Nervous System Diseases Commons^™

The Role Of Osteopontin And Its Gene On Glucocorticoid Response In Myasthenia Gravis., Yanchen Xie, Hai-Feng Li, Liang Sun, Linda L Kusner, Shuhui Wang, Yunxiao Meng, Xu Zhang, Yu Hong, Xiang Gao, Yao Li, Henry J Kaminski

Neurology Faculty Publications

Biomarkers that assess treatment response for patients with the autoimmune disorder, myasthenia gravis (MG), have not been evaluated to a significant extent. We hypothesized the pro-inflammatory cytokine, osteopontin (OPN), may be associated with variability of response to glucocorticoids (GCs) in patients with MG. A cohort of 250 MG patients treated with standardized protocol of GCs was recruited, and plasma OPN and polymorphisms of its gene, secreted phosphoprotein 1 (SPP1), were evaluated. Mean OPN levels were higher in patients compared to healthy controls. Carriers of rs11728697*T allele (allele definition: one of two or more alternative forms of a gene) were more …

Distinct Neural Bases Of Disruptive Behavior And Autism Symptom Severity In Boys With Autism Spectrum Disorder., Y.J. Daniel Yang, Denis G Sukhodolsky, Jiedi Lei, Eran Dayan, Kevin A. Pelphrey, Pamela Ventola

Pediatrics Faculty Publications

BACKGROUND: Disruptive behavior in autism spectrum disorder (ASD) is an important clinical problem, but its neural basis remains poorly understood. The current research aims to better understand the neural underpinnings of disruptive behavior in ASD, while addressing whether the neural basis is shared with or separable from that of core ASD symptoms.

METHODS: Participants consisted of 48 male children and adolescents: 31 ASD (7 had high disruptive behavior) and 17 typically developing (TD) controls, well-matched on sex, age, and IQ. For ASD participants, autism symptom severity, disruptive behavior, anxiety symptoms, and ADHD symptoms were measured. All participants were scanned while …

Reliability And Validity Of The Hd-Pro-Triadtm, A Health-Related Quality Of Life Measure Designed To Assess The Symptom Triad Of Huntington's Disease., Nicholas R Boileau, Julie C Stout, Janes S Paulsen, David Cella, Michael K Mccormack, Martha A Nance, Samuel Frank, Jin-Shei Lai, Noelle E Carlozzi

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Huntington's disease (HD), is a neurodegenerative disorder that is associated with cognitive, behavioral, and motor impairments that diminish health related quality of life (HRQOL). The HD-PRO-TRIADTM is a quality of life measure that assesses health concerns specific to individuals with HD. Preliminary psychometric characterization was limited to a convenience sample of HD participants who completed measures at home so clinician-ratings were unavailable.

OBJECTIVES: The current study evaluates the reliability and validity of the HD-PRO-TRIADTM in a well-characterized sample of individuals with HD.

METHODS: Four-hundred and eighty-two individuals with HD (n = 192 prodromal, n = 193 early, and n …

Resting State Functional Network Disruptions In A Kainic Acid Model Of Temporal Lobe Epilepsy., Ravnoor Singh Gill, Seyed M Mirsattari, L Stan Leung

Physiology and Pharmacology Publications

We studied the graph topological properties of brain networks derived from resting-state functional magnetic resonance imaging in a kainic acid induced model of temporal lobe epilepsy (TLE) in rats. Functional connectivity was determined by temporal correlation of the resting-state Blood Oxygen Level Dependent (BOLD) signals between two brain regions during 1.5% and 2% isoflurane, and analyzed as networks in epileptic and control rats. Graph theoretical analysis revealed a significant increase in functional connectivity between brain areas in epileptic than control rats, and the connected brain areas could be categorized as a limbic network and a default mode network (DMN). The …

“Whatever It Takes To Beat Parkinson’S”: A Controversial Approach For Symptom Relief, Sondra M. Deskins

WRIT: Journal of First-Year Writing

It is known that there is no cure for Parkinson's disease. So, physicians who treat Parkinson's patients must decide what is the best treatment option for the patients symptoms to improve their quality of life. Currently, there are pharmaceutical options for treatment, but they include adverse side effects. What if there were a way to treat patients for the side effects as well as improve the patient's symptoms? The recent commotion around the legalization of marijuana, both recreational and medicinal, has caused interest among patients and physicians. One must decide if the benefits of using marijuana as a form of …

Neurobehavioral Function In Adults Recovering Consciousness After Severe Traumatic Brain Injury: A Scoping Review, Jennifer Weaver, Ann Guernon, Trudy Mallinson, Theresa Louise-Bender Pape, Thomas Harrod

Clinical Research and Leadership Faculty Posters and Presentations

This scoping review aims to report the findings of current literature examining the assessment of neurobehavioral function and recovery along the continuum of disorders of consciousness (DOC) from coma to full consciousness.

•This study is designed to capture the range of constructs researchers have used to measure NBF during recovery of consciousness.

•The research question for this review was: “What constructs are most frequently used to assess neurobehavioral function in adults recovering consciousness after severe TBI?”

Unmasking Of Myoclonus By Lacosamide In Generalized Epilepsy, Daniel Birnbaum, Mohamad Z. Koubeissi

Neurology Faculty Publications

Lacosamide is a new-generation antiseizure medication that is approved for use as an adjunctive treatment and monotherapy in focal epilepsy. Its use in generalized epilepsy, however, has not been adequately evaluated in controlled trials. We report a 67-year-old woman who experienced new-onset myoclonic seizures after initiation of lacosamide. We presume that she had an undiagnosed generalized epilepsy syndrome, likely juvenile myoclonic epilepsy. Myoclonic seizures were not reported before introducing lacosamide and completely resolved after lacosamide was discontinued. This suggests that lacosamide may have the potential to worsen myoclonus, similar to what has been reported with another sodium channel agent, lamotrigine, …

Three Damn Letters, Katherine Ammon

Honors Program Theses

Amyotrophic lateral sclerosis (ALS) is a terminal disease that destroys a patient's motor neurons. In the play Three Damn Letters, a sarcastic woman must accept her own ALS diagnosis while also balancing her relationships with her father, husband, and son. This seriocomedic play explores themes of family roles, disability, love, and death.

Spinal Epidural Abscess Complicated By Meningitis, Sepsis And Thrombocytopenia In A Patient Lacking Traditional Risk Factors, Christian Spano, Michael Ward, Nicole Zagelbaum

Touro College of Osteopathic Medicine (Middletown) Publications and Research

Spinal epidural abscess is a rare diagnosis with a classic triad of fever, spinal pain and neurologic deficits. Only a small proportion of patients have all three findings, making the diagnosis challenging. Here we present a case of cervical and thoracic spinal epidural abscess complicated by meningitis, sepsis and thrombocytopenia in a patient lacking traditional risk factors. The patient was initially treated non-operatively secondary to thrombocytopenia but subsequently required transfer to a tertiary care facility for surgical drainage after clinical deterioration. This case report highlights the need for a high index of suspicion and low threshold for imaging when considering …

Altered Axon Initial Segment Structure And Function In Inflammatory Disease, Kareem C. Clark

Theses and Dissertations

Axonal pathology is a key contributor to long-term disability in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), but the mechanisms that underlie axonal insults remain unclear. While most axonal pathologies characterized in MS are a direct consequence of myelin loss, we propose that axonal pathologies also occur independent of demyelination. In support of this idea, we recently reported that mice that develop experimental autoimmune encephalomyelitis (EAE), a model commonly used to mimic the pathogenesis of MS, exhibit a structural and functional disruption of the axon initial segment (AIS), a subdomain of the axon that …

Meta Analysis Of Human Alzgene Database: Benefits And Limitations Of Using C. Elegans For The Study Of Alzheimer's Disease And Co-Morbid Conditions, Behrad Vahdati Nia, Christine Kang, Michelle G. Tran, Deborah Lee, Shin Murakami

Faculty Publications & Research of the TUC College of Osteopathic Medicine

Human genome-wide association studies (GWAS) and linkage studies have identified 695 genes associated with Alzheimer's disease (AD), the vast majority of which are associated with late-onset AD. Although orthologs of these AD genes have been studied in several model species, orthologs in the nematode, Caenorhabditis elegans, remain incompletely identified, with orthologs to only 17 AD-related genes identified in the C. elegans database, WormBase. Therefore, we performed a comprehensive search for additional C. elegans orthologs of AD genes using well-established programs, including OrthoList, which utilizes four ontology prediction programs. We also validated 680 of the AD genes as a unique …

Molecular Mechanisms Of Alzheimer’S Disease, Abraham Bordon

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease was first discovered in 1906 by Alois Alzheimer. It is a neurodegenerative disease characterized by the buildup of toxic amyloid plaque and intracellular neurofibrillary tangles, which results in the progressive loss of cognitive function and memory. Since its discovery, the disease has become a growing health concern, particularly in the developed world, where the ageing demographics have contributed to an increase in its prevalence and incidence. The earliest research into the disease focused on neurochemical analyses and resulted in the formulation of the cholinergic hypothesis. The mechanism of disease was explained as the degeneration of the cholinergic system …

Possible Causes Of Alzheimer’S Disease Related Amyloid-Β Plaques And Neurofibrillary Tangles, Rochelle Rubenstein

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a major cause of dementia in the elderly and is a global health concern. However, researchers are not sure what causes the characteristic amyloid-β plaque accumulation and neurofibrillary tangles in the brain. Several model mechanisms have been proposed to answer this question. This paper examines three of these possibilities. Research suggests that a particular allele of the apoE gene is responsible for the neurodegeneration found in Alzheimer’s disease. Another hypothesis is that the mechanism of Alzheimer’s is related to prion-mediated protein misfolding. Other studies indicate that certain environmental factors can cause the neuropathology of Alzheimer’s. Specifically, this …

Repurposing Diabetes Drugs To Treat Insulin Resistance In Alzheimer’S Disease‌, Yael Lazarus

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a neurodegenerative condition which results in a significant decline in cognitive status. Novel treatment approaches for Alzheimer’s are sorely needed, as current medications for the disease offer only marginal clinical benefit. Research has discovered a connection between the pathology of Alzheimer’s and Type 2 Diabetes, two serious and seemingly unrelated disorders. Clinical studies have shown that Alzheimer’s disease is associated with brain insulin resistance similar to the pathology of Type 2 Diabetes. This observation has led to the notion that drugs developed for the treatment of Type 2 Diabetes may be beneficial in modifying the cognitive function …

Luteinizing Hormone And Alzheimer’S Disease: Impact And Possibilities Of Treatment, Rachel Walkin

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a common neurodegenerative disease that is the 6th leading cause of death in the United States. An estimated 5 million Americans are afflicted nationwide and the cost to the economy is valued at 259 billion dollars. Additionally, unlike other major causes of death in the United States, there is no treatment for Alzheimer’s Disease. Alzheimer’s is a progressive disease and it is strongly tied to aging. In most cases symptoms make their first appearance in the late 60’s and gradually worsen, eventually leading to a loss of cognitive function and death. The two outstanding changes in the …

Neuroinflammation In Alzheimer's Disease And Vascular Cognitive Impairment, Erica M. Weekman

Theses and Dissertations--Physiology

It was once believed that the brain was immunologically privileged with no resident or infiltrating immune cells; however, now it is understood that the cells of the brain are capable of a wide range of inflammatory processes and phenotypes. Inflammation in the brain has been implicated in several disease processes such as Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID); however, the role of inflammation in these two dementias is poorly understood.

When we stimulated a pro-inflammatory phenotype with an adeno-associated viral vector in a transgenic mouse model of AD that develops Aβ plaques, we saw a pro-inflammatory …

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered …

Anti-Inflammatory And Neuroprotective Role Of Natural Product Securinine In Activated Glial Cells: Implications For Parkinson’S Disease, Dmitri Leonoudakis, Anand Rane, Suzanne Angeli, Gordon J. Lithgow, Julie K. Andersen, Shankar J. Chinta

Faculty Publications & Research of the TUC College of Pharmacy

Glial activation and subsequent release of neurotoxic proinflammatory factors are believed to play an important role in the pathogenesis of several neurological disorders including Parkinson’s disease (PD). Inhibition of glial activation and inflammatory processes may represent a therapeutic target to alleviate neurodegeneration. Securinine, a major natural alkaloid product from the root of the plant Securinega suffruticosa, has been reported to have potent biological activity and is used in the treatment of neurological conditions such as amyotrophic lateral sclerosis, poliomyelitis, and multiple sclerosis. In this study, we explored the underlying mechanisms of neuroprotection elicited by securinine, particularly its anti-inflammatory effects …

Single Low-Dose Lipopolysaccharide Preconditioning: Neuroprotective Against Axonal Injury And Modulates Glial Cells, Ryan C. Turner, Zachary J. Naser, Brandon P. Lucke-Wold, Aric F. Logsdon, Reyna L. Vangilder, Rae Reiko Matsumoto, Jason D. Huber

Faculty Publications & Research of the TUC College of Pharmacy

AIM: Over 7 million traumatic brain injuries (TBI) are reported each year in the United States. However, treatments and neuroprotection following TBI are limited because secondary injury cascades are poorly understood. Lipopolysaccharide (LPS) administration before controlled cortical impact can contribute to neuroprotection. However, the underlying mechanisms and whether LPS preconditioning confers neuroprotection against closed-head injuries remains unclear.

METHODS: The authors hypothesized that preconditioning with a low dose of LPS (0.2 mg/kg) would regulate glial reactivity and protect against diffuse axonal injury induced by weight drop. LPS was administered 7 days prior to TBI. LPS administration reduced locomotion, which recovered completely …

Metabolomic Profiling Of Chiari Malformation Type I: Comparison Of Bioinformatic Programs For Untargeted Analysis, Hunter W. Korsmo

Williams Honors College, Honors Research Projects

Chiari Malformation Type I is a neurodegenerative trait that can result from disease or from acquiring. Metabolomic analysis was done on normal pressure hydrocephalous and Chiari CSF samples using LC-MS and multiple bioinformatic programs. After analysis from multiple programs, we were able to analyze the stringency in statistical algorithms done by each program and determined qualities that are shared between programs that offer multiple details. We identified dysregulation in glucuronated metabolites in CSF of Chiari versus NPH. Using LC-MS, we established the experimental MS/MS of glucuronic acid in attempt to identify similarities in mass-to-charge features primarily identified. We could not …