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).

Brain metabolite levels in the post-acute stage of anti-NMDA receptor encephalitis and schizophrenia: a longitudinal case-control study.

Background: In-vivo assessment of glutamatergic metabolites in patients with anti-NMDA receptor (NMDAR) encephalitis compared to schizophrenia may help understand the pathophysiology of both conditions.

Methods: Twenty-four-month prospective case-control study including participants with anti-NMDAR encephalitis during the post-acute stage aged 12 to 60 years old, and age and sex-matched individuals with schizophrenia and healthy controls (HC). Single-voxel magnetic resonance spectroscopy was used to estimate brain concentrations of glutamatergic metabolites, myo-inositol and N-acetylaspartate in the left dorso-medial prefrontal region (dmPF) and medial temporal lobe.

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.

Autoimmune Encephalitis.

Autoimmune encephalitides (AE) constitute a broad group of inflammatory brain disorders characterized by prominent neuropsychiatric symptoms, frequently in association with autoantibodies against neural (neuronal or glial) antigens. The most frequent AE are anti-NMDA receptor encephalitis, acute disseminated encephalomyelitis (associated with MOG antibodies in 60% of patients), and limbic encephalitis (with several immunologic subtypes, anti-LGI1 encephalitis being the most frequent). The first 2 predominantly affect children and young adults, whereas limbic encephalitis usually affects patients older than 50 years.

Neuro-immunobiology and treatment assessment in a mouse model of anti-NMDAR encephalitis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a disorder mediated by autoantibodies against the GluN1 subunit of NMDAR. It occurs with severe neuropsychiatric symptoms that often improve with immunotherapy. Clinical studies and animal models based on patients' antibody transfer or NMDAR immunization suggest that the autoantibodies play a major pathogenic role.

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.

Neuropathological spectrum of anti-IgLON5 disease and stages of brainstem tau pathology: updated neuropathological research criteria of the disease-related tauopathy.

Anti-IgLON5 disease is a unique condition that bridges autoimmunity and neurodegeneration. Since its initial description 10 years ago, an increasing number of autopsies has led to the observation of a broader spectrum of neuropathologies underlying a particular constellation of clinical symptoms. In this study, we describe the neuropathological findings in 22 patients with anti-IgLON5 disease from 9 different European centers.

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.

Electroconvulsive therapy in N-methyl-d-aspartate receptor encephalitis: A retrospective cohort and scoping review of literature.

Neuropsychiatric symptoms in N-methyl-d-aspartate receptor encephalitis (NMDARE) have led some to pursue empiric trials of electroconvulsive therapy (ECT). A scoping review identified 39 patients diagnosed with NMDARE undergoing ECT. Separately, a retrospective cohort was reviewed to characterize 21 patients.

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.

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.

Searching for Neuronal Antibodies in Psychiatric Diseases: Uncertain Findings and Implications.

In recent years, neurology and psychiatry journals have been inundated with reports on individual symptoms of autoimmune encephalitis (AE) that are described as distinct entities such as autoimmune psychosis, obsessive-compulsive disorders, or depression. It is unquestionable that for AE the demonstration of antibodies against neuronal-surface proteins is intrinsically linked to distinct disorders (some defining new diseases) that are usually treatment-responsive and associate with comorbidities that vary according to the antigen. By contrast, for psychiatric diseases, the apparent detection of antibodies has not defined any disorder or affected the diagnosis and treatment of patients.

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.

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.

Neurofilament Light Chain Levels in Anti-NMDAR Encephalitis and Primary Psychiatric Psychosis.

Background And Objectives: An important challenge in diagnosing anti-NMDA receptor (NMDAR) encephalitis (NMDARe) is differentiating it from a first episode of psychosis (FEP) caused by a psychiatric disease (pFEP). CSF antibody testing distinguishes these diseases, but spinal taps are difficult to obtain in psychiatric facilities. A separate problem is the lack of biomarkers of NMDARe severity and outcome.

No Effects of Meteorological Factors on the SARS-CoV-2 Infection Fatality Rate.

Objective: Previous studies have shown that meteorological factors may increase COVID-19 mortality, likely due to the increased transmission of the virus. However, this could also be related to an increased infection fatality rate (IFR). We investigated the association between meteorological factors (temperature, humidity, solar irradiance, pressure, wind, precipitation, cloud coverage) and IFR across Spanish provinces ( = 52) during the first wave of the pandemic (weeks 10-16 of 2020).