A stroke volume of arterial blood that arrives to the brain housed in the rigid cranium must be matched over the cardiac cycle by an equivalent volume of ejected venous blood. We hypothesize that the ...brain maintains this equilibrium by organizing coherent arterial and venous pulse waves. To test this hypothesis, we applied wavelet computational methods to diagnostic cerebral angiograms in four human patients, permitting the capture and analysis of cardiac frequency phenomena from fluoroscopic images acquired at faster than cardiac rate. We found that the cardiac frequency reciprocal phase of a small region of interest (ROI) in a named artery predicts venous anatomy pixel-wise and that the predicted pixels reconstitute venous bolus passage timing. Likewise, a small ROI in a named vein predicts arterial anatomy and arterial bolus passage timing. The predicted arterial and venous pixel groups maintain phase complementarity across the bolus travel. We thus establish a novel computational method to analyze vascular pulse waves from minimally invasive cerebral angiograms and provide the first direct evidence of arteriovenous coupling in the intact human brain. This phenomenon of arteriovenous coupling may be a physiologic mechanism for how the brain precisely maintains mechanical equilibrium against volume displacement and kinetic energy transfer resulting from cyclical deformations with each heartbeat. The study also paves the way to study deranged arteriovenous coupling as an underappreciated pathophysiologic disturbance in a myriad of neurological pathologies linked by mechanical disequilibrium.
Timely dissemination of results from clinical studies is crucial for the advancement of knowledge and clinical decision making. A large body of research has shown that up to half of clinical trials ...do not publish their findings. In this study, we sought to determine whether clinical trial publication rates within neurology have increased over time. Focusing on neurology clinical trials completed between 2008 to 2014, we found that while the overall percentage of published trials has not changed (remaining at approximately 50%), time to publication has significantly decreased. Our findings suggest that clinical trials within neurology are being published in a more timely manner.
Research experience is believed to be an important component of the neurosurgery residency application process. One measure of research productivity is publication volume. The preresidency ...publication volume of U.S. neurosurgery interns and any potential association between applicant publication volume and the match results of top-ranked residency programs have not been well characterized.
In this study, we sought to characterize the preresidency publication volume of U.S. neurosurgery residents in the 2018–2019 intern class using the Scopus database.
For each intern, we recorded the total number of publications, total number of first or last author publications, total number of neuroscience-related publications, mean number of citations per publication, and mean impact factor of the journal per publication. Preresidency publication volumes of interns at the top-25 programs (based on a composite ranking score according to 4 different ranking metrics) were compared with those at all other programs.
We found that 82% of neurosurgery interns included in the analysis (190 interns from 95 programs) had at least 1 publication. The average number of publications per intern among all programs was 6 ± 0.63 (mean ± standard error of the mean). We also found that interns at top-25 neurosurgery residency programs tended to have a higher number of publications (8.3 ± 1.2 vs. 4.8 ± 0.7, P = 0.0137), number of neuroscience-related publications (6.8 ± 1.1 vs. 4.1 ± 0.7, P = 0.0419), and mean number of citations per publication (9.8 ± 1.7 vs. 5.7 ± 0.8, P = 0.0267) compared with interns at all other programs.
Our results provide a general estimate of the preresidency publication volume of U.S. neurosurgery interns and suggest a potential association between publication volume and matching in the top-25 neurosurgery residency programs.
To describe and assess the educational value of a functional neurosurgery clinical shadowing and research tutorial for pre-medical trainees.
Program participants observed functional neurosurgery ...procedures and conducted basic science and clinical research in neurosurgery fields. Former participants completed a brief online survey to evaluate their perspectives and experiences throughout the tutorial.
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
15 pre-medical and post-baccalaureate trainees participated in the tutorial. All former tutorial participants were emailed.
11/15 former participants responded to the survey. Survey results suggest that the tutorial program increased participants' understanding of and interest in neurosurgery and related fields in neuroscience.
The functional neurosurgery medical tutorial provides valuable clinical and research exposure in neurosurgery fields for pre-medical trainees. Our work is a preliminary step in addressing the crucial challenge of training the next generation of neurosurgeon-scientists by providing a pedagogical paradigm for development of formal experiences that integrate original scientific research with clinical neurosurgery exposure.
Hydrocephalus, characterized by progressive expansion of the cerebrospinal fluid (CSF)-filled ventricles (ventriculomegaly), is the most common reason for brain surgery. "Communicating" (i.e., ...non-obstructive) hydrocephalus is classically attributed to a primary derangement in CSF homeostasis, such as choroid plexus-dependent CSF hypersecretion, impaired cilia-mediated CSF flow currents, or decreased CSF reabsorption via the arachnoid granulations or other pathways. Emerging data suggest abnormal biomechanical properties of the brain parenchyma are an underappreciated driver of ventriculomegaly in multiple forms of communicating hydrocephalus across the lifespan. We discuss recent evidence from human and animal studies that suggests impaired neurodevelopment in congenital hydrocephalus, neurodegeneration in elderly normal pressure hydrocephalus, and, in all age groups, inflammation-related neural injury post-infectious and post-hemorrhagic hydrocephalus, can result in loss of stiffness and viscoelasticity of the brain parenchyma. Abnormal brain biomechanics creates barrier alterations at the brain-CSF interface that pathologically facilitates secondary enlargement of the ventricles, even at normal or low intracranial pressures. This "brain-centric" paradigm has implications for the diagnosis, treatment, and study of hydrocephalus from womb to tomb.
The strongest genetic risk factor for Alzheimer's disease (AD) is the Apolipoprotein E type 4 allele (ApoE ε4). The interaction between sex and ApoE ε4 carrier status on AD risk remains an area of ...intense investigation. We hypothesized that sex modulates the relationship between ApoE ε4 carrier status and brain tau deposition (a quantitative endophenotype in AD) in individuals with mild cognitive impairment (MCI).
: Preprocessed
F-AV-1451 tau and
F-AV-45 amyloid PET images, T1-weighted structural magnetic resonance imaging (MRI) scans, demographic information, and cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) measurements from 108 MCI subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. After downloading pre-processed images from ADNI, an iterative reblurred Van Cittertiteration partial volume correction (PVC) method was applied to all PET images. MRIs were used for PET spatial normalization. Regions of interest (ROIs) were defined in standard space, and standardized uptake value ratio (SUVR) images relative to cerebellum were computed. ApoE ε4 by sex interaction analyses on
F-AV-1451 and CSF tau (t-tau, p-tau) were assessed using generalized linear models. The association between
F-AV-1451 SUVR and CSF tau (t-tau, p-tau) was assessed.
: After applying PVC and controlling for age, education level and global cortical
F-AV-45 SUVR, we found that the entorhinal cortex, amygdala, parahippocampal gyrus, posterior cingulate, and occipital ROIs exhibited a significant ApoE ε4 by sex interaction effect (false discovery rate
< 0.1) among MCI individuals. We also found a significant ApoE ε4 by sex interaction effect on CSF t-tau and p-tau.
F-AV-1451 SUVR in the 5 ROIs with ApoE ε4 by sex interaction was significantly correlated with CSF p-tau and t-tau.
: Our findings suggest that women are more susceptible to ApoE ε4-associated accumulation of neurofibrillary tangles in MCI compared to males. Both CSF tau (p-tau, t-tau) and brain tau PET are robust quantitative biomarkers for studying ApoE ε4 by sex effects on brain tau deposition in MCI participants.
Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease ...pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated de novo mutation (p.Cys188Trp) in the GABAA receptor Cl− channel γ-1 subunit (GABRG1) exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na+ and Ca+ channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca2+ channel Cav3.2 (CACNA1H). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis.
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•Genomic analysis of trigeminal neuralgia (TN) using exome sequencing•Rare mutations in GABA signaling and ion transport genes are enriched in TN cases•Generation of a genetic TN mouse model engineered with a patient-specific mutation
Neuroscience; Structural Biology; Genomics
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