Jefferson Hospital for Neuroscience

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurological disease that leads to death within 2-5 years of diagnosis for more than 80% of people living with ALS (PLWALS). The American Academy of Neurology (AAN) developed practice parameters-general principles to guide clinicians in managing ALS-encouraging multidisciplinary care (MDC) but does not recommend specific healthcare delivery models. Three healthcare delivery models have evolved: a traditional model, a triage model, and a non-triage model. This study aims to describe preferences for and satisfaction with various models, among PLWALS and their caregivers (CALS), along with their perceptions of how their care aligns with AAN guidelines. A cross-sectional observational study utilizing a web-based survey was distributed via email to PLWALS and CALS. Three multi-assessment questionnaires were developed and tailored for PLWALS, CALS, and former CALS. Best-worst scaling (object case) data were analyzed using a best-minus-worst approach and descriptive statistics were calculated from means, t-tests and chi-square. The combined sample included 378 respondents: 254 PLWALS (67.20%) and 124 CALS (32.80%; composed of 79 current caregivers [20.90%] and 45 former caregivers [11.90%]). The mean respondent age was 61.09 years (SD 11.1). The majority of the sample was white (92.86%), insured by Medicare (61.11%), and married/partnered (79.10%). Respondents preferred a non-triage model the most and a traditional model the least; 88.20% (CI: 84.92-91.49) were extremely likely to choose a non-triage model if given the choice and 83.12% (CI: 79.29-86.92) of respondents ranked non-triage as most preferred. A traditional model was ranked as the least preferred model in 75.28% (CI: 70.78-79.78) of respondents. The most important factors driving respondent preferences were ALS expertise and team-based care. Overall, respondents are satisfied with their care teams. PLWALS utilizing non-triage MDC models reported more adherence to quality care measures compared with those utilizing triage and traditional models. Respondent preference for non-triage models is consistent with the importance they place on the features of non-triage models. However, these findings should be understood in the context of our sample in which a large majority of respondents were receiving care via a non-triage model. To ensure ALS care delivery is patient-centered, practice parameters that aim to guide clinicians in managing ALS should provide more guidance to MDCs to deliver care aligned with patient preferences and values. Efforts should focus on sustainable financial models that can better facilitate non-triage models of care.

Neurodegenerative diseases are defined by the propagation of neuroinflammation, driven in part by disease-associated microglia (DAM) that amplify inflammatory signaling and hasten neurodegeneration. Strategies to selectively eliminate DAM to attenuate disease progression remain elusive. Using existing datasets in combination with multiplexed immunofluorescence analysis of post-mortem ALS tissues, we identified the urokinase-type plasminogen activator receptor (uPAR) as a novel surface marker of DAM. uPAR protein is markedly elevated in IBA1⁺/CD68⁺ microglia within ALS-affected regions of both sporadic and familial cases, with negligible expression in unaffected areas or control tissues. These uPAR-high microglia drive neurite retraction in iPSC-derived neurons. To target these cells, we engineered 3rd-generation CAR-T cells expressing an anti-uPAR single-chain variable fragment, enabling specific recognition and elimination of uPAR-expressing microglia. Target specificity was assessed in human microglia C20 cells driven into a pathogenic state by poly(IC) or IFNγ stimulation, which resulted in robust surface uPAR expression alongside phagocytic (CD68⁺) and antigen-presenting (CD80⁺) markers. uPAR-CAR-T cells induced antigen-dependent cytolysis of uPAR-high microglia, reducing their viability by over 80% while sparing resting microglia and neurons in a mixed culture system. These results position uPAR-directed CAR-T cells as a viable immunotherapeutic approach to selectively disrupt disease-amplifying microglial subsets and modify the trajectories of neuroinflammatory diseases.

Abstract Purpose of Review This review synthesizes recent developments in vagus nerve stimulation (VNS) for stroke rehabilitation from 2021–2025, emphasizing the transition from experimental approaches to clinical implementation following FDA approval of implantable VNS. Recent Findings The 2021 FDA approval of the Vivistim Paired VNS System marked a watershed moment in stroke neuromodulation, providing the first regulatory-approved VNS therapy for upper extremity motor recovery. Long-term follow-up studies demonstrate sustained benefits at one year, with 66% of patients achieving clinically meaningful improvements. Concurrently, investigational transcutaneous approaches continue to evolve, though they remain limited by protocol heterogeneity and anatomical specificity concerns. Summary Implantable VNS paired with rehabilitation represents a paradigm shift in stroke care, offering evidence-based neuromodulation therapy for patients with chronic upper limb impairment. While transcutaneous approaches show promise in research settings, their clinical translation requires standardization and larger controlled trials. Current evidence strongly supports implantable VNS as a viable therapeutic option for carefully selected patients, while highlighting the importance of distinguishing proven treatments from investigational approaches in clinical practice.

Management of traumatic brain injury (TBI) patients on pre-TBI antithrombotic medications poses a clinical challenge in everyday practice. However, the safety profiles of antiplatelets (APs) have not been systematically studied and compared to anticoagulants (ACs) in this patient population.In this PRISMA-compliant systematic review the EMBASE and MEDLINE databases were systematically queried to identify comparative studies in patients with TBI and pre-injury AP and AC medications. Meta-analysis with random effect models were conducted for all outcomes. Forest plots were utilized to visually represent each study's effect and pooled estimates.Intracranial hemorrhage rates were statistically significantly higher for patients on single AP vs. AC (AP 19.7%; AC 9.3%; OR 1.35; CI 1.02-1.78; I2 49%, P = 0.03). Cumulative mortality rates (AP 6%; AC 2.5%; OR 0.72; CI; 0.39-1.32 I2 55%, P = 0.3), worsening ICH rates (AP 0.3%; AC 0.4%; OR 0.85; CI 0.16-4.55; I2 0%, P = 0.8) and need for neurosurgical intervention (AP 2.6%; AC 0.9%; OR 1.27; CI 0.48-3.39; I2 68%, P = 0.6) were comparable. For elderly patients (> 65 years old), ICH rates were comparable between groups (AP 46.8%; AC 28.3%; OR 1.03; CI 0.57-1.85; I2 66%, P = 0.9) and mortality was statistically significantly lower in the AP group (AP 19.4%; AC 29.5%; OR 0.46; CI 0.31-0.69; I2 0%, P < 0.001).Single pre-TBI AP carries more risk for ICH compared to AC. Mortality risk, worsening ICH risk and need for neurosurgical intervention are comparable. For elderly patients, ICH rates were comparable, but APs were associated with lower mortality.

As populations age, identifying the neurobiological basis of cognitive resilience is critical for delaying or preventing Alzheimer’s disease (AD). While most older adults experience memory decline, a subset known as superagers (SA) maintains youthful memory into late life, offering a unique window into protective mechanisms against neurodegeneration. Here, we identified a functional connectivity (FC) signature, termed Alzheimer’s-resilient connectome (ARC), that robustly differentiates SA from age-matched patients with AD. Using resting-state fMRI in a discovery cohort (N = 290), we identified ARC derived from machine learning classifiers that distinguished SA from AD with high accuracy (AUC = 0.85), and validated the replicability of the ARC in an independent replication cohort (N = 143). ARC involved prefrontal, temporal and insular networks and was strongly associated with brain age. When applied to cognitively unimpaired (CU) adults (discovery cohort: N = 818 and replication cohort: N = 497), ARC-based subtyping revealed SA-like and AD-like subgroups with similar baseline cognitive performance but markedly divergent longitudinal trajectories. SA-like CU individuals showed slower cognitive decline, reduced amyloid-β accumulation, and lower risk of conversion to mild cognitive impairment and AD, reinforcing the ARC signature as a potential early indicator of resilience. Genome-wide association analysis identified CLYBL and FRMD6 as novel genetic modulators associated with these divergent aging phenotypes. Together, our findings position ARC as a sensitive and generalizable biomarker of resilience, enabling early risk stratification and precision prevention for AD.

Compare clinical characteristics of refractory idiopathic intracranial hypertension (rIIH) in patients with body mass index (BMI) ≥35 vs. <35.

Sepsis is a potentially life-threatening condition recognized as a global health priority by the World Health Organization. Survivors who develop intensive care unit-acquired weakness (ICUAW) often face long-term motor and functional deficits that significantly impact their quality of life. Although some studies have investigated the mechanisms underlying ICUAW and its long-term effects, much remains unknown. Further research into ICUAW is therefore essential to gain a comprehensive understanding of this phenomenon, which may guide the development of effective treatments to restore patients' quality of life.

Study DesignSystematic Review and Meta-Analyses.ObjectiveTo assess the 30- and 90-day readmission rates after a traumatic spinal cord injury (SCI).MethodsA systematic search of MEDLINE and Embase was performed. The period was from inception to June 2022, with no language restrictions. All studies investigating the 30- and/or 90-day readmission rate following traumatic SCI were included. A random-effects model to combine effect sizes in our meta-analysis was applied.ResultsSeven out of 2959 reports met eligibility. The mean age of the patients was 50.2 ± 19.9, with a male-to-female ratio of 2.4:1. The most common traumatic SCI was cervical injury (55.3%). The meta-analysis model revealed a 30-day readmission rate of 14.2% after traumatic SCI, with heterogeneity in the studies. The 90-day readmission rate was 35.7%, with homogeneity in the studies. The meta-regression analysis found significant positive associations between cervical and thoracolumbar injuries and patient age and the 30-day readmission rate, while male sex demonstrated a negative association with the 30-day readmission rate. The 30-day readmission rate following index admission was 13.1% and the 30-day readmission rate after rehabilitation facilities was 15.8%. The study found that the 30-day readmission rate in the USA was 14.0%.ConclusionsThere is no doubt that readmission is an adverse health outcome. The outcome is also complex and multifaceted, which makes it difficult to predict. Injury level is 1 of the predictors that affect readmission, making it essential to consider factors during discharge planning for high-risk people to reduce 30-day readmission rates.

Cross-sectional, observational study. Investigate the frequency of intraoperative neuromonitoring (IONM) utilization among Medicare patients diagnosed with cervical spondylosis (CS), both with and without myelopathy. IONM is widely used as a tool in spine surgery. However, the overall prevalence of neuromonitoring utilization among CS undergoing surgical intervention is not well characterized. This study observed neuromonitoring usage in CS patients who had cervical spinal procedures from 2012 to 2020, using a 5% random sample of Medicare data. Logistic regression compared patient characteristics between those who received neuromonitoring and those who did not. The model included age, sex, region, Elixhauser Comorbidity Index score, year of surgery, elective status, and procedure type. Odds ratios with a 95% CI were generated for each covariate. Of the 6224 patients who underwent cervical procedures for CS, 4053 were included in the study, with 2845 having myelopathy and 1208 without. Myelopathy patients had a higher number of hospitalizations (2884) compared with non-myelopathy patients (1229). Among myelopathy patients, the prevalence of neuromonitoring increased from 49.2% in 2012 to 56.5% in 2020. The range of utilization for each type of monitoring was: 96.4%-100% for somatosensory evoked potential, 73.2%-86.1% for electromyography, 70.0%-86.1% for motor evoked potential, and 17.6%-33.6% for other modalities. For non-myelopathy patients, neuromonitoring prevalence increased from 33.1% in 2012 to 43.3% in 2020. The range of utilization for each type of monitoring was: 93.0%-100% for somatosensory evoked potential, 68.9%-89.7% for electromyography, 55.8%-77.4% for motor evoked potential, and 17.8%-36.4% for other modalities. This study investigates the utilization of IONM during cervical spinal surgeries in Medicare patients with cervical spondylotic myelopathy or CS between 2012 and 2020. Although IONM is employed in cervical spine procedures, its adoption and standardization appear to vary across the country and different health care settings.