Neurology Commons^™

Treatment Of Cervical Dystonia With Botox (Onabotulinumtoxina): Development, Insights, And Impact, Joseph Jankovic, Joseph Tsui, Mitchell F Brin

Faculty, Staff and Students Publications

Cervical dystonia (CD), the most common focal dystonia encountered in neurologic practice, is a chronic disorder in which the muscles of the neck involuntarily contract and cause abnormal postures and movements of the head, neck, and shoulders. Treatment of CD prior to botulinum toxin was unsatisfactory, as existing therapies often did not improve symptoms. The use of botulinum toxin for CD grew out of its success in treating blepharospasm, another type of focal dystonia. On the basis of results from a double-blind, placebo-controlled trial, onabotulinumtoxinA was approved in 2000 in the US for the treatment of CD in adults in …

Contrasting Features Between Tourette Syndrome And Secondary Tic Disorders, José Fidel Baizabal-Carvallo, Marlene Alonso-Juarez, Joseph Jankovic

Faculty, Staff and Students Publications

Tics are rapid, recurrent, non-rhythmic movements or emitted sounds. Tics are the hallmark of Tourette syndrome (TS); however, a number of other disorders may be associated with tics, so-called secondary tic disorders (STD). We assessed clinical history and performed blinded evaluations of video-recordings from patients with TS and STD in order to identify features that may differentiate tics associated with TS vs STD. There were 156 patients with TS and 38 with STD, 21 of whom had functional (psychogenic) tics. Patients with TS were more frequently male and had a younger age at onset. Tics in TS tend to involve …

Discriminating Mild Traumatic Brain Injury And Posttraumatic Stress Disorder Using Latent Neuroimaging And Neuropsychological Profiles In Active-Duty Military Service Members, Nicola L De Souza, Carrie Esopenko, Yuane Jia, J Scott Parrott, Tricia L Merkley, Emily L Dennis, Frank G Hillary, Carmen Velez, Douglas B Cooper, Jan E Kennedy, Jeffrey D Lewis, Gerald E York, Deleene S Menefee, Stephen R Mccauley, Amy O Bowles, Elisabeth A Wilde, David F Tate

Faculty, Staff and Students Publications

OBJECTIVE: Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) commonly occur among military Service Members and Veterans and have heterogenous, but also overlapping symptom presentations, which often complicate the diagnoses of underlying impairments and development of effective treatment plans. Thus, we sought to examine whether the combination of whole brain gray matter (GM) and white matter (WM) structural measures with neuropsychological performance can aid in the classification of military personnel with mTBI and PTSD.

METHODS: Active-Duty US Service Members ( n = 156; 87.8% male) with a history of mTBI, PTSD, combined mTBI+PTSD, or orthopedic injury completed a …

Induction Of Astrocytic Slc22a3 Regulates Sensory Processing Through Histone Serotonylation, Debosmita Sardar, Yi-Ting Cheng, Junsung Woo, Dong-Joo Choi, Zhung-Fu Lee, Wookbong Kwon, Hsiao-Chi Chen, Brittney Lozzi, Alexis Cervantes, Kavitha Rajendran, Teng-Wei Huang, Antrix Jain, Benjamin R Arenkiel, Ian Maze, Benjamin Deneen

Faculty, Staff and Students Publications

Neuronal activity drives alterations in gene expression within neurons, yet how it directs transcriptional and epigenomic changes in neighboring astrocytes in functioning circuits is unknown. We found that neuronal activity induces widespread transcriptional upregulation and downregulation in astrocytes, highlighted by the identification of a neuromodulator transporter Slc22a3 as an activity-inducible astrocyte gene regulating sensory processing in the olfactory bulb. Loss of astrocytic Slc22a3 reduced serotonin (5HT) levels in astrocytes, leading to alterations in histone serotonylation. Inhibition of histone serotonylation in astrocytes reduced expression of GABA biosynthetic genes and GABA release, culminating in olfactory deficits. Our study revealed that neuronal activity …

Neurocognitive Dysfunction With Neuronal Injury In People With Hiv On Long-Duration Antiretroviral Therapy, Cynthia Mcmahan, Devon K Dietrich, Elizabeth F Horne, Erin Kelly, Katrina Geannopoulos, Peter Selim Siyahhan Julnes, Lillian Ham, Ulisses Santamaria, Chuen-Yen Lau, Tianxia Wu, Hsing-Chuan Hsieh, Anuradha Ganesan, Catherine Berjohn, Suad Kapetanovic, Daniel S Reich, Govind Nair, Joseph Snow, Brian K Agan, Avindra Nath, Bryan R Smith

Staff and Researcher Publications

Background and objectives: Neurologic outcomes in people with HIV (PWH) on long-duration antiretroviral therapy (ART) are not fully understood, and the underlying pathophysiology is unclear. To address this, we established a cohort of such individuals and compared them with HIV-negative controls using a novel matching technique. Both groups underwent extensive cognitive testing, evaluation for psychiatric measures, and MRI and CSF analyses.

Methods: Participants underwent comprehensive neuropsychological testing and completed standardized questionnaires measuring depressive symptoms, perceptions of own functioning, and activities of daily living as part of an observational study. Brain MRI and lumbar puncture were optional. Coarsened Exact Matching was …

Declining Autozygosity Over Time: An Exploration In Over 1 Million Individuals From Three Diverse Cohorts, Sarah M C Colbert, Frank R Wendt, Gita A Pathak, Drew A Helmer, Elizabeth R Hauser, Matthew C Keller, Renato Polimanti, Emma C Johnson

Faculty, Staff and Students Publications

Previous studies have hypothesized that autozygosity is decreasing over generational time. However, these studies were limited to relatively small samples (n < 11,000) lacking in diversity, which may limit the generalizability of their findings. We present data that partially support this hypothesis from three large cohorts of diverse ancestries, two from the US (All of Us, n = 82,474; the Million Veteran Program, n = 622,497) and one from the UK (UK Biobank, n = 380,899). Our results from a mixed-effect meta-analysis demonstrate an overall trend of decreasing autozygosity over generational time (meta-analyzed slope = -0.029, SE = 0.009, p = 6.03e-4). On the basis of our estimates, we would predict F

Thirty-Day Outcomes Of Resolute Onyx Stent For Symptomatic Intracranial Stenosis: A Multicenter Propensity Score-Matched Comparison With Stenting Versus Aggressive Medical Management For Preventing Recurrent Stroke In Intracranial Stenosis Trial, Farhan Siddiq, Ravi S Nunna, Jonathan M Beall, Inamullah Khan, Musharaf Khan, Wondwossen G Tekle, Mohamad Ezzeldin, Omar Tanweer, Jan-Karl Burkhardt, Pascal M Jabbour, Stavropoula I Tjoumakaris, Nabeel A Herial, Adnan H Siddiqui, Ramesh Grandhi, Renee L Martin, Adnan I Qureshi, Ameer E Hassan

Faculty, Staff and Students Publications

BACKGROUND: Symptomatic intracranial atherosclerotic disease (sICAD) is estimated to cause 10% of strokes annually in the United States. However, treatment remains a challenge with several different stenting options studied in the past with unfavorable results.

OBJECTIVE: To report the 30-day stroke and/or death rate associated with intracranial stent placement for sICAD using Resolute Onyx Zotarolimus-Eluting Stent (RO-ZES) and provide a comparison with the results of Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial.

METHODS: Prospectively maintained databases across 8 stroke centers were used to identify adult patients treated with RO-ZES for sICAD between January …

Imaging Of Pediatric Cardiac Tumors: A Cog Diagnostic Imaging Committee/Spr Oncology Committee White Paper, Cara E Morin, Lindsay M Griffin, Rebecca S Beroukhim, Pablo Caro-Domínguez, Sherwin Chan, Jason N Johnson, Juan C Infante, Christopher Z Lam, Ladonna J Malone, Elizabeth R Tang, Michael D Taylor, James C Wilkinson, Prakash M Masand

Faculty, Staff and Students Publications

Cardiac tumors in children are rare and the majority are benign. The most common cardiac tumor in children is rhabdomyoma, usually associated with tuberous sclerosis complex. Other benign cardiac masses include fibromas, myxomas, hemangiomas, and teratomas. Primary malignant cardiac tumors are exceedingly rare, with the most common pathology being soft tissue sarcomas. This paper provides consensus-based imaging recommendations for the evaluation of patients with cardiac tumors at diagnosis and follow-up, including during and after therapy.

Occupation Based Program Enhancement: Promoting Social And Leisure Participation Post-Stroke, Emma Welch, Amy Lyons-Brown

Spring 2023 Virtual OTD Capstone Symposium

This presentation describes the importance of social and leisure participation for individuals who have had a stroke and explores the role of occupational therapy in promoting this area of occupation for the population.

Connecting Circuits With Networks In Addiction Neuroscience: A Salience Network Perspective, Adriana K Cushnie, Wei Tang, Sarah R Heilbronner

Faculty, Staff and Students Publications

Human neuroimaging has demonstrated the existence of large-scale functional networks in the cerebral cortex consisting of topographically distant brain regions with functionally correlated activity. The salience network (SN), which is involved in detecting salient stimuli and mediating inter-network communication, is a crucial functional network that is disrupted in addiction. Individuals with addiction display dysfunctional structural and functional connectivity of the SN. Furthermore, while there is a growing body of evidence regarding the SN, addiction, and the relationship between the two, there are still many unknowns, and there are fundamental limitations to human neuroimaging studies. At the same time, advances in …

Examining The Use Of Expressive Arts Therapies In Neurorehabilitation Treatment Planning, Rebecca J. Horner

Expressive Therapies Capstone Theses

Those undergoing neurorehabilitation after stroke and traumatic brain injury report a diminished sense of overall wellness. This paper examines the conceivable benefits of introducing expressive arts therapies, which is the therapeutic use and combination of the visual arts, movement, drama, music, writing and other intermodal creative processes, into physical therapy and neurorehabilitation treatment planning. Expressive arts therapies have the capacity to engage with an individual’s physical, emotional, social and spiritual states concurrently. They simultaneously offer the ability to promote an increased sense of well-being, address mind-body disconnects, and process trauma non-verbally.

The sections of this narrative literature review focus on …

Neutralizing Antibody Formation With Onabotulinumtoxina (Botox®) Treatment From Global Registration Studies Across Multiple Indications: A Meta-Analysis, Joseph Jankovic, Jean Carruthers, Markus Naumann, Patricia Ogilvie, Terry Boodhoo, Mayssa Attar, Swati Gupta, Ritu Singh, John Soliman, Irina Yushmanova, Mitchell F Brin, Jie Shen

Faculty, Staff and Students Publications

Though the formation of neutralizing antibodies (NAbs) during treatment with botulinum neurotoxin is rare, their presence may nonetheless affect the biological activity of botulinum toxin and negatively impact clinical response. The goal of this updated meta-analysis was to evaluate and characterize the rate of NAb formation using an expanded dataset composed of 33 prospective placebo-controlled and open-label clinical trials with nearly 30,000 longitudinal subject records prior to and following onabotulinumtoxinA treatment in 10 therapeutic and aesthetic indications. Total onabotulinumtoxinA doses per treatment ranged from 10 U to 600 U administered in ≤15 treatment cycles. The NAb formation at baseline and …

Tmem106b Regulates Microglial Proliferation And Survival In Response To Demyelination, Tingting Zhang, Weilun Pang, Tuancheng Feng, Jennifer Guo, Kenton Wu, Mariela Nunez Santos, Akshayakeerthi Arthanarisami, Alissa L Nana, Quynh Nguyen, Peter J Kim, Joanna L Jankowsky, William W Seeley, Fenghua Hu

Faculty, Staff and Students Publications

TMEM106B, a lysosomal transmembrane protein, has been closely associated with brain health. Recently, an intriguing link between TMEM106B and brain inflammation has been discovered, but how TMEM106B regulates inflammation is unknown. Here, we report that TMEM106B deficiency in mice leads to reduced microglia proliferation and activation and increased microglial apoptosis in response to demyelination. We also found an increase in lysosomal pH and a decrease in lysosomal enzyme activities in TMEM106B-deficient microglia. Furthermore, TMEM106B loss results in a significant decrease in the protein levels of TREM2, an innate immune receptor essential for microglia survival and activation. Specific ablation of TMEM106B …

The Correlation Between Traumatic Brain Injury And Incarceration Among Adult Males In The United States, Shadi Shams

Rowan-Virtua Research Day

The United States has one of the largest growing prison populations in the world. A large amount of social and economic resources go towards the cost and maintenance of correctional facilities each year. Additionally, the current correctional programs are insufficient in assisting inmates with getting back to society; especially those with traumatic brain injury (TBI) who often remain undiagnosed and are usually treated unfairly in the prison system instead of receiving the appropriate help. Prior scholarly work has shown that patients in the post-TBI stage are more likely to enter the judicial system. In the recent population-based cohort study, the …

Case Report: Abrupt Psychosis Or Nmda Receptor Encephalitis?, Alexis Dunn, Neelesh Parikh, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

We report a case of a 46-year-old female who was initially committed to a psychiatric facility for new onset schizophrenia symptoms. She later had an extensive workup in the hospital due to leukocytosis and was believed to have NMDA Receptor Encephalitis as the cause for her new behavioral symptoms. This case report aims to educate EM (emergency medicine) physicians to keep a broad differential diagnosis on patients who present with new onset, unprovoked psychosis later in life.

Examining The Utility Of The Canadian Occupational Performance Measure (Copm) Vs. Cognitive Mapping And Motivational Interviewing (Cm/Mi) To Provide Person-Centered Care (Pcc) For People With Parkinson’S Disease (Pwpd), Mary Lagasca, Karen Aranha

Spring 2023 Virtual OTD Capstone Symposium

Background: Parkinson’s disease (PD) limits occupational engagement and quality of life. Clinicians need tools to help understand the lived experiences of people with PD to provide more person-centered care (PCC). The Canadian Occupational Performance Model (COPM) is one tool used with this population, but its predetermined categories may be limiting. In contrast, Cognitive Mapping and Motivational Interviewing (CM/MI) is a non-standardized method that may provide more insight. Objective: To identify the benefits of the COPM to CM/MI in delivering more person-centered care (PCC). Methodology: A qualitative phenomenological self-study was used. Data collection compared the assessments and reflected on determining if …

The Clinical Characterization Of Blocking Tics In Patients With Tourette Syndrome, José Fidel Baizabal-Carvallo, Joseph Jankovic

Faculty, Staff and Students Publications

OBJECTIVE: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and phonic tics. Blocking phenomena, characterized by arrests in motor activity causing interruptions in movements or speech, have also been described in patients with TS. In this study, we aimed to characterize the frequency and features of blocking tics in patients with TS.

METHODS: We studied a cohort of 201 patients with TS evaluated at our movement disorders clinic.

RESULTS: We identified 12 (6%) patients with blocking phenomena. Phonic tic intrusion causing speech arrest was the most common (n = 8, 4%), followed by sustained isometric …

Covid19-Associated New-Onset Movement Disorders: A Follow-Up Study, Susanne A Schneider, Soaham Desai, Onanong Phokaewvarangkul, Elena Cecilia Rosca, Jirada Sringean, Pria Anand, Gary Álvarez Bravo, Francisco Cardoso, Anna M Cervantes-Arslanian, Harshad Chovatiya, David Crosiers, Femke Dijkstra, Conor Fearon, Francisco Grandas, Eric Guedj, Antonio Méndez-Guerrero, Muhammad Hassan, Joseph Jankovic, Anthony E Lang, Karim Makhoul, Lorenzo Muccioli, Sarah A O'Shea, Vahid Reza Ostovan, Javier Ricardo Perez-Sanchez, Ritesh Ramdhani, Victoria Ros-Castelló, Christina Schulte, Priyank Shah, Lars Wojtecki, Pramod Kumar Pal

Faculty, Staff and Students Publications

BACKGROUND: Neurological symptoms are common manifestation in acute COVID-19. This includes hyper- and hypokinetic movement disorders. Data on their outcome, however, is limited.

METHODS: Cases with new-onset COVID-19-associated movement disorders were identified by searching the literature. Authors were contacted for outcome data which were reviewed and analyzed.

RESULTS: Movement disorders began 12.6 days on average after the initial onset of COVID-19. 92% of patients required hospital admission (mean duration 23 days). In a fraction of patients (6 of 27; 22%; 4 males/2 females, mean age 66.8 years) the movement disorder (ataxia, myoclonus, tremor, parkinsonism) was still present after a follow-up …

Aspirin And Immunotherapy: A Faustian Bargain?, Eric A Goethe, Amy B Heimberger, Ganesh Rao

Faculty, Staff and Students Publications

Fibrinogen-like protein 1 (FGL1) has been associated with improved survival in hepatocellular carcinoma (HCC). However, recent evidence suggests that FGL1 may bind to surface receptors on lymphocytes and induce immune senescence. In this issue of the JCI, Lin and co-authors show that FGL1 may be acetylated by aspirin and targeted for degradation, which is associated with increased antitumor immunity and improved survival. Similar findings were obtained with inhibitors of sirtuin 2 (SIRT2), a histone deacetylase. These findings expand our current understanding of the role of FGL1 in cancer and provide an impetus for the evaluation of alternative immunotherapy combinations in …

Middle Meningeal Artery Embolization For Chronic Subdural Hematoma: Predictors Of Clinical And Radiographic Failure From 636 Embolizations, Mohamed M Salem, Okkes Kuybu, Alex Nguyen Hoang, Ammad A Baig, Mirhojjat Khorasanizadeh, Cordell Baker, Joshua C Hunsaker, Aldo A Mendez, Gustavo Cortez, Jason M Davies, Sandra Narayanan, C Michael Cawley, Howard A Riina, Justin M Moore, Alejandro M Spiotta, Alexander A Khalessi, Brian M Howard, Ricardo Hanel, Omar Tanweer, Elad I Levy, Ramesh Grandhi, Michael J Lang, Adnan H Siddiqui, Peter Kan, Christopher S Ogilvy, Bradley A Gross, Ajith J Thomas, Brian T Jankowitz, Jan-Karl Burkhardt

Faculty, Staff and Students Publications

Background

Knowledge regarding predictors of clinical and radiographic failures of middle meningeal artery (MMA) embolization (MMAE) treatment for chronic subdural hematoma (CSDH) is limited.

Purpose

To identify predictors of MMAE treatment failure for CSDH.

Materials and Methods

In this retrospective study, consecutive patients who underwent MMAE for CSDH from February 2018 to April 2022 at 13 U.S. centers were included. Clinical failure was defined as hematoma reaccumulation and/or neurologic deterioration requiring rescue surgery. Radiographic failure was defined as a maximal hematoma thickness reduction less than 50% at last imaging (minimum 2 weeks of head CT follow-up). Multivariable logistic regression models …

Inhibitory Input Directs Astrocyte Morphogenesis Through Glial Gababr, Yi-Ting Cheng, Estefania Luna-Figueroa, Junsung Woo, Hsiao-Chi Chen, Zhung-Fu Lee, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Communication between neurons and glia plays an important role in establishing and maintaining higher order brain function1. Astrocytes are endowed with complex morphologies which places their peripheral processes in close proximity to neuronal synapses and directly contributes to their regulation of brain circuits2–4. Recent studies have shown that excitatory neuronal activity promotes oligodendrocyte differentiation5–7; whether inhibitory neurotransmission regulates astrocyte morphogenesis during development is unknown. Here we show that inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis. We found that input from inhibitory neurons functions through astrocytic GABABR and …

Health Disparities In Multiple Sclerosis Among Hispanic And Black Populations In The United States, Michael Z Moore, Carlos A Pérez, George J Hutton, Hemali Patel, Fernando X Cuascut

Faculty, Staff and Students Publications

Multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system (CNS). Historically, research on MS has focused on White persons with MS. This preponderance of representation has important possible implications for minority populations with MS, from developing effective therapeutic agents to understanding the role of unique constellations of social determinants of health. A growing body of literature involving persons of historically underrepresented races and ethnicities in the field of multiple sclerosis is assembling. Our purpose in this narrative review is to highlight two populations in the United States: Black and Hispanic persons with multiple sclerosis. We will …

Social Deprivation Induces Astrocytic Trpa1-Gaba Suppression Of Hippocampal Circuits, Yi-Ting Cheng, Junsung Woo, Estefania Luna-Figueroa, Ehson Maleki, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Social experience is essential for the development and maintenance of higher order brain function. Social deprivation results in a host of cognitive deficits and cellular studies have largely focused on associated neuronal dysregulation; how astrocyte function is impacted by social deprivation is unknown. Here we show that hippocampal astrocytes from juvenile mice subjected to social isolation exhibit increased Ca2+ activity and global changes in gene expression. We found that the Ca2+ channel TRPA1 is upregulated in astrocytes after social deprivation and astrocyte-specific deletion of TRPA1 reverses the physiological and cognitive deficits associated with social deprivation. Mechanistically, TRPA1 inhibition of hippocampal …

Association Of Clinical Outcomes And Connectivity In Awake Versus Asleep Deep Brain Stimulation For Parkinson Disease, Ron Gadot, Nora Vanegas Arroyave, Huy Dang, Adrish Anand, Ricardo A Najera, Lisa Yutong Taneff, Steven Bellows, Arjun Tarakad, Joseph Jankovic, Andreas Horn, Ben Shofty, Ashwin Viswanathan, Sameer A Sheth

Faculty, Staff and Students Publications

OBJECTIVE: Deep brain stimulation (DBS) for Parkinson disease (PD) is traditionally performed with awake intraoperative testing and/or microelectrode recording. Recently, however, the procedure has been increasingly performed under general anesthesia with image-based verification. The authors sought to compare structural and functional networks engaged by awake and asleep PD-DBS of the subthalamic nucleus (STN) and correlate them with clinical outcomes.

METHODS: Levodopa equivalent daily dose (LEDD), pre- and postoperative motor scores on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III), and total electrical energy delivered (TEED) at 6 months were retroactively assessed in patients with PD who …

Interactive Mobile Application For Parkinson’S Disease Deep Brain Stimulation (Map Dbs): An Open-Label, Multicenter, Randomized, Controlled Clinical Trial, Gordon Duffley, Aniko Szabo, Barbara J Lutz, Emily C Mahoney-Rafferty, Christopher W Hess, Adolfo Ramirez-Zamora, Pamela Zeilman, Kelly D Foote, Shannon Chiu, Michael H Pourfar, Clarisse Goas Cnp, Jennifer L Wood, Ihtsham U Haq, Mustafa S Siddiqui, Mitra Afshari, Melissa Heiry, Jennifer Choi, Monica Volz, Jill L Ostrem, Marta San Luciano, Nicki Niemann, Andrew Billnitzer, Daniel Savitt, Arjun Tarakad, Joohi Jimenez-Shahed, Camila C Aquino, Michael S Okun, Christopher R Butson

Faculty, Staff and Students Publications

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), but its efficacy is tied to DBS programming, which is often time consuming and burdensome for patients, caregivers, and clinicians. Our aim is to test whether the Mobile Application for PD DBS (MAP DBS), a clinical decision support system, can improve programming.

METHODS: We conducted an open-label, 1:1 randomized, controlled, multicenter clinical trial comparing six months of SOC standard of care (SOC) to six months of MAP DBS-aided programming. We enrolled patients between 30 and 80 years old who received DBS to treat idiopathic PD at six …

Construction Of Semi-Supervised Spatial Projections To Identify The Source Of Beta- And High Frequency Oscillations In Parkinson’S Disease, Luciano R F Branco, Ashwin Viswanathan, Arjun Tarakad, Nuri F Ince

Faculty, Staff and Students Publications

Traditional deep brain stimulation (DBS) treatment for Parkinson's disease (PD) targets the placement of DBS leads into subthalamic nucleus (STN). Extraction of neurobiomarkers from STN local field potential activity can be used for the optimization of DBS. Beta (12-30 Hz) and high frequency oscillations (200-450 Hz, HFO) of STN and their phase-amplitude coupling have been previously correlated with symptom severity in PD. The typical approach is to take bipolar derivations of electrode contacts in order to enhance recordings of local brain activity and suppress noise levels. This approach can often cancel the signals in correlated neighboring contacts and create ambiguity …

Approaching Object Acceleration Differentially Affects The Predictions Of Neuronal Collision Avoidance Models, Fabrizio Gabbiani, Thomas Preuss, Richard B Dewell

Faculty, Staff and Students Publications

The processing of visual information for collision avoidance has been investigated at the biophysical level in several model systems. In grasshoppers, the (so-called) [Formula: see text] model captures reasonably well the visual processing performed by an identified neuron called the lobular giant movement detector as it tracks approaching objects. Similar phenomenological models have been used to describe either the firing rate or the membrane potential of neurons responsible for visually guided collision avoidance in other animals. Specifically, in goldfish, the [Formula: see text] model has been proposed to describe the Mauthner cell, an identified neuron involved in startle escape responses. …

Botulinum Neurotoxin Injections In Children With Self-Injurious Behaviors, Mariam Hull, Mered Parnes, Joseph Jankovic

Faculty, Staff and Students Publications

Self-injurious behaviors are repetitive, persistent actions directed toward one's body that threaten or cause physical harm. These behaviors are seen within a broad spectrum of neurodevelopmental and neuropsychiatric conditions, often associated with intellectual disability. Injuries can be severe and distressing to patients and caregivers. Furthermore, injuries can be life-threatening. Often, these behaviors are challenging to treat and require a tiered, multimodal approach which may include mechanical/physical restraints, behavioral therapy, pharmacotherapy, or in some cases, surgical management, such as tooth extraction or deep brain stimulation. Here, we describe a series of 17 children who presented to our institution with self-injurious behaviors …

In Vivo Functional Characterization Of Egfr Variants Identifies Novel Drivers Of Glioblastoma, Kwanha Yu, Kathleen Kong, Brittney Lozzi, Estefania Luna-Figueroa, Alexis Cervantes, Rachel Curry, Carrie A Mohila, Ganesh Rao, Ali Jalali, Gordon B Mills, Kenneth L Scott, Benjamin Deneen

Faculty, Staff and Students Publications

BACKGROUND: Glioblastoma is the most common and aggressive primary brain tumor. Large-scale sequencing initiatives have cataloged its mutational landscape in hopes of elucidating mechanisms driving this deadly disease. However, a major bottleneck in harnessing this data for new therapies is deciphering "driver" and "passenger" events amongst the vast volume of information.

METHODS: We utilized an autochthonous, in vivo screening approach to identify driver, EGFR variants. RNA-Seq identified unique molecular signatures of mouse gliomas across these variants, which only differ by a single amino acid change. In particular, we identified alterations to lipid metabolism, which we further validated through an unbiased …

Hypermitotic Meningiomas Harbor Dna Methylation Subgroups With Distinct Biological And Clinical Features, Abrar Choudhury, William C Chen, Calixto-Hope G Lucas, James C Bayley, Akdes S Harmanci, Sybren L N Maas, Sandro Santagata, Tiemo Klisch, Arie Perry, Wenya Linda Bi, Felix Sahm, Akash J Patel, Stephen T Magill, David R Raleigh

Faculty, Staff and Students Publications

BACKGROUND: Meningiomas, the most common primary intracranial tumors, can be separated into 3 DNA methylation groups with distinct biological drivers, clinical outcomes, and therapeutic vulnerabilities. Alternative meningioma grouping schemes using copy number variants, gene expression profiles, somatic short variants, or integrated molecular models have been proposed. These data suggest meningioma DNA methylation groups may harbor subgroups unifying contrasting theories of meningioma biology.

METHODS: A total of 565 meningioma DNA methylation profiles from patients with comprehensive clinical follow-up at independent discovery (n = 200) or validation (n = 365) institutions were reanalyzed and classified into Merlin-intact, Immune-enriched, or Hypermitotic DNA methylation …