Diffusivity anisotropy signature of the slowly expanding lesions predicts progression independent of relapse activity in multiple sclerosis.

Background: Slowly expanding lesions (SELs) in multiple sclerosis (MS) are markers of chronic active lesions and seem to trigger disability. This study aimed to analyse spatial features of SELs through diffusion MRI and their clinical impact on progression independent of relapse activity (PIRA).

Methods: An observational study of MS subjects prospectively followed since 2011; inclusion required at least three longitudinal T1/T2-weighted and diffusion-weighted MRIs.

Clinical Characterization and Long-Term Outcome in Children and Adults With Anti-AMPA Receptor Encephalitis.

Background And Objectives: Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (anti-AMPAR) encephalitis manifests as limbic encephalitis in adults and is often associated with cancer. Although some reports suggest that it may occur in children, the clinical features in this population, as well as the prognostic factors and long-term outcomes in children and adults, are unknown.

Methods: We performed a retrospective, international collaborative study of patients with anti-AMPAR encephalitis.

Autologous Hematopoietic Stem Cell Transplantation for Paraneoplastic Cerebellar Degeneration.

Background And Objectives: The aim of this study was to describe 2 patients with paraneoplastic cerebellar degeneration (PCD) treated with autologous hematopoietic stem cell transplantation (AHSCT).

Methods: Off-label AHSCT was performed at Hospital Clinic Barcelona, including stem cell mobilization (cyclophosphamide, filgrastim), plasma exchange, and a nonmyeloablative regimen (cyclophosphamide, antithymocyte globulin, rituximab [RTX]).

Results: A 38-year-old woman developed anti-Yo-associated PCD 17 months after treatment of a gynecologic cancer (without evidence of tumor recurrence).

Clinical Features of Children With MOG-IgG Who Fulfill Criteria of Multiple Sclerosis and Overlapping Disorders.

Objectives: The aim of this study was to report the clinical features, disease-modifying treatment (DMT) response, and outcomes of children with MOG-IgG who fulfill the 2017 McDonald criteria for multiple sclerosis (MS).

Methods: This prospective observational study included children (<18 years) with a suspected acquired demyelinating syndrome (ADS) whose serum or CSF was positive for MOG-IgG, who met the indicated MS criteria, and who had ≥1 year of clinical follow-up. MOG-IgG was tested using live cell-based assays.

Assessing Commercial Tissue-Based Assays for Autoimmune Neurologic Disorders (I): Antibodies to Intracellular Antigens.

Background And Objectives: Current strategies to detect autoantibodies against intracellular neural antigens (IC-Abs) include tissue-based assays (TBAs) alongside line blots or cell-based assays (CBAs). Many clinical laboratories use commercially available TBAs as a screening test, but their diagnostic yield has not been assessed. We determined the performance of 2 commercial TBAs in detecting IC-Abs.

Assessing Commercial Tissue-Based Assays for Autoimmune Neurologic Disorders (II): Antibodies to Surface Antigens.

Background And Objectives: Detecting neural surface antibodies (NSAbs) is essential for diagnosing autoimmune encephalitis. The recommended diagnostic strategy involves initial screening with tissue-based assays (TBAs), followed by confirmation with cell-based assays (CBAs). While specialized centers use in-house TBAs, many clinical laboratories depend on commercial TBAs, whose accuracy is yet to be fully assessed.

Differential diagnosis and comparison of diagnostic algorithms in children and adolescents with autoimmune encephalitis in Spain: a prospective cohort study and retrospective analysis.

Background: The usefulness of current diagnostic approaches in children with suspected autoimmune encephalitis is unknown. We aimed to assess the diagnosis of autoimmune encephalitis in clinical practice and to compare the performance of two international diagnostic algorithms (one intended for patients of any age [general], the other intended for paediatric patients), with particular emphasis on the evaluation of patients with probable antibody-negative autoimmune encephalitis because this diagnosis suggests that immunotherapy should be continued or escalated but is difficult to establish.

Methods: We did a prospective cohort study that included all patients (<18 years of age) with suspected autoimmune encephalitis recruited at 40 hospitals in Spain whose physicians provided clinical information every 6 months for 2 years or more.

Investigating the 2023 MOGAD Criteria in Children and Adults With MOG-Antibody Positivity Within and Outside Attacks.

Background And Objectives: The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children.

Methods: This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MOG-immunoglobulin G (IgG) positive at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic of Barcelona (Spain). Exclusion criteria were lack of clinical information and follow-up <1 year, and serum unavailable for antibody testing.

CD19-Directed CAR T-Cells in a Patient With Refractory MOGAD: Clinical and Immunologic Follow-Up for 1 Year.

Objectives: In MOG antibody-associated disease (MOGAD), relapse prevention and the treatment approach to refractory symptoms are unknown. We report a patient with refractory MOGAD treated with CD19-directed CAR T-cells.

Methods: CD19-directed CAR T-cells (ARI-0001) were produced in-house by lentiviral transduction of autologous fresh leukapheresis and infused after a conventional lymphodepleting regimen.

MOG Antibodies Restricted to CSF in Children With Inflammatory CNS Disorders.

Objectives: To assess the clinical significance of myelin oligodendrocyte glycoprotein antibodies (MOG-abs) restricted to CSF in children with inflammatory CNS disorders.

Methods: Patients included 760 children (younger than 18 years) from 3 multicenter prospective cohort studies: (A) acquired demyelinating syndromes, including acute disseminated encephalomyelitis (ADEM); (B) non-ADEM encephalitis; and (C) noninflammatory neurologic disorders. For all cases, paired serum/CSF samples were systematically examined using brain immunohistochemistry and live cell-based assays.

Neurological, psychiatric, and sleep investigations after treatment of anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis in Spain: a prospective cohort study.

Background: Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis is an autoimmune disorder that can be treated with immunotherapy, but the symptoms that remain after treatment have not been well described. We aimed to characterise the clinical features of patients with anti-LGI1 encephalitis for 1 year starting within the first year after initial immunotherapy.

Methods: For this prospective cohort study, we recruited patients with anti-LGI1 encephalitis as soon as possible after they had received conventional immunotherapy for initial symptoms; patients were recruited from 21 hospitals in Spain.

Excellent response to anti-CD38 therapy with daratumumab in a patient with severe refractory CANOMAD.

Background: Intravenous immunoglobulin (IVIG) and rituximab are considered the first-line and second-line treatments for Chronic Ataxic Neuropathy and Ophthalmoplegia with IgM-paraprotein, cold Agglutinins, and anti-Disialosyl antibodies (CANOMAD), with an overall clinical response around 50%. New anti-CD38 daratumumab, targeting long-lived plasma cells, has been reported as a promising therapy for treatment-refractory antibody-mediated disorders. We report the first case of a severe refractory CANOMAD, successfully treated with daratumumab.

Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study.

Background: Neurological immune-related adverse events associated with immune checkpoint inhibitors can have several clinical manifestations, but the syndromes and prognostic factors are still not well known. We aimed to characterise and group the clinical features, with a special focus in patients presenting with encephalopathy, and to identify predictors of response to therapy and survival.

Methods: This retrospective observational study included patients with neurological immune-related adverse events from 20 hospitals in Spain whose clinical information, serum samples, and CSF samples were studied at Hospital Clinic de Barcelona, Barcelona, Spain.

Antibody Investigations in 2,750 Children With Suspected Autoimmune Encephalitis.

Objectives: To assess the frequency and types of neuronal and glial (neural) antibodies in children with suspected autoimmune encephalitis (AE).

Methods: Patients younger than 18 years with suspected AE other than acute disseminated encephalomyelitis, whose serum or CSF samples were examined in our center between January 1, 2011, and April 30, 2022, were included in this study. Samples were systematically examined using brain immunohistochemistry; positive immunostaining was further investigated with cell-based assays (CBA), immunoblot, or live neuronal immunofluorescence.

mRNA COVID-19 Vaccination Does Not Exacerbate Symptoms or Trigger Neural Antibody Responses in Multiple Sclerosis.

Background And Objective: In people with multiple sclerosis (pwMS), concern for potential disease exacerbation or triggering of other autoimmune disorders contributes to vaccine hesitancy. We assessed the humoral and T-cell responses to SARS-CoV-2 after mRNA vaccination, changes in disease activity, and development of antibodies against central or peripheral nervous system antigens.

Methods: This was a prospective 1-year longitudinal observational study of pwMS and a control group of patients with other inflammatory neurologic disorders (OIND) who received an mRNA vaccine.

Neurologic complications in herpes simplex encephalitis: clinical, immunological and genetic studies.

Patients with herpes simplex virus (HSV) encephalitis (HSE) often develop neuronal autoantibody-associated encephalitis (AE) post-infection. Risk factors of AE are unknown. We tested the hypotheses that predisposition for AE post-HSE may be involved, including genetic variants at specific loci, human leucocyte (HLA) haplotypes, or the blood innate immune response against HSV, including type I interferon (IFN) immunity.

Frequency and Referral Patterns of Neural Antibody Studies During the COVID-19 Pandemic: Experience From an Autoimmune Neurology Center.

Objective: To determine whether the frequency of paraneoplastic or autoimmune encephalitis antibodies examined in a referral center changed during the COVID-19 pandemic.

Methods: The number of patients who tested positive for neuronal or glial (neural) antibodies during pre-COVID-19 (2017-2019) and COVID-19 (2020-2021) periods was compared. The techniques used for antibody testing did not change during these periods and included a comprehensive evaluation of cell-surface and intracellular neural antibodies.

The diagnosis of anti-LGI1 encephalitis varies with the type of immunodetection assay and sample examined.

Detection of Leucine-rich glioma inactivated 1 (LGI1) antibodies in patients with suspected autoimmune encephalitis is important for diagnostic confirmation and prompt implementation of immunomodulatory treatment. However, the clinical laboratory diagnosis can be challenging. Previous reports have suggested that the type of test and patient's sample (serum or CSF) have different clinical performances, however, there are no studies comparing different diagnostic tests on paired serum/CSF samples of patients with anti-LGI1 encephalitis.

Thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in the United Kingdom.

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Using data from the United Kingdom, here we compare observed rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 and infection with SARS-CoV-2 with background (expected) rates in the general population. First and second dose cohorts for ChAdOx1 or BNT162b2 between 8 December 2020 and 2 May 2021 in the United Kingdom were identified.

CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome.

Patients with coronavirus disease 2019 (COVID-19) frequently develop acute encephalopathy and encephalitis, but whether these complications are the result from viral-induced cytokine storm syndrome or anti-neural autoimmunity is still unclear. In this study, we aimed to evaluate the diagnostic and prognostic role of CSF and serum biomarkers of inflammation (a wide array of cytokines, antibodies against neural antigens, and IgG oligoclonal bands), and neuroaxonal damage (14-3-3 protein and neurofilament light [NfL]) in patients with acute COVID-19 and associated neurologic manifestations (neuro-COVID). We prospectively included 60 hospitalized neuro-COVID patients, 25 (42%) of them with encephalopathy and 14 (23%) with encephalitis, and followed them for 18 months.

Association between covid-19 vaccination, SARS-CoV-2 infection, and risk of immune mediated neurological events: population based cohort and self-controlled case series analysis.

Objective: To study the association between covid-19 vaccines, SARS-CoV-2 infection, and risk of immune mediated neurological events.

Design: Population based historical rate comparison study and self-controlled case series analysis.

Setting: Primary care records from the United Kingdom, and primary care records from Spain linked to hospital data.