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OBJECTIVE Characterizing changes in the geographic distribution of neurosurgeons in the United States (US) may inform efforts to provide a more equitable distribution of neurosurgical care. Herein, the authors performed a comprehensive analysis of the geographic movement and distribution of the neurosurgical workforce. METHODS A list containing all board-certified neurosurgeons practicing in the US in 2019 was obtained from the American Association of Neurological Surgeons membership database. Chi-square analysis and a post hoc comparison with Bonferroni correction were performed to assess differences in demographics and geographic movement throughout neurosurgeon careers. Three multinomial logistic regression models were performed to further evaluate relationships among training location, current practice location, neurosurgeon characteristics, and academic productivity. RESULTS The study cohort included 4075 (3830 male, 245 female) neurosurgeons practicing in the US. Seven hundred eighty-one neurosurgeons practice in the Northeast, 810 in the Midwest, 1562 in the South, 906 in the West, and 16 in a US territory. States with the lowest density of neurosurgeons included Vermont and Rhode Island in the Northeast; Arkansas, Hawaii, and Wyoming in the West; North Dakota in the Midwest; and Delaware in the South. Overall, the effect size, as measured by Cramér’s V statistic, between training stage and training region is relatively modest at 0.27 (1.0 is complete dependence); this finding was reflected in the similarly modest pseudo R2 values of the multinomial logit models, which ranged from 0.197 to 0.246. Multinomial logistic regression with L1 regularization revealed significant associations between current practice region and residency region, medical school region, age, academic status, sex, or race (p < 0.05). On subanalysis of the academic neurosurgeons, the region of residency training correlated with an advanced degree type in the overall neurosurgeon cohort, with more neurosurgeons than expected holding Doctor of Medicine and Doctor of Philosophy degrees in the West (p = 0.021). CONCLUSIONS Female neurosurgeons were less likely to practice in the South, and neurosurgeons in the South and West had reduced odds of holding academic rather than private positions. The Northeast was the most likely region to contain neurosurgeons who had completed their training in the same locality, particularly among academic neurosurgeons who did their residency in the Northeast.

OBJECTIVEThis study aimed to assess the safety and efficacy of MR-guided stereotactic laser ablation (SLA) therapy in the treatment of pediatric brain tumors.METHODSData from 17 North American centers were retrospectively reviewed. Clinical, technical, and radiographic data for pediatric patients treated with SLA for a diagnosis of brain tumor from 2008 to 2016 were collected and analyzed.RESULTSA total of 86 patients (mean age 12.2 ± 4.5 years) with 76 low-grade (I or II) and 10 high-grade (III or IV) tumors were included. Tumor location included lobar (38.4%), deep (45.3%), and cerebellar (16.3%) compartments. The mean follow-up time was 24 months (median 18 months, range 3–72 months). At the last follow-up, the volume of SLA-treated tumors had decreased in 80.6% of patients with follow-up data. Patients with high-grade tumors were more likely to have an unchanged or larger tumor size after SLA treatment than those with low-grade tumors (OR 7.49, p = 0.0364). Subsequent surgery and adjuvant treatment were not required after SLA treatment in 90.4% and 86.7% of patients, respectively. Patients with high-grade tumors were more likely to receive subsequent surgery (OR 2.25, p = 0.4957) and adjuvant treatment (OR 3.77, p = 0.1711) after SLA therapy, without reaching significance. A total of 29 acute complications in 23 patients were reported and included malpositioned catheters (n = 3), intracranial hemorrhages (n = 2), transient neurological deficits (n = 11), permanent neurological deficits (n = 5), symptomatic perilesional edema (n = 2), hydrocephalus (n = 4), and death (n = 2). On long-term follow-up, 3 patients were reported to have worsened neuropsychological test results. Pre-SLA tumor volume, tumor location, number of laser trajectories, and number of lesions created did not result in a significantly increased risk of complications; however, the odds of complications increased by 14% (OR 1.14, p = 0.0159) with every 1-cm3 increase in the volume of the lesion created.CONCLUSIONSSLA is an effective, minimally invasive treatment option for pediatric brain tumors, although it is not without risks. Limiting the volume of the generated thermal lesion may help decrease the incidence of complications.

Neprilysin-2 (NEP2), a close homolog of neprilysin (NEP), degrades amyloid-β (Aβ) and serves an important role in clearing Aβ in vivo. We measured NEP2 and NEP mRNA levels from non-impaired (NI), mild cognitive impaired (MCI), and clinical Alzheimer’s disease (AD) subjects in the mid-temporal gyrus, mid-frontal gyrus, caudate, and cerebellum. NEP2 activity levels were also determined. Our results indicate that NEP2 and NEP mRNA expression is altered in MCI subjects relative to NI subjects in AD-susceptible regions. NEP2 enzymatic activity was lowered in association with MCI and AD and was positively associated with level of cognitive function, independent of diagnostic category. Our finding that NEP2 expression and activity are altered in MCI is significant as these changes may potentially serve as preclinical markers for AD and reduced NEP2 activity may be associated with the development of AD.

Intranasal administration is emerging as a reliable and non-invasive method to bypass the blood-brain barrier and deliver drugs to the brain. This approach has been primarily used to explore therapeutic avenues for neurological diseases. However, intranasal administration could also be used to create animal models of brain disease. Beta-amyloid peptide (Aβ) accumulation is a key feature of Alzheimer's disease (AD), and the most common models of AD are transgenic mice expressing mutant human genes linked to familial AD. An alternative model of amyloidosis utilizes intracerebroventricular infusion of thiorphan or phosphoramidon to block the activity of key Aβ degrading enzymes (NEP, NEP2) resulting in accumulation of Aβ. Here, we demonstrate that intranasal administration of phosphoramidon produces significantly elevated cerebral Aβ levels in wild-type mice. Furthermore, intranasal phosphoramidon administration in double knockout mice lacking NEP and NEP2 also showed increased levels of Aβ(40). These data show that intranasal delivery of drugs can be used to model AD and suggest that other phosphoramidon-sensitive peptidases are degrading Aβ in NEP/NEP2-deficient mice.