Objective: Middle meningeal artery embolization (MMAe) has burgeoned as a treatment for chronic subdural hematoma (cSDH). This study evaluates the safety and short-term outcomes of MMAe patients relative to traditional treatment approaches. Methods: In this retrospective large database study, adult patients in the National Inpatient Sample from 2012-2019 with a diagnosis of cSDH were identified. Cost of admission, length of stay (LOS), discharge disposition, and complications were analyzed. Propensity score matching (PSM) was utilized. Results: A total of 123,350 patients with cSDH were identified: 63,450 without intervention, 59,435 surgery only, 295 MMAe only, and 170 surgery plus MMAe. On PSM analysis, MMAe did not increase the risk of inpatient complications or prolong the length of stay compared to conservative management (p>0.05); MMAe had higher cost ($31,170 vs. $10,768, p<0.001) than conservative management, and a lower rate of nonroutine discharge (53.8% vs. 64.3%, p=0.024). Compared to surgery, MMAe had shorter LOS (5 vs. 7 days, p<0.001), and lower rates of neurological complications (2.7% vs. 7.1%, p=0.029) and nonroutine discharge (53.8% vs. 71.7%, p<0.001). There was no significant difference in cost (p>0.05). Conclusions MMAe had similar LOS and decreased odds of adverse discharge with a modest cost increase compared to conservative management. There was no difference in inpatient complications. Compared to surgery, MMAe treatment was associated with decreased LOS and rates of neurological complications and nonroutine discharge. This nationwide analysis supports the safety of MMAe to treat cSDH.

Human-induced pluripotent stem cells (hiPSCs) derived from somatic cells of patients have opened possibilities for in vitro modeling of the physiology of neural (and other) cells in psychiatric disease states. Issues in early stages of technology development include (1) establishing a library of cells from adequately phenotyped patients, (2) streamlining laborious, costly hiPSC derivation and characterization, (3) assessing whether mutations or other alterations introduced by reprogramming confound interpretation, (4) developing efficient differentiation strategies to relevant cell types, (5) identifying discernible cellular phenotypes meaningful for cyclic, stress induced or relapsing-remitting diseases, (6) converting phenotypes to screening assays suitable for genome-wide mechanistic studies or large collection compound testing and (7) controlling for variability in relation to disease specificity amidst low sample numbers. Coordination of material for reprogramming from patients well-characterized clinically, genetically and with neuroimaging are beginning, and initial studies have begun to identify cellular phenotypes. Finally, several psychiatric drugs have been found to alter reprogramming efficiency in vitro, suggesting further complexity in applying hiPSCs to psychiatric diseases or that some drugs influence neural differentiation moreso than generally recognized. Despite these challenges, studies utilizing hiPSCs may eventually serve to fill essential niches in the translational pipeline for the discovery of new therapeutics.
Animals ; Antipsychotic Agents/pharmacology ; *Drug Discovery ; Humans ; Induced Pluripotent Stem Cells/cytology/*drug effects/metabolism ; Mental Disorders/*drug therapy/metabolism ; *Nuclear Reprogramming

Objective: Moyamoya disease (MMD) is a vasculopathy of the internal carotid arteries with ischemic and hemorrhagic sequelae. Surgical revascularization confers upfront peri-procedural risk and costs in exchange for long-term protective benefit against hemorrhagic disease. The authors present a cost-effectiveness analysis (CEA) of surgical versus non-surgical management of MMD. Methods: A Markov Model was used to simulate a 41-year-old suffering a transient ischemic attack (TIA) secondary to MMD and now faced with operative versus nonoperative treatment options. Health utilities, costs, and outcome probabilities were obtained from the CEA registry and the published literature. The primary outcome was incremental cost-effectiveness ratio which compared the quality adjusted life years (QALYs) and costs of surgical and nonsurgical treatments. Base-case, one-way sensitivity, two-way sensitivity, and probabilistic sensitivity analyses were performed with a willingness to pay threshold of $50,000. Results: The base case model yielded 3.81 QALYs with a cost of $99,500 for surgery, and 3.76 QALYs with a cost of $106,500 for nonsurgical management. One-way sensitivity analysis demonstrated the greatest sensitivity in assumptions to cost of surgery and cost of admission for hemorrhagic stroke, and probabilities of stroke with no surgery, stroke after surgery, poor surgical outcome, and death after surgery. Probabilistic sensitivity analyses demonstrated that surgical revascularization was the cost-effective strategy in over 87.4% of simulations. Conclusions Considering both direct and indirect costs and the postoperative QALY, surgery is considerably more cost-effective than non-surgical management for adults with MMD.

Objective: Moyamoya disease (MMD) is a vasculopathy of the internal carotid arteries with ischemic and hemorrhagic sequelae. Surgical revascularization confers upfront peri-procedural risk and costs in exchange for long-term protective benefit against hemorrhagic disease. The authors present a cost-effectiveness analysis (CEA) of surgical versus non-surgical management of MMD. Methods: A Markov Model was used to simulate a 41-year-old suffering a transient ischemic attack (TIA) secondary to MMD and now faced with operative versus nonoperative treatment options. Health utilities, costs, and outcome probabilities were obtained from the CEA registry and the published literature. The primary outcome was incremental cost-effectiveness ratio which compared the quality adjusted life years (QALYs) and costs of surgical and nonsurgical treatments. Base-case, one-way sensitivity, two-way sensitivity, and probabilistic sensitivity analyses were performed with a willingness to pay threshold of $50,000. Results: The base case model yielded 3.81 QALYs with a cost of $99,500 for surgery, and 3.76 QALYs with a cost of $106,500 for nonsurgical management. One-way sensitivity analysis demonstrated the greatest sensitivity in assumptions to cost of surgery and cost of admission for hemorrhagic stroke, and probabilities of stroke with no surgery, stroke after surgery, poor surgical outcome, and death after surgery. Probabilistic sensitivity analyses demonstrated that surgical revascularization was the cost-effective strategy in over 87.4% of simulations. Conclusions Considering both direct and indirect costs and the postoperative QALY, surgery is considerably more cost-effective than non-surgical management for adults with MMD.

Embolization of the middle meningeal artery (MMA) is a safe and effective adjunct in the treatment of chronic subdural hematoma. While prior authors describe the use of coils to assist embolization by preventing reflux through eloquent collaterals, we de- scribe the use of coils to further open the MMA, allowing the administration of greater amounts of embolisate for a more robust embolization. The objective of this study was to demonstrate that helical coils can safely open the MMA following the administration of polyvinyl alcohol (PVA) particles. This allows for more embolisate to be administered into the MMA for more effective treatment. A retrospective review was conducted at our institution including intraoperative images and postoperative clinical and radiographic follow up. Failure rates using MMA embolization with PVA and helical coil augmentation were compared to failure rates in the literature of MMA embolization with PVA or ethylene vinyl-alcohol copolymer alone. A total of 8 cases were reviewed in which this technique was implemented. There were no immediate complications after treatment. All patients that underwent helical coil embolization following the administration of PVA had increased amount of embolisate delivered into the MMA. All patients at follow up had resolution of the subdural hematoma on outpatient imaging. Helical coil embolization allows for more embolisate administration into the MMA and provides a technical advantage for patients that fail traditional techniques of embolization. Case series are taking place to further test this hypothesis and identify the ideal patient population that may gain maximal yield from this novel technique.

Objective: Diagnostic cerebral angiograms (DCAs) are widely used in neurosurgery due to their high sensitivity and specificity to diagnose and characterize pathology using ionizing radiation. Eliminating unnecessary radiation is critical to reduce risk to patients, providers, and health care staff. We investigated if reducing pulse and frame rates during routine DCAs would decrease radiation burden without compromising image quality. Methods: We performed a retrospective review of prospectively acquired data after implementing a quality improvement protocol in which pulse rate and frame rate were reduced from 15 p/s to 7.5 p/s and 7.5 f/s to 4.0 f/s respectively. Radiation doses and exposures were calculated. Two endovascular neurosurgeons reviewed randomly selected angiograms of both doses and blindly assessed their quality. Results: A total of 40 consecutive angiograms were retrospectively analyzed, 20 prior to the protocol change and 20 after. After the intervention, radiation dose, radiation per run, total exposure, and exposure per run were all significantly decreased even after adjustment for BMI (all p<0.05). On multivariable analysis, we identified a 46% decrease in total radiation dose and 39% decrease in exposure without compromising image quality or procedure time. Conclusions We demonstrated that for routine DCAs, pulse rate of 7.5 with a frame rate of 4.0 is sufficient to obtain diagnostic information without compromising image quality or elongating procedure time. In the interest of patient, provider, and health care staff safety, we strongly encourage all interventionalists to be cognizant of radiation usage to avoid unnecessary radiation exposure and consequential health risks.

Objective: Although stroke guidelines recommend antiplatelets be started 24 hoursafter tissue plasminogen activator (tPA), select mechanical thrombectomy (MT)patients with luminal irregularities or underlying intracranial atherosclerotic diseasemay benefit from earlier antiplatelet administration. Methods: We explore the safety of early (< 24 hours) post-tPA antiplatelet use byretrospectively reviewing patients who underwent MT and stent placement for acuteischemic stroke from June 2015 to April 2018 at our institution. Results: Six patients met inclusion criteria. Median presenting and pre-operativeNational Institutes of Health Stroke Scale scores were 14 (Interquartile Range [IQR]5.5-17.3) and 16 (IQR 13.7-18.7), respectively. Five patients received standard intravenous(IV) tPA and one patient received intra-arterial tPA. Median time from symptomonset to IV tPA was 120 min (IQR 78-204 min). Median time between tPA and antiplateletadministration was 4.9 hours (IQR 3.0-6.7 hours). Clots were successfullyremoved from the internal carotid artery (ICA) or middle cerebral artery (MCA) in 5patients, the anterior cerebral artery (ACA) in one patient, and the vertebrobasilarjunction in one patient. All patients underwent MT before stenting and achievedthrombolysis in cerebral infarction 2B recanalization. Stents were placed in the ICA(n=4), common carotid artery (n=1), and basilar artery (n=1). The median time fromstroke onset to endovascular access was 185 min (IQR 136-417 min). No patientsexperienced symptomatic post-procedure intracranial hemorrhage (ICH). Medianmodified Rankin Scale score on discharge was 3.5. Conclusions Antiplatelets within 24 hours of tPA did not result in symptomatic ICHin this series. The safety and efficacy of early antiplatelet administration after tPA inselect patients following mechanical thrombectomy warrants further study.