Neurology Commons^™

Impulsivity In Patients With Attempted Suicide Presenting At A Tertiary Care Hospital In Karachi, Ayesha Abdul Hameed, Haresh Kumar, Sarika Bai, Azra Shaheen, Ravi Athwani, Mohammad Munir Hamirani

Pakistan Journal of Neurological Sciences (PJNS)

OBJECTIVE: To determine the prevalence of impulsivity in patients who attempted suicide presenting at a tertiary care hospital, Karachi. STUDY DESIGN: Cross sectional study. STUDY SETTING: Study was led in the Psychiatry Department, Abbasi Shaheed Hospital, Karachi. DURATION OF STUDY:Six month after approval of synopsis. SUBJECTS AND METHODS: Data was prospectively collected from patients after taking verbal consent. Permission was taken from ethical review committee. 95 patients presenting to the Psychiatry Department who met the inclusion criteria were included. A brief history about suicide attempt and demographic data was taken from the patient and confirmed by an attendee. The researcher …

Chronic Tension-Type Headache As A Risk Factor Of Myofascial Trigger Points In Upper Trapezius Muscle Fibers In Neck Pain Patients, Aisha Amin, Umer Maqsood, Farah Niaz Awan, Hafiz Sheraz Arshad, Ali Hamza Arshad

Pakistan Journal of Neurological Sciences (PJNS)

Chronic tension type headache (CTTH) is one of the very common neurological conditions which have striking impact on daily functional activities. In tension type headaches the myofascial TrP's are frequently examined .It is observed that myofascial pain syndrome is frequent determinant of chronic nonspecific neck pain.

Kernohan–Woltman Notch Phenomenon:Case Report And Review Of Literature, Fareed Ahmed, Muhammad Shahzad Shamim, Sidra Asad Ali

Pakistan Journal of Neurological Sciences (PJNS)

Subdural hematoma (SDH) is usually secondary to mechanical trauma. Spontaneous subdural hematoma is still rare with unclear pathophysiology. The classic findings of subdural hematoma is sudden drop in mental status, an ipsilateralmydriasis with contralateral hemiparesis. However SDH can sometimes compress the contralaterl corticospinal tract resulting in ipsilateral motor weakness, this phenomenon is known as Kernohan-Woltman Notch Phenomenon.

A Prevalent Disease Missed Under Cover Of An Uncommon Disorder- A Learning Experience In Clinical Practice, Sarah Razaq, Saeed Bin Ayaz, Aleem Arshad, Hussain Rashid Ihsan

Pakistan Journal of Neurological Sciences (PJNS)

Musculoskeletal pains are secondary complication of a my apathic disorder but other causes must be ruled out through meticulous evaluation. We report a case of distal my apathy who developed back pain due to tuberculous spondylitis but was overlooked and his complaint of backache was considered outcome of mechanical deterioration of vertebral column resulting from weakness of para spinal muscles due to my apathy. After detailed evaluation, his unnoticed ailment was identified and he was started off with the right management.

Brain Injury-Induced Synaptic Reorganization In Hilar Inhibitory Neurons Is Differentially Suppressed By Rapamycin, Corwin R. Butler, Jeffery A. Boychuk, Bret N. Smith

Physiology Faculty Publications

Following traumatic brain injury (TBI), treatment with rapamycin suppresses mammalian (mechanistic) target of rapamycin (mTOR) activity and specific components of hippocampal synaptic reorganization associated with altered cortical excitability and seizure susceptibility. Reemergence of seizures after cessation of rapamycin treatment suggests, however, an incomplete suppression of epileptogenesis. Hilar inhibitory interneurons regulate dentate granule cell (DGC) activity, and de novo synaptic input from both DGCs and CA3 pyramidal cells after TBI increases their excitability but effects of rapamycin treatment on the injury-induced plasticity of interneurons is only partially described. Using transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed in …

Efficacy, Safety, And Timing Of Anticoagulant Thromboprophylaxis For The Prevention Of Venous Thromboembolism In Patients With Acute Spinal Cord Injury: A Systematic Review, Paul M. Arnold, James S. Harrop, Geno J. Merli, Lindsay G. Tetreault, Brain K. Kwon, Steve Casha, Katherine Palmieri, Jefferson R. Wilson, Michael G. Fehlings, Haley K. Holmer, Daniel C. Norvell

Department of Neurosurgery Faculty Papers

Study Design: Systematic review. Objectives: The objective of this study was to answer 5 key questions: What is the comparative effectiveness and safety of (1a) anticoagulant thromboprophylaxis compared to no prophylaxis, placebo, or another anticoagulant strategy for preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) after acute spinal cord injury (SCI)? (1b) Mechanical prophylaxis strategies alone or in combination with other strategies for preventing DVT and PE after acute SCI? (1c) Prophylactic inferior vena cava filter insertion alone or in combination with other strategies for preventing DVT and PE after acute SCI? (2) What is the optimal timing to …

Hemimegalencephaly With Intractable Epilepsy: A Case Report, Prem Chand, Muhammad Faraz Raghib, Muhammad Sohail Salat

Department of Paediatrics and Child Health

Isolated Hemimegalencephaly (iHME) is a rare form of congenital malformation of cortical development.It is characterized by enlargement of all or part of one cerebral hemisphere. It typically presents with intractable seizures, mental retardation, developmental delay, contralateral hemiparesis and hemianopia. The patient was a five and half month's old baby girl who presented first with focal seizures at 10th day of life. No other physical or behavioral abnormality was noted. However, Initial EEG showed excessive sharp EEG transients more over the right hemisphere, repeated EEG showed spikes, polyspikes, sharps and slow wave discharges predominately over right hemisphere. MRI brain showed asymmetric …

A Clinical Practice Guideline For The Management Of Patients With Degenerative Cervical Myelopathy: Recommendations For Patients With Mild, Moderate, And Severe Disease And Nonmyelopathic Patients With Evidence Of Cord Compression, Michael G. Fehlings, Lindsay A. Tetreault, K. Daniel Riew, James W. Middleton, Bizhan Aarabi, Paul M. Arnold, Darrel S. Brodke, Anthony S. Burns, Simon Carette, Robert Chen, Kazuhiro Chiba, Joseph R. Dettori, Julio C. Ferlan, James S. Harrop, Langston T. Holly, Sukhvinder Kalsi-Ryan, Mark Kotter, Brian K. Kwon, Allan R. Martin, James Milligan, Hiroaki Nakashima, Narihito Nagoshi, John Rhee, Anoushka Singh, Andrea C. Skelly, Sumeet Sodhi, Jefferson R. Wilson, Albert Yee, Jeffrey C. Wang

Department of Neurosurgery Faculty Papers

Study Design: Guideline development. Objectives: The objective of this study is to develop guidelines that outline how to best manage (1) patients with mild, moderate, and severe myelopathy and (2) nonmyelopathic patients with evidence of cord compression with or without clinical symptoms of radiculopathy. Methods: Five systematic reviews of the literature were conducted to synthesize evidence on disease natural history; risk factors of disease progression; the efficacy, effectiveness, and safety of nonoperative and surgical management; the impact of preoperative duration of symptoms and myelopathy severity on treatment outcomes; and the frequency, timing, and predictors of symptom development. A multidisciplinary guideline …

A Clinical Practice Guideline For The Management Of Acute Spinal Cord Injury: Introduction, Rationale, And Scope, Michael G. Fehlings, Lindsay A. Tetreault, Jefferson R. Wilson, Brian K. Kwon, Anthony S. Burns, Allan R. Martin, Gregory Hawryluk, James S. Harrop

Department of Neurosurgery Faculty Papers

Acute spinal cord injury (SCI) is a traumatic event that results in disturbances to normal sensory, motor, or autonomic function and ultimately affects a patient’s physical, psychological, and social well-being. The management of patients with SCI has drastically evolved over the past century as a result of increasing knowledge on injury mechanisms, disease pathophysiology, and the role of surgery. There still, however, remain controversial areas surrounding available management strategies for the treatment of SCI, including the use of corticosteroids such as methylprednisolone sodium succinate, the optimal timing of surgical intervention, the type and timing of anticoagulation prophylaxis, the role of …

Intracranial Eeg Fluctuates Over Months After Implanting Electrodes In Human Brain., Hoameng Ung, Steven N. Baldassano, Hank Bink, Abba M. Krieger, Shawniqua Williams, Flavia Vitale, Chengyuan Wu, Dean Freestone, Ewan Nurse, Kent Leyde, Kathryn A. Davis, Mark Cook, Brian Litt

Department of Neurosurgery Faculty Papers

OBJECTIVE: Implanting subdural and penetrating electrodes in the brain causes acute trauma and inflammation that affect intracranial electroencephalographic (iEEG) recordings. This behavior and its potential impact on clinical decision-making and algorithms for implanted devices have not been assessed in detail. In this study we aim to characterize the temporal and spatial variability of continuous, prolonged human iEEG recordings.

APPROACH: Intracranial electroencephalography from 15 patients with drug-refractory epilepsy, each implanted with 16 subdural electrodes and continuously monitored for an average of 18 months, was included in this study. Time and spectral domain features were computed each day for each channel for …

Timing Of Decompression In Patients With Acute Spinal Cord Injury: A Systematic Review, Jefferson R. Wilson, Lindsay A. Tetreault, Brian Kwon, Paul M. Arnold, Thomas E. Mroz, Christopher I. Shaffrey, James S. Harrop, Jens R. Chapman, Steven Casha, Andrea C. Skelly, Haley K. Holmer, Erika D. Brodt, Michael G. Fehlings

Department of Neurosurgery Faculty Papers

Study Design: Systematic review. Objective: To conduct a systematic review and synthesis of the literature to assess the comparative effectiveness, safety, and cost-effectiveness of early (≤24 hours) versus late decompression (>24 hours) in adults with acute spinal cord injury (SCI). Methods: A systematic search was conducted of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar to identify studies published through November 6, 2014. Studies published in any language, in humans, and with an abstract were considered for inclusion. Included studies were critically appraised and the overall strength of evidence was determined using methods proposed by the Grading of …

Efficacy And Safety Of Methylprednisolone Sodium Succinate In Acute Spinal Cord Injury: A Systematic Review, Michael G. Fehlings, Jefferson R. Wilson, James S. Harrop, Brian Kwon, Lindsay A. Tetreault, Paul M. Arnold, Jeffrey M. Singh, Gregory W.J. Hawryluk, Joseph R. Dettori

Department of Neurosurgery Faculty Papers

Study Design: Systematic review and meta-analysis. Objective: The objective of this study was to conduct a systematic review to assess the comparative effectiveness and safety of high-dose methylprednisolone sodium succinate (MPSS) versus no pharmacological treatment in patients with traumatic spinal cord injury (SCI). Methods: A systematic search was performed in PubMed and the Cochrane Collaboration Library for literature published between January 1956 and June 17, 2015. Included studies were critically appraised, and Grades of Recommendation Assessment, Development and Evaluation methods were used to determine the overall quality of evidence for primary outcomes. Previous systematic reviews on this topic were collated …

Ibrutinib Unmasks Critical Role Of Bruton Tyrosine Kinase In Primary Cns Lymphoma., Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S. Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Dan Rohle, Marc Rosenblum, Agnes Viale, Viviane S. Tabar, Cameron W. Brennan, Igor T. Gavrilovic, Thomas J. Kaley, Craig P. Nolan, Antonio Omuro, Elena Pentsova, Alissa A. Thomas, Elina Tsyvkin, Ariela Noy, M. Lia Palomba, Paul Hamlin, Craig S. Sauter, Craig H. Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C. Lallana, Vaios Hatzoglou, Anne S. Reiner, Philip H. Gutin, Jason T. Huse, Katherine S. Panageas, Thomas G. Graeber, Nikolaus Schultz, Lisa M. Deangelis, Ingo K. Mellinghoff

Department of Neurology Faculty Papers

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated …

Debate On Human Aging And Lifespan, Mohammad Rafi, Abass Alavi

Department of Neurology Faculty Papers

The issue of human lifespan has long been a matter of controversy among scientists. In spite of the recent claim by Dong et al that human lifespan is limited to 115 years, with the mounting improvements in biotechnology and scientific understanding of aging, we may be confident that aging will slow down over the course of the current century extending human longevity much longer than 115 years.

Clopidogrel Alone Is Safer Than Clopidogrel And Aspirin For Secondary Prevention Of Acute Ischemic Stroke., Bradford J. Woelke, Daniel Angell Do, Katherine Litow Md

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364(9431):331-337. doi: 10.1016/s0140-6736(04)16721-4

Delirium Reduction Strategies For The Critically Ill, June Chaves, Sam Canonico, Will Cheney, Tammy Corey, Gil Fraser, Alex Kowalewski, Jen Low, Cardiac Intensive Care Unit, Haley Pelletier, Cathy Palleschi, Stephen Tyzik, Suneela Nayak, Ruth Hanselman

MaineHealth Maine Medical Center

Delirium, an acute and fluctuating disturbance of consciousness and cognition, is a common manifestation of acute brain dysfunction in critically ill patients. Patients with delirium have longer hospital stays and a lower 6-month survival rate than do patients without delirium. Preliminary research suggests that delirium may be associated with cognitive impairment that persists months to years after discharge.

In a large acute care hospital, the cardiac intensive care staff became interested in mitigating their unit’s high delirium rate of ventilated patients. At baseline, many members of the healthcare team did not believe that delirium could be prevented and the predominant …

The Effects Of Dance Therapy On Patients With Parkinson’S Disease: An Integrative Literature Review, Jennifer Pence

Grace Peterson Nursing Research Colloquium

Abstract

Parkinson’s disease (PD) is a chronic, progressive, degenerative disease of the nervous system that affects more than one million Americans. Individuals who have PD generally exhibit bradykinesia, postural instability, shuffling steps and freezing during gait. These impairments in motor function cannot be fully addressed with pharmacological treatment and can eventually become unresponsive to this form of treatment. Dance therapy, on the other hand, is one non-pharmacological method that may prove beneficial for PD. It utilizes motor planning skills, which can lead to an improvement in muscle flexibility and balance. The purpose of the systematic integrative literature review was to …

Pineal Gland Tumor But Not Pinealoma: A Case Report, Syeda Naqvi, Chintan Rupareliya, Abdullah Shams, Maria Hameed, Zabeen Mahuwala, Pirthvi Raj Giyanwani

Neurology Faculty Publications

The pineal gland is a small pinecone-shaped and functionally endocrine structure located in the epithalamus region. Developmentally, the pineal gland is considered as a part of the epithalamus. It plays a role in the entrainment of the circadian rhythms of an organism by producing melatonin, a functionally important hormone. Lesions of the pineal region are rare compared to other parts of the brain. A lesion may be tumorous or non-tumorous in nature. The most common lesions are tumors that are pineal parenchymal tumors (PPT) in origin. Gliomas are the second most common tumors in the pineal region. We report a …

Anterior Inferior Cerebellar Arteries Juxtaposed With The Internal Acoustic Meatus And Their Relationship To The Cranial Nerve Vii/Viii Complex., Fernando Alonso, Mohammad W Kassem, Joe Iwanaga, Rod J Oskouian, Marios Loukas, Amin Demerdash, R Shane Tubbs

Articles, Abstracts, and Reports

Vascular loops in the cerebellopontine angle (CPA) and their relationship to cranial nerves have been used to explain neurological symptoms. The anterior inferior cerebellar artery (AICA) has variable branches producing vascular loops that can compress the facial cranial nerve (CN) VII and vestibulocochlear (CN VIII) nerves. AICA compression of the facial-vestibulocochlear nerve complex can lead to various clinical presentations, including hemifacial spasm (HFS), tinnitus, and hemiataxia. The formation of arterial loops inside or outside of the internal auditory meatus (IAM) can cause abutment or compression of CN VII and CN VIII. Twenty-five (50 sides) fresh adult cadavers underwent dissection of …

Coding Of Velocity Storage In The Vestibular Nuclei, Sergei B. Yakushin, Theodore Raphan, Bernard Cohen

Publications and Research

Semicircular canal afferents sense angular acceleration and output angular velocity with a short time constant of ≈4.5 s. This output is prolonged by a central integrative network, velocity storage that lengthens the time constants of eye velocity. This mechanism utilizes canal, otolith, and visual (optokinetic) information to align the axis of eye velocity toward the spatial vertical when head orientation is off-vertical axis. Previous studies indicated that vestibular-only (VO) and vestibular-pause-saccade (VPS) neurons located in the medial and superior vestibular nucleus could code all aspects of velocity storage. A recently developed technique enabled prolonged recording while animals were rotated and …

Tia1 Mutations In Amyotrophic Lateral Sclerosis And Frontotemporal Dementia Promote Phase Separation And Alter Stress Granule Dynamics., Ian R. Mackenzie, Alexandra M. Nicholson, Mohona Sarkar, James Messing, Maria D. Purice, Cyril Pottier, Kavya Annu, Matt Baker, Ralph B. Perkerson, Aishe Kurti, Billie J. Matchett, Tanja Mittag, Jamshid Temirov, Ging-Yuek R. Hsiung, Charles Krieger, Melissa E. Murray, Masato Kato, John D. Fryer, Leonard Petrucelli, Lorne Zinman, Sandra Weintraub, Marsel Mesulam, Julia Keith, Sasha A. Zivkovic, Veronica Hirsch-Reinshagen, Raymond P. Roos, Stephan Züchner, Neill R. Graff-Radford, Ronald C. Petersen, Richard J. Caselli, Zbigniew K. Wszolek, Elizabeth Finger, Carol Lippa, David Lacomis, Heather Stewart, Dennis W. Dickson, Hong Joo Kim, Ekaterina Rogaeva, Eileen Bigio, Kevin B. Boylan, J. Paul Taylor, Rosa Rademakers

Department of Neurology Faculty Papers

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 10

Chiari I Malformation And Spinal Cord Ischemia In A Cadaver., Faizullah Mashriqi, Marios Loukas, Rod J Oskouian, Anthony V D'Antoni, R Shane Tubbs

Articles, Abstracts, and Reports

With advanced imaging, the Chiari I malformation (CIM) is more frequently diagnosed than in the past when this entity was identified most commonly at autopsy. Herein, we report the rare case of an adult cadaver found not only to have CIM but also adjacent spinal cord ischemia. This case is discussed in the context of chronic compression of the spinal cord by a CIM and the need for close monitoring of these patients.

Cascaded Multi-View Canonical Correlation (Camcco) For Early Diagnosis Of Alzheimer's Disease Via Fusion Of Clinical, Imaging And Omic Features, Asha Singanamalli, Haibo Wang, Anant Madabhushi, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford Jack, William Jagust, John Trojanowki, Arthur Toga, Laurel Beckett, Robert Green, Andrew Saykin, John Morris, Leslie Shaw, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith Heidebrink, Charles Smith, Greg A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Neurology Faculty Publications

The introduction of mild cognitive impairment (MCI) as a diagnostic category adds to the challenges of diagnosing Alzheimer's Disease (AD). No single marker has been proven to accurately categorize patients into their respective diagnostic groups. Thus, previous studies have attempted to develop fused predictors of AD and MCI. These studies have two main limitations. Most do not simultaneously consider all diagnostic categories and provide suboptimal fused representations using the same set of modalities for prediction of all classes. In this work, we present a combined framework, cascaded multiview canonical correlation (CaMCCo), for fusion and cascaded classification that incorporates all diagnostic …

Linking Kindling To Increased Glutamate Release In The Dentate Gyrus Of The Hippocampus Through The Stxbp5/Tomosyn-1 Gene, Seth R. Batten, Elena A. Matveeva, Sidney W. Whiteheart, Thomas C. Vanaman, Greg A. Gerhardt, John T. Slevin

Psychology Faculty Publications

Introduction: In kindling, repeated electrical stimulation of certain brain areas causes progressive and permanent intensification of epileptiform activity resulting in generalized seizures. We focused on the role(s) of glutamate and a negative regulator of glutamate release, STXBP5/tomosyn-1, in kindling.

Methods: Stimulating electrodes were implanted in the amygdala and progression to two successive Racine stage 5 seizures was measured in wild-type and STXBP5/tomosyn-1^−/− (Tom^−/−) animals. Glutamate release measurements were performed in distinct brain regions using a glutamate-selective microelectrode array (MEA).

Results: Naïve Tom^−/− mice had significant increases in KCl-evoked glutamate release compared to naïve wild type as …

Stress Increases Peripheral Axon Growth And Regeneration Through Glucocorticoid Receptor-Dependent Transcriptional Programs, Jessica K. Lerch, Jessica K. Alexander, Kathryn M. Madalena, Dario Motti, Tam Quach, Akhil Dhamija, Alicia Zha, John C. Gensel, Jeanette Webster Marketon, Vance P. Lemmon, John L. Bixby, Phillip G. Popovich

Physiology Faculty Publications

Stress and glucocorticoid (GC) release are common behavioral and hormonal responses to injury or disease. In the brain, stress/GCs can alter neuron structure and function leading to cognitive impairment. Stress and GCs also exacerbate pain, but whether a corresponding change occurs in structural plasticity of sensory neurons is unknown. Here, we show that in female mice (Mus musculus) basal GC receptor (Nr3c1, also known as GR) expression in dorsal root ganglion (DRG) sensory neurons is 15-fold higher than in neurons in canonical stress-responsive brain regions (M. musculus). In response to stress or GCs, adult …

Burden Of Arrhythmias In Epilepsy Patients: A Nationwide Inpatient Analysis Of 1.4 Million Hospitalizations In The United States, Rupak Desai, Chintan Rupareliya, Upenkumar Patel, Syeda Naqvi, Smit Patel, Abhishek Lunagariya, Zabeen Mahuwala

Neurology Faculty Publications

Arrhythmias have been one of the common complications in epilepsy patients and have also been the reason for death. However, limited data exist about the burden and outcomes of arrhythmias by subtypes in epilepsy. Our study aims at evaluating the burden and differences in outcomes of various subtypes of arrhythmias in epilepsy patient population. The Nationwide Inpatient Sample (NIS) database from 2014 was examined for epilepsy and arrhythmias related discharges using appropriate International Classification of Disease, Ninth Revision Clinical Modification (ICD-9-CM) codes. The frequency of arrhythmias, gender differences in arrhythmia by subtypes, in-hospital outcomes and mortality predictors was analyzed. A …

Impact Of Cocaine Use On Acute Ischemic Stroke Patients: Insights From Nationwide Inpatient Sample In The United States, Rupak Desai, Upenkumar Patel, Chintan Rupareliya, Sandeep Singh, Manan Shah, Rikinkumar S. Patel, Smit Patel, Zabeen Mahuwala

Neurology Faculty Publications

Cocaine is the third most common substance of abuse after cannabis and alcohol. The use of cocaine as an illicit substance is implicated as a causative factor for multisystem derangements ranging from an acute crisis to chronic complications. Vasospasm is the proposed mechanism behind adverse events resulting from cocaine abuse, acute ischemic strokes (AIS) being one of the few. Our study looked into in-hospital outcomes owing to cocaine use in the large population based study of AIS patients. Using the national inpatient sample (NIS) database from 2014 of United States of America, we identified AIS patients with cocaine use using …

Functionally Pathogenic Ears2 Variants In Vitro May Not Manifest A Phenotype In Vivo, Nathan Mcneill, Alessia Nasca, Aurelio Reyes, Benjamin Lemoine, Brandi Cantarel, Adeline Vanderver, Raphael Schiffmann, Daniele Ghezzi

Neurology Faculty Publications

Objective: To investigate the genetic etiology of a patient diagnosed with leukoencephalopathy, brain calcifications, and cysts (LCC).

Methods: Whole-exome sequencing was performed on a patient with LCC and his unaffected family members. The variants were subject to in silico and in vitro functional testing to determine pathogenicity.

Results: Whole-exome sequencing uncovered compound heterozygous mutations in EARS2, c.328G>A (p.G110S), and c.1045G>A (p.E349K). This gene has previously been implicated in the autosomal recessive leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). The p.G110S mutation has been found in multiple patients with LTBL. In silico analysis supported pathogenicity …

Clinical And Experimental Studies Of A Novel P525r Fus Mutation In Amyotrophic Lateral Sclerosis, Lisha Kuang, Marisa Kamelgarn, Alexandra Arenas, Jozsef Gal, Deborah Taylor, Weiming Gong, Martin Brown, Daret St. Clair, Edward J. Kasarskis, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Objective: To describe the clinical features of a novel fused in sarcoma (FUS) mutation in a young adult female amyotrophic lateral sclerosis (ALS) patient with rapid progression of weakness and to experimentally validate the consequences of the P525R mutation in cellular neuronal models.

Methods: We conducted sequencing of genomic DNA from the index patient and her family members. Immunocytochemistry was performed in various cellular models to determine whether the newly identified P525R mutant FUS protein accumulated in cytoplasmic inclusions. Clinical features of the index patient were compared with 19 other patients with ALS carrying the P525L mutation in the same …

Brain Microvascular Injury And White Matter Disease Provoked By Diabetes-Associated Hyperamylinemia, Han Ly, Nirmal Verma, Fengen Wu, Miao Liu, Kathryn E. Saatman, Peter T. Nelson, John T. Slevin, Larry B. Goldstein, Geert Jan Biessels, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

OBJECTIVE: The brain blood vessels of patients with type 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It is not known whether vascular amylin deposition is a consequence or a trigger of vascular injury. We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins.

METHODS: Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with aggregated amylin were used for in vivo phenotyping. We also carried out biochemical analyses …