Faculty Bibliography

IMPORTANCE/UNASSIGNED:Classification of persons with long COVID (LC) or post-COVID-19 condition must encompass the complexity and heterogeneity of the condition. Iterative refinement of the classification index for research is needed to incorporate newly available data as the field rapidly evolves. OBJECTIVE/UNASSIGNED:To update the 2023 research index for adults with LC using additional participant data from the Researching COVID to Enhance Recovery (RECOVER-Adult) study and an expanded symptom list based on input from patient communities. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Prospective, observational cohort study including adults 18 years or older with or without known prior SARS-CoV-2 infection who were enrolled at 83 sites in the US and Puerto Rico. Included participants had at least 1 study visit taking place 4.5 months after first SARS-CoV-2 infection or later, and not within 30 days of a reinfection. The study visits took place between October 2021 and March 2024. EXPOSURE/UNASSIGNED:SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Presence of LC and participant-reported symptoms. RESULTS/UNASSIGNED:A total of 13 647 participants (11 743 with known SARS-CoV-2 infection and 1904 without known prior SARS-CoV-2 infection; median age, 45 years [IQR, 34-69 years]; and 73% were female) were included. Using the least absolute shrinkage and selection operator analysis regression approach from the 2023 model, symptoms contributing to the updated 2024 index included postexertional malaise, fatigue, brain fog, dizziness, palpitations, change in smell or taste, thirst, chronic cough, chest pain, shortness of breath, and sleep apnea. For the 2024 LC research index, the optimal threshold to identify participants with highly symptomatic LC was a score of 11 or greater. The 2024 index classified 20% of participants with known prior SARS-CoV-2 infection and 4% of those without known prior SARS-CoV-2 infection as having likely LC (vs 21% and 5%, respectively, using the 2023 index) and 39% of participants with known prior SARS-CoV-2 infection as having possible LC, which is a new category for the 2024 model. Cluster analysis identified 5 LC subtypes that tracked quality-of-life measures. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The 2024 LC research index for adults builds on the 2023 index with additional data and symptoms to help researchers classify symptomatic LC and its symptom subtypes. Continued future refinement of the index will be needed as the understanding of LC evolves.

PURPOSE/UNASSIGNED:People with blindness and low vision (pBLV) face challenges in navigating. Mobility aids are crucial for enhancing independence and safety. This paper presents an electronic travel aid that leverages a haptic-based, higher-order sensory substitution approach called Virtual Whiskers, designed to help pBLV navigate obstacles effectively, efficiently, and safely. MATERIALS AND METHODS/UNASSIGNED:Virtual Whiskers is equipped with a plurality of modular vibration units that operate independently to deliver haptic feedback to users. Virtual Whiskers features two navigation modes: open path mode and depth mode, each addressing obstacle negotiation from different perspectives. The open path mode detects and delineates a traversable area within an analyzed field of view and then guides the user in the most traversable direction with adaptive vibratory feedback. Depth mode assists users in negotiating obstacles by highlighting spatial areas with prominent obstacles; haptic feedback is generated by re-mapping proximity to vibration intensity. We recruited 10 participants with blindness or low vision for user testing of Virtual Whiskers. RESULTS/UNASSIGNED:Both approaches reduce hesitation time (idle periods) and decrease the number of cane contacts with objects and walls. CONCLUSIONS/UNASSIGNED:Virtual Whiskers is a promising obstacle negotiation strategy that demonstrates great potential to assist with pBLV navigation.

INTRODUCTION/UNASSIGNED:The impact of multiple feeding arteries on clinical outcomes of cerebral arteriovenous malformations (AVMs) is not well understood. This study aims to compare outcomes between AVMs with multiple versus single feeding arteries. PATIENTS AND METHODS/UNASSIGNED:Data from the Multicenter International Study for Treatment of Brain AVMs (MISTA) consortium were analyzed. Propensity score matching (PSM) was used to balance cohorts. Subgroup analysis was conducted for ruptured and unruptured AVMs and different treatment options, and multivariable logistic regression was applied to assess the impact of feeding artery origin. RESULTS/UNASSIGNED: = 0.002). DISCUSSION AND CONCLUSION/UNASSIGNED:AVMs with a single feeding artery were more likely to present with rupture, but no significant differences in obliteration rates or complications were observed between the groups after PSM. These findings suggest that while the number of feeding arteries may influence the initial presentation, it does not appear to impact overall treatment success or patient prognosis. Further prospective studies are needed to confirm these findings.

Curbs separate the edge of raised sidewalks from the street and are crucial to locate in urban environments as they help delineate safe pedestrian zones from dangerous vehicular lanes. However, the curbs themselves are also significant navigation hazards, particularly for people who are blind or have low vision (pBLV). The challenges faced by pBLV in detecting and properly orienting themselves for these abrupt elevation changes can lead to falls and serious injuries. Despite recent advancements in assistive technologies, the detection and early warning of curbs remains a largely unsolved challenge. This paper aims to tackle this gap by introducing a novel, multi-faceted sensory substitution approach hosted on a smart wearable; the platform leverages an RGB camera and an embedded system to capture and segment curbs in real time and provide early warning and orientation information. The system utilizes a YOLOv8 segmentation model which has been trained on our custom curb dataset to interpret camera input. The system output consists of adaptive auditory beeps, abstract sonifications, and speech, which convey curb distance and orientation. Through human-subjects experimentation, we demonstrate the effectiveness of the system as compared to the white cane. Results show that our system can provide advanced warning through a larger safety window than the cane, while offering nearly identical curb orientation information. Future enhancements will focus on expanding our curb segmentation dataset, improving distance estimations through advanced 3D sensors and AI-models, refining system calibration and stability, and developing user-centric sonification methods to cater for a diverse range of visual impairments.

Mobile applications are widely used in epilepsy, although their impact on clinical effectiveness (CE) and their feasibility, acceptability, and usability (FAU) remain unclear. We conducted a systematic review investigating CE and FAU of epilepsy mobile applications using MEDLINE and Embase from database inception to June 21, 2024. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting standards. The protocol was registered on PROSPERO (CRD42019134848). In duplicate, we determined study quality using the Newcastle-Ottawa Quality Assessment Scale (NOQAS) and the Joanna Briggs Critical Appraisal Checklist (to determine eligibility for inclusion), risk of bias using the Cochrane Risk of Bias tool, and usability study quality using the 15-point Silva scale. We identified 8953 studies, of which 20 were included. Twelve (60.0%) addressed CE, nine (45.0%) acceptability, five (25.0%) usability, and eight (40.0%) feasibility. Five (25.0%) evaluated CE and FAU. Studies comprised prospective cohort (n = 9, 45.0%), pilot (n = 3, 15.0%), randomized controlled trial (n = 7, 35.0%), and pre/post (n = 1, 5.0%) designs. Most apps were used for self-management or to enhance education or communication between patients and providers. Cohort studies demonstrated fair quality (median NOQAS score = 5, interquartile range [IQR] = 5.0-5.8), whereas of seven randomized controlled trials, four (57.1%) had some concern for bias. Usability studies demonstrated high quality (median Silva score = 10, IQR = 10-11). Apps were predominantly intended for patient use (n = 9, 75.0%). Symptom reporting and medication management were the most common app targets in both CE and FAU studies (n = 8, 66.7%; n = 9, 69.2%), although FAU studies more frequently used monitoring or tracking (n = 10, 76.9%) and reminder setting (n = 10, 76.9%) than CE apps (n = 7, 58.3%). Investigations of application use most commonly studied CE and patient-facing apps. Additional high-quality evidence is necessary to evaluate the CE and FAU of app use in epilepsy to work toward the standardization of FAU metrics and development of implementation guidelines.

BACKGROUND:Arteriovenous malformations (AVMs) are complex vascular anomalies with a high risk of hemorrhage and neurological deficits, especially when located in eloquent brain regions. The eloquence of an AVM location is a critical factor in the treatment planning, influencing both the risk of complications and long-term functional outcomes. This study aims to compare outcomes between eloquent and non-eloquent AVMs. METHODS:This multicenter, retrospective study utilized data from the Multicenter International Study for Treatment of Brain AVMs (MISTA) consortium. Patients with eloquent and non-eloquent AVMs were compared on baseline characteristics, angiographic outcomes, and functional outcomes using the modified Rankin Scale (mRS). Propensity score weighting (IPTW) was applied to adjust for confounding variables. RESULTS:The study included 1,013 patients, with 498 (49.2%) AVMs located in eloquent regions and 515 (50.8%) in non-eloquent regions. In unadjusted analysis, eloquent AVMs had lower complete obliteration rates (67.6% vs. 79.5%, OR: 0.53, 95% CI: 0.39-0.72, p < 0.001) and higher complication rates (24.5% vs. 19.0%, OR: 1.38, 95% CI: 1.02-1.86, p = 0.03) compared to non-eloquent AVMs. After IPTW adjustment, eloquent AVMs continued to show significantly higher odds of overall complications (OR: 1.68, 95% CI: 1.12-2.52, p = 0.01) and symptomatic complications (OR: 1.77, 95% CI: 1.12-2.80, p = 0.01). Secondary analysis within the eloquent group indicated that embolization was linked to an elevated risk of complications. Surgery and radiosurgery showed comparable functional outcomes at last follow-up and complications rates with higher complete obliteration rates in surgery. CONCLUSION/CONCLUSIONS:AVMs in eloquent brain areas present higher risks of complications and lower obliteration rates, emphasizing the need for cautious, individualized treatment planning. Within the eloquent group, embolization increased the risk of complications, while surgery and radiosurgery showed comparable functional outcomes at last follow-up and complication rates with higher complete obliteration rates in surgery. These findings highlight the importance of location in AVM management and support further research focusing on comparing treatment strategies for AVMs in eloquent brain areas.

Typical carotid webs are nonatherosclerotic shelf-like projections of fibromyxoid tissue extending from the posterior wall of the proximal internal carotid artery (ICA). Carotid webs may precipitate acute embolic stroke, especially in younger patients. We describe our experience with pathology-proven carotid webs of atypical appearance, or atypical carotid webs (ACWs), a subset of carotid webs exhibiting abnormal location, morphology, or association with atherosclerotic changes. Our electronic medical record database was queried for all imaging impressions containing "carotid web," "shelf," or "protrusion" from 2018-2024. Imaging was reviewed by an experienced neuroradiologist and neurosurgeon. Patients with typical carotid webs or those with different diagnoses (e.g. dissection/thrombus) were excluded. Twenty-seven patients were treated for typical carotid webs; 24 were treated with carotid endarterectomy (CEA) and had pathology-confirmed webs. Five patients (three male) were identified to have ACWs and included in this report. Mean age was 43.6 years. All ACWs were identified by computed tomography angiography (CTA). All patients presented with acute ischemic stroke or transient ischemic attack (TIA). One web was located on the anterior ICA wall, three were of abnormal morphology different from a "shelf-like" projection, and one was associated with atherosclerotic change. No patients experienced a further stroke or TIA following CEA. ACWs may precipitate ischemic stroke and can be treated and definitively diagnosed with CEA. Due to their unusual appearance, ACWs may evade radiographic identification or be misdiagnosed. As ACWs have not been previously reported in the literature, awareness of their existence must be raised to increase their detection and treatment.

OBJECTIVE:Seizures can impact cognition both acutely and chronically. However, among those without significant comorbidities and broadly average cognition at epilepsy onset, the relationship between cognitive function at the time of diagnosis and long-term seizure control has been relatively unexplored. This analysis investigated associations between participant characteristics including specific aspects of cognitive performance at the time of focal epilepsy diagnosis and antiseizure medication (ASM) treatment resistance. METHODS:This was a secondary analysis of Human Epilepsy Project (HEP) data, which enrolled people with newly diagnosed focal epilepsy and broadly average cognition (estimated IQ ≥ 70) from June 29, 2012, to September 1, 2019. Participants analyzed in this study were between 18 and 60 years old, and scored within an acceptable range (i.e., Standard Score of ≥80) on measures estimating premorbid cognitive ability were offered the Cogstate Brief Battery (CBB). Participant characteristics were analyzed, including the presence of any anxiety disorders or depression, and summary CBB scores. HEP participants who were classified by the study as treatment resistant if they had experienced failure to achieve seizure freedom after two adequate trials of ASMs. Treatment resistance was modeled using multiple logistic regression to assess for independent associations between attention and working memory after correcting for the presence of the other potentially explanatory variables. RESULTS:200 HEP participants had comprehensive enrollment records including CBB results and complete seizure outcome data for analysis in this study. After correcting for potentially confounding variables, there were no independent associations between cognitive measures on the CBB at the time of enrollment and subsequent development of ASM treatment resistance. Specifically, z-scores for reaction time on the CBB (an average of the CBB Identification and Detection tests) were not associated with treatment resistance (p = 0.51) and z-scores for memory performance (an average of the CBB One Card Learning test and One Back tests) were not associated with treatment resistance (p = 0.24). There were no significant independent associations between age or the presence of depression or anxiety disorders at the time of CBB testing and treatment resistance. However, there was an independent association between employment status and treatment resistance, with those who were employed or students (>18 years old) at the time of enrollment and CBB testing having 0.35 times lower odds of treatment resistance (95 %CI 0.15-0.81, p = 0.01). SIGNIFICANCE/CONCLUSIONS:The findings from this study suggest that in otherwise healthy people with new onset focal epilepsy who have broadly average intelligence, attention and working memory as measured by the CBB at the time of diagnosis is not associated with treatment resistance. Although performance on cognitive testing at epilepsy onset may not be predictive of risk of treatment resistance in this population, other individual characteristics such as employment status at the time of diagnosis may be indirect markers of long-term seizure outcomes and require further investigation.

Fatigue is a common and often debilitating feature of multiple sclerosis (MS) that lacks reliably effective treatment options for most patients. Transcranial direct current stimulation (tDCS), a safe and well-tolerated type of noninvasive brain stimulation, is a low-cost and home-based approach with the potential to reduce fatigue in MS. We conducted a double-blind, sham-controlled, randomized clinical trial to compare active vs. low-dose (sham) tDCS paired with computer-based cognitive training, delivered as a home-based intervention, to reduce MS-related fatigue. Participants with MS-related fatigue, but without depression, were stratified by neurologic disability using the Extended Disability Status Scale (EDSS) and randomized to complete 30 daily sessions over six weeks of either active or sham tDCS paired with online cognitive training (BrainHQ). The primary outcome was the change in PROMIS Fatigue score from baseline to the end of the intervention. A total of 117 participants were randomized, with 92% completing all treatment sessions. Both groups showed significant reductions in fatigue, with no significant difference between them. This suggests that tDCS does not provide any additional benefit over cognitive training alone in reducing fatigue, but confirms the feasibility and tolerance of this home-based intervention.