Stacey L. Clardy

Bio: Stacey L. Clardy is an academic researcher from United States Department of Veterans Affairs. The author has contributed to research in topics: Pediatrics & Veterans Affairs. The author has an hindex of 1, co-authored 3 publications receiving 4 citations. Previous affiliations of Stacey L. Clardy include University of Utah.

Stiff person syndrome with Anti-GAD65 antibodies within the national veterans affairs health administration.

Abstract: Introduction Stiff person syndrome (SPS) is a neurological disorder characterized by muscle rigidity primarily in the truncal muscles, commonly associated with autoantibodies to the glutamic acid-decarboxylase 65 kD receptor (GAD65) There is limited epidemiological information on patients with SPS Methods We performed a retrospective case review using the National United States Veterans Affairs Health Administration electronic medical record system We analyzed prevalence, demographics, disease characteristics, and treatment outcomes in SPS patients who were anti-GAD65 antibody positive Results Fifteen patients met our criteria Point prevalence was 206 per million, and period prevalence was 271 per million Men to women ratio was 14:1 All patients benefitted from treatment with symptomatic antispasmodic agents Ten of 15 patients received intravenous immunoglobulin, with a majority demonstrating stable or improved modified Rankin scores Discussion This investigation was a large North American epidemiological study of SPS with predominantly male patients Symptomatic therapy was beneficial for most patients, with less clear sustained benefit of immunotherapy Muscle Nerve 58:801-804, 2018

Aquaporin-4 Autoantibody Detection by ELISA: A Retrospective Characterization of a Commonly Used Assay.

Abstract: Objective. Aquaporin-4 (AQP4) serum autoantibodies are detected by a variety of methods. The highest sensitivity is achieved with cell-based assays, but the enzyme-linked immunosorbent assay (ELISA) is still commonly utilized by clinicians worldwide. Methods. We performed a retrospective review to identify all patients at the University of Utah who had AQP4 ELISA testing at ARUP Laboratories from 2010 to 2017. We then reviewed their diagnostic evaluation and final diagnosis based on the ELISA titer result. Results. A total of 750 tests for the AQP4 ELISA were analyzed, and 47 unique patients with positive titers were identified. Less than half of these patients (49%) met the clinical criteria for neuromyelitis optica spectrum disorder (NMOSD). In cases of low positive titers (3.0–7.9 U/mL, ), the most common final diagnosis was multiple sclerosis (52.6%). In the moderate positive cohort (8.0–79.9 U/mL, ), only a little more than half the cohort (64.3%) had NMOSD. In cases with high positives (80–160 U/mL, ), 100% of patients met clinical criteria for NMOSD. Conclusions. Our data illustrates diagnostic uncertainty associated with the AQP4 ELISA, an assay that is still commonly ordered by clinicians despite the availability of more sensitive and specific tests to detect AQP4 autoantibodies in patients suspected of having NMOSD. In particular, low positive titer AQP4 ELISA results are particularly nonspecific for the diagnosis of NMOSD. The importance of accessibility to both sensitive and specific AQP4 testing cannot be overemphasized in clinical practice.

Serum and Cerebrospinal Fluid Biomarkers in Neuromyelitis Optica Spectrum Disorder and Myelin Oligodendrocyte Glycoprotein Associated Disease

Abstract: The term neuromyelitis optica spectrum disorder (NMOSD) describes a group of clinical-MRI syndromes characterized by longitudinally extensive transverse myelitis, optic neuritis, brainstem dysfunction and/or, less commonly, encephalopathy. About 80% of patients harbor antibodies directed against the water channel aquaporin-4 (AQP4-IgG), expressed on astrocytes, which was found to be both a biomarker and a pathogenic cause of NMOSD. More recently, antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG), have been found to be a biomarker of a different entity, termed MOG antibody-associated disease (MOGAD), which has overlapping, but different pathogenesis, clinical features, treatment response, and prognosis when compared to AQP4-IgG-positive NMOSD. Despite important refinements in the accuracy of AQP4-IgG and MOG-IgG testing assays, a small proportion of patients with NMOSD still remain negative for both antibodies and are called “seronegative” NMOSD. Whilst major advances have been made in the diagnosis and treatment of these conditions, biomarkers that could help predict the risk of relapses, disease activity, and prognosis are still lacking. In this context, a number of serum and/or cerebrospinal fluid biomarkers are emerging as potentially useful in clinical practice for diagnostic and treatment purposes. These include antibody titers, cytokine profiles, complement factors, and markers of neuronal (e.g., neurofilament light chain) or astroglial (e.g., glial fibrillary acidic protein) damage. The aim of this review is to summarize current evidence regarding the role of emerging diagnostic and prognostic biomarkers in patients with NMOSD and MOGAD.

A Single-Health System Case Series of New-Onset CNS Inflammatory Disorders Temporally Associated With mRNA-Based SARS-CoV-2 Vaccines

Abstract: Background Since 2020, over 250 million doses of mRNA-based SARS-CoV-2 vaccines have been administered in the United States and hundreds of millions worldwide between the Pfizer-BioNTech and Moderna SARS-CoV-2 vaccines. To date, there have been rare reports associating mRNA-based SARS-CoV-2 vaccines with episodes of inflammatory and autoimmune CNS disorders. We report a case series of five patients with new-onset neurological disorders of inflammatory or immunological origin temporally associated with these vaccines. Methods A case-series of five patients within a single 23-hospital health system who developed new-onset CNS inflammatory disease within 2 weeks of receiving a dose of an mRNA-based SARS-CoV-2 vaccine. Results Five cases of post-vaccination CNS disorders of immune origin (fatal ADEM; n = 1, new-onset NMOSD; n = 2, new-clinical onset MS-like syndrome but with preexisting clinically silent mild demyelination; n = 1, meningoencephalitis; n = 1) observed within 2 weeks of inoculation with either the first or second dose of mRNA-based SARS-CoV-2 vaccines (Moderna = 3, Pfizer = 2). Discussion To our knowledge, these are among the emerging cases of CNS adverse events of immunological or inflammatory origin. These findings should be interpreted with great caution as they neither prove a mechanistic link nor imply a potential long-term increased risk in post-vaccination CNS autoimmunity. Larger prospective studies assessing the potential association between mRNA-based vaccination and the development of neurological adverse events of suspected immune origin, particularly among those with underlying CNS or systemic autoimmune disorders, are needed. The use of mRNA-based SARS-CoV-2 vaccines should continue to be strongly encouraged given their high efficacy in overcoming this pandemic.

Antibody-mediated autoimmune encephalitis: A practical approach.

Abstract: Antibody-mediated autoimmune encephalitis (AE) is a heterogeneous group of inflammatory central nervous system disorders. Symptoms typically include subacute, progressive neuropsychiatric symptoms with associated cognitive dysfunction, movement disorders, and autoimmune seizures. The diagnosis should be based on objective neurologic dysfunction in combination with auto antibody testing. Treatment with immunotherapies requires both short-term and long-term strategies depending on the specific syndrome and potential for relapse. In this paper, we review key features of AE, focusing on syndromes involving cell surface and synaptic proteins, and share a practical approach to the diagnosis and management, including common pitfalls associated with nonspecific antibody findings.

Testing for Antibodies Against Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein in the Diagnosis of Patients With Suspected Autoimmune Myelopathy

Abstract: Autoimmune myelopathies are immune-mediated disorders of the spinal cord that can cause significant neurologic disability. Discoveries of antibodies targeting aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) have facilitated the diagnosis of autoimmune myelopathies that were previously considered to be atypical presentations of multiple sclerosis (MS) or idiopathic, and represent major advancements in the field of autoimmune neurology. The detection of these antibodies can substantially impact patient diagnosis and management, and increasing awareness of this has led to a dramatic increase in testing for these antibodies among patients with suspected autoimmune myelopathy. In this review we discuss test methodologies used to detect these antibodies, the role of serum vs. cerebrospinal fluid testing, and the value of antibody titers when interpreting results, with the aim of helping laboratorians and clinicians navigate this testing when ordered as part of the diagnostic evaluation for suspected autoimmune myelopathy.