Nervous System Diseases Commons^™

Neuronal Activity-Dependent Gene Dysregulation In C9orf72 I3neuronal Models Of Als/Ftd Pathogenesis, Layla T. Ghaffari, Emily A. Welebob, Sarah E. Bond Newton, Ashley V. Boehringer, Kelly L. Cyliax, Piera Pasinelli, Davide Trotti, Aaron R. Haeusler

Farber Institute for Neuroscience Faculty Papers

The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9ORF72 (C9) gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE-induced pluripotent stem cell-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization or a blockade of K⁺ channels, followed by RNA sequencing, induces …

Migraine-Related Disability According To Headache Frequency Subclassifications: A Systematic Review And Meta-Analysis, Manjit Singh Matharu, Stephen Silberstein, Hsiangkuo Yuan, Deborah Edgar, Roos Colman, Todd Schwedt, Michel Lanteri-Minet, Mark Obermann

Department of Jefferson Headache Center Papers and Presentations

BackgroundThis systematic review and meta-analysis synthesized migraine-related disability outcomes according to headache frequency subclassifications, including low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM) and chronic migraine (CM).MethodsWe searched the PubMed and Cochrane Library (CENTRAL) up to 16 October 2024 for peer-reviewed non-interventional studies reporting migraine-related disability outcomes in CM and subclassifications of episodic migraine (e.g. LFEM and HFEM). Eligible studies with an HFEM subgroup were grouped by headache frequency measure (monthly migraine days [MMD] or monthly headache days [MHD]), HFEM subgroup, disability parameter and study setting. Random-effects meta-analyses were conducted on groups with three or more studies, with the results …

Neurofilament Light (Nfl) Chain Levels Predict Clinical Decline In Alzheimer’S Disease: A Systematic Review And Meta-Analysis, Kim Thomas, Paul Spin, Nikita Sir, Kevin Hou, Nicholas J. Ashton, Henrik Zetterberg, Sonya Miller, Carol Pringle, Richard G. Stefanacci, Claude M. Wischik, Serge Gauthier

College of Population Health Faculty Papers

BACKGROUND: Regulatory approval of new investigational Alzheimer's disease (AD) therapies could be accelerated if reasonably likely surrogate endpoints could be used. Neurofilament light chain (NfL) has potential utility as a prognostic biomarker of neurodegeneration in AD.

OBJECTIVE: To synthesize available evidence on the relationship between baseline NfL levels and longitudinal clinical decline.

METHODS: A systematic literature review identified 19 eligible studies, contributing 37 longitudinal statistical models evaluating the association between baseline NfL (plasma or cerebrospinal fluid [CSF]) with subsequent clinical decline based on validated clinical scales including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale, and Clinical Dementia Rating. …

Rapid Mapping Of Spinal And Supraspinal Connectome Via Self-Targeting Glucose-Based Carbon Dots, Yasin B. Seven, Elif S. Seven, Emel Kirbas Cilingir, Komal Parikh, Mehmet Aydin, Edward K. Luca, Jayakrishnan Nair, Roger M. Leblanc

Department of Physical Therapy Faculty Papers

The spinal cord is a highly dynamic network, playing significant roles in the vital functions of the brain. Disorders of the spinal cord, such as spinal cord injury and amyotrophic lateral sclerosis (ALS), are associated with neurodegeneration, often resulting in morbidity and mortality. The blood-brain barrier (BBB) poses a major challenge to imaging and therapeutic agents because less than 2% of small-molecule drugs and almost no large-molecule drugs can cross the BBB. Furthermore, spatial spectroscopy studies have shown highly heterogeneous BBB crossing with significant accumulation at the unintended brain regions. Thus, targeting systems that can cross the BBB at the …

Early Blood Pressure Targets In Acute Spinal Cord Injury: A Randomized Clinical Trial, Ruba Sajdeya, N. David Yanez, Michael Kampp, Michael D. Goodman, David Zonies, Brandon Togioka, Andrew Nunn, Robert D. Winfield, Niels D. Martin, Anirudh Kohli, Toan T. Huynh, David O. Okonkwo, Roy A. Poblete, Emily J. Gilmore, Randall M. Chesnut, Aaron E. Bunnell, Tetsu Ohnuma, Mona Hashemaghaie, Miriam M. Treggiari

Department of Surgery Faculty Papers

IMPORTANCE: Early blood pressure management is central to neurologic resuscitation of spinal cord injury; however, the role of augmented blood pressure is unclear.

OBJECTIVE: To compare the efficacy and safety of augmented vs conventional blood pressure on 6-month neurologic outcomes after acute spinal cord injury.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial took place from October 3, 2017, to July 26, 2023, and assessed patients 18 years or older with spinal cord injury followed up for 6 months at 13 large US trauma centers.

INTERVENTIONS: Patients were equally randomized to augmented (>85-90 mm Hg) or conventional ( …

Reaching International Consensus On The Definition Of Refractory Migraine Using The Delphi Method, Jennifer Robblee, Fawad A. Khan, Michael J. Marmura, Hope L. O'Brien, Lawrence D. Robbins, Marielle K. Samaha, Morris Levin, Simona Sacco, Raffaele Ornello, Stephanie J. Nahas, Heike Hesse, Annika Ehrlich, Adam S. Sprouse-Blum, Christina Sun-Edelstein, Bronwyn Jenkins, Elizabeth K, Seng, Shivang Joshi, Meredith J. Barad, Mi Ji Lee, Sheena K. Aurora, Mario Fernando Prieto Peres

Department of Neurology Faculty Papers

Aim: Despite its frequency in tertiary headache centers, the International Classification of Headache Disorders, 3rd edition (ICHD-3) does not include refractory migraine. Multiple definitions have been proposed with a recent 2020 proposal for both refractory migraine and resistant migraine by the European Headache Federation (EHF). The aim is to reach an international consensus on the definition of refractory migraine.

Methods: This study is a Delphi consensus carried out by a group of international experts in headache medicine. Following a focus group, a panel of 20 experts and one facilitator reviewed the EHF proposed criteria to build upon their definitions. The …

High Energy Consumption Characterizes Abnormal Brain State Transitions In Temporal Lobe Epilepsy, Sam S. Javidi, Qirui Zhang, Ankeeta Ankeeta, Michael R. Sperling, Joseph I. Tracy

Farber Institute for Neuroscience Faculty Papers

Temporal lobe epilepsy (TLE) patients experience shifts between non-seizing and seizing brain states, but the structural networks underlying these transitions remain undefined and poorly characterized. We detected dynamic brain states in resting-state fMRI and constructed linked structural networks utilizing multi-shell diffusion-weighted MR data. Leveraging network control theory, we interrogated the structural data for all possible brain state transitions, identifying those requiring abnormal levels of transition energy (low or high) in TLE compared to matched healthy participants (n's = 25). Results revealed three transitions requiring significantly higher energy in TLE; no abnormally low-energy transitions were observed. In HPs, transitions relied on …

Unrecognized And Unreported Concussions Among Community Rugby Players, Rachael Wittmer, Thomas A. Buckley, Charles Buz Swanik, Katelyn M. Costantini, Lisa Ryan, Ed Daly, Regan E. King, Arryana J. Daniels, Katherine J. Hunzinger

Department of Exercise Science Faculty Papers

This study examined the prevalence of intentionally unreported and potentially unrecognized concussions in community rugby players and whether nondisclosure reasons vary by sex, position, or playing history. An online survey was completed by 1037 players (41.0% female; mean age 31.6 ± 11.3 years; 10.1 ± 8.1 years playing) who reported diagnosed, unreported, and unrecognized concussions. Poisson regression models estimated prevalence ratios (PRs), and Fisher's exact tests compared reasons for nondisclosure. The diagnosed, unreported, and unrecognized concussion rates were 66.5%, 32.4%, and 42.2%, respectively. Players with diagnosed concussions had a 7.2-fold higher prevalence of nondisclosure and a 2.3-fold higher prevalence of …

Clinical Outcomes Following Endoscopic Carpal Tunnel Release With The Arthrex Nanoscopic Release System-A Single Surgeon Experience, Sina Ramtin, Asif M. Ilyas

Department of Orthopaedic Surgery Faculty Papers

PURPOSE: Endoscopic carpal tunnel release (ECTR) is a minimally invasive alternative to open release, offering faster recovery and reduced postoperative discomfort. The Arthrex NanoScopic ECTR system, a novel single-use device using chip-on-tip digital imaging and designed for use under local anesthesia without arthroscopic equipment, may further streamline care and expand surgical access.

METHODS: A retrospective review was conducted of the first 50 consecutive ECTR procedures performed using the Arthrex NanoScopic system by a single hand fellowship-trained hand surgeon. All procedures were completed under wide-awake local anesthesia no tourniquet technique in an outpatient surgical center. Outcomes included operative times, adverse events, …

Immediate-Use Rescue Medication And The Epilepsy Monitoring Unit: Experiences From An Expert Panel, Evelyn K. Shih, Brin E. Freund, Michael R. Sperling, Danielle A. Becker, Proleta Datta, Sandra Dewar, Edward Faught, Tracy Glauser, R. Edward Hogan, Randa Jarrar, Andres M. Kanner, David King-Stephens, Rebecca E. Matthews, Patricia Penovich, M. Scott Perry, Eric B. Segal, Joseph Sirven, John M. Stern, James W. Wheless, Enrique Carrazana, Adrian L. Rabinowicz, William O. Tatum

Department of Neurology Faculty Papers

BACKGROUND: People with epilepsy (PWE) may experience seizure clusters, broadly defined as ≥2 seizures that occur in close proximity. In epilepsy monitoring units (EMUs), seizure clusters can spontaneously occur during long-term videoelectroencephalogram monitoring (LTVEM) or as a result of antiseizure medication dose adjustments. In this survey, we examined the experiences and practices of expert clinicians with seizure clusters in EMUs.

METHODS: A 55-item survey was sent to members of an Epilepsy Education Council who are epilepsy experts. Items described experiences, treatment practices, and negative outcomes with seizure clusters in EMUs.

RESULTS: Of the 15 experts (aged 43-77 y), 14 are …

Comparative Outcomes Of Coil Embolization And Surgical Clipping In Elderly Patients With Subarachnoid Hemorrhage: A Systematic Review And Meta-Analysis, Yohanna Idsabella Rossi, Gabriel Bolner, Jonathan Costa Dall'acqua, Fabiana Dolovitsch De Oliveira, Lucas V. Zacaria, Taís L. Denicol, Michel Frudit, Natália Vasconcellos De Oliveira Souza

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Elderly patients with subarachnoid hemorrhage (SAH) face a disproportionately high burden of morbidity and mortality. While endovascular coiling is often favored in this population, direct comparisons with surgical clipping are limited. We conducted a meta-analysis to compare outcomes of clipping versus coiling in SAH patients aged ≥ 60 years.

METHODS: A systematic search of PubMed, Embase, and Cochrane databases identified studies comparing the two treatments in this age group. The primary outcome was a composite of unfavorable outcomes (modified Rankin Scale [mRS] > 2 and mortality). Secondary outcomes included mortality, favorable outcome (mRS 0-2), rebleeding, and hospital length …

Vascular Risk Factors And 1-Year Cognitive Change Among Individuals With Traumatic Brain Injury, Andrea L. C. Schneider, Katherine Hunzinger, Benjamin L. Brett, Danielle K Sandsmark, Sonia Jain, Xiaoying Sun, Raquel C. Gardner, Geoffrey T. Manley, Ramon Diaz-Arrastia, Lindsay D. Nelson, Patrick Belton, Shawn Eagle, Shankar Gopinath, Ramesh Grandhi, C. Dirk Keene, Vijay Krishnamoorthy, Christine Mac Donald, Michael Mccrea, Randall Merchant, Pratik Mukherjee, Laura B. Ngwenya, David Okonkwo, Claudia Robertson, David Schnyer, Sabrina R. Taylor, John K. Yue, Ross Zafonte

Department of Exercise Science Faculty Papers

IMPORTANCE: Traumatic brain injury (TBI) and vascular risk factors are associated with cognitive impairment, but it is unknown if individuals with vascular risk factors experience worse cognitive outcomes after TBI.

OBJECTIVE: To evaluate cognitive function among patients with TBI with vs without comorbid preinjury vascular risk factors.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study examined individuals with TBI enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Study between February 26, 2014, and August 8, 2018, with a 1-year follow-up. Analyses were conducted February 26, 2024, to May 29, 2025.

EXPOSURES: Vascular risk factors (ie, hypertension, diabetes, …

Chronic Cluster Headache Is A Rare Disease: Implications For Diagnosis, Treatment And Public Health, Hsiangkuo Yuan, Jan Hoffmann, Elena Ruiz De La Torre, Michael J. Marmura, Mario F. P. Peres

Department of Jefferson Headache Center Papers and Presentations

Cluster headache (CH) is a rare and painful primary headache disorder characterized by severe unilateral pain and cranial autonomic symptoms. This perspective examines the epidemiological evidence supporting the classification of chronic cluster headache (CCH) as a rare disease, noting a prevalence of CH of approximately 124 per 100,000 individuals, with only 3.5-13.7% manifesting CCH. This prevalence meets criteria established by both the US Food and Drug Administration and European Medicines Agency for rare disease designation. The rarity of CCH creates substantial clinical and research challenges, including prolonged diagnostic delays, limited research funding and a dearth of approved treatments. The economic …

Epigenetic Profiling Of Cell-Free Dna In Cerebrospinal Fluid: A Novel Biomarker Approach For Metabolic Brain Diseases, Kyle Sporn, Rahul Kumar, Kiran Marla, Puja Ravi, Swapna Vaja, Phani Paladugu, Nasif Zaman, Alireza Tavakkoli

SKMC Student Presentations and Publications

Due to their clinical heterogeneity, nonspecific symptoms, and the limitations of existing biomarkers and imaging modalities, metabolic brain diseases (MBDs), such as mitochondrial encephalopathies, lysosomal storage disorders, and glucose metabolism syndromes, pose significant diagnostic challenges. This review examines the growing potential of cell-free DNA (cfDNA) derived from cerebrospinal fluid (CSF) epigenetic profiling as a dynamic, cell-type-specific, minimally invasive biomarker approach for MBD diagnosis and monitoring. We review important technological platforms and their use in identifying CNS-specific DNA methylation patterns indicative of neuronal injury, neuroinflammation, and metabolic reprogramming, including cfMeDIP-seq, enzymatic methyl sequencing (EM-seq), and targeted bisulfite sequencing. By synthesizing current …

Uncharted Territory: The First Case Of Cardiac Myxoma In A Patient With Nf2, Muhammad Sabri, Zinya Talukder, Naila Ijaz, Joseph Neri

Rothman Institute Papers

BACKGROUND: Cardiac myxoma is a benign tumor, typically originating in the left atrium, and is often linked to Carney complex. In our literature review, there are no case reports of cardiac myxoma in patients with neurofibromatosis type 2 (NF2).

CASE SUMMARY: A 60-year-old man presented with dizziness and was found to have meningioma and vestibular schwannoma, consistent with NF2. Cardiac myxoma was incidentally diagnosed through echocardiography and confirmed by cardiac magnetic resonance imaging and tissue pathology. The mass was surgically resected. The patient was offered genetic testing; however, he decided to not undergo further testing.

DISCUSSION: NF2 is an inherited …

Amaurosis Fugax Progressing To Retinal Artery Occlusion With Anterior Migration Of A Retrobulbar Embolus On Orbital Color Doppler Imaging, Ari H. August, Turner D. Wibbelsman, Erik Massenzio, Sarah E. Thornton, Danijel J. Peričić

Wills Eye Hospital Papers

PURPOSE: Orbital color Doppler imaging (CDI) is useful in the evaluation of sudden monocular vision loss, providing information on etiology which may guide management. We present two cases of amaurosis fugax progressing to retinal artery occlusion (RAO) associated with migration of a hyperechoic particle within the central retinal artery (CRA) and altered vascular dynamics found on CDI.

OBSERVATIONS: Both patients presented with amaurosis fugax, and CDI revealed a hyperechoic particle 2.8 mm from the optic nerve head in both patients. Patient 1 was found to have severe aortic stenosis and a thoracic aortic aneurysm and was managed with dual antiplatelet …

Risk Factors For In-Stent Stenosis After Flow-Diverter Implantation For Intracranial Aneurysm: A Single Center Analysis Of 161 Consecutive Patients, Rabab Alshahrani, Spyridon Karadimas, Mohammed Ali Alvi, Patrick Joseph Nicholson, Timo Krings

Department of Neurosurgery Faculty Papers

INTRODUCTION: Flow diverters (FD) are used for the treatment of intracranial aneurysms, by redirecting flow and serving as a scaffold for endothelial coverage of the aneurysm ostium. However, in-stent stenosis has been observed in some patients treated with these devices, the cause of which and the epidemiology remaining elusive. In the current study we aimed to elucidate potential factors leading to higher degree of in-stent stenosis including gender, location, and type of FD.

METHODS: The authors queried their institutional Electronic Health Record (EHR) for all patients undergoing FD for intracranial saccular aneurysms. We excluded cases where an FD was performed …

Predictors Of Final Visual Outcome In Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy, Robert C Sergott, Valerio Carelli, Nancy Newman, Valérie Biousse, Patrick Yu-Wai-Man, Catherine Vignal-Clermont, Constant Josse, Magali Taiel, José-Alain Sahel, Piero Barboni

Wills Eye Hospital Papers

PURPOSE: This exploratory analysis aimed to identify predictive factors of final best-corrected visual acuity (BCVA) in patients with Leber hereditary optic neuropathy (LHON) harboring the m.11778G>A mutation who received lenadogene nolparvovec gene therapy.

METHODS: The following covariates were individually evaluated as possible factors associated with improved final BCVA: age, gender, timing of treatment, baseline BCVA value, and baseline optical coherence tomography (OCT) parameters. Univariate analyses were performed from three phase 3 studies (RESCUE, REVERSE, and REFLECT), using BCVA at 1.5 years post-treatment as the dependent variable.

RESULTS: In 113 eyes treated at least 6 months after disease onset, the …

Multiple Subcortical And Subcortico-Cortico Dynamic Network Reconfigurations Characterize Focal-To-Bilateral Tonic-Clonic Seizures, Shilpi Modi, A. Ankeeta, Walter Hinds, Michael R. Sperling, Xiaosong He, Joseph I. Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE) is the most common focal epilepsy, with focal to bilateral tonic-clonic seizures (FBTCS+) a more severe form of the disorder. Evidence has underscored the critical role of the thalamus, mesial temporal region, basal ganglia and cerebellum, along with the cortex, in the propagation, termination, and modulation of seizure activity. We examined time variant patterns of interaction within and between 7 cortical and 4 subcortical systems in 55 healthy controls and 56 patients with TLE (n = 40 with FBTCS+ and 15 without), isolating those patterns most distinctive of FBTCS+ utilizing tools from dynamic network neuroscience on …

Stress And Seizures: The October 7th Experience, Alon Doron, Firas Fahoum, Lilach Goldstein

Department of Neurology Faculty Papers

OBJECTIVE: Stress is a frequently self-reported seizure trigger in patients with epilepsy (PWE), with studies regarding this issue having conflicting results. On October 7th, 2023, a large-scale military invasion accompanied by massive rocket launches against Israel, including Tel Aviv, occurred, providing an opportunity to investigate the role of acute stress in provoking seizures.

METHODS: All adults who presented to the emergency department (ED) of Tel Aviv Sourasky Medical Center between January 1st, 2017, and February 29th, 2024, and were diagnosed with seizures were included. Data were collected using MDClone, a data acquisition tool. The overall seizure-related ED admissions were compared …

Brivaracetam For Spinal Cord Injury-Related Neuropathic Pain: Results Of A Pilot Double-Blinded, Randomized, Placebo-Controlled Clinical Trial, Leslie R. Morse, Ricardo A. Battaglino, Nguyen Nguyen, Brian Devries, Abigail Welch, Ana Lucia Battaglino, Clas Linnman, Michael Stillman, Robert Wudlick, Joda Glossner, Grant Anderton, Richard Goldstein, Scott P. Falci

Department of Medicine Faculty Papers

OBJECTIVE: Assess feasibility, safety, and tolerability of 3 months of oral brivaracetam for severe (9-10/10) spinal cord injury-related neuropathic pain.

METHODS: We conducted a multisite pilot study where adults were randomized to 3 months of brivaracetam (100 mg BID) or placebo. Pain was assessed via the Brief Pain Inventory, the International Spinal Cord Injury Pain Basic Dataset (version 2.0), and a daily pain diary.

RESULTS: We enrolled 24 participants across 2 sites and 14 participants were included in the final analysis (n = 8 placebo, n = 6 brivaracetam). The drug was tolerated with expected, nonserious side effects (nausea if …

Decompression With Intradural Dissection For The Chiari Malformation Type I: Toward Eliminating Wound Complications, Anna Lin, Lindsey Asti, Marissa Carroll, Jeffrey Campbell, Jospeh Piatt

Department of Neuroscience Faculty Papers

BACKGROUND: There is continuing conversation about surgical technique in the management of the Chiari malformation. Popular options include osseous decompression alone, decompression with dural splitting, and decompression with intradural dissection (DID) and duraplasty. Wound complications after intradural dissection are a persistent problem. The current study of an institutional series examines wound complication rates after intradural dissection without dural closure.

METHODS: A retrospective single-institution chart review was performed for patients < 21 years with Chari malformation type I who underwent DID without dural closure and had at least 6 months of follow-up. Bone removal corresponded to the area of attachment of the rectus capitis posterior minor muscles together with laminectomy of the atlas. The trapezius and semispinalis capitis muscles were retracted but were not separated from the occiput.

RESULTS: A total of 76 patients were treated from May 2010 through May 2024. Thirty-eight (50.0%) patients had syringomyelia. The median age at surgery was 9 years (interquartile range [IQR] 4-13), …

Cenobamate Use In Pregnancy: A Case Report, Tiara Paul, Maromi Nei

Department of Neurology Faculty Papers

No abstract provided.

Imaging Hallmarks Of Idiopathic Intracranial Hypertension And Insights Into Pathogenesis, Albalooshy Basimah, Scott Faro, Hsiangkuo Yuan, Kiran Talekar, Prabath Mondel, Enchao Qiu, Joga Chaganti

Department of Radiology Faculty Papers

Idiopathic Intracranial hypertension (IIH), also referred to as pseudotumor cerebri, is a term used to describe increased intracranial pressure in the absence of a known identifiable secondary cause. Despite advancements of neuroimaging techniques, imaging of the pathological underpinnings in the diagnosis of IIH has been limited. Although the causation of IIH has been ascribed to increased Cerebrospinal Fluid production and disordered drainage through the dural sinuses, new evidence shows that the glymphatic system which is an alternate pathway of drainage is likely to play a pivotal role. In this review, we address the pathophysiological underpinnings in the causation of IIH …

Optimal Diagnostic Strategies For Concussion-Related Vision Disorders: A Review, Iniya K. Adhan, Kammi B. Gunton

Wills Eye Hospital Papers

Concussions are a mild form of traumatic brain injury (TBI) that is typically self-limited and transient with a high prevalence within our communities. Due to the vast visual network interconnectivity, visual symptoms secondary to a concussion occur about 90% of the time. A gold standard to confirm concussion acutely has not been well established. Visual function testing based on symptoms remains the standard of care in off-site evaluation for diagnosis of oculomotor dysfunction. This review covers the current diagnostic strategies for vision based disorders post-concussion for sideline testing, off-site testing, and research driven testing.

Impaired Dnajb2 Response To Heat Shock In Fibroblasts From A Neuropathy Patient With Dnajb2/Hsj1 Mutation: Cystamine As A Potential Therapeutic Intervention, Raj K. Pradhan, Nikolas G. Kinney, Brigid K. Jensen, Hristelina Ilieva

Farber Institute for Neuroscience Faculty Papers

Background and Objectives: Neuropathy is a debilitating disorder characterized by peripheral nerve dysfunction and damage to sensory, motor, and autonomic neurons and their axons. While homozygous mutations in DNAJB2/HSJ1 have been linked to early-onset neuropathy, a heterozygous DNAJB2 c.823+6C>T was discovered in an adult patient with severe sensory–motor polyneuropathy. This mutation is predicted to affect both isoforms of the protein. DNAJB2 (HSP40), a key member of the heat shock protein family, plays a critical role in cellular protection and stress, including response to heat shock. DNAJB2 traffics unfolded proteins to another heat shock protein, HSP70, and activates its ATPase …

Reduced Vns Settings Paradoxically Decreases Seizure Burden In A Patient Following Resolution Of Sleep Disordered Breathing, Austin Sponaugle, Rebecca Stainman, Christopher M. Carosella

Abington Jefferson Health Papers

Vagus nerve stimulation (VNS) can be a highly effective treatment option for patients with drug resistant epilepsy. Notably, VNS has demonstrated side effects including a unique form of sleep disordered breathing known as vagus nerve stimulator associated sleep disordered breathing (VaS). However, the ways in which VaS interacts with seizure frequency is unknown. We report a case of a 28-year-old woman who presented to our department with complaints of worsening sleep quality 3 years following VNS implantation. Upon polysomnographic (PSG) evaluation, it was discovered that she suffered from VaS. The patient’s VNS output current was then down titrated during a …

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 …

Environmental Exposures And Familial Background Alter The Induction Of Neuropathology And Inflammation After Sars-Cov-2 Infection, Debotri Chatterjee, Drishya Kurup, Richard Jay Smeyne

Department of Neuroscience Faculty Papers

Post-infection sequela of several viruses have been linked with Parkinson's disease (PD). Here, we investigated whether mice infected with SARS-CoV-2 alone or in combination with two putative Parkinsonian toxins, MPTP and paraquat, increased the susceptibility to develop Parkinsonian pathology. We also examined if G2019S LRRK2 mice had any change in sensitivity to SARS-CoV-2 as well as if vaccination against this virus altered any neuropathology. Infection with WA-1/2020 or Omicron B1.1.529 strains sensitized both WT and G2019S LRRK2 mice to the neuropathological effects of a subtoxic exposure to MPTP, but not paraquat. These neuropathologies were rescued in WT mice vaccinated with …

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 …