AbstractObjectiveTo describe patient clinical characteristics associated with matched oligoclonal bands (OCB).MethodsA retrospective review at the University of Utah examined patients with matched OCB from 2015 to 2020. Clinical data, diagnosis, and outcomes were collected. Patients were classified with either multiple sclerosis (MS), other inflammatory neurologic disorder (other‐IND), or noninflammatory neurologic disorder (NIND).ResultsOf 539 identified patients, 436 (53.4% female) were matched‐only, while 103 (43.7% female) were matched + unique. Patients with matched‐only bands were older (57.4 ± 16 vs. 52 ± 14.2, p < 0.001) and more likely to have a history of autoimmune disease (40.1% vs. 28.2%, p = 0.024) and/or cancer (28.7% vs. 16.5%, p = 0.012). Patients with matched + unique bands were more likely to have CSF pleocytosis (52.4% vs. 25.9%, p < 0.001), high IgG index (52.2% vs. 7.6%, p < 0.001), and an abnormal MRI (86.9% vs. 63.1%, p < 0.001). More than two‐thirds of matched‐only patients had NIND, while 33% and 41.7% of matched + unique patients had MS and other‐IND, respectively. Patients exhibiting matched‐only bands and a high IgG index demonstrated a significantly higher incidence of other‐IND compared to those with matched‐only bands and a normal IgG index (55.6% vs. 30.4%, p = 0.013). While Kaplan–Meier survival curves demonstrated higher mortality in the matched‐only cohort compared to the matched + unique cohort (p = 0.02), multivariable Cox regression analysis showed this difference was not statistically significant when adjusting for various factors. A history of cancer was the significant predictor of increased mortality risk (Hazard ratio = 3.147, 95% CI [2.196, 4.51]).InterpretationPatients with matched only versus matched + unique OCB have distinct clinical profiles.

Paraneoplastic cerebellar and brainstem disorders are a heterogeneous group that requires prompt recognition and treatment to help prevent irreversible neurologic injury. Paraneoplastic cerebellar degeneration is best characterized by Yo antibodies in patients with breast or ovarian cancer. Tr (DNER) antibodies in patients with Hodgkin lymphoma can also present with a pure cerebellar syndrome and is one of the few paraneoplastic syndromes found with hematological malignancy. Opsoclonus-myoclonus-ataxia syndrome presents in both pediatric and adult patients with characteristic clinical findings. Other paraneoplastic brainstem syndromes are associated with Ma2 and Hu antibodies, which can cause widespread neurologic dysfunction. The differential for these disorders is broad and also includes pharmacological side effects, infection or postinfectious processes, and neurodegenerative diseases. Although these immune-mediated disorders have been known for many years, mechanisms of pathogenesis are still unclear, and optimal treatment has not been established.

Objective We present a patient who developed cerebellar degeneration and severe psychological symptoms leading to the diagnosis of Hodgkin9s disease and detection of anti-Tr/DNER antibodies. The patient failed to respond methylprednisolone intravenous immunoglobulin G, rituximab, and tumor treatment but had significant improvement with plasma exchange (PLEX). Background Paraneoplastic cerebellar degeneration accompanying Hodgkin9s disease may have its onset prior to detection of the underlying malignancy, during its course, or following treatment. The associated autoantibody, anti-Tr, is reactive with neuronal delta/notch-like epidermal growth factor-related receptors (DNER), an autoantibody not included in all paraneoplastic testing screens. The condition characterized by progressive cerebellar injury, and response to immunosuppressive therapy and tumor treatment is generally poor. Design/Methods Case Presentation: A 60-year-old male presented with diplopia, progressive loss of balance, and ataxia, with impaired short-term memory, confusion, and anger outbursts. Initial commercial screen for paraneoplastic autoantibodies was negative. Two months following his initial presentation he developed inguinal lymphadenopathy. He was diagnosed as having Hodgkin9s Lymphoma Stage 1B and found by a second laboratory to have anti-TR/DNER antibodies (Titer 1:3480; Reference range <1:240), an antibody not included in the initial testing panel. CSF analysis was notable for a protein of 92 mg/dL. MRI demonstrated normal findings for age. Results Treatment with Doxorubicin-Bleomycin-Vinblastine-Dacarbazine (ABVD), pulse methylprednisolone, and intravenous immunoglobulin did not affect disease progression. Plasma exchange PLEX resulted in marked improvement. Symptoms worsened during subsequent treatment with intravenous immunoglobulins and rituximab but improved with further plasma exchange. Conclusions Although Hodgkin9s disease is an important malignancy in paraneoplastic cerebellar degeneration, its associated autoantibody is not necessarily included in commercial paraneoplastic autoantibody screens, potentially leading to delay in diagnosis. Our patient9s dramatic improvement with PLEX suggests that PLEX should be considered early in treatment, or where there is poor response to other treatment modalities.

BACKGROUND AND OBJECTIVES:Common variable immunodeficiency is a systemic disease and not solely a disease of humoral immunity. Neurologic symptoms associated with common variable immunodeficiency are underrecognized and warrant further study. This work aimed to characterize the neurologic symptoms reported by people living with common variable immunodeficiency. METHODS:We conducted a single academic medical center study of neurologic symptoms reported by adults previously diagnosed with common variable immunodeficiency. We used a survey of common neurologic symptoms to determine the prevalence of these symptoms in a population with common variable immunodeficiency and further assessed these patient-reported symptoms with validated questionnaires and compared symptom burden with other neurologic conditions. RESULTS:A volunteer sample of adults (aged 18 years or older) previously diagnosed with common variable immunodeficiency at the University of Utah Clinical Immunology/Immune Deficiency Clinic who were able to read and comprehend English and willing and able to answer survey-based questions were recruited. Of 148 eligible participants identified, 80 responded and 78 completed the surveys. The mean age of respondents was 51.3 years (range 20-78 years); 73.1% female and 94.8% White. Patients with common variable immunodeficiency reported many common neurologic symptoms (mean 14.6, SD 5.9, range 1-25), with sleep issues, fatigue, and headache reported by more than 85%. Validated questionnaires addressing specific neurologic symptoms supported these results. T-scores on Neuro QoL questionnaires for sleep (mean 56.4, SD 10.4) and fatigue (mean 54.1, SD 11) were higher, indicating more dysfunction, than in the reference clinical population (p < 0.005). The Neuro QoL questionnaire for cognitive function showed a lower T-score (mean 44.8, SD 11.1) than that in the reference general population (p < 0.005), indicating worse function in this domain. DISCUSSION:Among survey respondents, there is a marked burden of neurologic symptoms. Given the impact of neurologic symptoms on health-related quality-of-life measures, clinicians should screen patients with common variable immunodeficiency for the presence of these symptoms and offer referral to neurologists and/or symptomatic treatment when indicated. Frequently prescribed neurologic medications may also affect the immune system, and neurologists should consider screening patients for immune deficiency before prescribing them.

ObjectiveTo assess the demographics, neurologic manifestations, comorbidities, and treatment of patients with seronegative primary Sjogren's syndrome (pSS). Patients and methodsWe conducted a retrospective chart review on patients with seronegative pSS evaluated by a neurologist at the University of Utah Health between January 2010 and October 2018. The diagnosis was based on characteristic symptoms, positive minor salivary gland biopsy according to the American-European Consensus Group 2002 criteria, and seronegative antibody status. ResultsOf 45 patients who met the study criteria, 42 (93.3%) were Caucasian, and 38 (84.4%) were female. The patients' mean age at diagnosis was 47.8 & PLUSMN; 12.6 (range 13-71) years. Paresthesia, numbness and dizziness, and headache were noted in 40 (88.9%), 39 (86.7%), and 36 patients (80.0%), respectively. Thirty-four patients underwent brain magnetic resonance imaging. Of these, 18 (52.9%) showed scattered nonspecific periventricular and subcortical cerebral white matter T2/fluid-attenuated inversion recovery hyperintense foci. Twenty-nine patients (64.4%) presented to the neurology clinic prior to pSS diagnosis, and the median delay in diagnosis from the first neurology clinic visit was 5 (interquartile ranges 2.0-20.5) months. Migraine and depression were the most common comorbidities in 31 patients (68.9%). Thirty-six patients received at least one immunotherapy, and 39 were on at least one medication for neuropathic pain. ConclusionPatients often display various nonspecific neurological symptoms. Clinicians should express a high degree of skepticism regarding seronegative pSS and consider minor salivary gland biopsy to avoid delaying diagnosis, as undertreatment can affect patients' quality of life.

Objective: To describe the clinical and immunologic findings of a large cohort of patients with stiff-person spectrum disorder (SPSD) while exploring for potential familial clustering within the Utah Population Database (UPDB). Background: There is limited understanding of the pathophysiology of SPSD. The common co-occurrence of autoimmune diseases in these patients suggests a shared genetic predisposition. Design/Methods: We performed a retrospective review of all confirmed SPSD patients diagnosed and managed in the Autoimmune Neurology Clinic at the University of Utah. Using the UPDB, a population-based genealogic resource containing medical and demographic information of over 11 million individuals, we identified high-risk pedigrees with excess familial aggregation of SPSD using the Familial Standardized Incidence Ratio (FSIR). Unaffected subjects were identified and matched 10:1 to SPSD patients by age, birth year, and pedigree structure in the UPDB. Familial risk analyses were performed to estimate the heritability of SPSD separately using multivariate logistic regression adjusting for sex, birth year, race, and ethnicity. Results: We identified a total of 46 patients with a SPSD. The median age was 52 years old (SD 14 years), and 78% were female and 93% self-identified as White. A total of 22 (47%) had classical SPS, 16 (34%) had SPS with an overlapping with ataxia, epilepsy, or encephalitis. The majority (95%) had glutamic acid decarboxylase (GAD65) antibodies, 11 (24%) had α1-subunit of the glycine receptor (GlyR) antibodies (8 with concomitant GAD65 antibodies), and one patient tested negative for all antibodies. Twenty-eight patients had a comorbid autoimmune disorder with the most frequent being insulin-dependent diabetes (30%) and autoimmune thyroid disease (17%). Conclusions: SPSD is a complex group of disorders predominantly defined by GAD65 and GlyR antibodies. The co-occurrence of autoimmune diseases and potential familial clustering suggests that genetic, inherited factors may play a role in SPSD. Disclosure: Dr. Abbatemarco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Abbatemarco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Abbatemarco has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech . The institution of Dr. Abbatemarco has received research support from Horizon. Dr. Crane has nothing to disclose. Dr. Galli has nothing to disclose. Dr. Rodenbeck has nothing to disclose. Mr. Yu has nothing to disclose. Ms. Date has stock in Astrazeneca. Ms. West has nothing to disclose. Ms. Fraser has nothing to disclose. Mr. Madsen has nothing to disclose. Mr. Wong has nothing to disclose. Dr. Greenlee has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink. Dr. Greenlee has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Sommers Schwartz Law Offices. Dr. Greenlee has received publishing royalties from a publication relating to health care. Dr. Greenlee has received publishing royalties from a publication relating to health care. Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from Sumaira Foundation for NMO. The institution of Dr. Clardy has received research support from Western Institute for Veteran Research. The institution of Dr. Clardy has received research support from NIH/NINDS. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel and Lodging with U of Iowa. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Barrow Neurological Institute. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Beaumont Health.

Objective: To ascertain the frequency of Neuromyelitis Optica Spectrum Disease (NMOSD) misdiagnosis as Multiple Sclerosis (MS), and thus related use of FDA-approved disease-modifying therapies (DMTs) for MS, in a national cohort. Background: NMOSD is an antibody-mediated inflammatory disease of the central nervous system (CNS) that targets the optic nerves, spinal cord, and certain brain regions. NMOSD patients may be misdiagnosed with the more common condition of MS, given some shared signs and symptoms. Misdiagnosed NMOSD patients may be exposed to certain MS DMTs that could potentially worsen the morbidity associated with NMOSD. Design/Methods: Preliminary de-identified aggregate data was obtained utilizing TriNetX, a federated health research network providing access to statistics on electronic medical records that included sixty-one health care organizations (HCOs) within the United States. Patients with the ICD-10 code of NMO (G36.0) were queried within the database from 2008 to 2022. Results: Of the 7768 NMO patients were identified from the TriNETX database, 75.0% were female (n=5826), the mean age (SD) was 49.1 (18.1) years, 53.0% were white (n=4,117), 27.0% (n=2097) were black, 3.0% were Asian (n=223), and the remain are unknown 17.0% (n= 1331). In the four Census Regions, we included 1750 patients from the Northeast, 1012 patients from the Midwest, 4048 from the South, and 872 from the West. Of all NMO patients, 44% (n=3,421) were diagnosed with MS at some point during their course, and 853 NMOSD patients received at least one FDA-approved MS therapy. Sensitive analysis will be completed on geographic variance based on the four censuses of misdiagnosis and prescribed FDA-approved MS DMTs. Conclusions: Many NMOSD patients were misdiagnosed with MS in this national population, and almost one-quarter of misdiagnosed patients were prescribed an FDA-approved MS DMT. An understanding of the specific characteristics of misdiagnosed NMOSD patients is warranted to better understand the factors increasing the risk of misdiagnosis. Disclosure: Mr. Wong has nothing to disclose. Dr. Noroozi Gilandehi has nothing to disclose. Miss Francis has nothing to disclose. Alen Delic has nothing to disclose. Dr. Germaine has nothing to disclose. Dr. Wright has nothing to disclose. Dr. Galli has nothing to disclose. Dr. Kadish has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. The institution of Dr. Kadish has received research support from Alexion Pharmaceuticals. Dr. Paz Soldan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Paz Soldan has received research support from National Institutes of Health. The institution of Dr. Paz Soldan has received research support from National Multiple Sclerosis Society. The institution of Dr. Paz Soldan has received research support from Western Institute for Biomedical Research. The institution of Dr. Paz Soldan has received research support from Biogen. The institution of Dr. Paz Soldan has received research support from Novartis. The institution of Dr. Paz Soldan has received research support from Clene Nanomedicine. An immediate family member of Ms. Klein has received personal compensation for serving as an employee of Amgen. An immediate family member of Ms. Klein has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Greenlee has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink. Dr. Greenlee has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Sommers Schwartz Law Offices. Dr. Greenlee has received publishing royalties from a publication relating to health care. Dr. Greenlee has received publishing royalties from a publication relating to health care. The institution of Dr. Rose has received research support from National Multiple Sclerosis Society. The institution of Dr. Rose has received research support from Guthy Jackson Charitable Foundation. The institution of Dr. Rose has received research support from NIH . The institution of Dr. Rose has received research support from VA. The institution of Dr. Rose has received research support from Biogen. The institution of Dr. Rose has received research support from Friends of MS. Dr. Rose has received intellectual property interests from a discovery or technology relating to health care. Dr. Smith has nothing to disclose. Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from Sumaira Foundation for NMO. The institution of Dr. Clardy has received research support from Western Institute for Veteran Research. The institution of Dr. Clardy has received research support from NIH/NINDS. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel and Lodging with U of Iowa. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Barrow Neurological Institute. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Beaumont Health.

Prior to 1982, ovarian and certain other cancers were known to have a rare complication of progressive cerebellar ataxia, a disorder characterized pathologically by severe-often total-obliteration of cerebellar Purkinje cells. However, the cause of cerebellar injury in these patients was unknown. In that year, we began studies in which sera from individuals with this disorder were reacted with frozen sections of human cerebellum. These studies revealed that patients with ovarian cancer and cerebellar degeneration had high titers of antibodies directed against cytoplasmic antigens of Purkinje cells and deep cerebellar nuclei-a previously undescribed pattern of antibody response which was subsequently found not to be present in ovarian cancer patients who remained neurologically normal. This antibody, now known as "anti-Yo" or "anti-PCA1" provides a marker for rapidly progressive cerebellar ataxia and is heavily associated with gynecological and breast malignancies. Although the role of anti-Yo antibody in cerebellar injury has not been established in living animals, in vitro studies have demonstrated that anti-Yo antibody causes Purkinje cell death in the absence of T lymphocytes. In this commentary, we describe our studies leading to initial discovery of anti-Yo antibody, discuss the relationship of this discovery to current knowledge of paraneoplastic neurological disease, and outline some important questions which remain to be resolved before we fully understand the pathogenesis and optimal treatment of this disorder.

Objective To describe the retinal nerve fiber layer (RNFL) with the demographic and clinical profile in patients with glutamic acid decarboxylase 65 (GAD65) and glycine receptor (GlyR) neurological autoimmunity. Background GAD65 and GlyR autoimmunity can cause a wide range of clinical phenomena, including stiff-person spectrum disorder (SPSD) and epilepsy. Both GAD65, through γ-aminobutyric acid-ergic neurons, and GlyR interact in the retina. Optical coherence tomography (OCT) has previously been used in a variety of neurological disorders to establish baseline characteristics and monitor disease course. This presents a noninvasive opportunity to evaluate for a biomarker that may assist with the treatment of these rare but debilitating disorders. Design/Methods OCT measures of RNFL by sectors were studied in patients with GAD65 and GlyR neurological autoimmunity and compared to that of 148 healthy control eyes. Patients9 baseline characteristics were also reviewed retrospectively from medical records. Results Of the 14 patients included in this study, 12 patients were female, and the mean age was 52.6 ± 16.8 (22-79) years when OCT was performed. Ten had GAD65 autoimmunity and 4 had GlyR autoimmunity. Patients with GAD or GlyR autoimmunity showed lower RNFL thickness in multiple sectors compared to the healthy control group. This result was most apparent in the anti-GAD65 antibody subgroup. Eleven patients had SPSD, one patient had epilepsy, and two had non-specific symptoms. Conclusions This study provides insight into baseline RNFL thickness in a group with GAD65 and GlyR autoimmunity, two conditions that may produce varied symptoms. While limited by sample size, RNFL thinning was seen in the GAD65 and GlyR autoimmunity groups, and it was most evident in the anti-GAD65 subgroup. This provides a baseline characterization and suggests that future studies should be conducted to determine the utility of OCT as a biomarker for these conditions.

Objective To describe the characteristics and outcomes in adult and pediatric patients diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at the two major referral centers in the Mountain West of the United States, a geographic area encompassing roughly 15% of the land mass of the continental US. Background Since the development of commercial assays, MOGAD has become increasingly recognized as an etiologic diagnosis for several CNS demyelinating phenotypes, yet the epidemiological characteristics, relapse rates and outcomes of large populations are not well-described Design/Methods A retrospective chart review for patients within the health systems at the University of Utah and the University of Colorado, and affiliated children's hospitals, was conducted. To identify MOGAD patients, we queried the ICD10 codes corresponding to demyelinating disease of CNS, neuromyelitis optic spectrum disease, optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis. These patients were then cross matched against antibody testing results and existing research databases at each institution. Search dates included 1/1/2016-12/1/2021 to encompass the period of commercially available MOG IgG testing. Patients were cross referenced with a list of positive MOG IgG assays at each institution. Results We describe the characteristics of over 50 patients (adults and children) with MOGAD, including age of onset, gender, symptoms at onset, associated autoimmunity, antibody titers, response to therapies and relapse rates. Conclusions This is a comprehensive characterization of a diverse population of pediatric and adult MOGAD patients seen at the two major referral hospitals in the Mountain West. The treatment regimens and outcomes in this population may inform approaches to current management and future clinical trials.

1) To determine whether anti-Yo and anti-Hu antibodies are taken up by neurons and cause neuronal death in living animals, as has been shown to occur in rodent brain slice cultures. 2) To determine whether methods of detecting neuronal death in slice culture can be used to study brains of animals following antibody infusion.

EDITORIAL article Front. Neurol., 12 May 2022Sec. Multiple Sclerosis and Neuroimmunology https://doi.org/10.3389/fneur.2022.900130

Objective To investigate the mechanisms by which neurons take up paraneoplastic and other antibodies. Background Our laboratory has previously demonstrated that neurons can take up both normal and paraneoplastic IgGs and that paraneoplastic autoantibodies such as anti-Yo and anti-Hu can bind to their intracellular target antigens to produce neuronal death. In this study we investigated how neuronal antibody uptake occurs. Design/Methods We first compared neuronal uptake of normal and paraneoplastic Fab fragments with that of normal IgG Fc fragments or whole paraneoplastic IgGs. To determine whether neurons expressed receptors capable of binding the Fc portion of the IgG molecule, paraformaldehyde-fixed mouse and rat brains sections were probed with antibodies for the three major types of Fc receptors: FcγRI (CD64), FcγRII, (CD32) and FcγRIII (CD16). Neuronal uptake of antineuronal IgGs was compared between wild type mice and knockout mice lacking the FcγRI receptor. We also investigated whether neuronal IgG uptake could be blocked by normal IgG. Results Neurons incorporated the Fc fragment of normal IgG but not the Fab fragment. Intact paraneoplastic IgGs were taken up by neurons, but immunospecific Fab fragments were excluded. Neurons throughout cerebrum, cerebellum, and brainstem showed immunolabeling for FcγRI, but only rare neurons expressed FcγRII or FcγRIII. Uptake of paraneoplastic IgG and neuronal death were not observed in cultures from FcγRI knockout mice but were extensive in cultures from wild type controls. Paraneoplastic antibody uptake could be inhibited by normal IgG. Conclusions Neuronal uptake of normal and paraneoplastic IgGs requires the interaction of the Fc portion of the IgG molecule with previously uncharacterized neuronal FcγRI receptors. Our study provides a mechanism through which antibodies reactive with intracellular neuronal proteins could gain access to their target antigens to cause neuronal injury and neurological disease. The observation that neuronal antibody uptake can be blocked by normal IgG has possible implications for patient treatment.

Autoimmune and paraneoplastic encephalitides represent an increasingly recognized cause of devastating human illness as well as an emerging area of neurological injury associated with immune checkpoint inhibitors. Two groups of antibodies have been detected in affected patients. Antibodies in the first group are directed against neuronal cell surface membrane proteins and are exemplified by antibodies directed against the N-methyl-D-aspartate receptor (anti-NMDAR), found in patients with autoimmune encephalitis, and antibodies directed against the leucine-rich glioma-inactivated 1 protein (anti-LGI1), associated with faciobrachial dystonic seizures and limbic encephalitis. Antibodies in this group produce non-lethal neuronal dysfunction, and their associated conditions often respond to treatment. Antibodies in the second group, as exemplified by anti-Yo antibody, found in patients with rapidly progressive cerebellar syndrome, and anti-Hu antibody, associated with encephalomyelitis, react with intracellular neuronal antigens. These antibodies are characteristically found in patients with underlying malignancy, and neurological impairment is the result of neuronal death. Within the last few years, major advances have been made in understanding the pathogenesis of neurological disorders associated with antibodies against neuronal cell surface antigens. In contrast, the events that lead to neuronal death in conditions associated with antibodies directed against intracellular antigens, such as anti-Yo and anti-Hu, remain poorly understood, and the respective roles of antibodies and T lymphocytes in causing neuronal injury have not been defined in an animal model. In this review, we discuss current knowledge of these two groups of antibodies in terms of their discovery, how they arise, the interaction of both types of antibodies with their molecular targets, and the attempts that have been made to reproduce human neuronal injury in tissue culture models and experimental animals. We then discuss the emerging area of autoimmune neuronal injury associated with immune checkpoint inhibitors and the implications of current research for the treatment of affected patients.

To characterize population-level data associated with transverse myelitis (TM) within the US Veterans Health Administration (VHA).This retrospective review used VHA electronic medical record from 1999 to 2015. We analyzed prevalence, disease characteristics, modified Rankin Scale (mRS) scores, and mortality data in patients with TM based on the 2002 Diagnostic Criteria.We identified 4,084 patients with an International Classification of Diseases (ICD) code consistent with TM and confirmed the diagnosis in 1,001 individuals (90.7% males, median age 64.2, 67.7% Caucasian, and 31.4% smokers). The point prevalence was 7.86 cases per 100,000 people. Less than half of the cohort underwent a lumbar puncture, whereas only 31.8% had a final, disease-associated TM diagnosis. The median mRS score at symptom onset was 3 (interquartile range 2-4), which remained unchanged at follow-up, although less than half (43.2%) of the patients received corticosteroids, IVIg, or plasma exchange. Approximately one-quarter of patients (24.3%) had longitudinal extensive TM, which was associated with poorer outcomes (p = 0.002). A total of 108 patients (10.8%) died during our review (94.4% males, median age 66.5%, and 70.4% Caucasian). Mortality was associated with a higher mRS score at follow-up (OR 1.94, 95% CI, 1.57-2.40) and tobacco use (OR 1.87, 95% CI, 1.17-2.99).This national TM review highlights the relatively high prevalence of TM in a modern cohort. It also underscores the importance of a precise and thorough workup in this disabling disorder to ensure diagnostic precision and ensure optimal management for patients with TM in the future.

To determine the effect of paraneoplastic anti-Ma2 antibodies on neurons in organotypic rat brain cultures.

To characterize the clinical findings associated with mortality in myelopathy and transverse myelitis (TM) patients evaluated at the National Veterans Affairs Health Administration (VA).