Faculty Bibliography

Background/UNASSIGNED:Treatment with aspirin plus clopidogrel, dual antiplatelet therapy (DAPT), within 24 hours of high-risk transient ischemic attack (TIA) or minor stroke symptoms to eligible patients is recommended by national guidelines. Whether or not this treatment has been adopted by emergency medicine (EM) physicians is uncertain. Methods/UNASSIGNED:We conducted an online survey of EM physicians in the United States. The survey consisted of 13 multiple choice questions regarding physician characteristics, practice settings, and usual approach to TIA and minor stroke treatment. We report participant characteristics and use chi-squared tests to compare between groups. Results/UNASSIGNED:We included 162 participants in the final study analysis. 103 participants (64%) were in practice for >5 years and 96 (59%) were at nonacademic centers; all were EM board-certified or board-eligible. Only 9 (6%) participants reported that they would start DAPT for minor stroke and 8 (5%) reported that they would start DAPT after high-risk TIA. Aspirin alone was the selected treatment by 81 (50%) participants for minor stroke patients who presented within 24 hours of symptom onset and were not candidates for thrombolysis. For minor stroke, 69 (43%) participants indicated that they would defer medical management to consultants or another team. Similarly, 75 (46%) of participants chose aspirin alone to treat high-risk TIA; 74 (46%) reported they would defer medical management after TIA to consultants or another team. Conclusion/UNASSIGNED:In a survey of EM physicians, we found that the reported rate of DAPT treatment for eligible patients with high-risk TIA and minor stroke was low.

Transcranial electrical stimulation (tES) comprises noninvasive neuromodulation techniques that deliver low-amplitude electrical currents to targeted brain regions with the goal of modifying neural activities. Expanding evidence from the past decade, specifically using transcranial direct current simulation and transcranial alternating current stimulation, presents promising applications of tES as a treatment for psychiatric disorders. In this review, the authors discuss the basic technical aspects and mechanisms of action of tES in the context of clinical research and practice and review available evidence for its clinical use, efficacy, and safety. They also review recent advancements in use of tES for the treatment of depressive disorders, schizophrenia, substance use disorders, and obsessive-compulsive disorder. Findings largely support growing evidence for the safety and efficacy of tES in the treatment of patients with resistance to existing treatment options, particularly demonstrating promising treatment outcomes for depressive disorders. Future directions of tES research for optimal application in clinical settings are discussed, including the growing home-based, patient-friendly methods and the potential pairing with existing pharmacological or psychotherapeutic treatments for enhanced outcomes. Finally, neuroimaging advancements may provide more specific mapping of brain networks, aiming at more precise tES therapeutic targeting in the treatment of psychiatric disorders.

Background/UNASSIGNED:Prior to the COVID-19 pandemic, about half of patients from populations that sought care in neurology tried complementary and integrative therapies (CITs). With the increased utilization of telehealth services, we sought to determine whether patients also increased their use of virtual CITs. Methods/UNASSIGNED:We examined datasets from two separate cross-sectional surveys that included cohorts of patients with neurological disorders. One was a dataset from a study that examined patient and provider experiences with teleneurology visits; the other was a study that assessed patients with a history of COVID-19 infection who presented for neurologic evaluation. We assessed and reported the use of virtual (and non-virtual) CITs using descriptive statistics, and determined whether there were clinical characteristics that predicted the use of CITs using logistic regression analyses. Findings/UNASSIGNED:Patients who postponed medical treatment for non-COVID-19-related problems during the pandemic were more likely to seek CITs. Virtual exercise, virtual psychotherapy, and relaxation/meditation smartphone applications were the most frequent types of virtual CITs chosen by patients. In both studies, age was a key demographic factor associated with mobile/virtual CIT usage. Interpretations/UNASSIGNED:Our investigation demonstrates that virtual CIT-related technologies were utilized in the treatment of neurologic conditions during the pandemic, particularly by those patients who deferred non-COVID-related care.

Patients admitted to the hospital with neurological problems are sometimes incapacitated and unable to make end-of-life decisions. In these instances, without an advanced directive from the patient, clinicians and family members must make critical medical decisions without input from the patient. This paper looks at two cases - one child and one adult - in which neuroprognosis was uncertain, and physician and family members' beliefs on end-of-life care clash. We provide insight into these disagreements and reflect on how best to manage them. We argue that when considering withdrawing treatment, respecting autonomy is of paramount importance, while decision-making about continuing life-sustaining treatment requires clinicians to ensure surrogates are adequately educated about the principle of beneficence.

OBJECTIVE:This study examined concordance between symptom and performance validity among clinically-referred patients undergoing neuropsychological evaluation for Attention-Deficit/Hyperactivity Disorder (ADHD). METHOD:Data from 203 patients who completed the WAIS-IV Working Memory Index, the Clinical Assessment of Attention Deficit-Adult (CAT-A), and ≥4 criterion performance validity tests (PVTs) were analyzed. RESULTS: CONCLUSION:Symptom and performance invalidity represent dissociable constructs in patients undergoing neuropsychological evaluation of ADHD and should be evaluated independently.

Cardiac arrest can cause hypoxic-anoxic ischemic brain injury due to signaling cascades that lead to damaged cell membranes and vital cellular organelles, resulting in cell death in the setting of low or no oxygen. Some brain areas are more prone to damage than others, so patients with hypoxic-anoxic ischemic brain injury present with several outcomes, including reduced level of consciousness or alertness, memory deficits, uncoordinated movements, and seizures. Some patients may have mild deficits, while others may have such severe injury that it can progress to brain death. High-quality cardiopulmonary resuscitation is a proven technique to improve outcome after cardiac arrest, although morbidity and mortality remain high. Induced hypothermia, which involves artificially cooling the body immediately after cardiac arrest, may reduce injury to the brain and improve morbidity and mortality. Neuroprognostication after cardiac arrest is challenging and requires a multimodal approach involving clinical neurologic examinations, brain imaging, electrical studies to assess brain activity, and biomarkers to predict outcome.

Background/UNASSIGNED:Medical residents must sustain acute sleep deprivation, which can lead to nonfatal and fatal consequences in hospitals due to cognitive decline. Anodal transcranial direct current stimulation (a-tDCS) is a safe noninvasive neuromodulation technique that can induce depolarization of neurons. Previous studies in pilots have shown benefits against fatigue increasing wakefulness and cognitive performance. However, the effects of a-tDCS on cognition in acute sleep deprived healthcare workers remains unknown. Purpose/UNASSIGNED:To evaluate cognitive changes in sleep deprived medical residents after one session of a-tDCS. Methods/UNASSIGNED:Open clinical test-re-test study including 13 medical residents with acute sleep deprivation. Subjects received 1 session of bifrontal a-tDCS (2mAx20min), anodal over the left dorsolateral prefrontal region. Pre-and-post treatment subjects were tested with Beck anxiety inventory, Beck depression and HVLT tests, Rey´s and Taylor´s figures, Trail Making A/B, Stroop, Aleatory Digit retention test (WAIS), Digits and symbols and MoCA tests. Post-intervention was added the Executive functions and Frontal Lobes Neuropsychological Battery (BANFE2) test and changing the Taylor figure for Reyfigure. Results/UNASSIGNED:Twelve medical residents were analyzed; 8 men and 4 women, 29.5 (+/-2.2) years mean age. All had a mean of 21.6 (+/-1.3) hours of sleep deprivation. There were no serious adverse events. We found statistically significant difference in Rey´s/Taylor´s figures (p=0.002), Trail Making Test (p=0.005), WAIS IV symbols (p=0.003), Word Stroop (p=0.021). BANFE-2 showed that the main affected area was the orbito-medial prefrontal region. Conclusion/UNASSIGNED:a-tDCS appears safe and improves working memory, attention, response time and distractors elimination in acute sleep deprived medical residents.

Primary age-related tauopathy (PART) is a neurodegenerative pathology with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amnestic cognitive impairment, PART develops independently of amyloid-β (Aβ) plaques. The pathogenesis of PART is not known, but evidence suggests an association with genes that promote tau pathology and others that protect from Aβ toxicity. Here, we performed a genetic association study in an autopsy cohort of individuals with PART (n = 647) using Braak neurofibrillary tangle stage as a quantitative trait. We found some significant associations with candidate loci associated with AD (SLC24A4, MS4A6A, HS3ST1) and progressive supranuclear palsy (MAPT and EIF2AK3). Genome-wide association analysis revealed a novel significant association with a single nucleotide polymorphism on chromosome 4 (rs56405341) in a locus containing three genes, including JADE1 which was significantly upregulated in tangle-bearing neurons by single-soma RNA-seq. Immunohistochemical studies using antisera targeting JADE1 protein revealed localization within tau aggregates in autopsy brains with four microtubule-binding domain repeats (4R) isoforms and mixed 3R/4R, but not with 3R exclusively. Co-immunoprecipitation in post-mortem human PART brain tissue revealed a specific binding of JADE1 protein to four repeat tau lacking N-terminal inserts (0N4R). Finally, knockdown of the Drosophila JADE1 homolog rhinoceros (rno) enhanced tau-induced toxicity and apoptosis in vivo in a humanized 0N4R mutant tau knock-in model, as quantified by rough eye phenotype and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) in the fly brain. Together, these findings indicate that PART has a genetic architecture that partially overlaps with AD and other tauopathies and suggests a novel role for JADE1 as a modifier of neurofibrillary degeneration.

OBJECTIVES/OBJECTIVE:The goals of this study were to 1) compare global protein expression in muscles of the larynx and hindlimb and 2) investigate differences in protein expression between aged and nonaged muscle using label-free global proteomic profiling methods. METHODS:Liquid chromatography-mass spectrometry (LC-MS/MS) analysis was performed on thyroarytenoid intrinsic laryngeal muscle and plantaris hindlimb muscle from 10 F344xBN F1 male rats (5 old and 5 young). Protein expression was compared and pathway enrichment analysis performed for each muscle type (larynx and limb) and age group (old and young muscle). RESULTS:Over 1,000 proteins were identified in common across both muscle types and age groups using LC-MS/MS analysis. Significant age-related differences were seen across 107 proteins in plantaris hindlimb and in 19 proteins in thyroarytenoid laryngeal muscle. Bioinformatic and enrichment analysis demonstrated protein differences between the hindlimb and larynx may relate to immune and stress redox responses and RNA repair. CONCLUSION/CONCLUSIONS:There are clear differences in protein expressions between the laryngeal and hindlimb skeletal muscles. Initial analysis suggests differences between the two muscle groups may relate to stress responses and repair mechanisms. Age-related changes in the thyroarytenoid appear to be less obvious than in the plantaris. Further in-depth study is needed to elucidate how aging affects protein expression in the laryngeal muscles. LEVEL OF EVIDENCE/METHODS:NA Laryngoscope, 2021.