Nervous System Diseases Commons^™

A Genome-Wide Association Meta-Analysis Of All-Cause And Vascular Dementia, Mega Vascular Cognitive Impairment And Dementia (Megavcid) Consortium

Faculty, Staff and Students Publications

INTRODUCTION: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.

METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors.

RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability …

Management Targeted Genetic Evaluation Of An Idiopathic Neuropathy Cohort Through Attrv Amyloidosis Screening, Kristy A. Fisher, Santiago Diaz, Jeffrey Gelblum, Charles Brock, Niraja Suresh, Meghan Towne

HCA Healthcare Journal of Medicine

Background

While the reported prevalence of polyneuropathies is 1%-3%, the incidence of hereditary transthyretin amyloidosis in the United States is estimated to be 1 in 100 000 individuals. Polyneuropathies are known to be difficult to treat and lead to significant morbidity. The aim of pain management is symptomatic treatment, with varying approaches to progression prevention being based on the causative pathophysiology.

We assessed the prevalence of hereditary amyloid transthyretin variant (ATTRv) amyloidosis, a progressive autosomal dominant multisystem disease caused by the abnormal formation and extracellular deposition of transthyretin protein fibrils in various tissues, in an idiopathic polyneuropathy population by using …

Clinical Features And Disease Progression In Older Individuals With Rett Syndrome, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Cary Fu, Robin C Ryther, Steven A Skinner, David N Lieberman, Timothy Feyma, Arthur Beisang, Peter Heydemann, Sarika U Peters, Amitha Ananth, Alan K Percy

Faculty, Staff and Students Publications

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in MECP2 associated with milder severity, and that clinical features would not be static in older individuals. To address these hypotheses, we compared the distribution of MECP2 variants and clinical severity between younger individuals with Classic RTT (under 30 years old) and older individuals (over 30 years old). Contrary to expectation, enrichment of a severe MECP2 variant (R106W) was observed in the older cohort. Overall severity was not different …

Trends In Central Nervous System-Active Polypharmacy Among People With Multiple Sclerosis, Hayden Naizer, Joseph Wozny, Trudy Millard Krause, Ethan Huson, Leorah Freeman

Faculty, Staff and Student Publications

BACKGROUND: People with multiple sclerosis (pwMS) are at risk of concurrently using multiple central nervous system (CNS)-active drugs, yet the prevalence of CNS-active polypharmacy remains unmeasured in pwMS.

OBJECTIVE: The objective is to measure the prevalence of CNS-active polypharmacy in pwMS.

METHODS: This serial, cross-sectional study measured CNS-active polypharmacy in people with MS in the United States from 2008 to 2021 using insurance claims data. CNS-active polypharmacy was defined as the concurrent prescription of ⩾3 CNS-active drugs for >30 continuous days. CNS-active drugs included antidepressants, antiepileptics, antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants.

RESULTS: The …

Self-Harm In Female Youth With Undiagnosed Adhd: Implementing American Academy Of Pediatrics Screening Guidelines, Roselie M. Woodard

Dissertations

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. If undiagnosed or untreated, ADHD can lead to severe psychosocial issues such as academic failure, substance abuse, unplanned pregnancy, and incarceration. The financial burden in the U.S. from diagnostic errors creates an immense, rising fiscal impact. Early diagnosis and management are crucial to prevent these complications.

Females with ADHD, particularly those with the inattentive subtype, often face diagnostic challenges due to symptom masking and over-compensation. This results in poorer cognitive functioning and self-esteem compared to males with ADHD. ADHD is linked to autonomic nervous …

Apomorphine Titration With And Without Anti-Emetic Pretreatment In Patients With Parkinson’S Disease Experiencing Off Episodes: A Modified Delphi Panel, Stuart H. Isaacson, Richard Dewey, Robert A. Hauser, Daniel Kremens, Rajeev Kumar, Mark Lew, William Ondo, Fernando Pagan, Kelly E. Lyons, Rajesh Pahwa

Department of Neurology Faculty Papers

INTRODUCTION: In the United States (US), prophylactic treatment with the antiemetic trimethobenzamide has been used before initiating apomorphine therapy. However, US trimethobenzamide stores have been depleted, leaving uncertainty regarding whether antiemetic pretreatment is needed.

METHODS: This modified Delphi panel aimed to inform circumstances when apomorphine is initiated without antiemetic pretreatment. During Round 1, a panel of 9 US movement disorder specialists rated the appropriateness of prescribing apomorphine therapy with and without antiemetic pretreatment across 192 patient scenarios and were able to review their scores in relation to other scores. During the Round 2, consensus was defined for each scenario as …

Magnetic Resonance Imaging Signs Of Idiopathic Intracranial Hypertension, Dagmar Beier, Johanne Juhl Korsbæk, Gabriel Bsteh, Stefan Macher, Wolfgang Marik, Berthold Pemp, Hsiangkuo Yuan, Areeba Nisar, Lisbeth Høgedal, Laleh Dehghani Molander, Snorre Malm Hagen, Christoph Patrick Beier, Simon Bang Kristensen, Rigmor Højland Jensen

Department of Neurology Faculty Papers

IMPORTANCE: The magnetic resonance imaging (MRI) criteria currently used to diagnose idiopathic intracranial hypertension (IIH) are based on expert opinion and have limited accuracy. Additional neuroimaging signs have been proposed and used with contradictory results; thus, prospective evidence is needed to improve diagnostic accuracy.

OBJECTIVE: To provide evidence-based, accurate MRI signs for IIH diagnosis.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted from January 2018 to May 2021 with 3 validation cohorts at 2 Danish headache centers and with 3 independent international cohorts. Consecutive patients with suspected IIH were enrolled. Eligibility required the clinical suspicion of IIH, age …

Subpial Resection Of Epileptogenic Tubers: Operative Nuances And Lessons Learned, Nisha Giridharan, Collin W English, Marcus Wong, Howard L Weiner

Faculty, Staff and Students Publications

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder. Tubers of the central nervous system are a hallmark of the disorder and often cause epilepsy. Many TSC patients fail to achieve seizure control with medication alone. Several case series have demonstrated high seizure freedom rates after resective surgery. However, the technique for the resection of epileptogenic tubers has largely been unreported. Here the authors present 2 cases to illustrate their multistage approach for localizing and resecting the seizure onset zone in patients with TSC. At their institution, they have excellent seizure outcomes and a low complication rate with this …

Feasibility Of Achieving Nutritional Adequacy In Critically Ill Children With Critical Neurological Illnesses (Cnis)?-A Quaternary Hospital Experience, Marwa Mansour, Nicole Knebusch, Jennifer Daughtry, Thomas P Fogarty, Fong Wilson Lam, Renan A Orellana, Yi-Chen Lai, Jennifer Erklauer, Jorge A Coss-Bu

Faculty, Staff and Students Publications

The literature on the nutritional needs and outcomes of critically ill children is scarce, especially on those with critical neurological illnesses (CNIs). Current evidence shows a lower mortality in patients who achieve two-thirds of their nutritional needs during the first week of pediatric intensive care unit (PICU) admission. We hypothesized that achieving 60% of the recommended dietary intake during the first week of a PICU stay is not feasible in patients with CNI. We designed an observational retrospective cohort study where we included all index admissions to the PICU in our institution of children (1 month to 18 years) with …

Perturbations In Risk/Reward Decision Making And Frontal Cortical Catecholamine Regulation Induced By Mild Traumatic Brain Injury, Christopher P Knapp, Eleni Papadopoulos, Jessica A Loweth, Ramesh Raghupathi, Stan B Floresco, Barry D Waterhouse, Rachel L Navarra

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers. Aberrant PFC catecholamine activity has been documented following TBI and may underlie TBI-induced risky behavior. The present study characterized the effects of rmTBI on risk/reward decision making behavior and catecholamine transmitter regulatory proteins within the PFC. Rats were exposed to sham, single (smTBI), or three closed-head controlled cortical impact (CH-CCI) injuries and …

Glioblastoma Disrupts Cortical Network Activity At Multiple Spatial And Temporal Scales, Jochen Meyer, Kwanha Yu, Estefania Luna-Figueroa, Benjamin Deneen, Jeffrey Noebels

Faculty, Staff and Students Publications

The emergence of glioblastoma in cortical tissue initiates early and persistent neural hyperexcitability with signs ranging from mild cognitive impairment to convulsive seizures. The influence of peritumoral synaptic density, expansion dynamics, and spatial contours of excess glutamate upon higher order neuronal network modularity is unknown. We combined cellular and widefield imaging of calcium and glutamate fluorescent reporters in two glioblastoma mouse models with distinct synaptic microenvironments and infiltration profiles. Functional metrics of neural ensembles are dysregulated during tumor invasion depending on the stage of malignant progression and tumor cell proximity. Neural activity is differentially modulated during periods of accelerated and …

Beyond Vertigo: Vestibular, Aural, And Perceptual Symptoms In Vestibular Migraine, Claire E.J. Ceriani

Department of Jefferson Headache Center Papers and Presentations

PURPOSE: To review the vestibular, aural, and perceptual symptoms of vestibular migraine (VM) that may present alongside vertigo.

RECENT FINDINGS: Increased research attention to the wide spectrum of symptoms presenting in VM patients has improved understanding of this disorder, with recent identification of five different VM phenotypes. Research into the clinical overlap between VM and other chronic vestibular syndromes such as persistent postural-perceptual dizziness and mal-de-debarquement syndrome reveals a range of vestibular symptoms and hints at pathophysiological connections between migraine and vestibular dysfunction. Studies of migraine treatment for hearing loss suggest patients presenting with aural symptoms may have an underlying …

Sustained Response To Atogepant In Episodic Migraine: Post Hoc Analyses Of A 12-Week Randomized Trial And A 52-Week Long-Term Safety Trial, Richard Lipton, Stephanie J. Nahas, Patricia Pozo-Rosich, Tanya Bilchik, Peter Mcallister, Michelle Finnegan, Yingyi Liu, Natty Chalermpalanupap, Brett Dabruzzo, David Dodick

Department of Neurology Faculty Papers

BACKGROUND: Atogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine in adults. These analyses evaluated the proportions of clinical trial participants who experienced sustained responses to atogepant over 12 or 52 weeks of treatment.

METHODS: These were post hoc analyses of ADVANCE, a 12-week, double-blind, randomized trial of atogepant 10, 30, and 60 mg once daily vs. placebo for the preventive treatment of episodic migraine, and a separate open-label long-term safety (LTS) trial of atogepant 60 mg once daily over 52 weeks. The 60 mg dose of atogepant was used to detect safety …

Speech, Voice, And Language Outcomes Following Deep Brain Stimulation: A Systematic Review, Fatemeh Tabari, Joel I. Berger, Oliver Flouty, Brian Copeland, Jeremy D. Greenlee, Karim Johari

School of Medicine Faculty Publications

Background Deep brain stimulation (DBS) reliably ameliorates cardinal motor symptoms in Parkinson’s disease (PD) and essential tremor (ET). However, the effects of DBS on speech, voice and language have been inconsistent and have not been examined comprehensively in a single study. Objective We conducted a systematic analysis of literature by reviewing studies that examined the effects of DBS on speech, voice and language in PD and ET. Methods A total of 675 publications were retrieved from PubMed, Embase, CINHAL, Web of Science, Cochrane Library and Scopus databases. Based on our selection criteria, 90 papers were included in our analysis. The …

A Stroke Or Not A Stroke? A Case Of Chronic Hemiplegic Migraines, Bum J. Kim, Matthew Orap, Bret Farrow-Cypel, Naseer Ahmed

Rowan-Virtua Research Day

Hemiplegic migraine (HM) is a rare subtype of migraine with both familial and sporadic patterns. These migraines present episodically with reversible attacks of unilateral motor weakness. Patients may experience visual changes, sensory loss, impaired level of consciousness, ataxia, and speech changes. Symptoms can last from hours to days and can mimic acute stroke.

The patient is a 45-year-old male with a past medical history of hypertension and possible cerebral vascular accident use who presents to the emergency department complaining of left extremity numbness and weakness. Neuroimaging showed no acute findings and CT angiogram showed no large vessel occlusion. Tenecteplase was …

Lower Extremity Weakness In The Setting Of Covid Myositis, Christopher Dellmyer, Frank Wheeler

Rowan-Virtua Research Day

Bilateral lower extremity weakness has numerable causes including stroke, peripheral neuropathy, deconditioning, Guillain-Barre, Multiple Sclerosis, anterior cord syndrome, trauma, spinal epidural abscess and many more. It is imperative however, that we investigate and understand more rare causes of lower extremity weakness. Here we present the case of a 74-year-old female presented to the ED with a complaint of lower extremity weakness due to Covid myositis causing significant bilateral lower extremity weakness.

A Case Of Hhv-6 Viral Meningitis, Mohammad A. Rattu, Wayne Tamaska

Rowan-Virtua Research Day

Meningitis is the inflammation of the meninges and associated with abnormal cell count in the cerebrospinal fluid (CSF). The lack of bacterial growth in cultures, most commonly referred to as aseptic meningitis, is frequently caused by viruses [2]. Viruses have become more common as the prevalence of bacterial meningitis has decreased secondary to vaccination use, with viral meningitis being the most common form among countries. Viral meningitis will present with fever, headache, photophobia, neck stiffness and nausea and vomiting. Younger children however may not show any signs of meningeal irritation. Viral meningitis is usually self-limiting and with good prognosis; however, …

Applications Of Deep Learning With Detecting Intracranial Aneurysms On Ct Angiograms: A Literature Review, Christian Fang, Emily Wang

Rowan-Virtua Research Day

INTRODUCTION

Deep learning is a method of artificial intelligence involving progressively layered neural networks to extrapolate patterns from data to provide predictions. Moreover, given the arduous nature required for examining CT scans for intracranial aneurysms, discovering ways to expedite this process is beneficial. The use of deep learning to evaluate CT angiograms for intracranial aneurysms has been sparsely studied. This literature review aims to determine the accuracy and reliability of deep learning to analyze CT angiograms in patients suspected to have intracranial aneurysms.

METHODS

A qualitative review of literature using PubMed, SCOPUS, and EMBASE was conducted. Inclusion criteria comprised articles …

A Preliminary Report On The Role Of Lipoxin A4 In Reinstating The Blood-Brain Barrier Integrity In A Rodent Model Of Acute Inflammation With Impaired Cerebrovasculature, Minjal Patel, Shruti Varshney, Ananya Nethikunta, George G. Godsey, Mary C. Kosciuk, Ana Rodriguez, Bernd Spur, Kingsley Yin, Randel L. Swanson, Venkat Venkataraman, Robert G. Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: The blood-brain barrier (BBB) is responsible for maintaining brain homeostasis and ultimately proper neuronal function. Disruption of the BBB, leading to increased BBB permeability, has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and traumatic brain injury (TBI). Lipoxins (LXs) are a class of arachidonate-derived eicosanoids, which are a class of specialized pro-resolving lipid mediators (SPMs). SPMs are known to inhibit immune response through inhibition of cellular infiltration, downregulation of pro-inflammatory mediators and upregulation of anti-inflammatory mediators. Hence, LXs are recognized as “breaking signals” in the inflammatory process. One form of LXs, Lipoxin A4 (LXA4) …

Pituitary Adenoma Presenting As Cranial Nerve Iii Palsy And Hemifacial Pain, Yoona Choe, Justin George, Matthew Boyle, Peter Maduka

Rowan-Virtua Research Day

Pituitary adenomas are common neoplasms arising from the pituitary adenohypophyseal cell. They can be classified by cell type, size and as nonfunctioning or functioning based on the secretion of pituitary hormones. Of these, approximately 48% are macroadenomas (>10 mm) and approximately 53% are prolactinomas. For how common these adenomas are, only 1 of 1100 persons manifest clinical symptoms¹ rendering detection and clinical management challenging.

Non-functioning adenomas are slow growing like most pituitary adenomas and are usually detected due to their mass effect on neighboring structures.² The majority of the reported symptoms as a results of these mass …

Overcoming Disparities In The Treatment Of Alzheimer’S Disease, Christian Gamboa, Tribhuvan Lanka, Elaine Flowers, Nayarith Lopez

Rowan-Virtua Research Day

Background: Deaths due to Alzheimer’s have been increasing at an exponential rate for the last 24 years, with an astounding 145% increase between the years 2000-2024. Early detection is key to slowing down the rate of decline. Unfortunately, Latino and African American individuals delay seeking care, which predisposes them to worse outcomes. To date, socioeconomic limitations are the main factors leading to delayed care in Latino and African American communities. A service project was developed with the aim of addressing limitations that result in delays to seeking care within Latino and African American communities.

Methods: A systematic review of available …

Gut Microbiome And Nutrition Interplay In Regulating And Improving Autism Spectrum Disorder Related Social Symptoms, Irenonsen Juliet Eigbe, Christian Moya Gamboa, Jana Gjini, Jaydeep Mukherjee, Susrut Dube

Rowan-Virtua Research Day

The composition of the gut microbiome has been shown to play a role in the onset of neurological disorders, including Autism Spectrum Disorder(ASD). A small variety of recent research articles identify a possible link between onset and severity of ASD related behaviors and the composition of the gut microbiome. The purpose of this review is to identify gaps in the current understanding of the role that nutrition plays in changing the gut microbiome and subsequently altering the onset and severity of behavioral phenotypes in children with ASD. Inclusion criteria comprises peer-reviewed publications relating to children with autism. Exclusion criteria consists …

Identifying The Relationship Between Post-Concussion Mental Health And Athletic Status: Is It The Same For All Demographics?, Mary Lorraine Zsolway, Jamie Shoop

Rowan-Virtua Research Day

Purpose: The purpose of this study is to investigate whether athletic status was linked to fewer symptoms of anxiety and depression post-concussion, as well as to explore whether the impact of athletic status on mental health varied by demographics (i.e. age, sex, race, insurance status). The results of this study may assist in identifying at-risk individuals early to help prioritize those who may benefit from early referral to mental health resources.

Introduction: Mental health concerns post-concussion are relatively common, with roughly 1 in 3 individuals experiencing these symptoms. It has been previously shown that youth who participate in …

Effect Of Dosage On Severity Of Dysphagia In A Toxicological Rat Model Of Parkinson's Disease, Shivam Patel, Taylor Good, Nicholas Zanghi, Francois Gould

Rowan-Virtua Research Day

Parkinson’s Disease (PD) is a prevalent and devastating neurodegenerative disorder that causes progressively worsening motor symptoms affecting locomotor and oropharyngeal function. There is limited research in animal models on swallowing dysfunction in PD. To examine how neurodegeneration in PD produces progressive impairment in the oropharyngeal and locomotor processes, rotenone, a type II mitochondrial inhibitor, was injected into Lewis rat models to reproduce a parkinsonian phenotype. We hypothesized that the animal models injected with the rotenone will exhibit both oropharyngeal dysfunction and locomotor deficiency with an increased deficit that correlates with prolonged treatment. We utilized 18 rats receiving either 2.75 mg/kg …

Moving On Up: A Case Study Of Hiv And Covid-Induced Guillain-Barre Syndrome, Victoria Wong Murray, Rebecca Chae, Isobel Moyer, Cindy Hou

Rowan-Virtua Research Day

COVID and HIV are both common diseases, with COVID affecting an estimated 775 million and HIV affecting 39 million people worldwide. Guillain-Barre is a rare but feared complication of immune stimulation in which the body generates autoantibodies against gangliosides, found in the nodes of Ranvier, in the myelin, and in the ganglia; causing ascending paralysis.

A mid-30s man with HIV maintained on Genvoya presented to the Jefferson Health New Jersey Early Intervention Program clinic with fatigue, fever, cough, and congestion and tested positive for SARS-CoV-2 on the following day. Two weeks later, he presented to the emergency department complaining of …

The Impact Of Vitamin Supplementation (D, B12, B9) On Behaviors Associated With Autism Spectrum Disorder, Rohan Mehra

Rowan-Virtua Research Day

Background: One in 36 children in the United States are diagnosed with Autism Spectrum Disorder (ASD). Although heritability of the condition ranges from 40 to 80%, other factors such as vitamin levels, may have a significant impact on the risk of development. These vitamins include D, B12, and B9.

Purpose: To assess the impact vitamin supplementation has on behaviors associated with ASD, and to determine which specific aspects of ASD may be improved with vitamin supplementation.

Methods: A literature review was performed. The search was utilized PubMed, JSTOR and Web of Science. Keyword strings included: “Vitamin D B12 B9 folate …

Analyzing The Effectiveness Of Transcutaneous Auricular Vagus Nerve Stimulation On Parkinson’S Disease Related Gait Function: A Systematic Review And Meta-Analysis, Sami Dakhel, Jonathan Elias, Alexander King

Rowan-Virtua Research Day

Background: Those suffering from Parkinson’s Disease often experience a shuffling gait, alongside many other symptoms, due to the degradation of dopaminergic neurons in the substantia nigra. Transcutaneous auricular vagus nerve stimulation (taVNS) operates by non-invasively applying an electrical current to the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear. We sought to determine if taVNS would serve as a non-invasive alternative to addressing Parkinson’s related gait dysfunction.

Purpose: This systematic review and meta-analysis analyzes the effectiveness of taVNS on the reduction of gait dysfunction caused by Parkinson’s Disease.

Methods: The systematic review …

Case Report: What’S That Smell? Olfactory Seizures, Devin Hoover, Neelesh Parikh, James A. Espinosa, Alan Lucerna

Rowan-Virtua Research Day

We report a case of a 64-year-old male who presented with transient episodes of near syncope followed by a noxious odor and was diagnosed with olfactory seizures. The differential diagnosis for near syncope is broad. This case demonstrates that unusual olfactory symptoms can lead to a diagnosis of seizure disorder in the emergency department.

Spontaneous Intracranial Hemorrhage In A 29-Year-Old Male: A Case Report, Md Fateha, Caroline Nguyen, Michael A. Morris

Rowan-Virtua Research Day

Spontaneous intracranial hemorrhage is rare, especially in a young patient population. Signs and symptoms of intracranial hemorrhage include facial droop, vision loss, motor deficits with extraocular movements, deficits with tongue movement, weakness in the arms or legs, sensation loss, and mental status change. This is a case report of a 29-year-old male with no past medical history who presented for a spontaneous intracranial hemorrhage. This patient's only neurologic deficit was the loss of visual field on the left inferior quadrant of his field of vision. The patient obtained a CT head non-contrast which showed 21 mm acute right occipital hemorrhage …

Case Report: Varicella Zoster Virus Encephalitis Presenting With Monochorea, Chetna Thawani, Frank Wheeler

Rowan-Virtua Research Day

Meningoencephalitis is a broad range of symptoms as a sequela of inflammation of the CNS system. It is a diagnosis that is often missed, especially in atypical presentations. We describe a case of HSV encephalitis that presented to the ER afebrile with atypical arm movements, most similar to a monochorea, and discuss other cases in the literature of atypical presentations of this disease.