Medical Specialties Commons^™

Consistency Of Efficacy Results Across Various Clinical Measures And Statistical Methods In The Lecanemab Phase 2 Trial Of Early Alzheimer’S Disease, Shobha Dhadda, Michio Kanekiyo, David Li, Chad J Swanson, Michael Irizarry, Scott Berry, Lynn D Kramer, Donald A Berry

Faculty, Staff and Student Publications

BACKGROUND: Lecanemab (BAN2401) is a humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ species (protofibrils) with activity at insoluble fibrils and slowed clinical decline in an 18-month phase 2 proof-of-concept study (Study 201; ClinicalTrials.gov NCT01767311) in 856 subjects with early Alzheimer's disease (AD). In this trial, subjects were randomized to five lecanemab dose regimens or placebo. The primary efficacy endpoint was change from baseline in the Alzheimer's Disease Composite Score (ADCOMS) at 12 months with Bayesian analyses. The key secondary endpoints were ADCOMS at 18 months and Clinical Dementia Rating-Sum-of-Boxes (CDR-SB) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) …

Goal Attainment After Treatment With Abobotulinumtoxina And A Tailored Home Therapy Programme In Children With Upper Limb Spasticity: Descriptive, Exploratory Analysis Of A Large Randomized, Controlled Studya, Jorge Carranza-Del Río, Nigar Dursun, Cigdem Cekmece, Marcin Bonikowski, Weronika Pyrzanowska, Edward Dabrowski, Ann Tilton, Joyce Oleszek, Magali Volteau, Simon Page, Angela Shierk, Mauricio R. Delgado

School of Medicine Faculty Publications

OBJECTIVE: This exploratory analysis of a large, randomized, double-blind study (NCT02106351) describes the effect of treatment with abobotulinumtoxinA followed by a tailored home exercises therapy programme in enabling children with upper limb spasticity due to cerebral palsy to achieve their functional goals using goal attainment scaling (GAS). METHODS: Children with cerebral palsy and spasticity in ≥ 1 upper limb received up to 4 injection cycles of abobotulinumtoxinA (2 U/kg (cycle 1 only), 8U/kg and 16U/kg) into the elbow and wrist flexors and other upper limb muscles selected to support individual treatment goals. Children followed a home exercises therapy programme, which …

Safety Of Lenadogene Nolparvovec Gene Therapy Over 5 Years In 189 Patients With Leber Hereditary Optic Neuropathy, Catherine Vignal-Clermont, Patrick Yu-Wai-Man, Nancy J. Newman, Valerio Carelli, Mark L. Moster, Valerie Biousse, Prem S. Subramanian, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Alfredo A. Sadun, Thomas Klopstock, Robert C. Sergott, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Magali Taiel, Michel Roux, José-Alain Sahel

Wills Eye Hospital Papers

Purpose

To evaluate the safety profile of lenadogene nolparvovec (Lumevoq) in patients with Leber hereditary optic neuropathy.

Design

Pooled analysis of safety data from 5 clinical studies.

Methods

A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination, and systemic immune responses against rAAV2/2.

Results

Almost all patients (95.2%) received 9 × …

Modulation Of Sirtuins During Monolayer Chondrocyte Culture Influences Cartilage Regeneration Upon Transfer To A 3d Culture Environment, Hannah K Heywood, Stephen D Thorpe, Renos M Jeropoulos, Paul W Caton, David A Lee

Faculty, Staff and Student Publications

This study examined the role of sirtuins in the regenerative potential of articular chondrocytes. Sirtuins (SIRT1-7) play a key role in regulating cartilage homeostasis. By inhibiting pro-inflammatory pathways responsible for cartilage degradation and promoting the expression of key matrix components, sirtuins have the potential to drive a favourable balance between anabolic and catabolic processes critical to regenerative medicine. When subjected to osmolarity and glucose concentrations representative of the in vivo niche, freshly isolated bovine chondrocytes exhibited increases in SIRT1 but not SIRT3 gene expression. Replicating methods adopted for the in vitro monolayer expansion of chondrocytes for cartilage regenerative therapies, we …

Responsive Neurostimulation (Rns) Of The Centromedian Nucleus Of The Thalamus For The Treatment Of Drug Resistant Idiopathic Generalized Epilepsy, Angelique Manasseh, Hannah Guider, Brooklynn Bondy, Ayman Haykal, Nour Baki, Ashleigh Terrell, Michael Staudt, Christopher Parres, Andrew Zillgitt

Conference Presentation Abstracts

Rationale: Idiopathic generalized epilepsy (IGE) accounts for approximately one-third of all epilepsies. The majority of people with IGE achieve seizure-freedom from treatment with anti-seizure medications (ASM). However, up to 25% of people with IGE continue to experience seizures despite adequate ASM trials. In patients with drug resistant IGE, neuromodulation with responsive neurostimulation (RNS) in the bilateral centromedian nucleus (CMN) of the thalamus may be an effective treatment option. Methods: Five patients with drug resistant IGE were evaluated through the Beaumont Adult Comprehensive Epilepsy Center and underwent an epilepsy presurgical evaluation including video-EEG monitoring in the epilepsy monitoring unit, brain MRI, …

Safety And Efficacy Of Salvage Therapy With Laser Interstitial Thermal Therapy For Malignant Meningioma Refractory To Cesium-131 Brachytherapy: Illustrative Case, Clifford Yudkoff, Aria Mahtabfar, Keenan Piper, Kevin Judy

Department of Neurosurgery Faculty Papers

BACKGROUND

Anaplastic meningioma are rare, cancerous tumors of the central nervous system that often require multimodal therapy for tumor control. Both laser interstitial thermal therapy (LITT) and brachytherapy with implanted cesium-131 metallic seeds have demonstrated efficacy in the treatment of recurrent and resistant anaplastic meningioma; however, their safety as a dual therapy has never been reported.

OBSERVATIONS

In this report, the authors present a case of a 53-year-old female who received LITT in combination with brachytherapy after surgical and radiation treatment options had been exhausted. The authors discuss the unique safety concern of thermal injury with this treatment combination and …

Nursing Considerations For Post-Traumatic Amnesia After A Traumatic Brain Injury, Hannah Grant

Senior Honors Theses

A period known as post-traumatic amnesia (PTA) often follows a traumatic brain injury (TBI). PTA is characterized by anterograde and retrograde amnesia, confusion, disorientation, and agitation. The duration and severity of PTA is a key indicator of the long-term prognosis after a TBI, so proper assessment and nursing care of a PTA patient is crucial. TBIs range from mild to severe, but primarily affect the fronto-temporal lobes. In PTA, both neural lesions and white matter damage within the parahippocampal region can cause PTA. A nurse must perform a thorough assessment of a TBI patient, but, since PTA is a key …

Remote Patient Monitoring: Decrease Rehospitalization For Spinal Cord Injury Patients, Abegail Cabunoc-Garcia

Student Scholarly Projects

Practice Problem: The lengthy distance required to access specialty care, the overall higher cost of SCI/D care, complications associated with SCI, and the potential negative impact of shortened hospital stays are all compelling reasons to use telehealth technologies to deliver specialty services for medical issues.

PICOT: The PICOT question that guided this project was in adult spinal cord injury patients with chronic disease receiving primary care at a spinal cord injury center (P), how does the implementation of a remote patient monitoring home telehealth for SCI patients recently discharged from acute-care setting (I) compared to the usual practice …

Treatment Of Epilepsy Using A Targeted P38Γ Kinase Gene Therapy, Nicolle Morey, Magdalena Przybyla, Julia Van Der Hoven, Yazi D Ke, Fabien Delerue, Janet Van Eersel, Lars M Ittner

Faculty, Staff and Student Publications

Hyperphosphorylated microtubule-associated protein tau has been implicated in dementia, epilepsy, and other neurological disorders. In contrast, site-specific phosphorylation of tau at threonine 205 (T205) by the kinase p38γ was shown to disengage tau from toxic pathways, serving a neuroprotective function in Alzheimer's disease. Using a viral-mediated gene delivery approach in different mouse models of epilepsy, we show that p38γ activity-enhancing treatment reduces seizure susceptibility, restores neuronal firing patterns, reduces behavioral deficits, and ameliorates epilepsy-induced deaths. Furthermore, we show that p38γ-mediated phosphorylation of tau at T205 is essential for this protection in epilepsy, as a lack of this critical interaction reinstates …

Education Research: Neurologic Education In Physician Assistant Programs, Carl Garubba

Physician Assistant Studies | Faculty Scholarship

Background and Objectives A growing number of advanced practice providers (APPs) are entering neurologic practice, and educational initiatives focused on postgraduate training in neurology for these providers are growing in turn. Neurologic education in APP degree programs is not well defined, which limits the ability to tailor these initiatives to the specific needs of APPs. We aim to describe neurologic education in physician assistant (PA) degree programs to better inform these efforts.

Methods The 2018 American Academy of Neurology clerkship director survey was adapted for directors of PA programs via an iterative approach. The survey was distributed to program directors …

Impairment-Based Multidisciplinary Rehabilitation Management In Multiple Sclerosis In Pakistan, Sarah Razaq, Fahim Anwar, Wasim Wali

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Psychiatric Manifestations Of Dengue Fever- A Case Report From Pakistan, Ifrah Hambal, Samrah Nasir, Tania Nadeem

Pakistan Journal of Neurological Sciences (PJNS)

A 29-year-old male presented to Aga Khan University Hospital with complaints of fever, body-aches, vomiting and one episode of gum bleeding. A Dengue antigen test done prior to presentation was positive. He was admitted for medical management. During hospital stay, the patient developed manic symptoms including over-talkativeness, expansive mood, disinhibited behavior, excessive planning, paranoia and aggression. He remained oriented to time, place and person and neurological examination was unremarkable. He was managed with anti-psychotics and benzodiazepines, and his psychiatric symptoms improved with improvement in his medical condition. This case highlights the possibility of psychiatric manifestations occurring in context of a …

Short, Medium And Long Term Neurological Manifestations And Outcome In Covid-19 Patients, Sajid Hameed, Bashir Soomro, Samar Iltaf, Abdul Malik, Anjum Farooq, Alam Ibrahim Siddiqi, Safia Awan, Mohammad Wasay

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: There is a need to improve the understanding of Covid-19 neurological complications in a temporal manner. The objective of our study was to find out temporal relationship of neurological manifestations and outcome in Covid-19 Patients.

Methods: This was a multi-center observational study from six centers in Pakistan. Data of covid patients with six months follow up was retrospectively collected from the hospital records. Time periods were divided into short-term (< 1 month), medium-term (2-3 months) and long-term (>4 months). SPSS version 26.0 (SPSS Inc., Chicago, IL, USA) was used to analyze the data.

Results: Neurological manifestations were reported in 208 out of 905 covid …

Decompressive Hemicraniectomy For Patients With Malignant Cerebral Venous Sinus Thrombosis, Sadaf Majid, Waseem Tariq Malik, Asfandyar Khan Niazi, Ehsan Ul Haq, Hina Yusuf, Raja Farhat Shoaib, Maimoona Siddiqui Siddiqui

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke and may lead to the development of raised intracranial pressure due to edema, infarct or bleed. These patients may require decompressive hemicraniectomy to reduce the raised intracranial pressure. However, the evidence for hemicraniectomy in these patients is scanty. Our objective was to perform a retrospective chart review to describe the clinical characteristics of patients who underwent decompressive hemicraniectomy for malignant CVST and their outcomes.

Methods: We retrospectively analyzed the medical records of patients with CVST who underwent decompressive hemicraniectomy between 2013 and 2020 at Shifa International …

Hurdles Of Intravenous Thrombolysis In Acute Ischemic Stroke At Balochistan, Anjum Farooq, Muhammad Essa, Nimra Shafique, Sakina Gull

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Intravenous thrombolysis (IVT) with alteplase tPA (tissue plasminogen Activator) is the FDA approved treatment for acute ischemic stroke. The objective of this study was to determine the hurdles of intravenous thrombolysis in acute ischemic stroke in Balochistan.

Methods: A prospective cross-sectional observational study was carried out from June 2021 to December 2021 at Neurology department of Bolan Medical Complex Hospital Quetta on 272 patients of acute ischemic stroke who fulfilled the criteria. Proforma was filled by relative or patient after informed consent. Proforma included sex, age, diagnosis, time of presentation after stroke and reason of delay. Data …

Multiple Sclerosis And Parkinson’S Disease: Poles Apart Or Cut From The Same Cloth?, Wajid Jawaid

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Neurological Manifestations Of Cerebral Venous Thrombosis: Experience From A Tertiary Care Center, Anum Irfan, Soban Khan, Zaid Waqar, Sumaira Nabi, Bushra Khalid, Muhammad Tariq

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Cerebral venous thrombosis (CVT) is a common cause of cerebrovascular accident (stroke). CVT is caused due to blockage in blood flow either in cerebral veins or in dural sinuses. The objective of this study was to determine prevalence of various clinical and imaging characteristics in patients with cerebral venous thrombosis.

Methods: A descriptive retrospective cross-sectional patient data was collected from November 2019 to February 2021. This study was conducted in Neurology Department in Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan. This study contains patient medical histories of 60 patients who were admitted in two and a …

48 Hours Holter Monitoring In Detecting Occult Atrial Fibrillation In Young Patients With Possible Cardioembolic Stroke, Bushra Khalid, Soban Khan, Muhammad Tariq, Sajid Ali, Ijaz Ali, Zaid Waqar

Pakistan Journal of Neurological Sciences (PJNS)

ABSTRACT

Background and objective: Atrial fibrillation (AF) is a common cause of ischemic stroke. AF is usually paroxysmal and could escape detection via single lead electrocardiogram ECG recorder. Holter monitoring is useful in this scenario. The objective of this study was to assess the role of 48 hours Holter monitoring in identifying clinically inapparent AF in young patients with ischemic stroke

Methods: A retrospective cross-sectional study was conducted with patient data from November 2019 to February 2021. It was conducted in Neurology department of Pakistan Institute of Medical Sciences, Islamabad, Pakistan. Study contained medical records of 60 patients which were …

Sars-Cov-2 Infection With Polymyositis- A Case Report, Muhammad Hassan, Fatima Mustafa, Naveed Ullah Khan, Taimoor Hassan, Mansoor Iqbal Chaudhry, Mazhar Badshah

Pakistan Journal of Neurological Sciences (PJNS)

Among the most prevalent and least addressed symptoms of SARS-CoV-2 infection are myalgia, muscle weakness, and body aches. Only a few studies have reported polymyositis in patients with Covid-19 infection. At least one-third of patients with Covid-19 syndrome had elevated CPK levels. The cause of elevated CPK can be a cytokine storm or viral infection of the muscles. We present a case in which our patient developed features of myositis following the resolution of an acute viral prodrome caused by SARS-CoV-2. Our patient had both radiological and biopsy-proven neuromuscular manifestations of SARS-CoV-2 associated with polymyositis. Proximal muscle weakness began shortly …

The Sub-Standardized Approach To Stroke Management In Low And Middle-Income Countries Including Pakistan: Limitations And Suggested Options To Overcome Some Of The Shortcomings Via Teleneurology/Telestroke Application, Rizwana Shahid

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Ischemic stroke still poses a significant health concern throughout the world. However, low and middle-income countries (LMIC) in Asia have more devastating outcome. The vascular risk factors are prevalent in most parts of Asia, contributing to increasing incidence. The recommended approved treatment for acute stroke is limited to a few areas in these countries. We aimed to identify stroke risk factors, its incidence and prevalence; treatment opportunities offered in various parts of the region and utilizing the alternate pathways to improve the disease recognition and management outcome.

Method: A comprehensive search using PubMed, MEDLINE, Medline Plus, PubMed …

A Substring Replacement Approach For Identifying Missing Is-A Relations In Snomed Ct, Xubing Hao, Rashmie Abeysinghe, Jay Shi, Licong Cui

Faculty, Staff and Student Publications

Biomedical ontologies provide formalized information and knowledge in the biomedical domain. Over the years, biomedical ontologies have played an important role in facilitating biomedical research and applications. Common quality issues of biomedical ontologies include inconsistent naming of concepts, redundant concepts, redundant relations, incomplete/incorrect concept definitions, and incomplete/incorrect class hierarchies. In this work, we focus on addressing the incompleteness of the class hierarchy in SNOMED CT. We develop a substring replacement approach, leveraging concepts’ lexical features and existing IS-A relations to identify potential missing IS-A relations in SNOMED CT. To evaluate the effectiveness of our approach, we performed both automated and …

Innate Lymphoid Cells In Depression: Current Status And Perspectives, Amit Kumar Madeshiya, Anilkumar Pillai

Faculty, Staff and Student Publications

The recent discovery of innate lymphoid cells (ILCs) has provided new insights into our understanding of the pathogenesis of many disease conditions with immune dysregulation. Type 1 innate lymphoid cells (ILC1s) induce type I immunity and are characterized by the expression of signature cytokine IFN-γ and the master transcription factor T-bet; ILC2s stimulate type II immune responses and are defined by the expression of signature cytokines IL-5 and IL-13, and transcription factors ROR-α and GATA3; ILC3s requires the transcription factor RORγt and produce IL-22 and IL-17. ILCs are largely tissue-resident and are enriched at barrier surfaces of the mammalian body. …

A Minimal Role For Synonymous Variation In Human Disease, Ryan S Dhindsa, Quanli Wang, Dimitrios Vitsios, Oliver S Burren, Fengyuan Hu, James E Dicarlo, Leonid Kruglyak, Daniel G Macarthur, Matthew E Hurles, Slavé Petrovski

Duncan NRI Faculty and Staff Publications

Synonymous mutations change the DNA sequence of a gene without affecting the amino acid sequence of the encoded protein. Although some synonymous mutations can affect RNA splicing, translational efficiency, and mRNA stability, studies in human genetics, mutagenesis screens, and other experiments and evolutionary analyses have repeatedly shown that most synonymous variants are neutral or only weakly deleterious, with some notable exceptions. Based on a recent study in yeast, there have been claims that synonymous mutations could be as important as nonsynonymous mutations in causing disease, assuming the yeast findings hold up and translate to humans. Here, we argue that there …

Propranolol Modulates Cerebellar Circuit Activity And Reduces Tremor., Joy Zhou, Meike E Van Der Heijden, Luis E Salazar Leon, Tao Lin, Lauren N Miterko, Dominic J Kizek, Ross M Perez, Matea Pavešković, Amanda M Brown, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Tremor is the most common movement disorder. Several drugs reduce tremor severity, but no cures are available. Propranolol, a β-adrenergic receptor blocker, is the leading treatment for tremor. However, the in vivo circuit mechanisms by which propranolol decreases tremor remain unclear. Here, we test whether propranolol modulates activity in the cerebellum, a key node in the tremor network. We investigated the effects of propranolol in healthy control mice and Car8^wdl/wdl mice, which exhibit pathophysiological tremor and ataxia due to cerebellar dysfunction. Propranolol reduced physiological tremor in control mice and reduced pathophysiological tremor in Car8^wdl/wdl mice to control levels. …

Neurobehavioral Deficits And A Progressive Ictogenesis In The Tetrodotoxin Model Of Epileptic Spasms, John T Le, Carlos J Ballester-Rosado, James D Frost, John W Swann

Duncan NRI Faculty and Staff Publications

Objective: Our goal was to determine whether animals with a history of epileptic spasms have learning and memory deficits. We also used continuous (24/7) long-term electroencephalographic (EEG) recordings to evaluate the evolution of epileptiform activity in the same animals over time.

Methods: Object recognition memory and object location memory tests were undertaken, as well as a matching to place water maze test that evaluated working memory. A retrospective analysis was undertaken of long-term video/EEG recordings from rats with epileptic spasms. The frequency and duration of the ictal events of spasms were quantified.

Results: Rats with a history of epileptic spasms …

Development Of Myelinating Glia: An Overview, Carlo D Cristobal, Hyun Kyoung Lee

Duncan NRI Faculty and Staff Publications

Myelin is essential to nervous system function, playing roles in saltatory conduction and trophic support. Oligodendrocytes (OLs) and Schwann cells (SCs) form myelin in the central and peripheral nervous systems respectively and follow different developmental paths. OLs are neural stem-cell derived and follow an intrinsic developmental program resulting in a largely irreversible differentiation state. During embryonic development, OL precursor cells (OPCs) are produced in distinct waves originating from different locations in the central nervous system, with a subset developing into myelinating OLs. OPCs remain evenly distributed throughout life, providing a population of responsive, multifunctional cells with the capacity to remyelinate …

Inpatient Teleneurology Follow-Up Has Comparable Outcomes To In-Person Neurology Follow-Up, Alicia M Zha, Alyssa D Trevino, Christy M Ankrom, Kristie M Chu, Michele M Joseph, Tushar Patni, Tiffany D Cossey, Sean I Savitz, Tzu-Ching Wu, Amanda Jagolino-Cole

Faculty, Staff and Student Publications

Background and Objectives

Community emergency departments often transfer patients for lack of neurology coverage, potentially burdening patients and accepting facilities. Telestroke improves access to acute stroke care, but there is a lack of data on inpatient teleneurology and telestroke care.

Methods

From our prospective telestroke registry, we retrospectively reviewed 3702 consecutive patients who were seen via telestroke between September 2015 and December 2018. Patients who required transfer after initial telestroke evaluation or who were kept at hospitals without consistent neurology coverage were excluded from analysis. We compared baseline demographics, clinical characteristics, and hospital outcomes in patients who were subsequently followed …

Predictors For Outcomes Of Noninvasive, Individualized Transcranial Magnetic Neuromodulation In Multiple Sclerosis Women With Neurogenic Voiding Dysfunction, Yongchang Jang, Khue Tran, Zhaoyue Shi, Karmonik Christof, Darshil Choksi, Betsy H Salazar, John A Lincoln, Rose Khavari

Faculty, Staff and Student Publications

Purpose:

Multiple sclerosis (MS) is a multifocal demyelinating disease that affects the central nervous system (CNS) and commonly leads to neurogenic lower urinary tract dysfunction (NLUTD). Proper storage and release of urine relies on synchronized activity of the LUT, which is meticulously regulated by supraspinal circuits, making it vulnerable to diseases such as MS. NLUTD, characterized by voiding dysfunction (VD), storage issues, or a combination of both is a common occurrence in MS. Unfortunately, there are limited treatment options for NLUTD, making the search for alternative treatments such as transcranial rotating permanent magnet stimulation (TRPMS) of utmost importance. To assess …

Extensive Accumulation Of Misfolded Protein Aggregates During Natural Aging And Senescence, Karina Cuanalo-Contreras, Jonathan Schulz, Abhisek Mukherjee, Kyung-Won Park, Enrique Armijo, Claudio Soto

Faculty, Staff and Student Publications

Accumulation of misfolded protein aggregates is a hallmark event in many age-related protein misfolding disorders, including some of the most prevalent and insidious neurodegenerative diseases. Misfolded protein aggregates produce progressive cell damage, organ dysfunction, and clinical changes, which are common also in natural aging. Thus, we hypothesized that aging is associated to the widespread and progressive misfolding and aggregation of many proteins in various tissues. In this study, we analyzed whether proteins misfold, aggregate, and accumulate during normal aging in three different biological systems, namely senescent cells,

Endovascular Repair Of Intercostal Patch Aneurysms In A Patient With Loyes-Dietz Syndrome, Guilherme B Lima, Laura Ocasio, Marina Dias-Neto, Emanuel R Tenorio, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Student Publications

No abstract provided.