Faculty Bibliography

Vision-based localization approaches now underpin newly emerging navigation pipelines for myriad use cases, from robotics to assistive technologies. Compared to sensor-based solutions, vision-based localization does not require pre-installed sensor infrastructure, which is costly, time-consuming, and/or often infeasible at scale. Herein, we propose a novel vision-based localization pipeline for a specific use case: navigation support for end users with blindness and low vision. Given a query image taken by an end user on a mobile application, the pipeline leverages a visual place recognition (VPR) algorithm to find similar images in a reference image database of the target space. The geolocations of these similar images are utilized in a downstream task that employs a weighted-average method to estimate the end user's location. Another downstream task utilizes the perspective-n-point (PnP) algorithm to estimate the end user's direction by exploiting the 2D-3D point correspondences between the query image and the 3D environment, as extracted from matched images in the database. Additionally, this system implements Dijkstra's algorithm to calculate a shortest path based on a navigable map that includes the trip origin and destination. The topometric map used for localization and navigation is built using a customized graphical user interface that projects a 3D reconstructed sparse map, built from a sequence of images, to the corresponding a priori 2D floor plan. Sequential images used for map construction can be collected in a pre-mapping step or scavenged through public databases/citizen science. The end-to-end system can be installed on any internet-accessible device with a camera that hosts a custom mobile application. For evaluation purposes, mapping and localization were tested in a complex hospital environment. The evaluation results demonstrate that our system can achieve localization with an average error of less than 1 m without knowledge of the camera's intrinsic parameters, such as focal length.

BACKGROUND:A Core Outcome Set (COS) is a standardised list of outcomes that should be reported as a minimum in all clinical trials. In epilepsy, the choice of outcomes varies widely among existing studies, particularly in clinical trials. This diminishes opportunities for informed decision-making, contributes to research waste and is a barrier to integrating findings in systematic reviews and meta-analyses. Furthermore, the outcomes currently being measured may not reflect what is important to people with epilepsy. Therefore, we aim to develop a COS specific to clinical effectiveness research for adults with epilepsy using Delphi consensus methodology. METHODS:The EPSET Study will comprise of three phases and follow the core methodological principles as outlined by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Phase 1 will include two focused literature reviews to identify candidate outcomes from the qualitative literature and current outcome measurement practice in phase III and phase IV clinical trials. Phase 2 aims to achieve international consensus to define which outcomes should be measured as a minimum in future trials, using a Delphi process including an online consensus meeting involving key stakeholders. Phase 3 will involve dissemination of the ratified COS to facilitate uptake in future trials and the planning of further research to identify the most appropriate measurement instruments to use to capture the COS in research practice. DISCUSSION/CONCLUSIONS:Harmonising outcome measurement across future clinical trials should ensure that the outcomes measured are relevant to patients and health services, and allow for more meaningful results to be obtained. CORE OUTCOME SET REGISTRATION/UNASSIGNED:COMET Initiative as study 118 .

INTRODUCTION/BACKGROUND:Family caregivers of people with advanced Parkinson's Disease (PD) are at high risk of caregiver strain, which independently predicts adverse patient outcomes. We tested the effects of one year of interdisciplinary, telehealth-enhanced home visits (IN-HOME-PD) with 16 weeks of peer mentoring on caregiver strain compared with usual care. METHODS:We enrolled homebound people with advanced PD (PWPD) and their primary caregiver as IN-HOME-PD dyads. We trained experienced PD family caregivers as peer mentors. Dyads received four structured home visits focused on advanced symptom management, home safety, medications, and psychosocial needs. Starting at approximately four months, caregivers spoke weekly with a peer mentor for 16 weeks. We compared one-year change in caregiver strain (MCSI, range 0-72) with historical controls, analyzed intervention acceptability, and measured change in anxiety, depression, and self-efficacy. RESULTS:Longitudinally, IN-HOME-PD caregiver strain was unchanged (n = 51, 23.34 (SD 9.43) vs. 24.32 (9.72), p = 0.51) while that of controls worsened slightly (n = 154, 16.45 (10.33) vs. 17.97 (10.88), p = 0.01). Retention in peer mentoring was 88.2%. Both mentors and mentees rated 100% of mentoring calls useful, with mean satisfaction of 91/100 and 90/100, respectively. There were no clinically significant improvements in anxiety, depression, or self-efficacy. CONCLUSIONS:Interdisciplinary telehealth-enhanced home visits combined with peer mentoring mitigated the worsening strain observed in caregivers of less advanced individuals. Mentoring was met with high satisfaction. Future caregiver-led peer mentoring interventions are warranted given the growing, unmet needs of PD family caregivers. TRIAL REGISTRATION/BACKGROUND:NCT03189459.

BACKGROUND:Intracranial stenosis (ICAS) is a common cause of stroke worldwide and patients with symptomatic ICAS exhibit a high rate of recurrence, particularly in the early period after the initial event. In this study, we aimed to study the association between borderzone infarct and recurrent ischemic stroke in patients hospitalized with symptomatic ICAS. METHODS:This is a retrospective single center study that included patients hospitalized with acute ischemic stroke in the setting of intracranial stenosis (50% or more and an acute ischemic stroke in the territory supplied by the stenosed artery) over a 32-month period. We excluded patients who did not receive a brain MRI or did not have an infarct on brain imaging. The primary predictor is infarct pattern (any borderzone vs. no borderzone infarct) and the primary outcome was recurrent cerebrovascular events (RCVE) within 90 days. We used unadjusted, and age and sex adjusted logistic regression models to determine associations between infarct pattern and RCVE at 90-days. RESULTS:Among 99 patients who met the inclusion criteria (4 tandem), the mean age was 70.1 ± 11.2 years and 41.4% were women; 43 had borderzone infarcts and 19 had RCVE. In adjusted binary logistic regression analysis, borderzone infarct was associated with increased risk of RCVE (adjusted OR 4.00 95% CI 1.33-11.99, p=0.013). The association between borderzone infarction and RCVE was not different among anterior circulation ICAD (adjusted HR 2.85 95% CI 0.64-12.76, p=0.172) vs. posterior circulation ICAD (adjusted HR 6.69 95% CI 1.06-42.11, p=0.043), p-value for interaction = 0.592. CONCLUSION/CONCLUSIONS:In real world post-SAMMPRIS medically treated patients with ICAD, the borderzone infarct pattern was associated with 90-day RCVE. Borderzone infarcts are likely a surrogate marker of impaired distal blood flow, highlighting the importance of targeting stroke mechanisms and developing alternative treatment strategies for high-risk cohorts.

Although visual symptoms are common following concussion, quantitative measures of visual function are missing from concussion evaluation protocols on the athletic sideline. For the past half century, rapid automatized naming (RAN) tasks have demonstrated promise as quantitative neuro-visual assessment tools in the setting of head trauma and other disorders but have been previously limited in accessibility and scalability. The Mobile Interactive Cognitive Kit (MICK) App is a digital RAN test that can be downloaded on most mobile devices and can therefore provide a quantitative measure of visual function anywhere, including the athletic sideline. This investigation examined the feasibility of MICK App administration in a cohort of Division 1 college football players. Participants (n = 82) from a National Collegiate Athletic Association (NCAA) Division 1 football team underwent baseline testing on the MICK app. Total completion times of RAN tests on the MICK app were recorded; magnitudes of best time scores and between-trial learning effects were determined by paired t-test. Consistent with most timed performance measures, there were significant learning effects between the two baseline trials for both RAN tasks on the MICK app: Mobile Universal Lexicon Evaluation System (MULES) (p < 0.001, paired t-test, mean improvement 13.3 s) and the Staggered Uneven Number (SUN) (p < 0.001, mean improvement 3.3 s). This study demonstrated that the MICK App can be feasibly administered in the setting of pre-season baseline testing in a Division I environment. These data provide a foundation for post-injury sideline testing that will include comparison to baseline in the setting of concussion.

Saccadic slowing as a component of supranuclear saccadic gaze palsy is an important diagnostic sign in multiple neurologic conditions, including degenerative, inflammatory, genetic, or ischemic lesions affecting brainstem structures responsible for saccadic generation. Little attention has been given to the accuracy with which clinicians correctly identify saccadic slowing. We compared clinician (n = 19) judgements of horizontal and vertical saccade speed on video recordings of saccades (from 9 patients with slow saccades, 3 healthy controls) to objective saccade peak velocity measurements from infrared oculographic recordings. Clinician groups included neurology residents, general neurologists, and fellowship-trained neuro-ophthalmologists. Saccades with normal peak velocities on infrared recordings were correctly identified as normal in 57% (91/171; 171 = 9 videos × 19 clinicians) of clinician decisions; saccades determined to be slow on infrared recordings were correctly identified as slow in 84% (224/266; 266 = 14 videos × 19 clinicians) of clinician decisions. Vertical saccades were correctly identified as slow more often than horizontal saccades (94% versus 74% of decisions). No significant differences were identified between clinician training levels. Reliable differentiation between normal and slow saccades is clinically challenging; clinical performance is most accurate for detection of vertical saccade slowing. Quantitative analysis of saccade peak velocities enhances accurate detection and is likely to be especially useful for detection of mild saccadic slowing.

BACKGROUND:Factors driving differences in disease burden between African American and White people with multiple sclerosis (pwMS) remain unclear. Here, we explored whether differences in disability outcomes could be observed after controlling for major sociodemographic factors and comorbidities, and assessed the presence of a possible interaction between MS and race. METHODS:In this cross-sectional study, 120 pwMS within 6 years from disease onset and 82 healthy controls between 18 and 70 years of age, self-identified as either African American or White, were prospectively enrolled. Inclusion criteria for pwMS were: diagnosis of MS according to the revised McDonald criteria, relapsing-remitting phenotype and Expanded Disability Status Scale (EDSS) < 6.5. Study outcomes included: (i) global disability (EDSS); (ii) quantitative mobility and leg function (Timed 25 Foot Walk Test-T25FWT); (iii) quantitative finger dexterity (9-Hole Peg Test-9HPT); (iv) cognitive efficiency and speed performance (Symbol Digit Modalities Test-SDMT). Differences in disability outcomes were assessed employing multivariable linear regression models. Based on their association with MS or disability, covariates included age, gender, race, years of education, total income, body mass index, comorbidities. The interaction between MS and race on disability outcomes was estimated via relative excess risk of interaction and attributable proportion. RESULTS:Accounting for age, gender, total income, education, body mass index and comorbidities, African American pwMS showed significantly worse performances in manual dexterity and cognition than White pwMS (White pwMS coeff. 3.24, 95% CI 1.55, 4.92 vs African American pwMS coeff. 5.52, 95% CI 3.55, 7.48 and White pwMS coeff. -5.87, 95% CI -8.86, -2.87 vs African American pwMS coeff. -7.99, 95% CI -11.58,-4.38). MS and race independently contributed to the observed gradient in disability severity. CONCLUSIONS:Complex social disparities and systemic racism might contribute to clinical heterogeneity in MS.

Demyelination is observed in both healthy aging and age-related neurodegenerative disorders. While the significance of myelin within the cortex is well acknowledged, studies focused on intracortical demyelination and depth-specific structural alterations in normal aging are lacking. Using the recently available Human Connectome Project Aging dataset, we investigated intracortical myelin in a normal aging population using the T1w/T2w ratio. To capture the fine changes across cortical depths, we employed a surface-based approach by constructing cortical profiles traveling perpendicularly through the cortical ribbon and sampling T1w/T2w values. The curvatures of T1w/T2w cortical profiles may be influenced by differences in local myeloarchitecture and other tissue properties, which are known to vary across cortical regions. To quantify the shape of these profiles, we parametrized the level of curvature using a nonlinearity index (NLI) that measures the deviation of the profile from a straight line. We showed that NLI exhibited a steep decline in aging that was independent of local cortical thinning. Further examination of the profiles revealed that lower T1w/T2w near the gray-white matter boundary and superficial cortical depths were major contributors to the apparent NLI variations with age. These findings suggest that demyelination and changes in other T1w/T2w related tissue properties in normal aging may be depth-specific and highlight the potential of NLI as a unique marker of microstructural alterations within the cerebral cortex.

Plexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors often cause significant morbidity, with treatment options limited historically to surgery. There have been tremendous advances over the past two decades in our understanding of PN, and the recent regulatory approvals of the MEK inhibitor selumetinib are reshaping the landscape for PN management. At present, there is no agreed upon PN definition, diagnostic evaluation, surveillance strategy, or clear indications for when to initiate treatment and selection of treatment modality. In this review, we address these questions via consensus recommendations from a panel of multi-disciplinary NF1 experts.

The wide variety of clinical manifestations of the genetic syndrome neurofibromatosis type 1 (NF1) are driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) block downstream targets of RAS. The recent regulatory approvals of the MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 has made it the first medical therapy approved for this indication in the United States, the European Union and elsewhere. Several recently published and ongoing clinical trials have demonstrated that MEKi may have potential benefit for a variety of other NF1 manifestations, and there is broad interest in the field regarding the appropriate clinical use of these agents. In this review, we present the current evidence regarding the use of existing MEKi for a variety of NF1-related manifestations, including tumor (neurofibromas, malignant peripheral nerve sheath tumors, low grade glioma, and juvenile myelomonocytic leukemia) and non-tumor (bone, pain, and neurocognitive) manifestations. We discuss the potential utility of MEKi in related genetic conditions characterized by overactivation of the RAS pathway (RASopathies). In addition, we review practical treatment considerations for the use of MEKi as well as provide consensus recommendations regarding their clinical use from a panel of experts.