Neurology Commons^™

Targeted Therapy In The Management Of Modern Craniopharyngiomas, Maikerly Reyes, Mohammad Taghvaei, Siyuan Yu, Anish Sathe, Sarah Collopy, Giyarpuram Prashant, James J. Evans, Michael Karsy

Department of Neurosurgery Faculty Papers

Background: The proximity of craniopharyngiomas (CPs) to critical neurovascular structures can lead to a host of neurologic and endocrine complications that lead to difficulty with surgical management. In this review, we examine the molecular and genetic markers implicated in CP, their involvement in tumorigenic pathways, and their impact on CP prognosis and treatment.

Methods: We undertook a focused review of relevant articles, clinical trials, and molecular summaries regarding CP.

Results: Genetic and immunological markers show variable expression in different types of CP. BRAF is implicated in tumorigenesis in papillary CP (pCP), whereas CTNNB1 and EGFR are often overexpressed in adamantinomatous …

Dynamics Of Huntingtin Protein Interactions In The Striatum Identifies Candidate Modifiers Of Huntington Disease, Todd M Greco, Christopher Secker, Eduardo Silva Ramos, Joel D Federspiel, Jeh-Ping Liu, Alma M Perez, Ismael Al-Ramahi, Jeffrey P Cantle, Jeffrey B Carroll, Juan Botas, Scott O Zeitlin, Erich E Wanker, Ileana M Cristea

Duncan NRI Faculty and Staff Publications

Huntington’s disease (HD) is a monogenic neurodegenerative disorder with one causative gene, huntingtin (HTT). Yet, HD pathobiology is multifactorial, suggesting that cellular factors influence disease progression. Here, we define HTT protein-protein interactions (PPIs) perturbed by the mutant protein with expanded polyglutamine in the mouse striatum, a brain region with selective HD vulnerability. Using metabolically labeled tissues and immunoaffinity purification-mass spectrometry, we establish that polyglutamine-dependent modulation of HTT PPI abundances and relative stability starts at an early stage of pathogenesis in a Q140 HD mouse model. We identify direct and indirect PPIs that are also genetic disease modifiers using in-cell two-hybrid …

Stroke Network Of Wisconsin (Snow) Scale Predicts Large Vessel Occlusion Stroke In The Prehospital Setting, Kessarin Panichpisal, Sarah Erpenbeck, Paul Vilar, Reji P. Babygirija, Maharaj Singh, M. Riccardo Colella, Richard A. Rovin

Journal of Patient-Centered Research and Reviews

Purpose: In previous trials, the Stroke Network of Wisconsin (SNOW) scale accurately predicted large vessel occlusion (LVO) stroke in the hospital setting. This study evaluated SNOW scale performance in the prehospital setting and its ability to predict LVO or distal medium vessel occlusion (DMVO) in patients suspected of having acute ischemic stroke (AIS), a scenario in which transport time to an endovascular treatment-capable facility (ECSC) is critical.

Methods: All potential AIS patients with last-known-well time of ≤ 24 hours were assessed by Milwaukee County Emergency Medical Services for LVO using SNOW. Patients with a positive SNOW score were transferred to …

Associations Between Residential Greenspace, Socioeconomic Status, And Stroke: A Matched Case-Control Study, Heloise Cheruvalath, Jennifer Homa, Maharaj Singh, Paul Vilar, Amin Kassam, Richard A. Rovin

Journal of Patient-Centered Research and Reviews

Purpose: Studies have shown increased residential greenspace is associated with improved outcome following stroke. This study sought to determine if residential greenspace is an independent stroke risk factor.

Methods: A retrospective 1:4 matched case-control study involving 1174 stroke and 4696 control patients over a 3-year period from Milwaukee County, Wisconsin, was conducted. Greenspace was determined using normalized difference vegetation index (NDVI) for a 250-meter radius surrounding a subject’s residence. The area deprivation index (ADI) for the census block tract of a subject’s residence was obtained from the Neighborhood Atlas® (University of Wisconsin School of Medicine and Public Health). …

New-Onset Acute Ischemic Stroke Following Covid-19: A Case-Control Study, Fariborz Khorvash, Mohammad Amin Najafi, Mohsen Kheradmand, Mohammad Saadatnia, Rojin Chegini, Farideh Najafi

Rothman Institute Papers

Background: Neurological manifestations of coronavirus disease 2019 (COVID-19) have been highlighted. COVID-19 potentially increases the risk of thromboembolism. We aimed to compare patients with COVID-19 with and without new-onset acute ischemic stroke (AIS).

Materials and methods: In this single-center retrospective case-control study, demographics, clinical characteristics, laboratory findings, and clinical outcomes were compared between 51 patients with both COVID-19 and AIS (group A) and 160 patients with COVID-19 and without AIS (group B).

Results: Patients in group A were significantly older, more likely to present with critical COVID-19 (P = 0.004), had higher rates of admission in the intensive care …

Actl6a Coordinates Axonal Caliber Recognition And Myelination In The Peripheral Nerve, Hye-Jin Park, Eric Tsai, Dennis Huang, Michael Weaver, Luciana Frick, Ace Alcantara, John J. Moran, Julia Patzig, Carmen V. Melendez-Vasquez, Gerald R. Crabtree, M.L. Feltri, John Svaren, Patricia Casaccia

Advanced Science Research Center

Cells elaborate transcriptional programs in response to external signals. In the peripheral nerves, Schwann cells (SC) sort axons of given caliber and start the process of wrapping their membrane around them. We identify Actin-like protein 6a (ACTL6a), part of SWI/SNF chromatin remodeling complex, as critical for the integration of axonal caliber recognition with the transcriptional program of myelination. Nuclear levels of ACTL6A in SC are increased by contact with large caliber axons or nanofibers, and result in the eviction of repressive histone marks to facilitate myelination. Without Actl6a the SC are unable to coordinate caliber recognition and myelin production. Peripheral …

Analysis Of Quality Of Life In Parkinson's Disease Caregivers: A Quantitative Research Study, Peyton Dooley, Claribell Bayona, Krisitin Domville

Spring 2022 Virtual OTD Capstone Symposium

Parkinson’s disease is a commonly known movement and neurodegenerative disorder affecting a large portion of the male population. This disease is gruesome and progressive; it often interferes with a person’s daily routines and activities due to deficits in postural stability, tremors, slowed movement, and rigidity (Tysnes et al., 2017). Most persons with Parkinson’s have informal caregivers, often female spouses, or significant others of the individual. Caregivers of Parkinson’s disease prioritize their loved ones needs over their own, neglecting their own daily activities and routines including self-care, social participation, leisure, and physical activity. Occupational therapists and other health care professionals often …

Exploration Of The Transference Of Cognitive Skills Gained From A Movement-Based Program Incorporating Modified Dance To Occupational Performance For Individuals With Parkinson’S Disease, Alyssa Kronstadt-Trapasso

Spring 2022 Virtual OTD Capstone Symposium

A movement-based program incorporating modified dance was used with individuals with Parkinson’s disease (PD) to assess changes in cognition as it relates to occupational performance. This qualitative research study provided 1-hour dance sessions 3 days per week over the course of 16 weeks with 6 participants who have mild-moderate PD. Various dance styles were used including salsa, tango, waltz, line dancing, and others. Cognition and occupational performance were assessed using the Montreal Cognitive Assessment (MOCA), the Canadian Occupational Performance Measure (COPM), and surveys. Findings indicated improvements in perceived occupational performance via the COPM and surveys, while MoCA results indicated improvements …

Suicide Prevention In Bangladesh: The Role Of Family, S M Yasir Arafat, Tamkeen Saleem, Todd M. Edwards, Syeda Ayat-E-Zainab Ali, Murad M. Khan

Department of Psychiatry

Background: Suicide is a public health problem that gets little attention in Bangladesh especially in prevention aspects. Recent studies revealed that a significant portion of risk factors is closely related to family events. However, potential prevention strategies considering the family structure and involving family dynamics of Bangladesh have not been discussed.
Objectives: We aim to highlight areas of family vulnerability and resilience when the threat of suicide is present, as well as the potential roles of family in suicide prevention in Bangladesh.
Methods: We conducted a thorough narrative and focused literature search and synthesized evidence based on available articles discussing …

Neuromotor Prosthetic To Treat Stroke-Related Paresis: N-Of-1 Trial, Mijail D. Serruya, Alessandro Napoli, Nicholas Satterthwaite, Joe Kardine, Joseph Mccoy, Namrata Grampurohit, Kiran Talekar, Devon M. Middleton, Feroze Mohamed, Michael Kogan, Ashwini Sharan, Chengyuan Wu, Robert H. Rosenwasser

Department of Neurology Faculty Papers

Background: Functional recovery of arm movement typically plateaus following a stroke, leaving chronic motor deficits. Brain-computer interfaces (BCI) may be a potential treatment for post-stroke deficits

Methods: In this n-of-1 trial (NCT03913286), a person with chronic subcortical stroke with upper-limb motor impairment used a powered elbow-wrist-hand orthosis that opened and closed the affected hand using cortical activity, recorded from a percutaneous BCI comprised of four microelectrode arrays implanted in the ipsilesional precentral gyrus, based on decoding of spiking patterns and high frequency field potentials generated by imagined hand movements. The system was evaluated in a home setting for 12 weeks …

Loss-Of-Function Variants In Tiam1 Are Associated With Developmental Delay, Intellectual Disability, And Seizures, Shenzhao Lu, Rebecca Hernan, Paul C Marcogliese, Yan Huang, Tracy S Gertler, Meltem Akcaboy, Shiyong Liu, Hyung-Lok Chung, Xueyang Pan, Xiaoqin Sun, Melahat Melek Oguz, Ulkühan Oztoprak, Jeroen H F De Baaij, Jelena Ivanisevic, Erin Mcginnis, Maria J Guillen Sacoto, Wendy K Chung, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

TIAM Rac1-associated GEF 1 (TIAM1) regulates RAC1 signaling pathways that affect the control of neuronal morphogenesis and neurite outgrowth by modulating the actin cytoskeletal network. To date, TIAM1 has not been associated with a Mendelian disorder. Here, we describe five individuals with bi-allelic TIAM1 missense variants who have developmental delay, intellectual disability, speech delay, and seizures. Bioinformatic analyses demonstrate that these variants are rare and likely pathogenic. We found that the Drosophila ortholog of TIAM1, still life (sif), is expressed in larval and adult central nervous system (CNS) and is mainly expressed in a subset of neurons, but not in …

Trigonella Foenum-Graecum Methanolic Extract On Isolated Smooth Muscles And Acetylcholinesterase Enzyme: An In Vitro And Mechanistic In Silico Investigation, Muhammad Nabeel Ghayur, Mohnad Abdalla, Asaad Khalid, Saeed Ahmad, Anwar Gilani

Department of Biological & Biomedical Sciences

Results: When tested on the baseline of isolated tissues, Tfg.Cr was devoid of any activity (stimulant or relaxant) till 10 mg/ml. This is an interesting finding, keeping in mind that the fenugreek seeds are used to alleviate constipation and diarrhoea. When Tfg.Cr was tried for any potential AChE inhibitory activity, it did show an inhibitory effect in increasing concentrations (47-380 μg/ml). This inhibitory effect was comparable to the effect produced by a standard AChE inhibitor physostigmine. One of the known fenugreek constituents, diosgenin, was also tested, and it also showed an AChE inhibitory effect in a concentration-dependent manner (11-190 …

Csf-1 Maintains Pathogenic But Not Homeostatic Myeloid Cells In The Central Nervous System During Autoimmune Neuroinflammation, Daniel Hwang, Maryam S Seyedsadr, Larissa Ishikawa, Alexandra Boehm, Ziver Sahin, Giacomo Casella, Soohwa Jang, Michael V Gonzalez, James P Garifallou, Hakon Hakonarson, Weifeng Zhang, Dan Xiao, A M Rostami, Guang-Xian Zhang, Bogoljub Ciric

Department of Neurology Faculty Papers

SignificanceMultiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by accumulation of myeloid cells in the central nervous system (CNS). Both harmful and beneficial myeloid cells are present in EAE/MS, and a goal of MS therapy is to preferentially remove harmful myeloid cells. The receptor for CSF-1 (CSF-1R) is found on myeloid cells and is important for their survival. CSF-1R can bind two ligands, CSF-1 and IL-34, but it is not known whether their functions in EAE/MS differ. We found that blocking CSF-1 depleted only harmful myeloid cells in the CNS and suppressed EAE, …

Decompression And Interlaminar Stabilization For Lumbar Spinal Stenosis: A Cohort Study And Two-Dimensional Operative Video, Olivia E. Gilbert, Sarah E. Lawhon, Twila L. Gaston, Jared M. Robichaux, Gabriel Claudiu Tender

School of Medicine Faculty Publications

Background and Objectives: Lumbar spinal stenosis is one of the most common causes of disability in the elderly and often necessitates surgical intervention in patients over the age of 65. Our study aimed to evaluate the clinical efficacy of interlaminar stabilization following decompressive laminectomy in patients with lumbar stenosis without instability. Materials and Methods: Twenty patients with lumbar stenosis underwent decompressive laminectomy and interlaminar stabilization at our academic institution. Clinical outcomes were measured using the visual analog scale (VAS) and Oswestry disability index (ODI) at the 2-month, 6-month, and 1-year postoperative visits, and these outcomes were compared to the preoperative …

Mcph1: A Novel Case Report And A Review Of The Literature, Stefano Giuseppe Caraffi, Marzia Pollazzon, Muhammad Farooq, Ambrin Fatima, Lars Allan Larsen, Roberta Zuntini, Manuela Napoli, Livia Garavelli

Department of Biological & Biomedical Sciences

Microcephaly primary hereditary (MCPH) is a congenital disease characterized by nonsyndromic reduction in brain size due to impaired neurogenesis, often associated with a variable degree of intellectual disability (ID). The genetic etiology of MCPH is heterogeneous and comprises more than 20 loci, nearly all following a recessive inheritance pattern. The first causative gene identified, MCPH1 or Microcephalin, encodes a centrosomal protein that modulates chromosome condensation and cell cycle progression. It is also involved in DNA damage response and telomere maintenance in the nucleus. Despite numerous studies on MCPH1 function, MCPH1-affected individuals are rare and the available clinical reports are …

Targeted Osmotic Lysis: A Novel Approach To Targeted Cancer Therapies, Harry J. Gould, Dennis Paul

School of Medicine Faculty Publications

The conventional treatment of cancer has been based on the delivery of non-selective toxins and/or ionizing energy that affect both the cancer and normal tissues in the hope of destroying the offending disease before killing the patient. Unfortunately, resistance often develops to these treatments and patients experience severe, dose-limiting adverse effects that reduce treatment efficacy and compromise quality of life. Recent advances in our knowledge of the biology of tumor cells and their microenvironment, the recognition of surface proteins that are unique to specific cancers and essential to cell growth and survival and signaling pathways associate with invasion and metastasis …

Regulatory Aspects Of Mild Cognitive Impairment: Toward A Harmonized Perspective, Peter J. Whitehouse

Faculty Scholarship

The development of the concept of mild cognitive impairment (MCI) and its practical application have been intimately tied to attempts to produce therapeutic agents. Understanding the regulatory environment and determining the way in which it can be influenced are critical to the development of drugs and their eventual approval. In this article, we review some of the current challenges surrounding the concept of MCI relevant to drug development, summarize activities in various regions of the world, and conclude with some suggested next steps and an alternative framing for approving drugs for MCI and related conditions.

Improved Cotard Delusion And Motor Function In Parkinson’S Disease Following Electroconvulsive Therapy (Ect), Sunihidi Ramesh, Jeffrey Ratliff

Department of Neurology Faculty Papers

No abstract provided.

The Role Of The Complement System In Chronic Inflammatory Demyelinating Polyneuropathy: Implications For Complement-Targeted Therapies., Luis A Querol, Hans-Peter Hartung, Richard A Lewis, Pieter A Van Doorn, Timothy R Hammond, Nazem Atassi, Miguel Alonso-Alonso, Marinos Dalakas

Department of Neurology Faculty Papers

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common, heterogeneous, immune-mediated neuropathy, characterized by predominant demyelination of motor and sensory nerves. CIDP follows a relapsing-remitting or a progressive course and causes substantial disability. The pathogenesis of CIDP involves a complex interplay of multiple aberrant immune responses, creating a pro-inflammatory environment, subsequently inflicting damage on the myelin sheath. Though the exact triggers are unclear, diverse immune mechanisms encompassing cellular and humoral pathways are implicated. The complement system appears to play a role in promoting macrophage-mediated demyelination. Complement deposition in sural nerve biopsies, as well as signs of increased complement activation in …

Complement In Autoimmune Inflammatory Myopathies, The Role Of Myositis-Associated Antibodies, Covid-19 Associations, And Muscle Amyloid Deposits., Marinos Dalakas

Department of Neurology Faculty Papers

Introduction

The inflammatory myopathies (IM) have now evolved into distinct subsets requiring clarification about their immunopathogenesis to guide applications of targeted therapies

Areas Covered

Immunohistopathologic criteria of IM with a focus on complement, anti-complement therapeutics, and other biologic immunotherapies. The COVID19-triggered muscle autoimmunity along with the correct interpretation of muscle amyloid deposits is discussed.

Expert Opinion

The IM, unjustifiably referred as idiopathic, comprise Dermatomyositis (DM), Necrotizing Autoimmune Myositis (NAM), Anti-synthetase syndrome-overlap myositis (Anti-SS-OM), and Inclusion-Body-Myositis (IBM). In DM, complement activation with MAC-mediated endomysial microvascular destruction and perifascicular atrophy is the fundamental process, while innate immunity activation factors, INF1 and …