Neurology Commons^™

Disruption Of Specific White Matter Tracts Is Associated With Neurogenic Lower Urinary Tract Dysfunction In Women With Multiple Sclerosis, Darshil Choksi, Bradley Schott, Khue Tran, Ryan Jang, Khader M Hasan, John A Lincoln, Ali Jalali, Christof Karmonik, Betsy Salazar, Rose Khavari

Faculty, Staff and Student Publications

OBJECTIVE: To identify specific white matter tracts (WMTs) whose disruption is associated with the severity of neurogenic lower urinary tract dysfunction (NLUTD) in two independent cohorts of women with multiple sclerosis (MS) and NLUTD.

METHODS: Cohort 1 consisted of twenty-eight women with MS and NLUTD. The validation cohort consisted of 10 women with MS and NLUTD. Eleven healthy women served as controls. Participants of both MS cohorts had the same inclusion and exclusion criteria. Both MS cohorts and the healthy controls underwent the same clinical assessment and functional MRI (fMRI) protocol, except that the validation MS cohort underwent 7-Tesla fMRI …

Framework For Accurate Classification Of Self-Reported Stress From Multisession Functional Mri Data Of Veterans With Posttraumatic Stress, Rahul Goel, Teresa Tse, Lia J Smith, Andrew Floren, Bruce Naylor, M Wright Williams, Ramiro Salas, Albert S Rizzo, David Ress

Faculty, Staff and Students Publications

Background: Posttraumatic stress disorder (PTSD) is a significant burden among combat Veterans returning from the wars in Iraq and Afghanistan. While empirically supported treatments have demonstrated reductions in PTSD symptomatology, there remains a need to improve treatment effectiveness. Functional magnetic resonance imaging (fMRI) neurofeedback has emerged as a possible treatment to ameliorate PTSD symptom severity. Virtual reality (VR) approaches have also shown promise in increasing treatment compliance and outcomes. To facilitate fMRI neurofeedback-associated therapies, it would be advantageous to accurately classify internal brain stress levels while Veterans are exposed to trauma-associated VR imagery. Methods: Across 2 sessions, we used fMRI …

The Tmem106b T186s Coding Variant Increases Neurite Arborization And Synaptic Density In Primary Hippocampal Neurons, Quynh Nguyen, Caleb A Wood, Peter J Kim, Joanna L Jankowsky

Faculty, Staff and Students Publications

The lysosomal protein TMEM106B was identified as a risk modifier of multiple dementias including frontotemporal dementia and Alzheimer’s disease. The gene comes in two major haplotypes, one associated with disease risk, and by comparison, the other with resilience. Only one coding polymorphism distinguishes the two alleles, a threonine-to-serine substitution at residue 185 (186 in mouse), that is inherited in disequilibrium with multiple non-coding variants. Transcriptional studies suggest synaptic, neuronal, and cognitive preservation in human subjects with the protective haplotype, while murine in vitro studies reveal dramatic effects of TMEM106B deletion on neuronal development. Despite this foundation, the field has not …

Stereo-Eeg-Guided Network Modulation For Psychiatric Disorders: Surgical Considerations, Sameer A Sheth, Ben Shofty, Anusha Allawala, Jiayang Xiao, Joshua A Adkinson, Raissa K Mathura, Victoria Pirtle, John Myers, Denise Oswalt, Nicole R Provenza, Nisha Giridharan, Angela M Noecker, Garrett P Banks, Ron Gadot, Ricardo A Najera, Adrish Anand, Ethan Devara, Huy Dang, Eleonora Bartoli, Andrew Watrous, Jeffrey Cohn, David Borton, Sanjay J Mathew, Cameron C Mcintyre, Wayne Goodman, Kelly Bijanki, Nader Pouratian

Faculty, Staff and Students Publications

BACKGROUND: Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders.

OBJECTIVE: /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field.

METHODS: We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy …

Cerebral Microdialysis And Glucopenia In Traumatic Brain Injury: A Review, Himanshu Sharma, John P Mcginnis, Katherine E Kabotyanski, Shankar P Gopinath, Jerry C Goodman, Claudia Robertson, Jovany Cruz Navarro

Faculty, Staff and Students Publications

Traditionally, intracranial pressure (ICP) and partial brain tissue oxygenation (PbtO2) have been the primary invasive intracranial measurements used to guide management in patients with severe traumatic brain injury (TBI). After injury however, the brain develops an increased metabolic demand which may require an increment in the oxidative metabolism of glucose. Simultaneously, metabolic, and electrical dysfunction can lead to an inability to meet these demands, even in the absence of ischemia or increased intracranial pressure. Cerebral microdialysis provides the ability to accurately measure local concentrations of various solutes including lactate, pyruvate, glycerol and glucose. Experimental and clinical data demonstrate that such …

Postsurgical Morbidity And Mortality Favorably Informs Deep Brain Stimulation For New Indications Including Schizophrenia And Schizoaffective Disorder, Judith M Gault, Patrick Hosokawa, Daniel Kramer, Elyn R Saks, Paul S Appelbaum, John A Thompson, Ann Olincy, Nicola Cascella, Akira Sawa, Wayne Goodman, Nidal Moukaddam, Sameer A Sheth, William S Anderson, Rachel A Davis

Faculty, Staff and Students Publications

BACKGROUND: Deep brain stimulation (DBS) shows promise for new indications like treatment-refractory schizophrenia in early clinical trials. In the first DBS clinical trial for treatment refractory schizophrenia, despite promising results in treating psychosis, one of the eight subjects experienced both a symptomatic hemorrhage and an infection requiring device removal. Now, ethical concerns about higher surgical risk in schizophrenia/schizoaffective disorder (SZ/SAD) are impacting clinical trial progress. However, insufficient cases preclude conclusions regarding DBS risk in SZ/SAD. Therefore, we directly compare adverse surgical outcomes for all surgical procedures between SZ/SAD and Parkinson's disease (PD) cases to infer relative surgical risk relevant to …

Attenuating Side Effects Of Deep Brain Stimulation In The Bed Nucleus Of The Stria Terminalis For Obsessive Compulsive Disorder Using Current-Steering Strategies, Huy Q Dang, Nicole R Provenza, Garrett P Banks, Nisha Giridharan, Michelle Avendano-Ortega, Sarah A Mckay, Ethan Devara, Ben Shofty, Eric A Storch, Sameer A Sheth, Wayne K Goodman

Faculty, Staff and Students Publications

No abstract provided.

Editorial: Surgical Techniques For The Management Of Pain, Anthony K Allam, Ashwin Viswanathan, Jason M Schwalb, Parag G Patil, M Benjamin Larkin

Faculty, Staff and Students Publications

No abstract provided.

Advances In Imaging Modalities For Pediatric Brain And Spinal Cord Tumors, Thierry A G M Huisman, Rajan Patel, Stephen Kralik, Nilesh K Desai, Avner Meoded, Karen Chen, Howard L Weiner, Daniel J Curry, Maarten Lequin, Mariette Kranendonk, Gunes Orman, George Jallo

Faculty, Staff and Students Publications

Background: Neuroimaging has evolved from anatomical imaging toward a multi-modality comprehensive anatomical and functional imaging in the past decades, important functional data like perfusion-weighted imaging, permeability imaging, diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI), tractography, metabolic imaging, connectomics, event-related functional imaging, resting state functional imaging, and much more is now being offered.

Summary: Precision diagnostics has proven to be essential for precision treatment. Many minimal invasive techniques have been developed, taking advantage of digital subtraction angiography and interventional neuroradiology. Furthermore, intraoperative CT and/or MRI and more recently MR-guided focused ultrasound have complemented the diagnostic and therapeutic armamentarium.

Key messages: …

Behavioral Improvements Following Lesion Resection For Pediatric Epilepsy: Pediatric Psychosurgery?, Huy Dang, Abdul Basit Khan, Nisha Gadgil, Himanshu Sharma, Cristina Trandafir, Fatema Malbari, Howard L Weiner

Faculty, Staff and Students Publications

Introduction: Resection of brain lesions associated with refractory epilepsy to achieve seizure control is well accepted. However, concurrent behavioral effects of these lesions such as changes in mood, personality, and cognition and the effects of surgery on behavior have not been well characterized. We describe 5 such children with epileptogenic lesions and significant behavioral abnormalities which improved after surgery.

Case descriptions: Five children (ages 3-14 years) with major behavioral abnormalities and lesional epilepsy were identified and treated at our center. Behavioral problems included academic impairment, impulsivity, self-injurious behavior, and decreased social interaction with diagnoses of ADHD, oppositional defiant disorder, and …

Editorial: Peripheral Stimulation: Neuromodulation Of The Central Nervous System Through Existing Pathways, Musa Ozturk, Julio Cesar Hernandez-Pavon, Alexander Kent, Jose L Pons, Ilknur Telkes, Arjun Tarakad

Faculty, Staff and Students Publications

No abstract provided.

Spatial Analysis Of Nanoparticle Distribution In Human Breast Xenografts Reveals Nanoparticles Targeted To Cancer Cells Localized With Tumor-Associated Stromal Cells, Sean Healy, Elizabeth T Henderson, Suqi Ke, Jacqueline Kelly, Brian W Simons, Chen Hu, Robert Ivkov, Preethi Korangath

Faculty, Staff and Students Publications

The biological influence of physicochemical parameters of “targeted” nanoparticles on their delivery to cancer tumors remains poorly understood. A comparative analysis of nanoparticle distributions in tumors following systemic delivery across several models can provide valuable insights.

Methods: Bionized nanoferrite nanoparticles (iron oxide core coated with starch), either conjugated with a targeted anti-HER2 antibody (BH), or unconjugated (BP), were intravenously injected into athymic nude or NOD-scid gamma (NSG) female mice bearing one of five human breast cancer tumor xenografts growing in a mammary fat pad. Tumors were harvested 24 hours after nanoparticle injection, fixed, mounted, and stained. We performed detailed histopathology …

Mass Spectrometry Imaging As An Emerging Tool For Studying Metabolism In Human Brain Organoids, Gerarda Cappuccio, Saleh M Khalil, Sivan Osenberg, Feng Li, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

Human brain organoids are emerging models to study human brain development and pathology as they recapitulate the development and characteristics of major neural cell types, and enable manipulation through an in vitro system. Over the past decade, with the advent of spatial technologies, mass spectrometry imaging (MSI) has become a prominent tool for metabolic microscopy, providing label-free, non-targeted molecular and spatial distribution information of the metabolites within tissue, including lipids. This technology has never been used for studies of brain organoids and here, we set out to develop a standardized protocol for preparation and mass spectrometry imaging of human brain …

Forniceal Deep Brain Stimulation In A Mouse Model Of Rett Syndrome Increases Neurogenesis And Hippocampal Memory Beyond The Treatment Period, Qi Wang, Bin Tang, Shuang Hao, Zhenyu Wu, Tingting Yang, Jianrong Tang

Faculty, Staff and Students Publications

BACKGROUND: Rett syndrome (RTT), caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2), severely impairs learning and memory. We previously showed that forniceal deep brain stimulation (DBS) stimulates hippocampal neurogenesis with concomitant improvements in hippocampal-dependent learning and memory in a mouse model of RTT.

OBJECTIVES: To determine the duration of DBS benefits; characterize DBS effects on hippocampal neurogenesis; and determine whether DBS influences MECP2 genotype and survival of newborn dentate granular cells (DGCs) in RTT mice.

METHODS: Chronic DBS was delivered through an electrode implanted in the fimbria-fornix. We tested separate cohorts of mice in contextual …

Subcortical Functional Connectivity And Its Association With Walking Performance Following Deployment Related Mild Tbi, Mary R Newsome, Sarah L Martindale, Nicholas Davenport, Emily L Dennis, Marlene Diaz, Carrie Esopenko, Cooper Hodges, George R Jackson, Qisheng Liu, Kimbra Kenney, Andrew R Mayer, Jared A Rowland, Randall S Scheibel, Joel L Steinberg, Brian A Taylor, David F Tate, J Kent Werner, William C Walker, Elisabeth A Wilde

Faculty, Staff and Students Publications

INTRODUCTION: The relation between traumatic brain injury (TBI), its acute and chronic symptoms, and the potential for remote neurodegenerative disease is a priority for military research. Structural and functional connectivity (FC) of the basal ganglia, involved in motor tasks such as walking, are altered in some samples of Service Members and Veterans with TBI, but any behavioral implications are unclear and could further depend on the context in which the TBI occurred.

METHODS: In this study, FC from caudate and pallidum seeds was measured in Service Members and Veterans with a history of mild TBI that occurred during combat deployment, …

Codon-Optimized Tdp-43 Mediates Neurodegeneration In A Drosophila Model Of Als/Ftld, Tanzeen Yusuff, Ya-Chu Chang, Tzu-Kang Sang, George R Jackson, Shreyasi Chatterjee

Faculty, Staff and Students Publications

Transactive response DNA binding protein-43 (TDP-43) is known to mediate neurodegeneration associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The exact mechanism by which TDP-43 exerts toxicity in the brains, spinal cord, and lower motor neurons of affected patients remains unclear. In a novel Drosophila melanogaster model, we report gain-of-function phenotypes due to misexpression of insect codon-optimized version of human wild-type TDP-43 (CO-TDP-43) using both the binary GAL4/UAS system and direct promoter fusion constructs. The CO-TDP-43 model showed robust tissue specific phenotypes in the adult eye, wing, and bristles in the notum. Compared to non-codon optimized …

Peripherally-Induced Movement Disorders: An Update, Abhishek Lenka, Joseph Jankovic

Faculty, Staff and Students Publications

BACKGROUND: Peripherally-induced movement disorders (PIMD) should be considered when involuntary or abnormal movements emerge shortly after an injury to a body part. A close topographic and temporal association between peripheral injury and onset of the movement disorders is crucial to diagnosing PIMD. PIMD is under-recognized and often misdiagnosed as functional movement disorder, although both may co-exist. Given the considerable diagnostic, therapeutic, and psychosocial-legal challenges associated with PIMD, it is crucial to update the clinical and scientific information about this important movement disorder.

METHODS: A comprehensive PubMed search through a broad range of keywords and combinations was performed in February 2023 …

Establishing An Online Resource To Facilitate Global Collaboration And Inclusion Of Underrepresented Populations: Experience From The Mjff Global Genetic Parkinson’S Disease Project, Eva-Juliane Vollstedt, Harutyun Madoev, Anna Aasly, Azlina Ahmad-Annuar, Bashayer Al-Mubarak, Roy N Alcalay, Victoria Alvarez, Ignacio Amorin, Grazia Annesi, David Arkadir, Soraya Bardien, Roger A Barker, Melinda Barkhuizen, A Nazli Basak, Vincenzo Bonifati, Agnita Boon, Laura Brighina, Kathrin Brockmann, Andrea Carmine Belin, Jonathan Carr, Jordi Clarimon, Mario Cornejo-Olivas, Leonor Correia Guedes, Jean-Christophe Corvol, David Crosiers, Joana Damásio, Parimal Das, Patricia De Carvalho Aguiar, Anna De Rosa, Jolanta Dorszewska, Sibel Ertan, Rosangela Ferese, Joaquim Ferreira, Emilia Gatto, Gençer Genç, Nir Giladi, Pilar Gómez-Garre, Hasmet Hanagasi, Nobutaka Hattori, Faycal Hentati, Dorota Hoffman-Zacharska, Sergey N Illarioshkin, Joseph Jankovic, Silvia Jesús, Valtteri Kaasinen, Anneke Kievit, Peter Klivenyi, Vladimir Kostic, Dariusz Koziorowski, Andrea A Kühn, Anthony E Lang, Shen-Yang Lim, Chin-Hsien Lin, Katja Lohmann, Vladana Markovic, Mika Henrik Martikainen, George Mellick, Marcelo Merello, Lukasz Milanowski, Pablo Mir, Özgür Öztop-Çakmak, Márcia Mattos Gonçalves Pimentel, Teeratorn Pulkes, Andreas Puschmann, Ekaterina Rogaeva, Esther M Sammler, Maria Skaalum Petersen, Matej Skorvanek, Mariana Spitz, Oksana Suchowersky, Ai Huey Tan, Pichet Termsarasab, Avner Thaler, Vitor Tumas, Enza Maria Valente, Bart Van De Warrenburg, Caroline H Williams-Gray, Ruey-Mei Wu, Baorong Zhang, Alexander Zimprich, Justin Solle, Shalini Padmanabhan, Christine Klein

Faculty, Staff and Students Publications

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, …

Hippocampal Δfosb Expression Is Associated With Cognitive Impairment In A Subgroup Of Patients With Childhood Epilepsies, Chia-Hsuan Fu, Jason C You, Carrie Mohila, Robert A Rissman, Daniel Yoshor, Angela N Viaene, Jeannie Chin

Faculty, Staff and Students Publications

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is often comorbid with other neurological and neurodegenerative diseases, such as Alzheimer's disease (AD). Patients with recurrent seizures often present with cognitive impairment. However, it is unclear how seizures, even when infrequent, produce long-lasting deficits in cognition. One mechanism may be seizure-induced expression of ΔFosB, a long-lived transcription factor that persistently regulates expression of plasticity-related genes and drives cognitive dysfunction. We previously found that, compared with cognitively-intact subjects, the activity-dependent expression of ΔFosB in the hippocampal dentate gyrus (DG) was increased in individuals with mild cognitive impairment (MCI) and …

Δfosb Is Part Of A Homeostatic Mechanism That Protects The Epileptic Brain From Further Deterioration, Jerome Clasadonte, Tania Deprez, Gabriel S Stephens, Georges Mairet-Coello, Pierre-Yves Cortin, Maxime Boutier, Aurore Frey, Jeannie Chin, Marek Rajman

Faculty, Staff and Students Publications

Activity induced transcription factor ΔFosB plays a key role in different CNS disorders including epilepsy, Alzheimer's disease, and addiction. Recent findings suggest that ΔFosB drives cognitive deficits in epilepsy and together with the emergence of small molecule inhibitors of ΔFosB activity makes it an interesting therapeutic target. However, whether ΔFosB contributes to pathophysiology or provides protection in drug-resistant epilepsy is still unclear. In this study, ΔFosB was specifically downregulated by delivering AAV-shRNA into the hippocampus of chronically epileptic mice using the drug-resistant pilocarpine model of mesial temporal epilepsy (mTLE). Immunohistochemistry analyses showed that prolonged downregulation of ΔFosB led to exacerbation …