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Translational Inefficiencies in Traumatic Brain Injury Research: Evidence From 94 399 Publications

de Souza, Daniel N; Frome, Spencer; Grin, Eric A; Grossman, Scott N; Huang, Paul P; Kurland, David B
BACKGROUND AND OBJECTIVES/OBJECTIVE:Despite extensive investigation, no proven neuroprotective therapy exists for traumatic brain injury. Although this translational gap has been widely discussed, it has not been objectively characterized through systematic analysis. We hypothesized that this deficit reflects not only biological intractability but also constraints within the research ecosystem that impede translational progress. METHODS:Web of Science, PubMed, and Scopus were searched without date or document type restrictions. A natural language processing pipeline screened results and classified study designs, topical areas, geographic affiliations, and funding sources. All analyses and visualizations were performed using open-source Python libraries. RESULTS:94 399 publications spanning 1829 to 2026 comprised the corpus. Research output was geographically concentrated. Thematic network analysis revealed 4 discrete research domains (preclinical, acute clinical, chronic/rehabilitation, and sports-related), with the preclinical domain spatially isolated from all 3 clinical clusters. Randomized controlled trials comprised 1.5% of publications, while reviews exceeded 20% of annual output throughout the 21st century. Preclinical research share peaked near 23% of annual publications around 2000 and subsequently declined without a commensurate rise in clinical trial activity (Chow test, P < .001). Diagnostic biomarker research comprised 3.8% of publications but remained poorly integrated with prospective trial designs. Postacute pharmacotherapy research represented 0.8% of publications and the smallest trial-integrated fraction of any area examined. Citation concentration was substantial (Gini 0.725), with nearly one-fifth of publications uncited. Journal-level analysis revealed a sustained decline in neurosurgery-specific journal representation from 1980 to 2025; in 1993, neurology and neuroscience journals surpassed neurosurgery journals in proportional share of annual publications and have maintained that lead since. National Institutes of Health-funded research, the largest funder by a factor of 5, produced randomized controlled trial rates indistinguishable from those of unfunded literature (1.6%). CONCLUSION/CONCLUSIONS:Traumatic brain injury literature has grown substantially without commensurate advances in high-evidence research, reflecting identifiable inefficiencies in infrastructure and funding strategy that represent targets for intervention.
PMID: 42725750
ISSN: 1524-4040
CID: 6072271

Education Research: Neuropalliative Care Education: A National Survey of Neurology Program and Fellowship Directors

Harrigan, Eileen; Kurzweil, Arielle M; Ekwebelem, Maureen I; Shalev, Daniel; Jacoby, Nuri
BACKGROUND AND OBJECTIVES/UNASSIGNED:Patients with neurologic disease have a variety of unmet palliative care needs. Both the Accreditation Council for Graduate Medical Education and Academy of Neurology have emphasized the need for neuropalliative care education in recent years. Neurology training programs have widely variable practices in teaching neuropalliative care. This study aims to characterize current practices in providing neuropalliative care education across graduate neurology training and to identify barriers to its delivery. METHODS/UNASSIGNED:We surveyed program directors (PDs) of neurology residency and fellowship training programs in the United States regarding their current methods of teaching neuropalliative care topics, perceived importance of these topics, relevant subspecialty resources, and perceived barriers to providing neuropalliative care education. RESULTS/UNASSIGNED:Our survey was emailed to 777 PDs and fellowship directors. In total, 118 responses were included in the analytic sample (response rate 15.2%). Program directors generally perceived neuropalliative care education as important, with a median rank of 7 of 10. 91% of adult neurology residency programs and 66% of fellowship programs included palliative care topics in their didactics curricula. Topics emphasized varied depending on the training program's subspecialty. Respondents highlighted barriers to implementing neuropalliative care training, including inadequate trainee and faculty time and lack of adequate teaching faculty. DISCUSSION/UNASSIGNED:Neurology training programs continue to exhibit considerable variability in palliative care education curricula. Although most programs reported a presence of palliative care in their institutions, variability exists in the amount of palliative care education taught, the topics emphasized, and the teaching methods. Notably, there is an opportunity for fellowship programs to increase the amount of neuropalliative care topics taught in their curricula. Neurology residency and fellowship directors may benefit from using existing neuropalliative care curricula to enhance this area of education, partnering with local non-neurology faculty to teach palliative topics, and integrating palliative care topics into subspecialty training.
PMCID:13545002
PMID: 42701390
ISSN: 2771-9979
CID: 6072191

The Time Is Now for an Upstream Palliative Approach to Alzheimer's Disease and Related Disorders [Letter]

Morgan, Brianna; Brody, Ab; Fleisher, Jori; Chodosh, Joshua
PMID: 42722041
ISSN: 1873-6513
CID: 6072261

Diagnosis and management after nondiagnostic EMU admissions: short-term follow-up study

Frontario, Ariana; Pawar, Anokhi; Reisch, Anne; Kandula, Padmaja; Chen, Hai
OBJECTIVE:Capturing a habitual event is often required to determine the etiology of events during video-EEG (vEEG) monitoring. vEEG studies that fail to capture a habitual event are typically considered non-diagnostic. In this study, we evaluated the clinical impact of non-diagnostic vEEG studies. METHODS:We identified non-diagnostic vEEG studies from a cohort of epilepsy monitoring unit (EMU) admissions. Patients were followed longitudinally in the outpatient clinic.Clinical impact was assessed by evaluating changes in diagnosis and antiseizure medication (ASM) management at EMU discharge and at the last clinic follow-up. RESULTS:Patients were categorized according to referral indication: (I) spell clarification in individuals with paroxysmal events (n = 10); (II) event differentiation in patients with epilepsy (n = 16); (III) reassessment of a prior epilepsy diagnosis (n = 20); and (IV) classification of seizure or epilepsy type (n = 18). Following EMU admission, one patient in Group I was diagnosed with seizures, while the prior epilepsy diagnosis was withdrawn in eight patients in Group III. At EMU discharge, ASM reduction was most frequent in Group III (11/20), whereas ASM escalation was most common in Group II (7/16). By the last clinic follow-up, two additional patients had been diagnosed with seizures. Further ASM escalation occurred in 14 patients: two in Group I, three in Group II, three in Group III, and six in Group IV. SIGNIFICANCE/CONCLUSIONS:Non-diagnostic vEEG studies can still provide meaningful diagnostic insight. Subsequent management strategies varied substantially depending on the indications for EMU admission and the clinical context.
PMID: 42107460
ISSN: 1525-5069
CID: 6072084

Longitudinal stability of dietary intake patterns in pediatric-onset multiple sclerosis: A multicenter prospective cohort study

Virupakshaiah, Akash; Schoeps, Vinicius A; Chang, Gina; Waltz, Michael; Race, Jonathan; Mar, Soe; Francisco, Carla; Casper, T Charles; Rose, John; Rodriguez, Moses; Tillema, Jan-Mendelt; Chitnis, Tanuja; Gorman, Mark P; Benson, Leslie A; Graves, Jennifer S; Rensel, Mary; Abrams, Aaron; Krupp, Lauren B; O'Neill, Kimberly A; Lotze, Timothy E; Aaen, Gregory; Wheeler, Yolanda; Schreiner, Teri; Waldman, Amy T; Chong, Janet; Titcomb, Tyler J; Tremlett, Helen; Waubant, Emmanuelle
BACKGROUND:Diet may influence MS activity, but most studies use a single dietary measure. The stability of diet over time in pediatric-onset MS (POMS) is unclear. OBJECTIVES/OBJECTIVE:To evaluate the reproducibility and short-term temporal stability of dietary intake in youth with POMS using repeated food frequency questionnaires (FFQ). METHODS:This longitudinal study included participants with a baseline FFQ (the Block Kids Food Screener, 2014). Intraclass correlation coefficients (ICCs) were estimated using random-intercept mixed-effects models to quantify the relative contributions of between-person and within-person variability. Temporal trends in intake were assessed by modeling time since baseline as a fixed effect, using log-transformed dietary variables to estimate percent change over time. RESULTS:Of 419 FFQs from 195 participants, 140 (71.8%) completed ≥2 FFQs over a median of 6.5 months (range 2.8-18). ICCs ranged from 0.41 to 0.78 across dietary measures, with the highest reproducibility observed for vegetables and fiber (ICCs 0.78 and 0.72). Log-transformed models showed small declines in several nutrients over time, corresponding to <10% change over a six-month period. CONCLUSIONS:Dietary intake demonstrated moderate to good reproducibility over the 6 to 18 month follow-up period. Vegetable and fiber intake had the strongest reliability. These findings suggest that reported dietary intake assessed by a single or infrequent FFQ may remain reasonably stable over a 6- to 18-month period in longitudinal POMS studies. However, the moderate-to-good reproducibility observed indicates that within-person variability persists and may attenuate diet-disease associations when only a single dietary assessment is available.
PMID: 42697107
ISSN: 2211-0356
CID: 6072028

Pharmacologic Treatment for Migraine Prevention in Adults Practice Guideline Recommendations: Report of the AAN Guidelines Subcommittee and the American Headache Society

Potrebic, Sonja; Tanveer, Sarah; Becker, Werner J; Burch, Rebecca; Cooke, Lara J; Fenton, Todd; Fletcher, Jeff J; Gordon Perue, Gillian L; Hershey, Andrew D; Jackson, Jeffrey L; Kessel, Shirley; Loder, Elizabeth W; Minen, Mia T; Oskoui, Maryam; Ramanan, Vijay K; Murren, Michelle; Schwedt, Todd J; Silberstein, Stephen D; Smith, Don B; Botchway-Doe, Kylie A; Silsbee, Heather M; Pringsheim, Tamara
This practice guideline provides updated evidence-based recommendations regarding the use of pharmacologic migraine prevention in adults. A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies published through June 6, 2024, and is available in a companion publication. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. Recommendations are provided on how to decide when it is appropriate to start a pharmacologic migraine preventive medication and how to decide which migraine preventive medication to start. Recommendations address decision making on appropriate choices of migraine preventive medications in specific situations and populations, including patients with fibromyalgia, obesity, or hypertension; considerations for older adults; treatment during pregnancy and lactation; sex-related factors in choosing medications; and treatment for patients with medication overuse. Recommendations on assessment of treatment efficacy, adverse effects, and discontinuing migraine preventive medications are provided.
PMID: 42673560
ISSN: 1526-632x
CID: 6071928

Systematic Review of Pharmacologic Treatment for Migraine Prevention in Adults: Report of the AAN Guidelines Subcommittee and the American Headache Society

Pringsheim, Tamara; Smith, Don B; Tanveer, Sarah; Becker, Werner J; Burch, Rebecca; Cooke, Lara J; Fenton, Todd; Fletcher, Jeff J; Gordon Perue, Gillian L; Hershey, Andrew D; Jackson, Jeffrey L; Kessel, Shirley; Loder, Elizabeth W; Minen, Mia T; Oskoui, Maryam; Ramanan, Vijay K; Murren, Michelle; Schwedt, Todd J; Silberstein, Stephen D; Botchway-Doe, Kylie A; Silsbee, Heather M; Potrebic, Sonja
BACKGROUND AND OBJECTIVES/OBJECTIVE:This systematic review (SR) provides updated evidence-based conclusions regarding the use of pharmacologic migraine prevention in adults to inform a new joint American Academy of Neurology (AAN) and American Headache Society practice guideline. METHODS:A multidisciplinary panel conducted an SR following the 2017 AAN Clinical Practice Guideline Process Manual. Randomized controlled trials evaluating pharmacologic preventive treatments for adults with episodic or chronic migraine were included. Searches encompassed MEDLINE, Embase, and ClinicalTrials.gov from database inception through June 6, 2024. Studies were screened in duplicate, with dual independent risk-of-bias assessment. Outcomes included change in monthly headache days, ≥50% responder rate, and validated patient-reported quality of life (QOL) measures. Raw mean differences, standardized mean differences, and risk ratios were calculated. A modified Grading of Recommendations Assessment, Development, and Evaluation process was used to classify certainty of evidence. RESULTS:A total of 217 studies met inclusion criteria. For episodic migraine, high-confidence evidence showed that galcanezumab and erenumab are more effective than placebo in reducing headache frequency. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate. Several additional oral agents including amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, and telmisartan had low-confidence evidence suggesting possible benefit. For chronic migraine, high-confidence evidence supported reductions in headache frequency with fremanezumab, galcanezumab, and onabotulinumtoxinA. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, erenumab, topiramate and valproate. Across both episodic and chronic migraine populations, erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate and onabotulinumtoxinA demonstrated improvements in patient-reported QOL outcomes on validated instruments. Evidence comparing active treatments was limited and generally of low or very low confidence, restricting conclusions about comparative effectiveness. DISCUSSION/CONCLUSIONS:This SR provides a comprehensive synthesis of evidence on pharmacologic migraine prevention in adults. High- and moderate-confidence findings confirm the efficacy of several established and newer preventive therapies and demonstrate improvements in patient-reported outcomes across multiple validated measures. These conclusions informed the development of evidence-based recommendations, presented in a companion publication, to guide clinicians in selecting preventive medications for adults with episodic and chronic migraine.
PMID: 42673559
ISSN: 1526-632x
CID: 6071927

Large language model responses to questions about brain death/death by neurologic criteria: ChatGPT 4o-mini and Gemini 3 Flash (Fast)

Lewis, Ariane; Avadhani, Nikhil; Mehta, Sanjiv D; Hunter, Ryan Brandon; Greer, David; Kirschen, Matthew P
BACKGROUND:Public understanding about brain death/death by neurologic criteria (BD/DNC) is generally poor. With the rising popularity of utilization of large language model (LLM) chatbots to answer medical questions, we sought to determine the quality of information about BD/DNC provided by ChatGPT 4o-mini and Gemini 3 Flash (Fast). METHODS:With the assistance of a family advocate, we developed 45 open-ended questions about BD/DNC and submitted them to ChatGPT 4o-mini and Gemini 3 Flash (Fast) in January 2026. We recorded response word count, Flesch-Kincaid Readability Score and source reputability (non-reputable sources were defined as nonmedical, nongovernmental, nonlegal and not affiliated with an organ donation organization). Two authors of the 2023 BD/DNC guidelines independently assessed response accuracy relative to accepted medical standards and a third adjudicated discrepancies. RESULTS:Most responses were ≥ 10th grade level [ChatGPT 4o-mini: 44/45 (98%), Gemini 3 Flash (Fast): 39/45 (86%)]. After adjudication, 22/45 (49%) responses from Gemini 3 Flash (Fast) and 20/45 (44%) from ChatGPT 4o-mini were considered completely correct (p = 0.673). There was no relationship between accuracy and: word count; readability; or citation of at least one non-reputable source. CONCLUSION/CONCLUSIONS:ChatGPT 4o-mini and Gemini 3 Flash (Fast) responses to questions about BD/DNC may include inaccuracies. This could promote confusion and distrust. There is remarkable potential for integration of artificial intelligence in public education about healthcare, but there is a need for improvement to ensure responses are accurate and readable. The healthcare team should be prepared to address misconceptions about BD/DNC based on use of LLMs.
PMID: 42691933
ISSN: 1878-5883
CID: 6072008

Nirmatrelvir-ritonavir targeting viral persistence in post-COVID-19 condition (long COVID) in the USA (RECOVER-VITAL): a randomised, double-blind, placebo-controlled, phase 2 trial

Baden, Lindsey R; Shah, Nirav S; Liu, Sean T H; Cohen, Jonathan; Moy, James; Kumar, Andre; McComsey, Grace A; Chen, Peter; Floris-Moore, Michelle; Singer, Nora G; Fernandez, Inti; Slandzicki, Alex J; Wiley, Zanthia; Kadl, Alexandra; Kaminsky, David A; Hsu, Harvey; Walker, Tiffany A; Hope, Aluko A; Ostrosky-Zeichner, Luis; Goldman, Jason D; Peluso, Michael J; Patterson, Thomas F; Parthasarathy, Sairam; Mullington, Janet M; Bolin, Paul; Jolley, Sarah E; Krishnan, Jerry A; Castro, Mario; Hodder, Sally L; Pemu, Priscilla; Chu, Helen Y; Risbano, Michael G; Jerath, Maya R; Mylonakis, Eleftherios; Hurt, Ryan T; Alicic, Radica; Azad, Nabila S; Sala, Marc A; Harkins, Michelle S; Parsonnet, Jeffrey; Stafford, Neil; Robinson, Philip; Hussain, Sabiha; Qiao, Xian; Hawk, Sophie Two; Lillestol, Michael; Erdmann, Nathan; Gebo, Kelly A; Sudhindra, Praveen; Sassine, Joseph; Marshall, Gailen D; Chatterjee, Tulika; Morse, Caryn G; Kedar, Eyal; Stringer, William W; Frontera, Jennifer A; Jordan, Michael; Blaskewicz, Caitlin; Santana, Jorge L; Foot, Rachel A; Wongtrakool, Cherry; McCarthy, Matthew William; Mehari, Alem; Amon, Arch; Cohen, Alison K; Jain, Nita; Maughan, Christine; Lindsay, Doug; Olson, Rachel; Broderick, Samuel; Rowe, Pearl; O'Brien, Sean M; Walt, David R; Levy, Bruce D; Jason, Leonard A; Low, Phillip A; Shibao, Cyndya A; Make, Barry; Bateman, Lucinda; Redline, Susan; Knopman, David; Hernandez, Adrian F; Nolen, Tracy L; Reist, Craig; Berdan, Lisa; Whitley, Richard; Zimmerman, Kanecia O; ,
BACKGROUND:Post-acute sequelae of SARS-CoV-2 infection, more commonly known as long COVID, has emerged as a major health problem. The pathogenesis of long COVID is unknown, but among the leading hypotheses is viral persistence. We aimed to investigate whether the use of the SARS-CoV-2 antiviral nirmatrelvir-ritonavir improved long COVID symptoms. METHODS:We conducted a double-blind, placebo-controlled, randomised trial involving adults who had developed persistent symptoms (≥12 weeks) associated with three major symptom phenotypes (cognitive, autonomic, or exercise) after acute SARS-CoV-2 infection at 69 US sites. Participants were eligible if they were 18 years or older and had a previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization. Eligible participants were also required to have either at least two moderate symptoms from the same phenotype or one severe phenotype-associated symptom, as identified with the Cluster Targeted COVID-19 Symptom Questions. Participants were randomly allocated in a double-blind manner in a 1:1:1 ratio using permuted blocks of size 30 to receive either 15 days of active intervention followed by 10 days of placebo (300 mg nirmatrelvir-100 mg ritonavir twice daily, then 100 mg ritonavir-placebo); 25 days of active intervention (300 mg nirmatrelvir-100 mg ritonavir twice daily); or 25 days of placebo-ritonavir (100 mg ritonavir-placebo). A clinically significant change in patient-reported outcomes at day 90 comprised the primary endpoint: Patient-Reported Outcomes Measurement Information System Cognitive Function Short Form 8a, Orthostatic Hypotension Questionnaire question 1, and a modified version of the DePaul Symptom Questionnaire Post-Exertional Malaise short form. Secondary outcomes were phenotype-specific performance measures. The study was registered at ClinicalTrials.gov (NCT05595369) and is complete. FINDINGS/RESULTS:Between July 27, 2023, and Sept 6, 2024, 1207 individuals were screened. Of these, 964 were randomly allocated and 959 participants, excluding four participants who were later found ineligible and one who did not initiate treatment, were enrolled in the three phenotypes: 332 to cognitive, 334 to autonomic, and 332 to exercise. In the 959 participants in the mITT population, 643 (67%) self-reported as female, 314 (33%) were male, and two participants had a sex of unknown or undifferentiated; 750 (78%) were White; and 108 (11%) were Hispanic, Latino, or Spanish. The median age was 49 years (IQR 38-59). No statistically significant benefits were observed for any phenotype for primary endpoints. For the cognitive phenotype, adjusted differences compared to placebo were 3·2% (95% CI -10·4 to 16·8, p=0·65) for the 25-day regimen and -2·2% (-15·5 to 11·1, p=0·74) for the 15-day regimen. For the autonomic phenotype, adjusted differences were -6·4% (-18·5 to 5·7, p=0·30) for the 25-day regimen compared to placebo and -0·1% (-12·5 to 12·3, p=0·99) for the 15-day regimen compared to placebo. For exercise, adjusted differences were -7·8% (-19·5 to 3·8, p=0·19) for the 25-day regimen compared to placebo and 0·9% (-11·4 to 13·2, p=0·88) for the 15-day regimen compared to placebo. There were no differences in secondary endpoints, and no safety signals were observed; there were no deaths, and 52 serious adverse events occurred in 42 (4%) of 963 participants over the course of the study. INTERPRETATION/CONCLUSIONS:Nirmatrelvir-ritonavir for 15 days or 25 days showed no evidence of benefit in long COVID in any of the three phenotypes studied. These findings suggest additional approaches to measuring the symptom burden and treating Long COVID are needed. FUNDING/BACKGROUND:National Institutes of Health.
PMID: 42673984
ISSN: 1474-4457
CID: 6071933

An Urban Transdisciplinary Concussion Center: A Model for Clinical Care, Education, and Research

Olivera, Anlys; Pagnotta, Geraldine; Sproul, Mara; Phillips, Laura; Syed, Nuha; Drattell, Julia D; Juanito, Ma Victoria Castaneda; Fay, Jennifer; Denham, Teresa V; Serrano, Liliana; Zhao, Jiangyue; Parkin, Catherine A; Datta, Shae; Im, Brian S; Cardone, Dennis; Hainline, Brian; Flanagan, Steven; Galetta, Steven L; Balcer, Laura J; Arciniega, Hector
BACKGROUND:Public awareness of concussion has grown significantly over the past 2 decades, driven largely by media coverage of sports-related injuries. This has paralleled a rise in traumatic brain injury (TBI)-related emergency department visits, underscoring the need for specialized concussion care centers. Despite this, most existing programs focus on sports or pediatric populations, leaving critical care gaps. RECENT FINDINGS/RESULTS:The NYU Langone Concussion Center was established in 2013 to address these gaps by providing interdisciplinary care for both sports-related and non-sports-related concussions. Approximately 60% of cases seen at the center are not sports related. This article outlines the center's inception, operational model, patient demographics, and evolution over the past decade. IMPLICATIONS FOR PRACTICE/CONCLUSIONS:Lessons learned from the NYU Langone model offer valuable guidance for developing comprehensive concussion programs that can serve diverse urban populations. Key strategies include cross-specialty collaboration, flexible infrastructure, and systems-level integration to address heterogeneous mechanisms of injury and outcomes.
PMCID:13240711
PMID: 42678908
ISSN: 2163-0933
CID: 6071946