Diagnostic Value of the "Insular Knife-Cut" Sign in Patients With Suspected Herpes Simplex Virus Encephalitis.

Background: The "insular knife-cut" sign is a sharp demarcation between hyperintense insular lesions on fluid-attenuated inversion recovery axial images and the basal ganglia, detected on brain MRI. This sign has been associated with herpes simplex virus encephalitis (HSVE); however, its specificity remains unknown. We assessed the frequency and specificity of the insular knife-cut sign in a real-life cohort of patients with suspected HSVE.

Real-Life Evaluation of the MOGAD Diagnostic Criteria: Application Challenges and Discrepancies.

Background And Objectives: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) international panel criteria have been recently proposed to guide MOGAD diagnosis. The aim of this study was to evaluate the criteria performance and assess the discrepancies in their application in the clinical practice in an Italian multicenter cohort and to discuss some challenging aspects.

Methods: We applied the 2023 MOGAD criteria to patients who tested MOG-Abs positive on cell-based assays and were retrospectively recruited from 29 centers.

Peripheral blood mononuclear cell secretome from patients with autoimmune encephalitis promotes seizures in vitro.

Objective: Autoimmune encephalitis (AE) is characterized by inflammatory processes in the central nervous system and frequently presents with seizures. Even though an ictogenic potential has been shown for some antibodies against neuronal surface antigens (NSAbs), AE pathophysiology is complex, and NSAbs-independent mechanisms are likely to contribute to seizures. We investigated whether the secretome released by peripheral blood mononuclear cells (PBMCs) from AE patients contributes to seizure generation independently of NSAbs.

Use of Corticosteroids in Myasthenia Gravis: Expert Opinion for Daily Management.

Introduction: Myasthenia gravis, a rare autoimmune disorder characterized by muscle weakness and fatigue, it is a mainly B-cell mediated condition with antibodies directed against the acetylcholine receptor or functionally related molecules at the neuromuscular junction. Corticosteroids are still the most used treatment, as they are cheap and characterized by a rapid response. However, their long-term administration is associated with frequent and often severe side effects.

Adoptive JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy: Experience from Two Italian Centers.

Unlabelled: Progressive multifocal leukoencephalopathy (PML) is a rare but fatal disease caused by John Cunningham virus (JCV) in immunocompromised individuals, with no effective antiviral treatment currently available. This study aimed to evaluate the feasibility of adoptive JCV-specific T lymphocyte therapy in patients with PML.

Methods: Nineteen patients meeting the 2013 consensus criteria for "definite PML" were included, and JCV-specific T lymphocytes expanded from autologous or allogeneic peripheral blood mononuclear cells (PBMCs) using JCV antigen-derived peptides were administered.

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.

LC-MS/MS-Based Determination of Ambroxol in Human Plasma and Cerebrospinal Fluid: Validation and Applicability in a Phase II Study on GBA-Associated Parkinson's Disease Patients.

Heterozygous mutations in the gene, encoding the enzyme glucocerebrosidase (GCase), are major risk factors for Parkinson's Disease (PD). Ambroxol, a small chaperone originally used as a mucolytic agent, has been shown to cross the blood-brain barrier, enhance GCase activity, and reduce α-synuclein levels, making it a promising therapeutic candidate for disease-modifying effects in GBA1-associated PD (GBA1-PD). This study aimed to develop a method to quantify ambroxol levels in human plasma and cerebrospinal fluid (CSF) using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Serum Autoantibody Titers and Neurofilament Light Chain Levels in CASPR2/LGI1 Encephalitis: A Longitudinal Study.

Background And Objectives: Autoantibodies against contactin-associated protein-like 2 (CASPR2-IgG) and leucine-rich glioma inactivated 1 protein (LGI1-IgG) identify a subgroup of autoimmune encephalitis (AE). Up to 65% of patients with LGI1/CASPR2 AE show cognitive sequelae that are unpredictable at onset. We aimed to assess the clinical relevance of serum autoantibody titers and neurofilament light chain (NfL) levels as biomarkers in CASPR2/LGI1 AE.

Long-Term Effectiveness and Safety of Rituximab in Neuromyelitis Optica Spectrum Disorder: A 5-Year Observational Study.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a severely disabling autoimmune disease that predominantly impacts the optic nerves and spinal cord. It is often linked to immunoglobulin G (IgG) antibodies targeting the aquaporin-4 water channel (AQP4-IgG). Rituximab, which depletes CD20-positive B cells, is effective in reducing the frequency of NMOSD relapses.

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.

Oligoclonal IgM band patterns in multiple sclerosis: A two-center study.

Background: Cerebrospinal fluid (CSF) oligoclonal IgM bands (OCMBs) have been suggested as prognostic biomarkers in MS, but serum OCMBs meaning is still uncertain.

Objectives: We aimed to assess frequency and clinical relevance of all OCMB patterns.

Methods: In this retrospective cohort study, 136 paired sera-CSF from consecutive persons with MS (pwMS) were tested in 2 centers for OCMBs using isoelectric focusing-immunoblotting.

Retrograde Amnesia in LGI1 and CASPR2 Limbic Encephalitis: Two Case Reports and a Systematic Literature Review.

Background: Both anterograde and retrograde amnesia can typically co-occur in limbic autoimmune encephalitis (LAE), including the forms associated with antibodies to CASPR2/LGI1, two protein complexed with the voltage-gated potassium channel (VGKC). However, isolated retrograde amnesia is very rare, and it has never been described in LAE.

Methods: We report two patients with CASPR2 LAE who showed isolated retrograde amnesia, without other significant cognitive impairments.

Chalcone Synthesis by Green Claisen-Schmidt Reaction in Cationic and Nonionic Micellar Media.

In this paper, micellar-mediated synthesis of chalcones was explored. After optimization of the reaction conditions, the cationic surfactant CTAB and the nonionic one, Tween 80, were taken into consideration. Both surfactants were used to study the scope of Claisen-Schmidt reactants, and a wide scope on both aromatic aldehydes and methyl ketones was explored, obtaining from good to very good yields in most cases and thus demonstrating that the chalcones can be proficiently synthesized in micellar solutions with a wide functional group tolerability.

Elevated Kappa Index in the Absence of Cerebrospinal Fluid IgG Oligoclonal Bands: Contribution of Intrathecal IgM and IgA Synthesis.

The kappa index is a well-established marker of intrathecal synthesis (IS) of immunoglobulin (Ig). Routinely used for diagnostic aims, IgG IS, which can be assessed quantitatively (ad hoc formulas) or qualitatively (oligoclonal bands, OCBs), may fail in detecting a humoral immune response within the central nervous system (CNS). The main aim of this study was to evaluate the kappa index for its ability to detect the presence of CNS humoral immunity and to associate it with a distinct group of disorders, in the absence of IgG IS/OCBs.

Conformational Antibodies to Proteolipid Protein-1 and Its Peripheral Isoform DM20 in Patients With CNS Autoimmune Demyelinating Disorders.

Background And Objectives: Antibodies to proteolipid protein-1 (PLP1-IgG), a major central myelin protein also expressed in the peripheral nervous system (PNS) as the isoform DM20, have been previously identified mostly in patients with multiple sclerosis (MS), with unclear clinical implications. However, most studies relied on nonconformational immunoassays and included few patients with non-MS CNS autoimmune demyelinating disorders (ADDs). We aimed to investigate conformational PLP1-IgG in the whole ADD spectrum.

Anti-Collapsin Response Mediator Protein 5(CV2/CRMP5) and Anti-Glutamic Acid Decarboxylase (GAD) Antibodies-Mediated Encephalopathy Mimicking Atypical Parkinsonism.

: Paraneoplastic neurological syndromes (PNSs) are rare conditions characterized by immune-mediated pathogenesis, frequently associated with the presence of a neoplasm. Although a single antineuronal antibody mediates a specific syndrome, atypical manifestations mediated by the same antibody have been described. : The aim of this study was to report on an atypical case of PNS with dual positivity for anti-GAD65 and anti-CRMP5/CV2 antibodies, simultaneously characterized by cognitive decline associated with progressive ataxia and parkinsonism.

Protective Coating for Stable Cycling of Li-Metal Batteries Based on Cellulose and Single-Ion Conducting Polymer.

The thermodynamically unstable interface between metallic lithium and electrolyte poses a major problem for the massive commercialization of Li-metal batteries. In this study, we propose the use of a multicomponent protective coating based on cellulose modified with dimethylthexylsilyl group (TDMSC), single-ion conducting polymer P(LiMTFSI), and LiNO (TDMSC-P(LiMTFSI)-LiNO, namely PTL). The coating shows its positive effect by increasing the Coulombic efficiency in Li || Cu cells from 95.

Unravelling the Acute, Chronic and Steroid-Refractory Management of High-Grade Neurological Immune-Related Adverse Events: A Call to Action.

Rare side effects of immune-checkpoint inhibitors (ICIs) are known as neurological immune-related adverse events (n-irAEs). Typically, n-irAEs affect the peripheral nervous system, primarily presenting as myositis, polyradiculoneuropathy, or cranial neuropathy. Less commonly, they impact the central nervous system, resulting in encephalitis, meningitis, or myelitis.

Kappa index in the diagnostic work-up of autoimmune encephalitis.

Background: The presence of inflammatory changes in the cerebrospinal fluid (CSF), including immunoglobulin intrathecal synthesis (IS), can support the diagnosis of autoimmune encephalitis (AE) and allow prompt treatment. The main aim of our study was to calculate the Kappa index as a marker of IS, in patients with AE.

Methods: Charts of patients undergoing a diagnostic work-up for suspected AE between 2009 and 2023 were reviewed and the Graus criteria applied.

Clinical, prognostic and pathophysiological implications of MOG-IgG detection in the CSF: the importance of intrathecal MOG-IgG synthesis.

Background: Cerebrospinal fluid myelin oligodendrocyte glycoprotein IgG (CSF MOG-IgG) are found in a proportion of patients with MOG antibody-associated disorder (MOGAD) and have been associated with severe disease presentations. However, most studies did not systematically investigate the role of MOG-IgG intrathecal synthesis (ITS).

Methods: We retrospectively studied 960 consecutive patients with paired serum and CSF samples screened for MOG-IgG using a live cell-based assays.