Medical Specialties Commons^™

Pakistan Ischemic Stroke Guidelines, Anjum Farooq, Maria Khan, Ayesha Zafar, Husnain Hashim, Fozan Khan, Abdul Malik, Ayeesha Kamran Kamal Aga Khan University, Karachi, Mohammad Wasay

Pakistan Journal of Neurological Sciences (PJNS)

Stroke is the second leading cause of death and disability. Mortality related to stroke is very high in low- and middle-income countries. Stroke imposes a great socioeconomical burden in Pakistan. It is important to take important steps for prevention and proper management of stroke in country. Purpose of developing stroke guidelines is to improve stroke care in Pakistan. Guidelines are designed to help neurologists and general practitioners for treating stroke. American stroke guidelines, NICE guidelines, Canadian guidelines and multiple important articles including those emphasizing stroke care in low- and middle-income countries were studied, and these current guidelines were designed in …

Endovascular Thrombectomy For Childhood Stroke (Save Childs Pro): An International, Multicentre, Prospective Registry Study, Peter B. Sporn, Kartik Bhatia, Todd Abruzzo, Lisa Pabst, Stuart Fraser, Melissa G. Chun, Warren Lo, Ahmed Othman, Sebastian Steinmetz, Ameer E. Hassan

School of Medicine Publications

Background

Emerging evidence suggests that endovascular thrombectomy is beneficial for treatment of childhood stroke, but the safety and effectiveness of endovascular thrombectomy has not been compared with best medical treatment. We aimed to prospectively analyse functional outcomes of endovascular thrombectomy versus best medical treatment in children with intracranial arterial occlusion stroke.

Methods

In this prospective registry study, 45 centres in 12 countries across Asia and Australia, Europe, North America, and South America reported functional outcomes for children aged between 28 days and 18 years presenting with arterial ischaemic stroke caused by a large-vessel or medium-vessel occlusion who received either endovascular …

Focused Ultrasound: A New Era In Tremor Control, Sajid Hameed

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Tocilizumab In The Management Of Neuromyelitis Optica Spectrum Disorder: A Narrative Review Of Literature And Critical Appraisal, Salman Mansoor, Samar Iltaf Mairajuddin, Saqib Gul

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective

Neuromyelitis Optica Spectrum disorder (NMOSD) mostly affects the spinal cord and optic nerves. This manuscript aims to explore the treatment potential of tocilizumab, a monoclonal antibody that targets the interleukin-6 (IL-6) receptor and regulates inflammatory cytokines implicated in the pathophysiology of NMOSD. Methods

A thorough search of the pertinent literature was done for this research utilising electronic databases, specifically PubMed, Cochrane Library, and Embase, which contained studies published from 2016 to 2024.

Results Clinical studies show that tocilizumab improves clinical outcomes and lowers recurrence rates in people with NMOSD, especially those who don't respond to traditional treatments. …

Chorea As A Rare Manifestation Of Neuropsychiatric Systemic Lupus Erythematosus: A Case Report, Qurat Ul Ain, Ashfeen Ishfaq, Farzana Kouser, Rabia Rasool

Pakistan Journal of Neurological Sciences (PJNS)

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multisystemic involvement. It has variable clinical presentations and a relapsing and remitting course. Clinical manifestations are broad, ranging from mild mucocutaneous involvement to major organ involvement. We present a case of a 32-year-old female with repeated movements of the right arm, and confusion with a background of pains in multiple joints. She was diagnosed as a case of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). She was managed with pulse therapy of cyclophosphamide (CYC) along with other supportive medications. After six months of intensive immunosuppressive therapy, she remained well and continued maintenance …

The Effects Of Mosaicism On Biological And Clinical Markers Of Alzheimer's Disease In Adults With Down Syndrome, Laura Xicota, Lam-Ha T. Dang, Alice Lee, Sharon Krinsky-Mchale, Deborah Pang, Lisa Melilli, Sid E. O’Bryant, Rachel L. Henson, Charles Laymon, Florence Lai, H. Diana Rosas, Beau Ances, Ira Lott, Christy Hom, Bradley Christian, Sigan Hartley, Shahid Zaman, Elizabeth Head, Mark Mapstone, Zhezhen Jin, Wayne Silverman, Nicole Schupf, Benjamin Handen, Joseph H. Lee, Alzheimer’S Biomarker Consortium – Down Syndrome (Abc-Ds)

Neurology Faculty Publications

Background Individuals with Down syndrome (DS) are at high risk of early-onset Alzheimer’s disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 21.

Methods We examined longitudinal neuropsychological and biomarker data from two large studies of DS: the Alzheimer Biomarker Consortium–Down syndrome study (ABC-DS) (n = 357); and a legacy study (n = 468). We assessed mosaicism using karyotyping or GWAS data. Participants had data on plasma …

Targeted Long-Read Sequencing To Quantify Methylation Of The C9orf72 Repeat Expansion, Evan Udine, Nicole Finch, Mariely Dejesus-Hernandez, Jazmyne L. Jackson, Matthew C. Baker, Siva Arumugam Saravanaperumal, Eric Wieben, Mark T. W. Ebbert, Jaimin Shah, Leonard Petrucelli, Rosa Rademakers, Björn Oskarsson, Marka Van Blitterswijk

Neurology Faculty Publications

Background The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia. While previous studies have estimated the length of this repeat expansion in multiple tissues, technological limitations have impeded researchers from exploring additional features, such as methylation levels.

Methods We aimed to characterize C9orf72 repeat expansions using a targeted, amplification-free long-read sequencing method. Our primary goal was to determine the presence and subsequent quantification of observed methylation in the C9orf72 repeat expansion. In addition, we measured the repeat length and purity of the expansion. To do this, we sequenced DNA extracted from …

An Innovative Community‐Led Education And Recruitment Program To Increase Clinical Research Participation Among Black Americans, Bahar Niknejad, Ethlyn Mcqueen Gibson, Travonia Brown-Hughes, Katie Mcdonough, Ebony Andrews, Deborah Hudson, Hamid Okhravi

Glennan Center for Geriatrics and Gerontology Faculty Publications

Background: Previous studies attest to a lack of awareness about Alzheimer’s Disease (AD) and limited participation of Black Americans in AD clinical trials. The AHEAD Study is a multicenter trial focused on preventing AD by evaluating the effectiveness and safety of Lecanemab in individuals with preclinical AD. The study aims to recruit at least 15% from underrepresented populations, including Black Americans. To achieve this goal, our study site utilizes a community-based participatory research (CBPR) approach and developed a Community Education and Recruitment Program (CERP) designed to increase the participation of Black individuals in the AHEAD Study.

Method: In a collaborative …

Biological Validation Of Peak-Width Of Skeletonized Mean Diffusivity As A Vcid Biomarker: The Markvcid Consortium, Alison M Luckey, Saptaparni Ghosh, Chen-Pin Wang, Alexa Beiser, Rebecca Bernal, Zhiguang Li, Djass Mbangdadji, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A Trevino, Monica Goss, Laura J Hillmer, Christopher E Bauer, Adam M Staffaroni, Lara Stables, Marilyn Albert, Jayandra J Himali, Thomas H Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Joel H Kramer, Gary A Rosenberg, Karl G Helmer, Steven M Greenberg, Mohamad Habes, Danny J J Wang, Brian T Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles Decarli, Pauline Maillard, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

METHODS: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure …

A Comprehensive Perspective On Intracranial Pressure Monitoring And Individualized Management In Neurocritical Care: Results Of A Survey With Global Experts, Sérgio Brasil, Daniel Agustín Godoy, Walter Videtta, Andrés Mariano Rubiano, Davi Solla, Fabio Silvio Taccone, Chiara Robba, Frank Rasulo, Marcel Aries, Peter Smielewski, Geert Meyfroidt, Denise Battaglini, Mohammad I Hirzallah, Robson Amorim, Gisele Sampaio, Fabiano Moulin, Cristian Deana, Edoardo Picetti, Angelos Kolias, Peter Hutchinson, Gregory W Hawryluk, Marek Czosnyka, Ronney B Panerai, Lori A Shutter, Soojin Park, Carla Rynkowski, Jorge Paranhos, Thiago H S Silva, Luiz M S Malbouisson, Wellingson S Paiva

Faculty, Staff and Students Publications

BACKGROUND: Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and …

Genetics Of Cerebral Palsy: Diagnosis, Differential Diagnosis, And Beyond, Dae-Hyun Jang, Jaewon Kim, Aloysia Leisanne Schwabe, Timothy Edward Lotze

Faculty, Staff and Students Publications

Cerebral palsy (CP) is the most common motor disability in children, characterized by diverse clinical manifestations and often uncertain etiology, which has spurred increasing interest in genetic diagnostics. This review synthesizes findings from various studies to enhance understanding of CP's genetic underpinnings. The discussion is structured around five key areas: monogenic causes and copy number variants directly linked to CP, differential genetic disorders including atypical CP and mimics, ambiguous genetic influences, co-occurrence with other neurodevelopmental disorders, and polygenic risk factors. Case studies illustrate the clinical application of these genetic insights, underscoring the complexity of diagnosing CP due to the phenotypic …

Retinal Ganglion Cell Circuits And Glial Interactions In Humans And Mice, Kang-Chieh Huang, Mohamed Tawfik, Melanie A Samuel

Faculty, Staff and Students Publications

Retinal ganglion cells (RGCs) are the brain's gateway for vision, and their degeneration underlies several blinding diseases. RGCs interact with other neuronal cell types, microglia, and astrocytes in the retina and in the brain. Much knowledge has been gained about RGCs and glia from mice and other model organisms, often with the assumption that certain aspects of their biology may be conserved in humans. However, RGCs vary considerably between species, which could affect how they interact with their neuronal and glial partners. This review details which RGC and glial features are conserved between mice, humans, and primates, and which differ. …

Analysis Of Dna Methylation In Gliomas: Assessment Of Preanalytical Variables, Karol Bomsztyk, Daniel Mar, Oleg Denisenko, Suzanne Powell, Monika Vishnoi, Zheng Yin, Jennifer Delegard, Caroline Hadley, Nitin Tandon, Akash J Patel, Anoop P Patel, Richard G Ellenbogen, Rohan Ramakrishna, Robert C Rostomily

Faculty, Staff and Students Publications

Precision oncology is driven by biomarkers. For glioblastoma multiforme (GBM), the most common malignant adult primary brain tumor, O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation is an important prognostic and treatment clinical biomarker. Time consuming pre-analytical steps such as biospecimen storage, fixation, sampling, and processing are sources of data irreproducibility, and all these pre-analytical variables are confounded by intratumor heterogeneity of MGMT promoter methylation. To assess the effect of pre-analytical variables on GBM DNA methylation, tissue storage/sampling (CryoGrid), sample preparation multi-sonicator (PIXUL), and 5-methylcytosine (5mC) DNA immunoprecipitation (Matrix MeDIP-qPCR/seq) platforms were used. MGMT promoter methylation status assayed by MeDIP-qPCR was …

A Reproducible Pipeline For Parcellation Of The Anterior Limb Of The Internal Capsule, Karianne Sretavan, Henry Braun, Zoe Liu, Daniel Bullock, Tara Palnitkar, Remi Patriat, Jayashree Chandrasekaran, Samuel Brenny, Matthew D Johnson, Alik S Widge, Noam Harel, Sarah R Heilbronner

Faculty, Staff and Students Publications

Background: The anterior limb of the internal capsule (ALIC) is a white matter structure that connects the prefrontal cortex (PFC) to the brainstem, thalamus, and subthalamic nucleus. It is a target for deep brain stimulation for obsessive-compulsive disorder. There is strong interest in improving deep brain stimulation targeting by using diffusion tractography to reconstruct and target specific ALIC fiber pathways, but this methodology is susceptible to errors and lacks validation. To address these limitations, we developed a novel diffusion tractography pipeline that generates reliable and biologically validated ALIC white matter reconstructions.

Methods: Following algorithm development and refinement, we analyzed 43 …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project;, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Faculty, Staff and Student Publications

INTRODUCTION: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

METHODS: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

RESULTS: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10

DISCUSSION: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

HIGHLIGHTS: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

Impact Of Prenatal Genomics On Clinical Genetics Practice, Roni Zemet, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

Genetic testing for prenatal diagnosis in the pre-genomic era primarily focused on detecting common fetal aneuploidies, using methods that combine maternal factors and imaging findings. The genomic era, ushered in by the emergence of new technologies like chromosomal microarray analysis and next-generation sequencing, has transformed prenatal diagnosis. These new tools enable screening and testing for a broad spectrum of genetic conditions, from chromosomal to monogenic disorders, and significantly enhance diagnostic precision and efficacy. This chapter reviews the transition from traditional karyotyping to comprehensive sequencing-based genomic analyses. We discuss both the clinical utility and the challenges of integrating prenatal exome and …

Outcomes Of Mechanical Thrombectomy In Anticoagulated Patients With Acute Distal And Medium Vessel Stroke, Hamza Salim, Basel Musmar, Nimer Adeeb, Vivek Yedavalli, Dhairya Lakhani, Sahibjot Singh Grewal, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Xavier Barreau, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Mohammad Ali Aziz-Sultan, Constantin Hecker, Hamza Shaikh, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Adam A Dmytriw, Mad Mt Investigators

Faculty, Staff and Student Publications

Background: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood.

Methods: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, …

Evaluating Novel In Silico Tools For Accurate Pathogenicity Classification In Epilepsy-Associated Genetic Missense Variants, Ludovica Montanucci, Tobias Brünger, Christian M Boßelmann, Alina Ivaniuk, Eduardo Pérez-Palma, Samden Lhatoo, Costin Leu, Dennis Lal

Faculty, Staff and Student Publications

Objective: Determining the pathogenicity of missense variants in clinical genetic tests for individuals with epilepsy is crucial for guiding personalized treatment. However, achieving a definitive pathogenic classification remains challenging, with most missense variants still classified as variants of uncertain significance (VUS) and with the availability of many computational tools which may provide conflicting predictions. Here, we aim to evaluate the performance of state-of-the-art computational tools in pathogenicity prediction of missense variants in epilepsy-associated genes. This will assist in selecting the most appropriate tool and critically assess their use in clinical setting.

Methods: We assessed the performance of nine in silico …

Normative Neuroimaging Library: Designing A Comprehensive And Demographically Diverse Dataset Of Healthy Controls To Support Traumatic Brain Injury Diagnostic And Therapeutic Development, Allyson T Gage, James R Stone, Elisabeth A Wilde, Stephen R Mccauley, Robert C Welsh, John P Mugler, Nick Tustison, Brian Avants, Christopher T Whitlow, Lee Lancashire, Seema D Bhatt, Magali Haas

Faculty, Staff and Students Publications

The past decade has seen impressive advances in neuroimaging, moving from qualitative to quantitative outputs. Available techniques now allow for the inference of microscopic changes occurring in white and gray matter, along with alterations in physiology and function. These existing and emerging techniques hold the potential of providing unprecedented capabilities in achieving a diagnosis and predicting outcomes for traumatic brain injury (TBI) and a variety of other neurological diseases. To see this promise move from the research lab into clinical care, an understanding is needed of what normal data look like for all age ranges, sex, and other demographic and …

Cadasil: A Notch3-Associated Cerebral Small Vessel Disease, Lamei Yuan, Xiangyu Chen, Joseph Jankovic, Hao Deng

Faculty, Staff and Students Publications

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease (CSVD), pathologically characterized by a non-atherosclerotic and non-amyloid diffuse angiopathy primarily involving small to medium-sized penetrating arteries and leptomeningeal arteries. In 1996, mutation in the notch receptor 3 gene (NOTCH3) was identified as the cause of CADASIL. However, since that time other genetic CSVDs have been described, including the HtrA serine peptidase 1 gene-associated CSVD and the cathepsin A gene-associated CSVD, that clinically mimic the original phenotype. Though NOTCH3-associated CSVD is now a well-recognized hereditary disorder and the number of …

Safety And Clinical Outcomes Of Endovascular Therapy Versus Medical Management In Late Presentation Of Large Ischemic Stroke, Adnan Mujanovic, Daniel Strbian, Jelle Demeestere, João Pedro Marto, Volker Puetz, Raul G Nogueira, Mohamad Abdalkader, Simon Nagel, Jean Raymond, Marc Ribo, Patrik Michel, Shinichi Yoshimura, Osama O Zaidat, Simon Winzer, Santiago Ortega-Gutierrez, Sunil A Sheth, James E Siegler, Anne Dusart, Diogo C Haussen, Hilde Henon, Bettina L Serrallach, Mahmoud H Mohammaden, Markus A Möhlenbruch, Marta Olive-Gadea, Ajit S Puri, Nobuyuki Sakai, Piers Klein, Liisa Tomppo, Francois Caparros, João Nuno Ramos, Mouhammad Jumaa, Syed Zaidi, Tomas Dobrocky, Nicolas Martinez-Majander, Stefania Nannoni, Flavio Bellante, Aaron Rodriguez-Calienes, Sergio Salazar-Marioni, Pekka Virtanen, Daniel Po Kaiser, Rita Ventura, Jessica Jesser, Alicia C Castonguay, Muhammad M Qureshi, Hesham E Masoud, Milagros Galecio-Castillo, Manuel Requena, Riikka Lauha, Wei Hu, Eugene Lin, Zhongrong Miao, Daniel Roy, Hiroshi Yamagami, David J Seiffge, Davide Strambo, Peter A Ringleb, Robin Lemmens, Urs Fischer, Thanh N Nguyen, Johannes Kaesmacher

Faculty, Staff and Student Publications

Introduction: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings.

Patients and methods: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed …

Brain Gray Matter Changes In Children At Risk For Sudden Unexpected Death In Epilepsy, Bhaswati Roy, Jennifer A Ogren, Luke A Allen, Beate Diehl, Raman Sankar, Samden D Lhatoo, Rajesh Kumar, Ronald M Harper

Faculty, Staff and Student Publications

Background: Potential failing adult brain sites, stratified by risk, mediating Sudden Unexpected Death in Epilepsy (SUDEP) have been described, but are unknown in children.

Methods: We examined regional brain volumes using T1-weighted MRI images in 21 children with epilepsy at high SUDEP risk and 62 healthy children, together with SUDEP risk scores, calculated from focal seizure frequency. Gray matter tissue type was partitioned, maps normalized, smoothed, and compared between groups (SPM12; ANCOVA; covariates, age, sex, and BMI). Partial correlations between regional volumes and seizure frequency were examined (SPM12, covariates, age, sex, and BMI); 67% were at high risk for SUDEP. …

Mortality Risks Associated With Depression In Men With Prostate Cancer, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

Background: Men diagnosed with prostate cancer (PC) have an increased risk of depression; however, it is unclear to what extent depression affects long-term survival. A better understanding of such effects is needed to improve long-term care and outcomes for men with PC.

Objective: To determine the associations between major depression and mortality in a national cohort of men with PC.

Design, setting, and participants: A national cohort study was conducted of all 180 189 men diagnosed with PC in Sweden during 1998-2017. Subsequent diagnoses of major depression were ascertained from nationwide outpatient and inpatient records through 2018.

Outcome measurements and …

Neurocognitive Functioning Of Patients With Sinonasal And Nasopharyngeal Cancers Treated With Multimodality Therapy, Dan Yaniv, Lindsay M Niccolai, Jeffrey S Wefel, Catherine M Sullaway, Jack Phan, Clifton David Fuller, Kareem B Haroun, Ehab Y Hanna, Shirley Y Su

Faculty, Staff and Student Publications

Importance Few recent studies have examined neurocognitive functioning (NCF) in patients with sinonasal and nasopharyngeal cancers (NPCs) prior to and following multimodality therapy or the potential differences in NCF by disease variables such as disease site.

Objective The objective of this study is to determine rates of NCF impairments prior to and following multimodality therapy, declines in NCF following radiotherapy (RT), and possible differences in NCF by the disease site.

Design, Setting, and Participants We conducted a retrospective chart review of 39 patients with sinonasal and NPCs who underwent comprehensive neuropsychological evaluations. Twenty patients were evaluated prior to RT, of …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

Methods: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

Results: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10-8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10-9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10-8).

Discussion: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

Highlights: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Excellent Registry: A Prospective, Multicenter, Global Registry Of Endovascular Stroke Treatment With The Embotrap Device., Raul G Nogueira, Tommy Andersson, Diogo C Haussen, Albert J Yoo, Ricardo A Hanel, Osama O Zaidat, Werner Hacke, Tudor G Jovin, Jens Fiehler, Simon F De Meyer, Waleed Brinjikji, Karen M Doyle, David F Kallmes, David S Liebeskind, Renu Virmani, Malgosia A Kokoszka, Violiza Inoa, William Humphries, Keith B Woodward, Pascal M Jabbour, Olivier François, Elad I Levy, Hormozd Bozorgchami, Stephan Boor, Jose E Cohen, Shervin R Dashti, Muhammad A Taqi, Ronald F Budzik, Clemens M Schirmer, M Shazam Hussain, Laurent Estrade, Reade A De Leacy, Ajit S Puri, Rohan V Chitale, Caspar Brekenfeld, Adnan H Siddiqui

Neuroscience Articles

BACKGROUND: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots.

METHODS: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee.

RESULTS: After screening 3799 patients, a total of 997 subjects (mean age, …

Clinical Utility Of Abbreviated Eeg Monitoring In Patients Unable To Tolerate A Long-Term, Ambulatory Eeg, Jack T. Mcconnell

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Lee C, Lim S-N, Lien F, et al. Duration of electroencephalographic recordings in patients with epilepsy. Seizure. 2013;22(6):438-442. https://10.1016/j.seizure.2013.02.016

for a patient with an inability to tolerate a long-term, ambulatory EEG.

Mechanisms Of Memory-Supporting Neuronal Dynamics In Hippocampal Area Ca3, Yiding Li, John J Briguglio, Sandro Romani, Jeffrey C Magee

Faculty, Staff and Students Publications

Hippocampal CA3 is central to memory formation and retrieval. Although various network mechanisms have been proposed, direct evidence is lacking. Using intracellular Vm recordings and optogenetic manipulations in behaving mice, we found that CA3 place-field activity is produced by a symmetric form of behavioral timescale synaptic plasticity (BTSP) at recurrent synapses among CA3 pyramidal neurons but not at synapses from the dentate gyrus (DG). Additional manipulations revealed that excitatory input from the entorhinal cortex (EC) but not the DG was required to update place cell activity based on the animal’s movement. These data were captured by a computational model that …

The Brain Initiative Data-Sharing Ecosystem: Characteristics, Challenges, Benefits, And Opportunities, Sudhanvan Iyer, Kathryn Maxson Jones, Jill O Robinson, Nicole R Provenza, Dominique Duncan, Gabriel Lázaro-Muñoz, Amy L Mcguire, Sameer A Sheth, Mary A Majumder

Faculty, Staff and Students Publications

In this paper, we provide an overview and analysis of the BRAIN Initiative data-sharing ecosystem. First, we compare and contrast the characteristics of the seven BRAIN Initiative data archives germane to data sharing and reuse, namely data submission and access procedures and aspects of interoperability. Second, we discuss challenges, benefits, and future opportunities, focusing on issues largely specific to sharing human data and drawing on N = 34 interviews with diverse stakeholders. The BRAIN Initiative-funded archive ecosystem faces interoperability and data stewardship challenges, such as achieving and maintaining interoperability of data and archives and harmonizing research participants’ informed consents for …