Faculty Bibliography

Neurologists in both the inpatient and outpatient settings are increasingly using ultrasound to diagnose and manage common neurological diseases. Advantages include cost-effectiveness, the lack of exposure to ionizing radiation, and the ability to perform at the bedside to provide real-time data. There is a growing body of literature that supports using ultrasonography to improve diagnostic accuracy and aid in performing procedures. Despite the increasing utilization of this imaging modality in medicine, there has been no comprehensive review of the clinical applications of ultrasound in the field of neurology. We discuss the current uses and limitations of ultrasound for various neurological conditions. We review the role for ultrasound in commonly performed neurologic procedures including lumbar puncture, botulinum toxin injections, nerve blocks, and trigger point injections. We specifically discuss the technique for ultrasound-assisted lumbar puncture and occipital nerve block as these are commonly performed. We then focus on the utility of ultrasound in the diagnosis of neurologic conditions. This includes neuromuscular diseases such as motor neuron disorders, focal neuropathies, and muscular dystrophy as well as vascular conditions such as stroke and vasospasm in subarachnoid hemorrhage. We also address ultrasound's use in critically ill patients to aid in identifying increased intracranial pressure, hemodynamics, and arterial and/or venous catheterization. Finally, we address the importance of standardized ultrasound curricula in trainee education and make recommendations for the future directions of research and competency guidelines within our specialty.

BACKGROUND:Headache disorders are among the most common and disabling medical conditions worldwide, have a great societal impact and are a common reason to seek medical care. Headache disorders are often misdiagnosed and undertreated, and the number of headache fellowship-trained physicians cannot meet patient demand. Educational initiatives for non-headache-specialist clinicians may be an avenue to increase clinician competency and patient access to appropriate management. OBJECTIVE:To undertake a scoping review of the educational initiatives in headache medicine for medical students, trainees, general practitioners/primary care physicians, and neurologists. METHODS:Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews, an author (M.D.), with the help of a medical librarian, conducted a search of the Embase, Ovid Medline, and PsychInfo databases for articles related to medical educational initiatives on headache medicine in medical students, residents, and physicians over the last 20 years. RESULTS:A total of 17 articles met the inclusion criteria for this scoping review. Six articles were identified for medical students, seven for general practitioners/primary care physicians, one for emergency medicine residents, two for neurology residents, and one for neurologists. Certain educational initiatives were headache-focused while others had headaches as one of the educational topics. Educational content was delivered and assessed via diverse and innovative means, such as flipped classroom, simulation, theatrical performance, repeated quizzing and study, and a formalized headache elective. CONCLUSION/CONCLUSIONS:Education initiatives in headache medicine are important to improve competency and patient access to appropriate management of various headache disorders. Future research should focus on using innovative and evidence-based methods of content delivery, knowledge, and procedural assessment, and evaluating changes in practice behaviors.

BACKGROUND/UNASSIGNED:Patients with postoperative spinal epidural hematomas (pSEH) typically require emergency treatment to avoid paralysis; these hematomas should not be ignored. pSEH patients need to undergo immediate MR studies to document the location/extent of their hematomas, and emergent surgical decompression with/ without fusion if warranted. METHODS/UNASSIGNED:The frequencies of symptomatic pSEH ranged in various series from 0.1%-4.46%. Major predisposing factors included; perioperative/postoperative coagulation abnormalities/disorders, multilevel spine surgeries, previous spine surgery, and intraoperative cerebrospinal fluid (CSF) leaks. For surgery at all spinal levels, one study observed pSEH developed within an average of 2.7 postoperative hours. Another series found 100% of cervical/thoracic, and 50% of lumbar pSEH were symptomatic within 24 postoperative hrs., while a third series noted a 24-48 postoperative window for pSEH to develop. RESULTS/UNASSIGNED:Early recognition of postoperative symptoms/signs of pSEH, warrant immediate MR examinations to diagnose the local/extent of hemorrhages. Subsequent emergent spinal decompressions/fusions are critical to limit/avert permanent postoperative neurological deficits. Additionally, patients undergoing open or minimally invasive spinal procedures where pSEH are suspected, warrant immediate postoperative MR studies. CONCLUSION/UNASSIGNED:Patients undergoing spinal surgery at any level typically become symptomatic from pSEH within 2.7 to 24 postoperative hours. Early recognition of new neurological deficits, immediate MR studies, and emergent surgery (i.e., if indicated) should limit/minimize postoperative neurological sequelae. Thus, pSEH should be treated, not ignored.

BACKGROUND/UNASSIGNED:The 2016 WHO classification described a subtype of midline gliomas harboring histone 3 (H3) K27M alterations, and the 2021 edition added a new subtype of hemispheric diffuse gliomas with H3 G34R/V mutations. The incidence and clinical behavior of leptomeningeal disease (LMD) in these patients is not well defined. METHODS/UNASSIGNED:Retrospective study of patients with H3-altered gliomas diagnosed from 01/2012 to 08/2021; histone mutations were identified through next-generation sequencing (NGS) of tumor biopsy and/or cerebrospinal fluid (CSF). RESULTS/UNASSIGNED:< .0001). CONCLUSIONS/UNASSIGNED:In our cohort, 50% of patients developed LMD. Although further studies are needed, CSF ctDNA characterization may aid in identifying molecular tumor profiles in glioma patients with LMD, and neuroaxis imaging and CSF NGS should be considered for early LMD detection.

INTRODUCTION:For drug resistant epilepsy patients who are either not candidates for resective surgery or have already failed resective surgery, neuromodulation is a promising option. Neuromodulatory approaches include responsive neurostimulation (RNS), deep brain stimulation (DBS), and vagal nerve stimulation (VNS). Thalamocortical circuits are involved in both generalized and focal onset seizures. This paper explores the use of RNS in the centromedian nucleus of the thalamus (CMN) and in the anterior thalamic nucleus (ANT) of patients with drug resistant epilepsy. METHODS:This is a retrospective multicenter study from seven different epilepsy centers in the United States. Patients that had unilateral or bilateral thalamic RNS leads implanted in the CMN or ANT for at least 6 months were included. Primary objectives were to describe the implant location and determine changes in the frequency of disabling seizures at 6 months, 1 year, 2 years, and > 2 years. Secondary objectives included documenting seizure free periods, anti-seizure medication regimen changes, stimulation side effects, and serious adverse events. In addition, the global clinical impression scale was completed. RESULTS:Twelve patients had at least one lead placed in the CMN, and 13 had at least one lead placed in the ANT. The median baseline seizure frequency was 15 per month. Overall, the median seizure reduction was 33% at 6 months, 55% at 1 year, 65% at 2 years, and 74% at >2 years. Seizure free intervals of at least 3 months occurred in nine patients. Most patients (60%, 15/25) did not have a change in anti-seizure medications post RNS placement. Two serious adverse events were recorded, one related to RNS implantation. Lastly, overall functioning seemed to improve with 88% showing improvement on the global clinical impression scale. DISCUSSION:Meaningful seizure reduction was observed in patients who suffer from drug resistant epilepsy with unilateral or bilateral RNS in either the ANT or CMN of the thalamus. Most patients remained on their pre-operative anti-seizure medication regimen. The device was well tolerated with few side effects. There were rare serious adverse events. Most patients showed an improvement in global clinical impression scores.

Haptic technology is a critical component of human-computer interfaces. Traditional haptic actuators are often unable to provide the broad frequency range and latency that is required in many advanced applications. To address this problem, we propose a new type of tactor based on macro-fiber composites (MFCs), composites of piezoelectric fibers. We propose a physics-based model for the actuation of the tactors, calibrated and validated through experiments. As our tactors are intended for haptic applications, we consider the role of skin on their response, an aspect seldom analyzed in the literature. In our experiments, we simulate the presence of the skin with a rubber membrane in contact with the tactor, with varying pre-stretch, mimicking different indentations of the tactor on the skin. The MFC-based tactor can always generate vibration amplitudes higher than skin discrimination thresholds, over the range of frequencies of interest for haptics, with a latency much smaller than traditional actuators. We theoretically investigate the effect of the skin on tactor vibrations, highlighting the individual roles of skin stiffness and damping and their combined effect across a series of pre-stretches. Our tactor shows promise in haptic applications, including assistive technologies and real-time feedback systems for training, safety, and monitoring.

BACKGROUND/UNASSIGNED:Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis. METHODS/UNASSIGNED:We performed a prospective study using DNA methylation analysis as a primary diagnostic method for 1921 brain tumors. All tumors received a pathology diagnosis and profiling by whole genome DNA methylation, followed by next-generation DNA and RNA sequencing. Results were stratified by concordance between DNA methylation and histopathology, establishing diagnostic utility. RESULTS/UNASSIGNED:Of the 1602 cases with a World Health Organization histologic diagnosis, DNA methylation identified a diagnostic mismatch in 225 cases (14%), 78 cases (5%) did not classify with any class, and in an additional 110 (7%) cases DNA methylation confirmed the diagnosis and provided prognostic information. Of 319 cases carrying 195 different descriptive histologic diagnoses, DNA methylation provided a definitive diagnosis in 273 (86%) cases, separated them into 55 methylation classes, and changed the grading in 58 (18%) cases. CONCLUSIONS/UNASSIGNED:DNA methylation analysis is a robust method to diagnose primary CNS tumors, improving diagnostic accuracy, decreasing diagnostic errors and inconclusive diagnoses, and providing prognostic subclassification. This study provides a framework for inclusion of DNA methylation profiling as a primary molecular diagnostic test into professional guidelines for CNS tumors. The benefits include increased diagnostic accuracy, improved patient management, and refinements in clinical trial design.

INTRODUCTION/UNASSIGNED:Alzheimer's disease (AD) and epilepsy are reciprocally related. Among sporadic AD patients, clinical seizures occur in 10-22% and subclinical epileptiform abnormalities occur in 22-54%. Cognitive deficits, especially short-term memory impairments, occur in most epilepsy patients. Common neurophysiological and molecular mechanisms occur in AD and epilepsy. The choroid plexus undergoes pathological changes in aging, AD, and epilepsy, including decreased CSF turnover, amyloid beta (Aβ), and tau accumulation due to impaired clearance and disrupted CSF amino acid homeostasis. This pathology may contribute to synaptic dysfunction in AD and epilepsy. METHODS/UNASSIGNED:= 12) using laser capture microdissection (LCM) followed by label-free quantitative mass spectrometry on the choroid plexus adjacent to the hippocampus at the lateral geniculate nucleus level. RESULTS/UNASSIGNED: DISCUSSION/UNASSIGNED:We found altered signaling pathways in the choroid plexus of severe AD cases and many correlated changes in the protein expression of cell metabolism pathways in AD and epilepsy cases. The shared molecular mechanisms should be investigated further to distinguish primary pathogenic changes from the secondary ones. These mechanisms could inform novel therapeutic strategies to prevent disease progression or restore normal function. A focus on dual-diagnosed AD/epilepsy cases, specific epilepsy syndromes, such as temporal lobe epilepsy, and changes across different severity levels in AD and epilepsy would add to our understanding.

INTRODUCTION/UNASSIGNED:Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. Complementary and alternative therapies are increasingly utilized to address its complex multisystem symptomatology. Art therapy involves motoric action and visuospatial processing while promoting broad biopsychosocial wellness. The process involves hedonic absorption, which provides an escape from otherwise persistent and cumulative PD symptoms, refreshing internal resources. It involves the expression in nonverbal form of multilayered psychological and somatic phenomena; once these are externalized in a symbolic arts medium, they can be explored, understood, integrated, and reorganized through verbal dialogue, effecting relief and positive change. METHODS/UNASSIGNED:42 participants with mild to moderate PD were treated with 20 sessions of group art therapy. They were assessed before and after therapy with a novel arts-based instrument developed to match the treatment modality for maximum sensitivity. The House-Tree-Person PD Scale (HTP-PDS) assesses motoric and visuospatial processing-core PD symptoms-as well as cognition (thought and logic), affect/mood, motivation, self (including body-image, self-image, and self- efficacy), interpersonal functioning, creativity, and overall level of functioning. It was hypothesized that art therapy will ameliorate core PD symptoms and that this will correlate with improvements in all other variables. RESULTS/UNASSIGNED:HTP-PDS scores across all symptoms and variables improved significantly, though causality among variables was indeterminate. DISCUSSION/UNASSIGNED:Art therapy is a clinically efficacious complementary treatment for PD. Further research is warranted to disentangle causal pathways among the aforementioned variables, and additionally, to isolate and examine the multiple, discrete healing mechanisms believed to operate simultaneously in art therapy.

BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with largely unknown pathogenesis and no effective cure. It is believed that several, not mutually exclusive mechanisms contribute to the pathogenesis and progression of this disease, including, among others, elevated oxidative stress, excitotoxicity, increased neuroinflammation, and protein aggregation. Receptor for advanced glycation end products (RAGE) is a part of immunoglobulin superfamily; it is believed to participate in ALS pathogenesis. OBJECTIVES/OBJECTIVE:Our previous studies on ALS demonstrated that RAGE is likely one of the key players in ALS, acting on its own and in tandem with its oxidative stress and pro-inflammatory ligands, such as advanced glycation end products (AGEs) or advanced oxidation protein products (AOPPs). In this study, based on our previous results, we aimed to establish blood levels of soluble RAGE, AGE and AOPP in ALS patients. MATERIAL AND METHODS/METHODS:Forty-six coded and anonymized surplus plasma samples from ALS patients and non-neurological control were used in the study. The plasma levels of RAGE, AGE and AOPP were measured using enzyme-linked immunosorbent assay (ELISA) commercially available kits. Statistical evaluation of data was performed using one-way non-parametric analysis of variance (ANOVA) with Kruskal-Wallis post hoc test. RESULTS:Our results revealed a decline in soluble RAGE level, concurrent with an increase in the levels of AGEs and AOPPs in blood samples from ALS patients, signifying a loss of neuroprotective form of RAGE and a simultaneous increase in AGE and AOPP production and uptake at the early stage of the disease. CONCLUSIONS:The results obtained from our study indicate that further longitudinal study of RAGE, AGE and AOPP levels would be beneficial, outlining the dynamics between RAGE and its ligand levels as the disease progresses, and making them valuable diagnostic tools and potential therapeutic targets.