Faculty Bibliography

BACKGROUND/UNASSIGNED:High intensity focused ultrasound (HiFU) is a relatively new incisionless intervention used for treatment of essential tremor and Parkinson's disease tremor. Understanding the indications, benefits, risks and limitations of HiFU, as well as how it compares to deep brain stimulation (DBS), is important in guiding appropriate recommendations for prospective patients. METHODS/UNASSIGNED:Current literature on efficacy and safety of HiFU in essential tremor and Parkinson's disease was reviewed. We additionally reviewed data on the patients who presented to our center for HiFU consultation, including outcomes of patients with low skull density ratios, and distances traveled for the procedure. RESULTS/DISCUSSION/UNASSIGNED:HiFU is an effective and generally well-tolerated treatment for tremor. Adverse events, especially gait instability, are typically temporary but should be discussed with patients. The risk of tremor recurrence in certain patients with Parkinson's disease is also of note. Identifying appropriate candidates for either intervention remains crucial and involves considering each patient's circumstances and preferences, potential adverse effects, and practical aspects like access to follow-up and expectations. Data on bilateral HiFU lesioning, use of HiFU in patients with low skull density ratios, and emerging targets like the pallidothalamic tract are discussed as well.

Individuals with Lewy body dementia (LBD) rely on family caregivers. Caregiving demands limit caregivers' ability to attend to their own health needs, increasing their vulnerability to the psychological effects of caregiving. We previously piloted a peer mentoring intervention with experienced (mentor) and less experienced (mentee) LBD caregivers. Matched mentor-mentee dyads spoke weekly for 16 weeks, guided by an intervention handbook. LBD knowledge and attitudes towards dementia improved post-intervention. We hypothesized that caregiver health status moderates response to peer mentoring. Post hoc analyses (N = 30 dyads) showed that 75% of mentees and 66% of mentors endorsed ≥1 comorbidity. Mentees and mentors with comorbidities showed greater improvement in LBD knowledge postintervention (P = 0.039) and dementia attitudes post-training (P = 0.016), respectively. Caregivers with comorbidities and thus greater exposure to health care may derive excess benefit from an effective LBD caregiver intervention than healthier counterparts, enhancing both the objective knowledge and their confidence in caring for their loved ones.

BACKGROUND:Despite fall-related injuries accounting for over two-thirds of older adult trauma injuries, fall-related injuries are more likely to be under-triaged. The Score for Trauma Triage in the Geriatric and Middle-Aged (STTGMA) is an injury risk-triage tool. This study aims to validate STTGMA's accuracy in predicting fall-related mortality among older adult trauma patients and compare its predictive accuracy with the Geriatric Trauma Outcome Score (GTOS) and the Revised Trauma Score (RTS). METHODS:Using a retrospective cohort design, we selected 6,458 older adult trauma patients (aged 65 years and older) from a single institutional trauma database (2017-2023). The primary outcome variable was in-hospital death, measured as a binary variable. The primary predictor variable was the STTGMA score, measured as a continuous variable and a four-level categorical variable. The secondary predictor variables were the GTOS and the RTS. We compared the predictive accuracy (95% confidence interval (CI)) of the STTGMA, GTOS, and RTS. We further assessed the relationships between the STTGMA risk categories and time-to-death and hospital length of stay using multivariable time-varying Cox proportional hazard analysis and multivariable quantile regression analysis, respectively. RESULTS:A total of 130 patients (2.0%) died during admission, and the median hospital length of stay was 2 days. STTGMA exhibited 84% (95% CI: 77.3-89.8) accuracy in predicting in-hospital fall-related mortality, while the GTOS and RTS both exhibited 71% diagnostic accuracies. Compared to the minimal risk category, older adult trauma patients classified as low, moderate, and high risks each had significantly longer hospital stays and adjusted mortality risks, in a dose-response pattern. CONCLUSION/CONCLUSIONS:STTGMA can accurately predict in-hospital mortality and risk-stratify the length of stay and the time to death among older adult trauma patients with fall-related injuries.

Flickering light is a new promising, fully non-invasive brain stimulation technique that utilizes intermittent sensory stimulation to induce brainwave synchronization (entrainment). While the effects of 40 Hz externally induced neural entrainment have been extensively described, little is known about 60 Hz entrainment in humans. This study presents preliminary observations on the neural and somatic response to flickering 60 Hz light in healthy volunteers over a 3-week period. Fourteen volunteers were randomized to receive either 60 Hz flickering white light or constant light as sham (30-min sessions, 3 weeks, 5 days/week on weekdays). Neural entrainment was assessed with EEG on days 1, 5 and 19. Salivary cortisol and C-reactive protein (CRP) levels, measured with ELISA, assessed the somatic response to stimulation. Side effects and well-being were monitored via questionnaires. EEG recordings showed neural entrainment and synchrony in response to 60 Hz flickering light across multiple cortical regions, including occipital, central, temporal, and frontal areas. The entrainment power and synchronization between different cortical regions declined significantly by day 19 compared to day 1, indicating possible neural habituation. Cortisol and CRP salivary levels were unchanged, and minor side effects were reported with equal frequency in the active and sham groups. Our findings show that 60 Hz flickering light can induce significant neural entrainment and synchrony in healthy adults and is well tolerated. The decline in entrainment strength and neural synchrony observed with repeated 60 Hz stimulations suggests plastic changes in the cortex. To the best of our knowledge, this is the first study to characterize neural and somatic responses to repeated 60 Hz flickering visual stimuli. Given the well-known connection between 60 Hz brain oscillations and cognition, neuroplasticity, and their role in neuropsychiatric disorders, additional research in both preclinical and clinical settings is warranted.

There are more than two million amputees in the USA, and almost all will experience phantom limb sensations (PLS), describing the missing limb as still present. They may also experience intense pain, known as phantom limb pain (PLP), a considerable factor in poor quality of life. In some upper extremity amputees and following brachial plexus avulsion injury (BPAI), hand digits can be detected and mapped to distinct facial skin areas, termed hand-to-face remapping. In this study, we analysed PLS following brachial plexus anaesthesia (BPA) administered prior to upper limb surgeries. Our 39 participants had planned shoulder, wrist or hand surgery. We sought to determine the time course for the emergence of phantom limb experiences after BPA up to the following 24 hours in participants with intact limbs. We also investigated whether there was hand-to-face remapping, suggesting potential cortical reorganization, or changes in proprioception before and after the induction of BPA. Twenty (54%) participants reported PLS immediately after the onset of BPA (T2), and 28 (72%) participants altered proprioception (AP) after surgery (T3). However, neither PLP nor hand mapping onto the face was reported or evoked. PLS were seen earlier than AP. We conclude that PLS arise rapidly after BPA-induced temporary deafferentation of the upper limb and might serve as a model for the permanent deafferentation experienced in individuals with a major upper limb amputation or BPAI. These results contribute to defining a time course for changes after BPA and increase our understanding of how phantom limb phenomena might arise following limb amputation or BPAI.

Amid the dismantling of state structures in Haiti, the first Black republic faces significant health disparities compared to its former colonial power, France. These disparities include lower life expectancy (64.8 vs. 82.3 years) and higher infant and maternal mortality rates. The situation is further exacerbated by widespread mental health issues, severe food insecurity (50% acute vs. 37% moderate), and elevated homicide rates (13.35 vs. 1.35 per 100,000 inhabitants). As calls grow for France to return the independence ransoms extracted from Haiti, there remains limited data on how reparations could impact the country's public health, community well-being, or effective implementation of healing programs. Between Spring and Fall 2023, we conducted 4 focus groups: 1st with Haitian men and women residing in the United States, a 2nd-with men in Haiti, a 3rd with women in Cap-Haïtien and Les Cayes, and a 4th with women in Cité Soleil. We conducted focus groups structured interview protocol, comprised of open-ended questions categorized into 4 thematic sections. These questions provided insights into participants' perceptions on mental health, the daily challenges and barriers to access care, and community-based healing. Participants emphasized need for policies that address the social determinants of health, ensure safety and justice, and promote healthier workplace environments. They also advocated for mental health education aimed at reducing stigma, cultivating trust, and strengthening community support systems; with an emphasis on developing professional training, ethics, and sustainable long-term mental health services accessible for individuals of all ages. Haitian participants underscore the critical need to restore security, address the social determinants of health, and implement community-based mental health initiatives. We propose a biopsychosocial-ecological approach to guide reparations efforts. A targeted investment of $30 billion could yield substantial improvements in healthcare, mental health services, and public safety-contributing to increased life expectancy, reduced mortality rates, and decreased violence.

INTRODUCTION/UNASSIGNED:Recent investigations have identified patients of African ancestry (AA) with Multiple Sclerosis (MS), who display more rapid B-cell repopulation after standard semi-annual infusions with an anti-CD20 monoclonal antibody for B cell depletion. In this study, we explored the immunologic and genetic factors, with, serum drug monitoring that may contribute to a faster rate of B-cell repletion that follows during recovery from treatment with anti-CD20 antibody. METHODS/UNASSIGNED:In AA MS patients treated with an anti-CD20 antibody that had early repopulation of peripheral blood B cells, we assessed for extrinsic factors, including the presence of anti-drug antibodies against ocrelizumab, which may contribute to early repletion. We also documented the associated serum drug levels. In addition, we examined for inheritance of intrinsic gene polymorphisms associated with B cell survival and immune function. RESULTS/UNASSIGNED:Our findings identified a subset of AA patients with early B cell repletion after anti-CD20 treatment associated with anti-drug antibodies and an absence of detectable drug. Furthermore, a separate set of AA patients with the early B cell repletion phenotype without anti-drug antibodies had significant over-representation of genetic polymorphisms that map to genes for the B cell survival factor, BAFF, to antibody-dependent cytotoxicity, and to pathways involved in inflammation, leukocyte activation and B cell differentiation. DISCUSSION/UNASSIGNED:In AA patients with MS, after anti-CD20 antibody treatment we found an unexpected high occurrence of early B cell replenishment. This was associated with the presence of anti-drug antibodies and/or specific genetic polymorphisms. Larger studies are now needed to determine whether these factors may lead to impaired therapeutic benefits of B cell targeted therapy and clinical progression, and these findings may be useful to guide future optimized personalized therapeutic strategies.

BACKGROUND/UNASSIGNED:A central vestibular neural mechanism known as velocity storage may be inappropriately conditioned in mal de débarquement syndrome (MdDS), a rare chronic vestibular disorder with a continuous false sensation of self-motion described as non-spinning vertigo. Visual-vestibular therapy approaches designed to recondition the three-dimensional properties of velocity storage have yielded much clinical success, but not without limitations. An alternative therapeutic approach, designed to attenuate the contribution of malfunctioning velocity storage in higher-order neural processing, has also yielded positive results, but at a lower success rate. We sought a possible explanation for the latter shortcoming using a mathematical model. METHODS/UNASSIGNED:The three-dimensional orientation properties of velocity storage can be modeled as a dynamical system using a 3 × 3 system matrix. For normal upright, the system matrix is diagonal, with its eigenvectors aligning with the head-fixed roll, pitch, and yaw axes, and the yaw eigenvector with gravity. A pull sensation of MdDS has been expressed with a system matrix with off-diagonal elements representing cross-axis coupling and interpreted as a misalignment between the yaw eigenvector and the head vertical. We manipulated the velocity storage's yaw time constant and output weight. RESULTS/UNASSIGNED:The model predicted that attenuating the velocity storage contribution could exaggerate the pull sensation. CONCLUSION/UNASSIGNED:The present model-based exploration points to a possible weakness in the MdDS treatment approach focused on velocity storage attenuation, while likely beneficial otherwise. When a pulling sensation is present, the treatment protocol may need to be supplemented with another approach that specifically counters this problem, such as optokinetic stimulation.

INTRODUCTION/UNASSIGNED:Gait is a critical indicator of neurological health, with changes often signaling underlying decline. We developed a remote gait monitoring protocol using off-the-shelf shoe-based sensors (RunScribe) to assess gait parameters in real-world home settings. This protocol, known as Gait Assessment with Innovative Technologies - Home-based Use and Benefit (GAIT-HUB), was tested in individuals with multiple sclerosis (MS), a population at high risk for gait impairment due to the disease's variable progression. METHODS/UNASSIGNED:Participants with MS completed an in-clinic baseline gait assessment using a validated sensor (G-Sensor®) and three weekly, remotely supervised gait assessments at home using the RunScribe sensors. Gait parameters were compared across devices using intra-class correlation coefficients (ICCs) and Bland-Altman analyses. Longitudinal reliability of remote assessments and system usability score (SUS) were evaluated. RESULTS/UNASSIGNED:Twenty-nine participants (76% women, ages 19-67, PDDS range 0-5) successfully completed the home-based assessments. High agreement between devices was observed for gait speed, stride length, and cadence (ICCs >0.90), though phases like stance and swing showed more variability. Bland-Altman analyses indicated minimal bias in most parameters. Longitudinal assessments demonstrated strong reliability (ICCs >0.87) for key metrics, and SUS indicated good-to-excellent usability of the remote protocol. CONCLUSION/UNASSIGNED:The GAIT-HUB protocol enables reliable and feasible home-based gait monitoring using wearable sensors that patients can easily self-apply. This approach provides valuable insights into daily mobility patterns beyond clinical visits, supporting more precise and timely assessments of functional status between appointments and offering the potential for seamless integration into telemedicine routine care.

BACKGROUND/UNASSIGNED:Cognitive impairment is common in multiple sclerosis (MS). Transcranial direct current stimulation (tDCS) combined with adaptive cognitive training (aCT) may improve clinical outcomes. OBJECTIVE/UNASSIGNED:To evaluate the effect of active vs. sham home-based tDCS + aCT on cognitive function. METHODS/UNASSIGNED:-scores. RESULTS/UNASSIGNED: = .411). CONCLUSIONS/UNASSIGNED:Active vs. sham tDCS + aCT resulted in significantly better cognitive outcomes, with the greatest benefit in those with high neurologic disability.CLINICALTRIALS.GOV; https://clinicaltrials.gov/study/NCT03838770; IDENTIFIER: NCT03838770.