Medical Specialties Commons^™

Rare Variants In Bmal1 Are Associated With A Neurodevelopmental Syndrome, Vishnu Anand Cuddapah, Dechun Chen, Bumsik Cho, Rebecca Moore, Mohnish Suri, Hana Safraou, Frederic Tran-Mau-Them, Ashley Wilson, Jacqueline Odgis, Atteeq U Rehman, Carol Saunders, Shiva Ganesan, Vaidehi Jobanputra, Stephen W Scherer, Ingo Helbig, Amita Sehgal

Duncan NRI Faculty and Staff Publications

Children with neurodevelopmental disorders exhibit highly penetrant sleep and circadian dysfunction, but the underlying mechanisms are unclear. We asked whether a subset of individuals with neurodevelopmental disorders might have genetic variants in genes known to drive circadian rhythms. Through international collaboration, we identified ten individuals with very rare genetic variants in BMAL1, a core component of the molecular clock. These individuals exhibited overlapping signs and symptoms including developmental delay, autism spectrum disorder, and variably penetrant marfanoid features. We functionally tested the identified BMAL1 variants in cell culture and in vivo and found disrupted BMAL1 function. These findings demonstrate that …

Maladjustment In Minority Youth From Community Network Disparities In The Covid-19 Lockdown Environment, Michael Okoronkwo, Aaron Mack, Keyana Varnado, Michael Alfred, Kevin Hardy, Amarachi Osuji, Percy Takyi, Gabriel I. Onor, Oluwatomi Akingbola, Rahn Bailey

Department of Medicine Faculty Papers

Pandemic lockdown orders resulted in closures to critical community networks. One such infrastructure was community recreation centers/parks. This infrastructure serves a critical role in building psychosocial wellness for youth. Socioeconomic minority youth face baseline disparity in center/park distribution and services. Youth recreation activity declined 50% as result of lockdown orders with corresponding decline in youth mental health status. Despite overall youth activity decline, White and high socioeconomic demographic categories were associated with greatest recreation access during the pandemic. Thus, the pandemic exacerbated preexisting disparities in recreation access for minority youth and its benefit towards adaptive development. Minority youth experienced greater …

Comparative Outcomes Of Coil Embolization And Surgical Clipping In Elderly Patients With Subarachnoid Hemorrhage: A Systematic Review And Meta-Analysis, Yohanna Idsabella Rossi, Gabriel Bolner, Jonathan Costa Dall'acqua, Fabiana Dolovitsch De Oliveira, Lucas V. Zacaria, Taís L. Denicol, Michel Frudit, Natália Vasconcellos De Oliveira Souza

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Elderly patients with subarachnoid hemorrhage (SAH) face a disproportionately high burden of morbidity and mortality. While endovascular coiling is often favored in this population, direct comparisons with surgical clipping are limited. We conducted a meta-analysis to compare outcomes of clipping versus coiling in SAH patients aged ≥ 60 years.

METHODS: A systematic search of PubMed, Embase, and Cochrane databases identified studies comparing the two treatments in this age group. The primary outcome was a composite of unfavorable outcomes (modified Rankin Scale [mRS] > 2 and mortality). Secondary outcomes included mortality, favorable outcome (mRS 0-2), rebleeding, and hospital length …

Kenyan Dietitians’ Knowledge Of Ketogenic Dietary Therapies For Drug-Resistant Epilepsy, Pauline Samia, Violet Naanyu, Perry Ndila, Helen Cross, Richard Idro, Paul Boon, Jo Wilmshurst, Stanley Luchters

Paediatrics and Child Health, East Africa

Background: Ketogenic dietary therapy (KDT) has been proven to be efficacious for people with drug-resistant epilepsy. However, it is rarely utilized in low-resource settings. Due to the complexity of implementation, dietitians play a crucial role in managing KDT.

Methods: We conducted a cross-sectional survey of 253 out of the 1,000 registered dietitians. We assessed their knowledge of and interest in further training in KDT.

Results: Most participants were female (78%), with a median age of 33 years (IQR=28–38). A total of 171 (67.6%) reported knowledge of KDT. However, only 13 respondents (7.6%) answered all five knowledge-specific questions correctly. A …

Summit Max: A Randomized Trial Of The Super Large Bore Hipoint Reperfusion System Versus Vecta System For Aspiration Thrombectomy., Thanh N Nguyen, Guilherme Dabus, Ben Mcguinness, James Caldwell, Ryan Priest, Ansaar T Rai, Osama O Zaidat, Bradley A Gross, Ricardo Hanel, Shane Lee, Shazam Hussain, Hamza Shaikh, Mohamad Abdalkader, Ronald Budzik, Craig Kilburg, Keith Woodward, Marco Colasurdo, Jesse Liu, Albert J Yoo, Priyank Khandelwal, Sohyun Boo, Phong Vu, Eugene Lin, Mohammad Almajali, Jasmeet Singh, Alhamza Al-Bayati, Michael J Lang, Michael Abraham, Ameer E Hassan, Peter Pema, Coleman Martin, Ramesh Grandhi, Daniel A Tonetti, Harry R Hixson, Amin Aghaebrahim, Eric Sauvageau, Santiago Ortega-Gutierrez, Dileep R Yavagal, Esteban Cheng-Ching, Jane Khalife, Italo Linfante, Volodymyr Vulkanov, Jazba Soomro, Johanna T Fifi, Lucien Maidan, Alexander Copelan, Clemens M Schirmer, Mark Bain, Gabor Toth, Mahesh Jayaraman, Roberta Novakovic-White, Sudhakar Satti, Nicolas Villelli, Pascal Jabbour, Matthew Page, Davina J Mcallister, Robert Araujo Contreras, Edgar A Samaniego, David S Liebeskind, Steven W Hetts, Raul G Nogueira, Joey English, Ajit S Puri

Neuroscience Articles

BACKGROUND: Rapid and complete recanalization is a primary goal in the endovascular treatment of large vessel occlusion stroke. The effectiveness and safety of super large bore aspiration catheters (0.088″ inner diameter) for the treatment of large vessel occlusion stroke have not been demonstrated in a randomized trial.

METHODS: SUMMIT MAX (A Prospective, Randomized, Controlled, Interventional Clinical Trial to Evaluate the Safety and Effectiveness of the Route 92 Medical MonoPoint Reperfusion System for Aspiration Embolectomy in Acute Ischemic Stroke Patients) was a prospective, randomized, controlled, open-label clinical trial of patients with internal carotid artery and middle cerebral artery M1 occlusions, comparing …

Prevalence And Risk Factors Of Cerebral Microhemorrhages And Superficial Siderosis In Cognitively Unimpaired Older Adults: Analysis From The Chariot-Pro Substudy, Sujin Kang, Dimitra Kafetsouli, Jamie Ford, Janice Wong, Luc Bracoud, Joyce Suhy, Parthenia Giannakopoulou, Chinedu Momoh, Tom Russ, Craig Ritchie

Brain and Mind Institute

Introduction: Cerebral microhemorrhages (CMHs) and superficial siderosis (SS) are relatively common side effects of anti-amyloid immunotherapies, termed amyloid-related imaging abnormalities (ARIA-H). They are also observed in treatment-naïve older adults. This study explored relationships with modifiable and non-modifiable risk factors.

Methods: This cross-sectional study included 1414 cognitively unimpaired, treatment-naïve individuals aged 60 to 85 years from the Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy. Relationships between CMHs/SS and cardiovascular risk factors, amyloid beta (Aβ) load, apolipoprotein E (APOE) ε4 status, educational attainment, and white matter hyperintensities were …

Chronic Cluster Headache Is A Rare Disease: Implications For Diagnosis, Treatment And Public Health, Hsiangkuo Yuan, Jan Hoffmann, Elena Ruiz De La Torre, Michael J. Marmura, Mario F. P. Peres

Department of Jefferson Headache Center Papers and Presentations

Cluster headache (CH) is a rare and painful primary headache disorder characterized by severe unilateral pain and cranial autonomic symptoms. This perspective examines the epidemiological evidence supporting the classification of chronic cluster headache (CCH) as a rare disease, noting a prevalence of CH of approximately 124 per 100,000 individuals, with only 3.5-13.7% manifesting CCH. This prevalence meets criteria established by both the US Food and Drug Administration and European Medicines Agency for rare disease designation. The rarity of CCH creates substantial clinical and research challenges, including prolonged diagnostic delays, limited research funding and a dearth of approved treatments. The economic …

Chronic Pain After Traumatic Brain Injury: Treatment Experiences And Effects On Cognition And Functioning, Rachael L. Snyder

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Traumatic brain injury (TBI) can contribute to changes in cognitive and emotional functioning, quality of life, and psychosocial reintegration. Chronic pain is a common consequence of TBI which can uniquely impact such outcomes. Still, the exact nature of the contribution of pain on post-TBI outcomes remains unclear, and there are few existing studies exploring the treatment journey for chronic pain and injury rehabilitation through qualitative methods, specifically individual interviews with TBI survivors. This study aimed to document these narratives and to identify precisely how the experiences of TBI survivors seeking treatments, rather than the treatments themselves, impact outcomes. It also …

Notice-Ed: Nurse Or Technician Insights Into Cognitive Evaluations In The Emergency Department, Sarah J Nessen, Anita N Chary, Annika R Bhananker, K Jane Muir, Lauren T Southerland, Kyra O'Brien, Ari B Friedman

Faculty, Staff and Students Publications

Background: Several strategies have been proposed to increase chronic cognitive impairment (CI) screening in the emergency department (ED). Our goal was to assess the feasibility and acceptability of implementing specific CI screening tools and strategies in the ED from an ED registered nurse and technician perspective.

Methods: We performed a qualitative study using semi-structured interviews with a purposive sample of ED nurses and ED technicians (EDTs). Participants worked at an urban academic hospital and were interviewed between November 2023 and March 2024. Interviews assessed participants' opinions on the feasibility and acceptability of CI screening and the use of machine learning …

Rest-Activity Rhythm Phenotypes In Adults With Epilepsy And Intellectual Disability, Nandani Adhyapak, Grace E Cardenas, Mark A Abboud, Vaishnav Krishnan

Faculty, Staff and Students Publications

Objective: Rest-activity rhythms (RARs) are perturbed in many forms of neuropsychiatric illness. In this study, we applied wrist actigraphy to describe RAR perturbations in intellectually disabled adults with epilepsy ("E + ID"), using a cross-sectional case-control design. We examined whether RAR phenotypes correlated with epilepsy severity, deficits in adaptive function, and/or comorbid psychopathology.

Methods: Caregivers of E + ID subjects provided informed consent during routine ambulatory clinic visits and were asked to complete standardized surveys of overall epilepsy severity (GASE, Global Assessment of Severity of Epilepsy), adaptive function (ABAS-3, Adaptive Behavior Assessment System-3) and psychopathology (ABCL, Adult Behavior Checklist). Caregivers …

Genetic Diversity And Expanded Phenotypes In Dystonia: Insights From Large-Scale Exome Sequencing, Mirja Thomsen, Fabian Ott, Sebastian Loens, Gamze Kilic-Berkmen, Ai Huey Tan, Shen-Yang Lim, Ebba Lohmann, Kaja M Schröder, Lea Ipsen, Lena A Nothacker, Linn Welzel, Alexandra S Rudnik, Frauke Hinrichs, Thorsten Odorfer, Kirsten E Zeuner, Friederike Schumann, Andrea A Kühn, Simone Zittel, Marius Moeller, Robert Pfister, Christoph Kamm, Anthony E Lang, Yi Wen Tay, Ana Luísa De Almeida Marcelino, Marie Vidailhet, Emmanuel Roze, Joel S Perlmutter, Jeanne S Feuerstein, Victor S C Fung, Florence Chang, Richard L Barbano, Steven Bellows, Aparna A Wagle Shukla, Alberto J Espay, Mark S Ledoux, Brian D Berman, Stephen Reich, Andres Deik, Andre Franke, Michael Wittig, Sören Franzenburg, Jens Volkmann, Norbert Brüggemann, H A Jinnah, Tobias Bäumer, Christine Klein, Hauke Busch, Katja Lohmann

Faculty, Staff and Students Publications

Objective: Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%), the etiology in most patients remains elusive. Moreover, understanding correlations between clinical manifestations and genetic variants has become increasingly complex.

Methods: Exome sequencing was conducted on 1924 genetically unsolved, mainly late-onset isolated dystonia patients, recruited primarily from two dystonia registries (DysTract and the Dystonia Coalition). Rare variants in genes previously linked to dystonia (n = 406) were examined, confirmed via Sanger sequencing, and analyzed for segregation when possible.

Results: We identified 137 distinct likely pathogenic/pathogenic variants (according to ACMG …

The Synaptic Architecture Of Layer 5 Thick Tufted Excitatory Neurons In Mouse Visual Cortex, Agnes L Bodor, Casey M Schneider-Mizell, Chi Zhang, Leila Elabbady, Alex Mallen, Andi Bergeson, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Rachel Dalley, Clare Gamlin, Emily Joyce, Daniel Kapner, Sam Kinn, Gayathri Mahalingam, Sharmishtaa Seshamani, Shelby Suckow, Marc Takeno, Russel Torres, Wenjing Yin, J Alexander Bae, Manuel A Castro, Sven Dorkenwald, Akhilesh Halageri, Zhen Jia, Chris Jordan, Nico Kemnitz, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, William Silversmith, Nicholas L Turner, Szi-Chieh Yu, William Wong, Jingpeng Wu, Brendan Celii, Luke Campagnola, Stephanie C Seeman, Tim Jarsky, Naixin Ren, Anton Arkhipov, Jacob Reimer, H Sebastian Seung, R Clay Reid, Forrest Collman, Nuno Maçarico Da Costa

Faculty, Staff and Students Publications

Despite significant progress in characterizing neocortical cell types, a complete understanding of the synaptic connections of individual excitatory cells remains elusive. This study investigates the connectivity of mouse visual cortex thick tufted layer 5 pyramidal cells, also known as extratelencephalic neurons (L5-ETns), using a 1 mm3 publicly available electron microscopy dataset. The analysis reveals that, in their immediate vicinity, L5-ETns primarily establish connections with a group of inhibitory cell types, which, in turn, specifically target the L5-ETns back. The most common excitatory targets of L5-ETns are layer 5 intertelencephalic neurons (L5-ITns) and layer 6 (L6) pyramidal cells, whereas synapses with …

Ruptured Arteriovenous Malformation Mortality: Incidence, Risk Factors, And Inpatient Outcome Score, Eric Feldstein, Allison Zhong, Kevin Clare, Bridget Nolan, Smit Patel, Nir Lavi-Romer, Zehavya Stadlan, Alis Dicpinigaitis, Jose Dominguez, Haris Kamal, Steven D Shapiro, Arundhati Biswas, Omar Tanweer, Ketan Bulsara, Carrie Muh, Jared Pisapia, Simon Hanft, Stephan Mayer, Chirag D Gandhi, Fawaz Al-Mufti

Faculty, Staff and Students Publications

Background

Limited literature exists on the morbidity and mortality of AVM associated intracerebral hemorrhage (ICH) compared with non-AVM ICH.

Objective

We examine morbidity and mortality in cAVM in a large nationwide inpatient sample to create a prognostic inpatient ruptured AVM mortality score.

Methods

This retrospective cohort study from 2008 to 2014 compares outcomes in cAVM related hemorrhages and ICH utilizing the National Inpatient Sample database. Diagnostic codes for ICH and AVM underlying ICH were identified. We compared case fatality according to medical complications. Multivariate analysis was used to derive hazard ratios and 95% confidence intervals to assess odds of mortality. …

Microbial Metabolite Regulation Of Microglial Ahr Signaling In Alzheimer’S Disease, Ghalya E. Alrousan

Dissertations and Theses (Open Access)

Introduction: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaque accumulation, neuroinflammation, and cognitive decline. Recent evidence suggests that systemic factors, particularly the gut microbiota and its metabolites, play a significant role in shaping brain immune responses, including microglial activation. However, the mechanisms linking gut dysbiosis to microglial dysfunction in AD are poorly understood. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor responsive to tryptophan metabolites, has recently gained attention as a key regulator of neuroinflammation and microglial function. I hypothesize that the loss of beneficial microbial AHR ligands, specifically indole derivatives, during aging and AD …

Bridging Psychiatry And Rare Genetic Diseases: A Scoping Review Of Therapeutic Strategies And Diagnostic Delay Paired With Healthcare Economic Burden Analysis, Sheldon R Garrison, Isaac J Siegel, Christopher R Takala, Sarah L Vaithilingam, Gene W Yang, Anthony W Zoghbi, Madeline M Hartig, Sreya Vadapalli, Margaret E Anderson

Duncan NRI Faculty and Staff Publications

Rare genetic diseases (RDs) with primary neuropsychiatric symptoms pose unique challenges for diagnosis and management. While the majority of these RDs have neuropsychiatric symptoms that are secondary to the RD, a subset presents with primary neuropsychiatric symptoms directly linked to their underlying pathophysiology. This subset has significant unmet medical need with delayed diagnoses leading to prolonged delays in treatment optimization and the trialing of medications that fail to target the underlying pathophysiology. This comprehensive review identifies 108 RDs with central neuropsychiatric symptoms that have a 7.7-year average diagnostic delay. Optimal management strategies for these RDs typically includes non-psychotropic medications, dietary …

Rapid Dissection And Dissociation Of The Mouse Olfactory Epithelium For Single-Nucleus Suspensions, Benjamin D W Belfort, Anthony M Insalaco, Claude C Chew, Johnathan D Jia, Julia Younis, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

The murine olfactory epithelium is the initial entry point of the olfactory system, housing various cell types that include olfactory sensory neurons, their regenerating progenitors, and support cells. Olfactory sensory neurons transduce chemical odorants into neural signals, yet the mechanisms underlying how these cells develop and turnover, create synapses with the olfactory bulb, and regulate their odorant receptors remain areas of intense study. Located on the dorsal aspect of the nasal cavity, the olfactory epithelium adheres to intricate bony structures known as turbinates. This anatomy poses unique challenges for its extraction and dissociation, especially in the context of preparing viable …

De Novo And Inherited Variants In Ddx39b Cause A Novel Neurodevelopmental Syndrome, Kevin T A Booth, Sharayu V Jangam, Martin M C Chui, Kayla Treat, Lorenzo Graziani, Alessia Soldano, Yao Ruan, Jeffrey Wan-Hei Hui, Kerry White, Celanie K Christensen, Ty Lynnes, Shinya Yamamoto, Oguz Kanca, Mandy H Y Tsang, Sally A Lynch, Sureni V Mullegama, Julia Baptista, Daniela Iancu, Shelagh K Joss, Sandra Y Y Wong, Christopher C Y Mak, Anna K Y Kwong, Hugo J Bellen, Erin Conboy, Remo Sanges, Anskar Yu-Hung Leung, Michael F Wangler, Brian H Y Chung, Francesco Vetrini

Duncan NRI Faculty and Staff Publications

DDX39B is a conserved member of the DEAD-box family of ATP-dependent RNA helicases, critical in mRNA metabolism across eukaryotes. DDX39B is also a core component of the TRanscription-EXport (TREX) super protein complex, and recent studies have highlighted the important role of its subunits in neurodevelopmental disorders. Here, we describe six individuals from five families, four harbouring de novo missense variants in DDX39B and one with an inherited splicing variant, presenting with variable developmental delay, congenital hypotonia, epilepsy, short stature, skeletal abnormalities, dysmorphic features and microcephaly in three patients.

3D molecular modelling predicts these variants would alter protein structure. In vitro …

Folliculin Depletion Results In Liver Cell Damage And Cholangiocarcinoma Through Mit/Tfe Activation, Bruno Maria Custode, Francesco Annunziata, Felipe Dos Santos Matos, Valentina Schiano, Veronica Maffia, Milena Lillo, Rita Colonna, Rossella De Cegli, Andrea Ballabio, Nunzia Pastore

Duncan NRI Faculty and Staff Publications

Mutations in the tumor suppressor gene Folliculin (FLCN) are responsible for Birt-Hogg-Dube’ (BHD) syndrome, a rare inherited condition that predisposes affected individuals to skin tumors, pulmonary cysts, and kidney tumors. FLCN regulates key cellular pathways, including TFEB, TFE3, and mTORC1, which are critical for maintaining cell homeostasis. Loss of FLCN leads to both hyperactivation of mTORC1 and constitutive activation of TFEB and TFE3, contributing to tumorigenesis. While previous studies showed that Flcn liver-specific conditional knockout (FlcnLiKO) mice are protected from developing liver fibrosis and damage upon high-fat diet exposure, the potential role of FLCN loss in liver carcinogenesis …

Contextualization Of Harmonized Cognitive Assessment Protocol (Hcap) In An Aging Population In Rural Low-Resource Settings In Africa: Experiences And Strategies Adopted To Optimize Effective Adaption Of Cognitive Tests In Kenya, Roselyter Riang’A, Eunice Muthoni, Niranjani Nagarajan, Felix Agoi, Patrick Mwangala, Alden Gross, Jean Ikanga, Kenneth Langa, Edward Miguel, Anthony Ngugi

Population Health, East Africa

Cross-cultural adaptation of cognitive assessments is crucial for detecting Alzheimer's disease (AD) and related dementias (ADRD) in aging populations. This study documents the adaptation of the Harmonized Cognitive Assessment Protocol (HCAP) for a pilot study on the Longitudinal Study of Health and Aging in Kenya (LOSHAK) in rural Kilifi County, Kenya, highlighting challenges and strategies for optimizing outcomes. As part of the LOSHAK feasibility phase, cognitive tests including: the Swahili Mental State Examination, 10-word recall, animal naming, story recall, clock drawing, and making change, were administered to 202 participants (≥45 years) from the Kaloleni/Rabai Health and Demographic Surveillance System (KRHDSS). …

Midlife Cognitive Testing In Africa: Validity Of The Harmonised Cognitive Assessment Protocol In The Kenya Life Panel Survey, Alden Gross, Madeline Duhon, Eric Ochieng, Jean Ikanga, William Dow, Jinkook Lee, Michael Walker, Michelle Layvant, Anthony Ngugi, Joshua Ehrlich

Population Health, East Africa

Objectives: Cohort studies of ageing and cognitive decline typically do not begin fielding comprehensive cognitive assessments until older adulthood. However, for identifying preventable dementia risk factors, there is strong value in beginning at earlier ages. The case is especially compelling in sub-Saharan Africa, where the number of older individuals is expected to triple in the next three decades, and where risk factors may operate more intensively at earlier ages. This study reports on the adaptation and validity of the Harmonised Cognitive Assessment Protocol (HCAP) approach in the Kenya Life Panel Survey (KLPS), collected among middle-aged respondents.

Design: To evaluate the …

Diagnostic Value Of Cell-Free Dna Fetal Fraction In Patients With Prenatally Suspected Placenta Accreta Spectrum Disorder, Danielle Chirumbole, Christian M Parobek, Alex Tai, Haleh Sangi-Haghpeykar, Yamely H Mendez, Spoorthi Kamepalli, Christina C Reed, Arthur Ladron De Guevara, Keneshia Lane, Claire Hoppenot, Amir A Shamshirsaz, Michael A Belfort, Jessian L Munoz, Hendrik A Lombaard

Faculty, Staff and Students Publications

Objective: The purpose of this study was to investigate the relationship between fetal fraction (FF) and placenta accreta spectrum (PAS) pathology in patients with prenatally suspected PAS.

Methods: This was a case-control study utilizing a database of pregnancies with suspected or proven PAS delivered between 6/2012 and 7/2024 at a single institution. Pregnancies were excluded if FF was not reported. The primary outcome was mean FF in pregnancies with a final clinical diagnosis of low FIGO grade (no PAS or FIGO1-2) versus high FIGO grade (FIGO3) placenta accreta. Results were reported as mean FF ± standard error of the mean. …

Effectiveness And Safety Of Abobotulinumtoxina In Pediatric Lower Limb Spasticity: A Phase Iv, Prospective, Observational, Multicenter Study, Mark E. Gormley, Edward Dabrowski, Mauricio R. Delgado, Ann Tilton, Asare Christian, Sarah Helen Evans, Anne-Sophie Grandoulier, Jumaah Goldberg

School of Medicine Faculty Publications

Aim: To assess the longitudinal attainment of patient-centered, function-related Goal Attainment Scaling Total (GAS T)-score after repeated abobotulinumtoxinA (AboBoNT-A) injections over a period of up to 30 months and up to 10 cycles. Method: In this prospective observational study, the investigators' clinical practices recruited patients aged 2 to 17 years with pediatric lower limb spasticity (PLLS). GAS T-scores were assessed for each injection, and goals could be redefined at each visit; scores of 50 reflected goal achievement. Adverse events were recorded. Results: Of 210 patients in the effectiveness population, 171 had cerebral palsy and 163 were previously treated with a …

High-Gamma And Beta Bursts In The Left Supramarginal Gyrus Can Differentiate Verbal Memory States And Performance, Shennan Aibel Weiss, Nicolás Sawczuk, Daniel Y. Rubinstein, Michael R Sperling, Katrina Wendel-Mitoraj, Päivi Österman, René Dumay-Roscher, Charles B. Mikell, Sima Mofakham, Kelly Coulehan, Petar M. Djuric, Diego Fernandez Slezak, Juan Esteban Kamienkowski

Department of Neurology Faculty Papers

INTRODUCTION: The left supramarginal gyrus (LSMG) contributes to attentional allocation for memory encoding and may also reflect memory state and performance. Given the roles of high-gamma and beta bursts in cognition and memory, this proof-of-concept study investigated whether these signals within the LSMG could classify memory state and performance.

METHODS: Using secondary data from 103 epilepsy patients undergoing presurgical iEEG evaluation, we analyzed 141 delayed verbal free recall experiments. Intracranial EEG (iEEG) data, recorded solely from LSMG electrode contacts, were processed to create two-dimensional (2D) tensors of convolved high-gamma (HG), and beta (15-40 Hz) burst activity. Convolutional neural networks (CNNs) …

Unusual Wave Morphologies In Ulnar Neuropathy With Marinacci Anastomosis: A Case Report, Micaela Owens

Marshall Journal of Medicine

Marinacci anastomosis is a normal but rare anatomic variant of the median and ulnar nerves, consisting of an interconnection from the ulnar nerve to the median nerve within the proximal forearm. This is a case of Marinacci anastomosis occurring in the presence of both median and ulnar neuropathies, producing unusual waveform characteristics. Knowledge of normal anatomic variation can improve diagnostic accuracy in nerve conduction studies.

Cell Type-Specific Purifying Selection Of Synonymous Mitochondrial Dna Variation, Caleb A Lareau, Patrick Maschmeyer, Yajie Yin, Jacob C Gutierrez, Ryan S Dhindsa, Anne-Sophie Gribling-Burrer, Sebastian Zielinski, Yu-Hsin Hsieh, Lena Nitsch, Veronika Dimitrova, Benan Nalbant, Frank A Buquicchio, Tsion Abay, Robert R Stickels, Jacob C Ulirsch, Patrick Yan, Fangyi Wang, Zhuang Miao, Katalin Sandor, Bence Daniel, Vincent Liu, Paul L Mendez, Petra Knaus, Manpreet Meyer, William J Greenleaf, Anshul Kundaje, Redmond P Smyth, Mathias Munschauer, Leif S Ludwig, Ansuman T Satpathy

Duncan NRI Faculty and Staff Publications

While somatic variants are well-characterized drivers of tumor evolution, their influence on cellular fitness in nonmalignant contexts remains understudied. We identified a mosaic synonymous variant (m.7076A > G) in the mitochondrial DNA (mtDNA)-encoded cytochrome c-oxidase subunit 1 (MT-CO1, p.Gly391=), present at homoplasmy in 47% of immune cells from a healthy donor. Single-cell multiomics revealed strong, lineage-specific selection against the m.7076G allele in CD8+ effector memory T cells, but not other T cell subsets, mirroring patterns of purifying selection of pathogenic mtDNA alleles. The limited anticodon diversity of mitochondrial tRNAs forces m.7076G translation to rely on wobble pairing, unlike the Watson-Crick-Franklin pairing …

Sleep Drive, Not Total Sleep Amount, Increases Seizure Risk, Vishnu Anand Cuddapah, Cynthia T Hsu, Fernanda Valle Sirias, Yongjun Li, Hrishit M Shah, Christopher Saul, Samantha Killiany, Camilo Guevara, Joy Shon, Zhifeng Yue, Gabrielle L Gionet, Mary E Putt, Amita Sehgal

Duncan NRI Faculty and Staff Publications

Sleep loss has been associated with increased seizure risk since antiquity. Using automated video detection of spontaneous seizures in Drosophila epilepsy models, we show that seizures worsen only when sleep restriction raises homeostatic "sleep drive," not simply when total sleep amount falls. This is supported by the paradoxical finding that acute activation of sleep-promoting circuits worsens seizures, because it increases sleep drive without changing sleep amount. Sleep-promoting circuits become hyperactive after sleep loss and are associated with increased whole-brain activity. During sleep restriction, optogenetic inhibition of sleep-promoting circuits to reduce sleep drive protects against seizures. Downregulation of the 5HT1A serotonin …

"Star Sign" Of Subarachnoid Hemorrhage, Shivani Ruf

Florida Journal of Emergency Medicine (FJEM)

A 60-year-old female who was brought to the emergency department after a syncopal episode. She was found to have a subarachnoid hemorrhage (SAH) from a ruptured anterior communicating artery aneurysm. Her CT showed the classic "star sign" of SAH.

The Sodium-Glutamate Antagonist Riluzole Improves Outcome After Acute Spinal Cord Injury: Results From The Riscis Randomised Controlled Trial Analysed Using A Global Statistical Analytic Technique, Michael G. Fehlings, Karlo M. Pedro, Mohammed Ali Alvi, Ali Moghaddamjou, James S. Harrop, Ralph Stanford, Jonathon Ball, Bizhan Aarabi, Paul M. Arnold, James D. Guest, Shekar N. Kurpad, James M. Schuster, Ahmad N. Nassr, Karl M. Schmitt, Jefferson R. Wilson, Darrel S. Brodke, Faiz U. Ahmad, Albert Yee, Wilson Z. Ray, Nathaniel P. Brooks, Jason Wilson, Diana S-L Chow, Elizabeth G. Toups, Kevin E. Thorpe, Jiaxin Huang, Peng Huang

Department of Neurosurgery Faculty Papers

BACKGROUND: Spinal cord injury (SCI) clinical trials typically rely on a single primary endpoint to assess drug efficacy. This strategy fails to adequately capture the full impact of treatment in heterogenous neurological conditions like SCI. A more patient-centric analysis requires assessment of neurological function, functional capacity, and quality of life, incorporating meaningful patient-reported outcomes. The global statistical test (GST) addresses this challenge using a unified statistical conclusion regarding the superiority of a treatment strategy over another by evaluating multiple trial endpoints simultaneously.

METHODS: The RISCIS trial (Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study) data was analysed …

Multi-Ancestry Genome-Wide Meta-Analysis Of 56,241 Individuals Identifies Known And Novel Cross-Population And Ancestry-Specific Associations As Novel Risk Loci For Alzheimer’S Disease, Farid Rajabli, Penelope Benchek, Giuseppe Tosto, Nicholas Kushch, Jin Sha, Katrina Bazemore, Congcong Zhu, Wan-Ping Lee, Jacob Haut, Kara L Hamilton-Nelson, Nicholas R Wheeler, Yi Zhao, John J Farrell, Michelle A Grunin, Yuk Yee Leung, Pavel P Kuksa, Donghe Li, Eder Lucio Da Fonseca, Jesse B Mez, Ellen L Palmer, Jagan Pillai, Richard M Sherva, Yeunjoo E Song, Xiaoling Zhang, Takeshi Ikeuchi, Taha Iqbal, Omkar Pathak, Otto Valladares, Dolly Reyes-Dumeyer, Amanda B Kuzma, Erin Abner, Larry D Adams, Perrie M Adams, Alyssa Aguirre, Marilyn S Albert, Roger L Albin, Mariet Allen, Lisa Alvarez, Liana G Apostolova, Steven E Arnold, Sanjay Asthana, Craig S Atwood, Sanford Auerbach, Gayle Ayres, Clinton T Baldwin, Robert C Barber, Lisa L Barnes, Sandra Barral, Thomas G Beach, James T Becker, Gary W Beecham, Duane Beekly, Bruno A Benitez, David Bennett, John Bertelson, Thomas D Bird, Deborah Blacker, Bradley F Boeve, James D Bowen, Adam Boxer, James Brewer, James R Burke, Jeffrey M Burns, Joseph D Buxbaum, Nigel J Cairns, Laura B Cantwell, Chuanhai Cao, Christopher S Carlson, Cynthia M Carlsson, Regina M Carney, Minerva M Carrasquillo, Scott Chasse, Marie-Francoise Chesselet, Nathaniel A Chin, Helena C Chui, Jaeyoon Chung, Suzanne Craft, Paul K Crane, David H Cribbs, Elizabeth A Crocco, Carlos Cruchaga, Michael L Cuccaro, Munro Cullum, Eveleen Darby, Barbara Davis, Philip L De Jager, Charles Decarli, John Detoledo, Malcolm Dick, Dennis W Dickson, Beth A Dombroski, Rachelle S Doody, Ranjan Duara, Nilüfer Ertekin-Taner, Denis A Evans, Kelley M Faber, Thomas J Fairchild, Kenneth B Fallon, David W Fardo, Martin R Farlow, Victoria Fernandez-Hernandez, Steven Ferris, Robert P Friedland, Tatiana M Foroud, Matthew P Frosch, Brian Fulton-Howard, Douglas R Galasko, Adriana Gamboa, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Rodney C P Go, Alison M Goate, Thomas J Grabowski, Neill R Graff-Radford, Robert C Green, John H Growdon, Hakon Hakonarson, James Hall, Ronald L Hamilton, Oscar Harari, John Hardy, Lindy E Harrell, Elizabeth Head, Victor W Henderson, Michelle Hernandez, Timothy Hohman, Lawrence S Honig, Ryan M Huebinger, Matthew J Huentelman, Christine M Hulette, Bradley T Hyman, Linda S Hynan, Laura Ibanez, Gail P Jarvik, Suman Jayadev, Lee-Way Jin, Kim Johnson, Leigh Johnson, M Ilyas Kamboh, Anna M Karydas, Mindy J Katz, John S Kauwe, Jeffrey A Kaye, C Dirk Keene, Aisha Khaleeq, Masataka Kikuchi, Ronald Kim, Janice Knebl, Neil W Kowall, Joel H Kramer, Walter A Kukull, Frank M Laferla, James J Lah, Eric B Larson, Alan Lerner, James B Leverenz, Allan I Levey, Andrew P Lieberman, Richard B Lipton, Mark Logue, Oscar L Lopez, Kathryn L Lunetta, Constantine G Lyketsos, Douglas Mains, Flanagan E Margaret, Daniel C Marson, Eden Rr Martin, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Paul Massman, Arjun Masurkar, Wayne C Mccormick, Susan M Mccurry, Andrew N Mcdavid, Stefan Mcdonough, Ann C Mckee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Thomas J Montine, Edwin S Monuki, John C Morris, Shubhabrata Mukherjee, Amanda J Myers, Trung Nguyen, Thomas Obisesan, Sid O'Bryant, John M Olichney, Marcia Ory, Raymond Palmer, Joseph E Parisi, Henry L Paulson, Valory Pavlik, David Paydarfar, Victoria Perez, Elaine Peskind, Ronald C Petersen, Helen Petrovitch, Aimee Pierce, Marsha Polk, Wayne W Poon, Huntington Potter, Liming Qu, Mary Quiceno, Joseph F Quinn, Ashok Raj, Murray Raskind, Eric M Reiman, Barry Reisberg, Joan S Reisch, John M Ringman, Erik D Roberson, Monica Rodriguear, Ekaterina Rogaeva, Howard J Rosen, Roger N Rosenberg, Donald R Royall, Marwan Sabbagh, A Dessa Sadovnick, Mark A Sager, Mary Sano, Andrew J Saykin, Julie A Schneider, Lon S Schneider, William W Seeley, Susan H Slifer, Scott Small, Amanda G Smith, Janet P Smith, Joshua A Sonnen, Salvatore Spina, Peter St George-Hyslop, Takiyah D Starks, Robert A Stern, Alan B Stevens, Stephen M Strittmatter, David Sultzer, Russell H Swerdlow, Rudolph E Tanzi, Jeffrey L Tilson, John Q Trojanowski, Juan C Troncoso, Magda Tsolaki, Debby W Tsuang, Vivianna M Van Deerlin, Linda J Van Eldik, Jeffery M Vance, Badri N Vardarajan, Robert Vassar, Harry V Vinters, Jean-Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Patrice L Whitehead, Ellen M Wijsman, Kirk C Wilhelmsen, Benjamin Williams, Jennifer Williamson, Henrik Wilms, Thomas S Wingo, Thomas Wisniewski, Randall L Woltjer, Martin Woon, Clinton B Wright, Chuang-Kuo Wu, Steven G Younkin, Chang-En Yu, Lei Yu, Xiongwei Zhu, Brian W Kunkle, William S Bush, Akinori Miyashita, Goldie S Byrd, Li-San Wang, Lindsay A Farrer, Jonathan L Haines, Richard Mayeux, Margaret A Pericak-Vance, Gerard D Schellenberg, Gyungah R Jun, Christiane Reitz, Adam C Naj, Alzheimer’S Disease Genetics Consortium (Adgc)

Faculty, Staff and Students Publications

Background: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis.

Results: We identify 13 loci with cross-population associations including known loci at/near CR1, …

Neonatal Seizures: Advances In Diagnosis And Management, Elissa G Yozawitz, Ronit M Pressler, Eli M Mizrahi

Faculty, Staff and Students Publications

The International League Against Epilepsy (ILAE) created the ILAE Neonatal Task Force that classified neonatal seizures, defined neonatal epilepsy syndromes, and specified treatment guidelines. These frameworks, in addition to improved access to genetic testing and other recent advances, have revolutionized the diagnosis and management of neonatal seizures. PLAIN LANGUAGE SUMMARY: Neonatal seizures, occurring within the first 4 weeks of life, present unique challenges due to the immature neonatal brain. The International League Against Epilepsy (ILAE) Neonatal Task Force revolutionized diagnosis and management through classification, syndrome definition, and treatment guidelines. Despite advancements, challenges persist, including accurate diagnosis and limited evidence-based treatment …