Medicine and Health Sciences Commons^™

Long-Term Effectiveness Of Ivig Maintenance Therapy In 36 Patients With Gad Antibody-Positive Stiff-Person Syndrome., Jessica Yi, Marinos Dalakas

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: IVIg has been the preferred immunotherapy in stiff-person syndrome (SPS) based on a 3-month controlled trial, but whether it is also effective in inducing long-term benefits or arresting disease progression is unknown. The information is needed because SPS is a progressively disabling disease and IVIg is liberally used as chronic therapy without efficacy data. The present study explores the long-term effects of IVIg in the largest cohort of well-characterized patients with SPS followed by the same clinicians over 10 years.

METHODS: Data of 36 patients (32 glutamic acid decarboxylase [GAD] positive), diagnosed and treated with monthly maintenance …

B- And T-Cell Subset Abnormalities In Monogenic Common Variable Immunodeficiency, Saba Fekrvand, Shaghayegh Khanmohammadi, Hassan Abolhassani, Reza Yazdani

Department of Neurology Faculty Papers

Common variable immunodeficiency (CVID) is a heterogeneous group of inborn errors of immunity characterized by reduced serum concentrations of different immunoglobulin isotypes. CVID is the most prevalent symptomatic antibody deficiency with a broad range of infectious and non-infectious clinical manifestations. Various genetic and immunological defects are known to be involved in the pathogenesis of CVID. Monogenic defects account for the pathogenesis of about 20-50% of CVID patients, while a variety of cases do not have a defined genetic background. Deficiencies in molecules of B cell receptor signaling or other pathways involving B-cell development, activation, and proliferation could be associated with …

Peripheral Neuropathy Evaluations Of Patients With Prolonged Long Covid., Anne Louise Oaklander, Alexander J Mills, Mary Kelley, Lisa S Toran, Bryan Smith, Marinos Dalakas, Avindra Nath

Department of Neurology Faculty Papers

Background and objectives: Recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears exponential, leaving a tail of patients reporting various long COVID symptoms including unexplained fatigue/exertional intolerance and dysautonomic and sensory concerns. Indirect evidence links long COVID to incident polyneuropathy affecting the small-fiber (sensory/autonomic) axons.

Methods: We analyzed cross-sectional and longitudinal data from patients with World Health Organization (WHO)-defined long COVID without prior neuropathy history or risks who were referred for peripheral neuropathy evaluations. We captured standardized symptoms, examinations, objective neurodiagnostic test results, and outcomes, tracking participants for 1.4 years on average.

Results: Among 17 patients (mean age …

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 …

Immunomodulatory Effects And Clinical Benefits Of Intravenous Immunoglobulin In Myasthenia Gravis., Marinos C Dalakas, Andreas Meisel

Department of Neurology Faculty Papers

Introduction Myasthenia gravis (MG) is an antibody-mediated disease that develops in the majority of patients mainly as a result of acetylcholine receptor (AChR) autoantibodies. This process is mediated by a series of immunoregulatory events. Therapeutic targets for MG include suppression of circulating antibodies or antibody production, suppression of complement activation, and immunomodulation of cytokines or T cells. Intravenous immunoglobulin (IVIg) has an effect on all of these mechanisms. Areas covered This narrative review explores the broad immunomodulatory effects of IVIg in MG and provides an update on IVIg treatment for MG. Expert opinion IVIg has a range of immunomodulatory effects …

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 …

Gender Parity In Authorship Of Published Randomized Clinical Trials In Stroke Neurology From 2000 To 2021., Noor F Shaik, Ali A Saherwala, Diana L Tzeng

Department of Neurology Faculty Papers

Gender parity is a crucial goal in clinical medicine so that women have equal access and representation. Although approximately half (46%) of US neurology residents and fellows are female, proportions of female assistant, associate, and full professors are 49%, 41%, and 23%, respectively. This has far-reaching effects, from clinical publications to invited speakerships.Although a study noted increasing trends in female authorship in high-impact neurology journals the current literature lacks evidence on a more informative benchmark—first and last authorship in randomized clinical trials (RCTs), which is typically considered for career advancement. This study assessed annual proportions and trends of female first …

Degenerative Cervical Myelopathy, Ratko Yurac, José Manuel Matamala, Juan José Zamorano, James S Harrop, Benjamin M Davies, Aria Nouri, Michael G Fehlings

Department of Neurology Faculty Papers

Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction in adults. Its prevalence is increasing as a result of population aging. The diagnosis of DCM is often delayed or overlooked, resulting in secondary neurologic morbidity. The natural course of DCM typically presents as a gradual neurological deterioration, with symptoms ranging from muscle weakness to complete paralysis, with variable degrees of sensory deficits and sphincter dysfunction. Magnetic resonance imaging (MRI) and electrophysiological studies allow the assessment of spinal cord function and its structural damage to determine treatment and clinical outcomes. All patients with signs and symptoms consistent …