Nervous System Diseases Commons^™

Complex Regional Pain Syndrome: A Review Of Current Treatments, Yosef Lewis

The Science Journal of the Lander College of Arts and Sciences

Complex Regional Pain Syndrome (CRPS) is a syndrome that develops infrequently in patients that experience a minor or severe trauma to a bodily extremity. CRPS has two subtypes; Type-I and II, both are clinically characterized by hyperalgesia. During its acute stage, CRPS hyperalgesia is clinically characterized by edema in the subcutaneous tissues of the epidermis, allodynia, and localized bone resorption. In the later chronic stage, hyperalgesia is aroused by the disregulation of blood flow to the extremity and permanent dystonic and trophic changes to the skin. Because the epidemiology and central causation of CRPS remains unknown until today, health professionals …

Is There An Alternative Way Of Treating Drug Resistant Epilepsy? The Effects Of The Ketogenic Diet In Children With Intractable Epilepsy, Chaya M. Weinberg

The Science Journal of the Lander College of Arts and Sciences

Many children with epilepsy experience seizures that cannot be resolved with medication. Since surgical intervention is not always an option, the ketogenic diet (KD). a high fat, low carbohydrate and protein diet, offers a chance for seizure reduction and in some cases freedom from seizures and medication. Side effects do exist, although none are serious. Efficacy has been proven through many studies. The mechanism of the KD's effectiveness is still unknown, although several hypotheses exist, including the theory that ketone bodies themselves are anticonvulsant, and the hypothesis that glucose restriction stops seizures. Adenosine A1 receptors are also thought to have …

Huntington's Disease And Its Effect On The Brain, Shaina Rivkin-Drizin

The Science Journal of the Lander College of Arts and Sciences

Huntington's disease is a neurodegenerative disease that leads to gradual extensive brain damage, especially in the striatum and the cerebral cortex. Initial symptoms are cognitive difficulties, loss of motor contra and sudden mood imbalances. Cognitive function slowly declines into dementia, coupled with behavioral and psychiatric problems. Sufferers die within 20 years due to illness complications: a fall, pneumonia, or heart disease (Walker, 2007). This paper reviews the principle biological cause of the disease, its effect on the brain, diagnosis, and treatment.

Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne

Theses and Dissertations--Neuroscience

Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.

Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …

Molecular And Cellular Characterization Of Dopamine Neuron Stimulating Peptides, Kristen Kelps

Theses and Dissertations--Neuroscience

Parkinson’s disease, the second most common neurodegenerative disease, is characterized by the loss of dopaminergic neurons within the substantia nigra. Currently, the treatments available for PD are symptomatic treatments that do not stop the progression of the disease. Trophic molecules, such as glial cell-line derived neurotrophic factor (GDNF), have been evaluated as potential therapeutic molecules that could stop the loss of neurons and potentially restore some of the neurons that have already been lost. However, these trophic molecules are large making them difficult to produce and delivery. Here we characterize three peptides (DNSP-5, DNSP-11, and DNSP-17) to determine it they …

A Machine Learning Approach To Diagnosis Of Parkinson’S Disease, Sumaiya F. Hashmi

CMC Senior Theses

I will investigate applications of machine learning algorithms to medical data, adaptations of differences in data collection, and the use of ensemble techniques.

Focusing on the binary classification problem of Parkinson’s Disease (PD) diagnosis, I will apply machine learning algorithms to a primary dataset consisting of voice recordings from healthy and PD subjects. Specifically, I will use Artificial Neural Networks, Support Vector Machines, and an Ensemble Learning algorithm to reproduce results from [MS12] and [GM09].

Next, I will adapt a secondary regression dataset of PD recordings and combine it with the primary binary classification dataset, testing various techniques to consolidate …

Is Modafinil (Provigil®) Effective In Improving Cognitive Function In Adults With Narcolepsy?, Stephanie V. Bui

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not modafinil (Provigil®) is effective in improving cognitive function in adults with narcolepsy.

STUDY DESIGN: Review of all English language primary randomized controlled trials from 1996 to 2010.

DATA SOURCES: Double-blind, randomized controlled trials that compared modafinil (Provigil®) to a visually matched placebo were found using OVID, MEDLINE, and Cochrane Databases.

OUTCOME(S) MEASURED: Each of the three trials assessed the effect of modafinil on cognitive and executive function by Low-Resolution Brain Electromagnetic Tomography (LORETA), and the following assessment tools: Epworth Sleepiness Scale (ESS), Multiple Sleep …

Is Local Infiltration Analgesia (Lia) A Safe And Effective Method For Post-Operative Pain Management After A Unilateral Total Knee Arthroplasty (Tka)?, Brooke A. Bonnette

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not local infiltration analgesia (LIA) is a safe and effective method for post-operative pain management after a unilateral total knee arthroplasty (TKA).
STUDY DESIGN: Review of three English language primary studies published in 2010 and 2011.

DATA SOURCES: Three randomized controlled trials comparing local infiltration analgesia to three separate controls: epidural analgesia, placebo infiltration and femoral nerve block found using PubMed.

OUTCOMES MEASURED: Clinical outcome was measured by total morphine use postoperatively and average knee pain intensity at rest and upon movement postoperatively. Total morphine use …

What Is The Effectiveness Of Onabotulinumtoxina (Botox®) In Reducing The Number Of Chronic Migraines (Cm) In Patients 18-65 Years Old?, Kristin A. Beddingfield

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not onabotulinumtoxinA (Botox®) is effective in reducing the number of chronic migraines (CM) in patients 18-65 years old? Study Design: Review of three published, double blind randomized controlled trials were used for this review, which were found on PubMed; were selected based on their relevance to the clinical question and if they included patient oriented outcomes.

OUTCOMES MEASURED: The outcomes measured were headache/migraine free days measured by >50% responder rate analysis, the Treatment Responder Rate based on Physician Global Assessment, and total adverse events reported by …

A Dna Computer For Glioblastoma Multiforme Diagnosis And Drug Delivery, Sumaiya F. Hashmi

CMC Senior Theses

Glioblastoma multiforme (GBM) is a debilitating malignant brain tumor with expected patient survival of less than a year and limited responsiveness to most treatments, often requiring biopsy for diagnosis and invasive surgery for treatment. We propose a DNA computer system, consisting of input, computation, and output components, for diagnosis and treatment. The input component will detect the presence of three GBM biomarkers: vascular endothelial growth factor (VEGF), caveolin-1α (CAV), and B2 receptors. The computation component will include indicator segments for each of these genes, and ensure that output is only released if all the biomarkers are present. The output component …

Oxysterols And Parkinson´S Disease. Evidence That Levels Of 24s-Hydroxycholesterol In Cerebrospinal Fluid Correlates With The Duration Of The Disease., Steve Meaney, Anita Lovgren-Sandblom, Lovisa Brodin, Lisette Salveson, Valerio Leoni, Kristian Winge, Sven Palhagen, Per Svenninson

Articles

Oxysterols are important for cholesterol homeostasis in the brain and may be affected in neurodegenerative diseases. The levels of the brain-derived oxysterol 24S-hydroxycholesterol (24S-OH) have been reported to be markedly reduced in the circulation of patients with Parkinson's disease (PD) (Lee et al., Antioxid. Redox Signal. 11 (2009) 407–420). The finding is surprising in view of the fact that other neurodegenerative diseases are associated with relatively modest effects on the circulating levels of 24S-OH. We determined the plasma and cerebrospinal fluid (CSF) levels of 24S-OH and 27-hydroxycholesterol (27-OH) in patients with PD with different disease duration using a highly accurate …

The Gifts, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Naturally Occurring Carboxypeptidase A6 Mutations: Effect On Enzyme Function And Association With Epilepsy, Matthew R. Sapio, Annick Salzmann, Monique Vessaz, Arielle Crespel, Peter J. Lyons, Alain Malafosse, Lloyd D. Fricker

Faculty Publications

Carboxypeptidase A6 (CPA6) is a member of the A/B subfamily of M14 metallocarboxypeptidases that is expressed in brain and many other tissues during development. Recently, two mutations in human CPA6 were associated with febrile seizures and/or temporal lobe epilepsy. In this study we screened for additional CPA6 mutations in patients with febrile seizures and focal epilepsy, which encompasses the temporal lobe epilepsy subtype. Mutations found from this analysis as well as CPA6 mutations reported in databases of single nucleotide polymorphisms were further screened by analysis of the modeled proCPA6 protein structure and the functional role of the mutated amino acid. …

The Incredible Lightness – And Responsibility – Of Exiting The Huntington's Closet, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Pharmacokinetics And Brain Uptake In The Rhesus Monkey Of A Fusion Protein Of Arylsulfatase A And A Monoclonal Antibody Against The Human Insulin Receptor, Ruben J. Boado, Jeff Zhiqiang Lu, Eric Ka-Wai Hui, Rachita K. Sumbria, William M. Pardridge

Pharmacy Faculty Articles and Research

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase A (ASA). It is not possible to treat the brain in MLD with recombinant ASA, because the enzyme does not cross the blood-brain barrier (BBB). In the present investigation, a BBB-penetrating IgG-ASA fusion protein is engineered and expressed, where the ASA monomer is fused to the carboxyl terminus of each heavy chain of an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor-mediated transport on the endogenous BBB insulin receptor, …

Hdsa’S Renewed Commitment To Critical Research, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Designing The Best Drug Possible To Defeat Huntington's Disease, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

The Definitive Step Out Of The Huntington’S Closet, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Hope Of Clinical Trials Creates New, Proactive Outlook On Huntington's Disease, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Lifting Huntington’S Families’ Spirits With The Promise Of Clinical Trials, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Superterry Destroys The Evil Monster Huntington’S Disease, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Playing In The Fourth Quarter Of Life As Huntington's Disease Looms, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

California Stem Cell Agency Approves $19 Million Clinical Trial Project As Huntington's Disease Families 'Change The Course Of Science', Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Exogenous Alpha-Synuclein Induces Cell Death Related Proteins In C6 Oligodendrocyte-Like Cells Corresponding To Protein Expression Observed In Multiple System Atrophy, Derrick Samuel Hilton

Dissertations

Multiple System Atrophy (MSA) consists of three disorders; Autonomic Dysfunction, Cerebellar Ataxia, and Parkinsonism. In MSA, the protein Alpha-Synuclein (SNCA) appears in the central nervous system as misfolded protein aggregates primarily in oligodendrocytes. This dissertation reports the results from studies examining the effect of exogenous SNCA has on a cell model: C6 oligodendrocyte-like cells. Treated cells were evaluated using western blot and DNA microarray. In addition the expression of proteins was evaluated using immunocytochemistry in MSA patient tissue.

C6 cells were shown to take up SNCA when added to the media. SNCA also underwent a truncation when taken up by …

The Wholehearted Embrace: My First Hdsa Convention, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Yale’S Partnership Against Huntington’S Disease: An Alumnus Reconnects And Finds Hope As Scientists Pursue 'Viagra For The Brain' And Other Solutions, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

A Compassionate Allowance, And Faster Social Security Benefits, For The Juvenile Huntington's Disease Community: A Key Step For Advocacy, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Development Of A Microfluidic Device Coupled To Microdialysis Sampling For The Pre-Concentration Of Cytokines, Randy Francisco Espinal Cabrera

Graduate Theses and Dissertations

A proof-of-concept microfluidic device combined with heparin-immobilized magnetic beads was created to concentrate cytokine proteins collected from microdialysis samples. Cytokines are known to be related to several diseases such as cancer, and Parkinson's diseases, so to be able to develop more effective diseases treatments their interactions have to be well understood. Amine-functionalized polystyrene and carboxyl-functionalized magnetic microspheres of ~6.0 ìm in diameter were used to immobilize heparin. The amount of heparin immobilized on polystyrene beads was 5.82 x 10-8 ± 0.36 x 10-8 M per 1.0 x 106 beads and for magnetic beads was 0.64 x 10-8 ± 0.01 x …

Improved Techniques For Acquisition And Analysis Of Dynamic Contrast-Enhanced Magnetic Resonance Imaging For Detecting Vascular Permeability In The Central Nervous System, Cheukkai Hui

Dissertations and Theses (Open Access)

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique for quantitative assessment of the integrity of blood-brain barrier and blood-spinal cord barrier (BSCB) in the presence of central nervous system pathologies. However, the results of DCE-MRI show substantial variability. The high variability can be caused by a number of factors including inaccurate T1 estimation, insufficient temporal resolution and poor contrast-to-noise ratio. My thesis work is to develop improved methods to reduce the variability of DCE-MRI results. To obtain fast and accurate T1 map, the Look-Locker acquisition technique was implemented with a novel and truly centric k-space segmentation scheme. In …

Novel Use Of Dual Anti-Inflammatory Therapy To Overcome Drug Resistance And Improve Functional Recovery Following Spinal Cord Injury, Jennifer Dulin

Dissertations and Theses (Open Access)

Over 1.2 million Americans are currently living with a traumatic spinal cord injury (SCI). Despite the need for effective therapies, there are currently no proven effective treatments that can improve recovery of function in SCI patients. Many therapeutic compounds have shown promise in preclinical models of SCI, but all of these have fallen short in clinical trials.

P-glycoprotein (Pgp) is an active transporter expressed on capillary endothelial cell membranes at the blood-spinal cord barrier (BSCB). Pgp limits passive diffusion of blood-borne drugs into the CNS, by actively extruding drugs from the endothelial cell membrane. Pgp can become pathologically up-regulated, thus …