Neurology Commons^™

A Randomized, Placebo-Controlled, Cross-Over Trial Of Ketamine In Rett Syndrome, Kathleen Campbell, Jeffrey L Neul, David N Lieberman, Elizabeth Berry-Kravis, Tim A Benke, Cary Fu, Alan Percy, Bernhard Suter, David Morris, Randall L Carpenter, Eric D Marsh, Jana Von Hehn

Faculty, Staff and Students Publications

BACKGROUND: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.

DESIGN: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.

METHODS: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite …

Atm Expression And Activation In Ataxia Telangiectasia Patients With And Without Class Switch Recombination Defects, Fereshte Salami, Tannaz Moeini Shad, Nazanin Fathi, Hanieh Mojtahedi, Marzie Esmaeili, Sepideh Shahkarami, Ladan Gol Mohammad Pour Afrakoti, Parisa Amirifar, Samaneh Delavari, Hassan Nosrati, Azadehsadat Razavi, Mohammad Reza Ranjouri, Mahsa Yousefpour, Zahra Hamidi Esfahani, Gholamreza Azizi, Mahmoudreza Ashrafi, Nima Rezaei, Reza Yazdani, Hassan Abolhassani

Department of Neurology Faculty Papers

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.

METHODS: A-T patients with defined genetic diagnoses were classified based on CSR and based on the severity of their medical complications. Isolated peripheral blood mononuclear cells from any patient were evaluated before and after exposure to 0.5 Gy ionizing radiation for one minute. Western blotting was performed to identify the expression …

The Biological Intersection Between Chemotherapy-Related Cognitive Impairment And Alzheimer Disease, Matthew Torre, Camila A Zanella, Mel B Feany

Duncan NRI Faculty and Staff Publications

Alzheimer disease (AD) is the most common type of dementia and one of the leading causes of death in elderly patients. The number of patients with AD in the United States is projected to double by 2060. Thus, understanding modifiable risk factors for AD is an urgent public health priority. In parallel with the number of patients with AD, the number of cancer survivors is estimated to increase significantly, and up to 80% of cancer patients treated with chemotherapy will develop cognitive deficits, termed chemotherapy-related cognitive impairment. This review discusses biologically plausible pathways underlying both disorders, with the goal of …

Advances In Multiple Sclerosis, Victor M Rivera

Faculty, Staff and Students Publications

Multiple sclerosis (MS) is the most common demyelinating and inflammatory disease of the CNS; it has a global distribution with increasing prevalence [...].

High Cellular Plasticity State Of Medulloblastoma Local Recurrence And Distant Dissemination, Hailong Liu, Jing Zhang, Ziwei Wang, Wei Wang, Dongming Han, Xuan Chen, Yu Su, Jiao Zhang, Craig Daniels, Olivier Saulnier, Zeyuan John Wang, Chunyu Gu, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yahui Zhao, Yifei Jiang, Yu Gao, Zijia Liu, Mingxu Ma, Yanong Li, Zitong Zhao, Hongyu Yuan, Youliang Sun, Yanfeng Shi, Tao Yang, Wenxing Li, Xueling Qi, Zejun Duan, Junping Zhang, Mingshan Zhang, Chunjiang Yu, Wei Jin, Xinguang Yu, Yu Tian, Shuaicheng Li, Chunde Li, Michael D Taylor, Jiankang Li, Yong-Qiang Liu, Xiaoguang Qiu, Tao Jiang

Faculty, Staff and Students Publications

Medulloblastoma (MB), a heterogeneous pediatric brain tumor, poses challenges in the treatment of tumor recurrence and dissemination. To characterize cellular diversity and genetic features, we comprehensively analyzed single-cell/nucleus RNA sequencing (sc/snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and spatial transcriptomics profiles and identified distinct cellular populations in SHH (sonic hedgehog) and Group_3 subgroups, with varying proportions in local recurrence or dissemination. Local recurrence showed higher cycling tumor cell enrichment, whereas disseminated lesions had a relatively notable presence of differentiated subsets. Chromosomal alteration evaluation revealed distinct genetic subclones during MB progression, such as chr7q gain and chr11 loss in Group_3 …

A Potential Vegf-Driven Hypothesis Of Calvarial Centripetal Proliferation In Cerebral Proliferative Angiopathy, Shigeta Miyake, Timo Krings, Tze Phei Kee, Thierry A G M Huisman

Faculty, Staff and Students Publications

Cerebral proliferative angiopathy (CPA) is a rare subtype of cerebral arteriovenous malformation, characterized by unique angiographic features and clinical presentations. Although the clinical and angiographic characteristics of CPA have been well described, their impact on the surrounding tissues remains underexplored. Herein, we investigated the presence of calvarial thickening in patients with CPA, and discuss its potential pathogenesis. This retrospective multicenter cohort study enrolled 16 CPA patients from our institutions. Patients were identified by a search of the hospital medical records for key words related to "cerebral proliferative angiopathy." Data on demographics, CPA characteristics, clinical symptoms, and calvarial thickening were collected …

Real-World Satisfaction And Experience With Injection And Autoinjector Device For Ofatumumab Indicated For Multiple Sclerosis., Amy Perrin Ross, Jacqueline Nicholas, Ming-Hui Tai, Stephen Yeung, Nazneen Fatima Shaikh, Helen Chen, Mariana Fernandes, Aaron Cortright, Kevin Hawkins

Neuroscience Articles

BACKGROUND: To evaluate the overall satisfaction, device usability, and injection experience of MS patients self-administering ofatumumab using the Sensoready

METHODS: This US-based, cross-sectional survey study included patients with MS (≥ 18 years) who self-administered ofatumumab using the Sensoready device within the previous 12 months of the survey. Eligible patients were administered a 30-item de novo questionnaire that focused on overall device satisfaction, device usability, convenience/flexibility for travel with the device, user confidence, injection experience, and time to administer the injection. Ratings were measured on Likert and numeric rating scales, with higher scores indicating positive responses.

RESULTS: Overall, 105 patients with …

Discontiguous Recurrences Of Idh-Wildtype Glioblastoma Share A Common Origin With The Initial Tumor And Are Frequently Hypermutated, Malcolm F Mcdonald, Sricharan Gopakumar, Tareq A Juratli, Ilker Y Eyüpoglu, Ganesh Rao, Jacob J Mandel, Ali Jalali

Faculty, Staff and Students Publications

Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences. In our institutional database, we identified 22 patients with targeted exome sequencing of pairs of initial and recurrent IDH-wildtype glioblastoma. Recurrences were classified as contiguous or discontiguous based on the presence or absence of T2 FLAIR signal connection to the initial site of disease on MRI. Exome analysis revealed shared driver and passenger mutations between discontiguous recurrences …

Associations Between Deficit Accumulation Frailty And Baseline Markers Of Lifestyle In The Us Pointer Trial, Mark A Espeland, Yitbarek N Demesie, Kayloni Olson, Samuel N Lockhart, Sarah E Tomaszewski Farias, Maryjo L Cleveland, Christy C Tangney, Lucia Crivelli, Heather M Snyder, Michele K York, Laura D Baker, Rachel A Whitmer, Rena R Wing, Katelyn R Garcia, Kathryn E Callahan

Faculty, Staff and Students Publications

BACKGROUND: Multidomain lifestyle interventions may have the potential to slow biological aging as captured by deficit accumulation frailty indices. We describe the distribution and composition of the 49-component frailty index developed by the U.S. POINTER clinical trial team of investigators and assess its cross-sectional associations with sociodemographic factors and markers chosen to be representative of behaviors targeted by the trial's multidomain interventions.

METHODS: We draw baseline data from the 2 111 volunteers enrolled in U.S. POINTER who were ages 60-79 years and at increased risk for cognitive decline. Frailty components were grouped into 9 domains. Associations that frailty index scores …

Detection Of Elder Abuse Through Emergency Care Technicians Screening Tool Revision For Home-Based Primary Care (Detect-Rpc): A Cluster Randomised Controlled Trial Study Protocol, Brad Cannell, Nicholas Sevey, Melvin D Livingston, Jason Burnett, Kristin Lees Haggerty, Carolyn Pickering

Faculty, Staff and Student Publications

Introduction: The annual prevalence of elder mistreatment (EM) in cognitively intact older adults is estimated to be 11%, yet the annual prevalence in older adults with Alzheimer's disease and related dementias (AD/ADRD) is estimated to be as high as 75%. Associated with a decrease in quality of life and increase in risk of mortality, EM represents a significant public health burden. Home-based primary care (HBPC) providers are uniquely positioned to address the critical need for robust EM screening and reporting, especially among individuals with AD/ADRD. This protocol seeks to adapt the Detection of Elder mistreatment Through Emergency Care Technicians (DETECT) …

Foxr2 Targets Lhx6+/Dlx+ Neural Lineages To Drive Central Nervous System Neuroblastoma, Selin Jessa, Antonella De Cola, Bhavyaa Chandarana, Michael Mcnicholas, Steven Hébert, Adam Ptack, Damien Faury, Jessica W Tsai, Andrey Korshunov, Timothy N Phoenix, Benjamin Ellezam, David T W Jones, Michael D Taylor, Pratiti Bandopadhayay, Manav Pathania, Nada Jabado, Claudia L Kleinman

Faculty, Staff and Students Publications

Central nervous system neuroblastoma with forkhead box R2 (FOXR2) activation (NB-FOXR2) is a high-grade tumor of the brain hemispheres and a newly identified molecular entity. Tumors express dual neuronal and glial markers, leading to frequent misdiagnoses, and limited information exists on the role of FOXR2 in their genesis. To identify their cellular origins, we profiled the transcriptomes of NB-FOXR2 tumors at the bulk and single-cell levels and integrated these profiles with large single-cell references of the normal brain. NB-FOXR2 tumors mapped to LHX6+/DLX+ lineages derived from the medial ganglionic eminence, a progenitor domain in the ventral telencephalon. In vivo prenatal …

Is Modulation Of Immune Checkpoints On Glioblastoma-Infiltrating Myeloid Cells A Viable Therapeutic Strategy?, Ruochen Du, Jianzhong Zhang, Rimas V Lukas, Shashwat Tripathi, Jared T Ahrendsen, Michael A Curran, Crismita Dmello, Peng Zhang, Roger Stupp, Ganesh Rao, Amy B Heimberger

Faculty, Staff and Students Publications

The field of immunology has traditionally focused on immune checkpoint modulation of adaptive immune cells. However, many malignancies such as glioblastoma are mostly devoid of T cells and rather are enriched with immunosuppressive myeloid cells of the innate immune system. While some immune checkpoint targets are shared between adaptive and innate immunity, myeloid-specific checkpoints could also serve as potential therapeutics. To better understand the impact of immune checkpoint blockade on myeloid cells, we systematically summarize the current literature focusing on the direct immunological effects of PD-L1/PD-1, CD24/Siglec-10, collagen/LAIR-1, CX3CL1/CX3CR1, and CXCL10/CXCR3. By synthesizing the molecular mechanisms and the translational implications, …

Alzheimer’S Disease: Relationship Of Cognition And Behavior To Neurochemistry, Peter J. Whitehouse

Faculty Scholarship

Alzheimer’s disease is characterized by loss of cells and synapses in specific neural systems. The development of more effective therapies will depend on understanding the relationships between this pathology and the cognitive and behavioral impairments. In this review, focusing primarily on work in our laboratory, we will examine both classic and neuropeptide neurotransmitter systems and will discuss conceptual and methodological problems in relating clinical and biological measures.

Building Toward Population Reserve And A Critical Positive Psychiatry, Peter J. Whitehouse

Faculty Scholarship

No abstract provided.

Molecular Logic For Cellular Specializations That Initiate The Auditory Parallel Processing Pathways, Junzhan Jing, Ming Hu, Tenzin Ngodup, Qianqian Ma, Shu-Ning Natalie Lau, M Cecilia Ljungberg, Matthew J Mcginley, Laurence O Trussell, Xiaolong Jiang

Faculty, Staff and Students Publications

The cochlear nuclear complex (CN), the starting point for all central auditory processing, encompasses a suite of neuronal cell types highly specialized for neural coding of acoustic signals. However, the molecular logic governing these specializations remains unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple hitherto unknown subtypes with anatomical and physiological identity. The resulting comprehensive cell-type taxonomy reconciles anatomical position, morphological, physiological, and molecular criteria, enabling the determination of the molecular basis of the specialized cellular phenotypes in the CN. In particular, …

Modulation Of Stemness And Differentiation Regulators By Valproic Acid In Medulloblastoma Neurospheres, Natália Hogetop Freire, Alice Laschuk Herlinger, Julia Vanini, Matheus Dalmolin, Marcelo A C Fernandes, Carolina Nör, Vijay Ramaswamy, Caroline Brunetto De Farias, André Tesainer Brunetto, Algemir Lunardi Brunetto, Lauro José Gregianin, Mariane Da Cunha Jaeger, Michael D Taylor, Rafael Roesler

Faculty, Staff and Students Publications

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest. These effects were accompanied by enhanced H3K9 histone acetylation (H3K9ac) and decreased expression of the MYC oncogene. VPA impaired the expansion of MB neurospheres enriched in stemness markers and reduced MYC while increasing TP53 …

Optimizing Electrode Configurations For Eeg Mild Cognitive Impairment Detection, Yi Jiang, Xin Zhang, Zhiwei Guo, Xiaobo Zhou, Jiayuan He, Ning Jiang

Faculty, Staff and Student Publications

The Optimal electrode configuration of Electroencephalograms (EEG) systems for mild cognitive impairment (MCI) detection and monitoring in non-clinical settings, i.e. number of electrodes and the positions of the electrodes, remains to be explored. In the current study, we explored the optimization of electrode configuration for MCI detection. We used a 32-channel EEG device to record the data of 21 MCI patients and 20 cognitively normal elderly (NC) undergoing working memory (WM) tasks. Based on the differential value (MCI group vs. NC group) from the Power Spectral Density (PSD) value of each electrode in θ and α frequency band during WM …

Minimally Invasive Non-Expansile Tubular Extradural Posterior Fossa Decompression (Minted Technique) For The Management Of Chiari I.5 Malformation: Historical Overview Of Surgical Techniques, Technical Note, Proof Of Concept, Illustrative Case And Case Series. Lesser Is Better, José Alberto Israel Romero Rangel, Manuel Eduardo Soto García, Sergio Soriano Solís, Carlos Raúl Rangel Morales, Gerson Reyes Rodríguez, José Antonio Soriano Sánchez

Archives of Neurosurgery

BACKGROUND: Chiari's Malformation surgical treatment has significantly changed since the "classical" technique description by Gardner (1950). It is probably the most commonly performed approach, even when multiple techniques are available because no substantial changes nor any clear surgical objectives have been made. OBJECTIVE: To demonstrate a new cutting-edge surgical technique mastering the advantage of each surgical procedure ever described in the history of Chiari's Malformation establishing three critical points in surgical technique: clear patient-specific surgical goals, dynamic posterior fossa reconstruction, and extradural occipitoatlantal dense-adhesions release. METHODS: A comprehensive review of historically described approaches, proof of concept of surgical technique in …

Traumatic Injuries Of The Common Peroneal Nerve And Current Surgical Strategies For Improving Foot Drop. A Clinical Series And Literature Review., Carlos Alberto Rodríguez Aceves, María Elena Córdoba Mosqueda, Racob Alberto García Velazco, Humberto González Ugalde, Héctor Antonio Soriano Solís, Fabiola Estela Elizabeth Ortega Ponce, Kartik G. Krishnan

Archives of Neurosurgery

Background: Common peroneal nerve injuries are the most frequent nerve injuries in the lower extremity. They may produce severe gait deficits because of weakness or absence in ankle dorsiflexion. Functional improvement after injury, despite any intervention, remains unpredictable. There are various surgical strategies aimed to restore foot drop, but no consensus exists regarding the best surgical treatment.

Objective: In this article, we report our experience and reviewing general aspects of common peroneal nerve anatomy and lesions, current surgical strategies to restore functionality, and the overall outcomes previously published in the literature.

Methods: Retrospective review of patients with foot drop secondary …

Suprameatal Tubercle Classification; Its Implementation On Clinical Cases, Humberto Reyna Mendez, Jose Alfredo Espinosa Mora, Laura Ubaldo Reyes, Alberto Angeles Castellanos, Ignacio Mora Magaña, Mauro Alberto Segura Lozano, Rachel Blue, John Yk Lee, Diego Mendez Rosito

Archives of Neurosurgery

Abstract:

Background: The suprameatal tubercle (SMT) is a variable prominence of the petrosal surface of the temporal bone that lies above the internal acoustic meatus. An enlarged SMT may present an obstacle during surgeries of the posterior fossa, including microvascular decompression or by itself cause trigeminal neuralgia.

Methods: Based on our prior study of 200 temporal bones, its data collection and establishing a classification of the SMT this extension study exemplifies its clinical application.

Results: According to the classification of the SMT four selected cases are clinically and anatomically correlated to exemplify the utility of this classification.

Conclusion: The SMT …