Neurology Commons^™

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 …

Stroke Preventive In African American Women Ages 20-40 That Are Using Or Have Used Oral Contraceptives, Ashanti L. N. Coleman

Electronic Theses and Dissertations

This Doctor of Nursing Practice project will inform the audience of stroke awareness as it pertains to oral contraceptives. The study’s focus was to enhance the knowledge of African American women ages 20–40 that have used or are currently using an oral contraceptive. It has been identified that this patient population lacked the knowledge regarding stroke and oral contraceptives, and African American women continue to have the highest incidence of stroke. African American women also make up more than half of the consumers utilizing oral contraceptives. An oral contraceptive knowledge questionnaire was utilized from previous research to determine if any …

Quality Of Life In Children Treated For Craniopharyngiomas, Mishal Gillani, Sheza Hassan, Umme Hani Abdullah, Muhammad Waqas Saeed Baqai, Muhammad Shahzad Shamim

Medical College Documents

Craniopharyngiomas are common but complex paediatric brain lesions that present interesting management challenges. Quality of life is an important consideration while choosing management options. In this review, we have discussed the existing literature on various aspects of quality of life in patients treated for craniopharyngioma, assessed by variety of measurement tools.

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 …

Identification Of Novel Candidate Risk Genes For Myelomeningocele Within The Glucose Homeostasis/Oxidative Stress And Folate/One-Carbon Metabolism Networks, Paul Hillman, Craig Baker, Luke Hebert, Michael Brown, James Hixson, Allison Ashley-Koch, Alanna C Morrison, Hope Northrup, Kit Sing Au

Faculty, Staff and Student Publications

BACKGROUND: Neural tube defects (NTDs) are the second most common complex birth defect, yet, our understanding of the genetic contribution to their development remains incomplete. Two environmental factors associated with NTDs are Folate and One Carbon Metabolism (FOCM) and Glucose Homeostasis and Oxidative Stress (GHOS). Utilizing next-generation sequencing of a large patient cohort, we identify novel candidate genes in these two networks to provide insights into NTD mechanisms.

METHODS: Exome sequencing (ES) was performed in 511 patients, born with myelomeningocele, divided between European American and Mexican American ethnicities. Healthy control data from the Genome Aggregation database were ethnically matched and …

Contribution Of Left Supramarginal And Angular Gyri To Episodic Memory Encoding: An Intracranial Eeg Study., Daniel Y. Rubinstein, Liliana Camarillo-Rodriguez, Mijail D. Serruya, Nora A. Herweg, Zachary J. Waldman, Paul A. Wanda, Ashwini D. Sharan, Shennan A. Weiss, Michael R. Sperling

Department of Neurology Faculty Papers

The role of the left ventral lateral parietal cortex (VPC) in episodic memory is hypothesized to include bottom-up attentional orienting to recalled items, according to the dual-attention model (Cabeza et al., 2008). However, its role in memory encoding could be further clarified, with studies showing both positive and negative subsequent memory effects (SMEs). Furthermore, few studies have compared the relative contributions of sub-regions in this functionally heterogeneous area, specifically the anterior VPC (supramarginal gyrus/BA40) and the posterior VPC (angular gyrus/BA39), on a within-subject basis. To elucidate the role of the VPC in episodic encoding, we compared SMEs in the intracranial …

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 …

Air Pollution And Non Communicable Diseases, Zafar Fatmi, Shafaq Mahmood, Zainab Samad, Mohammad Wasay

Community Health Sciences

No abstract provided.

Management Of Acute Ischemic Stroke., Franziska Herpich, Fred Rincon

Department of Neurology Faculty Papers

OBJECTIVES: Concise "synthetic" review of the state of the art of management of acute ischemic stroke.

DATA SOURCES: Available literature on PubMed.

STUDY SELECTION: We selected landmark studies, recent clinical trials, observational studies, and professional guidelines on the management of stroke including the last 10 years.

DATA EXTRACTION: Eligible studies were identified and results leading to guideline recommendations were summarized.

DATA SYNTHESIS: Stroke mortality has been declining over the past 6 decades, and as a result, stroke has fallen from the second to the fifth leading cause of death in the United States. This trend may follow recent advances in …

Perampanel-Induced Cataplexy In A Young Male With Generalized Epilepsy, Kelsey Kenaan, Mohsin Zafar, Ronnie Bond, Barbara L. Gracious

HCA Healthcare Journal of Medicine

Perampanel (Fycompa) is a newer anti-epileptic drug believed to exert its effects in the central nervous system by inhibiting post-synaptic glutamate receptors. However, the precise therapeutic mechanism is unknown. The most common neuropsychiatric side effect is affective dysregulation; there are also reports of psychosis. We describe a 32 year old African American male with recurring generalized tonic-clonic (GTC) seizures, who presented to our hospital with onset of mood lability for several months, after Perampanel was added to his antiepileptic medications. Perampanel administration was temporarily withheld, and subsequently on restarting, noted to be coincident with neuropsychiatric symptomatology, including motor weakness in …

Microhemorrhages In Professional Motocross Athletes: A Case Series, Brianna Millsaps, Phillip R. Worts, Scott O. Burkhart, David C. Berg

HCA Healthcare Journal of Medicine

Introduction: Motocross is a sport in which riders race 250–450 cc four-stroke dirt bikes and are potentially subjected to a high frequency of head injuries starting at a very young age. The objective of this case series is to present the findings following gradient echo T2-weighted MRI (SWI) upon clinical evaluation after a concussion in 4 young professional motocross racers.

Clinical Findings: Microhemorrhages were found in 2 of 4 riders. Areas of microhemorrhages were not aligned with a previously positive CT finding from a prior concussion in 1 rider.

Conclusions: Microhemorrhages were found in 2 young motocross riders following a …

Chronic Inflammatory Demyelinating Polyneuropathy (Cidp) In A Patient With Diabetes: A Primary Care Perspective, Jordan Dever, Adam M. Franks, Laura M. Given, William Rollyson, Adrienne Mays-Kingston

Marshall Journal of Medicine

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a recurrent and progressive disease that causes proximal, symmetrical extremity weakness. The disease is diagnosed using clinical features, electrophysiologic testing, albumino-cytological disassociation in the cerebrospinal fluid, and sural nerve plexus biopsy. However, because of the low sensitivity of diagnostic criteria and other similar neuropathies, including diabetic polyneuropathy (DPN), accurate diagnosis is difficult. Differentiating between these diseases is especially important as CIDP’s changes are reversible and DPN’s are not. Making this differentiation allows for symptomatic improvement in a patient’s quality of life that would not be achieved otherwise. Early recognition and treatment, with modalities including …

Microrna-Based Biomarkers In Alzheimer’S Disease (Ad), Yuhai Zhao, Vivian Jaber, Peter N. Alexandrov, Andrea Vergallo, Simone Lista, Harald Hampel, Walter J. Lukiw

School of Medicine Faculty Publications

Alzheimer’s disease (AD) is a multifactorial, age-related neurological disease characterized by complex pathophysiological dynamics taking place at multiple biological levels, including molecular, genetic, epigenetic, cellular and large-scale brain networks. These alterations account for multiple pathophysiological mechanisms such as brain protein accumulation, neuroinflammatory/neuro-immune processes, synaptic dysfunction, and neurodegeneration that eventually lead to cognitive and behavioral decline. Alterations in microRNA (miRNA) signaling have been implicated in the epigenetics and molecular genetics of all neurobiological processes associated with AD pathophysiology. These changes encompass altered miRNA abundance, speciation and complexity in anatomical regions of the CNS targeted by the disease, including modified miRNA expression …

Challenges And Opportunities For Improving The Landscape For Lewy Body Dementia Clinical Trials., Jennifer G Goldman, Leah K Forsberg, Bradley F Boeve, Melissa J Armstrong, David J Irwin, Tanis J Ferman, Doug Galasko, James E Galvin, Daniel Kaufer, James Leverenz, Carol F Lippa, Karen Marder, Victor Abler, Kevin Biglan, Michael Irizarry, Bill Keller, Leanne Munsie, Masaki Nakagawa, Angela Taylor, Todd Graham

Department of Neurology Faculty Papers

Lewy body dementia (LBD), including dementia with Lewy bodies and Parkinson's disease dementia, affects over a million people in the USA and has a substantial impact on patients, caregivers, and society. Symptomatic treatments for LBD, which can include cognitive, neuropsychiatric, autonomic, sleep, and motor features, are limited with only two drugs (cholinesterase inhibitors) currently approved by regulatory agencies for dementia in LBD. Clinical trials represent a top research priority, but there are many challenges in the development and implementation of trials in LBD. To address these issues and advance the field of clinical trials in the LBDs, the Lewy Body …