Neurology Commons^™

An Occupational Therapy Practice Guide For Sport-Related Concussion In Student Athletes, Jenny Park, Steven M. Gerardi, Mary Ann Smith

Summer 2021 Virtual OTD Capstone Symposium

Sport-related concussion (SRC) is a prevalent injury that affects millions of youth and young adults every year (McKeithan et al., 2019). The sequelae associated with an SRC can interfere with a student athletes’ ability to participate in school, return to play, and perform daily tasks (DeMatteo et al., 2018). Common practice in concussion management highlights the significance of getting individuals back to engaging in all areas of their lives; and this is consistent with the emphasis on participation by occupational therapy (OT) practitioners (DeMatteo et al., 2018). Despite the beneficial role that OT may offer, not only is there limited …

Developing Methods To Detect And Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, And Methodology For The Diagnose Cte Research Project, Jeffrey Cummings, Numerous Authors, See Full List Below

School of Medicine Faculty Research

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the “Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project.” The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine …

Macrocyclic Immunoproteasome Inhibitors As A Potential Therapy For Alzheimer's Disease, Min Jae Lee, Deepak Bhattarai, Hyeryung Jang, Ahreum Baek, In Jun Yeo, Seongsoo Lee, Zachary Miller, Sukyeong Lee, Jin Tae Hong, Dong-Eun Kim, Wooin Lee, Kyung Bo Kim

Faculty, Staff and Students Publications

Previously, we reported that immunoproteasome (iP)-targeting linear peptide epoxyketones improve cognitive function in mouse models of Alzheimer's disease (AD) in a manner independent of amyloid β. However, these compounds' clinical prospect for AD is limited due to potential issues, such as poor brain penetration and metabolic instability. Here, we report the development of iP-selective macrocyclic peptide epoxyketones prepared by a ring-closing metathesis reaction between two terminal alkenes attached at the P2 and P3/P4 positions of linear counterparts. We show that a lead macrocyclic compound DB-60 (

Pulmonary Function Decline In Amyotrophic Lateral Sclerosis, Terry D. Heiman-Patterson, Ossama Khazaal, Daohai Yu, Michael E. Sherman, Edward J. Kasarskis, Carlayne E. Jackson, Peg Niv Study Group

Neurology Faculty Publications

Background: There has been no comprehensive longitudinal study of pulmonary functions (PFTS) in ALS determining which measure is most sensitive to declines in respiratory muscle strength. Objective: To determine the longitudinal decline of PFTS in ALS and which measure supports Medicare criteria for NIV initiation first. Methods: Serial PFTs (maximum voluntary ventilation (MVV), maximum inspiratory pressure measured by mouth (MIP) or nasal sniff pressure (SNIP), maximum expiratory pressure (MEP), and Forced Vital Capacity (FVC)) were performed over 12 months on 73 ALS subjects to determine which measure showed the sentinel decline in pulmonary function. The rate of decline for each …

Hur Plays A Positive Role To Strengthen The Signaling Pathways Of Cd4+T Cell Activation And Th17 Cell Differentiation, Shiguang Yu, Morgan Tripod, Ulus Atasoy, Jing Chen

Department of Neurology Faculty Papers

After antigen and/or different cytokine stimulation, CD4⁺ T cells activated and differentiated into distinct T helper (Th) cells via differential T cell signaling pathways. Transcriptional regulation of the activation and differentiation of naïve CD4⁺ T cells into distinct lineage Th cells such as Th17 cells has been fully studied. However, the role of RNA-binding protein HuR in the signaling pathways of their activation and differentiation has not been well characterized. Here, we used HuR conditional knockout (HuR KO) CD4⁺ T cells to study mechanisms underlying HuR regulation of T cell activation and differentiation through distinct signaling pathways. …

Pathophysiology Of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Review., William S. Dodd, Dimitri Laurent, Aaron S. Dumont, David M. Hasan, Pascal M. Jabbour, Robert M. Starke, Koji Hosaka, Adam J. Polifka, Brian L. Hoh, Nohra Chalouhi

Department of Neurosurgery Faculty Papers

Delayed cerebral ischemia is a major predictor of poor outcomes in patients who suffer subarachnoid hemorrhage. Treatment options are limited and often ineffective despite many years of investigation and clinical trials. Modern advances in basic science have produced a much more complex, multifactorial framework in which delayed cerebral ischemia is better understood and novel treatments can be developed. Leveraging this knowledge to improve outcomes, however, depends on a holistic understanding of the disease process. We conducted a review of the literature to analyze the current state of investigation into delayed cerebral ischemia with emphasis on the major themes that have …

Rsv-Induced Guillain–Barré Syndrome, Priyanga Jayakumar, Christe Shen, Dylan Goldsmith, Steven Lippmann

The University of Louisville Journal of Respiratory Infections

A patient with respiratory syncytial virus-induced Guillain–Barré Syndrome and acute disseminated encephalomyelitis is presented. This virus is the most common cause of upper respiratory infections, and it can become an etiology for extra-pulmonary pathology with serious complications. Such a case is rare, but the possibility of adverse comorbidities makes early diagnosis and treatment important.

Treatment Of Thoracolumbar Type A3 Fractures Using A Percutaneous Intravertebral Expandable Titanium Implant: Long-Term Follow-Up Results Of A Pilot Single Center Study., David C Noriega, Jesus Crespo-Sanjuan, Wayne J. Olan, Ruben Hernandez-Ramajo, Douglas P Bell, J Javier Castrodeza Sanz, Gregorio De Jesus Labrador Hernandez, Israel Sanchez-Lite, Francisco Ardura

Neurological Surgery Faculty Publications

BACKGROUND: There are controversies about the optimal management of AO subtype A3 burst fractures. The most common surgical treatment consists of posterior fixation with pedicle screw and rod augmentation. Nevertheless, a loss of correction in height restoration and kyphotic reduction has been observed.

OBJECTIVES: The aim of this study was to assess long-term outcomes of a minimally invasive technique using a percutaneous intravertebral expandable titanium implant (PIETI).

STUDY DESIGN: This prospective, single center, pilot study was carried out on a consecutive case series of 44 patients with acute (< 2 weeks) traumatic thoracolumbar fractures AO type A3. The average follow-up was 5.6 years.

SETTING: A single center in Castilla y Leon, SpainMETHODS: Clinical outcomes …

In Adults Suffering Acute Large Cerebral Vessel Occlusion, Is Direct Mechanical Thrombectomy More Effective Than Treatment With Tpa For Reducing Long-Term Morbidity?, Collin Barry

Theses and Graduate Projects

Background: Discussion whether intravenous tPA or mechanical thrombectomy is the ideal choice for treatment of acute ischemic strokes has been debated around the medical community for last three decades. However still, after several clinical trials, it is still unclear if one is superior to the other.

Methods: This meta-analysis pooled several different results from studies revolving around treatment of acute ischemic stroke. The goal of this paper was to evaluate whether previous clinical trials favoring mechanical thrombectomy had sufficient research to prove it is superior to treatment with tPA in reducing long-term morbidity. Primary outcomes measured were the modified Rankin …

Solitary Langerhans Cell Histiocytosis Of Skull: Case Report With One-Year Follow-Up, Muhammad Junaid, Syed Sarmad Bukhari, Ali Afzal

Section of Neurosurgery

Langerhans cell histiocytosis (LCH) is a rare disorder characterised by increased production of Langerhans-type histiocytes. It is more common in the pediatric age group with a predilection for osseous involvement, though any organ may be involved. A 10-year male child was brought to the neurosurgical clinic with a slow growing painful tender mass on the head. Initial attempt to biopsy the lesion failed due to excessive bleeding. It was later imaged and removed with a frontal craniotomy. Histopathological evaluation along with immunohistochemistry revealed the true nature of the lesion. Follow-up revealed complete excision of the lesion and no recurrence at …

The Impacts Of Aging, Sedentarism, And Exercise On Neurotrophic Factor Expression And Innervation In The Heart And The Effects Of Treatment With Α-Cgrp On Heart Function, Gabriel Almeida Alves

Dissertations

Neurotrophic factors (NFs) are important molecules responsible for development, differentiation, regeneration, and maintenance of new and mature neurons. Neurotrophic factors act as neurocytokines and may assist with the regulation of axonal and dendritic arrangements and synaptic plasticity between neurons themselves or with other non-neural target tissues. In this study, we analyze the levels of two NFs: glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). Cardiomyocytes produce these neurotrophic factors which assist with the innervation pattern of the heart. The heart is innervated by the two branches of the autonomic nervous system; namely the sympathetic nervous system and …

“Old People Problems”, Uncertainty And Legitimacy: Challenges With Diagnosing Parkinson's Disease In Kenya, Natasha Fothergill-Misbah, Richard Walker, Judith Kwasa, Juzar Hooker, Kate Hampshire

Internal Medicine, East Africa

Very little is known about the experience of people living with Parkinson's disease (PD) in low- and middle-income countries, such as those in sub-Saharan Africa. The number of specialists in the region is low and awareness is limited among the population and healthcare professionals. Drawing on ten months of ethnographic fieldwork in urban and rural Kenya with 55 people living with PD (PwP), 23 family members and 22 healthcare professionals from public and private clinics, we set out to understand the experience of diagnosis among PwP in Kenya. The diagnostic journeys of our study participants were typically long, convoluted and …

Neurovascular Regulation In Diabetic Retinopathy And Emerging Therapies, Liyang Ji, Hong Tian, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Diabetic retinopathy (DR) is the leading cause of vision loss in working adults in developed countries. The disease traditionally classified as a microvascular complication of diabetes is now widely recognized as a neurovascular disorder resulting from disruption of the retinal neurovascular unit (NVU). The NVU comprising retinal neurons, glia and vascular cells coordinately regulates blood flow, vascular density and permeability to maintain homeostasis. Disturbance of the NVU during DR can lead to vision-threatening clinical manifestations. A limited number of signaling pathways have been identified for intercellular communication within the NVU, including vascular endothelial growth factor (VEGF), the master switch for …

A Phase 1b/2a Study Of Soticlestat As Adjunctive Therapy In Participants With Developmental And/Or Epileptic Encephalopathies., Jonathan J. Halford, Michael R. Sperling, Dimitrios Arkilo, Mahnaz Asgharnejad, Celia Zinger, Rengyi Xu, Matthew During, Jacqueline A. French

Department of Neurology Faculty Papers

OBJECTIVE: To evaluate the safety, tolerability, and pharmacokinetics of soticlestat, a first-in-class cholesterol 24-hydroxylase inhibitor, in adults with developmental and/or epileptic encephalopathies (DEE).

METHODS: The study comprised a 30-day, randomized, double-blind, placebo-controlled phase (Part A), followed by a 55-day open-label phase (Part B) (ClinicalTrials.gov ID: NCT03166215) . In Part A, patients with DEE and at least one bilateral motor seizure during the 4-week prospective baseline period were randomized 4:1 to receive soticlestat or placebo, in addition to their usual antiseizure medication. In Part B, all patients received open-label soticlestat. Soticlestat doses were titrated according to tolerability to a maximum of …

Seizure Control After Surgical Resection Of Insular Glioma, Fatima Gauhar, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Medical College Documents

Insular gliomas most commonly present with drug-resistant seizures, irrespective of the tumour grade. Even though surgery is the mainstay of treatment, complex anatomical location and close proximity to eloquent cortex makes surgical resection difficult. Herein the authors have reviewed the literature with regards to seizure control after surgical management of these tumours. The review does not address quality of life, or survival benefits of surgery. In summary, excision of these gliomas significantly improves seizure control, and extent of resection along-with trans-cortical approach are important predictors of seizure outcome.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Diagnosis Obscured By Concomitant Recreational Drug Use, Paige Lester Ms Ii, Adam M. Franks Md, William Rollyson Ms Iv, Jenna K. Barbour Md, Matthew B. Curry Md

Marshall Journal of Medicine

Anti-NMDA receptor encephalitis (aNMDAre) is a relatively newly discovered autoimmune and inflammatory disorder affecting the limbic system. It has a clinical course that includes Prodromal, Psychiatric, Unresponsive and Hyperkinetic stages. These stages are often confused with mental health issues in the medical literature, but they also share symptoms of various drug intoxication and withdrawal states. Implicit bias in physicians regarding substance use disorder and patient demographics can impair delivery of care and outcomes in patients with aNMDAre, especially in an environment of recreational drug use. When clinical presentation aligns, this diagnosis should be investigated as soon as possible, even in …

Bethlem Myopathy Demonstrated In Three Generations Of A Rural West Virginia Family Carrying An Autosomal Dominant Col6a3 Mutation, Holly Farkosh, Dominika Lozowska Md

Marshall Journal of Medicine

Mutations in the genes that code for type VI collagen can lead to what are known as the collagenopathies (collagen VI myopathies), such as Bethlem myopathy (BTHLM1), which affect structural tissues like muscles and tendons. We present the case of a young female and her two relatives, who were discovered to share the autosomal dominant COL6A3 mutation and whose presentation in clinic varied from mild to severe. Type VI collagenopathies represent a clinically and genetically heterogeneous spectrum of disorders generally characterized by muscle weakness and joint contractures. We highlight the importance of examining close relatives whenever possible and documenting a …

Trial Of Pimavanserin In Dementia-Related Psychosis, Pierre N. Tariot, Jeffrey L. Cummings, Maria E. Soto-Martin, Clive Ballard, Deniz E. Erten-Lyons, David L. Sultzer, Davangere P. Devanand, Daniel Weintraub, Bradley Mcevoy, James M. Youakim, Srdjan Stankovic, Erin P. Foff

School of Medicine Faculty Research

BACKGROUND Patients with dementia due to neurodegenerative disease can have dementia-related psychosis. The effects of the oral 5-HT2A inverse agonist and antagonist pimavanserin on psychosis related to various causes of dementia are not clear. METHODS We conducted a phase 3, double-blind, randomized, placebo-controlled discontinuation trial involving patients with psychosis related to Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, frontotemporal dementia, or vascular dementia. Patients received open-label pimavanserin for 12 weeks. Those who had a reduction from baseline of at least 30% in the score on the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D, with higher …

How Do Modifiable Risk Factors Impact The Progression Of Alzheimer’S Disease?, Shamso Jama

Theses and Graduate Projects

Alzheimer’s disease remains a significant health burden that affects millions in the United States. This research pursued to shed light on the modifiable risk factors and help individuals at high risk for Alzheimer’s disease minimize the chances of cognitive decline. A search of literature was conducted on databases such as PubMed, Google Scholar, and Medline. Randomized control trials, longitudinal studies, systematic reviews, and meta-analyses were identified and included in the paper. The modifiable risk factors that play a role in the onset and progression of Alzheimer’s disease include stress, inadequate physical exercise, lack of sleep hygiene, and lack of social …

Distinct Cortical Systems Reinstate The Content And Context Of Episodic Memories., James E. Kragel, Youssef Ezzyat, Bradley C. Lega, Michael R. Sperling, Gregory A. Worrell, Robert E. Gross, Barbara C. Jobst, Sameer A. Sheth, Kareem A. Zaghloul, Joel M. Stein, Michael J. Kahana

Department of Neurology Faculty Papers

Episodic recall depends upon the reinstatement of cortical activity present during the formation of a memory. Evidence from functional neuroimaging and invasive recordings in humans suggest that reinstatement organizes our memories by time or content, yet the neural systems involved in reinstating these unique types of information remain unclear. Here, combining computational modeling and intracranial recordings from 69 epilepsy patients, we show that two cortical systems uniquely reinstate the semantic content and temporal context of previously studied items during free recall. Examining either the posterior medial or anterior temporal networks, we find that forward encoding models trained on the brain's …

Aducanumab: Appropriate Use Recommendations, Jeffrey Cummings, P. Aisen, L. G. Apostolova, A. Atri, S. Salloway, M. Weiner

School of Medicine Faculty Research

Aducanumab has been approved by the US Food and Drug Administration for treatment of Alzheimer’s disease (AD). Clinicians require guidance on the appropriate use of this new therapy. An Expert Panel was assembled to construct Appropriate Use Recommendations based on the participant populations, conduct of the pivotal trials of aducanumab, updated Prescribing Information, and expert consensus. Aducanumab is an amyloid-targeting monoclonal antibody delivered by monthly intravenous infusions. The pivotal trials included patients with early AD (mild cognitive impairment due to AD and mild AD dementia) who had confirmed brain amyloid using amyloid positron tomography. The Expert Panel recommends that use …

The Experience Of Off Periods In Parkinson’S Disease: Descriptions, Triggers, And Alleviating Factors, Sneha Mantri, Madeline Lepore, Briana Edison, Margaret Daeschler, Catherine Kopil, Connie Marras, Lana Chahine

Journal of Patient-Centered Research and Reviews

Purpose: Wearing off of Parkinson’s disease medication is common, but triggers and coping strategies for this transient phenomenon are poorly understood. We aimed to assess the lived experience of OFF periods for people with Parkinson’s disease.

Methods: Participants in the longitudinal Fox Insight study who endorsed OFF periods were invited to complete a survey consisting of both multiple-choice and free-text responses. Descriptive statistics were used to summarize multiple-choice responses, and free-text responses were classified into themes through iterative discussion by 3 movement disorders specialists.

Results: A total of 2110 participants (52.4% male) completed the survey. Tremor was the most common …

Erratum To: Characterizing Benefit From Temozolomide In Mgmt Promoter Unmethylated And Methylated Glioblastoma: A Systematic Review And Meta-Analysis, Iyad Alnahhas, Mouaz Alsawas, Appaji Rayi, Joshua D Palmer, Raju Raval, Shirley Ong, Pierre Giglio, Mohammad Hassan Murad, Vinay Puduvalli

Department of Neurology Faculty Papers

[This corrects the article DOI: 10.1093/noajnl/vdaa082.].

Chronic Inflammatory Demyelinating Polyneuropathy As A Paraneoplastic Manifestation Of Colorectal Carcinoma: What Do We Know?, Talal Almas, Muhammad Ali Niaz, Yasar Sattar, Tarek Khedro, Ali Kanawati, Katia Yazji, Reema Alsufyani, Yousef Al-Khatib, Absam Akbar, Emad Mansoor

Medical College Documents

No abstract provided.

Assessing Clinical Change In Individuals Exposed To Repetitive Head Impacts: The Repetitive Head Impact Composite Index, Charles Bernick, Guogen Shan, Lauren Bennett, Jay Alberts, Jeffrey Cummings

School of Public Health Faculty Research

Background: There is a current lack of any composite measure for the effective tracking and monitoring of clinical change in individuals exposed to repetitive head impacts (RHI). The aim of this study is to create a composite instrument for the purposes of detecting change over time in cognitive and behavioral function in individuals exposed to RHI. Methods: The data to derive the composite instrument came from the Professional Fighters Brain Health Study (PFBHS), a longitudinal study of active and retired professional fighters [boxers and mixed martial arts (MMA) fighters] and healthy controls. Participants in the PFBHS underwent assessment on an …

Rapidly Progressive Acth-Dependent Cushing’S Disease Masquerading As Ectopic Acth-Producing Cushing’S Syndrome: Illustrative Case, Siyuan Yu, Michael Karsy, Jeffery Miller, Stephanie R. Beldick, Mark T. Curtis, Marc Rosen, James J. Evans

Department of Neurosurgery Faculty Papers

BACKGROUND Cushing’s disease (CD) remains a challenging condition to diagnose and treat. This case study highlights the challenges of diagnosing CDwhen faced with discrepant clinical, biochemical, and radiologicalfindings.

OBSERVATIONS A 62-year-old man presented with rapid evolution of symptoms, including depression, fatigue, and extreme muscle atrophy, whichresulted in the patient being a wheelchair user over the course of a few months. His rapid clinical course in conjunction with hypercortisolemia in thesetting of a pituitary macroadenoma involving the cavernous sinus, two large pulmonary nodules, and urine-free cortisol levels in the thousandssuggested an aggressive ectopic adrenocorticotropic hormone (ACTH) source. After extensive testing ruled …

Regulation Of Microrna Expression In Sleep Disorders In Patients With Epilepsy, Edyta Dziadkowiak, Justyna Chojdak-Łukasiewicz, Piotr Olejniczak, Bogusław Paradowski

School of Medicine Faculty Publications

The effects of epilepsy on sleep and the activating effects of sleep on seizures are well documented in the literature. To date, many sleep-related and awake-associated epilepsy syndromes have been described. The relationship between sleep and epilepsy has led to the recognition of polysomnographic testing as an important diagnostic tool in the diagnosis of epilepsy. The authors analyzed the available medical database in search of other markers that assess correlations between epilepsy and sleep. Studies pointing to microRNAs, whose abnormal expression may be common to epilepsy and sleep disorders, are promising. In recent years, the role of microRNAs in the …

Use Of Ultrasonic Aspirator For Cns Tumour Resection, Noman Ahmad, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

Ultrasonic aspirator (UA), or the Cavitron Ultrasonic Aspirator (CUSA) as it is commonly referred to, utilizes ultrasonic waves of variable range of frequencies to disintegrate and excise tumours. It is developed as a substitute of bipolar diathermy; a tool commonly employed for coagulation that uses focussed electric current and may damage tissues by virtue of contact, or by the heat that it produces. Over the last 30 years, CUSA has become increasingly popular in several soft tissue surgeries, especially brain and spine tumour resection, as it allows reduction in the use of bipolar diathermy. It is assumed that CUSA improves …

Smoking-Induced Sex Differences In Clinical Outcomes In Patients Undergoing Mechanical Thrombectomy For Stroke, Jacqueline A. Frank, Kara Jo Swafford, Jill M. Roberts, Amanda L. Trout, Ann M. Stowe, Douglas E. Lukins, Stephen Grupke, Keith R. Pennypacker, Justin F. Fraser

Neurology Faculty Publications

OBJECTIVE: Ischemic stroke is the fifth leading cause of death in the United States. Smoking accelerates the onset of stroke by 10 years. The effects of smoking status on percent change in National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and edema volume were examined following mechanical thrombectomy for large vessel occlusion in patients with acute ischemic stroke.

METHODS: Subjects (N = 90; >18 years old) were divided into 3 groups based on smoking status: current smokers, previous smokers (defined as having quit >6 months before the ischemic event), and nonsmokers. Percent change in NIHSS score was …

Astrocyte-Derived Thrombospondin Induces Cortical Synaptogenesis In A Sex-Specific Manner, Anna Mazur, Ean H. Bills, Kayla M. Deschepper, James C. Williams, Brandon J. Henderson, W. Christopher Risher

Biomedical Sciences

The regulation of synaptic connectivity in the brain is vital to proper functioning and development of the CNS. Formation of neural networks in the CNS has been shown to be heavily influenced by astrocytes, which secrete factors, including thrombospondin (TSP) family proteins, that promote synaptogenesis. However, whether this process is different between males and females has not been thoroughly investigated. In this study, we found that cortical neurons purified from newborn male rats showed a significantly more robust synaptogenic response compared with female-derived cells when exposed to factors secreted from astrocytes. This difference was driven largely by the neuronal response …