Trends in Demographics of Neurology House Staff in the United States.

Background The lack of an adequate number of neurologists is a worldwide problem. As populations age, the prevalence of neurological disorders will likely increase, thereby increasing the demand for neurologists. In addition to the growing demand, inadequate diversity in the neurology healthcare workforce still exists. The purpose of this study is to examine the demographic characteristics of neurology residents and fellows. Methodology This cross-sectional study used data from the following publicly available databases: Accreditation Council for Graduate Medical Education, Association of American Medical Colleges, and the United States Census Bureau. Trends (from 2007 to 2018) in demographic characteristics were assessed using the slope and the associated p-value of a simple linear regression model, with the year as the independent variable. All p-values of <0.05 were considered significant. Results From 2007 through 2018, the percentage of US medical school graduates in neurology residency decreased from 58% to 55% (slope = -0.25; p = 0.0004), while the percentage of international medical graduates (IMGs) decreased from 36% to 32% (slope = -0.29; p = 0.0141) and doctor of osteopathy (DO) graduates increased from 6% to 13% (slope = 0.58; p < 0.0001). Although the percentage of female neurology residents increased from 39.5% in 2007 to 43.1% in 2018 (slope = 0.03; p = 0.8659), female physicians were underrepresented in vascular neurology fellowship (34% in 2018). Collectively, the percentage of underrepresented minorities in neurology residencies was low and increased only slightly over time (from 8% in 2011 to 9% in 2018; slope = 0.17; p = 0.0788). In 2018, the proportion of underrepresented minorities was smaller in neurology fellowships (5.5% neurophysiology, 12.5% epilepsy, 10.4% neuromuscular, and 12.4% vascular) compared to the population as a whole (31.3%). Conclusions IMGs still play an important role in filling a significant portion of the neurology residencies and fellowships. DO graduates have slowly increased in neurology residencies and fellowships. Members of several racial/ethnic minority groups and women are underrepresented in neurology house staff and efforts need to be taken to increase diversity.

Continued Underutilization of stroke care during the COVID-19 pandemic.

OBJECTIVE: This study aims to investigate the utilization of acute ischemic stroke (AIS) services during the Corona Virus Disease 2019 (COVID-19) pandemic. Based on early observations among healthcare utilization on stroke and other healthcare services, we hypothesized that there would be a persistent significant decline in AIS patients presenting to hospitals as the pandemic has progressed for over a year. METHOD: TriNetX, a large research network, is used to collect real-time electronic medical data. Data on utilization of acute ischemic stroke service was collected for the years 2018, 2019, and 2020 for variables including overall stroke volume and the number of patients that received intravenous tissue plasminogen activator (tPA) and mechanical thrombectomy (MT). RESULT: We found a 13.2-15.4% decrease in total number of AIS patients in 2020 (n 77231) compared with the years 2018 and 2019 (n 88948 and 91270 respectively, p â€‹< â€‹0.001). In the year 2020 Stroke volume was significantly lower in Q4 comparing to Q1 (Q1 vs Q4, p â€‹< â€‹0.01, while there were no significant differences in stroke volume between Quarters 2, 3, and 4 in 2020 (Q2 vs Q3, p â€‹= â€‹0.39, Q2 vs Q4, p â€‹= â€‹0.61, Q3 vs Q4, p â€‹= â€‹0.18). The Proportion of patients receiving tPA in 2020 was significantly lower compared to prior years (5.4% in 2020 vs 6.4% in 2018 and 6.0% in 2019, p â€‹< â€‹0.01), however, the proportion of patients receiving MT was significantly higher in 2020 than in 2018 (0.024 vs 0.022, p â€‹< â€‹0.01). CONCLUSION: Despite significant alteration in practices to optimize healthcare delivery and mitigate the collateral impact of the pandemic on care for other conditions, a persistent decline in AIS volumes remains. Delayed presentation, fear-of-contagion, reallocation, and poor availability of health care resources are potential contributors. Prospective evaluation and further investigation for these trends is needed.

Infratentorial Glioblastoma Metastasis to Bone.

BACKGROUND: Glioblastoma multiforme (GBM) is a rapid-growing central nervous system neoplasm. We report a case of GBM with extensive intramedullary lumbar drop metastasis and highly unusual osseous spine metastasis from a primary infratentorial GBM occurring 10 years after the initial diagnosis, which to our knowledge has not been described previously. CASE DESCRIPTION: This 37-year-old man presented with new-onset headaches of increasing severity. Brain magnetic resonance imaging (MRI) demonstrated a heterogeneously enhancing mass in the left superior temporal lobe with adjacent edema. The lesion was initially biopsied in December 2006 and diagnosed as GBM (World Health Organization grade IV) with characteristic features of a highly cellular infiltrating glial neoplasm with nuclear pleomorphism, abundant microvascular proliferation, and abundant necrosis with pseudopalisading nuclei. Ki-67 immunostaining revealed that 15%-20% tumor cell nuclei were positive, indicating a high proliferative index. Histologically, this neoplasm demonstrated characteristic "cell wrapping." Immunoreactivity was variably but strongly positive for glial fibrillary acidic protein in neoplastic cells. In 2018, additional MRI revealed disease throughout the spine and bone biopsy of the thoracic spine showed the same glial neoplasm with primitive neuroectodermal tumor-like components (GBM-PNET). CONCLUSIONS: This case is meant to highlight that, although rare, infratentorial GBM-PNET has a higher frequency of isocitrate dehydrogenase 1 (IDH1) mutation and may metastasize to the spine years after the initial diagnosis despite the likely better prognosis.

FTY720 Improves Behavior, Increases Brain Derived Neurotrophic Factor Levels and Reduces α-Synuclein Pathology in Parkinsonian GM2+/- Mice.

Parkinson's disease (PD) is a progressive aging disorder that affects millions worldwide, thus, disease-modifying-therapies are urgently needed. PD pathology includes α-synuclein (aSyn) accumulation as synucleinopathy. Loss of GM1 gangliosides occurs in PD brain, which is modeled in GM2 synthase transgenic mice. GM2+/- mice have low, not absent GM1 and develop age-onset motor deficits, making them an excellent PD drug testing model. FTY720 (fingolimod) reduces synucleinopathy in A53T aSyn mice and motor dysfunction in 6-OHDA and rotenone PD models, but no one has tested FTY720 in mice that develop age-onset PD-like motor problems. We confirmed that GM2+/-mice had equivalent rotarod, hindlimb reflexes, and adhesive removal functions at 9 mo. From 11 mo, GM2+/- mice received oral FTY720 or vehicle 3x/week to 16 mo. As bladder problems occur in PD, we also assessed GM2+/- bladder function. This allowed us to demonstrate improved motor and bladder function in GM2+/- mice treated with FTY720. By immunoblot, FTY720 reduced levels of proNGF, a biomarker of bladder dysfunction. In humans with PD, arm swing becomes abnormal, and brachial plexus modulates arm swing. Ultrastructure of brachial plexus in wild type and GM2 transgenic mice confirmed abnormal myelination and axons in GM2 transgenics. FTY720 treated GM2+/- brachial plexus sustained myelin associated protein levels and reduced aggregated aSyn and PSer129 aSyn levels. FTY720 increases brain derived neurotrophic factor (BDNF) and we noted increased BDNF in GM2+/- brachial plexus and cerebellum, which contribute to rotarod performance. These findings provide further support for testing low dose FTY720 in patients with PD.

Parkinsonian GM2 synthase knockout mice lacking mature gangliosides develop urinary dysfunction and neurogenic bladder.

Parkinson's disease is a neurodegenerative disorder that reduces a patients' quality of life by the relentless progression of motor and non-motor symptoms. Among the non-motor symptoms is a condition called neurogenic bladder that is associated with detrusor muscle underactivity or overactivity occurring from neurologic damage. In Parkinson's disease, Lewy-body-like protein aggregation inside neurons typically contributes to pathology. This is associated with dopaminergic neuron loss in substantia nigra pars compacta (SNc) and in ventral tegmental area (VTA), both of which play a role in micturition. GM1 gangliosides are mature glycosphingolipids that enhance normal myelination and are reduced in Parkinson's brain. To explore the role of mature gangliosides in vivo, we obtained GM2 Synthase knockout (KO) mice, which develop parkinsonian pathology including a loss of SNc dopaminergic neurons, which we reconfirmed. However, bladder function and innervation have never been assessed in this model. We compared GM2 Synthase KO and wild type (WT) littermates' urination patterns from 9 to 19 months of age by counting small and large void spots produced during 1 h tests. Because male and female mice had different patterns, we evaluated data by sex and genotype. Small void spots were significantly increased in 12-16 month GM2 Synthase KO females, consistent with overactive bladder. Similarly, at 9-12 month GM2 KO males tended to have more small void spots than WT males. As GM2 Synthase KO mice aged, both females and males had fewer small and large void spots, consistent with detrusor muscle underactivity. Ultrasounds confirmed bladder enlargement in GM2 Synthase KO mice compared to WT mice. Tyrosine hydroxylase (TH) immunohistochemistry revealed significant dopaminergic loss in GM2 Synthase KO VTA and SNc, and a trend toward TH loss in the GM2 KO periaqueductal gray (PAG) micturition centers. Levels of the nerve growth factor precursor, proNGF, were significantly increased in GM2 Synthase KO bladders and transmission electron micrographs showed atypical myelination of pelvic ganglion innervation in GM2 Synthase KO bladders. Cumulatively, our findings provide the first evidence that mature ganglioside loss affects micturition center TH neurons as well as proNGF dysregulation and abnormal innervation of the bladder. Thus, identifying therapies that will counteract these effects should be beneficial for those suffering from Parkinson's disease and related disorders.

FTY720/Fingolimod Reduces Synucleinopathy and Improves Gut Motility in A53T Mice: CONTRIBUTIONS OF PRO-BRAIN-DERIVED NEUROTROPHIC FACTOR (PRO-BDNF) AND MATURE BDNF.

Patients with Parkinson's disease (PD) often have aggregated α-synuclein (aSyn) in enteric nervous system (ENS) neurons, which may be associated with the development of constipation. This occurs well before the onset of classic PD motor symptoms. We previously found that aging A53T transgenic (Tg) mice closely model PD-like ENS aSyn pathology, making them appropriate for testing potential PD therapies. Here we show that Tg mice overexpressing mutant human aSyn develop ENS pathology by 4 months. We then evaluated the responses of Tg mice and their WT littermates to the Food and Drug Administration-approved drug FTY720 (fingolimod, Gilenya) or vehicle control solution from 5 months of age. Long term oral FTY720 in Tg mice reduced ENS aSyn aggregation and constipation, enhanced gut motility, and increased levels of brain-derived neurotrophic factor (BDNF) but produced no significant change in WT littermates. A role for BDNF was directly assessed in a cohort of young A53T mice given vehicle, FTY720, the Trk-B receptor inhibitor ANA-12, or FTY720 + ANA-12 from 1 to 4 months of age. ANA-12-treated Tg mice developed more gut aSyn aggregation as well as constipation, whereas FTY720-treated Tg mice had reduced aSyn aggregation and less constipation, occurring in part by increasing both pro-BDNF and mature BDNF levels. The data from young and old Tg mice revealed FTY720-associated neuroprotection and reduced aSyn pathology, suggesting that FTY720 may also benefit PD patients and others with synucleinopathy. Another finding was a loss of tyrosine hydroxylase immunoreactivity in gut neurons with aggregated aSyn, comparable with our prior findings in the CNS.