Neurology Commons^™

Age Cutoff For Early‐Onset Parkinson's Disease:Recommendations From The International Parkinson And Movement Disorder Society Task Force On Early Onset Parkinson's Disease, Raja Mehanna, Katarzyna Smilowska, Jori Fleisher, Bart Post, Taku Hatano, Maria Elisa Pimentel Piemonte, Kishore Raj Kumar, Victor Mcconvey, Baorong Zhang, Eng-King Tan, Rodolfo Savica, International Parkinson And Movement Disorder Society Task Force On Early Onset Parkinson's Disease

Faculty, Staff and Student Publications

BACKGROUND: Early-onset Parkinson's disease (EOPD)/young-onset Parkinson's disease (YOPD) is defined as Parkinson's disease (PD) with an age at onset (AAO) after age 21 years but before the usual AAO for PD. Consensus is lacking, and the reported maximal age for EOPD/YOPD has varied from 40 to 60 years, leading to a lack of uniformity in published studies and difficulty in harmonization of data. EOPD and YOPD have both been used in the literature, somewhat interchangeably.

OBJECTIVE: To define the nomenclature and AAO cutoff for EOPD/YOPD.

METHODS: An extensive review of the literature and task force meetings were conducted. Conclusions were …

Wide-Necked Middle Cerebral Artery Aneurysm Clipping Following Failed Occlusion After Woven Endobridge Placement: 2-Dimensional Operative Video, Stephen Capone, Anil Roy, Matthew Kole, Spiros L Blackburn

Faculty, Staff and Student Publications

No abstract provided.

Ocrelizumab Reduces Thalamic Volume Loss In Patients With Rms And Ppms, Douglas L Arnold, Till Sprenger, Amit Bar-Or, Jerry S Wolinsky, Ludwig Kappos, Shannon Kolind, Ulrike Bonati, Stefano Magon, Johan Van Beek, Harold Koendgen, Oscar Bortolami, Corrado Bernasconi, Laura Gaetano, Anthony Traboulsee

Faculty, Staff and Student Publications

Background: In multiple sclerosis (MS), thalamic integrity is affected directly by demyelination and neuronal loss, and indirectly by gray/white matter lesions outside the thalamus, altering thalamic neuronal projections.

Objective: To assess the efficacy of ocrelizumab compared with interferon beta-1a (IFNβ1a)/placebo on thalamic volume loss and the effect of switching to ocrelizumab on volume change in the Phase III trials in relapsing MS (RMS, OPERA I/II; NCT01247324/NCT01412333) and in primary progressive MS (PPMS, ORATORIO; NCT01194570).

Methods: Thalamic volume change was computed using paired Jacobian integration and analyzed using an adjusted mixed-effects repeated measurement model.

Results: Over the double-blind period, …

Early Versus Delayed Treatment With Glatiramer Acetate: Analysis Of Up To 27 Years Of Continuous Follow-Up In A Us Open-Label Extension Study, Corey C Ford, Jeffrey A Cohen, Andrew D Goodman, John W Lindsey, Robert P Lisak, Christopher Luzzio, Amy Pruitt, John Rose, Horea Rus, Jerry S Wolinsky, Shaul E Kadosh, Emily Bernstein-Hanlon, Yafit Stark, Jessica K Alexander

Faculty, Staff and Student Publications

BACKGROUND: Glatiramer acetate (GA) is US-approved for relapsing multiple sclerosis.

OBJECTIVES: To describe GA long-term clinical profile. To compare effectiveness of early start (ES) versus delayed start (DS; up to 3 years) with GA.

METHODS: Phase 3 trial participants entered a randomized placebo-controlled period then an open-label extension (OLE) with GA.

RESULTS: Overall, 208 out of 251 (82.9%) randomized participants entered the OLE; 24 out of 101 (23.8%, ES) and 28 out of 107 (26.2%, DS) participants completed the OLE. Median GA treatment was 9.8 (0.1-26.3) years. Annualized change in Expanded Disability Status Scale (EDSS) score was lower with ES …

Towards Quality Improvement Of Vaccine Concept Mappings In The Omop Vocabulary With A Semi-Automated Method, Rashmie Abeysinghe, Adam Black, Denys Kaduk, Yupeng Li, Christian Reich, Alexander Davydov, Lixia Yao, Licong Cui

Faculty, Staff and Student Publications

The Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) provides a unified model to integrate disparate real-world data (RWD) sources. An integral part of the OMOP CDM is the Standardized Vocabularies (henceforth referred to as the OMOP vocabulary), which enables organization and standardization of medical concepts across various clinical domains of the OMOP CDM. For concepts with the same meaning from different source vocabularies, one is designated as the standard concept, while the others are specified as non-standard or source concepts and mapped to the standard one. However, due to the heterogeneity of source vocabularies, there may exist mapping …

Loss Of Lamp5 Interneurons Drives Neuronal Network Dysfunction In Alzheimer’S Disease, Yuanyuan Deng, Mian Bi, Fabien Delerue, Shelley L Forrest, Gabriella Chan, Julia Van Der Hoven, Annika Van Hummel, Astrid F Feiten, Seojin Lee, Ivan Martinez-Valbuena, Tim Karl, Gabor G Kovacs, Grant Morahan, Yazi D Ke, Lars M Ittner

Faculty, Staff and Student Publications

In Alzheimer's disease (AD), where amyloid-β (Aβ) and tau deposits in the brain, hyperexcitation of neuronal networks is an underlying disease mechanism, but its cause remains unclear. Here, we used the Collaborative Cross (CC) forward genetics mouse platform to identify modifier genes of neuronal hyperexcitation. We found LAMP5 as a novel regulator of hyperexcitation in mice, critical for the survival of distinct interneuron populations. Interestingly, synaptic LAMP5 was lost in AD brains and LAMP5 interneurons degenerated in different AD mouse models. Genetic reduction of LAMP5 augmented functional deficits and neuronal network hypersynchronicity in both Aβ- and tau-driven AD mouse models. …

A Potent Antibiotic-Loaded Bone-Cement Implant Against Staphylococcal Bone Infections, Sumana Ghosh, Mau Sinha, Ritwik Samanta, Suresh Sadhasivam, Anamika Bhattacharyya, Ashis Nandy, Swamini Saini, Nupur Tandon, Himanshi Singh, Swati Gupta, Anjali Chauhan, Keerthi Kumar Aavula, Sneha Susan Varghese, Pujie Shi, Sudip Ghosh, Mukesh Kumar Garg, Tanmoy Saha, Aparna Padhye, Shamik Ghosh, Hae Lin Jang, Shiladitya Sengupta

Faculty, Staff and Student Publications

New antibiotics should ideally exhibit activity against drug-resistant bacteria, delay the development of bacterial resistance to them and be suitable for local delivery at desired sites of infection. Here, we report the rational design, via molecular-docking simulations, of a library of 17 candidate antibiotics against bone infection by wild-type and mutated bacterial targets. We screened this library for activity against multidrug-resistant clinical isolates and identified an antibiotic that exhibits potent activity against resistant strains and the formation of biofilms, decreases the chances of bacterial resistance and is compatible with local delivery via a bone-cement matrix. The antibiotic-loaded bone cement exhibited …

Competency-Based Eeg Education: A List Of “Must-Know” Eeg Findings For Adult And Child Neurology Residents, Fábio A Nascimento, Jin Jing, Roy Strowd, Irfan S Sheikh, Dan Weber, Jay R Gavvala, Atul Maheshwari, Adriana Tanner, Marcus Ng, K P Vinayan, Saurabh R Sinha, Elza M Yacubian, Vikram R Rao, M Scott Perry, Nathan B Fountain, Ioannis Karakis, Elaine Wirrell, Fang Yuan, Daniel Friedman, Hatice Tankisi, Stefan Rampp, Rebecca Fasano, Jo M Wilmshurst, Cormac O'Donovan, Donald Schomer, Peter W Kaplan, Michael R Sperling, Selim Benbadis, M Brandon Westover, Sándor Beniczky

Faculty, Staff and Student Publications

No abstract provided.

Causal Evidence For A Role Of Cerebellar Lobulus Simplex In Prefrontal-Hippocampal Interaction In Spatial Working Memory Decision-Making, Yu Liu, Samuel S Mcafee, Meike E Van Der Heijden, Mukesh Dhamala, Roy V Sillitoe, Detlef H Heck

Duncan NRI Faculty and Staff Publications

Spatial working memory (SWM) is a cerebrocerebellar cognitive skill supporting survival-relevant behaviors, such as optimizing foraging behavior by remembering recent routes and visited sites. It is known that SWM decision-making in rodents requires the medial prefrontal cortex (mPFC) and dorsal hippocampus. The decision process in SWM tasks carries a specific electrophysiological signature of a brief, decision-related increase in neuronal communication in the form of an increase in the coherence of neuronal theta oscillations (4-12 Hz) between the mPFC and dorsal hippocampus, a finding we replicated here during spontaneous exploration of a plus maze in freely moving mice. We further evaluated …

Potential Interactions Between Cerebellar Dysfunction And Sleep Disturbances In Dystonia, Luis E Salazar Leon, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia is the third most common movement disorder. It causes debilitating twisting postures that are accompanied by repetitive and sometimes intermittent co- or over-contractions of agonist and antagonist muscles. Historically diagnosed as a basal ganglia disorder, dystonia is increasingly considered a network disorder involving various brain regions including the cerebellum. In certain etiologies of dystonia, aberrant motor activity is generated in the cerebellum and the abnormal signals then propagate through a "dystonia circuit" that includes the thalamus, basal ganglia, and cerebral cortex. Importantly, it has been reported that non-motor defects can accompany the motor symptoms; while their severity is not …

Identifying Phenotypic Expansions For Congenital Diaphragmatic Hernia Plus (Cdh+) Using Decipher Data, Amy Hardcastle, Aliska M Berry, Ian M Campbell, Xiaonan Zhao, Pengfei Liu, Amanda E Gerard, Jill A Rosenfeld, Saumya D Sisoudiya, Andres Hernandez-Garcia, Sara Loddo, Silvia Di Tommaso, Antonio Novelli, Maria L Dentici, Rossella Capolino, Maria C Digilio, Ludovico Graziani, Cecilie F Rustad, Katherine Neas, Giovanni B Ferrero, Alfredo Brusco, Eleonora Di Gregorio, Diana Wellesley, Claire Beneteau, Madeleine Joubert, Kris Van Den Bogaert, Anneleen Boogaerts, Dominic J Mcmullan, John Dean, Maria G Giuffrida, Laura Bernardini, Vinod Varghese, Nora L Shannon, Rachel E Harrison, Wayne W K Lam, Shane Mckee, Peter D Turnpenny, Trevor Cole, Jenny Morton, Jacqueline Eason, Marilyn C Jones, Rebecca Hall, Michael Wright, Karen Horridge, Chad A Shaw, Wendy K Chung, Daryl A Scott

Duncan NRI Faculty and Staff Publications

Congenital diaphragmatic hernia (CDH) can occur in isolation or in conjunction with other birth defects (CDH+). A molecular etiology can only be identified in a subset of CDH cases. This is due, in part, to an incomplete understanding of the genes that contribute to diaphragm development. Here, we used clinical and molecular data from 36 individuals with CDH+ who are cataloged in the DECIPHER database to identify genes that may play a role in diaphragm development and to discover new phenotypic expansions. Among this group, we identified individuals who carried putatively deleterious sequence or copy number variants affecting CREBBP, SMARCA4, …

Sex-Specific Epigenetic Development In The Mouse Hypothalamic Arcuate Nucleus Pinpoints Human Genomic Regions Associated With Body Mass Index, Harry Mackay, Chathura J Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa, Robert A Waterland

Duncan NRI Faculty and Staff Publications

Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and …

De Novo Variants In Emc1 Lead To Neurodevelopmental Delay And Cerebellar Degeneration And Affect Glial Function In Drosophila, Hyung-Lok Chung, Patrick Rump, Di Lu, Megan R Glassford, Jung-Wan Mok, Jawid Fatih, Adily Basal, Paul C Marcogliese, Oguz Kanca, Michele Rapp, Johanna M Fock, Erik-Jan Kamsteeg, James R Lupski, Austin Larson, Mark C Haninbal, Hugo Bellen, Tamar Harel

Duncan NRI Faculty and Staff Publications

Background: The endoplasmic reticulum (ER)-membrane protein complex (EMC) is a multi-protein transmembrane complex composed of 10 subunits that functions as a membrane-protein chaperone. Variants in EMC1 lead to neurodevelopmental delay and cerebellar degeneration. Multiple families with biallelic variants have been published, yet to date, only a single report of a monoallelic variant has been described, and functional evidence is sparse.

Methods: Exome sequencing was used to investigate the genetic cause underlying severe developmental delay in three unrelated children. EMC1 variants were modeled in Drosophila, using loss-of-function (LoF) and overexpression studies. Glial-specific and neuronal-specific assays were used to determine whether the …

Il-6 And Tnf-Α Responses To Acute And Regular Exercise In Adult Individuals With Multiple Sclerosis (Ms): A Systematic Review And Meta-Analysis, Parnian Shobeiri, Homa Seyedmirzaei, Nastaran Karimi, Fatemeh Rashidi, Antônio L Teixeira, Serge Brand, Dena Sadeghi-Bahmani, Nima Rezaei

Faculty, Staff and Student Publications

Background: In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of the possible protection of physical activity against disease progression in multiple sclerosis (MS). However, the question arises if acute or regular exercise has any impact on the immune system in PwMS. To answer this question, we performed a systematic review and meta-analysis on both plasma and serum cytokine levels (IL-6 and TNF-α) before and after acute and regular exercise among PwMS and compared to healthy controls.

Method: We performed an online search via PubMed, EMBASE, …

Analysis Of The Efficacy Of Autologous Peripheral Blood Stem Cell Transplantation In High-Risk Neuroblastoma, Jin Yan, Li Jie, Yang Jiaxing, Cao Yanna, Li Zhanglin, Li Zhongyuan, Wang Daowei, Zhao Guangzong, Zhong Benfu, Yan Jie, Zhao Qiang

Faculty, Staff and Student Publications

Objective: This study aimed to analyze the efficacy of autologous peripheral blood stem cell transplantation for high-risk neuroblastoma in China.

Methods: The data of 90 high-risk neuroblastoma patients treated with the CCCG-NB 2015 regimen were reviewed. The baseline clinicopathological characteristics and prognosis were analyzed and compared. In addition, the prognoses of tandem autologous stem cell transplantation and single autologous stem cell transplantation groups were compared.

Results: The results of survival analysis showed that autologous peripheral blood stem cell transplantation based on this pretreatment regimen significantly improved the prognosis of children in the high-risk group. The 3-year event-free survival (EFS) and …

Regional Variation In Brain Tissue Texture In Patients With Tonic-Clonic Seizures, Jennifer A Ogren, Luke A Allen, Bhaswati Roy, Beate Diehl, John M Stern, Dawn S Eliashiv, Samden D Lhatoo, Ronald M Harper, Rajesh Kumar

Faculty, Staff and Student Publications

Patients with epilepsy, who later succumb to sudden unexpected death, show altered brain tissue volumes in selected regions. It is unclear whether the alterations in brain tissue volume represent changes in neurons or glial properties, since volumetric procedures have limited sensitivity to assess the source of volume changes (e.g., neuronal loss or glial cell swelling). We assessed a measure, entropy, which can determine tissue homogeneity by evaluating tissue randomness, and thus, shows tissue integrity; the measure is easily calculated from T1-weighted images. T1-weighted images were collected with a 3.0-Tesla MRI from 53 patients with tonic-clonic (TC) …

Mucopolysaccharidoses And The Blood-Brain Barrier, Onur Sahin, Hannah P Thompson, Grant W Goodman, Jun Li, Akihiko Urayama

Faculty, Staff and Student Publications

Mucopolysaccharidoses comprise a set of genetic diseases marked by an enzymatic dysfunction in the degradation of glycosaminoglycans in lysosomes. There are eight clinically distinct types of mucopolysaccharidosis, some with various subtypes, based on which lysosomal enzyme is deficient and symptom severity. Patients with mucopolysaccharidosis can present with a variety of symptoms, including cognitive dysfunction, hepatosplenomegaly, skeletal abnormalities, and cardiopulmonary issues. Additionally, the onset and severity of symptoms can vary depending on the specific disorder, with symptoms typically arising during early childhood. While there is currently no cure for mucopolysaccharidosis, there are clinically approved therapies for the management of clinical symptoms, …

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 …

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 …

Transplantation Of Astrocytic Mitochondria Modulates Neuronal Antioxidant Defense And Neuroplasticity And Promotes Functional Recovery After Intracerebral Hemorrhage, Ryosuke Tashiro, Jesus Bautista-Garrido, Dan Ozaki, Guanghua Sun, Lidiya Obertas, Alexis S Mobley, Gab Seok Kim, Jaroslaw Aronowski, Joo Eun Jung

Faculty, Staff and Student Publications

Astrocytes release functional mitochondria (Mt) that play regulatory and prosurvival functions on entering adjacent cells. We recently demonstrated that these released Mts could enter microglia to promote their reparative/prophagocytic phenotype that assists in hematoma cleanup and neurological recovery after intracerebral hemorrhage (ICH). However, the relevance of astrocytic Mt transfer into neurons in protecting brain after ICH is unclear. Here, we found that ICH causes a robust increase in superoxide generation and elevated oxidative damage that coincides with loss of the mitochondrial enzyme manganese superoxide dismutase (Mn-SOD). The damaging effect of ICH was reversed by intravenous transplantation of astrocytic Mt, which …

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.

Smart-Home Concept For Remote Monitoring Of Instrumental Activities Of Daily Living (Iadl) In Older Adults With Cognitive Impairment: A Proof Of Concept And Feasibility Study, Myeounggon Lee, Ram Kinker Mishra, Anmol Momin, Nesreen El-Refaei, Amir Behzad Bagheri, Michele K York, Mark E Kunik, Marc Derhammer, Borna Fatehi, James Lim, Rylee Cole, Gregory Barchard, Ashkan Vaziri, Bijan Najafi

Center on Aging Staff Publications

Assessment of instrumental activities of daily living (IADL) is essential for the diagnosis and staging of dementia. However, current IADL assessments are subjective and cannot be administered remotely. We proposed a smart-home design, called IADLSys, for remote monitoring of IADL. IADLSys consists of three major components: (1) wireless physical tags (pTAG) attached to objects of interest, (2) a pendant-sensor to monitor physical activities and detect interaction with pTAGs, and (3) an interactive tablet as a gateway to transfer data to a secured cloud. Four studies, including an exploratory clinical study with five older adults with clinically confirmed cognitive impairment, who …

Erdheim-Chester Disease With Isolated Cns Involvement: A Systematic Review Of The Literature, Anam Haque, Carlos A Pérez, Thejasvi A Reddy, Rajesh K Gupta

Faculty, Staff and Student Publications

Erdheim-Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis that can have various presentations and higher mortality in patients presenting with neurological symptoms. We performed a systematic review to investigate and chronicle the frequency of neurological manifestations, imaging findings, treatments, and outcomes in published ECD patients presenting with neurological symptoms. A PubMed literature search was conducted for articles (published between January 1980 and June 2021) on ECD cases presenting with neurological manifestations. We analyzed the data of 40 patients, including our patient. Cranial neuropathies and ataxia were the most frequent clinical manifestations. A total of 50% of the symptomatic …

A Potential Role For Substance P In West Nile Virus Neuropathogenesis, Shannon E Ronca, Sarah M Gunter, Rebecca Berry Kairis, Allison Lino, Jonathan Romero, Robia G Pautler, Alan Nimmo, Kristy O Murray

Faculty, Staff and Students Publications

Of individuals who develop West Nile neuroinvasive disease (WNND), ~10% will die and >40% will develop long-term complications. Current treatment recommendations solely focus on supportive care; therefore, we urgently need to identify novel and effective therapeutic options. We observed a correlation between substance P (SP), a key player in neuroinflammation, and its receptor Neurokinin-1 (NK1R). Our study in a wild-type BL6 mouse model found that SP is upregulated in the brain during infection, which correlated with neuroinvasion and damage to the blood−brain barrier. Blocking the SP/NK1R interaction beginning at disease onset modestly improved survival and prolonged time to death in …

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 …

Idh1 Pr132h Ctdna And D-2-Hydroxyglutarate As Csf Biomarkers In Patients With Idh-Mutant Gliomas, Yoko Fujita, Luis Nunez-Rubiano, Antonio Dono, Allison Bellman, Mauli Shah, Juan C Rodriguez, Vasanta Putluri, Abu Hena Mostafa Kamal, Nagireddy Putluri, Roy F Riascos, Jay-Jiguang Zhu, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

INTRODUCTION: We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas.

METHODS: CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatography-mass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images.

RESULTS: The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. ctDNA was detected in 7 …

Development Of A Novel Pharmacophore Model To Screen Specific Inhibitors For The Serine-Threonine Protein Phosphatase Calcineurin, Abhisek Mukherjee, Karina Cuanalo-Contreras, Abha Sood, Claudio Soto

Faculty, Staff and Student Publications

Calcineurin (CaN) is a calcium/calmodulin-dependent serine/threonine phosphatase with a crucial role in cellular homeostasis. It is also the target of the Food and Drug Administration (FDA) approved immunosuppressant drugs FK506 and cyclosporine A. Recent work from our group and others indicated that an uncontrolled increase in CaN activity causes synaptic dysfunction and neuronal death in various models of neurodegenerative diseases associated with calcium dysregulation. Furthermore, pharmacological normalization of CaN activity can prevent disease progression in animal models. However, none of the FDA-approved CaN inhibitors bind CaN directly, leading to adverse side effects. The development of direct CaN inhibitors is required …

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.

Duration Of Ischemia Affects Outcomes Independent Of Infarct Size In Stroke, Youngran Kim, Swapnil Khose, Osama O Zaidat, Ameer E Hassan, Johanna T Fifi, Ashish Nanda, Benjamin Atchie, Britton Woodward, Arnd Doerfler, Alejandro Tomasello, Albert J Yoo, Sunil A Sheth

Faculty, Staff and Student Publications

Background: Delays in endovascular reperfusion for patients with large vessel occlusion stroke are known to worsen outcomes, and the mechanism is believed to be time-dependent expansion of the ischemic infarction. In this study, we hypothesize that delays in onset to reperfusion (OTR) assert an effect on outcomes independent of effects of final infarct (FI).

Methods: We performed a subgroup analysis from the prospective multicenter COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device; Penumbra, Inc) registry for 257 patients with anterior circulation large vessel occlusion who underwent endovascular therapy with successful reperfusion (modified …