Faculty Bibliography

Orthostatic hypotension is an unusually large decrease in blood pressure on standing that increases the risk of adverse outcomes even when asymptomatic. Improvements in haemodynamic profiling with continuous blood pressure measurements have uncovered four major subtypes: initial orthostatic hypotension, delayed blood pressure recovery, classic orthostatic hypotension, and delayed orthostatic hypotension. Clinical presentations are varied and range from cognitive slowing with hypotensive unawareness or unexplained falls to classic presyncope and syncope. Establishing whether symptoms are due to orthostatic hypotension requires careful history taking, a thorough physical examination, and supine and upright blood pressure measurements. Management and prognosis vary according to the underlying cause, with the main distinction being whether orthostatic hypotension is neurogenic or non-neurogenic. Neurogenic orthostatic hypotension might be the earliest clinical manifestation of Parkinson's disease or related synucleinopathies, and often coincides with supine hypertension. The emerging variety of clinical presentations advocates a stepwise, individualised, and primarily non-pharmacological approach to the management of orthostatic hypotension. Such an approach could include the cessation of blood pressure lowering drugs, adoption of lifestyle measures (eg, counterpressure manoeuvres), and treatment with pharmacological agents in selected cases.

Embedded performance validity tests (PVTs) are key components of neuropsychological evaluations. However, most are memory-based and may be less useful in the assessment of attention-deficit/hyperactivity disorder (ADHD). Four non-memory-based validity indices derived from processing speed and executive functioning measures commonly included in ADHD evaluations, namely Verbal Fluency (VF) and the Trail Making Test (TMT), were cross-validated using the Rey 15-Item Test (RFIT) Recall and Recall/Recognition as memory-based comparison measures. This consecutive case series included data from 416 demographically-diverse adults who underwent outpatient neuropsychological evaluation for ADHD. Validity classifications were established, with ≤1 PVT failure of five independent criterion PVTs as indicative of valid performance (374 valid performers/42 invalid performers). Among the statistically significant validity indicators, TMT-A and TMT-B T-scores (AUCs = .707-.723) had acceptable classification accuracy ranges and sensitivities ranging from 29%-36% (≥89% specificity). RFIT Recall/Recognition produced similar results as TMT-B T-score with 42% sensitivity/90% specificity, but with lower classification accuracy. In evaluating adult ADHD, VF and TMT embedded PVTs demonstrated comparable sensitivity and specificity values to those found in other clinical populations but necessitated alternate cut-scores. Results also support use of RFIT Recall/Recognition over the standard RFIT Recall as a PVT for adult ADHD evaluations.

There is an urgent need for an in-depth and systematic assessment of a wide range of predictive factors related to populations most at risk for delaying and refusing COVID-19 vaccination as cases of the disease surge across the United States. Many studies have assessed a limited number of general sociodemographic and health-related factors related to low vaccination rates. Machine learning methods were used to assess the association of 151 social and health-related risk factors derived from the American Community Survey 2019 and the Centers for Disease Control and Prevention (CDC) BRFSS with the response variables of vaccination rates and unvaccinated counts in 1,555 ZIP Codes in California. The performance of various analytical models was evaluated according to their ability to regress between predictive variables and vaccination levels. Machine learning modeling identified the Gradient Boosting Regressor (GBR) as the predictive model with a higher percentage of the explained variance than the variance identified through linear and generalized regression models. A set of 20 variables explained 72.90% of the variability of unvaccinated counts among ZIP Codes in California. ZIP Codes were shown to be a more meaningful geo-local unit of analysis than county-level assessments. Modeling vaccination rates was not as effective as modeling unvaccinated counts. The public health utility of this model provides for the analysis of state and local conditions related to COVID-19 vaccination use and future public health problems and pandemics.

BACKGROUND:The Curing Coma Campaign (CCC) is a multidisciplinary global initiative focused on evaluation, diagnosis, treatment, research, and prognostication for patients who are comatose due to any etiology. To support this mission, the CCC Ethics Working Group conducted a survey of CCC collaborators to identify the ethics priorities of the CCC and the variability in priorities based on country of practice. METHODS:An electronic survey on the ethics priorities for the CCC was developed using rank-choice questions and distributed between May and July 2021 to a listserv of the 164 collaborators of the CCC. The median rank for each topic and subtopic was determined. Comparisons were made on the basis of country of practice. RESULTS:The survey was completed by 93 respondents (57% response rate); 67% practiced in the United States. On the basis of respondent ranking of each topic, the prioritization of ethics topics across respondents was as follows: (1) clinical care, (2) diagnostic definitions, (3) clinical research, (4) implementation/innovation, (5) family, (6) data management, (7) public engagement/perceptions, and (8) equity. Respondents who practiced in the United States were particularly concerned about public engagement, the distinction between clinical care and research, disclosure of results from clinical research to families, the definition of "personhood," and the distinction between the self-fulfilling prophecy/nihilism and medical futility. Respondents who practiced in other countries were particularly concerned about diagnostic modalities for clinical care, investigational drugs/devices for clinical research, translation of research into practice, and the definition of "minimally conscious state." CONCLUSIONS:Collaborators of the CCC considered clinical care, diagnostic definitions, and clinical research the top ethics priorities of the CCC. These priorities should be considered as the CCC explores ways to improve evaluation, diagnosis, treatment, research, and prognostication of patients with coma and associated disorders of consciousness. There is some variability in ethics priorities based on country of practice.

The demand for intraoperative monitoring (IOM) of lumbar spine surgeries has escalated to accommodate more challenging surgical approaches to prevent perioperative neurologic deficits. Identifying impending injury of individual lumbar roots can be done by assessing free-running EMG and by monitoring the integrity of sensory and motor fibers within the roots by eliciting somatosensory (SEP), and motor evoked potentials. However, the common nerves for eliciting lower limb SEP do not monitor the entire lumbar plexus, excluding fibers from L1 to L4 roots. We aimed to technically optimize the methodology for saphenous nerve SEP (Sap-SEP) proposed for monitoring upper lumbar roots in the operating room. In the first group, the saphenous nerve was consecutively stimulated in two different locations: proximal in the thigh and distal close to the tibia. In the second group, three different recording derivations (10-20 International system) to distal saphenous stimulation were tested. Distal stimulation yielded a higher Sap-SEP amplitude (mean ± SD) than proximal: 1.36 ± 0.9 µV versus 0.62 ± 0.6 µV, (p < 0.0001). Distal stimulation evoked either higher (73%) or similar (12%) Sap-SEP amplitude compared to proximal in most of the nerves. The recording derivation CPz-cCP showed the highest amplitude in 65% of the nerves, followed by CPz-Fz (24%). Distal stimulation for Sap-SEP has advantages over proximal stimulation, including simplicity, lack of movement and higher amplitude responses. The use of two derivations (CPz-cCP, CPz-Fz) optimizes Sap-SEP recording.

BACKGROUND AND PURPOSE/OBJECTIVE:Skull base tumors are commonly supplied by dural branches of the meningohypophyseal and inferolateral trunks. Embolization through these arteries is often avoided due to technical challenges and inherent risks; however, successful embolization can be a valuable surgical adjunct. We aimed to review the success and complications in our series of tumor embolizations through the meningohypophyseal and inferolateral trunks. MATERIALS AND METHODS/METHODS:We performed a retrospective review of patients with tumor treated with preoperative embolization at our institution between 2010 and 2020. We reviewed the following data: patients' demographics, tumor characteristics, endovascular embolization variables, and surgical results including estimated blood loss, the need for transfusion, and operative time. RESULTS:= 4) trunk. In this group of patients, on average, 79% of tumors were embolized. No mortality or morbidity from the embolization procedure was observed in this subgroup of patients. The average estimated blood loss in the operation was 395 mL (range, 200-750 mL). None of the patients required a transfusion, and the average operative time was 7.3 hours. CONCLUSIONS:Some skull base tumors necessitate embolization through ICA branches such as the meningohypophyseal and inferolateral trunks. Our series demonstrates that an effective and safe embolization may be performed through these routes.

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.

Encephalopathy, a common condition among patients hospitalized with COVID-19, can be a challenge to manage and negatively affect prognosis. While encephalopathy may present clinically as delirium, subsyndromal delirium, or coma and may be a result of systemic causes such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma (with or without cerebrovascular involvement), demyelination, or seizures, which may be disproportionate to COVID-19 severity and require specific management. Given the large number of patients hospitalized with severe acute respiratory syndrome coronavirus-2 infection, even these relatively unlikely complications are increasingly recognized and are particularly important because they require specific management. Therefore, the aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through consensus agreement of the Global COVID-19 Neuro Research Coalition. A systematic literature search of MEDLINE, medRxiv, and bioRxiv was conducted between January 1, 2020, and June 21, 2021, with additional review of references cited within the identified bibliographies. A modified Delphi approach was then undertaken to develop recommendations, along with a parallel approach to score the strength of both the recommendations and the supporting evidence. This review presents analysis of contemporaneous evidence for the definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and both acute and long-term management.

HNRNPU encodes the heterogeneous nuclear ribonucleoprotein U, which participates in RNA splicing and chromatin organization. Microdeletions in the 1q44 locus encompassing HNRNPU and other genes and point mutations in HNRNPU cause brain disorders, including early-onset seizures and severe intellectual disability. We aimed to understand HNRNPU's roles in the developing brain. Our work revealed that HNRNPU loss of function leads to rapid cell death of both postmitotic neurons and neural progenitors, with an apparent higher sensitivity of the latter. Further, expression and alternative splicing of multiple genes involved in cell survival, cell motility, and synapse formation are affected following Hnrnpu's conditional truncation. Finally, we identified pharmaceutical and genetic agents that can partially reverse the loss of cortical structures in Hnrnpu mutated embryonic brains, ameliorate radial neuronal migration defects and rescue cultured neural progenitors' cell death.

BACKGROUND:Multiple sclerosis (MS) affects over 2.5 million individuals worldwide, yet much of the disease course is unknown. Hemispheric vulnerability in MS may elucidate part of this process but has not yet been studied. The current study assessed neuropsychological functioning as it relates to hemispheric vulnerability in MS. METHODS:Verbal IQ, as measured by verbal comprehension index (VCI), nonverbal IQ, as measured by perceptual reasoning index (PRI) and memory acquisition were compared in right-handed (dextral) and non-right-handed (non-dextral) persons with MS (PwMS). RESULTS:Linear mixed-effects modeling indicated a significant main effect of handedness, F(1, 195.35) = 3.95, p = .048, for a composite measure of VCI, PRI, and memory acquisition, with better performance for dextral PwMS. In examining differences for specific neuropsychological measures, the largest effect size between dextral and non-dextral participants was seen in PRI (d = 0.643), F(1,341) = 12.163, p = .001. No significant interaction effect between handedness and IQ was found, F(3, 525.60) = 0.75, p = .523. CONCLUSIONS:Dextral PwMS perform better than non-dextral PwMS when assessing neuropsychological performance for memory and IQ combined. Results are suggestive of increased vulnerability in the left brain to the pathological process of MS.