Neurology Commons^™

Longitudinally Extensive Transverse Myelitis: A Sub-Saharan Conundrum, Antonina Obayo, Sylvia Mbugua, Sayed Karar

Internal Medicine, East Africa

Spinal cord schistosomiasis is a rare, underdiagnosed manifestation of schistosomiasis. We present the case of a 36-year-old male who presented to our institution with a one-week history of low back pain with rapidly progressive lower limb weakness, loss of sensation, and flaccid paraparesis. An MRI of the spine showed a longitudinally extensive transverse myelitis from T6 to L1, with enhancement at the cauda equina region. Further review of the images and serological tests eventually led to diagnosis of spinal schistosomiasis. He was treated with praziquantel and high-dose steroids, with minimal improvement in his symptoms.

Network-Level Mechanisms Underlying Effects Of Transcranial Direct Current Stimulation (Tdcs) On Visuomotor Learning, Pejman Sehatpour, Clément Dondé, Matthew J. Hoptman, Johanna Kreither, Devin Adair, Elisa Dias, Blair Vail, Stephanie Rohrig, Gail Silipo, Javier Lopez-Calderon, Antigona Martinez, Daniel C. Javitt

Publications and Research

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation approach in which low level currents are administered over the scalp to influence underlying brain function. Prevailing theories of tDCS focus on modulation of excitation-inhibition balance at the local stimulation location. However, network level effects are reported as well, and appear to depend upon differential underlying mechanisms. Here, we evaluated potential network-level effects of tDCS during the Serial Reaction Time Task (SRTT) using convergent EEG- and fMRI-based connectivity approaches. Motor learning manifested as a significant (p <.0001) shift from slow to fast responses and corresponded to a significant increase in beta-coherence (p <.0001) and fMRI connectivity (p <.01) particularly within the visual-motor pathway. Differential patterns of tDCS effect were observed within different parametric task versions, consistent with network models. Overall, these findings demonstrate objective physiological effects of tDCS at the network level that result in effective behavioral modulation when tDCS parameters are matched to network-level requirements of the underlying task.

Low Cognitive Function Is Associated With Reduced Functional Fitness Among Community-Dwelling Older Adults, Michelle Gray, Joshua Gills, Jordan Glenn, Erica Madero, Aidan Hall, Nami Fuseya, Jennifer Vincenzo, Nick Bott

Health, Human Performance and Recreation Faculty Publications and Presentations

Among older adults over 70, 22-30% report difficulty performing at least one activity of daily living (ADL). While the precipitants of ADL decline are multifactorial, over 50% of cognitively impaired adults require assistance with ADLs. The exact relationship between cognitive and functional decline remains unknown, but it is important to understand their relationship. Eighty-three older adults (80.9 + 5.4 years) enrolled in this study and completed functional fitness and cognitive assessments. Functional fitness assessments included: Short Physical Performance Battery (SPPB), 10-meter walk, dual-task, and power chair stand (average and peak). Cognition was assessed using the Montreal Cognitive Assessment (MoCA) and …

Epilepsy Risk Prediction Model For Patients With Tuberous Sclerosis Complex, Laura S Farach, Melissa A Richard, Philip J Lupo, Mustafa Sahin, Darcy A Krueger, Joyce Y Wu, Elizabeth M Bebin, Kit Sing Au, Hope Northrup, Tacern Study Group

Faculty, Staff and Student Publications

BACKGROUND: Individuals with tuberous sclerosis complex are at increased risk of epilepsy. Early seizure control improves developmental outcomes, making identifying at-risk patients critically important. Despite several identified risk factors, it remains difficult to predict. The purpose of the study was to evaluate the combined risk prediction of previously identified risk factors for epilepsy in individuals with tuberous sclerosis complex.

METHODS: The study group (n = 333) consisted of individuals with tuberous sclerosis complex who were enrolled in the Tuberous Sclerosis Complex Autism Center of Excellence Research Network and UT TSC Biobank. The outcome was defined as having an epilepsy diagnosis. …

A Signal Detection Framework For Evaluating The Effects Of Feedback On Stroke Recognition, Jordan D. Bailey

Dissertations

The impact of stroke on the lives of individuals and the healthcare system is considerable. Damage from stroke can be reduced if the treatment is administered at the appropriate time so early recognition is essential. One problem is that strokes present in a variety of ways that sometimes do not fit into the Facial drooping, Arm weakness, Speech difficulties and Time (FAST; American Heart Association, 2019) acronym. Signal detection is one way to measure decision making under conditions of uncertainty (e.g., discriminating stroke symptoms and risk factors from other symptoms, and non-risk factors). The methodology also allows us to consider …

A Narrative Review Of Targeted Therapy In Meningioma, Pituitary Adenoma, And Craniopharyngioma Of The Skull Base., Nina L. Martinez, Omaditya Khanna, Christopher J. Farrell

Department of Neurosurgery Faculty Papers

Management of solid tumors involving the skull base are primarily managed with surgery and radiation, though proximity to important vascular and neuroanatomic structures often limit the extent of resection and permissible radiation dose. Meningiomas are the most common primary brain tumor in adults, and although the majority of skull base meningiomas are low-grade, their location in proximity to critical anatomical structures precludes aggressive surgical resection, and larger tumors are often resistant to radiation treatment. In patients with clinically aggressive, unresectable meningiomas, several molecular biomarkers of angiogenesis, as well as genetic mutations (SMO, AKT1, PIK3CA, KLF4, POLR2, SMARCE1, and TRAF7), have …

Inflammatory Myopathies: Update On Diagnosis, Pathogenesis And Therapies, And Covid-19-Related Implications., Marinos C. Dalakas

Department of Neurology Faculty Papers

The inflammatory myopathies constitute a heterogeneous group of acquired myopathies that have in common the presence of endomysial inflammation. Based on steadily evolved clinical, histological and immunopathological features and some autoantibody associations, these disorders can now be classified in five characteristic subsets: Dermatomyositis (DM) Polymyositis (PM), Necrotizing Autoimmune Myositis (NAM), Anti-synthetase syndrome-overlap myositis (Anti-SS-OM), and Inclusion-Body-Myositis (IBM). Each inflammatory myopathy subset has distinct immunopathogenesis, prognosis and response to immunotherapies, necessitating the need to correctly identify each subtype from the outset to avoid disease mimics and proceed to early therapy initiation. The review presents the main clinicopathologic characteristics of each subset …

Acute Ischemic Stroke As The Presenting Feature Of Covid-19 In The Young And Pregnant, Nermila A. Ballmick, Jiri F. Kubac, Hossein Akhondi

HCA Healthcare Journal of Medicine

Introduction: Coronavirus disease (COVID-19) is an emerging and rapidly evolving public health issue that has become globally widespread and an overwhelming pandemic. Clinical manifestations of the disease include asymptomatic carrier states, acute respiratory distress syndrome, and even multiorgan dysfunction. Here, we present a unique and rare case of an acute ischemic stroke (AIS) in an asymptomatic pregnant woman with no predisposing medical illnesses.

Discussion: An 18-year-old G2P1 African American woman at 7 weeks gestational age with no significant medical or family history presenting to the Emergency Department during the initial phases of the pandemic with complaints of new onset left …

Neuropsychiatric Presentation Of Covid-19: A Case Report Of Disinhibition In An Acute Sars-Cov-2 Infection, I. Jack Abramson, Kristy A. Fisher, Clara V. Alvarez, Jacqueline Horan Fisher

HCA Healthcare Journal of Medicine

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) viral infection is notable for a high degree of symptom diversity. Emerging evidence suggests viral invasion of the central nervous system; therefore, serious neurological and psychiatric manifestations are anticipated. We present the case of a 67-year-old male physician with a history of stable Bipolar Disorder for decades, hospitalized for persistent COVID-19 symptoms with documented positive serology, who presented with new and acute onset neuropsychiatric symptoms of disinhibition proximate the viral infection. We postulate neuroinvasion as the putative origin of the patient’s psychiatric instability. Further investigation is needed to expand upon our understanding of the …

Dynamic Body-Weight Support To Boost Rehabilitation Outcomes In Patients With Non-Traumatic Spinal Cord Injury: An Observational Study, Justin P. Huber, Lumy Sawaki

Neurology Faculty Publications

BACKGROUND: Dynamic body-weight support (DBWS) may play an important role in rehabilitation outcomes, but the potential benefit among disease-specific populations is unclear. In this study, we hypothesize that overground therapy with DBWS during inpatient rehabilitation yields greater functional improvement than standard-of-care in adults with non-traumatic spinal cord injury (NT-SCI).

METHODS: This retrospective cohort study included individuals diagnosed with NT-SCI and undergoing inpatient rehabilitation. All participants were recruited at a freestanding inpatient rehabilitation hospital. Individuals who trained with DBWS for at least three sessions were allocated to the experimental group. Participants in the historical control group received standard-of-care (i.e., no DBWS). …

Applications Of Non-Invasive Neuromodulation For The Management Of Disorders Related To Covid-19, Abrahão Fontes Baptista, Adriana Baltar, Alexandre Hideki Okano, Alexandre Moreira, Ana Carolina Pinheiro Campos, Ana Mércia Fernandes, André Russowsky Brunoni, Bashar W. Badran, Clarice Tanaka, Daniel Ciampi De Andrade, Daniel Gomes Da Silva Machado, Edgard Morya, Eduardo Trujillo, Jaiti K. Swami, Joan A. Camprodon, Katia Monte-Silva, Katia Nunes Sá, Isadora Nunes, Juliana Barbosa Goulardins, Marom Bikson, Pedro Sudbrack-Oliveira, Priscila De Carvalho, Rafael Jardim Duarte-Moreira, Rosana Lima Pagano, Samuel Katsuyuki Shinjo, Yossi Zana

Publications and Research

Background: Novel coronavirus disease (COVID-19) morbidity is not restricted to the respiratory system, but also affects the nervous system. Non-invasive neuromodulation may be useful in the treatment of the disorders associated with COVID-19.

Objective: To describe the rationale and empirical basis of the use of non-invasive neuromodulation in the management of patients with COVID-10 and related disorders.

Methods: We summarize COVID-19 pathophysiology with emphasis of direct neuroinvasiveness, neuroimmune response and inflammation, autonomic balance and neurological, musculoskeletal and neuropsychiatric sequela. This supports the development of a framework for advancing applications of non-invasive neuromodulation in the management COVID-19 and related disorders.

Results: …

Diagnosing And Managing Post-Stroke Aphasia, Shannon M. Sheppard, Rajani Sebastian

Communication Sciences and Disorders Faculty Articles and Research

Introduction: Aphasia is a debilitating language disorder and even mild forms of aphasia can negatively affect functional outcomes, mood, quality of life, social participation, and the ability to return to work. Language deficits after post-stroke aphasia are heterogeneous.

Areas covered: The first part of this manuscript reviews the traditional syndrome-based classification approach as well as recent advances in aphasia classification that incorporate automatic speech recognition for aphasia classification. The second part of this manuscript reviews the behavioral approaches to aphasia treatment and recent advances such as noninvasive brain stimulation techniques and pharmacotherapy options to augment the effectiveness of …

Sleep Deprivation And Neurological Disorders, Muhammed Bishir

Brain and Mind Institute

Sleep plays an important role in maintaining neuronal circuitry, signalling and helps maintain overall health and wellbeing. Sleep deprivation (SD) disturbs the circadian physiology and exerts a negative impact on brain and behavioural functions. SD impairs the cellular clearance of misfolded neurotoxin proteins like α-synuclein, amyloid-β, and tau which are involved in major neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease. In addition, SD is also shown to affect the glymphatic system, a glial-dependent metabolic waste clearance pathway, causing accumulation of misfolded faulty proteins in synaptic compartments resulting in cognitive decline. Also, SD affects the immunological and …

Social And Leisure Activities Predict Transitions In Cognitive Functioning In Older Mexican Adults: A Latent Transition Analysis Of The Mexican Health And Aging Study, Heather Mary Brown, Stephen A Murray, Hope Northrup, Kit Sing Au, Lee A Niswander

Faculty, Staff and Student Publications

Disruptions in neural tube (NT) closure result in neural tube defects (NTDs). To understand the molecular processes required for mammalian NT closure, we investigated the role of Snx3, a sorting nexin gene. Snx3−/− mutant mouse embryos display a fully-penetrant cranial NTD. In vivo, we observed decreased canonical WNT target gene expression in the cranial neural epithelium of the Snx3−/− embryos and a defect in convergent extension of the neural epithelium. Snx3−/− cells show decreased WNT secretion, and live cell imaging reveals aberrant recycling of the WNT ligand-binding protein WLS and mis-trafficking to the lysosome for degradation. The importance …

Efficacy And Safety Of Abobotulinumtoxina For Upper Limb Spasticity In Children With Cerebral Palsy: A Randomized Repeat-Treatment Study, Mauricio R. Delgado, Ann Tilton, Jorge Carranzo-Del Rio, Nigar Dursun, Marcin Bonikowski, Resa Aydin, Iwona Maciag-Tymecka, Joyce Oleszek, Edward Dabrowski, Anne-Sophie Grandoulier, Philippe Picaut, The Dysport In Pul Study Group

School of Medicine Faculty Publications

Aim: To assess the efficacy and safety of repeat abobotulinumtoxinA injections in reducing upper limb spasticity in children with cerebral palsy (CP). Method: This was a double-blind, repeat-cycle study (NCT02106351) in children with CP (2–17y). Children were randomized to receive 2U/kg (control), 8U/kg, or 16U/kg abobotulinumtoxinA injections into the target muscle group (wrist or elbow flexors) and additional muscles alongside occupational therapy via a home-exercise therapy program (HETP; minimum five 15min sessions/wk). Children received 8U/kg or 16U/kg plus HETP in cycles 2 to 4. Results: During cycle 1, 210 children (126 males, 84 females; mean age [SD] 9y [4y 5mo], …

Metabolic Network Analysis Reveals Altered Bile Acid Synthesis And Metabolism In Alzheimer's Disease., Priyanka Baloni, Cory C Funk, Jingwen Yan, James T Yurkovich, Alexandra Kueider-Paisley, Kwangsik Nho, Almut Heinken, Wei Jia, Siamak Mahmoudiandehkordi, Gregory Louie, Andrew J Saykin, Matthias Arnold, Gabi Kastenmüller, William J Griffiths, Ines Thiele, Alzheimer’S Disease Metabolomics Consortium, Rima Kaddurah-Daouk, Nathan D Price

Articles, Abstracts, and Reports

Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes and identify genes in the alternative bile acid synthesis pathway to be expressed in the brain. A targeted metabolomic analysis of primary and secondary bile acids measured from post-mortem brain samples of 111 individuals supports these results. Our metabolic network analysis suggests that taurine transport, bile acid synthesis, and cholesterol metabolism differ in AD and cognitively normal individuals. We also identify putative transcription factors regulating metabolic genes and influencing altered metabolism in AD. …

Pharmacological Intervention In Children With Autism Spectrum Disorder With Standard Supportive Therapies Significantly Improves Core Signs And Symptoms: A Single-Center, Retrospective Case Series, Hamza A. Alsayouf, Haitham Talo, Marisa L. Biddappa, Mohammad Qasaymeh, Shadi Qasem, Emily De Los Reyes

Pathology and Laboratory Medicine Faculty Publications

Purpose: Autism spectrum disorder (ASD) is a debilitating neurodevelopmental disorder with high heterogeneity and no clear common cause. Several drugs, in particular risperidone and aripiprazole, are used to treat comorbid challenging behaviors in children with ASD. Treatment with risperidone and aripiprazole is currently recommended by the Food and Drug Administration (FDA) in the USA for children aged 5 and 6 years and older, respectively. Here, we investigated the use of these medications in younger patients aged 4 years and older.

Patients and Methods: This retrospective case series included 18 children (mean age, 5.7 years) with ASD treated at the Kids …

Safety And Tolerability Of Srx246, A Vasopressin 1a Antagonist, In Irritable Huntington's Disease Patients-A Randomized Phase 2 Clinical Trial., Michael J Brownstein, Neal G Simon, Jeffrey D Long, Jon Yankey, Hilda T Maibach, Merit Cudkowicz, Christopher Coffey, Robin A Conwit, Codrin Lungu, Karen E Anderson, Steven M Hersch, Dixie J Ecklund, Eve M Damiano, Debra E Itzkowitz, Shifang Lu, Marianne K Chase, Jeremy M Shefner, Andrew Mcgarry, Brenda Thornell, Catherine Gladden, Michele Costigan, Padraig O'Suilleabhain, Frederick J Marshall, Amy M Chesire, Paul Deritis, Jamie L Adams, Peter Hedera, Kelly Lowen, H Diana Rosas, Amie L Hiller, Joseph Quinn, Kellie Keith, Andrew P Duker, Christina Gruenwald, Angela Molloy, Cara Jacob, Stewart Factor, Elaine Sperin, Danny Bega, Zsazsa R Brown, Lauren C Seeberger, Victor W Sung, Melanie Benge, Sandra K Kostyk, Allison M Daley, Susan Perlman, Valerie Suski, Patricia Conlon, Matthew J Barrett, Stephanie Lowenhaupt, Mark Quigg, Joel S Perlmutter, Brenton A Wright, Elaine Most, Guy J Schwartz, Jessica Lamb, Rosalind S Chuang, Carlos Singer, Karen Marder, Joyce A Moran, John R Singleton, Meghan Zorn, Paola V Wall, Richard M Dubinsky, Carolyn Gray, Carolyn Drazinic

Articles, Abstracts, and Reports

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington's disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic …

Longitudinal Assessment Of Dementia Measures In Down Syndrome, Lisa Mason Koehl, Jordan P. Harp, Kathryn L. Van Pelt, Elizabeth Head, Frederick A. Schmitt

Neurology Faculty Publications

Introduction: Early detection of dementia symptoms is critical in Down syndrome (DS) but complicated by clinical assessment barriers. The current study aimed to characterize cognitive and behavioral impairment using longitudinal trajectories comparing several measures of cognitive and behavioral functioning.

Methods: Measures included global cognitive status (Severe Impairment Battery [SIB]), motor praxis (Brief Praxis Test [BPT]), and clinical dementia informant ratings (Dementia Questionnaire for People with Learning Disabilities [DLD]). One-year reliability was assessed using a two-way mixed effect, consistency, single measurement intraclass correlation among non-demented participants. Longitudinal assessment of SIB, BPT, and DLD was completed using linear mixed effect models.

Results: …

Update On The Use Of Transcranial Electrical Brain Stimulation To Manage Acute And Chronic Covid-19 Symptoms, Giuseppina Pilloni, Marom Bikson, Bashar W. Badran, Mark S. George, Steven A. Kautz, Alexandre Hideki Okano, Abrahão Fontes Baptista, Leigh E. Charvet

Publications and Research

The coronavirus disease 19 (COVID-19) pandemic has resulted in the urgent need to develop and deploy treatment approaches that can minimize mortality and morbidity. As infection, resulting illness, and the often prolonged recovery period continue to be characterized, therapeutic roles for transcranial electrical stimulation (tES) have emerged as promising non-pharmacological interventions. tES techniques have established therapeutic potential for managing a range of conditions relevant to COVID-19 illness and recovery, and may further be relevant for the general management of increased mental health problems during this time. Furthermore, these tES techniques can be inexpensive, portable, and allow for trained self-administration. Here, …

Can Awake Glioma Surgery Be The New Standard Of Care In Developing Countries?, Syed Sarmad Bukhari, Muhammad Shahzad Shamim

Section of Neurosurgery

No abstract provided.

Understanding The Neuroprotective Effect Of Tranexamic Acid: An Exploratory Analysis Of The Crash-3 Randomised Trial, Amy Brenner, Antonio Belli, Rizwana Chaudhri, Timothy Coats, Lauren Frimley, Sabariah Faizah Jamaluddin, Rashid Jooma, Raoul Mansukhani, Peter Sandercock, Haleema Shakur-Still

Section of Neurosurgery

Background: The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death.
Methods: The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with …

Time Cells In The Human Hippocampus And Entorhinal Cortex Support Episodic Memory., Gray Umbach, Pranish Kantak, Joshua Jacobs, Michael Kahana, Brad E. Pfeiffer, Michael R Sperling, Bradley Lega

Department of Neurology Faculty Papers

The organization of temporal information is critical for the encoding and retrieval of episodic memories. In the rodent hippocampus and entorhinal cortex, evidence accumulated over the last decade suggests that populations of "time cells" in the hippocampus encode temporal information. We identify time cells in humans using intracranial microelectrode recordings obtained from 27 human epilepsy patients who performed an episodic memory task. We show that time cell activity predicts the temporal organization of retrieved memory items. We also uncover evidence of ramping cell activity in humans, which represents a complementary type of temporal information. These findings establish a cellular mechanism …

Ceramide Analog [18F]F-Hpa-12 Detects Sphingolipid Disbalance In The Brain Of Alzheimer’S Disease Transgenic Mice By Functioning As A Metabolic Probe, Simone M. Crivelli, Daan Van Kruining, Qian Luo, Jo A. A. Stevens, Caterina Giovagnoni, Andreas Paulus, Matthias Bauwens, Dusan Berkes, Helga E. De Vries, Monique T. Mulder, Jochen Walter, Etienne Waelkens, Rita Derua, Johannes V. Swinnen, Jonas Dehairs, Felix M. Mottaghy, Mario Losen, Erhard Bieberich, Pilar Martinez-Martinez

Physiology Faculty Publications

The metabolism of ceramides is deregulated in the brain of Alzheimer’s disease (AD) patients and is associated with apolipoprotein (APO) APOE4 and amyloid-β pathology. However, how the ceramide metabolism changes over time in AD, in vivo, remains unknown. Distribution and metabolism of [¹⁸F]F-HPA-12, a radio-fluorinated version of the ceramide analog N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide, was investigated in the brain of AD transgenic mouse models (FAD) on an APOE4 or APOE3 genetic background, by positron emission tomography and by gamma counter. We found that FAD mice displayed a higher uptake of [¹⁸F]F-HPA-12 in the brain, independently from the APOE4 …

New Generation Vmat2 Inhibitors Induced Parkinsonism, Rani Priyanka Vasireddy, Brent Sokola, Zain Guduru

Neurology Faculty Publications

Highlights

• Drug induced parkinsonism caused by valbenazine and deutetrabenazine.
• Possible side effects of VMAT-2 inhibitors.
• Valbenazine and deutetrabenazine can unmask underlying Parkinson’s Disease.

Mitigating Alemtuzumab-Associated Autoimmunity In Ms: A "Whack-A-Mole" B-Cell Depletion Strategy, Ethan Meltzer, Sarah Campbell, Benjamin Ehrenfeld, Roberto A. Cruz, Lawrence Steinman, Matthew S. Parsons, Scott S. Zamvil, Elliot M. Frohman, Teresa C. Frohman

School of Medicine Publications

Objective: To determine whether the punctuated administration of low-dose rituximab, temporally linked to B-cell hyperrepopulation (defined when the return of CD19+ B cells approximates 40%-50% of baseline levels as measured before alemtuzumab treatment inception), can mitigate alemtuzumab-associated secondary autoimmunity.

Methods: In this hypothesis-driven pilot study, 10 patients received low-dose rituximab (50-150 mg/m2), a chimeric anti-CD20 monoclonal antibody, after either their first or second cycles of alemtuzumab. These patients were then routinely assessed for the development of autoimmune disorders and safety signals related to the use of dual monoclonal antibody therapy.

Results: Five patients received at least 1 IV infusion of …

Intracranial Mesenchymal Tumor With Fet-Creb Fusion - A Unifying Diagnosis For The Spectrum Of Intracranial Myxoid Mesenchymal Tumors And Angiomatoid Fibrous Histiocytoma-Like Neoplasms, Emily A. Sloan, Jason Chiang, Javier E. Villanueva-Meyer, Sanda Alexandrescu, Jennifer M. Eschbacher, Wesley Wang, Manuela Mafra, Nasir Ud Din, Emily Carr-Boy, Michael Watson

Department of Pathology and Laboratory Medicine

Intracranial mesenchymal tumors with FET-CREB fusions are a recently described group of neoplasms in children and young adults characterized by fusion of a FET family gene (usually EWSR1, but rarely FUS) to a CREB family transcription factor (ATF1, CREB1, or CREM), and have been variously termed intracranial angiomatoid fibrous histiocytoma or intracranial myxoid mesenchymal tumor. The clinical outcomes, histologic features, and genomic landscape are not well defined. Here we studied twenty patients with intracranial mesenchymal tumors proven to harbor FET-CREB fusion by next-generation sequencing (NGS). The 16 female and 4 male patients had a median age of 14 years (range …

Distinct Clinicopathologic Clusters Of Persons With Tdp-43 Proteinopathy, Yuriko Katsumata, Erin L. Abner, Shama Karanth, Merilee A. Teylan, Charles N. Mock, Matthew D. Cykowski, Edward B. Lee, Kevin L. Boehme, Shubhabrata Mukherjee, John S. K. Kauwe, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Peter T. Nelson

Biostatistics Faculty Publications

To better understand clinical and neuropathological features of TDP-43 proteinopathies, data were analyzed from autopsied research volunteers who were followed in the National Alzheimer’s Coordinating Center (NACC) data set. All subjects (n = 495) had autopsy-proven TDP-43 proteinopathy as an inclusion criterion. Subjects underwent comprehensive longitudinal clinical evaluations yearly for 6.9 years before death on average. We tested whether an unsupervised clustering algorithm could detect coherent groups of TDP-43 immunopositive cases based on age at death and extensive neuropathologic data. Although many of the brains had mixed pathologies, four discernible clusters were identified. Key differentiating features were age at …

Anaesthetic Management Of Patients Undergoing Deep Brain Simulation: A Retrospective Review Of 8 Cases From A Tertiary Care Center Of Pakistan, Usama Ahmed, Faraz Shafiq, Dileep Kumar, Khalid Ahsan, Waleed Bin Ghaffar, Muhammad Ehsan Bari

Department of Anaesthesia

Objectives: To review anaesthesia related outcome, perioperative complications and overall length of stay (LOS) in hospital for patients who had deep brain stimulation (DBS).
Methods: The study was retrospective review of patients medical records diagnosed with Parkinson disease (PD) and underwent DBS at The Aga Khan University Hospital, Karachi from 2017-2019. Data was reviewed from file notes and patient chart and recorded on predesigned Performa. Frequency and percentages were used to present the data.
Results: All patients were anaesthetized using Sleep-Awake-Sleep technique (SAS). Dexmedetomidine was mainly used for conscious sedation. Bispectral index monitor (BIS) was used to monitor the depth …

Childhood Medulloblastoma, Naureen Mushtaq, Shahzadi Resham, Muhammad Shahzad Shamim, Bilal Mazhar Qureshi, Quratulain Riaz, Eric Bouffet

Section of Haematology/Oncology

Medulloblastoma is the most common malignant brain tumour in children and is a major cause of mortality and morbidity, particularly in low- and middle-income countries. It has been risk-stratified on the basis of clinical (age, metastasis and extent of resection) and histological subtypes (classic, desmoplastic and anaplastic). However, recently medulloblastoma has been sub-grouped by using a variety of different genomic approaches, such as gene expression profiling, micro-ribonucleic acid profiling and methylation array into 4 groups, namely Wingless, Sonic hedgehog, Group 3 and Group 4. This new sub-grouping has important therapeutic and prognostic implications. After acute leukaemia, brain tumour is the …