Neurology Commons^™

The Role Of Reproductive Aging And Surgeries For Alzheimer’S Disease And Related Dementias (Adrd) Diagnoses In The Cardiovascular Health Study, Alexis Reeves, Oscar L. Lopez, Michelle D. Shardell, Hoda S. Abdel Magid, C. Elizabeth Shaaban, Michelle C. Odden

Department of Neurology Faculty Papers

Abstract

Background

Most US individuals with ADRD are women. Menopause typically occurs in midlife, accompanied by declines in potentially neuroprotective and cardioprotective hormones. Earlier menopause leads to earlier exposure to decreased sex hormones, potentially increasing ADRD risk. Surgical menopause via reproductive surgeries may cause a sudden loss of hormones and may represent be a modifiable risk factor for ADRD. We aimed to determine if menopausal type and age are associated with physician adjudicated-ADRD diagnoses.

Methods

Data were from 3371 women prospectively followed from age 65+ years. Participants self-reported age of menopause and/or surgeries, hormone-therapy, education, and race (Black/White). For this …

Synergistic Effects Of Gfap With Tnfr1 And Tnfr2 On Conversion To Ad Dementia And Overall Survival Across The Alzheimer’S Disease Spectrum, Laura Alejandra Ramirez Tirado, Ann D. Cohen, C. Elizabeth Shaaban, Cristy Matan, Brian J. Lopresti, Milos D. Ikonomovic, Thomas K. Karikari, Victor L. Villemagne, Oscar L. Lopez

Department of Neurology Faculty Papers

Background: We recently reported synergistic effects of TNFR1 and TNFR2 with
astrogliosis resulting in greater vascular burden and neurodegeneration, particularly in
Aβ+ participants. Here, we aimed to assess the interactions of peripheral inflammation
and astrogliosis on incidence of AD dementia and mortality. We hypothesized
synergistic effects with astrogliosis resulting in increased incidence of dementia, and
mortality, particularly in Aβ+ participants.
Methods: Participants of the Gingko evaluation of memory (GEM) study underwent
PiB-PET scans between 2009-2018. GFAP and peripheral inflammatory markers were
measured in 2009 by immunoassay. We evaluated the relationship of peripheral
markers of inflammation (TNFR1,TNFR2) and astrogliosis (GFAPdementia incidence …

Discovery Of Small Molecules And A Druggable Groove That Regulate Dna Binding And Release Of The Ap-1 Transcription Factor Δfosb, Sean Mcneme, Yun Young Yim, Ashwani Kumar, Yi Li, Brandon Hughes, Corey Peyton St Romain, Galina Aglyamova, Jianping Chen, Nghi D Nguyen, Shanghua Fan, Gabriel S Stephens, Wen-Ning Zhao, Samantha Kruzshak, Molly Estill, Corrine Brener, Solange Tofani, Anil Kumar, Earnest P Chen, Nadeen Takatka, Alfred J Robison, Haiying Chen, Reid T Powell, Stephen J Haggarty, Clifford Stephan, Eric J Nestler, Jeannie Chin, Mischa Machius, Jia Zhou, Gabby Rudenko

Faculty, Staff and Students Publications

ΔFOSB, a member of the AP-1 family of transcription factors, mediates long-term neuroadaptations underlying drug addiction, seizure-related cognitive decline, dyskinesias, and several other chronic conditions. AP-1 transcription factors are notoriously difficult to modulate pharmacologically due to the absence of well-defined binding pockets. Here, we identify a novel site on ΔFOSB, located outside the DNA-binding cleft, that accommodates small molecules. We show that sulfonic acid-containing compounds bind to this site via an induced-fit mechanism, reorienting side chains critical for DNA binding, and that they may hinder the ΔFOSB bZIP α-helix from binding to the major groove of DNA. In vivo, direct …

Efficacy Of Intravenous Immunoglobulin In Patients With Chronic Inflammatory Demyelinating Polyneuropathy With Or Without Diabetes: Insights From A Multicenter Prospective Comparative Study., Samir P. Macwan, Shalini Mahajan, Peter Novak, Khosro Farhad, Ericka Wong, Thomas H. Brannagan, Sohail Masood, Fawad Piracha, Marinos C. Dalakas

Department of Neurology Faculty Papers

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most frequently observed autoimmune neuropathy in patients with diabetes mellitus (DM). While intravenous immune globulin (IVIG) is a well-established treatment for CIDP, its efficacy in diabetic patients remains uncertain due to their exclusion from prior randomized trials, largely because of concerns about confounding diabetic axonal neuropathy.

OBJECTIVES: To evaluate the effectiveness of IVIG therapy in CIDP patients with diabetes mellitus (CIDP-DM) compared to those without diabetes (CIDP).

DESIGN: Multi-center, prospective, observational study after at least 3 monthly infusions of IVIG therapy.

METHODS: Thirty-six patients meeting diagnostic criteria for CIDP were enrolled and …

Metabolomic Profiling Reveals Brain Lipid Alterations In Pex7-Deficient Models Of Rhizomelic Chondrodysplasia Punctata, Riya Sankhe, Meredith I Williams, Wedad Fallatah, Laura Mackay, Mary Layne Brown, Pranjali Bhagwat, Sarah H Elsea, Nancy Braverman, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a peroxisomal disorder characterized by skeletal shortening, intellectual disability, seizures, cataracts, and reduced lifespans. RCDP1 is caused by biallelic loss-of-function variants in PEX7, which encodes a protein required for importing select enzymes into the peroxisome matrix, including those essential for ether lipid synthesis (e.g., plasmalogens) and the branched-chain fatty acid catabolism. Plasmalogen deficiency is a hallmark of RCDP1 and other peroxisomal disorders, including RCDP types 2-5 (RCDP2-5) and Zellweger spectrum disorders (ZSD). Here, we performed comprehensive metabolomic profiling of clinical samples from RCDP patients and Pex7-deficient mouse models. We identified profound …

A Comparison Of Tenecteplase To Alteplase For Treatment Of Acute Ischemic Stroke Using Epic Cosmos Database, Marco Gonzalez Castellon

Theses & Dissertations

Ischemic stroke is highly prevalent and an important cause of morbidity, mortality, and long-term disability in the in the United States. The incidence and prevalence of stroke is expected to increase in the next few years due to several factors including aging of the U. S. population, improved treatment, and socioeconomic factors. In 1996, the FDA approved rtPA for the treatment of ischemic stroke patients. Patients had a greater likelihood of recovering successfully. However, rtPA has significant limitations, such as an elevated risk of intracranial hemorrhage, administration difficulties, and limited effectiveness. In March 2025, the FDA approved the use of …

Factors Influencing The Choice Of Neurology As A Specialty Among Medical Students And Physicians In Saudi Arabia: A Cross-Sectional Study, Muhannad A. Alahmadi, Moath M. Alomairi, Aseel O. Banasir, Omar Babateen

Saudi Toxicology Journal

Neurological disorders represent a substantial global health burden and contribute to the rising demand for neurologists. In Saudi Arabia, the shortage of neurologists underscores the importance of understanding how medical students and physicians perceive neurology as a career. This study aimed to explore the level of interest in neurology and identify factors influencing specialty selection. This cross-sectional study was conducted between November and December 2024 among undergraduate medical students and medical graduates (residents, fellows, specialists, and consultants) in Saudi Arabia. First-year students and those without prior exposure to neurology were excluded. Data were collected through a structured online questionnaire distributed …

Point Of Care Ultrasound For Rapid Identification Of Central Retinal Artery Occlusion And Subsequent Vision Rescue Utilizing Intravenous Alteplase, Joseph Pepe, Karl Kasischke, Calen Hart

Florida Journal of Emergency Medicine (FJEM)

Central retinal artery occlusion (CRAO) is a rare but critical diagnosis to make in patients with acute vision loss. Cases of central retinal artery occlusion historically have a poor prognosis due to delayed presentation, lack of early identification, and limited effective treatment options. Due to these challenges, patients are often left with permanent loss of vision.

We present a case of a male patient in his late 70s with sudden onset of loss of vision to the right eye. Identification of CRAO was made utilizing point of care ultrasound (POCUS). After discussion with neurology, the patient was treated with alteplase …

Dose Adjustment Of The Anti-Seizure Medications Levetiracetam And Lamotrigine During The Postpartum Period. Schedule Plan, Safety And Efficacy, Nadejda Khmelev, Firas Fahoum, Lilach Goldstein

Department of Neurology Faculty Papers

INTRODUCTION: Lamotrigine (LTG) and Levetiracetam (LEV) are anti-seizure medications (ASMs) widely used for treatment of women with epilepsy (WWE) of childbearing age due to low teratogenic potential. Physiological changes during gestation results in enhanced clearance. Drug level monitoring and frequent dose adjustments are required to avoid decline in serum levels and compromised seizure control. Postpartum, physiological changes reverse and ASM clearance trends back to pre-pregnancy rate. Rapid metabolic changes make drug level monitoring and dose adjustments challenging. A delay in dose decrement could result in toxicity. The optimal postpartum dose reduction rate hasn't been established.

METHODS: We retrospectively examined medical …

A Nationwide Registry Study Of Surgical And Patient-Reported Outcomes Following Anterior Cervical Discectomy And Fusion: Part 2 - Cage With Versus Without Local Bone Graft, Daniel De Wilde, Victor Gabriel El-Hajj, Patrick Vigren, Victor E. Staartjes, Elias Atallah, Erik Edström, Adrian Elmi-Terander

Department of Neurosurgery Faculty Papers

BACKGROUND: Local bone grafts are commonly used as filling material in cages during anterior cervical discectomy and fusion (ACDF). Alternatively, cages without filling materials can be used. The literature comparing these approaches is limited, and their respective effects on patient-reported outcomes (PROM) have been scarcely studied. This study was conducted to compare surgical outcomes and PROMs between local bone graft-packed cages and empty cages in ACDF surgery.

METHODS: This observational study utilized data from the Swedish nationwide registry, Swespine. All adults who underwent ACDF between 2006 and 2020 were considered for inclusion. Exclusion criteria included missing baseline or outcome data. …

Functional Vs Anatomical Cortico-Striatal Connectivity In The Macaque Brain, Wei Tang, Megan E Monko, Zoe Liu, Ana M G Manea, Fernando A Ortega, Damyan Hart, Jason Zhou, Jan Zimmermann, Sarah R Heilbronner

Faculty, Staff and Students Publications

The cerebral cortex provides the main input to the striatum, constituting the first step in cortico-basal ganglia loops. Decades of careful anatomical tract-tracing research have established the exquisite topography of each cortical region's projection to the striatum in nonhuman primates. In parallel, neuroimaging research has demonstrated the relationship between cortico-striatal resting-state functional connectivity and specific cognitive, behavioral, psychiatric, and neurological states in humans. However, still unclear is the extent to which functional connectivity recapitulates the specific topographies of cortico-striatal anatomical connectivity. Here, we combined datasets of cortico-striatal anatomical and functional connectivity in macaques to determine the degree of overlap between …

Comprehensive Analysis Platform To Understand, Remedy, And Eliminate Amyotrophic Lateral Sclerosis (Capture Als): Study Protocol For A Canadian Multicenter, Multimodal, Longitudinal Observational Study, Natalie Saunders, Claire Magnussen, Hyungmo Kang, Mathieu Blais, Harpreet Bhinder, Gerald Pfeffer, Shelagh K. Genuis, Liziane Bouvier, Tanushka Anand, Tania M. Bubela

Office of the Provost

Background: The marked heterogeneity of Amyotrophic Lateral Sclerosis (ALS) combined with a lack of biomarkers are key contributing factors to the lack of disease-modifying treatments. The Comprehensive Analysis Platform to Understand Remedy and Eliminate ALS (CAPTURE ALS) is a Canadian platform designed to create the most comprehensive picture of people living with ALS with the objective of facilitating ALS research initiatives worldwide.
Objectives: The main aims of CAPTURE ALS include: (1) to characterize ALS and healthy controls with biosamples and data in order to provide the most comprehensive picture of individuals living with ALS to date; (2) to create a …

Super-Fast, Super-Early: High-Frequency Oscillations May Be A Prelude To Alzheimer's Dementia In Down Syndrome, Manuel Silva-Pérez, Jeannie Chin

Faculty, Staff and Students Publications

Alzheimer's disease (AD) dementia has near full penetrance in adults with Down syndrome (DS) and is strongly linked to late-onset myoclonic epilepsy in Down syndrome (LOMEDS). However, promising biomarkers of epileptogenicity, such as high-frequency oscillations (HFOs >250 Hz), have not been studied. This study is the first to use wideband polysomnography in DS to investigate if HFOs occurred and preceded AD dementia and LOMEDS. Methods: Wideband (0.1 to 500 Hz, 2048 Hz) polysomnography was performed using the international 10–20 system. HFOs were automatically detected during slow-wave sleep, followed by manual review. Results: Fourteen individuals with DS and five age-matched euploid …

A Distinct Pp2a Subunit Regulates Local Protein Phosphorylation At The Axon Initial Segment, Andrew P Anderson, Sanghyun Kim, Allison J Melton, Xiaoyun Ding, Wei Zhang, Alexander B Saltzman, Anna Malovannaya, Matthew N Rasband, Yudong Gao

Faculty, Staff and Students Publications

Protein phosphorylation plays a crucial role in regulating the cytoskeletal and membrane proteins at the axon initial segment (AIS). However, our knowledge of AIS-specific kinases and phosphatases is very limited. Here, we report the identification of a protein phosphatase 2A (PP2A) B55 regulatory subunit enriched at the AIS in mice: Ppp2r2c. Our results demonstrate that PP2A-B55 subunits exhibit substantial heterogeneity in their subcellular localization and function. Notably, the Ppp2r2c subunit is selectively concentrated at the AIS, and this enrichment is driven by its unique structure. Utilizing a microelectrode array system (MEA), we show that Ppp2r2c modulates neuronal activity during in …

The Perspectives And Experiences Of Prospective Parents Declining Diagnostic Prenatal Genome Sequencing In Continuing Pregnancies With Fetal Structural Anomalies, Lisa S Weingarten, Allison Rosenbaum, Jessica De Voest, Stephanie Galloway, Jessica L Giordano, Samantha Stover, Lauren E Westerfield, Grant Bonesteele, Kelly L Gilmore, Leandra Tolusso, Beatrix Wong, A Theresa Wittman, Daniel T Swarr, Nancy Leslie, Anthony Johnson, Ignatia B Van Den Veyver, Neeta L Vora, Rebecca G Clifton, Aaron B Caughey, Ronald J Wapner, Wendy K Chung

Duncan NRI Faculty and Staff Publications

Objective: This study evaluates an understudied perspective: the experiences of prospective parents who decline prenatal genome sequencing (pGS) for continuing pregnancies with fetal structural anomalies.

Method: We recruited a total cohort of 300 parents of 150 pregnancies who declined pGS, including 33 individuals who underwent an invasive procedure. These parents were invited to participate in a semi-structured interview between 1 and 15 months post-partum. We used Thematic Analysis to code and analyze interviews.

Results: We interviewed 22 parents of 16 pregnancies. Reasons for declining testing included risks of invasive procedures (n = 19, 86%), lack of prenatally actionable findings (n …

Targeting Tet3 Suppresses Group 3 Medulloblastoma Stemness And Progression Via Impairing Hypomethylation Of Otx2 Super-Enhancer, Xuan Chen, Ziwei Wang, Yan Song, Yu Su, Yahui Zhao, Jiankang Li, Wei Wang, Jiao Zhang, Craig Daniels, Xiaochong Wu, Olivier Saulnier, Yanan Wang, Fei Liu, Kaiwen Deng, Dongming Han, Zijia Liu, Meiyu Li, Liam D Hendrikse, Alexandra Rasnitsyn, Evan Y Wang, Dongyang Wang, Zhaoyang Feng, Yanong Li, Zitong Zhao, Hongyu Yuan, Youliang Sun, Yifei Jiang, Yanfeng Shi, Tao Yang, Xueling Qi, Yong Hou, Chunde Li, Yong-Qiang Liu, Yu Tian, Shuaicheng Li, Xiaoguang Qiu, Michael D Taylor, Guo Liang Li, Tao Jiang, Hailong Liu

Faculty, Staff and Students Publications

Medulloblastoma (MB), particularly Group_3 (G3-MB), remains the most aggressive subgroup due to strong stemness and therapeutic resistance. Through genome-wide DNA methylation and transcriptomic analysis of human MB samples, we identify enhancer hypomethylation as a key feature sustaining G3-MB stemness and tumor progression. Notably, hypomethylation of the Otx2 super-enhancer (SE) is a prognostic marker and potential therapeutic target for G3-MB patients. We demonstrate that disrupting Otx2 SE activity effectively reduces tumor growth in vivo, highlighting its critical role in G3-MB maintenance. TET3, recruited by OTX2, demethylates the Otx2 SE, promoting chromatin opening and sustaining tumor proliferation and stemness. To translate these …

A Double-Edged Sword: Ethical And Psychological Implications Of Apoe Genotype Disclosure Across The Lifespan, Diego Iacono

Department of Neurology Faculty Papers

The apolipoprotein E (APOE) gene is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD), with the ε4 allele increasing risk and decreasing the average age of onset. While APOE genotyping is primarily used in research or clinical settings for patients with memory concerns, interest in disclosing APOE status to asymptomatic individuals—particularly during early adulthood—is growing. This trend is fueled by the rise of direct-to-consumer genetic testing and emerging prevention-focused clinical trials. However, ethical debates remain unresolved about the potential harms of early disclosure, including anxiety, stigma, and misunderstanding of probabilistic risk. Conversely, some argue that knowledge of APOE …

Spectrum Of Headache Disorders In Pakistan: A Multicenter Study, Amina Javed, Shafaq Saleem, Safia Awan, Saba Zaidi, Manzoor Lakhair, Fahad Saleem, Waleed Shahzad, Ahmed Wali

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objective:

Headache disorders represent some of the most prevalent neurological conditions worldwide. While community-based

studies provide general prevalence, data on their diagnostic spectrum in specialized clinical settings in Pakistan remain

limited. The objective of this multicenter study was to evaluate the demographic distribution and spectrum of headache

disorders among patients presenting to neurological services across Pakistan.

Methods:

This cross-sectional observational study was carried out at 39 neurology centers across Pakistan, from August 2017

to December 2019. Diagnosis was made using International Classification of Headache Disorders, 3rd edition

(ICHD-3). Demographic details, and headache subtypes were compared across gender and …

Electrophysiological Localization And Prognostic Indicators In Radial Neuropathy Presenting As Wrist Drop: A Three-Year Retrospective Observational Study, Assad Ullah Khan, Muhammad Farooq, Saad Ali, Sadiq Ali Shah

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objective:

Radial neuropathy is a common cause of wrist drop, and accurate lesion localization is essential for appropriate

management and prognostication. The objective of this study was to analyze electrophysiological localization patterns

of radial nerve lesions presenting as wrist drop and to assess whether earlier referral for electrophysiological evaluation

was associated with recovery outcomes.

Methods:

This retrospective observational study was conducted at Lady Reading Hospital Peshawar, a tertiary care setting, over

a three-year period (January 2022–December 2024). Adult patients with wrist drop and electrophysiological confirmed

radial neuropathy were included. Nerve conduction studies and needle electromyography were used to …

Visual And Brainstem Evoked Potentials: A Retrospective Cross-Sectional Audit From A Tertiary Care Hospital In Pakistan, Zuha Amin Alvi, Sundus Mehtab Shafee, Zahra Talib Shah, Dureshahwar Kanwar, Sajid Hameed

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objective:

Visual and brainstem auditory evoked potentials (VEPs and BAEPs) are standard techniques for evaluating the integrity of visual and auditory pathways respectively. The objective of our audit study was to assess demographic trends,referral indications, and electrophysiological outcomes of patients undergoing VEP and BAEP testing in a tertiary care neurophysiology laboratory in Pakistan.

Methods:

A retrospective, cross-sectional audit was conducted of 952 patient records (VEP, n=219; BAEP, n=733) over a three-year period from neurophysiology laboratory of Aga Khan University Hospital. Demographic characteristics,clinical referral indications, and electrophysiological findings were collected. Standard ACNS guidelines were used for all recordings. Statistical …