Neurology Commons^™

Expert Panel Curation Of 113 Primary Mitochondrial Disease Genes For The Leigh Syndrome Spectrum, Elizabeth M Mccormick, Kierstin Keller, Julie P Taylor, Alison J Coffey, Lishuang Shen, Danuta Krotoski, Brian Harding, Xiaowu Gai, Marni J Falk, Zarazuela Zolkipli-Cunningham, Shamima Rahman

Children’s Nutrition Research Center Staff Publications

Objective: Primary mitochondrial diseases (PMDs) are heterogeneous disorders caused by inherited mitochondrial dysfunction. Classically defined neuropathologically as subacute necrotizing encephalomyelopathy, Leigh syndrome spectrum (LSS) is the most frequent manifestation of PMD in children, but may also present in adults. A major challenge for accurate diagnosis of LSS in the genomic medicine era is establishing gene-disease relationships (GDRs) for this syndrome with >100 monogenic causes across both nuclear and mitochondrial genomes.

Methods: The Clinical Genome Resource (ClinGen) Mitochondrial Disease Gene Curation Expert Panel (GCEP), comprising 40 international PMD experts, met monthly for 4 years to review GDRs for LSS. The GCEP …

A Blunted Th17 Cytokine Signature In Women With Mild Cognitive Impairment: Insights From Inflammatory Profiling Of A Community-Based Cohort Of Older Adults, Adam D. Bachstetter, Jenny Lutshumba, Edric D. Winford, Erin L. Abner, Barbra J. Martin, Jordan P. Harp, Linda J. Van Eldik, Frederick A. Schmitt, Donna M. Wilcock, Ann M. Stowe, Gregory A. Jicha, Barbara S. Nikolajczyk

Markey Cancer Center Faculty Publications

People with dementia have an increase in brain inflammation, caused in part by innate and adaptive immune cells. However, it remains unknown whether dementia-associated diseases alter neuro-immune reflex arcs to impact the systemic immune system. We examined peripheral immune cells from a community-based cohort of older adults to test if systemic inflammatory cytokine signatures associated with early stages of cognitive impairment. Human peripheral blood mononuclear cells were cultured with monocyte or T-cell-targeted stimuli, and multiplex assays quantitated cytokines in the conditioned media. Following T-cell-targeted stimulation, cells from women with cognitive impairment produced lower amounts of TH17 cytokines compared with cells …

Proteasome Inhibition Protects Blood–Brain Barrier P-Glycoprotein And Lowers Aβ Brain Levels In An Alzheimer’S Disease Model, Milica Vulin, Yu Zhong, Bryan J. Maloney, Björn Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background Loss of P-glycoprotein (P-gp) at the blood–brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer’s disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin–proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor, bortezomib (Velcade®; BTZ), protects blood–brain barrier P-gp from degradation in hAPP mice in vivo.

Methods We treated hAPP mice with …

National Prescribing Practices For Dystonia Among Providers In The United States, Sarah Paige Davis, Natalie J. Kane, Haley Botteron, Rose N. Gelineau-Morel

Posters

Objective: While multiple oral medications are used to treat dystonia, limited information exists on current prescribing practices. This study analyzes prescribing practices for dystonia in the United States, evaluating variations in dosing and impact of co-morbidities. Methods: Querying the Cerner Real World database from 2014 to 2019 for children age 0-18 with an ICD-10 diagnosis containing “dystonia” resulted in 11,300 inpatient and outpatient encounters. Information extracted included current dystonia medications (baclofen, clonidine, carbidopa-levodopa, gabapentin, tetrabenazine, trihexyphenidyl, and benzodiazepines including diazepam, clonazepam, midazolam, and lorazepam), medication dosing, and co-morbid diagnoses of cerebral palsy, epilepsy, or spasticity. Encounters without current weight were …

Pirh2-Dependent Dna Damage In Neurons Induced By The G-Quadruplex Ligand Pyridostatin, Rocio Diaz Escarcega, Abhijeet A Patil, Jose F Moruno-Manchon, Akihiko Urayama, Sean P Marrelli, Nayun Kim, David Monchaud, Louise D Mccullough, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Noncanonical base pairing between four guanines (G) within single-stranded G-rich sequences leads to formation of а G-quartet. Self-stacking of G-quartets results in a columnar four-stranded DNA structure known as the G-quadruplex (G4 or G4-DNA). In cancer cells, G4-DNA regulates multiple DNA-dependent processes, including transcription, replication, and telomere function. How G4s function in neurons is poorly understood. Here, we performed a genome-wide gene expression analysis (RNA-Seq) to identify genes modulated by a G4-DNA ligand, pyridostatin (PDS), in primary cultured neurons. PDS promotes stabilization of G4 structures, thus allowing us to define genes directly or indirectly responsive to G4 regulation. We found …

Normative Spatiotemporal Fetal Brain Maturation With Satisfactory Development At 2 Years, Ana I. L. Namburete, Bartłomiej W. Papież, Michelle Fernandes, Madeleine K. Wyburd, Linde S. Hesse, Felipe A. Moser, Leila Cheikh Ismail, Robert B. Gunier, Waney Squier, Maria Carvalho

Obstetrics and Gynaecology, East Africa

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1 . We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2 , selected using World Health Organization recommendations for growth standards3 . Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5 . The atlas was produced using 1,059 optimal quality, three dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6–8 …

Sepsis Exacerbates Alzheimer’S Disease Pathophysiology, Modulates The Gut Microbiome, Increases Neuroinflammation And Amyloid Burden, Vijayasree V Giridharan, Celso S G Catumbela, Carlos Henrique R Catalão, Juneyoung Lee, Bhanu P Ganesh, Fabricia Petronilho, Felipe Dal-Pizzol, Rodrigo Morales, Tatiana Barichello

Faculty, Staff and Student Publications

While our understanding of the molecular biology of Alzheimer's disease (AD) has grown, the etiology of the disease, especially the involvement of peripheral infection, remains a challenge. In this study, we hypothesize that peripheral infection represents a risk factor for AD pathology. To test our hypothesis, APP/PS1 mice underwent cecal ligation and puncture (CLP) surgery to develop a polymicrobial infection or non-CLP surgery. Mice were euthanized at 3, 30, and 120 days after surgery to evaluate the inflammatory mediators, glial cell markers, amyloid burden, gut microbiome, gut morphology, and short-chain fatty acids (SCFAs) levels. The novel object recognition (NOR) task …

X, But Not Y, Chromosomal Complement Contributes To Stroke Sensitivity In Aged Animals, Shaohua Qi, Conelius Ngwa, Abdullah Al Mamun, Sharmeen Romana, Ting Wu, Sean P Marrelli, Arthur P Arnold, Louise D Mccullough, Fudong Liu

Faculty, Staff and Student Publications

Post-menopausal women become vulnerable to stroke and have poorer outcomes and higher mortality than age-matched men, and previous studies suggested that sex chromosomes play a vital role in mediating stroke sensitivity in the aged. It is unknown if this is due to effects of the X or Y chromosome. The present study used the XY* mouse model (with four genotypes: XX and XO gonadal females and XY and XXY gonadal males) to compare the effect of the X vs. Y chromosome compliment in stroke. Aged (18-20 months) and gonadectomized young (8-12 weeks) mice were subjected to a 60-min middle cerebral …

Hiccups: Nerve Irritation Or Masquerading As Acute Coronary Syndrome, Dessiree Cordero, Patrik Schmidt, Franklin Sosa, Maulin Patel, Eduard Sklyar

Faculty, Staff and Student Publications

The typical clinical presentation of acute coronary syndrome (ACS) includes chest pain that may radiate to the left arm, shoulder, jaw, and neck, accompanied by diaphoresis, dyspnea, nausea, vomiting, and hiccups, which have been observed as the sole symptom of presentation. The mechanism of hiccups involves the activation of the vagus and phrenic nerves, leading to the activation of the diaphragm and intercostal muscles. Several hypotheses link hiccups to ACS, associating irritation of the left anterior descending artery with activation of sympathetic phrenic and vagal nerves. This case report highlights the occurrence of hiccups in patients with inferior and right …

The Role Of Zinc In Psd-95 Palmitoyl Modification, Luis F. Acosta, Lili Guerra, Safiya Syed, Ivonn Ruvalcaba, Yonghong Zhang, Xiaoqian Fang

Research Symposium

Postsynaptic density-95 (PSD-95) is a membrane-associated guanylate kinase that mediates localization of receptors in the excitatory postsynaptic density. It has been reported that PSD-95 mediates postsynaptic localization of NMDA receptors and anchors postsynaptic AMPAR receptors mainly through its postsynaptic membrane targeting by its N-terminal palmitoylation. Recent studies have shown that Ca2+/calmodulin blocks palmitoylation of PSD-95 by binding at the N-terminus of PSD-95, which promotes dissociation of PSD-95 from the postsynaptic membrane and causes loss of surface AMPARs in cultured neurons. Another metal ion zinc is found in various areas of the brain. As an endogenous neuromodulator, zinc plays a role …

Pediatric Covid-19 Encephalitis, Nelson D. Gonzalez, Dustin Paul, Ana Almeda, Samuel Serna, Linette Linsangan

Research Symposium

Background: Neurologic complications of COVID-19 in the pediatric population have been reported in a limited number of reports. There have been reports of COVID-19-associated encephalitis in pediatric cases along with neuroimaging findings revealing involvement of some parts of the nervous system. We present the first case of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - associated encephalitis targeting the parietal lobes.

Case: A 14-year-old morbidly obese Hispanic male with no past medical history presented to the hospital for new onset seizures. Family reported exposure to his COVID-19 positive mother, a one-week history of fever, and a three-month history of …

Efficacy Of Scrambler Therapy In Patients With Painful Diabetic Peripheral Neuropathy: A Single-Arm, Prospective, Pilot Study, Seung Hee Yoo, Won-Joong Kim, Ji Seon Chae, Bo Kyung Kang, Min Jeong Kang, Min Hyouk Beak

Faculty, Staff and Student Publications

BACKGROUND: A variety of medications are available to manage painful diabetic peripheral neuropathy (DPN), but the proper treatment remains challenging. Accordingly, various neuromodulation modalities have been used. However, no prospective clinical trials have evaluated the use of scrambler therapy (ST) in painful DPN. This study aimed to explore the long-term effects of ST in managing painful DPN.

METHODS: The patients received 10 consecutive STs of 45 minutes every 1 to 2 days. The primary outcome was pain score. We measured the visual analog scale (VAS) pain scores at baseline, during ST, immediately after ST, and at 1, 2, 3, and …

Neurologic Outcomes For Adult Spinal Cord Ependymomas Stratified By Tumor Location: A Retrospective Cohort Study And 2-Year Outlook, Keanu Chee, Grégoire P Chatain, Michael W Kortz, Stephanie Serva, Keshari Shrestha, Timothy H Ung, Jens-Peter Witt, Michael Finn

Department of Neurosurgery Faculty Papers

Determine whether craniocaudal spinal cord tumor location affects long-term neurologic outcomes in adults diagnosed with spinal ependymomas (SE). A retrospective cohort analysis of patients aged ≥ 18 years who underwent surgical resection for SE over a ten-year period was conducted. Tumor location was classified as cervical, thoracic, or lumbar/conus. Primary endpoints were post-operative McCormick Neurologic Scale (MNS) scores at < 3 days, 6 weeks, 1 year, and 2 years. One-way ANOVA was performed to detect significant differences in MNS scores between tumor locations. Twenty-eight patients were identified. The average age was 44.2 ± 15.4 years. Sixteen were male, and 13 were female. There were 10 cervical-predominant SEs, 13 thoracic-predominant SEs, and 5 lumbar/conus-predominant SEs. No significant differences were observed in pre-operative MNS scores between tumor locations (p = 0.73). One-way ANOVA testing demonstrated statistically significant differences in post-operative MNS scores between tumor locations at < 3 days (p = 0.03), 6 weeks (p = 0.009), and 1 year (p = 0.003); however, no significant difference was observed between post-operative MNS scores at 2 years (p = 0.13). The mean MNS score for patients with thoracic SEs were higher at all follow-up time points. Tumors arising in the thoracic SE are associated with worse post-operative neurologic outcomes in comparison to SEs arising in other spinal regions. This is likely multifactorial in etiology, owing to both anatomical differences including spinal cord volume as well as variations in tumor characteristics. No significant differences in 2-year MNS scores were observed, suggesting that patients ultimately recover from neurological insult sustained at the time of surgery.

Palmitoylation As A Regulator Of Maguk Proteins Postsynaptic Localization, Rozena Shirvani-Arani, Santiago Balderas, Yonghong Zhang, Xioaqian Fang

Research Symposium

Synaptic plasticity is the ability of the brain to make changes and the changes occur at synapses. To achieve the complicated functions, a good number of proteins are present at synapse and are called synaptic proteins. To stabilize these proteins at synapses, proteins are modified through posttranslational modifications (PTMs). The most studied PTMs include phosphorylation, acetylation, ubiquitination, glycosylation, palmitoylation, etc. Palmitoylation is a type of lipid modification and has received more attention recently for its contribution to protein trafficking, localization, and interaction in various synaptic plasticity. The membrane-associated guanylate kinase (MAGUK) family includes PSD-95, PSD-93 (also known as chapsyn-110), SAP102, …

Frequency Of Icu Specific Interventions After Middle Meningeal Artery, Niti Dharwadkar, Sohum Desai, Ameer E. Hassan, Wondwossen G. Tekle

Research Symposium

Background: Middle meningeal artery embolization (MMAE) is increasingly performed for the treatment of chronic subdural hematomas. Some authors have described managing minimally symptomatic patients with MMAE in the outpatient setting. Our practice, however, has been to routinely admit patients after MMAE to the neuro-intensive care setting. Objective of this research is to analyze the frequency of ICU level interventions after MMAE in the neuro-intensive care unit.

Methods: A consecutive series of MMA embolizations for cSDH were retrospectively reviewed from 2020 to 2022 at Valley Baptist Medical Center in Harlingen, TX, USA. Frequency of ICU specific interventions such as need for …

A Case Of Osteogenesis Imperfecta In A Patient Diagnosed In Adulthood, Khalid Sheikh, M. Lastovica, N. S. Appareddy, R. Wagner, E. Luna

Research Symposium

Background: Osteogenesis imperfecta (OI) is an extremely rare inherited connective tissue disorder, with an incidence of 1 in 20,000 births in the United States. Our aim is to assist other providers in diagnosing and managing patients with OI and concurrent medical morbidities.

Case Presentation: A 21 year old male with a BMI of 34 and a lifetime history of over 10 fractures presented to the Emergency department after a complex seizure at home. The seizure was witnessed by his mother and lasted less than one minute. He had another seizure two weeks prior to presentation. In the ED, the patient …

Comparing Stroke Symptom Recognition And Intervention Times In The Rio Grande Valley, Joshua M. Ninan, Kelsey Baker

Research Symposium

This is a retrospective study that aims to evaluate the duration from onset of stroke-like symptoms to presentation to medical facilities for aid in the Rio Grande Valley. The main goal of the study is to understand the extent of pre-hospital delays with regards to the treatment of stroke in the RGV.

Advances In Diagnosis And Management Of Atypical Spinal Infections: A Comprehensive Review, Glenn A. Gonzalez, Guilherme Porto, Eric Tecce, Yazan Shamli Oghli, J. Miao, Matthew O'Leary, Daniela Perez Chadid, Michael Vo, James Harrop

Department of Neurosurgery Faculty Papers

Atypical spinal infections (ASIs) of the spine are a challenging pathology to management with potentially devastating morbidity and mortality. To identify patients with atypical spinal infections, it is important to recognize the often insidious clinical and radiographic presentations, in the setting of indolent and smoldering organism growth. Trending of inflammatory markers, and culturing of organisms, is essential. Once identified, the spinal infection should be treated with antibiotics and possibly various surgical interventions including decompression and possible fusion depending on spine structural integrity and stability. Early diagnosis of ASIs and immediate treatment of debilitating conditions, such as epidural abscess, correlate with …

Can Alternative Medical Methods Evoke Neuro-Functional Somatosensory Responses? A Case Study Suggesting Functional Improvement, Alhasn Otaif, Mashan E. Alshammari, Christine G. Gerin

Research Symposium

Somatosensory pathways act as the avenue in transferring information concerning the body and its interaction with the external environment to the brain. We aim to demonstrate that through studying somatosensory, motor cortical and subcortical networks, we can explain functional recovery after stimulations applied as an alternative medical treatment. Those stimulations might have evidenced neural pathways and networks important in recovery of function. Materials and methods: The de-identified medical reports of nine patients with initial presentations of cerebral trauma or stroke inducing paralysis were studied.These included the alternative treatments they received and other available materials such as videos and photographs. Patients …

Circulating Endocannabinoids And N-Acylethanolamines In Individuals With Cannabis Use Disorder-Preliminary Findings, Nadia Boachie, Erin Gaudette, Richard P. Bazinet, Lin Lin, Rachel F. Tyndale, Esmaeil Mansouri, Marilyn A. Huestis, Junchao Tong, Bernard Le Foll, Stephen J. Kish, Tony P. George, Isabelle Boileau

Institute of Emerging Health Professions Faculty Papers

BACKGROUND: Endocannabinoids and related N-acylethanolamines (NAEs) are bioactive lipids with important physiological functions and putative roles in mental health and addictions. Although chronic cannabis use is associated with endocannabinoid system changes, the status of circulating endocannabinoids and related NAEs in people with cannabis use disorder (CUD) is uncertain.

METHODS: Eleven individuals with CUD and 54 healthy non-cannabis using control participants (HC) provided plasma for measurement by high-performance liquid chromatography-mass spectrometry of endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and related NAE fatty acids (N-docosahexaenoylethanolamine (DHEA) and N-oleoylethanolamine (OEA)). Participants were genotyped for the functional gene variant of FAAH (rs324420, C385A) which …