Neurology Commons^™

Hippocampal-Prefrontal Functional Neural Networks In A Rat Model Of Fragile X Syndrome Are Poorly Organized With Limited Resiliency, Mohamed Ouardouz, Patrick Jasinski, Mohamed Khalife, J. Matthew Mahoney, Amanda E. Hernan, Rod C. Scott

Department of Neurology Faculty Papers

Fragile X Syndrome (FXS) is a common cause of autism spectrum symptoms. The genetic mutation results in multiple molecular alterations that are hypothesized to negatively impact neural circuit development although the nature of any functional neural dynamic consequences remain unclear. Therefore, the characteristics of hippocampal-prefrontal (H-PFC) network dysfunction were investigated in a rat model of FXS. FMR-KO and control rats underwent behavioral tests assessing sociability, memory, and anxiety to validate and replicate previously recognized deficits. Single-unit electrophysiology in the H-PFC circuit during exploration was used to measure patterns of action potential firing that were then compared between groups using generalized …

Characterising Acute And Chronic Care Needs: Insights From The Global Burden Of Disease Study 2019, A. A. Asadi-Pooya

Department of Neurology Faculty Papers

Chronic care manages long-term, progressive conditions, while acute care addresses short-term conditions. Chronic conditions increasingly strain health systems, which are often unprepared for these demands. This study examines the burden of conditions requiring acute versus chronic care, including sequelae. Conditions and sequelae from the Global Burden of Diseases Study 2019 were classified into acute or chronic care categories. Data were analysed by age, sex, and socio-demographic index, presenting total numbers and contributions to burden metrics such as Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLD), and Years of Life Lost (YLL). Approximately 68% of DALYs were attributed to chronic …

Comparison Of Outcomes Among Neurovascular Patients Managed In Dedicated Neurological Intensive Care Units Vs. General Intensive Care Units, Joanna Roy, Basel Musmar, Nassos Tziviskos, Saarang Patel, Roberto Deleon, Ashley Thommana, Shady Mina, Stavropoula Tjoumakaris, Michael Gooch, Robert Rosenwasswer, Pascal Jabbour

Department of Neurosurgery Faculty Papers

Background/Objectives: Patients with neurovascular conditions often require multidisciplinary management to optimize recovery. Our systematic review identifies literature comparing outcomes among neurovascular patients managed at dedicated neurological intensive care units (ICUs) compared to general ICUs. Methods: PubMed was searched to identify articles that reported outcomes among patients managed at dedicated neurological ICUs versus general ICUs. Articles that reported outcomes among patients with neurovascular conditions were included. Articles that reported outcomes among patients managed at stroke units were excluded. The Newcastle Ottawa Scale (NOS) was used to assess for risk of bias across individual studies. Results: After a title and abstract screen …

Difference In Clinical Presentation And Surgical Outcomes In Pediatric And Adult Patients With Chiari Malformation Type 1: A Single Center Retrospective Study, Erik Öhlén, Victor Gabriel El-Hajj, Victor E. Staartjes, Pascal Jabbour, Erik Edström, Adrian Elmi-Terander

Department of Neurosurgery Faculty Papers

INTRODUCTION: Chiari malformation type 1 (CM1) is a common congenital disorder affecting both children and adults. Although pediatric and adult CM1 patients share many characteristics, the differences between the groups are not fully described.

METHOD: A comparative analysis was made of two previously defined cohorts of adult and pediatric non-syndromic CM1, surgically treated at the study center. Clinical outcomes were assessed using the Chicago Chiari outcome scale (CCOS) and radiological outcomes were measured as change in cerebellar tonsil and syringomyelia status.

RESULTS: A total of 209 patients (73 pediatric, 136 adults) were included, with median ages of 11 and 33 …

Epilepsy Diagnosis When The Routine Ancillary Tests Are Normal, Boulenouar Mesraoua, Bassel Abou-Khalil, Bernhard Schuknecht, Hassan Al Hail, Musab Ali, Majd A. Abualrob, Khaled Zammar, Ali A. Asadi-Pooya

Department of Neurology Faculty Papers

Background/Objectives: In a patient suspected of having epilepsy, routine EEG primarily contributes to the recording of interictal epileptiform discharges (IEDs). Similarly, magnetic resonance imaging (MRI) has become the gold standard imaging technique for identifying epileptogenic structural brain abnormalities. Various EEG and MRI tools to improve epilepsy diagnosis will be presented. Methods: When the initial EEG fails to record IEDs, various EEG measures that can improve EEG performance are presented; a comprehensive epilepsy-targeted MRI protocol to identify, localize, and characterize an epileptogenic lesion will also be described. Results: Studies show that the initial routine EEG fails to record IEDs in approximately …

Sleep Deprivation Increases Mortality Risk Among Older Adults With Epilepsy, Srikanta Banerjee, Jagdish Khubchandani, Stanley Nkemjika

Department of Psychiatry and Human Behavior Faculty Papers

Introduction: Among U.S. adults, over 3 million report a history of epilepsy, accounting for nearly 1.2% of the population. Sleep deprivation is a well-known risk factor for increased likelihood, intensity, and length of seizures. However, the long-term impact of sleep deprivation on people with epilepsy is not well explored. The purpose of this study was to assess mortality risk among individuals with epilepsy based on sleep duration.

Methods: Data from the 2008–2018 National Health Interview Survey (NHIS) were linked with mortality data from the National Death Index (NDI) for US adults aged 65 years and older. Survival curves showed the …

Statins And Middle Meningeal Artery Embolization: A Literature Review In The Treatment Of Chronic Subdural Hematoma, Basel Musmar, Joanna M. Roy, Samantha Spellicy, Stavropoula I. Tjoumakaris, Michael R. Gooch, Robert H. Rosenwasswer, David Hasan, Pascal Jabbour

Department of Neurosurgery Faculty Papers

Chronic subdural hematoma (cSDH) presents a multifaceted challenge in contemporary neurological practice, necessitating innovative therapeutic strategies. This comprehensive review explores the convergence of two promising interventions: statins and middle meningeal artery (MMA) Embolization. With cSDH incidence on the rise, particularly among the aging population and those with long-term anticoagulant usage, the traditional surgical avenues face limitations in recurrence rates and associated risk factors. Statins, heralded for their anti-inflammatory, vasculogenic, and angiogenic properties, are emerging as potential allies in cSDH management. Concurrently, MMA embolization offers a nuanced approach to target the neomembrane's blood supply, with evidence supporting its efficacy and safety. …

Spetzler-Martin Grade Iv Cerebral Arteriovenous Malformations In Adult Patients: A Propensity-Score Matched Analysis Of Resection And Stereotactic Radiosurgery, Salem M. Tos, Mahmoud Osama, Georgios Mantziaris, Bardia Hajikarimloo, Nimer Adeeb, Sandeep Kandregula, Hamza Adel Salim, Basel Musmar, Christopher Ogilvy, Douglas Kondziolka, Adam A. Dmytriw, Kareem El Naamani, Ahmed Abdelsalam, Deepak Kumbhare, Sanjeev Gummadi, Cagdas Ataoglu, Muhammed Amir Essibayi, Ufuk Erginoglu, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Howard Riina, Arwin Rezai, Johannes Pöppe, Rajeev D. Sen, Louis J. Kim, Omar Alwakaa, Christoph J. Griessenauer, Pascal Jabbour, Stavropoula I. Tjoumakaris, Jan-Karl Burkhardt, Robert M. Starke, Mustafa K. Baskaya, Laligam N. Sekhar, Michael R. Levitt, David J. Altschul, Neil Haranhalli, Malia Mcavoy, Abdallah Abushehab, Assala Aslan, Christian Swaid, Adib Abla, Christopher Stapleton, Matthew Koch, Visish M. Srinivasan, Peng R. Chen, Spiros Blackburn, Omar Choudhri, Bryan Pukenas, Darren Orbach, Edward Smith, Markus Möhlenbruch, Ali Alaraj, Ali Aziz-Sultan, Aman B. Patel, Amey Savardekar, Hugo H. Cuellar, Kathleen Dlouhy, Tarek El Ahmadieh, Michael Lawton

Department of Neurosurgery Faculty Papers

Spetzler-Martin Grade IV arteriovenous malformations (AVMs) are challenging due to high risks associated with both treatment and natural progression. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) in high-grade AVMs, analyzing obliteration rates, complications, and functional outcomes. A retrospective cohort of 96 patients treated with either microsurgical resection (33 patients) or SRS (63 patients) was analyzed. Propensity-score matching was employed to account for baseline variables such as AVM size (cm), preoperative embolization and rupture status. Primary endpoints included AVM obliteration, complication rates, and modified Rankin Scale (mRS) scores. After matching, 31 patients per group were analyzed. …

Management Of Parkinson's Disease Psychosis: First-Line Antipsychotic Selection And Rationale For Continuing, Combining, Or Switching, Stuart H. Isaacson, Henry Nasrallah, Rajesh Pahwa, Gustavo Alva, Daniel Kremens, Stephen M. Stahl

Department of Neurology Faculty Papers

INTRODUCTION: The past decade has seen a paradigm shift in the evaluation and management of Parkinson's disease psychosis (PDP), with the first approval of an antipsychotic in the US in 2016. An evidence-based review by the Movement Disorder Society found pimavanserin and clozapine to be clinically useful, (low-dose) quetiapine to be possibly useful, and all other antipsychotics to be avoided due to motor worsening. Clozapine and quetiapine use can be limited by provoking Parkinson's disease (PD) nonmotor symptoms of somnolence and hypotension. Quetiapine may also be limited by its risk in cognitive impairment. Pimavanserin is not associated with these symptoms. …

Stingers—A Review Of Current Understanding And Management, Teleale Gebeyehu, James Harrop, Stavros Matsoukas, Alexander Vaccaro

Department of Neurosurgery Faculty Papers

Abstract: A stinger is the transient sensory and motor loss of one upper extremity caused by a stretch or compression injury to the brachial plexus or the exiting cervical nerve roots. Athletes from contact sports like American football, rugby, wrestling, and horseback riding are most affected. Given today’s competitive athletic culture and recent advancements in sports medicine, understanding the clinical, diagnostic, and therapeutic aspects of stingers is crucial. Thus, this narrative review highlights current knowledge of pathology, clinical features, diagnostic modalities, radiologic measurements, management, rehabilitation, and return-to-play protocols. Recent and prominent English publications on adult athletes revealed that the brachial …

Prediction Of Persistent Incomplete Occlusion Of Intracranial Aneurysms Treated With Woven Endobridge Device, Muhammed Amir Essibayi, Mohamed Sobhi Jabal, Hasan Jamil, Hamza Adel Salim, Basel Musmar, Nimer Adeeb, Mahmoud Dibas, Nicole M. Cancelliere, Jose Danilo Bengzon, Oktay Algin, Sherief Ghozy, Sovann V. Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Markus Möhlenbruch, Michael Kral, Charlotte Chung, Mohamed M. Salem, Ivan Lylyk, Paul M. Foreman, Hamza Shaikh, Vedran Župančić, Muhammad U. Hafeez, Joshua Catapano, Muhammad Waqas, Muhammed Said Besler, Yasin Celal Gunes, James D. Rabinov, Julian Maingard, Clemens M. Schirmer, Mariangela Piano, Anna L. Kühn, Caterina Michelozzi, Robert M. Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie T. Nawka, Marios Psychogios, Christian Ulfert, Bryan Pukenas, Jan-Karl Burkhardt, Thien Huynh, Juan Carlos Martinez-Gutierrez, Sunil A. Sheth, Diana Slawski, Rabih Tawk, Benjamin Pulli, Boris Lubicz, Pietro Panni, Ajit S. Puri, Guglielmo Pero, Eytan Raz, Christoph J. Griessenauer, Hamed Asadi, Adnan Siddiqui, Elad I. Levy, Deepak Khatri, Neil Haranhalli, Andrew F. Ducruet, Felipe C. Albuquerque, Robert W. Regenhardt, Christopher J. Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Stavropoula I. Tjoumakaris, Hugo H. Cuellar-Saenz, Pascal Jabbour, Frédéric Clarençon, Nicola Limbucci, Vitor Mendes Pereira, Aman B. Patel, David J. Altschul, Adam A. Dmytriw, Worldwideweb Consortium Collaborators

Department of Neurosurgery Faculty Papers

While the Woven EndoBridge (WEB) device has transformed the treatment of wide-neck intracranial aneurysms, incomplete occlusion remains a significant challenge requiring better understanding of contributing factors. A retrospective analysis was conducted on multicenter data from patients who underwent WEB device treatment for intracranial aneurysms between January 2011 and December 2022. Using machine learning models, Cox regression, and time-stratified analyses, we evaluated factors associated with persistent incomplete occlusion, defined as non-improving Raymond-Roy Occlusion Classification grade 2 or 3 at final follow-up. Among 813 patients (607 with < 24 months follow-up, 206 with ≥ 24 months), machine learning analysis identified aneurysm height, Acom location, neck diameter, and pretreatment mRS as predictors of persistent incomplete occlusion. On Cox regression. larger aneurysm neck diameter (HR 1.13, 95% CI 1.01-1.27, p = 0.027) and height (HR 1.14, 95% CI 1.02-1.26, p = 0.017), and radial …

What Single-Cell Rna Sequencing Taught Us About Mgmt Expression In Glioblastoma, Iyad Alnahhas, Mehak Majid Khan, Wenyin Shi

Department of Neurology Faculty Papers

Background.

The promoter methylation status of O-6-methylguanine-DNA methyltransferase (MGMTp) is an important prognostic marker in GBM. Previous studies showed that the expression of MGMT based on immunohistochemistry did not correlate with survival. This is partly because nontumor cells express MGMT. Single-cell sequencing assesses gene expression in tumor cells specifically.

Methods.

We used publicly available data from 3 recent single-cell/nucleus sequencing GBM studies that included MGMTp methylation status data for patients to evaluate MGMT expression at the single-cell level.

Results.

In the CPTAC study, a median of 0.82% and 5.7% of tumor cells expressed MGMT in the …

Seizure Freedom And Reducing The Risk Of Sudden Unexpected Death In Patients With Focal Epilepsy Treated With Cenobamate Or Other Antiseizure Medications, Michael R. Sperling, William E. Rosenfeld, John Watson, Pavel Klein

Department of Neurology Faculty Papers

People with epilepsy who have uncontrolled seizures are at increased risk of all-cause mortality, injuries, comorbidities, mood and psychosocial disorders, and diminished quality of life. For those with focal epilepsy, focal to bilateral tonic-clonic seizures (FBTCS) pose the greatest risk for sudden unexpected death in epilepsy (SUDEP), a leading cause of premature mortality in people with epilepsy. Cenobamate is a third-generation antiseizure medication with demonstrated efficacy in controlling focal seizures, including FBTCS, in people with drug-resistant epilepsy. Treatment with cenobamate in clinical trials was associated with a reduction in all-cause mortality to a rate statistically indistinguishable from that seen in …

Editorial: Old Drugs: Confronting Recent Advancements And Challenges, Anna Wiktorowska-Owczarek, Diego Iacono, Magdalena Jasińska-Stroschein

Department of Neurology Faculty Papers

No abstract provided.

Mind Matters: How Anxiety And Depression Shape Low-Risk Prostate Cancer Active Surveillance Adherence In A Real-World Population, Zachariah Taylor, Kayla Meyer, Danielle Terrenzio, Ryan Wong, Sharon L. Larson, Stephanie Kjelstrom, Natalina Contoreggi, Laurence Belkoff, Ilia Zeltser

Jefferson Hospital Staff Papers and Presentations

PURPOSE: While the mental health impact of a prostate cancer diagnosis, including low-risk prostate cancer, is well-documented, the effect of pre-existing anxiety and/or depression on adherence to active surveillance protocols in low-risk prostate cancer patients remains unclear. This study assessed the association between prior anxiety and/or depression and active surveillance adherence in men with low-risk prostate cancer.

METHODS: We conducted a retrospective, multicenter study involving 426 men diagnosed with low-risk prostate cancer who were recommended active surveillance as the primary management strategy. Active surveillance adherence was defined by completion of both a prostate-specific antigen test and a prostate biopsy within …

Should Proximal Fixation Be At C2 Or C3-C4? An Application Of The Operative Value Index For Elective Posterior Cervical Decompression And Fusion, Advith Sarikonda, D. Mitchell Self, Danyal Quraishi, Ashmal Sami, Emily L. Isch, Steven Glener, Joshua Heller, Srinivas Prasad, Ashwini Sharan, Jack Jallo, Alex R. Vaccaro, James Harrop, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

BACKGROUND: There is clinical equipoise regarding the ideal upper instrumented vertebrae (UIV) for elective posterior cervical decompression and fusion (PCDF). Instrumentation may be performed at the axial C2 level, or at the subaxial C3/C4 vertebrae. To our knowledge, a true "value" (outcomes per dollar spent) comparison axial versus subaxial UIV for PCDF has never been performed.

METHODS: We retrospectively identified 275 long-segment (≥3-levels fused) PCDFs with available Neck Disability Index (NDI) scores at baseline and at 3 months postoperatively. C2 UIV (n = 67) was compared to C3/C4 UIV (n = 208). Time-driven activity-based costing was applied to identify the …

Are Mildly Disabled Patients Appropriate For Spine Bundles? An Application Of The Operative Value Index, Advith Sarikonda, Ashmal Sami, D. Mitchell Self, Emily Isch, Alexander Zavitsanos, Antony A. Fuleihan, Ayra Khan, Conor Dougherty, Danyal A. Quraishi, Jack Jallo, Joshua Heller, Srinivas K. Prasad, Ashwini Sharan, James Harrop, Alex R. Vaccaro, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

BACKGROUND: Many studies have evaluated the effect of preoperative disability status on functional outcomes following spine surgery. However, no research has compared the "value" (outcomes per dollar spent) of surgery for patients with different levels of diagnosis-specific disability.

METHODS: We retrospectively reviewed 429 patients who underwent neurosurgical anterior cervical discectomy and fusion. Time-driven activity-based costing was used to calculate total intraoperative costs. Neck Disability Index (NDI) scores were recorded at baseline and 3 months postsurgery. Patients were categorized into groups based on their preoperative NDI score. Our primary outcome was a novel Operative Value Index (OVI), defined as the percent …

Future Applications Of Fluorescence Lifetime Imaging Ophthalmoscopy In Neuro-Ophthalmology, Neurology, And Neurodegenerative Conditions, Daniel M. Markowitz, Elizabeth Affel, György Hajnóczky, Robert C. Sergott

Farber Institute for Neuroscience Faculty Papers

Fluorescence lifetime imaging ophthalmoscopy (FLIO) has emerged as an innovative advancement in retinal imaging, with the potential to provide in vivo non-invasive insights into the mitochondrial metabolism of the retina. Traditional retinal imaging, such as optical coherence tomography (OCT) and fundus autofluorescence (FAF) intensity imaging, focus solely on structural changes to the retina. In contrast, FLIO provides data that may reflect retinal fluorophore activity, some of which may indicate mitochondrial metabolism. This review builds upon the existing literature to describe the principles of FLIO and established uses in retinal diseases while introducing the potential for FLIO in neurodegenerative conditions.

Pre-Hospital And Post-Hospital Quality Of Care In Traumatic Spinal Column And Cord Injuries In Iran, Arman Zeinaddini-Meymand, Vali Baigi, Mohammad Mehdi Mousavi-Nasab, Sina Shool, Mohsen Sadeghi-Naini, Zahra Azadmanjir, Seyed Behnam Jazayeri, Samuel Berchi Kankam, Mohammad Dashtkoohi, Aidin Shakeri, Esmail Fakharian, Leila Kouchakinejad-Eramsadati, Habibollah Pirnejad, Homayoun Sadeghi-Bazargani, Laleh Bagheri, Yasaman Pourandish, Malihe Amiri, Ahmad Pour-Rashidi, James Harrop, Vafa Rahimi-Movaghar

Department of Neurosurgery Faculty Papers

STUDY DESIGN: A retrospective study.

OBJECTIVES: The quality of care (QoC) for spinal column/cord injury patients is a major health care concern. This study aimed to implement the QoC assessment tool (QoCAT) in the National Spinal Cord/Column Injury Registry of Iran (NSCIR-IR) to define the current state of pre- and post-hospital QoC of individuals with Traumatic Spinal Column and Spinal Cord Injuries (TSC/SCIs).

METHODS: The QoCAT, previously developed by our team to measure the QoC in patients with TSC/SCIs, was implemented in the NSCIR-IR. The pre-hospital QoC was evaluated through a retrospective analysis of NSCIR-IR registry data. Telephone interviews and …

Antiseizure Medications And Their Differing Effects On Cardiovascular Risk, Aleena Abbasi, Bassil Abbasi, Scott Mintzer, Carla Lopinto-Khoury

Department of Neurology Faculty Papers

This review discusses the differing effects of enzyme-inducing and non-inducing antiseizure medications on cardiovascular risk and their implications for the management strategies of epilepsy patients. Traditional risk markers, including low density lipoprotein, high density lipoprotein and triglycerides, can be altered by both enzyme induction and inhibition. Other markers of vascular risk, including c-reactive protein, non-high-density lipoprotein and homocysteine, are affected by antiseizure medications, although adults and children may have different responses. The overall atherosclerotic risk picture is more complex due to indirect effects such as neuroendocrine function and the metabolic syndrome. Large scale data shows an evolving understanding of cardiovascular …

Immunogenetic Studies In Patients With Gad-Positive Stiff-Person Syndrome Reveal Novel Lymphocytic Genes And Klk10 -Gene Variants, Popianna Tsiortou, Harry Alexopoulos, Konstantinos Kyriakidis, Michalis Kosmidis, Chrysanthi Barba, Sofia Akrivou, Ioannis Michalopoulos, Panagiotis Politis, Marinos Dalakas

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: The aim of this study was to identify genetic markers and immunologic characteristics of glutamic acid decarboxylase (GAD) antibody-positive patients with stiff-person syndrome (SPS).

METHODS: We conducted systemic immunogenetic studies in 11 GAD-positive patients: 8 with sporadic SPS and 3 from a three-generation family with very high GAD-ab titers but diverse symptomatology (one with GAD-epilepsy and SPS and 2 only with diabetes), by performing complete immunologic profile and whole-exome sequencing analysis.

RESULTS: Two genes expressed in immune and neuronal tissues were identified: the ORAI1 that codes for a calcium release–activated channel protein with a role in the …

Fluorescence Lifetime Imaging Ophthalmoscopy (Flio): A Novel Retinal Metabolic Biomarker For Multiple Sclerosis, Daniel Markowitz, Kylee Shivok, Elizabeth Affel, Ms, Jose S. Pulido, Md, Ms, Mba, Mph, Thomas P. Leist, Md, Phd, Gyorgy Hajnoczky, Md, Phd, Mahdi Alizadeh, Phd, Robert Sergott, Md

Farber Institute for Neuroscience Staff Papers and Presentations

Introduction

- Fluorescence lifetime imaging ophthalmoscopy (FLIO, Heidelberg Engineering, Figures 1 and 2), a novel in vivo retinal imaging biomarker, generates fluorescence decay lifetimes in 2 spectral channels corresponding to the following metabolic processes:

- Short Spectral Channel (SSC): 498 – 560 nm

• Corresponds to macular pigment, flavin adenine dinucleotide (FAD) and oxidative phosphorylation.

- Long Spectral Channel (LSC): 560 – 720nm

• Corresponds to predominantly lipofuscin and lysosomal function

- Based upon animal experimental models and clinical data, mitochondrial dysfunction has a role in the pathophysiology of both inflammatory and degenerative components of Multiple Sclerosis

Neural Signal Analysis In Chronic Stroke: Advancing Intracortical Brain-Computer Interface Design, Nabila Shawki, Alessandro Naopli, Carlos E. Vargas-Irwin, Christopher K. Thompson, John P. Donoghue, Mijail D. Serruya

Department of Medicine Faculty Papers

INTRODUCTION: Intracortical Brain-computer interfaces (iBCIs) are a promising technology to restore function after stroke. It remains unclear whether iBCIs will be able to use the signals available in the neocortex overlying stroke affecting the underlying white matter and basal ganglia.

METHODS: Here, we decoded both local field potentials (LFPs) and spikes recorded from intracortical electrode arrays in a person with chronic cerebral subcortical stroke performing various tasks with his paretic hand, with and without a powered orthosis. Analysis of these neural signals provides an opportunity to explore the electrophysiological activities of a stroke affected brain and inform the design of …

Treatment Of Small Intracranial Aneurysms Using The Smallss Scoring System: A Novel System For Decision Making, Mira Salih, Michael Young, Thomas B. Fodor, Alexander Andreev, Samuel D. Pettersson, Joanna M. Roy, Basel Musmar, Max Shutran, Phillip Taussky, Christopher S. Ogilvy

Department of Neurosurgery Faculty Papers

BACKGROUND: Treatment of unruptured intracranial aneurysms (UIA) less than 7 mm is controversial. We created a scoring system to guide decision making and validated the system utilizing over 700 cases treated with microsurgery or endovascular procedures.

METHODS: The scoring system SMALLSS included Size, (4-7 mm: 1 point, < 3.9 mm: 0 point), Multiple aneurysms (yes: 1, no: 0), Anatomic location (posterior: 1, anterior: 0), Lineage- family history of aneurysm (yes:1, no: 0), Lifetime risk (age < 65: 1, age > 65: 0), Smoking history (yes: 1, no: 0 ), Shape (irregular:1, smooth:0 ). Validation of this system was performed through retrospective review of prospectively maintained data for UIA patients treated between 2014 and 2021. We then performed an external validation of a cohort of 200 small aneurysms < 7 mm treated at a high volume cerebrovascular center.

RESULTS: A total of 1152 cases …

Mexiletine Dosing And Tolerability In Refractory Chronic Migraine: Insights From Post-Lidocaine Infusion Treatment, Lucia Liao, Hsiangkuo Yuan, Dylan Selbst, Emily Casaletto, Jiangang Liao, Clinton Lauritsen

Department of Neurology Faculty Papers

Background: Mexiletine is used as a preventive medication for refractory chronic migraine (rCM) and to prolong migraine improvement following intravenous lidocaine infusion. However, published evidence supporting its use in migraine remains limited. This retrospective study describes the dosing, treatment duration, and adverse effects of mexiletine in a group of patients with rCM following lidocaine infusion. Methods: Electronic medical records were reviewed at the Jefferson Headache Center. Baseline pain intensity and monthly headache days were collected at baseline and up to 6 office visits within 1-year post-discharge. The duration of mexiletine treatment was evaluated for up to 40 months post-discharge. Results: …

Tdp43 Negtively Regulates Tbk1-Medicated Ifn1 Production Through Irf7 Pathway In Neurodegenerative Diseases, Wenjuan Zhang, Zhen Yi, Daihe Yang, Yifan Hao, Feng Zhou, Guohua Song, Cao Huang, Yun Zhou, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mutations in the genes encoding TAR DNA-binding protein 43 (TDP43) or TANK- binding kinase 1 (TBK1) have been strongly associated with neurological disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. TDP43 is a key component of pathological protein aggregates found in more than 90% of ALS cases, while TBK1 plays a critical role in innate immune signaling and autophagy. Despite these associations, the precise molecular mechanisms linking TDP43 or TBK1 dysfunction to neurodegeneration remain poorly understood. The present study examined the impact of TDP43 on TBK1-mediated type I interferon (IFN1) production in HEK-293T cells. The findings demonstrated that co-expression …

Five-Year Outcomes Of Lenadogene Nolparvovec Gene Therapy In Leber Hereditary Optic Neuropathy, Patrick Yu-Wai-Man, Nancy Newman, Valérie Biousse, Valerio Carelli, Mark Moster, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo Sadun, Robert C Sergott, Rabih Hage, Simona Degli Esposti, Chiara La Morgia, Claudia Priglinger, Rustum Karanja, Magali Taiel, José-Alain Sahel

Department of Neurology Faculty Papers

IMPORTANCE: Limited studies have assessed the long-term benefit/risk of gene therapy for Leber hereditary optic neuropathy (LHON).

OBJECTIVE: To determine the safety and efficacy of lenadogene nolparvovec in patients with LHON due to the MT-ND4 gene variant for up to 5 years after administration.

DESIGN, SETTING, AND PARTICIPANTS: The RESCUE and REVERSE Long-Term Follow-up Study (RESTORE), conducted from 2018 to 2022, is the 5-year follow-up study of the 2 phase 3 clinical studies RESCUE (Efficacy Study of Lenadogene Nolparvovec for the Treatment of Vision Loss Up to 6 Months From Onset in LHON Due to the MT-ND4 Mutation) and REVERSE …

Recanalization Outcomes And Procedural Complications In Patients With Acute Ischemic Stroke And Covid-19 Receiving Endovascular Treatment, João Pedro Marto, Davide Strambo, George Ntaios, Thanh N. Nguyen, Pawel Wrona, Simon Escalard, Simona Marcheselli, Ossama Yassin Mansour, Blanca Fuentes, Malgorzata Dorobek, Marta Nowakowska-Kotas, Elena Oana Terecoasa, Jonathan M. Coutinho, Mariana Carvalho-Dias, Patricia Calleja, João Sargento-Freitas, Ana Paiva-Nunes, Martin Šrámek, Priyank Khandelwal, Torcato Meira, Mohamad Abdalkader, Pascal Jabbour, Martin Kovář, Oscar Ayo-Martin, Patrik Michel, Roman Herzig, Anna Członkowksa, Jelle Demeestere, Raul G. Nogueira, Alexander Salerno, Susanne Wegener, Philipp Baumgartner, Carlo W. Cereda, Giovanni Bianco, Morin Beyeler, Marcel Arnold, Emmanuel Carrera, Paolo Machi, Valerian Altersberger, Leo Bonati, Henrik Gensicke, Manuel Bolognese, Nils Peters, Stephan Wetzel, Marta Magriço, João Nuno Ramos, Rita Machado, Carolina Maia, Egídio Machado, Patrícia Ferreira, Teresa Pinho-E-Melo, André Paula, Manuel Alberto Correia, Pedro Castro, Elsa Azevedo, Luís Albuquerque, José Nuno-Alves, Joana Ferreira-Pinto, Liliana Pereira, Miguel Rodrigues, André Araújo, Marta Rodrigues, Mariana Rocha, Ângelo Pereira-Fonseca, Luís Ribeiro, Ricardo Varela, Sofia Malheiro, Manuel Cappellari, Cecilia Zivelonghi, Giulia Sajeva, Andrea Zini, Mauro Gentile, Stefano Forlivesi, Ludovica Migliaccio, Maria Sessa, Sara La Gioia, Alessandro Pezzini, Davide Sangalli, Marialuisa Zedde, Rosario Pascarella, Carlo Ferrarese, Simone Beretta, Susanna Diamanti, Ghil Schwarz, Giovanni Frisullo, Pierre Seners, Candice Sabben, Michel Piotin, Benjamin Maier, Guillaume Charbonnier, Fabrice Vuillier, Loic Legris, Pauline Cuisenier, Francesca R. Vodret, Gaultier Marnat, Jean-Sebastien Liegey, Igor Sibon, Fabian Flottmann, Gabriel Broocks, Nils-Ole Gloyer, Ferdinand O. Bohmann, Jan Hendrik Schaefer, Christian H. Nolte, Heinrich Audebert, Eberhard Siebert, Marek Sykora, Wilfried Lang, Julia Ferrari, Lukas Mayer-Suess, Michael Knoflach, Elke-Ruth Gizewski, Jeffrey Stolp, Lotte J. Stolze, Paul J. Nederkoorn, Ido Van-Den-Wijngaard, Joke De Meris, Robin Lemmen, Sylvie De Raedt, Fenne Vandervorst, Matthieu Pierre Rutgers, Antoine Guilmot, Anne Dusart, Flavio Bellante, Fernando Ostos, Guillermo Gonzalez-Ortega, Paloma Martín-Jiménez, Sebastian García-Madrona, Antonio Cruz-Culebras, Rocio Vera, Maria-Consuelo Matute, María Alonso-De-Leciñana, Ricardo Rigual, Exuperio Díez-Tejedor, Soledad Pérez-Sánchez, Joan Montaner, Fernando Díaz-Otero, Natalia Perez-De-La-Ossa, Belén Flores-Pina, Lucia Muñoz-Narbona, Angel Chamorro, Alejandro Rodríguez-Vázquez, Arturo Renú, Francisco Hernandez-Fernandez, Tomas Segura, Herbert Tejada-Meza, Daniel Sagarra-Mur, Marta Serrano-Ponz, Thant Hlaing, Isaiah See, Robert Simister, David J. Werring, Espen Saxhaug Kristoffersen, Annika Nordanstig, Katarina Jood, Alexandros Rentzos, Libor Šimu Ne, Dagmar Krajíčková, Antonín Krajina, Robert Mikulík, Martina Cviková, Jan Vinklárek, David Školoudík, Martin Roubec, Eva Hurtikova, Rostislav Hrubý, Svatopluk Ostry, Ondrej Skoda, Marek Pernicka, Lubomír Kočí, Zuzana Eichlová, Martin Jíra, Michal Panský, Pavel Mencl, Hana Paloušková, Aleš Tomek, Petr Janský, Anna Olšerová, Roman Havlíček, Petr Malý, Lukáš Trakal, Jan Fiksa, Matěj Slovák, Michał Karlińsk, Maciej Nowak, Halina Sienkiewicz-Jarosz, Anna Bochynska, Tomasz Homa, Katarzyna Sawczynska, Agnieszka Slowik, Ewa Wlodarczyk, Marcin Wiącek, Izabella Tomaszewska-Lampart, Bartosz Sieczkowski, Halina Bartosik-Psujek, Marta Bilik, Anna Bandzarewicz, Justyna Zielińska-Turek, Krystian Obara, Paweł Urbanowski, Sławomir Budrewicz, Maciej Guziński, Milena Świtońska, Iwona Rutkowska, Paulina Sobieszak-Skura, Beata Łabuz-Roszak, Aleksander Dębiec, Jacek Staszewski, Adam Stępień, Jacek Zwiernik, Grzegorz Wasilewski, Cristina Tiu, Razvan-Alexandru Radu, Anca Negrila, Bogdan Dorobat, Cristina Panea, Vlad Tiu, Simona Petrescu, Atilla Özcan-Özdemir, Mostafa Mahmoud, Hussam El-Samahy, Hazem Abdelkhalek, Jasem Al-Hashel, Ismail Ibrahim Ismail, Athari Salmeen, Abdoreza Ghoreishi, Sergiu Sabetay, Hana Gross, Piers Klein, Kareem El Naamani, Stavropoula Tjoumakaris, Rawad Abbas, Ghada-A Mohamed, Alex Chebl, Jiangyong Min, Majesta Hovingh, Jenney-P Tsai, Muhib-A Khan, Krishna Nalleballe, Sanjeeva Onteddu, Hesham-E Masoud, Mina Michael, Navreet Kaur, Laith Maali, Michael Abraham, Ivo Bach, Melody Ong, Denis Babici, Ayaz-M Khawaja, Maryam Hakemi, Kumar Rajamani, Vanessa Cano-Nigenda, Antonio Arauz, Pablo Amaya, Natalia Llanos, Akemi Arango, Miguel A. Vences, José-Domingo Barrientos, Rayllene Caetano, Rodrigo Targa, Sergio Scollo, Patrick Yalung, Shashank Nagendra, Abhijit Gaikwad, Kwon-Duk Seo

Department of Neurosurgery Faculty Papers

No abstract provided.

Atm Expression And Activation In Ataxia Telangiectasia Patients With And Without Class Switch Recombination Defects, Fereshte Salami, Tannaz Moeini Shad, Nazanin Fathi, Hanieh Mojtahedi, Marzie Esmaeili, Sepideh Shahkarami, Ladan Gol Mohammad Pour Afrakoti, Parisa Amirifar, Samaneh Delavari, Hassan Nosrati, Azadehsadat Razavi, Mohammad Reza Ranjouri, Mahsa Yousefpour, Zahra Hamidi Esfahani, Gholamreza Azizi, Mahmoudreza Ashrafi, Nima Rezaei, Reza Yazdani, Hassan Abolhassani

Department of Neurology Faculty Papers

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.

METHODS: A-T patients with defined genetic diagnoses were classified based on CSR and based on the severity of their medical complications. Isolated peripheral blood mononuclear cells from any patient were evaluated before and after exposure to 0.5 Gy ionizing radiation for one minute. Western blotting was performed to identify the expression …

Tryptophan Kynurenine Pathway-Based Imaging Agents For Brain Disorders And Oncology-From Bench To Bedside, Erik Stauff, Wenqi Xu, Heidi H. Kecskemethy, Sigrid A. Langhans, Vinay V. R. Kandula, Lauren W. Averill, Xuyi Yue

Jefferson Hospital Staff Papers and Presentations

Tryptophan (Trp)-based radiotracers have excellent potential for imaging many different types of brain pathology because of their involvement with both the serotonergic and kynurenine (KYN) pathways. However, radiotracers specific to the kynurenine metabolism pathway are limited. In addition, historically Trp-based radiopharmaceuticals were synthesized with the short-lived isotope carbon-11. A newer generation of Trp-based imaging agents using the longer half-lived and commercially available isotopes, such as fluorine-18 and iodine-124, are being developed. The newly developed amino acid-based tracers have been demonstrated to have favorable radiochemical and imaging characteristics in pre-clinical studies. However, many barriers still exist in the clinical translation of …