Neurology Commons^™

Safety And Tolerability Of Atogepant For The Preventive Treatment Of Migraine: A Post Hoc Analysis Of Pooled Data From Four Clinical Trials, Paul Rizzoli, Michael Marmura, Jennifer Robblee, Jennifer Mcvige, Sara Sacco, Stephanie Nahas, Jessica Ailani, Rosa De Abreu Ferreira, Julia Ma, Jonathan Smith, Brett Dabruzzo, Messoud Ashina

Department of Jefferson Headache Center papers and presentations

BACKGROUND: Conventional, non-specific preventive migraine treatments often demonstrate low rates of treatment persistence due to poor efficacy or tolerability. Effective, well-tolerated preventive treatments are needed to reduce migraine symptoms, improve function, and enhance quality of life. Atogepant is a migraine-specific oral calcitonin gene-related peptide receptor antagonist that is indicated for the preventive treatment of migraine in adults. This analysis evaluated the safety and tolerability profile of atogepant for the preventive treatment of migraine, including adverse events (AEs) of interest, such as constipation, nausea, hepatic safety, weight changes, and cardiac disorders.

METHODS: This post hoc analysis was performed using data pooled …

Comparative Efficacy, Quality Of Life, Safety, And Tolerability Of Atogepant And Rimegepant In Migraine Prevention: A Matching-Adjusted Indirect Comparison Analysis, Cristina Tassorelli, Kateryna Onishchenko, Rashmi B. Halker Singh, Molly Duan, Laure Dupont-Benjamin, Matthew Hemstock, Corey Voller, Peter Mcallister, Stephanie J. Nahas, Pranav Gandhi, Jessica Ailani

Department of Neurology Faculty Papers

BACKGROUND: Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice.

METHODS: An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly …

Comparing Cognitive Tests And Smartphone-Based Assessment In 2 Us Community-Based Cohorts., Ileana De Anda-Duran, Preeti Sunderaraman, Edward Searls, Shirine Moukaled, Xuanyi Jin, Zachary Popp, Cody Karjadi, Phillip H Hwang, Huitong Ding, Sherral Devine, Ludy C Shih, Spencer Low, Honghuang Lin, Vijaya B Kolachalama, Lydia Bazzano, David J Libon, Rhoda Au

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Smartphone-based cognitive assessments have emerged as promising tools, bridging gaps in accessibility and reducing bias in Alzheimer disease and related dementia research. However, their congruence with traditional neuropsychological tests and usefulness in diverse cohorts remain underexplored.

METHODS AND RESULTS: A total of 406 FHS (Framingham Heart Study) and 59 BHS (Bogalusa Heart Study) participants with traditional neuropsychological tests and digital assessments using the Defense Automated Neurocognitive Assessment (DANA) smartphone protocol were included. Regression models investigated associations between DANA task digital measures and a neuropsychological global cognitive

CONCLUSIONS: Our findings demonstrate that smartphone-based cognitive assessments exhibit concurrent validity with a …

An Ewas Of Dementia Biomarkers And Their Associations With Age, African Ancestry, And Ptsd, Mark W. Miller, Erika J. Wolf, Xiang Zhao, Mark W. Logue, Sage E. Hawn

Psychology Faculty Publications

Background

Large-scale cohort and epidemiological studies suggest that PTSD confers risk for dementia in later life but the biological mechanisms underlying this association remain unknown. This study examined this question by assessing the influences of PTSD, APOE ε4 genotypes, DNA methylation, and other variables on the age- and dementia-associated biomarkers Aβ40, Aβ42, GFAP, NfL, and pTau-181 measured in plasma. Our primary hypothesis was that PTSD would be associated with elevated levels of these markers.

Methods

Analyses were based on data from a PTSD-enriched cohort of 849 individuals. We began by performing factor analyses of the biomarkers, the results of which …

Digital Clock Drawing As An Alzheimer's Disease Susceptibility Biomarker: Associations With Genetic Risk Score And Apoe In Older Adults, L I Thompson, M Cummings, S Emrani, David J. Libon, A Ang, C Karjadi, R Au, C Liu

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.

OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker.

DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures.

SETTING: We used existing data …

Characteristic Dynamic Functional Connectivity During Sevoflurane-Induced General Anesthesia, J. Miao, M. Tantawi, Mahdi Alizadeh, Sara Thalheimer, Faezeh Vedaei, Victor Romo, Feroze B. Mohamed, Chengyuan Wu

Department of Neurosurgery Faculty Papers

General anesthesia (GA) during surgery is commonly maintained by inhalational sevoflurane. Previous resting state functional MRI (rs-fMRI) studies have demonstrated suppressed functional connectivity (FC) of the entire brain networks, especially the default mode networks, transitioning from the awake to GA condition. However, accuracy and reliability were limited by previous administration methods (e.g. face mask) and short rs-fMRI scans. Therefore, in this study, a clinical scenario of epilepsy patients undergoing laser interstitial thermal therapy was leveraged to acquire 15 min of rs-fMRI while under general endotracheal anesthesia to maximize the accuracy of sevoflurane level. Nine recruited patients had fMRI acquired during …

Durable Responses At 24 Months With High-Frequency Spinal Cord Stimulation For Nonsurgical Refractory Back Pain, Naresh P. Patel, Jessica Jameson, Curtis Johnson, Daniel Kloster, Aaron Calodney, Peter Kosek, Julie Pilitsis, Markus Bendel, Erika Petersen, Chengyuan Wu, Taissa Cherry, Shivanand Lad, Cong Yu, Dawood Sayed, Johnathan Goree, Mark K. Lyons, Andrew Sack, Diana Bruce, Manish Bharara, Rose Province-Azalde, David Caraway, Leonardo Kapural

Department of Neurosurgery Faculty Papers

OBJECTIVE: The objective of this study was to evaluate the 24-month durability of pain relief, function, quality of life, and safety outcomes for patients with nonsurgical refractory back pain (NSRBP) treated with high-frequency spinal cord stimulation (SCS) within a large, national, multicenter randomized controlled trial (RCT).

METHODS: Following the completion of an RCT comparing high-frequency SCS plus CMM with CMM alone for the treatment of NSRBP, patients gave additional consent for a follow-up extension to 24 months. Presented is the cohort analysis of all patients treated with high-frequency SCS following the optional crossover at 6 months. The outcomes assessed to …

Neurologic Outcomes For Adult Spinal Cord Ependymomas Stratified By Tumor Location: A Retrospective Cohort Study And 2-Year Outlook, Keanu Chee, Grégoire P Chatain, Michael W Kortz, Stephanie Serva, Keshari Shrestha, Timothy H Ung, Jens-Peter Witt, Michael Finn

Department of Neurosurgery Faculty Papers

Determine whether craniocaudal spinal cord tumor location affects long-term neurologic outcomes in adults diagnosed with spinal ependymomas (SE). A retrospective cohort analysis of patients aged ≥ 18 years who underwent surgical resection for SE over a ten-year period was conducted. Tumor location was classified as cervical, thoracic, or lumbar/conus. Primary endpoints were post-operative McCormick Neurologic Scale (MNS) scores at < 3 days, 6 weeks, 1 year, and 2 years. One-way ANOVA was performed to detect significant differences in MNS scores between tumor locations. Twenty-eight patients were identified. The average age was 44.2 ± 15.4 years. Sixteen were male, and 13 were female. There were 10 cervical-predominant SEs, 13 thoracic-predominant SEs, and 5 lumbar/conus-predominant SEs. No significant differences were observed in pre-operative MNS scores between tumor locations (p = 0.73). One-way ANOVA testing demonstrated statistically significant differences in post-operative MNS scores between tumor locations at < 3 days (p = 0.03), 6 weeks (p = 0.009), and 1 year (p = 0.003); however, no significant difference was observed between post-operative MNS scores at 2 years (p = 0.13). The mean MNS score for patients with thoracic SEs were higher at all follow-up time points. Tumors arising in the thoracic SE are associated with worse post-operative neurologic outcomes in comparison to SEs arising in other spinal regions. This is likely multifactorial in etiology, owing to both anatomical differences including spinal cord volume as well as variations in tumor characteristics. No significant differences in 2-year MNS scores were observed, suggesting that patients ultimately recover from neurological insult sustained at the time of surgery.

Global Outcomes For Microsurgical Clipping Of Unruptured Intracranial Aneurysms: A Benchmark Analysis Of 2245 Cases, Richard Drexler, Thomas Sauvigny, Tobias F. Pantel, Franz L. Ricklefs, Joshua S. Catapano, John E. Wanebo, Michael T. Lawton, Aminaa Sanchin, Nils Hecht, Peter Vajkoczy, Kunal Raygor, Daniel Tonetti, Adib Abla, Kareem El Naamani, Stavropoula I. Tjoumakaris, Pascal Jabbour, Brian T. Jankowitz, Mohamed M. Salem, Jan-Karl Burkhardt, Arthur Wagner, Maria Wostrack, Jens Gempt, Bernhard Meyer, Michael Gaub, Justin R. Mascitelli, Philippe Dodier, Gerhard Bavinzski, Karl Roessler, Nico Stroh, Matthias Gmeiner, Andreas Gruber, Eberval G. Figueiredo, Antonio Carlos Samaia Da Silva Coelho, Anatoliy V. Bervitskiy, Egor D. Anisimov, Jamil A. Rzaev, Harald Krenzlin, Naureen Keric, Florian Ringel, Dougho Park, Mun-Chul Kim, Eleonora Marcati, Marco Cenzato, Manfred Westphal, Lasse Dührsen

Department of Neurosurgery Faculty Papers

BACKGROUND AND OBJECTIVES: Benchmarks represent the best possible outcome and help to improve outcomes for surgical procedures. However, global thresholds mirroring an optimal and reachable outcome for microsurgical clipping of unruptured intracranial aneurysms (UIA) are not available. This study aimed to define standardized outcome benchmarks in patients who underwent clipping of UIA.

METHODS: A total of 2245 microsurgically treated UIA from 15 centers were analyzed. Patients were categorized into low- ("benchmark") and high-risk ("nonbenchmark") patients based on known factors affecting outcome. The benchmark was defined as the 75th percentile of all centers' median scores for a given outcome. Benchmark outcomes …

Bisphenol-A And Phthalate Metabolism In Children With Neurodevelopmental Disorders, T Peter Stein, Margaret D Schluter, Robert A Steer, Xue Ming

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.

HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.

METHODS: We measured the efficiency of glucuronidation in three groups of children, …

Examining The Latent Structure And Correlates Of Sensory Reactivity In Autism: A Multi-Site Integrative Data Analysis By The Autism Sensory Research Consortium, Zachary J. Williams, Roseann Schaaf, Karla K. Ausderau, Grace T. Baranek, D. Jonah Barrett, Carissa J. Cascio, Rachel L. Dumont, Ekomobong E. Eyoh, Michelle D. Failla, Jacob I. Feldman, Jennifer H. Foss-Feig, Heather L. Green, Shulamite A. Green, Jason L. He, Elizabeth A. Kaplan-Kahn, Bahar Keçeli-Kaysılı, Keren Maclennan, Zoe Mailloux, Elysa J. Marco, Lisa E. Mash, Elizabeth P. Mckernan, Sophie Molholm, Stewart H. Mostofsky, Nicolaas A.J. Puts, Caroline E. Robertson, Natalie Russo, Nicole Shea, John Sideris, James S. Sutcliffe, Teresa Tavassoli, Mark T. Wallace, Ericka L. Wodka, Tiffany G. Woynaroski

Department of Occupational Therapy Faculty Papers

BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population.

METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to …

Isolated Cerebral Mucormycosis And Aspergillosis Coinfection In An Immunocompromised Adult, George Sun, Allison Weiss, Joy Zhao, Mitchell Silver, Michael Demaio, Sara Dehbashi

Department of Neurology Faculty Papers

Opportunistic fungal infections are a major cause of mortality in immunosuppressed patients, with mucormycosis and aspergillosis as two of the most commonly identified fungal organisms. Coinfection with mucormycosis and aspergillosis is rare, but cases have been reported in literature, most commonly presenting as disseminated invasive fungal infection with cerebrorhino-orbital involvement in an immunocompromised patient. Infections are most commonly caused by direct implantation of spores with localised angioinvasion. Haematogenous spread is rare, with most cases secondary to haematological malignancies or intravenous drug use. Coinfection with mucormycosis and aspergillosis portends a poor prognosis, with a high mortality rate. Thus, prompt recognition and …

Electric Field Navigated 1-Hz Rtms For Poststroke Motor Recovery: The E-Fit Randomized Controlled Trial, Dylan J. Edwards, Charle Y. Liu, Kari Dunning, Felipe Fregni, Jarmo Laine, Benjamin E. Leiby, Lynn M. Rogers, Richard L. Harvey

Moss-Magee Rehabilitation Papers

BACKGROUND: To determine if low-frequency repetitive transcranial magnetic stimulation targeting the primary motor cortex contralateral (M1_CL) to the affected corticospinal tract in patients with hemiparetic stroke augments intensive training–related clinical improvement; an extension of the NICHE trial (Navigated Inhibitory rTMS to Contralesional Hemisphere Trial) using an alternative sham coil.

METHODS: The present E-FIT trial (Electric Field Navigated 1Hz rTMS for Post-stroke Motor Recovery Trial) included 5 of 12 NICHE trial outpatient US rehabilitation centers. The stimulation protocol remained identical (1 Hz repetitive transcranial magnetic stimulation, M1_CL, preceding 60-minute therapy, 18 sessions/6 wks; parallel arm randomized clinical …

A Biologic-Device Combination Product Delivering Tumor-Derived Antigens Elicits Immunogenic Cell Death-Associated Immune Responses Against Glioblastoma, Christopher Cultrara, Christopher Uhl, Kenneth Kirby, Essam Abed Elrazaq, Amelia Zellander, David W. Andrews, Charles B. Scott, Lorenzo Galluzzi, Mark A. Exley, Jenny Zilberberg

Department of Neurosurgery Faculty Papers

Background IGV-001 is a personalized, autologous cancer cell-based immunotherapy conceived to deliver a tumor-derived antigenic payload in the context of immunostimulatory signals to patients with glioblastoma (GBM). IGV-001 consists of patient-derived GBM cells treated with an antisense oligodeoxynucleotide against insulin-like growth factor 1 receptor (IGF1R) and placed in proprietary biodiffusion chambers (BDCs). The BDCs are then exposed to 5–6 Gy radiation and implanted at abdominal sites for ~48 hours. IGV-001 has previously been shown to be generally safe with promising clinical activity in newly diagnosed GBM patients.

Methods Mouse (m) or human (h) variants of IGV-001 …

Persistence To Anti-Cgrp Monoclonal Antibodies And Onabotulinumtoxina Among Patients With Migraine: A Retrospective Cohort Study, Larry Charleston, Brian Talon, Christine Sullivan, Carlton Anderson, Steven Kymes, Stephane A. Regnier, Seema Soni-Brahmbhatt, Stephanie J. Nahas

Department of Jefferson Headache Center papers and presentations

BACKGROUND: To date, real-world evidence on persistence to anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) or onabotulinumtoxinA have excluded eptinezumab. This retrospective cohort study was performed to compare treatment persistency among patients with migraine on anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, or eptinezumab) or onabotulinumtoxinA.

METHODS: This retrospective study used IQVIA PharmMetrics data. Adult patients with migraine treated with an anti-CGRP mAb or onabotulinumtoxinA who had 12 months of continuous insurance enrollment before starting treatment were included. A "most recent treatment episode" analysis was used in which the most recent episode was defined as the latest treatment period with the same …

Genetics Of Functional Seizures; A Scoping Systematic Review, Ali A. Asadi-Pooya, Mark Hallett, Nafiseh Mirzaei Damabi, Khatereh Fazelian Dehkordi

Department of Neurology Faculty Papers

Background: Evidence on the genetics of functional seizures is scarce, and the purpose of the current scoping systematic review is to examine the existing evidence and propose how to advance the field.

Methods: Web of science and MEDLINE were searched, from their initiation until May 2023. The following key words were used: functional neurological disorder(s), psychogenic neurological disorder(s), functional movement disorder(s), psychogenic movement disorder(s), functional seizures(s), psychogenic seizure(s), nonepileptic seizure(s), dissociative seizure(s), or psychogenic nonepileptic seizure(s), AND, gene, genetic(s), polymorphism, genome, epigenetics, copy number variant, copy number variation(s), whole exome sequencing, or next-generation sequencing.

Results: We identified three original studies. …

Secondary Analysis Of A James Lind Alliance Priority Setting Partnership To Facilitate Knowledge Translation In Degenerative Cervical Myelopathy (Dcm): Insights From Ao Spine Recode-Dcm, Benjamin Davies, Jamie Brannigan, Oliver D. Mowforth, Danyal Khan, Angus G.K. Mcnair, Lindsay Tetreault, Iwan Sadler, Ellen Sarewitz, Bizhan Aarabi, Brian Kwon, Toto Gronlund, Vafa Rahimi-Movaghar, Carl Moritz Zipser, Peter John Hutchinson, Shekar Kurpad, James S. Harrop, Jefferson R. Wilson, James D. Guest, Michael G. Fehlings, Mark R.N. Kotter

Department of Neurosurgery Faculty Papers

OBJECTIVES: To explore whether a James Lind Alliance Priority Setting Partnership could provide insights on knowledge translation within the field of degenerative cervical myelopathy (DCM).

DESIGN: Secondary analysis of a James Lind Alliance Priority Setting Partnership process for DCM.

PARTICIPANTS AND SETTING: DCM stake holders, including spinal surgeons, people with myelopathy and other healthcare professionals, were surveyed internationally. Research suggestions submitted by stakeholders but considered answered were identified. Sampling characteristics of respondents were compared with the overall cohort to identify subgroups underserved by current knowledge translation.

RESULTS: The survey was completed by 423 individuals from 68 different countries. A total …

Treatment Of Adult Spasticity With Botox (Onabotulinumtoxina): Development, Insights, And Impact, Alberto Esquenazi, Wolfgang H. Jost, Catherine C. Turkel, Theodore Wein, Rozalina Dimitrova

Moss-Magee Rehabilitation Papers

Upper and lower limb spasticity (ULS, LLS) often occur following a stroke or in patients with other neurological disorders, leading to difficulties in mobility and daily living and decreased quality of life. Prior to the use of onabotulinumtoxinA, antispastic medications had limited efficacy and often caused sedation. Phenol injections were difficult for physicians to perform, painful, and led to tissue destruction. The success of onabotulinumtoxinA in treating cervical dystonia led to its use in spasticity. However, many challenges characterized the development of onabotulinumtoxinA for adult spasticity. The wide variability in the presentation of spasticity among patients rendered it difficult to …

Occupational Therapists' Perceptions Of Sensory Processing Evaluation Methods, Grace Hong, Jazminne Orozco Arteaga, Karen Park

Summer 2023 Virtual OTD Capstone Symposium

Background: This study aimed to obtain occupational therapists’ (OTs) experiences and perspectives on current evaluation tools who work with clients with sensory processing challenges in their clinical settings. Method: This research was a mixed-method study. Data was collected from surveys (n = 11) which had a mix of nominal, interval, close-ended, and open-ended questions. Following survey completion, participants were given the option to complete a semi-structured interview (n = 2) consisting of open-ended questions to clarify survey responses and gather additional information about their experiences. Results: The results indicated a high number of various barriers and limitations …

Association Of Brain Age, Lesion Volume, And Functional Outcome In Patients With Stroke, Sook-Lei Liew, Nicolas Schweighofer, James H. Cole, Artemis Zavaliangos-Petropulu, Bethany P. Lo, Laura K.M. Han, Tim Hahn, Lianne Schmaal, Miranda R. Donnelly, Jessica N. Jeong, Zhizhuo Wang, Aisha Abdullah, Jun H. Kim, Alexandre Hutton, Giuseppe Barisano, Michael R. Borich, Lara A. Boyd, Amy Brodtmann, Cathrin M. Buetefisch, Winston D. Byblow, Jessica M. Cassidy, Charalambos C. Charalambous, Valentina Ciullo, Adriana Bastos Conforto, Rosalia Dacosta-Aguayo, Julie A. Dicarlo, Martin Domin, Adrienne N. Dula, Natalia Egorova-Brumley, Wuwei Feng, Fatemeh Geranmayeh, Chris M. Gregory, Colleen A. Hanlon, Kathryn Hayward, Jess A. Holguin, Brenton Hordacre, Neda Jahanshad, Steven A. Kautz, Mohamed Salah Khlif, Hosung Kim, Amy Kuceyeski, David J. Lin, Jingchun Liu, Martin Lotze, Bradley J. Macintosh, John L. Margetis, Maria Mataro, Feroze B. Mohamed, Emily R. Olafson, Gilsoon Park, Fabrizio Piras, Kate P. Revill, Pamela Roberts, Andrew D. Robertson, Nerses Sanossian, Heidi M. Schambra, Na Jin Seo, Surjo R. Soekadar, Gianfranco Spalletta, Cathy M. Stinear, Myriam Taga, Wai Kwong Tang, Greg T. Thielman, Daniela Vecchio, Nick S. Ward, Lars T. Westlye, Carolee J. Winstein, George F. Wittenberg, Steven L. Wolf, Kristin A. Wong, Chunshui Yu, Steven C. Cramer, Paul M. Thompson

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in …

Cancer Stem Cell Assay-Guided Chemotherapy Improves Survival Of Patients With Recurrent Glioblastoma In A Randomized Trial, Tulika Ranjan, Soma Sengupta, Michael J. Glantz, Richard M. Green, Alexander Yu, Dawit Aregawi, Rekha Chaudhary, Ricky Chen, Mario Zuccarello, Christine Lu-Emerson, Hugh D. Moulding, Neil Belman, Jon Glass, Aaron Mammoser, Mark Anderson, Jagan Valluri, Nicholas Marko, Jason Schroeder, Steven Jubelirer, Frances Chow, Pier Paolo Claudio, Anthony M. Alberico, Seth T. Lirette, Krista L. Denning, Candace M. Howard

Department of Neurosurgery Faculty Papers

Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors.

In a randomized clinical trial (NCT03632135), the ChemoID assay, a personalized approach for selecting the most effective treatment from FDA-approved chemotherapies, improves the survival of patients with rGBM (2016 WHO classification) over physician-chosen chemotherapy. In the ChemoID assay-guided group, median survival is 12.5 months (95% confidence interval [CI], 10.2-14.7) compared with 9 months (95% CI, 4.2-13.8) in the physician-choice group (p = …

Therapies In Stiff-Person Syndrome: Advances And Future Prospects Based On Disease Pathophysiology, Marinos Dalakas

Department of Neurology Faculty Papers

Among the glutamic acid decarboxylase (GAD)-antibody-spectrum disorders, the most common phenotypic subset is the stiff-person syndrome (SPS), caused by impaired GABAergic inhibitory neurotransmission and autoimmunity characterized by very high titers of GAD antibodies and increased GAD-IgG intrathecal synthesis. If not properly treated or untreated because of delayed diagnosis, SPS progresses leading to disability; it is therefore fundamental to apply the best therapeutic schemes from the outset. This article is focused on the rationale of specific therapeutic strategies based on the SPS pathophysiology targeting both the impaired reciprocal GABAergic inhibition to symptomatically improve the main clinical manifestations of stiffness in the …

Lived Experience-Centred Word Clouds May Improve Research Uncertainty Gathering In Priority Setting Partnerships, Oliver D. Mowforth, Lance Burn, Danyal Z. Khan, Xiaoyu Yang, Sybil R.L. Stacpoole, Toto Gronlund, Lindsay Tetreault, Sukhvinder Kalsi-Ryan, Michelle L. Starkey, Iwan Sadler, Ellen Sarewitz, Delphine Houlton, Julia Carter, Paige Howard, Vafa Rahimi-Movaghar, James D. Guest, Bizhan Aarabi, Brian K. Kwon, Shekar N. Kurpad, James Harrop, Jefferson R. Wilson, Robert Grossman, Emma K. Smith, Angus Mcnair, Michael G. Fehlings, Mark R.N. Kotter, Benjamin M. Davies

Department of Neurosurgery Faculty Papers

INTRODUCTION: AO Spine RECODE-DCM was a multi-stakeholder priority setting partnership (PSP) to define the top ten research priorities for degenerative cervical myelopathy (DCM). Priorities were generated and iteratively refined using a series of surveys administered to surgeons, other healthcare professionals (oHCP) and people with DCM (PwDCM). The aim of this work was to utilise word clouds to enable the perspectives of people with the condition to be heard earlier in the PSP process than is traditionally the case. The objective was to evaluate the added value of word clouds in the process of defining research uncertainties in National Institute for …

Optimized Acute Treatment Of Migraine Is Associated With Greater Productivity In People With Migraine: Results From The Chronic Migraine Epidemiology And Outcomes (Cameo) Study., Dawn C Buse, Stephanie J. Nahas, Walter Buzz F Stewart, Cynthia E Armand, Michael L Reed, Kristina M Fanning, Aubrey Manack Adams, Richard B Lipton

Department of Neurology Faculty Papers

OBJECTIVE: This study aimed to ascertain whether level of optimization of acute treatment of migraine is related to work productivity across the spectrum of migraine.

METHODS: Data were from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, an internet-based longitudinal survey. Respondents with migraine who reported full-time employment and use of ≥1 acute prescription medication for migraine were included. We determined relationships among lost productive time (LPT; measured with the Migraine Disability Assessment Scale), acute treatment optimization (Migraine Treatment Optimization Questionnaire- ), and monthly headache days (MHDs).

RESULTS: There was a direct relationship between LPT and MHD category. Greater acute …

A Learned Map For Places And Concepts In The Human Medial Temporal Lobe, Nora A. Herweg, Lukas Kunz, Daniel Schonhaut, Armin Brandt, Paul A. Wanda, Ashwini D. Sharan, Michael R. Sperling, Andreas Schulze-Bonhage, Michael J. Kahana

Department of Neurology Faculty Papers

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL microwire recordings from 20 patients (9 female, 11 male) navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings. The array of local field potentials in the MTL contains sufficient information …

Sleep Duration, Hypnotic Drug Use, And Risk Factors: Cross- Sectional Study, Nazanin Jalali, Parvin Khalili, Zahra Jamali, Zahra Jalali, Amir Moghadam-Ahmadi, Alireza Vakilian, Fatemeh Ayoobi

Department of Neurology Faculty Papers

Both short sleep duration (SSD) and long sleep duration (LSD) are associated with an increased risk of morbidity and mortality. Here, we aimed to assess the prevalence of sleep duration disturbances among adults in association with demographic, medication use, personal habits, and chronic diseases, while also considering the impact of hypnotic drug use. We performed a cross-sectional study of 9991 adult participants of the Rafsanjan Cohort Study (RCS), as part of the Prospective epidemiological research studies in Iran (PERSIAN). Multivariate logistic regression analyses were conducted to assess the association between short (< 6 h) and long (> 9 h) sleep duration with demographic and lifestyle …

Dissociating Statistically Determined Normal Cognitive Abilities And Mild Cognitive Impairment Subtypes With Dctclock., Emily F. Matusz, Catherine C. Price, Melissa Lamar, Rod Swenson, Rhoda Au, Sheina Emrani, Victor Wasserman, David J Libon, Louisa I. Thompson

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

OBJECTIVE: To determine whether the DCTclock can detect differences across groups of patients seen in the memory clinic for suspected dementia.

METHOD: Patients (n = 123) were classified into the following groups: cognitively normal (CN), subtle cognitive impairment (SbCI), amnestic cognitive impairment (aMCI), and mixed/dysexecutive cognitive impairment (mx/dysMCI). Nine outcome variables included a combined command/copy total score and four command and four copy indices measuring drawing efficiency, simple/complex motor operations, information processing speed, and spatial reasoning.

RESULTS: Total combined command/copy score distinguished between groups in all comparisons with medium to large effects. The mx/dysMCI group had the lowest total …

Graph Theoretical Measures Of Fast Ripple Networks Improve The Accuracy Of Post-Operative Seizure Outcome Prediction, Shennan A Weiss, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Daniel Y. Rubinstein, Jerome Engel, Michael R Sperling, Richard J Staba

Department of Neurosurgery Faculty Papers

Fast ripples (FR) are a biomarker of epileptogenic brain, but when larger portions of FR generating regions are resected seizure freedom is not always achieved. To evaluate and improve the diagnostic accuracy of FR resection for predicting seizure freedom we compared the FR resection ratio (RR) with FR network graph theoretical measures. In 23 patients FR were semi-automatically detected and quantified in stereo EEG recordings during sleep. MRI normalization and co-registration localized contacts and relation to resection margins. The number of FR, and graph theoretical measures, which were spatial (i.e., FR rate-distance radius) or temporal correlational (i.e., FR mutual information), …

Feasibility Of And Experience Using A Portable Mri Scanner In The Neonatal Intensive Care Unit., Maura Sien, Amie L. Robinson, Houchun H. Hu, Christopher R. Nitkin, Ara Hall, Marcie G. Files, Nathan S. Artz, John T. Pitts, Sherwin S. Chan

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: A portable, low-field MRI system is now Food and Drug Administration cleared and has been shown to be safe and useful in adult intensive care unit settings. No neonatal studies have been performed. The objective is to assess our preliminary experience and assess feasibility of using the portable MRI system at the bedside in a neonatal intensive care unit (NICU) at a quaternary children's hospital.

STUDY DESIGN: This was a single-site prospective cohort study in neonates ≥2 kg conducted between October and December 2020. All parents provided informed consent. Neonates underwent portable MRI examination in the NICU with support …

Safety And Tolerability Results Of Atogepant For The Preventive Treatment Of Episodic Migraine From A 40-Week, Open-Label Multicenter Extension Of The Phase 3 Advance Trial, Brad C Klein, Rosa Miceli, Lawrence Severt, Peter Mcallister, Laszlo Mechtler, Jennifer Mcvige, Merle Diamond, Michael J. Marmura, Hua Guo, Michelle Finnegan, Joel M Trugman

Department of Neurology Faculty Papers

Background: Atogepant is a United States Food and Drug Administration-approved oral calcitonin gene-related peptide receptor antagonist for the preventive treatment of episodic migraine. The study objective was to evaluate the long-term safety and tolerability of atogepant in participants who completed the phase 3 ADVANCE trial (NCT03777059).

Methods: This 40-week, open-label extension trial (NCT03939312) monitored safety in participants receiving oral atogepant 60 mg once daily, followed by a four-week safety follow-up period.

Results: Of the 685 participants taking at least one dose of atogepant, the treatment period was completed by 74.6% of participants with a mean (standard …