Neurology Commons^™

Mri Signal Intensity Differentiation Of Brainstem Encephalitis Induced By Enterovirus 71: A Classification Approach For Acute And Convalescence Stages, Hongwu Zeng, Wenxian Huang, Feiqiu Wen, Yonker Wang, Yungen Gan, Weibin Zeng, Ranran Chen, Yanxia He, Zaiyi Liu, Changhong Liang, Kelvin K. L. Wong

Radiology Faculty Publications

Background: The objective of this study is to assess standardized histograms of signal intensities of T1 signal and T2 signal on sagittal view without enhancement during (1) acute stage, and (2) convalescence stage of pediatric patients with Enterovirus 71 related brainstem encephalitis (BE), and with respect to (3) healthy normal.

Methods: Our subjects were hospitalized between March 2010 and October 2012, and underwent pre- and post-contrast MRI studies. The research question to be answered is whether the comparison of the MRI image intensity histograms and relevant statistical quantification can add new knowledge to the diagnosis of BE patients. So, both …

Mechanical Conflict System: A Novel Operant Method For The Assessment Of Nociceptive Behavior, Steven E. Harte, Jessica B. Meyers, Renee R. Donahue, Bradley K. Taylor, Thomas J. Morrow

Physiology Faculty Publications

A new operant test for preclinical pain research, termed the Mechanical Conflict System (MCS), is presented. Rats were given a choice either to remain in a brightly lit compartment or to escape to a dark compartment by crossing an array of height-adjustable nociceptive probes. Latency to escape the light compartment was evaluated with varying probe heights (0, .5, 1, 2, 3, and 4 mm above compartment floor) in rats with neuropathic pain induced by constriction nerve injury (CCI) and in naive control rats. Escape responses in CCI rats were assessed following intraperitoneal administration of pregabalin (10 and 30 mg/kg), morphine …

Abnormal Tau Induces Cognitive Impairment Through Two Different Mechanisms: Synaptic Dysfunction And Neuronal Loss, J. Di, L. S. Cohen, C. P. Corbo, Greg R. Phillips, Abdeslem El Idrissi, Alejandra D. Alonso

Publications and Research

The hyperphosphorylated microtubule-associated protein tau is present in several neurodegenerative diseases, although the causal relationship remains elusive. Few mouse models used to study Alzheimerlike dementia target tau phosphorylation. We created an inducible pseudophosphorylated tau (Pathological Human Tau, PH-Tau) mouse model to study the effect of conformationally modified tau in vivo. Leaky expression resulted in two levels of PH-Tau: low basal level and higher upon induction (4% and 14% of the endogenous tau, respectively). Unexpectedly, low PH-Tau resulted in significant cognitive deficits, decrease in the number of synapses (seen by EM in the CA1 region), reduction of synaptic proteins, and localization …

Mesial Temporal Lobe Epilepsy With Childhood Febrile Seizure., Ali Akbar Asadi-Pooya, Maromi Nei, Cyrus Rostami, Michael R. Sperling

Department of Neurology Faculty Papers

OBJECTIVES: To evaluate the demographic and clinical manifestations of patients with mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) with childhood febrile seizure (FS) and establishing the potential differences as compared to those without FS. We also investigated the surgery outcome in these two groups of patients.

MATERIALS AND METHODS: In this retrospective study, all patients with a clinical diagnosis of drug-resistant TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure-free or relapsed. …

Alzheimer's Biomarkers Are Correlated With Brain Connectivity In Older Adults Differentially During Resting And Task States, Yang Jiang, Haiqing Huang, Erin Abner, Lucas S. Broster, Gregory A. Jicha, Frederick A. Schmitt, Richard Kryscio, Anders H. Andersen, David Powell, Linda J. Van Eldik, Brian T. Gold, Peter T. Nelson, Charles D. Smith, Mingzhou Ding

Behavioral Science Faculty Publications

β-amyloid (Aβ) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ₄₂ and pTau₁₈₁), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aβ …

The Role Of Ng2 Proteoglycan In Glioma., Sridevi Yadavilli, Eugene I Hwang, Roger J. Packer, Javad Nazarian

Neurology Faculty Publications

Neuron glia antigen-2 ((NG2), also known as chondroitin sulphate proteoglycan 4, or melanoma-associated chondroitin sulfate proteoglycan) is a type-1 membrane protein expressed by many central nervous system (CNS) cells during development and differentiation and plays a critical role in proliferation and angiogenesis. 'NG2' often references either the protein itself or the highly proliferative and undifferentiated glial cells expressing high levels of NG2 protein. NG2 glia represent the fourth major type of neuroglia in the mammalian nervous system and are classified as oligodendrocyte progenitor cells by virtue of their committed oligodendrocyte generation in developing and adult brain. Here, we discuss NG2 …

Response To: Computed Tomography-Guided Biopsy For Potts Disease: An Institutional Experience From An Endemic Developing Country, Muhammad Waqas, Faizuddin Najmuddin, Mohammad Ali Alvi, Muhammad Ehsan Bari

Section of Neurosurgery

No abstract provided.

Dietary Supplementation With Organoselenium Accelerates Recovery Of Bladder Expression, But Does Not Improve Locomotor Function, Following Spinal Cord Injury, Carolyn A. Meyer, Ranjana Singh, Mackenzie T. Jones, Chen-Guang Yu, Ronan F. Power, James W. Geddes

Spinal Cord and Brain Injury Research Center Faculty Publications

Selenium is an essential element required for activity of several antioxidant enzymes, including glutathione peroxidase. Because of the critical role of the antioxidant system in responding to traumatic events, we hypothesized that dietary selenium supplementation would enhance neuroprotection in a rodent model of spinal cord injury. Rats were maintained on either a control or selenium-enriched diet prior to, and following, injury. Dietary selenium supplementation, provided as selenized yeast added to normal rat chow, resulted in a doubling of selenium levels in the spinal cord. Dietary selenium reduced the time required for recovery of bladder function following thoracic spinal cord injury. …

Neurocognitive Dysfunction In Brain Tumor Patients Following Radiation Therapy: A Review Of Biological Hypotheses, Current Treatment Outcomes, And Novel Therapeutic Strategies, Raj Singh

Marshall Journal of Medicine

Given the difficulty of surgical resection of brain neoplasms located adjacent to vital structures of the brain as well as the challenges posed by the blood-brain-barrier for the efficacy of chemotherapeutic agents, whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are often turned to for patients with brain metastases as well as primary brain neoplasms. Though radiation therapy may be successful in local control of these tumors, many patients experience treatment-related neurocognitive issues later in life. In this review, we examine cognitive dysfunction in brain tumor patients following radiation therapy, with an emphasis on the pediatric population. Articles were …

Neural Substrate Expansion For The Restoration Of Brain Function., H Isaac Chen, Dennis Jgamadze, Mijail Serruya, D Kacy Cullen, John A Wolf, Douglas H Smith

Department of Neurology Faculty Papers

Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity. This latter approach has been explored to some degree using both biological and electronic means but thus far has not …

Cerebellopontine Angle Primitive Neuroectodermal Tumor Mimicking Trigeminal Schwannoma, Saad Akhtar Khan, Badar Uddin Ujjan, Adnan Salim, Muhammad Shahzad Shamim

Section of Neurosurgery

Background: Primitive neuroectodermal tumors (PNETs) comprise a group of aggressive, poorly differentiated embryonal tumors occurring in central nervous system as well as in peripheral locations. Primary cerebellopontine angle (CPA) PNET is an extremely rare entity. It is important to have knowledge of this pathology and to be able to differentiate it from other commonly occurring CPA tumors, such as vestibular and trigeminal schwannomas. This distinction is essential because of the difference in the overall treatment plan and prognosis.
Case description: This report describes a case of a young male presenting with diplopia and numbness of face; magnetic resonance imaging showed …

Non-Alcoholic Fatty Liver Disease Induces Signs Of Alzheimer’S Disease (Ad) In Wild-Type Mice And Accelerates Pathological Signs Of Ad In An Ad Model, Do-Geun Kim, Antje Krenz, Leon E. Toussaint, Kirk J. Maurer

Dartmouth Scholarship

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease afflicting about one third of the world's population and 30 % of the US population. It is induced by consumption of high-lipid diets and is characterized by liver inflammation and subsequent liver pathology. Obesity and consumption of a high-fat diet are known to increase the risk of Alzheimer's disease (AD). Here, we investigated NAFLD-induced liver inflammation in the pathogenesis of AD.

Methods: WT and APP-Tg mice were fed with a standard diet (SD) or a high-fat diet (HFD) for 2, 5 months, or 1 year to induce NAFLD. Another …

Repeated Low-Dose Organophosphate Dfp Exposure Leads To The Development Of Depression And Cognitive Impairment In A Rat Model Of Gulf War Illness, Laxmikant Deshpande, Kristin Phillips

Neurology Publications

Approximately 175,000 to 250,000 of the returning veterans from the 1991 Persian Gulf War exhibit chronic multi-symptom illnesses that includes neurologic co-morbidities such as depression, anxiety and cognitive impairments. Amongst a host of causative factors, exposure to low levels of the nerve agent Sarin has been strongly implicated for expression of Gulf War Illness (GWI). Nerve agents similar to pesticides are organophosphate (OP) compounds. There is evidence from civilian population that exposure to OPs such as in agricultural workers and nerve agents such as the survivors and first-responders of the Tokyo subway Sarin gas attack suffer from chronic neurological problems …

Baseline Results Of The Neuronext Spinal Muscular Atrophy Infant Biomarker Study, Stephen J. Kolb, Christopher S. Coffey, Jon W. Yankey, Kristin Krosschell, David Arnold, Mathula Thangarajh, +20 Additoinal Authors, Neuronext Clinical Trial Network

Neurology Faculty Publications

Objective

This study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA).

Methods

This prospective, multi-center natural history study targeted the enrollment of SMA infants and healthy control infants less than 6 months of age. Recruitment occurred at 14 centers within the NINDS National Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) Network. Infant motor function scales and putative electrophysiological, protein and molecular biomarkers were assessed at baseline and subsequent visits.

Results

Enrollment began November, 2012 and ended September, 2014 with 26 SMA infants and 27 healthy infants enrolled. Baseline demographic characteristics of the …

Role Of The Calcium Plateau In The Neuronal Injury And Behavioral Morbidities Following Organophosphate Intoxication, Laxmikant S. Deshpande, Robert E. Blair, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) chemicals include nerve agents and pesticides, and there is a growing concern of OP based chemical attacks against civilians. Current antidotes are essential in limiting immediate mortality associated with OP exposure. However, further research is needed to identify molecular mechanisms underlying long-term neurological deficits following survival of OP toxicity in order to develop effective therapeutics. We have developed rat survival models of OP induced status epilepticus (SE) that mimic chronic mortality and morbidity following OP intoxication. We have observed significant elevations in hippocampal calcium levels after OP SE that persisted for weeks following initial survival. Drugs inhibiting intracellular …

Cannabinoid Receptor Interacting Protein Suppresses Agonist-Driven Cb1 Receptor Internalization And Regulates Receptor Replenishment In An Agonist-Biased Manner, Lawrence C. Blumes, Sandra Leone-Kabler, Deborah J. Luessen, Glenn S. Marrs, Erica Lyons, Caroline E. Bass, Rong Chen, Dana E. Selley, Allyn C. Howlett

Neurology Publications

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown …

Spatial And Temporal Homogeneity Of Driver Mutations In Diffuse Intrinsic Pontine Glioma., Hamid Nikbakht, Eshini Panditharatna, Leonie G Mikael, Rui Li, Tenzin Gayden, Alan Siu, Roger J. Packer, Javad Nazarian, +16 Additional Authors

Neurology Faculty Publications

Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M-including H3.2K27M-mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often …

Molecular And Behavioral Profiling Of Dbx1-Derived Neurons In The Arcuate, Lateral And Ventromedial Hypothalamic Nuclei., Katie Sokolowski, Tuyen Tran, Shigeyuki Esumi, Yasmin Kamal, Livio Oboti, Julieta Lischinsky, Meredith Goodrich, Andrew Lam, Margaret Carter, Yasushi Nakagawa, Joshua G. Corbin

Pediatrics Faculty Publications

BACKGROUND: Neurons in the hypothalamus function to regulate the state of the animal during both learned and innate behaviors, and alterations in hypothalamic development may contribute to pathological conditions such as anxiety, depression or obesity. Despite many studies of hypothalamic development and function, the link between embryonic development and innate behaviors remains unexplored. Here, focusing on the embryonically expressed homeodomain-containing gene Developing Brain Homeobox 1 (Dbx1), we explored the relationship between embryonic lineage, post-natal neuronal identity and lineage-specific responses to innate cues. We found that Dbx1 is widely expressed across multiple developing hypothalamic subdomains. Using standard and inducible fate-mapping to …

Radioresistance Of Brain Tumors, K. Kelley, J. Knisely, M. Symons, R. Ruggieri

Journal Articles

Radiation therapy (RT) is frequently used as part of the standard of care treatment of the majority of brain tumors. The efficacy of RT is limited by radioresistance and by normal tissue radiation tolerance. This is highlighted in pediatric brain tumors where the use of radiation is limited by the excessive toxicity to the developing brain. For these reasons, radiosensitization of tumor cells would be beneficial. In this review, we focus on radioresistance mechanisms intrinsic to tumor cells. We also evaluate existing approaches to induce radiosensitization and explore future avenues of investigation.

Outcomes In Patients With Vestibular Schwannoma After Subtotal Resection And Adjuvant Radiosurgery, H. Radwan, M. Bruce Eisenberg, J. P. S. Knisely, M. M. Ghaly, M. Schulder

Journal Articles

No abstract provided.

Estradiol-Mediated Spine Changes In The Dorsal Hippocampus And Medial Prefrontal Cortex Of Ovariectomized Female Mice Depend On Erk And Mtor Activation In The Dorsal Hippocampus, J. J. Tuscher, V. Luine, M. Frankfurt, K. M. Frick

Journal Articles

No abstract provided.

Key Perspectives On Auditory Outcomes Following Radiosurgery For Vestibular Schwannoma, Tumor Treating Fields For Glioblastoma, And A Proposed Myelopathy Score For Cervical Decompression Surgery, Intracranial Pressure Monitoring In Diffuse Traumatic Brain Injury., Jonathan H. Sherman, Gordon Li, Jin Mo Cho, Winward Choy, Isaac Yang, Zachary A Smith

Neurological Surgery Faculty Publications

No abstract provided.

Neurologists Take Heed Lyme Neuroborreliosis Mimicry Is Afoot, Robert Ollar

NYMC Faculty Publications

No abstract provided.

Pharmacological Blockade Of The Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus In Rats, Laxmikant S. Deshpande, Robert E. Blair, Beverly A. Huang, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10 mg/kg, i.m.) and carisbamate (90 mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury …

Differential Rna Expression Profile Of Skeletal Muscle Induced By Experimental Autoimmune Myasthenia Gravis In Rats, Henry J. Kaminski, Keiichi Himuro, Jumana Alshaikh, Bendi Gong, Georgiama Cheng, Linda L. Kusner

Neurology Faculty Publications

The differential susceptibility of skeletal muscle by myasthenia gravis (MG) is not well understood. We utilized RNA expression profiling of extraocular muscle (EOM), diaphragm (DIA), and extensor digitorum (EDL) of rats with experimental autoimmune MG (EAMG) to evaluate the hypothesis that muscles respond differentially to injury produced by EAMG. EAMG was induced in female Lewis rats by immunization with acetylcholine receptor purified from the electric organ of the Torpedo. Six weeks later after rats had developed weakness and serum antibodies directed against the AChR, animals underwent euthanasia and RNA profiling performed on DIA, EDL, and EOM. Profiling results were validated …

A Urinary Metabolic Signature For Multiple Sclerosis And Neuromyelitis Optica, Teklab Gebregiworgis, Helle H. Nielsen, Chandirasegara Massilamany, Arunakumar Gangaplara, Jay Reddy, Zsolt Illes, Robert Powers

Jay Reddy Publications

Urine is a metabolite-rich biofluid that reflects the body’s effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples because the collection process is easy and noninvasive. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). Nuclear magnetic resonance spectroscopy (NMR) has become a common approach for analyzing urinary metabolites for disease diagnosis and biomarker discovery. For illustration of the potential of urinary metabolites for diagnosing and treating MS patients, and for differentiating between MS and other illnesses, 38 urine samples were collected from healthy controls, MS patients, and neuromyelitis optica-spectrum …

Spatial And Temporal Homogeneity Of Driver Mutations In Diffuse Intrinsic Pontine Glioma., Hamid Nikbakht, Eshini Panditharatna, Leonie G Mikael, Rui Li, Tenzin Gayden, Alan Siu, Javad Nazarian, + 17 More

Neurological Surgery Faculty Publications

Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M-including H3.2K27M-mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often …

Neurosurgery Concepts: Key Perspectives On Intrathecal Fluorescein For Detecting Intraoperative Cerebrospinal Fluid Leak During Endoscopic Endonasal Surgery, Spinal Intraarterial Chemotherapy, Oligoastrocytoma Classification By In Situ Molecular Genetics, And Prenatal Myelomeningocele Closure And The Need For Cerebrospinal Fluid Shunt Placement., Anand V Germanwala, Winward Choy, Jonathan H. Sherman, Sandi Lam, Isaac Yang, Zachary A Smith

Neurological Surgery Faculty Publications

No abstract provided.

Response To The Comments: "Prospective Case Control Evaluation Of Epidural Midazolam For Improving Pain And Ambulation After Microdiscectomy", Muhammad Shahzad Shamim

Section of Neurosurgery

No abstract provided.

Prenatal Nicotine Exposure As A Teratogen In Neurological Pathways, Monica Grover

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Attention-deficit/hyperactivity disorder (ADHD) is the most heritable and commonly diagnosed childhood psychiatric disorder with 4% of all children being diagnosed with this disorder. Prenatal smoking has been found to be a risk factor for ADHD, a disorder that has been believed to be linked to the fluctuation of dopamine levels. Prenatal nicotine exposure in the second trimester influences dopaminergic neurological pathways by altering dopamine release levels. The altered dopamine levels make the fetus brain more sensitive to the nicotine, causing the nicotine exposure to be more dangerous in causing ADHD symptoms. Prenatal nicotine exposure alters the neurological pathway of the …