Neurology Commons^™

Current Controversies In Prenatal Diagnosis 2: Conventional Postmortem Examination Remains The Gold Standard For The Anatomical Examination Of Fetal Loss, J Ciaran Hutchinson, Lorraine Potocki, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

A comprehensive postmortem examination is an essential component of a work-up after stillbirth. Its findings can support accurate counseling of parents about causes and risk of recurrence. It also supports providers' decisions about most appropriate testing and management plans for future pregnancy to prevent recurrence. Informing parents about fetal autopsy and obtaining their consent is challenging, and conducting a fetal autopsy requires expertise that is, not universally available. Newer non-invasive or minimally invasive methods such as postmortem MRI and targeted biopsies can replace or supplement autopsies, but one must recognize that expertise in these methods is likewise not broadly available. …

Prenatal Genetic Consultation And Testing, Sarah Araji, Lauren Westerfield, Roni Zemet, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

The evolution of prenatal genetic testing has transformed prenatal diagnosis into a more precise and individualized approach. Advanced tools such as chromosomal microarray analysis and exome sequencing have enabled the prenatal diagnosis of more genetic conditions, including anomalies and disorders eligible for fetal therapy. When in utero therapy is considered, accurate genetic diagnosis is essential for guiding providers' and patients' decisions regarding management and outcomes. This chapter reviews available prenatal genetic screens and tests, their indications, and counseling strategies. It also explores genetic abnormalities associated with fetal structural anomalies and their implications for decision-making in fetal interventions.

Adaptive Filters At The First Olfactory Synapse, Elizabeth H Moss, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

The olfactory system is able to filter odor representations based on attention and learning. Two PLoS Biology studies reveal how short axon cells in the olfactory bulb integrate cholinergic input from the basal forebrain to dynamically regulate olfactory input.

Diagnostic Yield Of Exome Sequencing For Pregnancies With And Without Fetal Anomalies And For Stillbirth, Roni Zemet, Christian M Parobek, April D Adams, Mohamad Ali Maktabi, Lena Shay, Linyan Meng, Pengfei Liu, Hongzheng Dai, Fan Xia, Christine Eng, Ignatia B Van Den Veyver, Liesbeth Vossaert

Duncan NRI Faculty and Staff Publications

Objective: Exome sequencing (ES) benefits the genetic work-up for fetuses with structural anomalies, but data on its utility for fetuses without anomalies and stillbirths is more limited. We report our experience with prenatal ES for all three indications.

Method: We retrospectively reviewed results from 344 trio-ES performed for fetuses with structural anomalies (N = 262), stillbirths (N = 39), and fetuses without anomalies (N = 43), many of which had a relevant family history. We classified pathogenic variants (P), likely pathogenic variants (LP), or variants of uncertain significance (VUS) favoring pathogenicity in a gene consistent with the fetal phenotype as …

Coenzyme Q Headgroup Intermediates Can Ameliorate A Mitochondrial Encephalopathy, Guangbin Shi, Claire Miller, Sota Kuno, Alejandro G Rey Hipolito, Salsabiel El Nagar, Giulietta M Riboldi, Megan Korn, Wyatt C Tran, Zixuan Wang, Lia Ficaro, Tao Lin, Quentin Spillier, Begoña Gamallo-Lana, Drew R Jones, Matija Snuderl, Soomin C Song, Adam C Mar, Alexandra L Joyner, Roy V Sillitoe, Robert S Banh, Michael E Pacold

Duncan NRI Faculty and Staff Publications

Decreased brain levels of coenzyme Q10 (CoQ10), an endogenously synthesized lipophilic antioxidant1,2, underpin encephalopathy in primary CoQ10 deficiencies3,4 and are associated with common neurodegenerative diseases and the ageing process5,6. CoQ10 supplementation does not increase CoQ10 pools in the brain or in other tissues. The recent discovery of the mammalian CoQ10 headgroup synthesis pathway, in which 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) makes 4-hydroxymandelate (4-HMA) to synthesize the CoQ10 headgroup precursor 4-hydroxybenzoate (4-HB)7, offers an opportunity to pharmacologically restore CoQ10 synthesis and mechanistically treat CoQ10 deficiencies. To test whether 4-HMA …

Society Of Vascular And Interventional Neurology (Svin) Stroke Interventional Laboratory Consensus (Silc) Criteria For Training Standards And Maintenance Of Certification In Neurointervention, Ossama Y. Mansour, Kaiz S. Asif, Roberta Novakovic-White, Boris Pabon, Santiago Ortega-Gutierrez, Atilla Ozcan Ozdemar, Alicia Castonguay, Brijesh Mehta, Dileep R. Yavagal, Ameer E. Hassan

School of Medicine Publications

The global shortage of neurointerventionalists presents a challenge to timely stroke care, particularly in low‐ and middle‐income countries. The Society of Vascular and Interventional Neurology Stroke Interventional Laboratory Consensus criteria aim to standardize training and certification in neurointervention to address these disparities. This white paper reviews existing training standards in various regions, identifies gaps, and proposes a structured framework encompassing entry requirements, program structure, and certification processes. The Stroke Interventional Laboratory Consensus criteria further outline requirements for training centers and program directors. By establishing global standards, the Stroke Interventional Laboratory Consensus criteria seek to improve patient outcomes and expand access …

Catheter Erosion Through The Rectum 8 Years After Uncomplicated Ventriculoperitoneal Shunt Placement: Illustrative Case, Matthew Wierzbicki, India Shelley, Matthews Lan, Aria Mahtabfar, Christopher J. Farrell

Department of Neurosurgery Faculty Papers

BACKGROUND: Distal bowel perforation by peritoneal catheter (BPPC) is a rare complication following ventriculoperitoneal shunt (VPS) placement for the treatment of hydrocephalus. In some cases, BPPC may present with extrusion through the anus and can occur years after VPS placement.

OBSERVATIONS: The authors report the case of a 30-year-old woman who had a VPS placed 8 years prior and found a catheter protruding from her rectum. Having pulled out 1 foot of catheter, she presented to the hospital where the shunt was externalized before concurrent VPS removal and laparotomy to repair the bowel perforation.

LESSONS: BPPC with anal extrusion is …

Risk Of Major Depression In Partners Of People With Alzheimer's Disease: A National Cohort Study, Casey Crump, Jingkai Wei, Barbara G Vickrey, Alexis C Edwards, Paul E Schulz, Weiva Sieh, Jan Sundquist, Kristina Sundquist

Faculty, Staff and Student Publications

Background: Alzheimer's disease (AD) may cause significant psychosocial distress not only in the patient but also their partner. However, long-term risks of major depression in partners of AD patients are largely unknown.

Methods: A national cohort study was conducted of all 145 289 partners of people diagnosed with all-cause dementia, including 57 113 partners of people diagnosed with AD, in Sweden during 1998-2017, and 1 300 561 population-based controls. Cox regression was used to compute hazard ratios (HRs) for subsequent risk of major depression identified from nationwide outpatient and inpatient diagnoses through 2018, adjusting for sociodemographic factors and prior mental …

Conventional Versus Advanced Imaging Selection For Endovascular Treatment Of Basilar Artery Occlusion Strokes, Huanwen Chen, Marco Colasurdo, Hidetoshi Matsukawa, Conor Cunningham, Ilko Maier, Sami Al Kasab, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M Starke, Marios-Nikos Psychogios, Edgar A Samaniego, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Jonathan A Grossberg, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Roberto Crosa, Charles Matouk, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Travis Dumont, Ergun Daglioglu, Richard Williamson, Pedro Navia, Reade De Leacy, Shakeel Chowdhry, David J Altschul, Alejandro M Spiotta, Peter Kan

Faculty, Staff and Students Publications

Introduction: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear.

Patients and methods: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in …

Heterozygous Variants In Plcg1 Affect Hearing, Vision, Cardiac, And Immune Function, Mengqi Ma, Yiming Zheng, Mingxi Deng, Shenzhao Lu, Xueyang Pan, Xi Luo, Michelle Etoundi, David Li-Kroeger, Kim C Worley, Lindsay C Burrage, Lauren S Blieden, Aimee Allworth, Wei-Liang Chen, Giuseppe Merla, Barbara Mandriani, Catherine E Otten, Pierre Blanc, Jill A Rosenfeld, Debdeep Dutta, Shinya Yamamoto, Michael F Wangler, Ian A Glass, Jingheng Chen, Elizabeth Blue, Paolo Prontera, Jeremie Rosain, Sandrine Marlin, Seema R Lalani, Hugo J Bellen, Undiagnosed Diseases Network

Duncan NRI Faculty and Staff Publications

Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP₂) into inositol 1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG), important signaling molecules involved in many cellular processes including Ca²⁺ release from the endoplasmic reticulum (ER). PLCG1 encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of PLCG1 are observed in multiple cancers, but only one germline variant has been reported. Here, we describe seven individuals with heterozygous missense variants in PLCG1 [p.(Asp1019Gly), p.(His380Arg), p.(Asp1165Gly), and p.(Leu597Phe)] who present with hearing impairment (5/7), ocular pathology (4/7), cardiac septal defects (3/6), and various immunological issues (5/7). To model these …

A Protective Role Of Src-1 Against Aging Associated Cognitive Decline, Hesong Liu, Yongjie Yang, Jonathan C Bean, Yang He, Hailan Liu, Rambabu Majji, Chen Liang, Nan Zhang, Meng Yu, Longlong Tu, Qingzhuo Liu, Yue Deng, Kristine M Conde, Na Yin, Mengjie Wang, Yongxiang Li, Junying Han, Sanika Vattakuzhiyil Jossy, Megan Elyse Burt, Hari Krishna Yalamanchili, Chunmei Wang

Duncan NRI Faculty and Staff Publications

Introduction: Research indicates a strong correlation between obesity and the risk of dementia, both are linked to steroid receptor coactivator-1 (SRC-1), a transcriptional coactivator.

Methods: We used RNA sequencing analysis (RNA-Seq) to investigate the transcriptome of SRC-1-KO mice, and identified S100 calcium-binding protein A6 (S100A6), an AD associated gene, as one target of SRC-1. We tested cognitive behaviors in SRC-1-KO mice and mice with a humanized SRC-1 mutation (SRC-1L1376P), and performed promoter luciferase assays on S100A6.

Results: Loss of SRC-1 caused alterations in gene signatures that are commonly associated with neurodegenerative diseases, including AD, and diminished the neural plasticity of …

Mri-Guided Focused Ultrasound Thalamotomy For Neuropathic Pain In An Adolescent With Cranial Metastases: Illustrative Case, Sarah G Van Winkle, Danika L Paulo, Ashwin Viswanathan, Daniel Curry, Nisha Gadgil

Faculty, Staff and Students Publications

Background: Neuropathic cancer pain (NCP) is a debilitating condition that is often refractory to conventional medical management. MRI-guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) is an incisionless neurosurgical option for neuropathic pain palliation, but its use in pediatric patients and those with cranial metastases, a relative contraindication to MRgFUS, remains largely unexamined.

Observations: A 16-year-old male with metastatic rhabdomyosarcoma (RMS) with numerous cranial metastases experienced severe, diffuse, refractory NCP. The patient underwent bilateral CLT with MRgFUS. After the procedure, the patient experienced complete and durable resolution of his neuropathic pain. He only reported occasional somatic pain at sites of …

A Case Of Adrenal Insufficiency Presenting With Seizures, Complicated By Developmental Cerebral Venous Anomaly And Takotsubo Cardiomyopathy: A Case Report, Katrina Villegas, Brittany Eason, Karolina Janiec, Alaa Musallam, Ahmed Hammouda, Samia Ammar Aldwaik, Radhika Tailor

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Adrenal insufficiency is a potentially life-threatening condition that often presents with nonspecific symptoms. While fatigue, hypotension, and electrolyte disturbances are common features, seizures and stress-induced cardiomyopathy are rare initial manifestations. This case is reported for its atypical presentation and to highlight the diagnostic challenge it posed in the absence of classic biochemical findings.

CASE PRESENTATION: We report a case of a 68-year-old Hispanic woman with diabetes, hypertension, dyslipidemia, and hypopituitarism secondary to Sheehan syndrome, who presented with new-onset seizures after abruptly discontinuing chronic steroid therapy. Her symptoms included progressive weakness and behavioral changes over several weeks. Initial evaluation revealed …

Gm-Csf Production By Immune Cells In Steady State And Autoimmune Neuroinflammation Mapped Using Fate Reporting Mice, Gholamreza Azizi, Javad Rasouli, Hamed Naziri, Michael V. Gonzalez, James Garifallou, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad M. Rostami

Department of Neurology Faculty Papers

INTRODUCTION: GM-CSF is a pro-inflammatory cytokine that promotes an inflammatory phenotype in myeloid cells. The extent and pattern of GM-CSF expression in immune cells have not been fully elucidated. Our goal was to advance this topic using novel GM-CSF reporter/fate reporter transgenic mice.

METHODS: We tracked ongoing and past GM-CSF expression in various immune cells from multiple organs, in steady-state and autoimmune inflammation of the central nervous system (CNS).

RESULTS: The GM-CSF expression patterns varied by cell type and organ, with CD4

DISCUSSION: These findings identified distinct GM-CSF cellular sources across organs, highlighting the transient nature of GM-CSF expression and …

Current Practices In The Study Of Biomolecular Acondensates: A Community Comment, Simon Alberti, Paolo Arosio, Robert B Best, Steven Boeynaems, Danfeng Cai, Rosana Collepardo-Guevara, Gregory L Dignon, Rumiana Dimova, Shana Elbaum-Garfinkle, Nicolas L Fawzi, Monika Fuxreiter, Amy S Gladfelter, Alf Honigmann, Ankur Jain, Jerelle A Joseph, Tuomas P J Knowles, Keren Lasker, Edward A Lemke, Kresten Lindorff-Larsen, Reinhard Lipowsky, Jeetain Mittal, Samrat Mukhopadhyay, Sua Myong, Rohit V Pappu, Karsten Rippe, Tatyana A Shelkovnikova, Anthony G Vecchiarelli, Susanne Wegmann, Huaiying Zhang, Mingjie Zhang, Chloe Zubieta, Markus Zweckstetter, Dorothee Dormann, Tanja Mittag

Duncan NRI Faculty and Staff Publications

The realization that the cell is abundantly compartmentalized into biomolecular condensates has opened new opportunities for understanding the physics and chemistry underlying many cellular processes, fundamentally changing the study of biology. The term biomolecular condensate refers to non-stoichiometric assemblies that are composed of multiple types of macromolecules in cells, occur through phase transitions, and can be investigated by using concepts from soft matter physics. As such, they are intimately related to aqueous two-phase systems and water-in-water emulsions. Condensates possess tunable emergent properties such as interfaces, interfacial tension, viscoelasticity, network structure, dielectric permittivity, and sometimes interphase pH gradients and electric potentials–. …

High-Grade Glioma With Pleomorphic And Pseudopapillary Features: A Single-Institution Series Of Three Cases, Eric A Goethe, Rasha Alfattal, Subhiksha Srinivasan, Pushan Dasgupta, Vinay Puduvalli, Shiao-Pei Weathers, Leomar Y Ballester, Jeffrey S Weinberg, Sujit Prabhu, Sherise D Ferguson, Maria A Gubbiotti

Faculty, Staff and Students Publications

Introduction: Modern molecular diagnostic techniques such as DNA methylation profiling are leading to the reclassification of several central nervous system malignancies and discovery of novel diagnostic entities, such as high-grade glioma with pleomorphic and pseudopapillary features (HPAP).

Methods: We performed a retrospective chart review of all patients with HPAP confirmed with methylation profiling at a single institution between 2023 and 2025. Demographic, radiographic, surgical, and outcome data were collected.

Results: Three patients were identified: two females and one male with a mean age of 49.7 years (range 25-62). No patients had a prior cancer history. One patient had an incidentally …

Botulinum Toxin For The Treatment Of Tremors, Steven Bellows, Joseph Jankovic

Faculty, Staff and Students Publications

Tremor, an oscillatory movement disorder, is commonly encountered in clinical practice in the setting of a variety of etiologies, such as essential tremor and Parkinson's disease. Despite its high prevalence, treatment options are somewhat limited. Oral medications are often ineffective or limited by side effects, and other treatments, such as deep brain stimulation, are more invasive and costly. Botulinum toxin (BoNT) injections are a well-established therapy in the treatment of dystonia, but its use in the treatment of tremors has not been fully explored. In this review, we discuss the available randomized controlled trials and open-label evidence for the use …

Mirna-Mediated Regulation Of S100b: A Review, Animesh Dali, Suhana Basnyat, Rachel Delancey, Nipun Chopra

Psychology and Neuroscience Faculty Publications

S100β is a significant signaling molecule and biomarker that is primarily expressed in the brain. At low physiological concentrations, S100β induces astrocyte maturation, microglial migration, and neural proliferation. However, high concentrations activate inflammatory and pro-apoptotic pathways. Due to this dual role, increased research is being invested into the role of S100β in neuronal homeostasis and inflammation. In fact, increased S100β expression is seen in many neuropathologies including Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, and traumatic brain injury. High S100β is generally associated with worsened disease outcome. Here, we provide an overview of the structure and role of S100β in various …

Immediate-Use Rescue Medication And The Epilepsy Monitoring Unit: Experiences From An Expert Panel, Evelyn K. Shih, Brin E. Freund, Michael R. Sperling, Danielle A. Becker, Proleta Datta, Sandra Dewar, Edward Faught, Tracy Glauser, R. Edward Hogan, Randa Jarrar, Andres M. Kanner, David King-Stephens, Rebecca E. Matthews, Patricia Penovich, M. Scott Perry, Eric B. Segal, Joseph Sirven, John M. Stern, James W. Wheless, Enrique Carrazana, Adrian L. Rabinowicz, William O. Tatum

Department of Neurology Faculty Papers

BACKGROUND: People with epilepsy (PWE) may experience seizure clusters, broadly defined as ≥2 seizures that occur in close proximity. In epilepsy monitoring units (EMUs), seizure clusters can spontaneously occur during long-term videoelectroencephalogram monitoring (LTVEM) or as a result of antiseizure medication dose adjustments. In this survey, we examined the experiences and practices of expert clinicians with seizure clusters in EMUs.

METHODS: A 55-item survey was sent to members of an Epilepsy Education Council who are epilepsy experts. Items described experiences, treatment practices, and negative outcomes with seizure clusters in EMUs.

RESULTS: Of the 15 experts (aged 43-77 y), 14 are …

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 …

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 …

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 …

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 …

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 …

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 …