193 [15.3%]; 90-R: n = 913 [6.3%]; Non-R: n = 11,249). The most prevalent 30- and 90-day diagnoses seen among the readmitted cohorts were postoperative infection (30-R: 10.5%, 90-R: 13.0%) and epilepsy (30-R: 3.7%, 90-R: 1.1%). On multivariate logistic regression analysis, Medicare, Medicaid, hypertension, diabetes, renal failure, congestive heart failure, and coagulopathy were independently associated with 30-day readmission; Medicare and rheumatoid arthritis/collagen vascular disease were independently associated with 90-day readmission. CONCLUSIONS: In this study, we determine the relationship between readmission rates and complications associated with surgical intervention for traumatic subdural hematoma.

Direct carotid puncture for mechanical thrombectomy in acute ischemic stroke patients with prohibitive vascular access.

OBJECTIVE: While the benefit of mechanical thrombectomy (MT) for patients with anterior circulation acute ischemic stroke with large-vessel occlusion (AIS-LVO) has been clearly established, difficult vascular access may make the intervention impossible or unduly prolonged. In this study, the authors evaluated safety as well as radiographic and functional outcomes in stroke patients treated with MT via direct carotid puncture (DCP) for prohibitive vascular access. METHODS: The authors retrospectively studied patients from their prospective AIS-LVO database who underwent attempted MT between 2015 and 2018. Patients with prohibitive vascular access were divided into two groups: 1) aborted MT (abMT) after failed transfemoral access and 2) attempted MT via DCP. Functional outcome was assessed using the modified Rankin Scale at 3 months. Associations with outcome were analyzed using ordinal logistic regression. RESULTS: Of 352 consecutive patients with anterior circulation AIS-LVO who underwent attempted MT, 37 patients (10.5%) were deemed to have prohibitive vascular access (mean age [± SD] 82 ± 11 years, mean National Institutes of Health Stroke Scale [NIHSS] score 17 ± 5, with females accounting for 75% of the patients). There were 20 patients in the DCP group and 17 in the abMT group. The two groups were well matched for the known predictors of clinical outcome: age, sex, and admission NIHSS score. Direct carotid access was successfully obtained in 19 of 20 patients. Successful reperfusion (thrombolysis in cerebral infarction score 2b or 3) was achieved in 16 (84%) of 19 patients in the DCP group. Carotid access complications included an inability to catheterize the carotid artery in 1 patient, neck hematomas in 4 patients, non-flow-limiting common carotid artery (CCA) dissections in 2 patients, and a delayed, fatal carotid blowout in 1 patient. The neck hematomas and non-flow-limiting CCA dissections did not require any subsequent interventions and remained clinically silent. Compared with the abMT group, patients in the DCP group had smaller infarct volumes (11 vs 48 ml, p = 0.04), a greater reduction in NIHSS score (-4 vs +2.9, p = 0.03), and better functional outcome (shift analysis for 3-month modified Rankin Scale score: adjusted OR 5.2, 95% CI 1.02-24.5; p = 0.048). CONCLUSIONS: DCP for emergency MT in patients with anterior circulation AIS-LVO and prohibitive vascular access is safe and effective and is associated with higher recanalization rates, smaller infarct volumes, and improved functional outcome compared with patients with abMT after failed transfemoral access. DCP should be considered in this patient population.

High-resolution Vessel Wall Magnetic Resonance Imaging in Intracranial Aneurysms and Brain Arteriovenous Malformations.

Over the last several years, the advent of intracranial high-resolution vessel wall magnetic resonance imaging (VW-MRI) has provided a new lens with which to view cerebrovascular disease that has not previously been available with conventional imaging. It has already fundamentally changed the way that steno-occlusive diseases are evaluated at many academic centers. This review focuses on current and emerging applications of intracranial high-resolution VW-MRI in the clinical evaluation of intracranial aneurysms and brain arteriovenous malformations. Examples are provided from our clinical practice.

Aneurysmal subarachnoid hemorrhage and severe, catheter-induced vasospasm associated with excessive consumption of a caffeinated energy drink.

Excessive consumption of over-the-counter stimulants is associated with coronary vasospasm, thrombotic complications, and sudden cardiac death. Their effects on cerebrovascular physiology are not yet described in the neurointerventional literature. Patients are increasingly exposed to high levels of these vasoactive substances in the form of caffeinated energy drinks and specialty coffees. We report a case of aneurysmal subarachnoid hemorrhage (SAH) and severe, catheter-induced vasospasm during attempted endovascular repair of a ruptured anterior communicating artery (AComA) aneurysm in the setting of excessive energy drink consumption. We review the literature and alert clinicians to this potentially serious complication.

Effect of glucoprivation on serotonin neurotoxicity induced by substituted amphetamines.

The present studies were conducted to further explore the potential role of metabolic compromise in substituted amphetamine-induced serotonin (5-HT) neurotoxicity. To this end, we examined the glucoprivic effects of 2-deoxy-D-glucose (2-DG) on the 5-HT neurotoxic effects of fenfluramine (FEN) and methylenedioxymethamphetamine (MDMA). Rats were treated with either FEN or MDMA, alone and in combination, with doses of 2-DG known to produce glucoprivic effects at either 22 +/- 1 or 28 +/- 1 degrees C. At 22 +/- 1 degrees C, FEN produced hypothermia, MDMA induced hyperthermia, and both drugs produced significant long-term reductions in regional brain 5-HT neuronal markers. 2-DG did not enhance 5-HT neurotoxicity induced by either FEN or MDMA; indeed, in some instances, it afforded partial neuroprotection. Although 2-DG afforded partial protection from both FEN and MDMA-induced 5-HT neurotoxic changes, it also caused significant hypothermia, raising the possibility that protection was due to a lowered temperature. Increasing the ambient temperature to 28 +/- 1 degrees C largely eliminated drug-induced hypothermia and eliminated the neuroprotective effects of 2-DG. Thus, even without the confounding effect of temperature, 2-DG still did not potentiate FEN or MDMA-induced 5-HT neurotoxicity. These findings suggest that the role of metabolic compromise in amphetamine-induced 5-HT neurotoxicity merits further study.

RETRACTED: Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA ("ecstasy").

The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or "ecstasy") is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.