Faculty Bibliography
Searched for:
Department/Unit:Neurology
Total Results:
24318
Surveillance of athlete mental health symptoms and disorders: a supplement to the International Olympic Committee's consensus statement on injury and illness surveillance
In 2019, the International Olympic Committee (IOC) published a consensus statement outlining the principles for recording and reporting injury and illness in elite sport. The authors encouraged sport federations to adapt the framework to their sport-specific context. Since this publication, several sports have published extensions to the IOC consensus statement.In response to a paucity of epidemiological data on athlete mental health, the IOC mental health working group adapted the IOC consensus statement on injury and illness surveillance to improve the capturing of athlete mental health data. In addition to the members of the working group, other experts and athlete representatives joined the project team to address gaps in expertise, and to add stakeholder perspective, respectively. Following an in-person meeting, the authors worked remotely, applying the scientific literature on athlete mental health to the IOC injury and illness surveillance framework. A virtual meeting was held to reach consensus on final recommendations.Practical outcomes based on the analysis of the scientific literature are provided with respect to surveillance design, data collection and storage, data analysis and reporting of athlete mental health data. Mental health-specific report forms for athlete and health professional utilisation are included for both longitudinal and event-specific surveillance.Ultimately, this publication should encourage the standardisation of surveillance methodology for mental health symptoms and disorders among athletes, which will improve consistency in study designs, thus facilitating the pooling of data and comparison across studies. The goal is to encourage systematic surveillance of athlete mental health.
PMID: 37468210
ISSN: 1473-0480
CID: 5775082
Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease
The abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from AD patients. We found filaments of truncated tau enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD.
PMID: 37163117
ISSN: 2692-8205
CID: 5773922
Earnings of US Physicians With and Without Disabilities
PMCID:10692836
PMID: 38038987
ISSN: 2689-0186
CID: 5773302
Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2023:120(3).DOI: 10.1073/pnas.2207291120
Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity
A small proportion of multiple sclerosis (MS) patients develop new disease activity soon after starting anti-CD20 therapy. This activity does not recur with further dosing, possibly reflecting deeper depletion of CD20-expressing cells with repeat infusions. We assessed cellular immune profiles and their association with transient disease activity following anti-CD20 initiation as a window into relapsing disease biology. Peripheral blood mononuclear cells from independent discovery and validation cohorts of MS patients initiating ocrelizumab were assessed for phenotypic and functional profiles using multiparametric flow cytometry. Pretreatment CD20-expressing T cells, especially CD20dimCD8+ T cells with a highly inflammatory and central nervous system (CNS)-homing phenotype, were significantly inversely correlated with pretreatment MRI gadolinium-lesion counts, and also predictive of early disease activity observed after anti-CD20 initiation. Direct removal of pretreatment proinflammatory CD20dimCD8+ T cells had a greater contribution to treatment-associated changes in the CD8+ T cell pool than was the case for CD4+ T cells. Early disease activity following anti-CD20 initiation was not associated with reconstituting CD20dimCD8+ T cells, which were less proinflammatory compared with pretreatment. Similarly, this disease activity did not correlate with early reconstituting B cells, which were predominantly transitional CD19+CD24highCD38high with a more anti-inflammatory profile. We provide insights into the mode-of-action of anti-CD20 and highlight a potential role for CD20dimCD8+ T cells in MS relapse biology; their strong inverse correlation with both pretreatment and early posttreatment disease activity suggests that CD20-expressing CD8+ T cells leaving the circulation (possibly to the CNS) play a particularly early role in the immune cascades involved in relapse development.
PMID: 36634138
ISSN: 1091-6490
CID: 5773282
Anti-CD20 monoclonal antibody therapy in postpartum women with neurological conditions
OBJECTIVE:Postpartum, patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) have increased risk for disease activity. Anti-CD20 IgG1 monoclonal antibodies (mAb) are increasingly used as disease-modifying therapies (DMTs). Patients may wish to both breastfeed and resume DMT postpartum. This study aimed to determine the transfer of anti-CD20 IgG1 mAbs, ocrelizumab, and rituximab (OCR/RTX), into mature breastmilk and describe maternal and infant outcomes. METHODS:Fifty-seven cis-women receiving OCR/RTX after 59 pregnancies and their infants were enrolled and followed up to 12M postpartum or 90 days post-infusion. Breastmilk was collected pre-infusion and serially up to 90 days and assayed for mAb concentration. Medical records and patients' questionnaire responses were obtained to assess neurologic, breastfeeding, and infant development outcomes. RESULTS:The median average concentration of mAb in breastmilk was low (OCR: 0.08 μg/mL, range 0.05-0.4; RTX: 0.03 μg/mL, range 0.005-0.3). Concentration peaked 1-7 days post-infusion in most (77%) and was nearly undetectable after 90 days. Median average relative infant dose was <1% (OCR: 0.1%, range 0.07-0.7; RTX: 0.04%, range 0.005-0.3). Forty-three participants continued to breastfeed post-infusion. At 8-12 months, the proportion of infants' growth between the 3rd and 97th World Health Organization percentiles did not differ for breastfed (36/40) and non-breastfed (14/16, p > 0.05) infants; neither did the proportion with normal development (breastfed: 37/41, non-breastfed: 11/13; p > 0.05). After postpartum infusion, two mothers experienced a clinical relapse. INTERPRETATION:These confirm minimal transfer of mAb into breastmilk. Anti-CD20 mAb therapy stabilizes MS activity before conception to the postpartum period, and postpartum treatments appears to be safe and well-tolerated for both mother and infant.
PMCID:10647007
PMID: 37675826
ISSN: 2328-9503
CID: 5773292
CDKN2A/B mutations and allele-specific alterations stratify survival outcomes in IDH-mutant astrocytomas
PMCID:10628020
PMID: 37831210
ISSN: 1432-0533
CID: 5770572
Reviews in Medical Education: Advances in Simulation to Address New Challenges in Neurology
Simulation is an engaging modality of medical education that leverages adult learning theory. Since its inception, educators have used simulation to train clinicians in bedside procedures and neurologic emergencies, as well as in communication, teamwork, and leadership skills. Many applications of simulation in neurology are yet to be fully adopted or explored. However, challenges to traditional educational paradigms, such as the shift to competency-based assessments and the need for remote or hybrid platforms, have created an impetus for neurologists to embrace simulation. In this article, we explore how simulation might be adapted to meet these current challenges in neurologic education by reviewing the existing literature in simulation from the field of neurology and beyond. We discuss how simulation can engage neurology trainees who seek interactive, contextualized, on-demand education. We consider how educators can incorporate simulation for competency-based evaluations and procedural training. We foresee a growing role of simulation initiatives that assess bias and promote equity. We also provide tangible solutions that make simulation an educational tool that is within reach for any educator in both high-resource and low-resource settings.
PMCID:11473088
PMID: 39411112
ISSN: 2771-9979
CID: 5770682
Cerebrospinal fluid: The new frontier for methylome-based diagnostic classification of brain tumors [Comment]
PMID: 37078878
ISSN: 1523-5866
CID: 5770502
Cerebrospinal fluid: A unique source of circulating tumor DNA with broad clinical applications
Malignancies involving the central nervous system present unique challenges for diagnosis and monitoring due to the difficulties and risks of direct biopsies and the low specificity and/or sensitivity of other techniques for assessment. In recent years, liquid biopsy of the cerebrospinal fluid (CSF) has emerged as a convenient alternative that combines minimal invasiveness with the ability to detect disease-defining or therapeutically actionable genetic alterations from circulating tumor DNA (ctDNA). Since CSF can be obtained by lumbar puncture, or an established ventricular access device at multiple time points, ctDNA analysis enables initial molecular characterization and longitudinal monitoring throughout a patient's disease course, promoting optimization of treatment regimens. This review outlines some of the key aspects of ctDNA from CSF as a highly suitable approach for clinical assessment, the benefits and drawbacks, testing methods, as well as potential future advancements in this field. We anticipate wider adoption of this practice as technologies and pipelines improve and envisage significant improvements for cancer care.
PMCID:10205485
PMID: 37196447
ISSN: 1936-5233
CID: 5770512
Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design
IMPORTANCE/UNASSIGNED:The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS/UNASSIGNED:cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE/UNASSIGNED:RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALSGOV IDENTIFIER/UNASSIGNED:Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT05172011.
PMID: 37214806
CID: 5770522
