Faculty Bibliography

Light speckle fluctuations provide a means for noninvasive measurements of cerebral blood flow index (CBFi). While conventional Diffuse Correlation Spectroscopy (DCS) quantifies these fluctuations to provide marginal brain sensitivity for CBFi in adult humans, new techniques have emerged to improve diffuse light throughput and brain sensitivity. Here we further optimize one such approach, interferometric diffusing wave spectroscopy (iDWS), with respect to the number of independent channels, camera duty cycle and full well capacity, incident laser power, noise and artifact mitigation, and data processing. We build the system on a cart and define conditions for stable operation. We show pulsatile CBFi monitoring at 4-4.5 cm source-collector separation in adults with moderate pigmentation (Fitzpatrick 4). We also report preliminary clinical measurements of patient CBFi in the Neuro Intensive Care Unit (Neuro ICU). These results push the boundaries of iDWS CBFi monitoring performance beyond previous reports.

Nusinersen, an antisense oligonucleotide, modulates pre-mRNA splicing to produce full length survival motor neuron protein in spinal muscular atrophy (SMA). It was approved in the US for SMA in all ages based on evidence in children. In adults, studies of nusinersen rely on real-world observational data and show stability or small improvements over time. We performed a prospective, 30 month longitudinal, observational multi-center study of adults initiating nusinersen with SMA types II/III to examine its safety, tolerability, and effectiveness. 43 participants (20 female; 14 ambulatory; 3, 17, and 23 with 2, 3, and ≥4 SMN2 copies, respectively), mean (SD) age 37.1 (11.9) years) enrolled and completed baseline assessments. Serial assessments over 30 months showed small but not significant improvements in the six minute walk test (16.1 m), Revised Upper Limb Module (0.7), Revised Hammersmith Scale (0.8), maximal inspiratory (-2.6 cm H20) and expiratory pressure (12.3 cm H20). Muscle strength and forced vital capacity did not change. The patient reported outcome Total SMA-HI improved (-11 (95% CI: -17,-5); p < 0.001)). No new safety effects were identified. This study of nusinersen in adults with SMA demonstrates stability over time in contrast to the expected decline in untreated patients, with a favorable safety profile.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Impaired consciousness in epilepsy negatively affects quality of life. Previous work has focused on temporal lobe seizures, where cortical slow waves are associated with depressed subcortical arousal and impaired consciousness. However, it is unknown whether frontal lobe seizures also show cortical slow waves or a different activity pattern with impaired consciousness. METHODS:Intracranial EEG (icEEG) recordings from patients at 3 centers were retrospectively assessed to identify seizures originating in the frontal lobe. Seizures were classified as focal preserved consciousness (FPC), focal impaired consciousness (FIC), or focal to bilateral tonic-clonic (FBTC) based on video review. Changes in icEEG power from preictal baseline were calculated in different cortical regions and across frequency ranges in these 3 seizure categories. RESULTS:< 0.001, 95% CI 330.1-781.9 and 375.3-818.2, respectively). DISCUSSION/CONCLUSIONS:The widespread power increases across frequencies in frontal lobe FIC seizures contrast with those in focal temporal lobe epilepsy, where impaired consciousness is associated with cortical slow waves. These findings suggest that different focal seizure types produce impaired consciousness by affecting widespread cortical regions but through different physiologic mechanisms. Insights gained by studying the physiology of impaired consciousness may be the first step toward developing novel treatments to prevent this significant negative consequence of epilepsy and improve quality of life.

Assistive technologies can enhance safety, independence, and quality of life for people with blindness and low vision. Despite their benefits, abandonment of these technologies remains widespread, and recent research on this issue is limited. In this Perspective article, we draw on both professional experiences and relevant scientific literature to examine adoption and abandonment in the context of new artificial intelligence-powered applications. We highlight risks arising from misaligned design, inconsistent industry support, and inadequate user training. We synthesize existing knowledge on factors that influence abandonment and propose three priorities to realign assistive technology development: participatory and transdisciplinary research, integrated technology ecosystems, and socially supported engagement. Taken collectively, these priorities ensure that emerging assistive technologies better align with the needs of people with blindness and low vision, promoting lasting adoption rather than abandonment.

OBJECTIVE/UNASSIGNED:Chronic non-specific lower back pain (cNSLBP) is a prevalent and disabling condition, imposing a substantial socioeconomic burden due to high healthcare costs and productivity losses, with limited accessible and effective long-term treatment options. Automated Thermo-mechanical Therapy (ATT) is a promising, non-drug intervention that leverages innovative technical advances to provide multimodal pain relief, offering accessibility and low-cost delivery. This study tested ATT for immediate pain relief in individuals with cNSLBP in a single-session, double-blind, randomized controlled trial. METHODS/UNASSIGNED:= 20) in a 40-min session with urn randomization. The active device applied heated cylindrical rollers along the spine, using far-infrared heat and mechanical tissue stimulation tailored to spinal alignment. In the control condition, the device used minimal mechanical therapy intensity without heat, targeting only the cervical area to avoid lower back therapeutic effects. Pre- and post-intervention assessments measured changes in pain intensity (primary outcome) via a 100-mm Visual Analog Scale for Pain (VAS-P100), alongside secondary outcomes assessing pain characteristics, anxiety, and functional mobility. RESULTS/UNASSIGNED:= 0.0031). No adverse events were reported, and all participants tolerated the intervention well. CONCLUSIONS/UNASSIGNED:A single session of ATT provides immediate, significant pain relief in individuals with cNSLBP, supporting its potential as a safe, non-invasive option for managing chronic back pain. Future studies should examine the long-term benefits of repeated ATT sessions and explore mechanistic insights into thermo-mechanical stimulation's effects on pain and function. CLINICAL TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov, identifier: NCT06769321.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Hand-sewn (HS) microsuturing is limited by tremor and fatigue. Robotic systems may improve performance, but quantitative comparisons remain limited. This study evaluates the precision of robot-assisted vs manual suturing during end-to-side microanastomosis. METHODS:Under simulation, microsurgical robot-assisted and HS sutures for end-to-side microanastomosis were performed by a single surgeon. One thousand four hundred and ninety-four total frames were assessed within 4 videos. Each robotic clip was paired with a corresponding HS clip. Tracker software extracted 2-dimensional positional data. Motion trajectories were smoothed using Savitzky-Golay filtering for an ideal suture trajectory. Deviation from an ideal path was quantified using Euclidean distance. Mean and SD of path deviation were calculated. Group comparisons were made as fold-change reductions and standardized effect sizes (Cohen d) to quantify the magnitude of observed differences. RESULTS:Robotic-assisted sutures demonstrated significantly lower mean path deviation and variability than HS sutures, particularly for the dominant (right) hand, with consistently large effect sizes for the right hand (all = 1.2, r = 0.5) and smaller for the left hand (d = 0.36-0.71, r = 0.18-0.33). CONCLUSION/CONCLUSIONS:Robotic microsuturing with microsurgical assistant significantly improves path fidelity, particularly in dominant-hand tasks. Manual sutures showed larger deviations between the ideal suture and raw data, supporting robotic integration into cerebrovascular neurosurgery and warranting study in live models.

This guideline summarizes updated safety data (2017-2025) and provides expert recommendations on the use of low intensity transcranial electrical stimulation (tES) in humans. tES encompasses several techniques including transcranial direct current stimulation (tDCS), oscillatory transcranial direct current stimulation (otDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), transcranial temporal interference stimulation (tTIS), and their combinations or variations. Across over 300,000 sessions involving healthy individuals, patients with neuropsychiatric conditions, and other clinical populations, no tES-related serious adverse events (AEs) have been reported. Moderate AEs are rare and limited to a small range of specific applications. Mild AEs are common and include transient symptoms such as localized sensations (e.g., tingling or burning), headaches, and fatigue. Similar mild AEs are also reported by individuals receiving placebo stimulation. The frequency, magnitude, and type of AEs are comparable across healthy, clinical, and vulnerable groups, including children, elderly, or pregnant women. Combined interventions (e.g., co-application with EEG, TMS, or neuroimaging) have not shown increased safety risks. Safety is well-established for both bipolar and multichannel tES when applied up to 4 mA and up to 60 min per day. Higher intensities and longer stimulation durations may also be safe. Nevertheless, the number of studies using intensities above 4 mA or stimulating longer than 60 min is low. Home-based use of treatments is growing rapidly, leveraging remote supervision to provide patients with greater access and enable repeated, sustained dosing paradigms. We recommend using screening and AE questionnaires in future controlled studies, in particular when planning to extend the stimulation parameters applied. We discuss recent regulatory and ethical issues.

BACKGROUND/UNASSIGNED:Fingolimod is an immunomodulatory drug that has shown promising effects in stroke treatment, including improvements in neurofunctional recovery and a reduction in infarct size. Fingolimod modulates the sphingosine-1-phosphate receptors, which leads to the internalization of sphingosine-1-phosphate receptors on T and B lymphocytes, thereby preventing their egress from secondary lymphoid organs. Here, we report a secondary analysis from the Stroke Preclinical Assessment Network trial. We assessed the effects of fingolimod versus vehicle on stroke outcomes to better evaluate its therapeutic potential. METHODS/UNASSIGNED:The animal population (n=409) comprised male and female animals treated with fingolimod or vehicle. We used 4 clinically relevant models: young healthy mice (10-12 weeks-old), aging mice (16±1 month-old), obesity induced-hyperglycemic mice fed with a high-fat diet for 12 weeks (16 weeks-old), and spontaneously hypertensive rats (16±1 weeks-old). Stroke was induced by the middle cerebral artery occlusion for 1 hour, followed by reperfusion. Animals received a total of 6 intraperitoneal injections of 0.5 mg/kg twice daily of fingolimod or vehicle. Functional outcomes in the corner test and foot-faults test were measured at days 7 and 28. Lesion size and brain morphometry were evaluated at days 2 and 30 by magnetic resonance imaging. RESULTS/UNASSIGNED:Overall, fingolimod did not improve morphological and functional outcomes. However, fingolimod effects varied depending on sex or the comorbidity model. Fingolimod promoted a better outcome in the corner test in aging females. In contrast, it favored a worse outcome in obesity-induced hyperglycemic mice at day 7. Despite having no effect on survival rates or lesion size, fingolimod attenuated the midline retraction at day 30 in aging males, consistent with less atrophy. CONCLUSIONS/UNASSIGNED:Although fingolimod did not significantly benefit the overall primary functional outcome, its effects varied with sex and comorbidity models, underscoring how the therapeutic potential of a particular drug can differ in a heterogeneous population.

BACKGROUND/UNASSIGNED:Guidelines recommend palliative care (PC) for patients with heart failure. However, little research has been performed assessing the effect of PC consultation in patients with heart failure with preserved ejection fraction (HFpEF). OBJECTIVES/UNASSIGNED:The purpose of this study was to investigate the impact of PC consultation on symptom burden and health care utilization among individuals with HFpEF during the last 3 years of their lives. METHODS/UNASSIGNED:We retrospectively analyzed electronic medical records from 72 centers, mainly in the United States. All patients with HFpEF, identified using International Classification of Diseases codes, who died within 3 years of the diagnosis were selected and then stratified based on receipt of PC consultation. Propensity score matching was used to control for between-group differences. RESULTS/UNASSIGNED:Two hundred twenty-six thousand nine hundred twenty-one patients with HFpEF died within 3 years, only 26.4% of whom received a PC consult. In the unmatched cohort, patients who received a PC consult were more likely to be female, Black, and had more comorbidities. After propensity matching, patients receiving PC consultation were less likely to experience an emergency room visit or hospitalization (2.2% vs 4.6%), surgery or anesthesia (1.1% vs 4.2%), critical care (0.7% vs 1.9%), or receive cardiovascular procedures or tests (1.7% vs 4.7%). Furthermore, they were also less likely to have cardiorespiratory symptoms (2.5% vs 5.7%), heart failure exacerbations (1.6% vs 3.3%), cognitive symptoms (1.7% vs 3.4%), falls (0.3% vs 0.6%), and depression or anxiety (1.3% vs 2.8%). CONCLUSIONS/UNASSIGNED:PC consultation is associated with reduced potential unwanted health care utilization and improvement in symptoms in patients with HFpEF in their last 3 years of life. However, PC continues to be underused in this population.

BACKGROUND:Glucagon-like peptide-1 receptor agonists (GLP-1RAs) promote weight loss and improve heart failure-related symptoms, quality of life, and functional capacity in patients with obesity and heart failure with preserved ejection fraction (HFpEF). However, their clinical effectiveness in nonobese patients with diabetes and HFpEF is understudied. METHODS:The TriNetX research network was used to identify adult patients (≥18 years) with type 2 diabetes mellitus (T2DM), heart failure with preserved ejection fraction (left ventricular ejection fraction ≥45%), elevated brain natriuretic peptide (≥ 150 pg/mL) or N-terminal pro-B-type natriuretic peptide(≥ 450 pg/mL) and a body mass index (BMI) <30 kg/m2 on or before August 31, 2022. Patients were divided into two groups based on GLP-1RA use. After propensity score matching, Cox proportional hazard ratios (HRs) were used to compare outcomes over a 12-month follow-up period. RESULTS:The study included 84,990 patients (n= 42,495 per group, mean age 64 years, 49% females, 65% white). Patients on GLP-1RAs were associated with lower incidence of heart failure exacerbation events (HR 0.60, 95% CI 0.58-0.62, p<0.001) and all-cause emergency room visits or hospitalizations (HR, 0.67, 95% CI 0.66-0.69; P < .001) compared with those not on GLP-1RAs. Other outcomes, including acute myocardial infarction, atrial fibrillation, ischemic stroke, pulmonary hypertension, C-reactive protein ≥ 5 mg/L, acute kidney injury, and the need for renal replacement therapy, were also significantly less frequent in the GLP-1RA group. These associated benefits persisted even among patients on a sodium-glucose cotransporter-2 inhibitor (SGLT2i). CONCLUSION/CONCLUSIONS:GLP-1RA use is associated with improved cardiovascular outcomes in nonobese patients with T2DM and HFpEF and has an associated incremental benefit even among patients on SGLT2i.