Neurosciences Commons^™

A Rare Cause Of Recurrent Hypersomnia- Klein-Levin Syndrome, Mohammed Khalid, Tariq Karim Dr, Waqas Anwar Dr

Manipal Journal of Medical Sciences

Recurrent episodes of severe hypersomnia coupled with cognitive and behavioral abnormalities like disorientation, apathy, derealization, compulsive eating and hypersexuality are hallmarks of unusual sleep disease known as Klein-Levin syndrome. We hereby discuss a 46-year-old gentleman who came with recurrent episode of loss of muscle tone, was diagnosed with Klein-Levin syndrome and responded well to medications.

Tracking Health Behaviors In People With Multiple Sclerosis (Trac-Ms): Study Protocol And Description Of The Study Sample., Ruchika S Prakash, Heena R Manglani, Elizabeth J Duraney, Anita Shankar, Megan E Fisher, Alisha Janssen, Lauren Cea, Rick Petosa, Rebecca Andridge, Jacqueline Nicholas

Ambulatory and Primary Care Articles

INTRODUCTION: People with multiple sclerosis (PwMS) experience a range of physical, cognitive, and affective symptoms. Behavioral interventions targeting increased physical activity show promising support as low-cost methods to improve working memory, episodic memory, and processing speed in PwMS. In this randomized controlled trial, we will examine the efficacy of a pedometer-tracking intervention, designed to increase low-to-moderate levels of physical activity, for improving working memory in PwMS.

METHODS AND ANALYSIS: Eighty-seven PwMS, between the ages of 30-59, have been recruited for the study. Seventy-five of the eligible and interested individuals were randomized to six-month health behavior monitoring groups: a Step-track group …

Breakdown Of The Central Synapses In C9orf72-Linked Als/Ftd, Layla T. Ghaffari, Davide Trotti, Aaron R. Haeusler, Brigid K Jensen

Department of Neuroscience Faculty Papers

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease that leads to the death of motor and cortical neurons. The clinical manifestations of ALS are heterogenous, and efficacious treatments to significantly slow the progression of the disease are lacking. Cortical hyper-excitability is observed pre-symptomatically across disease-causative genetic variants, as well as in the early stages of sporadic ALS, and typically precedes motor neuron involvement and overt neurodegeneration. The causes of cortical hyper-excitability are not yet fully understood but is mainly agreed to be an early event. The identification of the nucleotide repeat expansion (GGGGCC)n in the C9ORF72 gene has …

Dataset Of Middle Cerebral Artery Blood Flow Stability In Response To High-Definition Transcranial Electrical Stimulation, Luiz H. Stefano, Diandra B. Favoretto, Diego C. Nascimento, Luan R.A. Santos, Marom Bikson, Joao P. Leite, Octavio M. Pontes-Neto, Dylan J. Edwards, Taiza G.S. Edwards

Moss-Magee Rehabilitation Papers

This supplementary dataset is supportive of the randomized sham-controlled, double-blind, crossover clinical trial investigating polarity- and intensity-dependent effects of high-definition transcranial electrical stimulation (HD-tDCS) applied over the right temporo-parietal junction on mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally. Data of eleven healthy right-handed adults (6 women, 5 men; mean age 31 ± 5.6 years old) were analyzed for MCA-BFv, assessed using transcranial doppler ultrasound on the stimulated and the contralateral hemisphere concomitantly, during and after 3 blocks of 2 min HD-tDCS at 1, 2, and 3 mA. Participants received three electrical stimulation conditions (anode center, cathode center, and …

The Complex Relationship Between Integrins And Oncolytic Herpes Simplex Virus 1 In High-Grade Glioma Therapeutics, Kimberly Ann Rivera-Caraballo, Mitra Nair, Tae Jin Lee, Balveen Kaur, Ji Young Yoo

Faculty, Staff and Student Publications

High-grade gliomas (HGGs) are lethal central nervous system tumors that spread quickly through the brain, making treatment challenging. Integrins are transmembrane receptors that mediate cell-extracellular matrix (ECM) interactions, cellular adhesion, migration, growth, and survival. Their upregulation and inverse correlation in HGG malignancy make targeting integrins a viable therapeutic option. Integrins also play a role in herpes simplex virus 1 (HSV-1) entry. Oncolytic HSV-1 (oHSV) is the most clinically advanced oncolytic virotherapy, showing a superior safety and efficacy profile over standard cancer treatment of solid cancers, including HGG. With the FDA-approval of oHSV for melanoma and the recent conditional approval of …

Transcranial Magnetic Stimulation (Tms) Seeded Tractography Provides Superior Prediction Of Eloquence Compared To Anatomic Seeded Tractography, Matthew Muir, Sarah Prinsloo, Hayley Michener, Arya Shetty, Dhiego Chaves De Almeida Bastos, Jeffrey Traylor, Chibawanye Ene, Sudhakar Tummala, Vinodh A Kumar, Sujit S Prabhu

Faculty, Staff and Student Publications

BACKGROUND: For patients with brain tumors, maximizing the extent of resection while minimizing postoperative neurological morbidity requires accurate preoperative identification of eloquent structures. Recent studies have provided evidence that anatomy may not always predict eloquence. In this study, we directly compare transcranial magnetic stimulation (TMS) data combined with tractography to traditional anatomic grading criteria for predicting permanent deficits in patients with motor eloquent gliomas.

METHODS: We selected a cohort of 42 glioma patients with perirolandic tumors who underwent preoperative TMS mapping with subsequent resection and intraoperative mapping. We collected clinical outcome data from their chart with the primary outcome being …

A Case Of Intractable Hyperhidrosis In Spinal Cord Injury: Role Of Stellate Ganglion Block, Soun Sheen, Hemant Kalia, Victoria Kung

Advances in Clinical Medical Research and Healthcare Delivery

Objective:

Autonomic dysreflexia (AD) in spinal cord injury (SCI) can present as hyperhidrosis due to sudomotor dysfunction. Hyperhidrosis can also occur without an identifiable etiology. There are no standard treatment guidelines for refractory hyperhidrosis in the setting of persistent noxious stimulation. Stellate ganglion blockade may prevent hyperhidrosis by inhibiting profound sympathetic surge and vasoconstriction.

Case:

58-year-old female with C7 ASIA-A quadriplegia was admitted to the hospital for episodes of profuse sweating in the setting of autonomic dysreflexia secondary to underlying T7-8 discitis. Despite conservative treatment of discitis, patient continued experience 50-60 episodes of profuse sweating daily. Stellate ganglion block was …

Identification Of Risk Genes For Alzheimer’S Disease By Gene Embedding, Yashwanth Lagisetty, Thomas Bourquard, Ismael Al-Ramahi, Carl Grant Mangleburg, Samantha Mota, Shirin Soleimani, Joshua M Shulman, Juan Botas, Kwanghyuk Lee, Olivier Lichtarge

Duncan NRI Faculty and Staff Publications

Most disease-gene association methods do not account for gene-gene interactions, even though these play a crucial role in complex, polygenic diseases like Alzheimer’s disease (AD). To discover new genes whose interactions may contribute to pathology, we introduce GeneEMBED. This approach compares the functional perturbations induced in gene interaction network neighborhoods by coding variants from disease versus healthy subjects. In two independent AD cohorts of 5,169 exomes and 969 genomes, GeneEMBED identified novel candidates. These genes were differentially expressed in post mortem AD brains and modulated neurological phenotypes in mice. Four that were differentially overexpressed and modified neurodegeneration in vivo are …

Role Of Sympathetic Pathway In Light-Phase Time-Restricted Feeding-Induced Blood Pressure Circadian Rhythm Alteration, Tianfei Hou, Aaron Chacon, Wen Su, Yuriko Katsumata, Zhenheng Guo, Ming Gong

Sanders-Brown Center on Aging Faculty Publications

Disruption of blood pressure (BP) circadian rhythm, independent of hypertension, is emerging as an index for future target organ damage and is associated with a higher risk of cardiovascular events. Previous studies showed that changing food availability time alters BP rhythm in several mammalian species. However, the underlying mechanisms remain largely unknown. To address this, the current study specifically investigates (1) the relationship between rhythms of food intake and BP in wild-type mice; (2) effects of light-phase time-restricted feeding (TRF, food only available during light-phase) on BP circadian rhythm in wild-type and diabetic db/db mice; (3) the roles of the …

Fighting For Recovery On Multiple Fronts: The Past, Present, And Future Of Clinical Trials For Spinal Cord Injury, Valerie A Dietz, Nolan Roberts, Katelyn Knox, Sherilynne Moore, Michael Pitonak, Chris Barr, Jesus Centeno, Scott Leininger, Kent C New, Peter Nowell, Matthew Rodreick, Cedric G Geoffroy, Argyrios Stampas, Jennifer N Dulin

Faculty, Staff and Student Publications

Through many decades of preclinical research, great progress has been achieved in understanding the complex nature of spinal cord injury (SCI). Preclinical research efforts have guided and shaped clinical trials, which are growing in number by the year. Currently, 1,149 clinical trials focused on improving outcomes after SCI are registered in the U.S. National Library of Medicine at ClinicalTrials.gov. We conducted a systematic analysis of these SCI clinical trials, using publicly accessible data downloaded from ClinicalTrials.gov. After extracting all available data for these trials, we categorized each trial according to the types of interventions being tested and the types of …

Why Study Mechanisms Of Brain Stimulation Therapies? To Modulate The Right Neurons, In The Right Way, At The Right Time, Matthew J Mcginley, Steven T Lee

Duncan NRI Faculty and Staff Publications

Clinical applications of vagus nerve stimulation (VNS) are burgeoning, but mechanistic work lags behind. In this issue of Neuron, Bowles and colleagues show that VNS timed with positive reinforcement improves motor learning and cortical function by a cholinergic mechanism.

Non-Invasive Transcutaneous Spinal Dc Stimulation As A Neurorehabilitation Als Therapy In Awake G93a Mice: The First Step To Clinical Translation, Morgan M. Highlander, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal direct current stimulation (sDCS) modulates motoneuron (MN) excitability beyond the stimulation period, making it a potential neurorehabilitation therapy for amyotrophic lateral sclerosis (ALS), a MN degenerative disease in which MN excitability dysfunction plays a critical and complex role. Recent evidence confirms induced changes in MN excitability via measured MN electrophysiological properties in the SOD1 ALS mouse during and following invasive subcutaneous sDCS (ssDCS). The first aim of our pilot study was to determine the clinical potential of these excitability changes at symptom onset (P90-P105) in ALS via a novel non-invasive transcutaneous sDCS (tsDCS) treatment paradigm on un-anesthetized SOD1-G93A mice. …

Suppression Of Store-Operated Calcium Entry Channels And Cytokine Release By Cannabinoids, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.

The Tfeb-Tgif1 Axis Regulates Emt In Mouse Epicardial Cells, Elena Astanina, Gabriella Doronzo, Davide Corà, Francesco Neri, Salvatore Oliviero, Tullio Genova, Federico Mussano, Emanuele Middonti, Edoardo Vallariello, Chiara Cencioni, Donatella Valdembri, Guido Serini, Federica Limana, Eleonora Foglio, Andrea Ballabio, Federico Bussolino

Duncan NRI Faculty and Staff Publications

Epithelial-mesenchymal transition (EMT) is a complex and pivotal process involved in organogenesis and is related to several pathological processes, including cancer and fibrosis. During heart development, EMT mediates the conversion of epicardial cells into vascular smooth muscle cells and cardiac interstitial fibroblasts. Here, we show that the oncogenic transcription factor EB (TFEB) is a key regulator of EMT in epicardial cells and that its genetic overexpression in mouse epicardium is lethal due to heart defects linked to impaired EMT. TFEB specifically orchestrates the EMT-promoting function of transforming growth factor (TGF) β, and this effect results from activated transcription of thymine-guanine-interacting …

The Trend Of Disruption In The Functional Brain Network Topology Of Alzheimer’S Disease, Alireza Fathian, Yousef Jamali, Mohammad Reza Raoufy, The Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Norbert Schuf, Howard J. Rosen, Bruce L. Miller, Thomas Neylan, Jacqueline Hayess, Shannon Finley, Paul Aisen, Zaven Khachaturian, Ronald G. Thomas, Charles D. Smith, Gregory A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) is a progressive disorder associated with cognitive dysfunction that alters the brain’s functional connectivity. Assessing these alterations has become a topic of increasing interest. However, a few studies have examined different stages of AD from a complex network perspective that cover different topological scales. This study used resting state fMRI data to analyze the trend of functional connectivity alterations from a cognitively normal (CN) state through early and late mild cognitive impairment (EMCI and LMCI) and to Alzheimer’s disease. The analyses had been done at the local (hubs and activated links and areas), meso (clustering, assortativity, and …

The Differential Effects Of Acoustic Discriminations On Operant Learning Performance And Neurogenesis In Male And Female Zebra Finches, Kristena L. Newman

Dissertations, Theses, and Capstone Projects

Adult neurogenesis, the creation of new neurons, occurs throughout the lifespan in most organisms. However, though neuronal proliferation occurs daily, most of these neurons do not survive to become incorporated into preexisting neural circuitry and become fully functioning neurons. In the mammalian brain, adult neurogenesis occurs within the hippocampus, a brain region known to be important in learning and memory. In rats, successful acquisition of certain learning tasks increased new neuron numbers when the learning was sufficiently challenging (Curlik and Shors, 2011). It has also been demonstrated that a spatial discrimination task requires new neurons when the discrimination is more …

Treating Phantom Limb Pain: Cryoablation Of The Posterior Tibial Nerve, Matthew Fiala, Abana Azariah, Jean Woo, Ahmed Kamel Abdel Aal, Alexa Levey

Faculty, Staff and Student Publications

Phantom limb pain (PLP) is a complex pathophysiologic process involving both the central and peripheral nervous system for which there is no definitive treatment. The number of individuals living with amputated limbs is predicted to increase to 3.5 million by 2050, and up to 80% of these patients will have PLP. In this case report, we will demonstrate successful reduction of PLP in a patient with bilateral phantom toe pain utilizing nerve blockade and subsequent cryoablation of the posterior tibial nerves.

Safety Experience With Continued Exposure To Ofatumumab In Patients With Relapsing Forms Of Multiple Sclerosis For Up To 3.5 Years., Stephen L Hauser, Anne H Cross, Kevin Winthrop, Heinz Wiendl, Jacqueline Nicholas, Sven G Meuth, Paul S Giacomini, Francesco Saccà, Linda Mancione, Ronald Zielman, Morten Bagger, Ayan Das Gupta, Dieter A Häring, Valentine Jehl, Bernd C Kieseier, Ratnakar Pingili, Dee Stoneman, Wendy Su, Roman Willi, Ludwig Kappos

Ambulatory and Primary Care Articles

BACKGROUND: Ofatumumab is approved for the treatment of relapsing multiple sclerosis (RMS). Ongoing safety reporting is crucial to understand its long-term benefit-risk profile.

OBJECTIVE: Report the safety and tolerability of ofatumumab in RMS after extended treatment up to 3.5 years.

METHODS: Patients completing ASCLEPIOS I/II (phase 3), APLIOS, or APOLITOS (phase 2) trials could enter ALITHIOS, a phase 3b, open-label, long-term safety study. We analyzed cumulative data of continuous ofatumumab treatment and of patients newly switched from teriflunomide.

RESULTS: The safety population had 1969 patients: 1292 continuously treated with ofatumumab (median time-at-risk 35.5 months, 3253 patient-years) and 677 newly switched …

Kctd7 Deficiency Induces Myoclonic Seizures Associated With Purkinje Cell Death And Microvascular Defects, Justine H Liang, Jonathan Alevy, Viktor Akhanov, Ryan Seo, Cory A Massey, Danye Jiang, Joy Zhou, Roy V Sillitoe, Jeffrey L Noebels, Melanie A Samuel

Duncan NRI Faculty and Staff Publications

Mutations in the potassium channel tetramerization domain-containing 7 (KCTD7) gene are associated with a severe neurodegenerative phenotype characterized by childhood onset of progressive and intractable myoclonic seizures accompanied by developmental regression. KCTD7-driven disease is part of a large family of progressive myoclonic epilepsy syndromes displaying a broad spectrum of clinical severity. Animal models of KCTD7-related disease are lacking, and little is known regarding how KCTD7 protein defects lead to epilepsy and cognitive dysfunction. We characterized Kctd7 expression patterns in the mouse brain during development and show that it is selectively enriched in specific regions as the brain matures. We further …

Evidence For An Association Between Coffin-Siris Syndrome And Congenital Diaphragmatic Hernia, Yoel Gofin, Xiaonan Zhao, Amanda Gerard, Fernando Scaglia, Michael F Wangler, Samantha A Schrier Vergano, Daryl A Scott

Duncan NRI Faculty and Staff Publications

Coffin-Siris syndrome (CSS) is an autosomal dominant neurodevelopmental syndrome that can present with a variety of structural birth defects. Pathogenic variants in 12 genes have been shown to cause CSS. Most of these genes encode proteins that are a part of the mammalian switch/sucrose non-fermentable (mSWI/SNF; BAF) complex. An association between genes that cause CSS and congenital diaphragmatic hernia (CDH) has been suggested based on case reports and the analysis of CSS and CDH cohorts. Here, we describe an unpublished individual with CSS and CDH, and we report additional clinical information on four published cases. Data from these individuals, and …