Treatment of pediatric intracranial aneurysms: institutional case series and systematic literature review.

INTRODUCTION: Pediatric intracranial aneurysms (IAs) are rare and have distinct clinical profiles compared to adult IAs. They differ in location, size, morphology, presentation, and treatment strategies. We present our experience with pediatric IAs over an 18-year period using surgical and endovascular treatments and review the literature to identify commonalities in epidemiology, treatment, and outcomes. METHODS: We identified all patients < 20 years old who underwent treatment for IAs at our institution between 2005 and 2020. Medical records and imaging were examined for demographic, clinical, and operative data. A systematic review was performed to identify studies reporting primary outcomes of surgical and endovascular treatment of pediatric IAs. Demographic information, aneurysm characteristics, treatment strategies, and outcomes were collected. RESULTS: Thirty-three patients underwent treatment for 37 aneurysms over 18 years. The mean age was 11.4 years, ranging from one month to 19 years. There were 21 males (63.6%) and 12 females (36.4%), yielding a male: female ratio of 1.75:1. Twenty-six (70.3%) aneurysms arose from the anterior circulation and 11 (29.7%) arose from the posterior circulation. Aneurysmal rupture occurred in 19 (57.5%) patients, of which 8 (24.2%) were categorized as Hunt-Hess grades IV or V. Aneurysm recurrence or rerupture occurred in five (15.2%) patients, and 5 patients (15.2%) died due to sequelae of their aneurysms. Twenty-one patients (63.6%) had a good outcome (modified Rankin Scale score 0-2) on last follow up. The systematic literature review yielded 48 studies which included 1,482 total aneurysms (611 with endovascular treatment; 656 treated surgically; 215 treated conservatively). Mean aneurysm recurrence rates in the literature were 12.7% and 3.9% for endovascular and surgical treatment, respectively. CONCLUSIONS: Our study provides data on the natural history and longitudinal outcomes for children treated for IAs at a single institution, in addition to our treatment strategies for various aneurysmal morphologies. Despite the high proportion of patients presenting with rupture, good functional outcomes can be achieved for most patients.

Serial dilation to enable ulnar artery access for endovascular neurointervention: Technical report and systematic review of the literature.

BACKGROUND: For rare neuro-endovascular cases in which transfemoral access is not feasible and the palmar circulation is insufficient for radial artery access, ulnar artery access may be considered. MATERIALS AND METHODS: Mechanical thrombectomy via ulnar artery access was performed to preserve the dominant radial artery. The ulnar artery was serial dilated to 7-French with microdilator. Angiography was performed using a diagnostic catheter. The sheath was exchanged for a guide catheter, and a triaxial system was inserted. A mechanical thrombectomy was performed. The systematic literature review included all studies pertaining to techniques for ulnar artery access for neurointervention in the last 20 years (2003-2023) published in the PubMed, Web of Science, and Embase databases. RESULTS: 67-year-old male developed left MCA syndrome in the setting of an infected abdominal aortic endograft. A transfemoral approach was ruled out due to concern for crossing the infected endograft. Allen test and ultrasound demonstrated that the right radial artery was of adequate size for access, but the ulnar artery was insufficient to support the palmar arch. Mechanical thrombectomy resulted in TICI 3 reperfusion. Systematic review of the literature yielded 2 case series and 1 case report of transulnar neurovascular procedures. Access site complications were rare and included 3 access site hematomas and 1 ulnar artery occlusion. CONCLUSION: We report our technique of serial dilation of the ulnar artery for neuroendovascular procedures and provide a systematic review of the literature for complication avoidance in ulnar artery access.

Application of Antibiotic-Impregnated Polymethyl-Methacrylate Bone Cement for the Treatment of Infected Cranioplasties: Initial Experience.

BACKGROUND: Management of infected cranioplasty implants remains a surgical challenge. Surgical debridement, removal of the infected implant, and prolonged antibiotic therapy are part of the acute management. In addition, cranioplasty removal poses the risk of dural tear. Reconstruction of the cranial defect is usually delayed for several months to years, increasing the difficulty due to soft tissue contraction and scarring. OBJECTIVE: The aim of the study was to propose an alternative to delayed reconstruction in the face of infection with a dual purpose: treat the infection with a material which delivers antibiotic to the area (polymethyl-methacrylate antibiotic) and which functions as a temporary or permanent cranioplasty. METHODS: We reviewed the records of 3 consecutive patients who underwent single-stage polymethyl-methacrylate antibiotic salvage cranioplasty. RESULTS: All patients underwent debridement of infected tissue. Titanium mesh was placed over the bony defect. Polymethyl methacrylate impregnated with vancomycin and tobramycin was then spread over the plate and defect before closure. Patients also received extended treatment with systemic antimicrobials. Early outcomes have been encouraging for both cosmesis and treatment of infection. CONCLUSIONS: Benefits of this treatment strategy include immediate reconstruction rather than staged procedures and delivery of high concentrations of antibiotics directly to the affected area in addition to systemic antibiotics.

Racial and ethnic disparities in brain tumour survival by age group and tumour type.

PURPOSE: The extent to which racial/ethnic brain tumour survival disparities vary by age is not very clear. In this study, we assess racial/ethnic brain tumour survival disparities overall by age group and type. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) 18 registries for US-based individuals diagnosed with a first primary malignant tumour from 2007 through 2016. Cox proportional hazards regression was used to compute adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between race/ethnicity and brain tumour survival, stratified by age group and tumour type. RESULTS: After adjusting for sex, socioeconomic status, insurance status, and tumour type, non-Hispanic (NH) Blacks (HR: 1.26; 95% CI: 1.02-1.55), NH Asian or Pacific Islanders (HR: 1.29; 95% CI: 1.01-1.66), and Hispanics (any race) (HR: 1.28; 95% CI: 1.09-1.51) all showed a survival disadvantage compared with NH Whites for the youngest age group studied (0-9 years). Furthermore, NH Blacks (HR: 0.88; 95% CI: 0.91-0.97), NH Asian or Pacific Islanders (HR: 0.84; 95% CI: 0.77-0.92), and Hispanics (any race) (HR: 0.91; 95% CI: 0.85-0.97) all showed a survival advantage compared with NH Whites for the 60-79 age group. Tests for interactions showed significant trends, indicating that racial/ethnic survival disparities disappear and even reverse for older age groups (P < 0.001). This reversal appears to be driven by poor glioblastoma survival among NH Whites (P < 0.001). CONCLUSION: Disparities in brain tumour survival among minorities exist primarily among children and adolescents. NH White adults show worse survival than their minority counterparts, which is possibly driven by poor glioblastoma biology.

Evidence-Based Recommendations for Seizure Prophylaxis in Patients with Brain Metastases Undergoing Stereotactic Radiosurgery.

Symptomatic epilepsy is frequently encountered in patients with brain metastases (BM), affecting up to 25% of them. However, it generally remains unknown whether the risk of seizures in such cases is affected by stereotactic radiosurgery (SRS), which involves highly conformal delivery of high-dose irradiation to the tumor with a minimal effect on adjacent brain tissue. Thus, the role of prophylactic administration of antiepileptic drugs (AED) after SRS remains controversial. A comprehensive review and analysis of the available literature reveals that according to prospective studies, the incidence of seizures after SRS for BM varies from 8% to 22%, and there is no evidence that SRS increases the incidence of symptomatic epilepsy. Therefore, routine prophylactic administration of AED prior to, during, or after SRS in the absence of a seizure history is not recommended. Nevertheless, short-course administration of an AED may be judiciously considered (on the basis of class III evidence) for selected high-risk individuals.

Cost-effectiveness of Intraoperative MRI for Treatment of High-Grade Gliomas.

Background Intraoperative MRI has been shown to improve gross-total resection of high-grade glioma. However, to the knowledge of the authors, the cost-effectiveness of intraoperative MRI has not been established. Purpose To construct a clinical decision analysis model for assessing intraoperative MRI in the treatment of high-grade glioma. Materials and Methods An integrated five-state microsimulation model was constructed to follow patients with high-grade glioma. One-hundred-thousand patients treated with intraoperative MRI were compared with 100 000 patients who were treated without intraoperative MRI from initial resection and debulking until death (median age at initial resection, 55 years). After the operation and treatment of complications, patients existed in one of three health states: progression-free survival (PFS), progressive disease, or dead. Patients with recurrence were offered up to two repeated resections. PFS, valuation of health states (utility values), probabilities, and costs were obtained from randomized controlled trials whenever possible. Otherwise, national databases, registries, and nonrandomized trials were used. Uncertainty in model inputs was assessed by using deterministic and probabilistic sensitivity analyses. A health care perspective was used for this analysis. A willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained was used to determine cost efficacy. Results Intraoperative MRI yielded an incremental benefit of 0.18 QALYs (1.34 QALYs with intraoperative MRI vs 1.16 QALYs without) at an incremental cost of $13 447 ($176 460 with intraoperative MRI vs $163 013 without) in microsimulation modeling, resulting in an incremental cost-effectiveness ratio of $76 442 per QALY. Because of parameter distributions, probabilistic sensitivity analysis demonstrated that intraoperative MRI had a 99.5% chance of cost-effectiveness at a willingness-to-pay threshold of $100 000 per QALY. Conclusion Intraoperative MRI is likely to be a cost-effective modality in the treatment of high-grade glioma. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Bettmann in this issue.

The impact of rural residence on adult brain cancer survival in the United States.

PURPOSE: Rural/urban disparities in brain cancer survival have been reported. However, disparities by cancer type or in the United States as a whole remain poorly understood. Using the Surveillance, Epidemiology, and End Results (SEER) 18 registries database, we examined brain cancer survival by rural/urban residence defined by Rural-Urban Continuum Codes (RUCCs). METHODS: We obtained data from SEER 18 registries for individuals aged 20 years and older with a first primary malignant brain cancer from 2001 to 2011. Rural/urban residence at diagnosis was defined using both metropolitan/non-metropolitan county classifications and individual RUCC categories. We used Cox proportional hazards regression to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between rural/urban residence and brain cancer survival. RESULTS: Among 37,581 cancer cases, 77.9% were non-Hispanic White, 56.5% were male, and 88.7% lived in a metropolitan county. Brain cancer patients living in the most rural counties had a significant increased risk of cancer death compared to those living in the most urban counties (HR 1.15; 95% CI 1.01-1.31). Those living in non-metropolitan counties had a similar risk of cancer death compared to those living in metropolitan counties (HR 1.01; 95% CI 0.97-1.06). Effect modification was observed overall by cancer type, with non-specified oligodendroglioma (HR 1.35; 95% CI 1.01-1.81) showing the greatest effect. CONCLUSION: After adjusting for confounding factors, our results suggest that rural residence has a modest effect on brain cancer survival, and that this disparity may vary by cancer type. Future research should explore differences in treatment strategies between rural and urban brain cancer patients.

The impact of traveling distance and hospital volume on post-surgical outcomes for patients with glioblastoma.

BACKGROUND: High-volume hospitals are associated with improved outcomes in glioblastoma (GBM). However, the impact of travel burden to high-volume centers is poorly understood. We examined post-operative outcomes between GBM patients that underwent treatment at local, low-volume hospitals with those that traveled long distances to high-volume hospitals. METHODS: The National Cancer Database was queried for GBM patients that underwent surgery (2010-2014). We established two cohorts: patients in the lowest quartile of travel distance and volume (Short-travel/Low-Volume: STLV) and patients in the highest quartile of travel and volume (Long-travel/High-Volume: LTHV). Outcomes analyzed were 30-day, 90-day mortality, overall survival, 30-day readmission, and hospital length of stay. RESULTS: Of 35,529 cases, STLV patients (n = 3414) traveled a median of 3 miles (Interquartile range [IQR] 1.8-4.2) to low-volume centers (5 [3-7] annual cases) and LTHV patients (n = 3808) traveled a median of 62 miles [44.1-111.3] to high-volume centers (48 [42-71]). LTHV patients were younger, had lower Charlson scores, largely received care at academic centers (84.4% vs 11.9%), were less likely to be minorities (8.1% vs 17.1%) or underinsured (6.9% vs 12.1), and were more likely to receive trimodality therapy (75.6% vs 69.2%; all p < 0.001). On adjusted analysis, LTHV predicted improved overall survival (HR 0.87, p = 0.002), decreased 90-day mortality (OR 0.72, p = 0.019), lower 30-day readmission (OR 0.42, p < 0.001), and shorter hospitalizations (RR 0.79, p < 0.001). CONCLUSIONS: Glioblastoma patients who travel farther to high-volume centers have superior post-operative outcomes compared to patients who receive treatment locally at low-volume centers. Strategies that facilitate patient travel to high-volume hospitals may improve outcomes.

Efficacy of riluzole in the treatment of spinal cord injury: a systematic review of the literature.

OBJECTIVERiluzole is a glutamatergic modulator that has recently shown potential for neuroprotection after spinal cord injury (SCI). While the effects of riluzole are extensively documented in animal models of SCI, there remains heterogeneity in findings. Moreover, there is a paucity of data on the pharmacology of riluzole and its effects in humans. For the present study, the authors systematically reviewed the literature to provide a comprehensive understanding of the effects of riluzole in SCI.METHODSThe PubMed database was queried from 1996 to September 2018 to identify animal studies and clinical trials involving riluzole administration for SCI. Once articles were identified, they were processed for year of publication, study design, subject type, injury model, number of subjects in experimental and control groups, dose, timing/route of administration, and outcomes.RESULTSA total of 37 studies were included in this study. Three placebo-controlled clinical trials were included with a total of 73 patients with a mean age of 39.1 years (range 18-70 years). For the clinical trials included within this study, the American Spinal Injury Association Impairment Scale distributions for SCI were 42.6% grade A, 25% grade B, 26.6% grade C, and 6.2% grade D. Key findings from studies in humans included decreased nociception, improved motor function, and attenuated spastic reflexes. Twenty-six animal studies (24 in vivo, 1 in vitro, and 1 including both in vivo and in vitro) were included. A total of 520 animals/in vitro specimens were exposed to riluzole and 515 animals/in vitro specimens underwent other treatment for comparison. The average dose of riluzole for intraperitoneal, in vivo studies was 6.5 mg/kg (range 1-10 mg/kg). Key findings from animal studies included behavioral improvement, histopathological tissue sparing, and modified electrophysiology after SCI. Eight studies examined the pharmacology of riluzole in SCI. Key findings from pharmacological studies included riluzole dose-dependent effects on glutamate uptake and its modified bioavailability after SCI in both animal and clinical models.CONCLUSIONSSCI has many negative sequelae requiring neuroprotective intervention. While still relatively new in its applications for SCI, both animal and human studies demonstrate riluzole to be a promising pharmacological intervention to attenuate the devastating effects of this condition.

Role of pregnancy and female sex steroids on aneurysm formation, growth, and rupture: a systematic review of the literature.

OBJECTIVE: Women have been shown to have a higher risk of cerebral aneurysm formation, growth, and rupture than men. The authors present a review of the recently published neurosurgical literature that studies the role of pregnancy and female sex steroids, to provide a conceptual framework with which to understand the various risk factors associated with cerebral aneurysms in women at different stages in their lives. METHODS: The PubMed database was searched for "("intracranial" OR "cerebral") AND "aneurysm" AND ("pregnancy" OR "estrogen" OR "progesterone")" between January 1980 and February 2019. A total of 392 articles were initially identified, and after applying inclusion and exclusion criteria, 20 papers were selected for review and analysis. These papers were then divided into two categories: 1) epidemiological studies about the formation, growth, rupture, and management of cerebral aneurysms in pregnancy; and 2) investigations on female sex steroids and cerebral aneurysms (animal studies and epidemiological studies). RESULTS: The 20 articles presented in this study include 7 epidemiological articles on pregnancy and cerebral aneurysms, 3 articles reporting case series of cerebral aneurysms treated by endovascular therapies in pregnancy, 3 epidemiological articles reporting the relationship between female sex steroids and cerebral aneurysms through retrospective case-control studies, and 7 experimental studies using animal and/or cell models to understand the relationship between female sex steroids and cerebral aneurysms. The studies in this review report similar risk of aneurysm rupture in pregnant women compared to the general population. Most ruptured aneurysms in pregnancy occur during the 3rd trimester, and most pregnant women who present with cerebral aneurysm have caesarean section deliveries. Endovascular treatment of cerebral aneurysms in pregnancy is shown to provide a new and safe form of therapy for these cases. Epidemiological studies of postmenopausal women show that estrogen hormone therapy and later age at menopause are associated with a lower risk of cerebral aneurysm than in matched controls. Experimental studies in animal models corroborate this epidemiological finding; estrogen deficiency causes endothelial dysfunction and inflammation, which may predispose to the formation and rupture of cerebral aneurysms, while exogenous estrogen treatment in this population may lower this risk. CONCLUSIONS: The aim of this work is to equip the neurosurgical and obstetrical/gynecological readership with the tools to better understand, critique, and apply findings from research on sex differences in cerebral aneurysms.

Management of glioblastoma at safety-net hospitals.

BACKGROUND: Safety-net hospitals (SNHs) provide disproportionate care for underserved patients. Prior studies have identified poor outcomes, increased costs, and reduced access to certain complex, elective surgeries at SNHs. However, it is unknown whether similar patterns exist for the management of glioblastoma (GBM). We sought to determine if patients treated at HBHs receive equitable care for GBM, and if safety-net burden status impacts post-treatment survival. METHODS: The National Cancer Database was queried for GBM patients diagnosed between 2010 and 2015. Safety-net burden was defined as the proportion of Medicaid and uninsured patients treated at each hospital, and stratified as low (LBH), medium (MBH), and high-burden (HBH) hospitals. The impact of safety-net burden on the receipt of any treatment, trimodality therapy, gross total resection (GTR), radiation, or chemotherapy was investigated. Secondary outcomes included post-treatment 30-day mortality, 90-day mortality, and overall survival. Univariate and multivariate analyses were utilized. RESULTS: Overall, 40,082 GBM patients at 1202 hospitals (352 LBHs, 553 MBHs, and 297 HBHs) were identified. Patients treated at HBHs were significantly less likely to receive trimodality therapy (OR = 0.75, p < 0.001), GTR (OR = 0.84, p < 0.001), radiation (OR = 0.73, p < 0.001), and chemotherapy (OR = 0.78, p < 0.001) than those treated at LBHs. Patients treated at HBHs had significantly increased 30-day (OR = 1.25, p = 0.031) and 90-day mortality (OR = 1.24, p = 0.001), and reduced overall survival (HR = 1.05, p = 0.039). CONCLUSIONS: GBM patients treated at SNHs are less likely to receive standard-of-care therapies and have increased short- and long-term mortality. Additional research is needed to evaluate barriers to providing equitable care for GBM patients at SNHs.

Impact of preoperative endovascular embolization on immediate meningioma resection outcomes.

OBJECTIVE Preoperative embolization of meningiomas can facilitate their resection when they are difficult to remove. The optimal use and timing of such a procedure remains controversial given the risk of embolization-linked morbidity in select clinical settings. In this work, the authors used a large national database to study the impact of immediate preoperative embolization on the immediate outcomes of meningioma resection. METHODS Meningioma patients who had undergone elective resection were identified in the National (Nationwide) Inpatient Sample (NIS) for the period 2002-2014. Patients who had undergone preoperative embolization were propensity score matched to those who had not, adjusting for patient and hospital characteristics. Associations between preoperative embolization and morbidity, mortality, and nonroutine discharge were investigated. RESULTS Overall, 27,008 admissions met the inclusion criteria, and 633 patients (2.34%) had undergone preoperative embolization and 26,375 (97.66%) had not. The embolization group was younger (55.17 vs 57.69 years, p < 0.001) with a lower proportion of females (63.5% vs 69.1%, p = 0.003), higher Charlson Comorbidity Index (p = 0.002), and higher disease severity (p < 0.001). Propensity score matching retained 413 embolization and 413 nonembolization patients. In the matched cohort, preoperative embolization was associated with increased rates of cerebral edema (25.2% vs 17.7%, p = 0.009), posthemorrhagic anemia or transfusion (21.8% vs 13.8%, p = 0.003), and nonroutine discharge (42.8% vs 35.7%, p = 0.039). There was no difference in mortality (≤ 2.4% vs ≤ 2.4%, p = 0.82). Among the embolization patients, the mean interval from embolization to resection was 1.49 days. On multivariate analysis, a longer interval was significantly associated with nonroutine discharge (OR 1.33, p = 0.004) but not with complications or mortality. CONCLUSIONS Relative to meningioma patients who do not undergo preoperative embolization in the same admission, those who do have higher rates of cerebral edema and nonroutine discharge but not higher rates of stroke or death. Thus, meningiomas requiring preoperative embolization represent a distinct clinical entity that requires prolonged, more complex care. Further, among embolization patients, the timing of resection did not affect the risk of in-hospital complications, suggesting that the timing of surgery can be determined according to surgeon discretion.

Markov modeling for the neurosurgeon: a review of the literature and an introduction to cost-effectiveness research.

OBJECTIVE Markov modeling is a clinical research technique that allows competing medical strategies to be mathematically assessed in order to identify the optimal allocation of health care resources. The authors present a review of the recently published neurosurgical literature that employs Markov modeling and provide a conceptual framework with which to evaluate, critique, and apply the findings generated from health economics research. METHODS The PubMed online database was searched to identify neurosurgical literature published from January 2010 to December 2017 that had utilized Markov modeling for neurosurgical cost-effectiveness studies. Included articles were then assessed with regard to year of publication, subspecialty of neurosurgery, decision analytical techniques utilized, and source information for model inputs. RESULTS A total of 55 articles utilizing Markov models were identified across a broad range of neurosurgical subspecialties. Sixty-five percent of the papers were published within the past 3 years alone. The majority of models derived health transition probabilities, health utilities, and cost information from previously published studies or publicly available information. Only 62% of the studies incorporated indirect costs. Ninety-three percent of the studies performed a 1-way or 2-way sensitivity analysis, and 67% performed a probabilistic sensitivity analysis. A review of the conceptual framework of Markov modeling and an explanation of the different terminology and methodology are provided. CONCLUSIONS As neurosurgeons continue to innovate and identify novel treatment strategies for patients, Markov modeling will allow for better characterization of the impact of these interventions on a patient and societal level. The aim of this work is to equip the neurosurgical readership with the tools to better understand, critique, and apply findings produced from cost-effectiveness research.

Prophylactic anticonvulsants in patients with primary glioblastoma.

Glioblastoma is the most common form of primary brain cancer in adults and one of the deadliest of human cancers. Seizures are one of the most frequent presentations of glioblastoma. The use of anti-epileptic drugs (AEDs) in glioblastoma patients suffering from seizures is well accepted. However, the role of long-term AED use in patients with glioblastoma without a history of seizures is controversial. Here, we performed a review of the literature to identify studies that examined the use of AEDs in seizure-free glioblastoma patients. We identified one randomized controlled study suggesting no clinical benefit of seizure prophylaxis in this population. Three of the four retrospective studies identified in our search recapitulated this finding, while the remaining study suggested a benefit for prophylactic AED use. All identified studies were focused on seizure incidence in the post-operative period, ranging from 1 week to long-term follow up. Implications of these findings are reviewed herein.

Analyzing cost-effectiveness of ulnar and median nerve transfers to regain forearm flexion.

OBJECTIVE Peripheral nerve transfers to regain elbow flexion via the ulnar nerve (Oberlin nerve transfer) and median nerves are surgical options that benefit patients. Prior studies have assessed the comparative effectiveness of ulnar and median nerve transfers for upper trunk brachial plexus injury, yet no study has examined the cost-effectiveness of this surgery to improve quality-adjusted life years (QALYs). The authors present a cost-effectiveness model of the Oberlin nerve transfer and median nerve transfer to restore elbow flexion in the adult population with upper brachial plexus injury. METHODS Using a Markov model, the authors simulated ulnar and median nerve transfers and conservative measures in terms of neurological recovery and improvements in quality of life (QOL) for patients with upper brachial plexus injury. Transition probabilities were collected from previous studies that assessed the surgical efficacy of ulnar and median nerve transfers, complication rates associated with comparable surgical interventions, and the natural history of conservative measures. Incremental cost-effectiveness ratios (ICERs), defined as cost in dollars per QALY, were calculated. Incremental cost-effectiveness ratios less than $50,000/QALY were considered cost-effective. One-way and 2-way sensitivity analyses were used to assess parameter uncertainty. Probabilistic sampling was used to assess ranges of outcomes across 100,000 trials. RESULTS The authors' base-case model demonstrated that ulnar and median nerve transfers, with an estimated cost of $5066.19, improved effectiveness by 0.79 QALY over a lifetime compared with conservative management. Without modeling the indirect cost due to loss of income over lifetime associated with elbow function loss, surgical treatment had an ICER of $6453.41/QALY gained. Factoring in the loss of income as indirect cost, surgical treatment had an ICER of -$96,755.42/QALY gained, demonstrating an overall lifetime cost savings due to increased probability of returning to work. One-way sensitivity analysis demonstrated that the model was most sensitive to assumptions about cost of surgery, probability of good surgical outcome, and spontaneous recovery of neurological function with conservative treatment. Two-way sensitivity analysis demonstrated that surgical intervention was cost-effective with an ICER of $18,828.06/QALY even with the authors' most conservative parameters with surgical costs at $50,000 and probability of success of 50% when considering the potential income recovered through returning to work. Probabilistic sampling demonstrated that surgical intervention was cost-effective in 76% of cases at a willingness-to-pay threshold of $50,000/QALY gained. CONCLUSIONS The authors' model demonstrates that ulnar and median nerve transfers for upper brachial plexus injury improves QALY in a cost-effective manner.

Nerve transfer versus muscle transfer to restore elbow flexion after pan-brachial plexus injury: a cost-effectiveness analysis.

OBJECTIVE Pan-brachial plexus injury (PBPI), involving C5-T1, disproportionately affects young males, causing lifelong disability and decreased quality of life. The restoration of elbow flexion remains a surgical priority for these patients. Within the first 6 months of injury, transfer of spinal accessory nerve (SAN) fascicles via a sural nerve graft or intercostal nerve (ICN) fascicles to the musculocutaneous nerve can restore elbow flexion. Beyond 1 year, free-functioning muscle transplantation (FFMT) of the gracilis muscle can be used to restore elbow flexion. The authors present the first cost-effectiveness model to directly compare the different treatment strategies available to a patient with PBPI. This model assesses the quality of life impact, surgical costs, and possible income recovered through restoration of elbow flexion. METHODS A Markov model was constructed to simulate a 25-year-old man with PBPI without signs of recovery 4.5 months after injury. The management options available to the patient were SAN transfer, ICN transfer, delayed FFMT, or no treatment. Probabilities of surgical success rates, quality of life measurements, and disability were derived from the published literature. Cost-effectiveness was defined using incremental cost-effectiveness ratios (ICERs) defined by the ratio between costs of a treatment strategy and quality-adjusted life years (QALYs) gained. A strategy was considered cost-effective if it yielded an ICER less than a willingness-to-pay of $50,000/QALY gained. Probabilistic sensitivity analysis (PSA) was performed to address parameter uncertainty. RESULTS The base case model demonstrated a lifetime QALYs of 22.45 in the SAN group, 22.0 in the ICN group, 22.3 in the FFMT group, and 21.3 in the no-treatment group. The lifetime costs of income lost through disability and interventional/rehabilitation costs were $683,400 in the SAN group, $727,400 in the ICN group, $704,900 in the FFMT group, and $783,700 in the no-treatment group. Each of the interventional modalities was able to dramatically improve quality of life and decrease lifelong costs. A Monte Carlo PSA demonstrated that at a willingness-to-pay of $50,000/QALY gained, SAN transfer dominated in 88.5% of iterations, FFMT dominated in 7.5% of iterations, ICN dominated in 3.5% of iterations, and no treatment dominated in 0.5% of iterations. CONCLUSIONS This model demonstrates that nerve transfer surgery and muscle transplantation are cost-effective strategies in the management of PBPI. These reconstructive neurosurgical modalities can improve quality of life and lifelong earnings through decreasing disability.

Pipeline embolization device versus coiling for the treatment of large and giant unruptured intracranial aneurysms: a cost-effectiveness analysis.

OBJECTIVE Rupture of large or giant intracranial aneurysms leads to significant morbidity, mortality, and health care costs. Both coiling and the Pipeline embolization device (PED) have been shown to be safe and clinically effective for the treatment of unruptured large and giant intracranial aneurysms; however, the relative cost-to-outcome ratio is unknown. The authors present the first cost-effectiveness analysis to compare the economic impact of the PED compared with coiling or no treatment for the endovascular management of large or giant intracranial aneurysms. METHODS A Markov model was constructed to simulate a 60-year-old woman with a large or giant intracranial aneurysm considering a PED, endovascular coiling, or no treatment in terms of neurological outcome, angiographic outcome, retreatment rates, procedural and rehabilitation costs, and rupture rates. Transition probabilities were derived from prior literature reporting outcomes and costs of PED, coiling, and no treatment for the management of aneurysms. Cost-effectiveness was defined, with the incremental cost-effectiveness ratios (ICERs) defined as difference in costs divided by the difference in quality-adjusted life years (QALYs). The ICERs < $50,000/QALY gained were considered cost-effective. To study parameter uncertainty, 1-way, 2-way, and probabilistic sensitivity analyses were performed. RESULTS The base-case model demonstrated lifetime QALYs of 12.72 for patients in the PED cohort, 12.89 for the endovascular coiling cohort, and 9.7 for patients in the no-treatment cohort. Lifetime rehabilitation and treatment costs were $59,837.52 for PED; $79,025.42 for endovascular coiling; and $193,531.29 in the no-treatment cohort. Patients who did not undergo elective treatment were subject to increased rates of aneurysm rupture and high treatment and rehabilitation costs. One-way sensitivity analysis demonstrated that the model was most sensitive to assumptions about the costs and mortality risks for PED and coiling. Probabilistic sampling demonstrated that PED was the cost-effective strategy in 58.4% of iterations, coiling was the cost-effective strategy in 41.4% of iterations, and the no-treatment option was the cost-effective strategy in only 0.2% of iterations. CONCLUSIONS The authors' cost-effective model demonstrated that elective endovascular techniques such as PED and endovascular coiling are cost-effective strategies for improving health outcomes and lifetime quality of life measures in patients with large or giant unruptured intracranial aneurysm.

The circle of Willis predicts the antihypertensive effects of carotid artery stenting.

OBJECTIVE Carotid artery stenting (CAS) has antihypertensive effects, but the durability and degree of this response remain variable. The authors propose that this clinical variability is a function of the presence or absence of a complete circle of Willis (COW). Incomplete COWs perfuse through a higher-resistance pial collateral pathway, and therefore patients may require a higher mean arterial pressure (MAP). Carotid artery revascularization in these patients would reduce the end-organ collateral demand that has been hypothesized to drive the MAP response. METHODS Using a retrospective, nonrandomized within-subject case-control design, the authors compared the postoperative effects of CAS in patients with and without a complete COW by using changes in MAP and antihypertensive medication as end points. They recorded MAP and antihypertensive medications 3 months prior to surgery, preoperatively, immediately postoperatively, and at the 3-month follow-up. RESULTS Data were collected from 64 consecutive patients undergoing CAS. Patients without a complete COW (25%) were more likely to demonstrate a decrease in BP response to stenting (i.e., a drop in MAP of 10 mm Hg and/or a reduction or cessation of BP medications at 3 months postoperatively). Of the patients in the incomplete COW cohort, 75% had this outcome, whereas of those in the complete COW cohort, only 41% had it (p < 0.041). These findings remained statistically significant in a logistic regression analysis for possible confounders (p < 0.024). A receiver operating curve analysis of preoperative data indicated that a MAP > 96.3 mm Hg was 55.5% sensitive and 57.4% specific for predicting a complete COW and that patients with a MAP > 96.3 mm Hg were more likely to demonstrate a good MAP decrease following CAS (p < 0.0092). CONCLUSIONS CAS is associated with a significant decrease in MAP and/or a reduction/cessation in BP medications in patients in whom a complete COW is absent.

Vessel wall signal enhancement on 3-T MRI in acute stroke patients after stent retriever thrombectomy.

OBJECTIVE In vivo and in vitro studies have demonstrated histological evidence of iatrogenic endothelial injury after stent retriever thrombectomy. However, noncontrast vessel wall (VW)-MRI is insufficient to demonstrate vessel injury. Authors of this study prospectively evaluated iatrogenic endothelial damage after stent retriever thrombectomy in humans by utilizing high-resolution contrast-enhanced VW-MRI. Characterization of VW-MRI changes in vessels subject to mechanical injury from thrombectomy may allow better understanding of the biological effects of this intervention. METHODS The authors prospectively recruited 11 patients for this study. The treatment group included 6 postthrombectomy patients and the control group included 5 subjects undergoing MRI for nonvascular indications. All subjects were evaluated on a Signa HD× 3.0-T MRI scanner with an 8-channel head coil. Both pre- and postcontrast T1-weighted Cube VW images as well as MR angiograms were acquired. Sequences obtained for evaluation of the brain parenchyma included diffusion-weighted, gradient echo, and T2-FLAIR imaging. Two independent neuroradiologists, who were blinded to the treatment status of each patient, determined the presence of VW enhancement. Patient age, National Institutes of Health Stroke Scale score on presentation, location of occlusion, stroke etiology, type of device used, number of device deployments, Thrombolysis in Cerebral Infarction (TICI) reperfusion score, stroke volume, and 90-day modified Rankin Scale score were also noted. RESULTS Postcontrast T1-weighted VW enhancement was detected in the M2 segment in 100% of the thrombectomy patients, in the M1 segment in 83%, and in the internal carotid artery in 50%. One patient also demonstrated A1 segment enhancement, which was attributable to thrombectomy treatment of that vessel segment during the same procedure. None of the control patients demonstrated VW enhancement of their intracranial vasculature on T1-weighted images. CONCLUSIONS The study findings suggest that VW injury incurred during stent retriever thrombectomy can be reliably detected utilizing contrast-enhanced 3-T VW-MRI. The results further demonstrate that endothelial injury is associated with oversizing of stent retrievers relative to the treated vessel. Further studies are needed to evaluate the clinical significance of endothelial injury and to characterize the differential effects of various devices.