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Nervous System Diseases Commons™

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Thomas Jefferson University

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Articles 1 - 30 of 114

Full-Text Articles in Nervous System Diseases

Management Of Non-Survivable Head Trauma: Opportunities For Improvement, Sanjana R. Salwi, Mackenzie D. Castellanos, Therese Murphy, Pious D. Patel, Sonia Ajmera, Alex P. Vaz, Connor A. Wathen, Niels D. Martin, Monisha A. Kumar, James M. Schuster, Dmitriy Petrov Sep 2026

Management Of Non-Survivable Head Trauma: Opportunities For Improvement, Sanjana R. Salwi, Mackenzie D. Castellanos, Therese Murphy, Pious D. Patel, Sonia Ajmera, Alex P. Vaz, Connor A. Wathen, Niels D. Martin, Monisha A. Kumar, James M. Schuster, Dmitriy Petrov

Department of Neurosurgery Faculty Papers

BACKGROUND: Managing patients with non-survivable head trauma who do not meet brain death criteria presents significant ethical and clinical challenges. Decisions frequently fall to surrogates with limited guidance, particularly when organ donation status is unknown. This study assessed physician perspectives on communication, interventions, and institutional factors.

METHODS: We conducted a national survey of academic neurosurgery, trauma surgery, and neurocritical care programs. Items examined communication barriers, interventions by donor status, institutional support, and a dissonance measure for interventions viewed as inappropriate.

RESULTS: A total of 133 physicians responded. Top communication barriers were medical literacy, unclear patient values, and intrafamily conflict. Physicians …


Discovering Repurposable Drugs For Alzheimer's Disease And Related Dementias: Target Trial Emulation Using Decentralised Real-World Data, Qiong Wu, Lu Li, Yuqing Lei, Ting Zhou, Huilin Tang, Bingyu Zhang, Yiwen Lu, Maxwell Salvatore, Dazheng Zhang, Jiayi Tong, Tingyin Wang, Siqi Chen, Haoyang Li, Zhenxing Xu, Yu Huang, Yu Hu, Na Hong, Yujia Zhou, Fongci Lin, Kyra O'Brien, Yong Chen, Ruowang Li, Hua Xu, Fei Wang, Jiang Bian, David Wolk, Yong Chen Sep 2026

Discovering Repurposable Drugs For Alzheimer's Disease And Related Dementias: Target Trial Emulation Using Decentralised Real-World Data, Qiong Wu, Lu Li, Yuqing Lei, Ting Zhou, Huilin Tang, Bingyu Zhang, Yiwen Lu, Maxwell Salvatore, Dazheng Zhang, Jiayi Tong, Tingyin Wang, Siqi Chen, Haoyang Li, Zhenxing Xu, Yu Huang, Yu Hu, Na Hong, Yujia Zhou, Fongci Lin, Kyra O'Brien, Yong Chen, Ruowang Li, Hua Xu, Fei Wang, Jiang Bian, David Wolk, Yong Chen

College of Population Health Faculty Papers

BACKGROUND: Alzheimer's disease and related dementias (ADRD) affect nearly 6.9 million Americans, with the number expected to triple by 2050, while disease-modifying therapies remain unavailable. Drug repurposing, which identifies new indications for already approved medications, offers a more efficient and cost-effective pathway to accelerate development of effective therapies for ADRD. The aim of this study is to identify potential drug repurposing signals by systematically screening routinely prescribed drugs for associations with progression from mild cognitive impairment (MCI) to ADRD.

METHODS: We conducted a multi-site target trial emulation using electronic health record (EHR) data from four decentralised databases: INSIGHT Clinical Research …


Remarkable Seizure Reduction With Trofinetide Treatment In An Adult With Rett Syndrome: A Case Report, Semihan Adegbite, Pooneh Memar Ardestani, Maromi Nei Aug 2026

Remarkable Seizure Reduction With Trofinetide Treatment In An Adult With Rett Syndrome: A Case Report, Semihan Adegbite, Pooneh Memar Ardestani, Maromi Nei

Department of Neurology Faculty Papers

No abstract provided.


Nuclear Activities And Interactome Of The Ns5 Protein Of Tick-Borne Encephalitis Virus, Maxime Chazal, Aïssatou Aïcha Sow, Elodie Le Seac'h, Dana Hawasheen, Margarida Bonifacio, Mikael Feracci, Ségolène Gracias, Adrià Sogues, Melissa Molho, Heng Pan, Boris Bonaventure, Jean-Pierre Quivy, Geneviève Almouzni, Etienne Decroly, Holly Ramage, Jeffrey R. Johnson, Vincent Caval, Nolwenn Jouvenet Aug 2026

Nuclear Activities And Interactome Of The Ns5 Protein Of Tick-Borne Encephalitis Virus, Maxime Chazal, Aïssatou Aïcha Sow, Elodie Le Seac'h, Dana Hawasheen, Margarida Bonifacio, Mikael Feracci, Ségolène Gracias, Adrià Sogues, Melissa Molho, Heng Pan, Boris Bonaventure, Jean-Pierre Quivy, Geneviève Almouzni, Etienne Decroly, Holly Ramage, Jeffrey R. Johnson, Vincent Caval, Nolwenn Jouvenet

Department of Microbiology and Immunology Faculty Papers

Orthoflaviviruses are RNA viruses responsible for significant diseases in humans, domesticated animals, and wildlife. Their NS5 protein is central in viral replication, functioning both as an RNA-dependent RNA polymerase and a methyltransferase, while also modulating cellular processes, including the interferon response. Although viral replication is cytoplasmic, the NS5 protein of several mosquito-borne orthoflaviviruses cycles between the cytoplasm and the nucleus of infected human cells. However, the nuclear localization and function of NS5 of tick-borne orthoflaviviruses, such as tick-borne encephalitis virus (TBEV), remain poorly understood. Microscopy analysis and cell fractionation revealed that the NS5 protein of TBEV localized to both the …


Persistent Chemotherapy-Induced Peripheral Neuropathy As A Chronic Cancer Pain Syndrome: Mechanisms, Therapeutic Limitations, And Future Directions, Reed Firestone, Jamin Morrison Jul 2026

Persistent Chemotherapy-Induced Peripheral Neuropathy As A Chronic Cancer Pain Syndrome: Mechanisms, Therapeutic Limitations, And Future Directions, Reed Firestone, Jamin Morrison

Department of Medicine Faculty Papers

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting complication of cancer therapy and a major contributor to chronic neuropathic pain among cancer survivors. Although traditionally managed as a treatment-related toxicity, persistent CIPN frequently persists long after chemotherapy completion and is increasingly recognized as a major survivorship and palliative care challenge. This review synthesizes current mechanistic, clinical, and translational evidence and reframes persistent CIPN as a chronic neuropathic cancer pain syndrome. Methods: A narrative review of peer-reviewed literature was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library, supplemented by manual review of key references and clinical guidelines. Emphasis was placed …


Spontaneous Intracranial Hypotension With Negative Brain Mri Findings: A Systematic Review Of Diagnostic Strategies And Clinical Outcomes, Marina Romozzi, Giuseppe Garignano, Valid Rastegar, Francesco Onorati, Catello Vollono, Federico Tosto, Masahito Katsuki, Yasuhiko Matsumori, Francesco Signorelli Jul 2026

Spontaneous Intracranial Hypotension With Negative Brain Mri Findings: A Systematic Review Of Diagnostic Strategies And Clinical Outcomes, Marina Romozzi, Giuseppe Garignano, Valid Rastegar, Francesco Onorati, Catello Vollono, Federico Tosto, Masahito Katsuki, Yasuhiko Matsumori, Francesco Signorelli

Student Papers, Posters & Projects

BACKGROUND: Spontaneous intracranial hypotension (SIH) is a debilitating syndrome typically characterized by orthostatic headache and classic brain MRI findings. However, brain MRI abnormalities are indirect manifestations of cerebrospinal fluid (CSF) volume depletion rather than direct evidence of the leak, and some patients may present with unrevealing or absent typical brain MRI findings, posing a considerable diagnostic challenge.

METHODS: A comprehensive search of PubMed/Medline, Web of Science, and Scopus was conducted to perform a systematic review, according to PRISMA guidelines, analyzing the available evidence on MRI-negative SIH (patients without typical SIH findings on their initial brain MRI), including its clinical features, …


From Combustion Emissions To Neurotoxicity: Brain Health Risks Of Military Burn Pits Exposure, Katherine M. Eggers, Zoe A. Keller, Paul Barach, Julie M. Tomáška, Joshua P. Nixon, Janeen H. Trembley, Tammy A. Butterick Jun 2026

From Combustion Emissions To Neurotoxicity: Brain Health Risks Of Military Burn Pits Exposure, Katherine M. Eggers, Zoe A. Keller, Paul Barach, Julie M. Tomáška, Joshua P. Nixon, Janeen H. Trembley, Tammy A. Butterick

College of Population Health Faculty Papers

Military burn pits used during post-9/11 U.S. military deployments functioned as uncontrolled combustion systems and were widely utilized to dispose of large volumes of outdoor waste by burning. Burn pits involved heterogeneous waste materials burned under variable temperature and oxygen conditions. These combustion environments generated complex, toxic, multipollutant airborne emission mixtures that included particulate matter (PM2.5), polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). This narrative review synthesizes epidemiologic, experimental, and mechanistic evidence linking burn pit emissions to disruption of the lung–brain axis and adverse neurological outcomes. We specifically aim to address a critical gap in understanding how combustion-derived …


Sleep-Circadian Modulation Of Autophagy And Glymphatic Function: Failure Of Coordinated Brain Clearance In Parkinson's Disease, Shamaila Zafar, Jay S. Schneider Jun 2026

Sleep-Circadian Modulation Of Autophagy And Glymphatic Function: Failure Of Coordinated Brain Clearance In Parkinson's Disease, Shamaila Zafar, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson's disease (PD) involves α-synuclein accumulation and progressive neurodegeneration. This review proposes that PD reflects failure of sleep-circadian regulated brain clearance network integrating intracellular autophagy and extracellular glymphatic transport across neurons, glia, and blood-brain-barrier. Disruption of sleep-architecture and circadian-timing desynchronizes these processes, impairing protein clearance and promoting pathology. This framework positions sleep-circadian dysfunction as an upstream mechanism, suggesting that restoring sleep-circadian regulation may improve protein clearance and support disease-modifying strategies.


Objective Oculomotor, Vestibular, Reaction Time, And Cognitive Signatures Of Vestibular Migraine, Claire E. J. Ceriani, Alexandr Braverman, Alexander Kiderman May 2026

Objective Oculomotor, Vestibular, Reaction Time, And Cognitive Signatures Of Vestibular Migraine, Claire E. J. Ceriani, Alexandr Braverman, Alexander Kiderman

Department of Neurology Faculty Papers

OBJECTIVE: To evaluate oculomotor, vestibular, reaction time, and cognitive (OVRT-C) function in patients with vestibular migraine (VM) using objective eye-tracking-based metrics and to identify patterns of dysfunction relative to healthy controls.

BACKGROUND: Vestibular migraine is a common yet underdiagnosed cause of vertigo. Diagnosis remains primarily clinical, because objective neurologic and vestibular findings are often absent or inconsistent. Quantitative methods capable of capturing the multisystem manifestations of VM may improve objective characterization of the disorder.

METHODS: Participants with a clinical diagnosis of vestibular migraine were recruited from a tertiary headache center and assessed using a battery of OVRT-C tests administered with …


Safety And Efficacy Of Individualised Exercise And Nad+ Precursor Supplementation In Patients With Friedreich’S Ataxia In The Usa: A Single-Centre, 2 × 2 Factorial, Randomised Controlled Trial, Kimberly Lin, Anna Bucha, Kara Mcsweeney, Kristin Wade, Antoneta Karaj, Jaclyn Tamaroff, Shannon O'Malley, Nicole Chung, Nicolette Cilenti, Julianne Wanner, Gabriel Adzika, Clementina Mesaros, Ian Blair, Teerapat Rojsajjakul, Suraj Serai, Jennifer Farmer, Kyle Bryant, Yingying Lu, Michael Harhay, David Weber, Stephen Paridon, Erin Seifert, Mary Putt, Payman Zamani, Joseph Baur, David Lynch, Shana Mccormack May 2026

Safety And Efficacy Of Individualised Exercise And Nad+ Precursor Supplementation In Patients With Friedreich’S Ataxia In The Usa: A Single-Centre, 2 × 2 Factorial, Randomised Controlled Trial, Kimberly Lin, Anna Bucha, Kara Mcsweeney, Kristin Wade, Antoneta Karaj, Jaclyn Tamaroff, Shannon O'Malley, Nicole Chung, Nicolette Cilenti, Julianne Wanner, Gabriel Adzika, Clementina Mesaros, Ian Blair, Teerapat Rojsajjakul, Suraj Serai, Jennifer Farmer, Kyle Bryant, Yingying Lu, Michael Harhay, David Weber, Stephen Paridon, Erin Seifert, Mary Putt, Payman Zamani, Joseph Baur, David Lynch, Shana Mccormack

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND:Friedreich's ataxia is a rare, chronic, progressive, neurodegenerative condition affecting multiple organ systems, including neurological, musculoskeletal, cardiac, and endocrine systems, and is marked by low cardiopulmonary fitness. We tested the effect of exercise and NAD+ precursor supplementation with nicotinamide riboside, which have each shown benefits in animal and early clinical studies, on cardiopulmonary fitness in individuals with Friedreich's ataxia.

METHODS: This 12-week, outpatient, phase 2, single-site (Children's Hospital of Philadelphia, Philadelphia, PA, USA), randomised, 2 × 2 factorial clinical trial recruited individuals aged 10–40 years with an ejection fraction of 45% or greater who were able to exercise. A …


Assessment Of Clinical And Neuroimaging Efficacy Of Treatment Targeting Tau Pathology In Mild Cognitive Impairment And Mild To Moderate Alzheimer’S Disease With Hydromethylthionine Mesylate Using External Control Data, Bjoern O. Schelter, Helen Shiells, Serena Lo, Nafeesa Nazlee, Emily Evans, Peter Bentham, Serge Gauthier, Henrik Zetterberg, Gordon K. Wilcock, Lutz Froelich, Alistair Burns, Emer Macsweeney, Clive Ballard, Jin-Tai Yu, Tay Siew Choon, Vahe Asvatourian, Natalia Muehlemann, Jan Priel, Karin Kook, Tenecia Sullivan, Diane Downie, Sonya Miller, Carol Pringle, John M. D. Storey, Tom Baddeley, Charles R. Harrington, Roger Staff, Anca-Larisa Sandu, Claire Hull, Richard G. Stefanacci, Claude M. Wischik Apr 2026

Assessment Of Clinical And Neuroimaging Efficacy Of Treatment Targeting Tau Pathology In Mild Cognitive Impairment And Mild To Moderate Alzheimer’S Disease With Hydromethylthionine Mesylate Using External Control Data, Bjoern O. Schelter, Helen Shiells, Serena Lo, Nafeesa Nazlee, Emily Evans, Peter Bentham, Serge Gauthier, Henrik Zetterberg, Gordon K. Wilcock, Lutz Froelich, Alistair Burns, Emer Macsweeney, Clive Ballard, Jin-Tai Yu, Tay Siew Choon, Vahe Asvatourian, Natalia Muehlemann, Jan Priel, Karin Kook, Tenecia Sullivan, Diane Downie, Sonya Miller, Carol Pringle, John M. D. Storey, Tom Baddeley, Charles R. Harrington, Roger Staff, Anca-Larisa Sandu, Claire Hull, Richard G. Stefanacci, Claude M. Wischik

College of Population Health Faculty Papers

BACKGROUND: Hydromethylthionine mesylate (HMTM) targets tau pathology and also has tau-independent symptomatic activity. A traditional randomised placebo-controlled trial (RCT) was precluded by loss of blinding due to urinary colouration and therapeutic activity at the minimum dose required to maintain blinding.

OBJECTIVE: To evaluate the efficacy of HMTM in participants with mild cognitive impairment (MCI) and mild to moderate dementia due to Alzheimer's disease (AD).

METHODS: Because a traditional RCT was not feasible without loss of blinding, we compared HMTM 16 mg/day in TRx-237-039 with propensity score matched true placebo controls from the FDA-sponsored Critical Path for AD (CPAD) database with …


Transcranial Alternating Current Stimulation As An Adjuvant For Nonfluent Aphasia: A Proof-Of-Concept Study, Lynsey M. Keator, Lisa Johnson, Roger Newman-Norlund, Kyler Spell, Samaneh Nemati, Leigh Ann Spell, Dirk B. Den Ouden, Christopher Rorden, Julius Fridriksson Mar 2026

Transcranial Alternating Current Stimulation As An Adjuvant For Nonfluent Aphasia: A Proof-Of-Concept Study, Lynsey M. Keator, Lisa Johnson, Roger Newman-Norlund, Kyler Spell, Samaneh Nemati, Leigh Ann Spell, Dirk B. Den Ouden, Christopher Rorden, Julius Fridriksson

Department of Speech-Language Pathology Faculty Papers

Effective rehabilitation tools are essential for improving language outcomes in chronic aphasia. Speech entrainment is a behavioral treatment that has shown promise in enhancing speech output in nonfluent aphasia, potentially by acting as an external mechanism to synchronize anterior and posterior language regions in the left hemisphere. Transcranial alternating current stimulation has been hypothesized to enhance functional connectivity between brain regions by amplifying endogenous oscillations. This proof-of-concept study explored whether high-definition tACS (HD-tACS) could improve speech fluency in nonfluent aphasia when paired with speech entrainment. In a double-blind, pseudorandomized study, 1 mA of HD-tACS at 7 Hz was applied to …


Editorial: Clinical Imaging, Neurophysiological, Neuropathology And Neuroethics Studies On Disorders Of Consciousness, Coma Mechanisms, And Theories Of Consciousness: A Unifying Attempt, Diego Iacono, Manuel Trachsel, Thanh Phan, Charlène Aubinet Mar 2026

Editorial: Clinical Imaging, Neurophysiological, Neuropathology And Neuroethics Studies On Disorders Of Consciousness, Coma Mechanisms, And Theories Of Consciousness: A Unifying Attempt, Diego Iacono, Manuel Trachsel, Thanh Phan, Charlène Aubinet

Department of Neurology Faculty Papers

No abstract provided.


Epidemiology Of Healthcare-Associated Ventriculitis And Meningitis (Hcavm) And Community-Acquired Meningitis/Encephalitis And Evaluation Of An Off-Label Pcr Panel For Hcavm Diagnosis, Jaime Nassur, Katarina Schnell, Christine Dolon, Laura Walters, Devin Weber, Matthew Pettengill Feb 2026

Epidemiology Of Healthcare-Associated Ventriculitis And Meningitis (Hcavm) And Community-Acquired Meningitis/Encephalitis And Evaluation Of An Off-Label Pcr Panel For Hcavm Diagnosis, Jaime Nassur, Katarina Schnell, Christine Dolon, Laura Walters, Devin Weber, Matthew Pettengill

Department of Medicine Faculty Papers

Healthcare-associated ventriculitis and meningitis (HCAVM) is associated with high morbidity and mortality, but rapid diagnostic tests intended to cover microorganisms that typically cause HCAVM are not commercially available. We sought to evaluate the etiology of HCAVM compared to community-acquired meningitis/encephalitis (CAME) at our healthcare system, and to study the utility of repurposing a multiplex molecular panel intended for positive blood cultures for HCAVM cases. Our epidemiologic review demonstrated that HCAVM cases were primarily caused by bacteria and fungi also associated with bloodstream infections, in contrast with CAME cases, which were primarily caused by herpesviruses and Cryptococcus. Eighty-two cerebrospinal fluid …


Increasing Physical Activity In Moderate-Severe Traumatic Brain Injury: Protocol For A Two-Stage Randomized Controlled Trial Of A Remote, Mhealth-Enhanced Intervention, Tessa Hart, Monica Vaccaro, Lauren Krasucki, Inna Chervoneva, Amanda Rabinowitz Feb 2026

Increasing Physical Activity In Moderate-Severe Traumatic Brain Injury: Protocol For A Two-Stage Randomized Controlled Trial Of A Remote, Mhealth-Enhanced Intervention, Tessa Hart, Monica Vaccaro, Lauren Krasucki, Inna Chervoneva, Amanda Rabinowitz

Moss-Magee Rehabilitation Papers

OBJECTIVE: Protocol for randomized controlled trial (RCT) examining effects of novel, remotely delivered intervention (called GetUp&Go) to increase physical activity (PA) in chronic, moderate-severe traumatic brain injury (msTBI), including a mobile health (mHealth) component.

DESIGN: RCT (Clinicaltrials.gov NCT06028334) with 1:1 randomization to 10 weeks of immediate treatment (IT) or waitlist (WL), with primary outcome measured at 10 weeks. A second randomization to 10 weeks of continued mHealth support vs. no treatment will allow for examination of effects of mHealth on maintenance of treatment gains.

PARTICIPANTS: 70 community-dwelling adults ≥6 months post msTBI; medically cleared and physically/ cognitively able to participate; …


Recurrent Miller Fisher Syndrome: A Case Report, Larry Vernier, Griffin B. Gilmore, Kelsey Van Housen, Xiao C. Zhang Feb 2026

Recurrent Miller Fisher Syndrome: A Case Report, Larry Vernier, Griffin B. Gilmore, Kelsey Van Housen, Xiao C. Zhang

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Guillain-Barré syndrome can manifest with progressive paralysis, requiring careful monitoring and treatment with steroids or intravenous (IV) immunoglobin. While this disease can be devastating and require intensive care unit level of care, there are few incidences of relapses.

CASE REPORT: A 67-year-old man with a past medical history of Miller Fisher syndrome variant of Guillain-Barré syndrome, with complete recovery, presented to the emergency department (ED) with ataxia, ophthalmoplegia, dysphonia, and ambulatory dysfunction. The patient noticed his neurologic symptoms after waking up, and he presented to the ED with physical examination positive for difficulty with upward gaze, mild right lower …


N-Acetylcysteine Is Associated With Changes In Functional Connectivity In Patients With Parkinson's Disease, Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Faezeh Vedaei, Emily Navarreto, Monisha Gupta, Alicia Steinmetz, Anthony J. Bazzan, Feroze Mohamed, Andrew B. Newberg Jan 2026

N-Acetylcysteine Is Associated With Changes In Functional Connectivity In Patients With Parkinson's Disease, Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Faezeh Vedaei, Emily Navarreto, Monisha Gupta, Alicia Steinmetz, Anthony J. Bazzan, Feroze Mohamed, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

INTRODUCTION: This study assessed the changes in functional connectivity from resting functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease (PD) given N-Acetylcysteine (NAC), the prodrug to L-cysteine and a precursor to the natural biological antioxidant glutathione (GSH). The aim of this study was to determine whether NAC is associated with changes in functional connectivity, particularly in the basal ganglia, and improvements in Parkinson's symptoms.

METHODS: Forty-four patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for six months plus standard of care, or standard of …


Apolipoprotein E4 And Its Later-Life Health Effects On The Multiple Sclerosis Population, Dean Zeldich, Chia Hsin Cheng, Yi Guan, Sriman Narain, Bang-Bon Koo Jan 2026

Apolipoprotein E4 And Its Later-Life Health Effects On The Multiple Sclerosis Population, Dean Zeldich, Chia Hsin Cheng, Yi Guan, Sriman Narain, Bang-Bon Koo

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer's Disease, accelerates cognitive decline and neuroinflammatory processes, including blood-brain-barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.

METHODS: MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic …


Clinical, Imaging And Blood Biomarker Outcomes In A Phase 3 Clinical Trial Of Tau Aggregation Inhibitor Hydromethylthionine Mesylate In Mild Cognitive Impairment And Mild To Moderate Dementia Due To Alzheimer’S Disease, Claude Wischik, Richard G. Stefanacci, Peter Bentham, Serge Gauthier, Henrik Zetterberg, Gordon Wilcock, Lutz Froelich, Alistair Burns, Emer Macsweeney, Clive Ballard, Jin-Tai Yu, Tay Siew Choon, Vahe Asvatourian, Natalia Muehlemann, Jan Priel, Karin Kook, Tenecia Sullivan, Diane Downie, Sonya Miller, Carol Pringle, John Storey, Tom Baddeley, Charles R Harrington, Lewis Penny, Mohammad Arastoo, Roger Staff, Anca-Larisa Sandu, Helen Shiells, Serena Lo, Nafeesa Nazlee, Emily Evans, Claire Hull, Bjoern Schelter Jan 2026

Clinical, Imaging And Blood Biomarker Outcomes In A Phase 3 Clinical Trial Of Tau Aggregation Inhibitor Hydromethylthionine Mesylate In Mild Cognitive Impairment And Mild To Moderate Dementia Due To Alzheimer’S Disease, Claude Wischik, Richard G. Stefanacci, Peter Bentham, Serge Gauthier, Henrik Zetterberg, Gordon Wilcock, Lutz Froelich, Alistair Burns, Emer Macsweeney, Clive Ballard, Jin-Tai Yu, Tay Siew Choon, Vahe Asvatourian, Natalia Muehlemann, Jan Priel, Karin Kook, Tenecia Sullivan, Diane Downie, Sonya Miller, Carol Pringle, John Storey, Tom Baddeley, Charles R Harrington, Lewis Penny, Mohammad Arastoo, Roger Staff, Anca-Larisa Sandu, Helen Shiells, Serena Lo, Nafeesa Nazlee, Emily Evans, Claire Hull, Bjoern Schelter

College of Population Health Faculty Papers

BACKGROUND: Hydromethylthionine mesylate (HMTM) targets tau pathology and has tau-independent symptomatic activity.

OBJECTIVES: To evaluate the safety and efficacy of HMTM in participants with mild cognitive impairment (MCI) and mild to moderate dementia due to Alzheimer's disease (AD).

SETTING: 82 centres in Canada, European Union, United Kingdom and United States of America.

PARTICIPANTS: A total of 598 amyloid β-PET positive participants were included; 44% (263) met clinical criteria for MCI due to Alzheimer's disease and 56% (335) were diagnosed with mild to moderate dementia due to AD.

INTERVENTION: HMTM 16 mg/day and 8 mg/day were compared with methylthioninium chloride (MTC) …


Plans4care, A Web Application Providing Caregivers Personalized Solutions To Manage Dementia-Related Care Challenges: Proof Of Concept And Efficacy Trial, Laura N. Gitlin, Eric Jutkowitz, Catherine V. Piersol, Sokha Koeuth, Taylor Sivori, Melinda J. Webster, Rachel N. Barnett, David L. Roth Jan 2026

Plans4care, A Web Application Providing Caregivers Personalized Solutions To Manage Dementia-Related Care Challenges: Proof Of Concept And Efficacy Trial, Laura N. Gitlin, Eric Jutkowitz, Catherine V. Piersol, Sokha Koeuth, Taylor Sivori, Melinda J. Webster, Rachel N. Barnett, David L. Roth

Department of Occupational Therapy Faculty Papers

OBJECTIVE: Few dementia caregivers have access to evidence-based support programs. Web applications (app) may address this gap. Plans4Care, a web app, provides caregivers with on-demand personalized solutions to address care challenges. We present results of a proof-of-concept study and describe a trial protocol to test efficacy.

METHODS: To use Plans4Care, caregivers respond to brief onboarding questions, assess dementia patients' cognitive function, identify care challenges, and generate "action plans" (personalized strategies). Telehealth sessions with dementia-trained care advisors are available. A proof-of-concept study evaluated a clickable prototype using standardized technology scales to determine if >75 % scored positively on four criteria (acceptability, …


Associations Between Contralesional Neuroplasticity And Motor Impairment Through Deep Learning-Derived Mri Regional Brain Age In Chronic Stroke (Enigma): A Multicohort, Retrospective, Observational Study, Gilsoon Park, Mahir Khan, Justin Andrushko, Nerisa Banaj, Michael Borich, Lara Boyd, Amy Brodtmann, Truman Brown, Cathrin Buetefisch, Adriana Conforto, Steven Cramer, Michael Dimyan, Martin Domin, Miranda Donnelly, Natalia Egorova-Brumley, Elsa Ermer, Wuwei Feng, Fatemeh Geranmayeh, Colleen Hanlon, Brenton Hordacre, Neda Jahanshad, Steven Kautz, Mohamed Salah Khlif, Jingchun Liu, Martin Lotze, Bradley Macintosh, Feroze Mohamed, Jan Nordvik, Fabrizio Piras, Kate Revill, Andrew Robertson, Christian Schranz, Nicolas Schweighofer, Na Jin Seo, Surjo Soekadar, Shraddha Srivastava, Bethany Tavenner, Gregory Thielman, Sophia Thomopoulos, Daniela Vecchio, Emilio Werden, Lars Westlye, Carolee Winstein, George Wittenberg, Jennifer Ferris, Chunshui Yu, Paul Thompson, Sook-Lei Liew, Hosung Kim Jan 2026

Associations Between Contralesional Neuroplasticity And Motor Impairment Through Deep Learning-Derived Mri Regional Brain Age In Chronic Stroke (Enigma): A Multicohort, Retrospective, Observational Study, Gilsoon Park, Mahir Khan, Justin Andrushko, Nerisa Banaj, Michael Borich, Lara Boyd, Amy Brodtmann, Truman Brown, Cathrin Buetefisch, Adriana Conforto, Steven Cramer, Michael Dimyan, Martin Domin, Miranda Donnelly, Natalia Egorova-Brumley, Elsa Ermer, Wuwei Feng, Fatemeh Geranmayeh, Colleen Hanlon, Brenton Hordacre, Neda Jahanshad, Steven Kautz, Mohamed Salah Khlif, Jingchun Liu, Martin Lotze, Bradley Macintosh, Feroze Mohamed, Jan Nordvik, Fabrizio Piras, Kate Revill, Andrew Robertson, Christian Schranz, Nicolas Schweighofer, Na Jin Seo, Surjo Soekadar, Shraddha Srivastava, Bethany Tavenner, Gregory Thielman, Sophia Thomopoulos, Daniela Vecchio, Emilio Werden, Lars Westlye, Carolee Winstein, George Wittenberg, Jennifer Ferris, Chunshui Yu, Paul Thompson, Sook-Lei Liew, Hosung Kim

Department of Radiology Faculty Papers

BACKGROUND: Stroke leads to complex chronic structural and functional brain changes that specifically affect motor outcomes. The brain predicted age difference (PAD) has emerged as a sensitive biomarker of both sensorimotor and cognitive function after stroke. Our previous study showed a higher global brain PAD associated with poorer motor function after stroke. However, the association between local stroke lesion load, regional brain age, and motor impairment is unclear. This study aimed to investigate the associations between focal lesion damage, regional brain PAD in both hemispheres, and motor outcomes in chronic stroke, and to identify key predictors of motor impairment.

METHODS: …


The Mechanism Of Action Of Remote Electrical Neuromodulation (Ren) In Treating Migraine And Potentially Other Idiopathic Pain Conditions, Marius Birlea, Christopher L. Robinson, Eden Mama, Alit Stark-Inbar, Alon Ironi, Daniel Atashsokhan, Thomas Berk Nov 2025

The Mechanism Of Action Of Remote Electrical Neuromodulation (Ren) In Treating Migraine And Potentially Other Idiopathic Pain Conditions, Marius Birlea, Christopher L. Robinson, Eden Mama, Alit Stark-Inbar, Alon Ironi, Daniel Atashsokhan, Thomas Berk

College of Nursing Faculty Papers & Presentations

Purpose of Review

This review provides evidence for the mechanism of action (MOA) of Remote Electrical Neuromodulation (REN), a non-pharmacological therapeutic technology for treating migraine and other symptoms manifested by certain idiopathic pain diseases. It discusses the main physiological and anatomical aspects associated with conditioned pain modulation (CPM), and how REN is applied for the treatment of migraine pain and other symptoms.

Recent Findings

The REN wearable device (Nerivio®) is FDA cleared for acute and preventive treatment of migraine in patients aged 8 years and above, and CE marked in patients aged 12 and above. In brief, the REN MOA …


Promising Effects Of Car T-Cell Therapy In Refractory Stiff Person Syndrome And A Hopeful Future For All Neuroautoimmunities, Marinos Dalakas Nov 2025

Promising Effects Of Car T-Cell Therapy In Refractory Stiff Person Syndrome And A Hopeful Future For All Neuroautoimmunities, Marinos Dalakas

Department of Neurology Faculty Papers

Chimeric antigen receptor (CAR) T cells are genetically modified T cells expressing CARs, initially developed to recognize tumor antigens and kill cancer cells that evade T-cell recognition. Because of their impressive success in hemato-oncologic malignancies, CAR T cells are being repurposed with redesigned constructs for safety and sustained efficacy to target refractory systemic autoimmune or neurologic diseases. The CD19 CAR T cells-targeting those CD19-positive, antibody-secreting, long-lived plasma cells, and plasmablasts-are now extensively explored in refractory neuroautoimmunities with promising benefits based on case series in patients with myasthenia gravis (MG), stiff person syndrome (SPS), neuromyelitis, myositis, and multiple sclerosis; some patients …


Repetitive Head Impacts: Definitional Challenges, Clinical Implications, And Research Directions, Amanda Rabinowitz, Allie Tracey, Yevgeniya Sergeyenko Nov 2025

Repetitive Head Impacts: Definitional Challenges, Clinical Implications, And Research Directions, Amanda Rabinowitz, Allie Tracey, Yevgeniya Sergeyenko

Department of Rehabilitation Medicine Faculty Papers

Purpose of Review: Repetitive head impacts (RHI)—repeated head trauma that may or may not result in clinically identified injury—are a growing public health concern due to links with neurodegenerative disease and long-term dysfunction. This review aimed to synthesize current knowledge of RHI and evaluate methodological challenges that limit conclusions about its clinical consequences. Recent Findings: Emerging studies highlight associations between RHI and cognitive, emotional, and functional outcomes across vulnerable populations including athletes, military personnel, and survivors of intimate partner violence. However, definitional ambiguity, difficulties in measuring exposure, and population-specific confounds continue to hinder progress. Clinical approaches emphasize individualized assessment and …


Botulinum Toxin In Stiff Person Syndrome: How Useful Is It In Helping Muscle Stiffness And Spasms?, Marinos Dalakas Nov 2025

Botulinum Toxin In Stiff Person Syndrome: How Useful Is It In Helping Muscle Stiffness And Spasms?, Marinos Dalakas

Department of Neurology Faculty Papers

No abstract provided.


Cerebellar Dysfunction In Glaucoma Patients, Anisha Kasi, Ji Won Bang, Vivek Trivedi, Jeannie Au, Ian Conner, Gadi Wollstein, Joel Schuman, Rakie Cham, Kevin Chan Oct 2025

Cerebellar Dysfunction In Glaucoma Patients, Anisha Kasi, Ji Won Bang, Vivek Trivedi, Jeannie Au, Ian Conner, Gadi Wollstein, Joel Schuman, Rakie Cham, Kevin Chan

Wills Eye Hospital Papers

Glaucoma patients often have higher injurious fall rates compared to healthy older adults. However, little is known about the underlying neural mechanisms. Recent evidence shows cerebral changes beyond the visual pathway of glaucoma patients, yet it remains unclear whether the cerebellum, which plays an important role in balance and motor control, is involved in glaucoma. In this study, we sought to investigate cerebellar functional connectivity changes in glaucoma by comparing 32 glaucoma subjects and 10 age-matched healthy control subjects who underwent resting-state functional magnetic resonance imaging at 3 Tesla with eyes closed. After conducting both regions-of-interest and seed-to-voxel analyses, we …


Organism-Specific Sequence Motifs Link Ribosomal Rnas To Brain Disorders, Isidore Rigoutsos, Stepan Nersisyan, Eric Londin, Iliza Nazeraj, Bonnie Dong, Anastasios Vourekas, Phillipe Loher Oct 2025

Organism-Specific Sequence Motifs Link Ribosomal Rnas To Brain Disorders, Isidore Rigoutsos, Stepan Nersisyan, Eric Londin, Iliza Nazeraj, Bonnie Dong, Anastasios Vourekas, Phillipe Loher

Computational Medicine Center Faculty Papers

We report that in humans, mice, fruit flies, and worms, the ribosomal RNAs and the transcribed spacers of 45S are densely packed with organism-specific sequence motifs that are primarily shared with nervous system genes. The human ribosomal RNAs and 45S spacers contain 1,723 such motifs. Specific combinations of these motifs are predominantly found in 3,430 human nervous system genes, of which 1,046 are genes associated with brain disorders, including autism spectrum disorder and schizophrenia. The sequences of the 1,723 motifs and their locations in the introns and exons of nervous system genes are unique to primates. Experimental evidence indicates that …


The Importance Of Treating Migraine Attacks Early - Even In Youth: A Real-World Argument For Neuromodulation, Mario F. P. Peres, Hsiangkuo Yuan, Cristina Tassorelli Oct 2025

The Importance Of Treating Migraine Attacks Early - Even In Youth: A Real-World Argument For Neuromodulation, Mario F. P. Peres, Hsiangkuo Yuan, Cristina Tassorelli

Department of Jefferson Headache Center Papers and Presentations

No abstract provided.


Clinical Utility Of Diffusion Tensor Imaging In Sport-Related Concussion: A Systematic Review, Shiv Patil, Rithvik Kata, Serhat Aydin, Mert Karabacak, Konstantinos Margetis, Sotirios Bisdas Oct 2025

Clinical Utility Of Diffusion Tensor Imaging In Sport-Related Concussion: A Systematic Review, Shiv Patil, Rithvik Kata, Serhat Aydin, Mert Karabacak, Konstantinos Margetis, Sotirios Bisdas

Student Papers, Posters & Projects

OBJECTIVE: Sport-related concussion (SRC) is a prevalent form of traumatic brain injury that is associated with long-term neurological and psychiatric impairment, particularly among athletes with a history of repetitive concussions. The biological variability of SRC's impact on the brain, as well as a lack of objective biomarkers to diagnose and prognosticate concussion, has prompted interest in advanced neuroimaging methods such as diffusion tensor imaging (DTI). By measuring disruptions in water diffusivity due to head trauma, DTI can detect alterations in white matter integrity that are not visualized by conventional imaging methods. This systematic review aims to synthesize major trends and …


International Headache Society Evidence-Based Guidelines On The Use Of Non-Invasive Neuromodulation Devices For The Acute And Preventive Treatment Of Migraine, Hsiangkuo Yuan, Serena L. Orr, Mohammad A. M. Al-Karagholi, Messoud Ashina, Fred Cohen, Hans-Christoph Diener, David W. Dodick, Rigmor Højland Jensen, Michael J. Marmura, Daniele Martinelli, Manjit S. Matharu, Anja S. Petersen, Patricia Pozo-Rosich, Simona Sacco, Lucy Simmonds, Cristina Tassorelli, Stewart J. Tepper, Gisela M. Terwindt, Shuu-Jiun Wang, Jiunn-Tyng Yeh, Stephen D. Silberstein Oct 2025

International Headache Society Evidence-Based Guidelines On The Use Of Non-Invasive Neuromodulation Devices For The Acute And Preventive Treatment Of Migraine, Hsiangkuo Yuan, Serena L. Orr, Mohammad A. M. Al-Karagholi, Messoud Ashina, Fred Cohen, Hans-Christoph Diener, David W. Dodick, Rigmor Højland Jensen, Michael J. Marmura, Daniele Martinelli, Manjit S. Matharu, Anja S. Petersen, Patricia Pozo-Rosich, Simona Sacco, Lucy Simmonds, Cristina Tassorelli, Stewart J. Tepper, Gisela M. Terwindt, Shuu-Jiun Wang, Jiunn-Tyng Yeh, Stephen D. Silberstein

Department of Jefferson Headache Center Papers and Presentations

ObjectiveTo develop evidence-based clinical practice guidelines for non-invasive neuromodulation devices in acute and preventive migraine treatment.MethodsA systematic review was conducted across six databases from 1946 to April 2025. Randomized controlled trials evaluating Food and Drug Administration-cleared or Conformité Européenne (CE)-marked non-invasive neuromodulation devices were included. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, and recommendations were developed through consensus following GRADE Evidence-to-Decision frameworks. The working group comprised 15 senior members and six junior members.ResultsFrom 1536 initial records, 15 studies met the inclusion criteria and were finally used to develop evidence-based recommendations. …