Association Between NK Cell Genetic Variants and the Development of Long COVID Associated- and Prepandemic Small Fiber Neuropathy.

Long coronavirus disease 2019 (COVID) (LC) symptoms including pain and autonomic dysfunction are in some patients associated with small-fiber neuropathy (SFN). The pathomechanisms underlying SFN are mostly unclear. Natural killer (NK) cells play a crucial role in immune regulation, viral clearance and nerve metabolism.

Long-Term Follow Up in Anti-Contactin-1 Autoimmune Nodopathy.

Objective: To analyze long-term clinical and biomarker features of anti-contactin-1 (CNTN1) autoimmune nodopathy (AN).

Methods: Patients with anti-CNTN1 autoimmune nodopathy detected in our laboratory from which clinical information was available were included. Clinical features and treatment response were retrospectively collected.

Antibody-Mediated Nodo- and Paranodopathies.

The recent discovery of pathogenic antibodies targeting cell adhesion molecules of the node of Ranvier has prompted efforts to develop a new classification for a subset of antibody-mediated peripheral neuropathies. These autoimmune nodo- and paranodopathies encompass epitopes such as neurofascin 155, neurofascin 186, contactin-1, and contactin-associated protein 1, with a high likelihood of involving additional yet unidentified proteins. So far, the investigation of this subset of patients was primarily focused on adults, with only rare reports of pediatric cases.

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.

Progressive Encephalomyelitis With Rigidity and Myoclonus With Glycine Receptor and GAD65 Antibodies: Case Report and Potential Mechanisms.

Objectives: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder that can be associated with antibodies against surface antigens (glycine receptor (GlyR), dipeptidyl-peptidase-like-protein-6) and intracellular antigens (glutamate decarboxylase (GAD65), amphiphysin).

Methods: We report clinico-pathologic findings of a PERM patient with coexisting GlyR and GAD65 antibodies.

Results: A 75-year-old man presented with myoclonus and pain of the legs, subsequently developed severe motor symptoms, hyperekplexia, a pronounced startle reflex, hallucinations, dysautonomia, and died 10 months after onset despite extensive immunotherapy, symptomatic treatment, and continuous intensive care support.

Single-nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke in male rodents.

Neuroglia critically shape the brain´s response to ischemic stroke. However, their phenotypic heterogeneity impedes a holistic understanding of the cellular composition of the early ischemic lesion. Here we present a single cell resolution transcriptomics dataset of the brain´s acute response to infarction.

HLA dependency and possible clinical relevance of intrathecally synthesized anti-IgLON5 IgG4 in anti-IgLON5 disease.

Background: Anti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance.

Methods: IgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry.

Cell-mediated cytotoxicity within CSF and brain parenchyma in spinal muscular atrophy unaltered by nusinersen treatment.

5q-associated spinal muscular atrophy (SMA) is a motoneuron disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Adaptive immunity may contribute to SMA as described in other motoneuron diseases, yet mechanisms remain elusive. Nusinersen, an antisense treatment, enhances SMN2 expression, benefiting SMA patients.

ARID1B controls transcriptional programs of axon projection in an organoid model of the human corpus callosum.

Mutations in ARID1B, a member of the mSWI/SNF complex, cause severe neurodevelopmental phenotypes with elusive mechanisms in humans. The most common structural abnormality in the brain of ARID1B patients is agenesis of the corpus callosum (ACC), characterized by the absence of an interhemispheric white matter tract that connects distant cortical regions. Here, we find that neurons expressing SATB2, a determinant of callosal projection neuron (CPN) identity, show impaired maturation in ARID1B neural organoids.

Targeting the EGFR pathway: An alternative strategy for the treatment of tuberous sclerosis complex?

Introduction: Tuberous sclerosis complex (TSC) is caused by variants in TSC1/TSC2, leading to constitutive activation of the mammalian target of rapamycin (mTOR) complex 1. Therapy with everolimus has been approved for TSC, but variations in success are frequent. Recently, caudal late interneuron progenitor (CLIP) cells were identified as a common origin of the TSC brain pathologies such as subependymal giant cell astrocytomas (SEGA) and cortical tubers (CT).

Impact of muscle biopsy on the clinical decision-making process in patients with suspected idiopathic inflammatory myopathy.

Background: The significance of muscle biopsy as a diagnostic tool in idiopathic inflammatory myopathies (IIM) remains elusive. We aimed to determine the diagnostic weight that has been given to muscle biopsy in patients with suspected IIM, particularly in terms of clinical diagnosis and therapeutic decisions.

Material And Methods: In this retrospective multicentric study, we analyzed muscle biopsy results of adult patients with suspected IIM referred to a tertiary center between January 1, 2007, and October 31, 2021.

Encephalitis associated with anti-mGluR5 antibodies.

A 30-year-old woman had 5 days of visual hallucinations, nystagmus, memory impairment and mutism. On examination, she was disorientated with reduced attention span, gaze-evoked nystagmus, paratonia and abnormal frontal reflexes. Cerebrospinal fluid (CSF) showed 80 cells, protein 0.

Rituximab treatment in pediatric-onset multiple sclerosis.

Background And Purpose: Rituximab (RTX) is frequently used off-label in multiple sclerosis. However, studies on the risk-benefit profile of RTX in pediatric-onset multiple sclerosis are scarce.

Methods: In this multicenter retrospective cohort study, patients with pediatric-onset multiple sclerosis from Sweden, Austria and Germany, who received RTX treatment were identified by chart review.

New insights into neuropathology and pathogenesis of autoimmune glial fibrillary acidic protein meningoencephalomyelitis.

Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype.

Autoantibody status, neuroradiological and clinical findings in children with acute cerebellitis.

Background: Acute cerebellitis (AC) in children and adolescents is an inflammatory disease of the cerebellum due to viral or bacterial infections but also autoimmune-mediated processes.

Objective: To investigate the frequency of autoantibodies in serum and CSF as well as the neuroradiological features in children with AC.

Material And Methods: Children presenting with symptoms suggestive of AC defined as acute/subacute onset of cerebellar symptoms and MRI evidence of cerebellar inflammation or additional CSF pleocytosis, positive oligoclonal bands (OCBs), and/or presence of autoantibodies in case of negative cerebellar MRI.

The relation between BTK expression and iron accumulation of myeloid cells in multiple sclerosis.

Activation of Bruton's tyrosine kinase (BTK) has been shown to play a crucial role in the proinflammatory response of B cells and myeloid cells upon engagement with B cell, Fc, Toll-like receptor, and distinct chemokine receptors. Previous reports suggest BTK actively contributes to the pathogenesis of multiple sclerosis (MS). The BTK inhibitor Evobrutinib has been shown to reduce the numbers of gadolinium-enhancing lesions and relapses in relapsing-remitting MS patients.

Brazilian autoimmune encephalitis network (BrAIN): antibody profile and clinical characteristics from a multicenter study.

Background: The frequency of antibodies in autoimmune encephalitis (AIE) may vary in different populations, however, data from developing countries are lacking. To describe the clinical profile of AIE in Brazil, and to evaluate seasonality and predictors of AIE in adult and pediatric patients.

Methods: We evaluated patients with possible AIE from 17 centers of the Brazilian Autoimmune Encephalitis Network (BrAIN) between 2018 and 2022.

Exploring the heterogeneous transcriptional response of the CNS to systemic LPS and Poly(I:C).

Peripheral contact to pathogen-associated molecular patterns (PAMPs) evokes a systemic innate immune response which is rapidly relayed to the central nervous system (CNS). The remarkable cellular heterogeneity of the CNS poses a significant challenge to the study of cell type and stimulus dependent responses of neural cells during acute inflammation. Here we utilized single nuclei RNA sequencing (snRNAseq), serum proteome profiling and primary cell culture methods to systematically compare the acute response of the mammalian brain to the bacterial PAMP lipopolysaccharide (LPS) and the viral PAMP polyinosinic:polycytidylic acid (Poly(I:C)), at single cell resolution.