Faculty Bibliography

OBJECTIVES/OBJECTIVE:Carotid interventions are indicated for both patients with symptomatic and a subset of patients with severe asymptomatic carotid artery stenosis (CAS). Symptomatic CAS accounts for up to 12%-25% of overall carotid interventions, but predictors of symptomatic presentation remain poorly defined. The aim of this study was to identify factors associated with symptomatic CAS in our patient population. METHODS:Between January 2015 and February 2022, an institutional retrospective cohort study of prospectively collected data on patients undergoing interventions for CAS was performed. Procedures included carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), and transfemoral carotid artery stenting (TF-CAS). Demographic data, comorbidities, procedural details, and anatomic features from various imaging modalities were collected. Comparisons were made between symptomatic (symptoms within the prior 6 months) and asymptomatic patients. RESULTS:< .001), and symptomatic patients with ulcerated plaques more frequently had less than 50% compared to moderate/severe CAS. Nine patients who presented with symptoms had mild CAS and underwent intervention. CONCLUSIONS:Symptomatic CAS was associated with a history of remote prior symptoms and lack of anti-platelet therapy at time of presentation. Furthermore, symptomatic patients not on anti-platelet agents were more likely to have a greater area of parenchymal involvement when presenting with stroke and symptomatic patients with ulcerated plaques were more likely to have mild CAS, suggesting the role of plaque instability in symptomatic presentation. These findings underscore the importance of appropriate medical management and adherence in all patients with CAS and perhaps a role for more frequent surveillance in those with potentially unstable plaque morphology.

OBJECTIVES/OBJECTIVE:The primary objective of this proposed guideline is to update the prior 2016 guideline on parenteral pharmacotherapies for the management of adults with a migraine attack in the emergency department (ED). METHODS:We will conduct an updated systematic review and meta-analysis using the 2016 guideline methodology to provide clinical recommendations. The same search strategy will be used for studies up to 2023, with a new search strategy added to capture studies of nerve blocks and sphenopalatine blocks. Medline, Embase, Cochrane, clinicaltrials.gov, and the World Health Organization International Clinical Trial Registry Platform will be searched. Our inclusion criteria consist of studies involving adults with a diagnosis of migraine, utilizing medications administered intravenously, intramuscularly, or subcutaneously in a randomized controlled trial design. Two authors will perform the selection of studies based on title and abstract, followed by a full-text review. A third author will intervene in cases of disagreements. Data will be recorded in a standardized worksheet and subjected to verification. The risk of bias will be assessed using the American Academy of Neurology tool. When applicable, a meta-analysis will be conducted. The efficacy of medications will be evaluated, categorizing them as "highly likely," "likely", or "possibly effective" or "ineffective." Subsequently, clinical recommendations will be developed, considering the risk associated with the medications, following the American Academy of Neurology recommendation development process. RESULTS:The goal of this updated guideline will be to provide guidance on which injectable medications, including interventional approaches (i.e., nerve blocks, sphenopalatine ganglion), should be considered effective acute treatment for adults with migraine who present to an ED. CONCLUSIONS:The methods outlined in this protocol will be used in the design of a future systematic review and meta-analysis-informed guideline, which will then be assessed by and submitted for endorsement by the American Headache Society.

BACKGROUND:The Uniform Law Commission paused work of the Drafting Committee to Revise the Uniform Determination of Death Act (UDDA) in September 2023. METHODS:Thematic review was performed of comments submitted to the Uniform Law Commission by medical organizations (MO), organ procurement organizations (OPO), and advocacy organizations (AO) from 1/1/2023 to 7/31/2023. RESULTS:Of comments from 41 organizations (22 AO, 15 MO, 4 OPO), 34 (83%) supported UDDA revision (50% OPO, 33% MO recommended against revision). The most comments addressed modifications to "all functions of the entire brain, including the brainstem" (31; 95% AO, 75% OPO, 47% MO), followed by irreversible versus permanent (25; 77% AO, 50% OPO, 40% MO), accommodation of brain death/death by neurologic criteria (BD/DNC) objections (23; 100% OPO, 80% MO, 32% AO), consent for BD/DNC evaluation (18; 75% OPO, 47% MO, 36% AO), "accepted medical standards" (13; 36% AO, 33% MO, 0% OPO), notification before BD/DNC evaluation (14; 100% OPO, 53% MO, 9% AO), time to gather before discontinuation of organ support after BD/DNC determination (12; 60% MO, 25% OPO, 9% AO), and BD/DNC examiner credential requirements (2; 13% MO, 0% AO, 0% OPO). The predominant themes were that the revised UDDA should include the term "irreversible" and shouldn't (1) stipulate specific medical guidelines, (2) require notification before BD/DNC evaluation, or (3) require time to gather before discontinuation of organ support after BD/DNC determination. Views on other topics were mixed, but MO and OPO generally advocated for the revised UDDA to take a functional approach to BD/DNC, not require consent for BD/DNC evaluation, and not require opt-out accommodation of BD/DNC objections. Contrastingly, many AO and some MO with religious affiliations or a focus on advocacy favored the revised UDDA take an anatomic approach to BD/DNC or eliminate BD/DNC altogether, require consent for BD/DNC evaluation, and require opt-out accommodation of BD/DNC objections. CONCLUSIONS:Most commenting organizations support UDDA revision, but perspectives on the approach vary, so the Drafting Committee could not formulate revisions that would be agreeable to all stakeholders.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Moyamoya disease (MMD) is a rare noninflammatory disorder involving progressive intracranial vasculopathy and impaired cerebral blood flow in the anterior circulation, resulting in stroke and cognitive impairment. We aimed to characterize cognitive impairment and the possible predictive value of sociodemographic and clinical characteristics of adults with MMD. METHODS:This cross-sectional study examined neurocognitive performance in a group of 42 consecutive adult patients (mean age = 40.52 years; 69% female) referred for a presurgical neuropsychological evaluation. Neuropsychological functioning was assessed with a comprehensive battery, and cognitive dysfunction was defined as 1.5 SDs below the mean. Neurocognitive performance correlated with clinical/demographic characteristics and disease markers. RESULTS:Most patients (91%) had a history of stroke, and 45% had cognitive deficits, most notably on measures of attention/speed (48%), executive functioning (47%), visuoconstruction (41%), and memory (31%-54%). Only higher educational attainment and poor collateral blood flow in the right hemisphere differentiated cognitively impaired (n = 19) and intact groups (n = 23), and MMD-related characteristics (eg, disease duration, stroke history) did not differentiate the 2 groups. CONCLUSION/CONCLUSIONS:Consistent with previous work, frontal-subcortical cognitive deficits (eg, deficits in mental speed, attention, executive functioning) were found in nearly half of patients with MMD and better cognitive performance was associated with factors related to cognitive reserve. Angiographic metrics of disease burden (eg, Suzuki rating, collateral flow) and hemodynamic reserve were not consistently associated with poorer cognitive outcomes, suggesting that cognition is a crucial independent factor to assess in MMD and has relevance for treatment planning and functional status.

Music provides a reward that can enhance learning and motivation in humans. While music is often combined with exercise to improve performance and upregulate mood, the relationship between music-induced reward and motor output is poorly understood. Here, we study music reward and motor output at the same time by capitalizing on music playing. Specifically, we investigate the effects of music improvisation and live accompaniment on motor, autonomic, and affective responses. Thirty adults performed a drumming task while (i) improvising or maintaining the beat and (ii) with live or recorded accompaniment. Motor response was characterized by acceleration of hand movements (accelerometry), wrist flexor and extensor muscle activation (electromyography), and the drum strike count (i.e., the number of drum strikes played). Autonomic arousal was measured by tonic response of electrodermal activity (EDA) and heart rate (HR). Affective responses were measured by a 12-item Likert scale. The combination of improvisation and live accompaniment, as compared to all other conditions, significantly increased acceleration of hand movements and muscle activation, as well as participant reports of reward during music playing. Improvisation, regardless of type of accompaniment, increased the drum strike count and autonomic arousal (including tonic EDA responses and several measures of HR), as well as participant reports of challenge. Importantly, increased motor response was associated with increased reward ratings during music improvisation, but not while participants were maintaining the beat. The increased motor responses achieved with improvisation and live accompaniment have important implications for enhancing dose of movement during exercise and physical rehabilitation.

PURPOSE/OBJECTIVE:DNA methylation profiling stratifies isocitrate dehydrogenase (IDH)-mutant astrocytomas into methylation low-grade and high-grade groups. We investigated the utility of the T2-FLAIR mismatch sign for predicting DNA methylation grade and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion, a molecular biomarker for grade 4 IDH-mutant astrocytomas, according to the 2021 World Health Organization (WHO) classification. EXPERIMENTAL DESIGN/METHODS:Preoperative MRI scans of IDH-mutant astrocytomas subclassified by DNA methylation profiling (n=71) were independently evaluated by two radiologists for the T2-FLAIR mismatch sign. The diagnostic utility of T2-FLAIR mismatch in predicting methylation grade, CDKN2A/B status, copy number variation, and survival was analyzed. RESULTS:The T2-FLAIR mismatch sign was present in 21 of 45 (46.7%) methylation low-grade and 1 of 26 (3.9%) methylation high-grade cases (p<0.001), resulting in 96.2% specificity, 95.5% positive predictive value, and 51.0% negative predictive value for predicting low methylation grade. The T2-FLAIR mismatch sign was also significantly associated with intact CDKN2A/B status (p=0.028) with 87.5% specificity, 86.4% positive predictive value, and 42.9% negative predictive value. Overall multivariable Cox analysis showed that retained CDKN2A/B status remained significant for PFS (p=0.01). Multivariable Cox analysis of the histologic grade 3 subset, which was nearly evenly divided by CDKN2A/B status, CNV, and methylation grade, showed trends toward significance for DNA methylation grade with OS (p=0.045) and CDKN2A/B status with PFS (p=0.052). CONCLUSIONS:The T2-FLAIR mismatch sign is highly specific for low methylation grade and intact CDKN2A/B in IDH-mutant astrocytomas.

PURPOSE OF REVIEW/OBJECTIVE:Multiple system atrophy (MSA) is a rapidly progressive synucleinopathy characterized by autonomic failure, parkinsonism, and cerebellar ataxia. Here, we provide an update on α-synuclein's role in MSA pathophysiology and review the new Movement Disorders Society (MDS) diagnostic criteria and the utility of α-synuclein-based biomarkers. We also highlight ongoing efforts toward clinical trial readiness and review potential disease-modifying therapies undergoing clinical trials. RECENT FINDINGS/RESULTS:A role of urinary tract infections in triggering α-synuclein aggregation and contribution of genes implicated in oligodendroglial development have been suggested in the MSA pathophysiology. The clinically probable MSA category of the new diagnostic criteria shows improved accuracy in early disease stages. Predictors of phenoconversion from pure autonomic failure to MSA are now better defined. Alpha-synuclein strains in CSF and serum, phosphorylated α-synuclein deposits in the skin, and brain α-synuclein pathology visualized using PET ligand [18F]ACI-12589 are emerging as valuable diagnostic tools. Clinical trials in MSA investigate drugs targeting α-synuclein aggregation or preventing α-synuclein expression, along with stem cell and gene therapies to halt disease progression. SUMMARY/CONCLUSIONS:New MSA diagnostic criteria and α-synuclein-based biomarkers may enhance diagnostic accuracy while promising therapies are in development to address disease progression.

PURPOSE OF REVIEW/OBJECTIVE:This review provides an overview of the current and future role of artificial intelligence (AI) and virtual reality (VR) in addressing the complexities inherent to the diagnosis, classification, and management of headache disorders. RECENT FINDINGS/RESULTS:Through machine learning and natural language processing approaches, AI offers unprecedented opportunities to identify patterns within complex and voluminous datasets, including brain imaging data. This technology has demonstrated promise in optimizing diagnostic approaches to headache disorders and automating their classification, an attribute particularly beneficial for non-specialist providers. Furthermore, AI can enhance headache disorder management by enabling the forecasting of acute events of interest, such as migraine headaches or medication overuse, and by guiding treatment selection based on insights from predictive modeling. Additionally, AI may facilitate the streamlining of treatment efficacy monitoring and enable the automation of real-time treatment parameter adjustments. VR technology, on the other hand, offers controllable and immersive experiences, thus providing a unique avenue for the investigation of the sensory-perceptual symptomatology associated with certain headache disorders. Moreover, recent studies suggest that VR, combined with biofeedback, may serve as a viable adjunct to conventional treatment. Addressing challenges to the widespread adoption of AI and VR in headache medicine, including reimbursement policies and data privacy concerns, mandates collaborative efforts from stakeholders to enable the equitable, safe, and effective utilization of these technologies in advancing headache disorder care. This review highlights the potential of AI and VR to support precise diagnostics, automate classification, and enhance management strategies for headache disorders.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Individuals with epilepsy have increased risk of suicidal ideation (SI) and behaviors when compared with the general population. This relationship has remained largely unexplored in adolescents. We investigated the prevalence of suicidality in adolescents with newly diagnosed focal epilepsy within 4 months of treatment initiation and over the following 36 months. METHODS:This was a post hoc analysis of the enrollment and follow-up data from the Human Epilepsy Project, an international, multi-institutional study that enrolled participants between 2012 and 2017. Participants enrolled were 11-17 years of age within 4 months of treatment initiation for focal epilepsy. We used data from the Columbia Suicide Severity Rating Scale (C-SSRS), administered at enrollment and over the 36-month follow-up period, along with data from medical records. RESULTS:A total of 66 adolescent participants were enrolled and completed the C-SSRS. At enrollment, 14 (21%) had any lifetime SI and 5 (8%) had any lifetime suicidal behaviors (SBs). Over the following 36 months, 6 adolescents reported new onset SI and 5 adolescents reported new onset SB. Thus, the lifetime prevalence of SI within this population increased from 21% to 30% (14-20 adolescents), and the lifetime prevalence of SB increased from 8% to 15% (5-10). DISCUSSION/CONCLUSIONS:The prevalence of suicidality in adolescents with newly diagnosed focal epilepsy reported in our study is consistent with previous findings of significant suicidality observed in epilepsy. We identify adolescents as an at-risk population at the time of epilepsy diagnosis and in the following years.