Nervous System Diseases Commons^™

Tough News For Huntington’S, Other Neurological Disease Patients: Roche Halts Dosing In Historic Clinical Trials On Signs Of Inefficacy, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Intepirdine As Adjunctive Therapy To Donepezil For Mild-To-Moderate Alzheimer’S Disease: A Randomized, Placebo-Controlled, Phase 3 Clinical Trial (Mindset), Frederick M. Lang, Yi Mo, Marwan Sabbagh, Paul Solomon, Merce Boada, Roy W. Jones, Giovanni B. Frisoni, Timo Grimmer, Bruno Dubois, Mark Harnett, Sarah R. Friedhoff, Shari Coslett, Jeffrey L. Cummings

Brain Health Faculty Research

Introduction: A previous phase 2b study supported the use of the 5-HT6 receptor antagonist intepirdine as adjunctive therapy to donepezil for Alzheimer's disease (AD) dementia. A phase 3 study, MINDSET, was performed to test this hypothesis. Methods: MINDSET was a global, double-blind, randomized, placebo-controlled trial in 1315 mild-to-moderate AD dementia patients on stable donepezil. Patients received 35 mg/day intepirdine or placebo for 24 weeks. The co-primary endpoints were change from baseline to week 24 on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL). Results: There were no statistically significant differences between intepirdine …

Blog Article No. 300: Who Exactly Is Gene Veritas?, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Management Of Intracranial Haemangiopericytomas, Noman Ahmad, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

Haemangiopericytomas are rare tumours, commonly mistaken as meningiomas on radiology. These tumours are considered malignant and treatment involves aggressive surgery, followed by adjuvant radiation therapy, and close radiological and clinical follow ups. Herein the authors have reviewed the recent literature on the management of these tumours.

Occupational Therapy’S Role In Addressing Sexuality And Intimacy For Individuals With Progressive Neuromuscular Disorders, Lindsay N. Richards

Student Capstone Papers

Individuals with progressive neuromuscular disorders (PND); specifically, Parkinson’s disease (PD), Multiple Sclerosis (MS), Huntington’s Disease (HD), and Amyotrophic Lateral Sclerosis (ALS) often face physical, psychological, and social challenges related to sex and intimacy. Occupational therapy (OT) practitioners are experts in activity analysis and are equipped with unique knowledge of performance skills and client factors to address deficits in occupational performance.

Though there is literature presenting the effects of PND on sexual occupations, a gap exists as it relates to qualitative data from the perspective of the individual and their partners. A mixed-methods survey was conducted examining the lived experience of …

Getting The Covid-19 Vaccine And A New Exercise Bike To Keep Stable In The Fight Against Huntington's Disease, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

My Arduous, Lucky, And Enlightening Journey Since My Mother's Death From Huntington's Disease 15 Years Ago, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Characterization Of Abin-1 In The Traumatically Injured Brain, Aaron Orellana, Alana C. Conti

Medical Student Research Symposium

Traumatic brain injury (TBI) is associated with chronic pain and persistent neuroinflammation. Opioids are often prescribed in order to relieve pain symptoms, but recent evidence suggests that their use negatively impacts the neuropathology of TBI leading to behavioral impairments and exacerbated neuroinflammation. The de-ubiquinating enzyme tumor necrosis factor alpha-induced protein (TNFAIP)3 or A20, inhibits the inflammatory signaling transcription factor nuclear factor (NF)-kB leading to attenuation of the inflammatory response. A20-binding inhibitor of nuclear factor kB (ABIN-1), which physically interacts with A20, also plays a role in the inhibition of NF-kB and is poorly researched in the central nervous system (CNS). …

A Pathogenic Ufsp2 Variant In An Autosomal Recessive Form Of Pediatric Neurodevelopmental Anomalies And Epilepsy, Min Ni, Bushra Afroze, Chao Xing, Chunxiao Pan, Yanqiu Shao, Ling Cai, Brandi L. Cantarel, Jimin Pei, Nick V. Grishin, Stacy Hewson

Department of Paediatrics and Child Health

Purpose: Neurodevelopmental disabilities are common and genetically heterogeneous. We identified a homozygous variant in the gene encoding UFM1-specific peptidase 2 (UFSP2), which participates in the UFMylation pathway of protein modification. UFSP2 variants are implicated in autosomal dominant skeletal dysplasias, but not neurodevelopmental disorders. Homozygosity for the variant occurred in eight children from four South Asian families with neurodevelopmental delay and epilepsy. We describe the clinical consequences of this variant and its effect on UFMylation.
Methods: Exome sequencing was used to detect potentially pathogenic variants and identify shared regions of homozygosity. Immunoblotting assessed protein expression and post-translational modifications in patient-derived fibroblasts. …

Clinical Utility Of Molecular Profiling In Recurrent Glioblastoma Multiforme, Rebecca P. Bystrom, Pavalan Selvam, Jens Rueter, Honey Reddi, Christine Lu-Emerson

Journal of Maine Medical Center

Introduction: Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor found in adults. GBM has limited therapeutic options. Initial tumor sampling establishes the histopathologic diagnosis, identifies prognostic and therapeutic biomarkers, and provides an opportunity for molecular profiling. By contrast, the utility of repeat tumor sampling and molecular profiling in recurrent GBM is not well established.

Clinical Findings: We present a 69-year-old woman with GBM whose tumor recurred after standard treatment with temozolomide (TMZ) and concurrent radiation, followed by adjuvant TMZ. This patient had a methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter, which ordinarily predicts a favorable response to …

Open Neuroscience Initiative, Austin Lim

College of Science and Health Full Text Publications

The Open Neuroscience Initiative is a free-to-use textbook

This project began as a means to overcoming the financial burden that face undergraduate neuroscience students when buying textbooks. By compiling and writing a completely free-to-access textbook that covers the foundations of a typical college introduction to neuroscience course, students would have one less obstacle to overcome in their educational career, allowing them to focus their valuable time and attention on learning rather than finances. To make this project a reality, I began with a humble tweet in May 2019 that managed to gain a tiny bit of traction among the neuroscience …

Genus Applications For Alzheimer's Disease Pathology, Whitney L Carter

Undergraduate Arts and Research Showcase

Estimates vary, but it is thought that 5.5 million Americans age 60 and up may be living with Alzheimer’s diseases (AD). AD is the most common type of dementia and is characterized by a decline in episodic memories, long-term memory, language, attention, and personality changes. The first symptoms can vary, but for most people memory is the first capacity to become impaired. However, symptoms can also be a decline in non-memory aspects of cognition like work-finding, vision/spatial issues, and impaired reasoning or judgement. AD is identified mainly by two histopathological features: extracellular plague of amyloid-beta protein and intracellular neuronal tangles …

Risk Factors For Suicide In Bangladesh: Case-Control Psychological Autopsy Study, S M Yasir Arafat, M A. Mohit, Mohammad S I. Mullick, Russell Kabir, Murad M. Khan

Department of Psychiatry

Background: Suicide is an important, understudied public health problem in Bangladesh, where risk factors for suicide have not been investigated by case-control psychological autopsy study.
Aims: To identify the major risk factors for suicide in Dhaka, Bangladesh.
Methods: We designed a matched case-control psychological autopsy study. We conducted a semi-structured interview with the next-of-kin of 100 individuals who died by suicide and 100 living controls, matched for age, gender and area of residence. The study was conducted from July 2019 to July 2020.
Results: The odds ratios for the risk factors were 15.33 (95% CI, 4.76-49.30) for the presence of …

The Influence Of Coronavirus Disease-2019 (Covid-19) On Parkinson’S Disease: An Updated Systematic Review, Vikash Jaiswal, Danah Alquraish, Zouina Sarfraz, Azza Sarfraz, Shavy Nagpal, Prakriti Singh Shrestha, Dattatreya Mukherjee, Prathima Guntipalli, Diana F. Sánchez Velazco, Arushee Bhatnagar

Department of Paediatrics and Child Health

Background: COVID-19 has affected global communities with multiple neurological complications in addition to other critical medical issues. COVID-19 binds to the host's angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in the neurons and glial cells, acting as an entry port to the central nervous system (CNS). ACE2 receptors are abundantly expressed on dopamine neurons, which may worsen the prognosis of motor symptoms in Parkinson's disease (PD). SARS-CoV-2 may lead to an indirect response via immune-mediated cytokine storms and propagate through the CNS leading to damage. In this systematic review, we aim to provide thorough analyses of associations between COVID-19 …

Structural Changes In Neurons In Multiple Sclerosis, Saad Bhatti

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

No abstract provided.

The Role Of Microtubule-Associated Protein Tau In Neuronal Excitability And Epileptogenesis, Ryan A. Cloyd

Theses and Dissertations--Physiology

Tauopathies, including Alzheimer’s disease (AD), are devastating diseases with an immense burden on society which is predicted to increase in coming decades. In addition to progressive loss of memory and cognitive function, patients with tauopathies have a 6-10 fold increase in lifetime risk for seizures, and many are diagnosed with epilepsy. The presence of epileptiform activity on electroencephalogram (EEG) recordings from patients with AD predicts faster cognitive decline compared to patients without abnormal EEG readings. Electrophysiological measurements in murine models of AD have identified neuronal hyperexcitability. Furthermore, reducing tau phosphorylation or expression confers seizure resistance in animal epilepsy models. Although …

Novel Mechanistic Insights Towards The Repositioning Of Alogliptin In Parkinson's Disease, Eman Ramadan, Marwa M. Safar

Pharmacy

Parkinson's disease (PD) is a progressive neurodegenerative disease that impairs people's lives tremendously. The development of innovative treatment modalities for PD is a significant unmet medical need. The critical function of glucagon-like peptide-1 (GLP-1) in neurodegenerative diseases has raised impetus in investigating the repositioning of a dipeptidyl peptidase IV inhibitor, alogliptin (ALO), as an effective treatment for PD. As a result, the focus of this research was to assess the effect of ALO in a rat rotenone (ROT) model of PD. For 21 days, ROT (1.5 mg/kg) was delivered subcutaneously every other day. ALO (30 mg/kg/day), delivered by gavage for …

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports (ETD)

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and consistent …

The Role Of Cannabidiol In The Treatment Of Pediatric Patients With Refractory Epilepsy, Evan Chidley

Capstone Showcase

THE ROLE OF CANNABIDIOL IN THE TREATMENT OF PEDIATRIC PATIENTS WITH REFRACTORY EPILEPSY

Author(s) and affiliations: Evan Chidley¹, MMS (c), MPH (c)

¹Arcadia University; [email protected]; (515) 201-6901

Introduction: Intractable epilepsy in children can significantly impair quality of life and anti-epileptic drugs (AEDs) do not adequately reduce seizures for all pediatric patients. Recently, cannabidiol (CBD), one of the main compounds of marijuana, has shown promise as a potential treatment for uncontrolled seizure activity. This paper poses the following question: In pediatric patients with drug-resistant epilepsy, is cannabidiol (CBD) more effective in reducing seizure activity than traditional anti-epileptic drugs …

Potential Perioperative Complications Due To Difference In Timing Of Systemic Heparinization During Ruptured Aneurysm Coiling, Rouzbeh Kotaki, Ameer E. Hassan, Wondwossen G. Tekle

MEDI 9331 Scholarly Activities Clinical Years

Potential Perioperative Complications Due To Differences in Timing Of Systemic Heparin Distribution During Ruptured Aneurysm Coiling

Introduction:

In general, systematic heparin anticoagulation is standard in regards to neurovascular intervention. When coiling ruptured aneurysms, many neurointerventionalists have their own protocol as to timing of systemic heparinization. There is ample research and literature reviewing the frequency of perioperative events, predictors and outcomes, as well as the efficacy in the use of anticoagulants and/or antiplatelets before, during, and after neurovascular procedures to prevent adverse outcomes. However, there currently exists a dearth of research in regards to timing of distribution of heparin intraoperatively and …

Pre-Clinical Advancements In Biomarkers, Tools, And Therapeutics For A Metabolic Neurodegenerative Disease, Zoë Simmons

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the storage form of glucose and a highly important substrate for cellular metabolism. Characterization of the enzymes and mechanisms of glycogen metabolism began over 70 years ago and over the last 20 years, a previously unknown protein called laforin has emerged as an important contributor to glycogen metabolism homeostasis. Multiple labs demonstrated that laforin is a glycogen phosphatase and mutations in the gene encoding laforin cause the formation of aberrant glycogen-like aggregates called Lafora bodies (LBs). LBs are cytoplasmic, water-insoluble aggregates that drive neurodegeneration and early death in Lafora disease (LD) patients. The direct relationship between mutated laforin, …

Cornelia De Lange Syndrome Research From 1953 To 2020: A Bibliometric Analysis, Dr. Mirza Muhammad Naseer, Dr. Abu Waris

Library Philosophy and Practice (e-journal)

The present study was conducted to explore various aspects of Cornelia de Lange Syndrome (CdLS) research publications including annual scientific productivity, top contributing authors and their impact, top contributing countries and organizations, most relevant sources of publication, highly cited documents, and most frequently used words. Bibliometric methods were used to investigate these aspects of CdLS research publications. Results of the study disclosed that the annual scientific productivity of CdLS literature is increasing gradually with the passage of time. A. Selicorni contributed the highest number of publications (45) to CdLS literature while I. D. Krantz had the highest impact in the …

The Effect Of The Interaction Of Exercise Training And Isolation On The Serotonergic System Of App/Ps1 Mice, Bailey J. Dansby

Graduate Theses/Dissertations

Alzheimer’s disease (AD) is a complex neurodegenerative disease that is characterized by the deposition of amyloid beta (Ab) peptides and, consecutively, by a loss of memory and cognitive functions. The amyloid cascade hypothesis suggests that Ab deposition is the main pathogenic of AD. There is evidence that both changes in production and clearance of Ab may be involved in AD pathology. Past studies have shown that exercise training leads to an upregulation in proteins directly involved with Ab clearance. Chronic stress is thought to exacerbate AD pathology by increasing production of Ab. Studies have also demonstrated a link between serotonin …

Targeting The Cerebrovasculature In Sepsis: A Focus On The Brain Microvascular Endothelium, Divine C. Nwafor

Graduate Theses, Dissertations, and Problem Reports (ETD)

The blood-brain barrier (BBB) is a critical interface between the systemic circulation and the brain. It is a specialized multicellular unit composed of brain microvascular endothelial cells (BMECs), pericytes, a basement membrane, and astrocytic end foot processes. BMECs are a principal component of the BBB that provide the structural framework needed for the stringent transport of molecules into the brain. BMEC dysfunction permits the trafficking of neurotoxins from systemic circulation into the brain, which ultimately exacerbates BBB dysfunction and neuroinflammation. Studies have shown that BBB dysfunction is a key determinant of cognitive decline in sepsis. However, there are critical knowledge …

Investigations On Novel Cyp26a1/B1 Inhibitor, Dx308: Using Atra Response As A Theraputic Target For Traumatic Brain Injury And Parkinson’S Disease, Jacob Morgan Leatherwood

Graduate Student Theses, Dissertations, & Professional Papers

Neurodegenerative diseases (NDs) take a wide spectrum of pathologies and have a tendency to present themselves later in life. Neurodegenerative diseases affect 6 million Americans annually with ~1 million currently living with Parkinson’s disease (PD). One of the greatest contributors to the pathogenesis of neurodegenerative diseases is the occurrence of a traumatic brain injury (TBI) during life.

All-trans-retinoic acid (atRA) is the active metabolite of Vitamin A. The retinoic acid pathway is known to be activated following TBI and is reduced in PD patients. Previous studies found a decrease in inflammation and behavioral deficits following administration of Vitamin …

Risk Factors For Amyotrophic Lateral Sclerosis: A Regional United States Case-Control Study., Angeline S Andrew, Walter G Bradley, Daniel Peipert, Tanya Butt, Kwadwo Amoako, Erik P Pioro, Rup Tandan, John Novak, Adam Quick, K Doug Pugar, Komal Sawlani, Bashar Katirji, Todd A Hayes, Pamela Cazzolli, Jiang Gui, Paul Mehta, D Kevin Horton, Elijah W Stommel

Ambulatory and Primary Care Articles

Most amyotrophic lateral sclerosis (ALS) cases are considered sporadic, without a known genetic basis, and environmental exposures are thought to play a causal role. To learn more about sporadic ALS etiology, we recruited n = 188 ALS patients from northern New England and Ohio and matched controls 2:1 from the general population of the same regions. Questionnaires evaluated the association between a variety of lifestyle, behavioral (ie, hobbies and activities), and occupational factors and the risk of ALS, including the duration of time between exposure and ALS onset, and exposure frequency. Head trauma was associated with increased ALS risk (adjusted …

Annual Cost Burden By Level Of Relapse Severity In Patients With Multiple Sclerosis., Jacqueline Nicholas, Huanxue Zhou, Chinmay Deshpande

Ambulatory and Primary Care Articles

INTRODUCTION: The severity of relapses varies in multiple sclerosis (MS) and may lead to a differential cost burden. This study aimed to characterize the direct healthcare costs associated with relapses in patients with MS by the level of relapse severity.

METHODS: This retrospective analysis used claims data extracted from the MarketScan

RESULTS: In total, 8775 patients with MS were analyzed: 6341 (72%) in the NR cohort, 1929 (22%) in the MMR cohort, and 505 (6%) in the SR cohort. Overall, patients were mostly female (76%), mean age was 50 years, and 25% were on a disease-modifying therapy. Mean (standard deviation …

Plasma Glial Fibrillary Acidic Protein Is Elevated In Cognitively Normal Older Adults At Risk Of Alzheimer’S Disease, Pratishtha Chatterjee, Steve Pedrini, Erik Stoops, Kathryn Goozee, Victor L. Villemagne, Prita R. Asih, Inge M. W. Verberk, Preeti Dave, Kevin Taddei, Hamid R. Sohrabi, Henrik Zetterberg, Kaj Blennow, Charlotte E. Teunissen, Hugo M. Vanderstichele, Ralph N. Martins

Research outputs 2014 to 2021

© 2021, The Author(s). Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood samples, and has been associated with Alzheimer’s disease (AD). However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for plasma GFAP and plasma Aβ1–42/Aβ1–40 ratio, a blood-based marker associated with brain Aβ load, in participants (65–90 years) categorised into low (Aβ−, n = 63) and high (Aβ+, n = 33) brain Aβ load groups via Aβ positron emission tomography. Plasma GFAP, Aβ1–42, and Aβ1–40 …

Asymmetric Thinning Of The Cerebral Cortex Across The Adult Lifespan Is Accelerated In Alzheimer’S Disease, James M. Roe, Didac Vidal-Piñeiro, Øystein Sørensen, Andreas M. Brandmaier, Sandra Düzel, Hector A. Gonzalez, Rogier A. Kievit, Ethan Knights, Simone Kühn, Ulman Lindenberger, Athanasia M. Mowinckel, Lars Nyberg, Denise C. Park, Sara Pudas, Melissa M. Rundle, Kristine B. Walhovd, Anders M. Fjell, René Westerhausen, Colin L. Masters, Ashley I. Bush, Christopher Fowler, David Darby, Kelly Pertile, Carolina Restrepo, Blaine Roberts, Jo Robertson, Rebecca Rumble

Research outputs 2014 to 2021

© 2021, The Author(s). Aging and Alzheimer’s disease (AD) are associated with progressive brain disorganization. Although structural asymmetry is an organizing feature of the cerebral cortex it is unknown whether continuous age- and AD-related cortical degradation alters cortical asymmetry. Here, in multiple longitudinal adult lifespan cohorts we show that higher-order cortical regions exhibiting pronounced asymmetry at age ~20 also show progressive asymmetry-loss across the adult lifespan. Hence, accelerated thinning of the (previously) thicker homotopic hemisphere is a feature of aging. This organizational principle showed high consistency across cohorts in the Lifebrain consortium, and both the topological patterns and temporal dynamics …