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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. CSF and serum were tested with TBAs and CBAs. Data on clinical presentation, complementary investigation, and treatment were compiled. Seasonality and predictors of AIE in adult and pediatric populations were analyzed. Results: Of the 564 patients, 145 (25.7%) were confirmed as seropositive, 69 (12.23%) were seronegative according to Graus, and 58% received immunotherapy. The median delay to diagnosis confirmation was 5.97 ± 10.3 months. No seasonality variation was observed after 55 months of enrolment. The following antibodies were found: anti-NMDAR (n=79, 54%), anti-MOG (n=14, 9%), anti-LGI1(n=12, 8%), anti-GAD (n=11, 7%), anti-GlyR (n=7, 4%), anti-Caspr2 (n=6, 4%), anti-AMPAR (n=4, 2%), anti-GABA-BR (n=4, 2%), anti-GABA-AR (n=2, 1%), anti-IgLON5 (n=1, 1%), and others (n=5, 3%). Predictors of seropositive AIE in the pediatric population (n=42) were decreased level of consciousness (p=0.04), and chorea (p=0.002). Among adults (n=103), predictors of seropositive AIE were movement disorders (p=0.0001), seizures (p=0.0001), autonomic instability (p=0.026), and memory impairment (p=0.001). Conclusion: Most common antibodies in Brazilian patients are anti-NMDAR, followed by anti-MOG and anti-LGI1. Only 26% of the possible AIE patients harbor antibodies, and 12% were seronegative AIE. Patients had a 6-month delay in diagnosis and no seasonality was found. Findings highlight the barriers to treating AIE in developing countries and indicate an opportunity for cost-effect analysis. In this scenario, some clinical manifestations help predict seropositive AIE such as decreased level of consciousness, chorea, and dystonia among children, and movement disorders and memory impairment among adults.

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Relapsing-remitting multiple sclerosis (RRMS) is an autoimmune neurological disease and is the most common subtype of MS. In addition, it is associated with the development of depression and anxiety. To date, depressive- and anxiety-like behaviours were only studied using models of progressive MS, which causes severe motor alterations. Thus, we sought to standardise the depressive and anxiety-like behaviours in an RRMS model induced by experimental autoimmune encephalomyelitis (RR-EAE) in mice. The RR-EAE model was induced in C57BL/6 female mice using myelin oligodendrocyte glycoprotein (MOG35-55) antigen and Quillaja saponin (Quil A) as an adjuvant. The immunisation of RR-EAE did not induce locomotor alteration but caused relapsing-remitting induction of clinical scores in mice until 35 post-immunization (p.i.). Also, increased levels of tumour necrosis factor alpha (TNF-α), astrocyte marker (GFAP), and microglial markers (IBA-1) were detected in the prefrontal cortex at 35 p.i. of RR-EAE. In the open field test, RR-EAE mice showed decreased time spent at the centre and sniffing behaviour (at days 21 and 34 p.i.). Also, on day 35 p.i. the RR-EAE group spent less time in the open arms and had decreased open-arm entries compared to control mice in the elevated plus maze (EPM) test, confirming the anxiety-like behaviour. At day 36° p.i. in the tail suspension test, mice showed depression-like behaviour with decreased latency time and increased immobility time. Thus, the RR-EAE model mimics the neuroinflammatory and behavioural features of the RRMS, including depression- and anxiety-like symptoms.

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BACKGROUND: Anti-Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Associated Disease (MOGAD) is an emerging disorder recognized as a clinical entity distinct from Multiple Sclerosis and Aquaporin-4-positive Neuromyelitis Optica Spectrum Disorders (NMOSD-AQP4+), and its phenotypic spectrum continues to expand. Most information about its clinical course has emerged from retrospective studies, and treatment response both in acute and chronic-relapsing disease is still limited. We aimed to describe the clinical and paraclinical characteristics of monophasic and relapsing, paediatric and adult patients with MOGAD under regular clinical care in Chile, highlighting some challenging cases that are far from being considered benign. METHODS: Observational, retrospective, and prospective longitudinal multicentre study including patients with positive serum MOG-IgG assessed by cell-based assay. RESULTS: We include 35 patients, 71% women, median age at onset 30 years (range 1-68), 23% had paediatric onset, with a median disease-duration 24 months (range 12-348). In the whole cohort, the most frequent symptoms at onset were isolated optic neuritis (ON) (34%) and myelitis (22%). Encephalitis with seizures or encephalomyelitis was the most common presentation in paediatric-onset patients 75% (n = 6), compared to 11% (n = 3) of the adult-onset patients (p < 0.001). A relapsing course was observed in 34%, these patients were younger (25 vs. 34 years, p = 0.004) and with a longer disease duration (64 vs. 6 months, p = 0.004) compared to monophasic patients. Two patients developed encephalitis with seizures/status epilepticus, with concomitant positive CSF anti-NMDAR-IgG. Chronic immunotherapy was ever prescribed in 77%, the most frequent was rituximab (35%). Relapses under chronic immunotherapy occurred in 5/27 patients (18.5%), two of them under rituximab, one paediatric patient who started combined therapy with monthly IVIG and one adult patient that switched to satralizumab plus mycophenolate. The median EDSS at the last follow-up was 1.5 (range 0-6.0). CONCLUSION: In Chile, patients with MOGAD exhibit a wide spectrum of clinical presentations at disease onset and during relapses. Close monitoring is needed, particularly in younger patients with short follow-up periods.

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Current pharmacological therapies against demyelinating diseases are not quite satisfactory to promote remyelination. Epidermal growth factor (EGF) can expand the population of oligodendrocyte precursor cells (OPCs) that may help with the remyelination process, but its delivery into the injured tissue is still a biomedical challenge. Gold nanoparticles (GNPs) may be a useful tool for drug delivery into the brain. To evaluate remyelination in the septal nucleus, we administered intracerebral GNPs coupled with EGF (EGF-GNPs). C57BL6/J mice were demyelinated with 0.4% cuprizone (CPZ) and divided into several groups: Sham, Ctrl, GNPs, EGF, and EGF-GNPs. We evaluated the remyelination process at two time-points: 2 weeks and 3 weeks post-injection (WPI) of each treatment. We used the rotarod for evaluating motor coordination. Then, we did a Western blot analysis myelin-associated proteins: CNPase, MAG, MOG, and MBP. EGF-GNPs increase the expression of CNPase, MAG, and MOG at 2 WPI. At 3 WPI, we found that the EGF-GNPs treatment improves motor coordination and increases MAG, MOG, and MBP. EGF-GNPs enhance the expression of myelin-associated proteins and improve the motor coordination in mice. Thus, EGF-associated GNPs may be a promising pharmacological vehicle for delivering long-lasting drugs into the brain.

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Here, a study of NMOSD in Central America and the Caribbean with a multinational collaborative, multicentric and descriptive approach involving 25 institutions from 9 countries is presented. Demographics, clinical manifestations, expanded disability scale status (EDSS), brain and spinal cord MRI, serological anti-AQP4-IgG and anti-MOG-IgG antibodies, and cerebrospinal fluid (CSF) oligoclonal bands were included. A central serological repository utilized the cell-based assay. The specimens outside of this network employed diverse methodologies. Data were collected at the Gorgas Commemorative Institute of Health Studies (ICGES), Panama, and included 186 subjects, of which 84% were females (sex ratio of 5.6:1). Mestizos constituted 72% of the study group. The median age was 42.5 years (IQR: 32.0-52.0). Associated autoimmune diseases (8.1%) were myasthenia gravis, Sjögren's syndrome and systemic lupus erythematosus. The most common manifestation was optic neuritis-transverse myelitis (42.5%). A relapsing course was described in 72.3% of cases. EDSS scores of 0-3.5 were reported in 57.2% of cases and higher than 7.0 in 14.5%. Positive anti-AQP4-IgG antibody occurred in 59.8% and anti-MOG-IgG antibody in 11.5% of individuals. Antibody testing was lacking for 13.4% of patients. The estimated crude prevalence of NMOSD from Panama and the Dominican Republic was 1.62/100,000 (incidence of 0.08-0.41) and 0.73/100,000 (incidence 0.02-0.14), respectively. This multinational study contributes additional insights and data on the understanding of NMOSD in this Latin American region.

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INTRODUCTION: Myelin oligodendrocyte glycoprotein (MOG) is a nervous system protein expressed by oligodendrocytes to constitute the myelin sheath. Autoantibodies against MOG have been widely described in neurological and autoimmune diseases such as MOG-IgG-associated disorder (MOGAD).Although underlying mechanisms have not yet been understood, an overlap of MOGAD and Systemic Lupus Erythematosus (SLE) has been shown in the literature. OBJECTIVES: The aim of this systematic review was to assess the possible correlations between MOGAD and SLE based on reported features found in the literature that support the association of the two. METHODS: A keyword-based literature search was conducted, applying a ten-year filter and using the following key-words: "MOG autoantibody-associated disease and Systemic Lupus Erythematosus"; "MOG and Systemic Lupus Erythematosus" "Anti-MOG and Lupus"; "MOG and SLE"; "MOG and LUPUS" on MEDLINE/PUBMED, ScienceDirect, SciELO, LILACS and Cochrane; and "MOG antibody-associated disease and SLE" on Google Scholar. RESULTS: Eleven publications reporting on the MOGAD and SLE correlation were included in qualitative synthesis: animal experiment (1), cross-sectional (3), prospective (2), retrospective (1), non-systematic review (3), and case report (1) studies. CONCLUSION: Not much is known about the connection between MOG-IgG-associated disorder and SLE. Unfortunately, only observational studies have been conducted in humans so far, providing us with limited data. While MOGAD features have been reported to develop in SLE patients, this is not an universal finding. In fact, many different issues impair these results, making it difficult to match the findings of different studies.

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Acute disseminated encephalomyelitis (ADEM) is an immune-mediated central nervous system (CNS) disorder, characterized by polyfocal symptoms, encephalopathy and typical magnetic resonance imaging (MRI) findings, that especially affects young children. Advances in understanding CNS neuroimmune disorders as well as the association of myelin oligodendrocyte glycoprotein antibody (MOG-Ab) with both monophasic and recurrent forms of ADEM have led to new insights into its definition, management and outcome. In this review, we aim to provide an update based on current epidemiologic, clinical, radiological and immunopathological aspects and clinical outcome of ADEM.

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Neurocysticercosis (NC) presents two broad clinical entities: extraparenchymal (EP-NC) and parenchymal (P-NC). Using ELISA methodology, we demonstrate autoantibodies to tubulin and the Major oligodendrocyte glycoprotein (MOG) in the CSF of most, but not all, EP-NC samples. Levels of these autoantibodies were considerably reduced or absent in the P-NC samples. There was a striking correlation between levels of anti-tubulin and anti-MOG, and the significant correlation between the levels of autoantibodies and cellularity in the CSF, suggests that stimulation of the autoantibody response may be a function of cerebral inflammation. A hypothetical model to describe the pathogenesis of EP-NC is presented.

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Neuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS) primarily affecting the optic nerves and spinal cord, but also involving other regions of the CNS including the area postrema, periaqueductal gray matter, and hypothalamus. Knowledge related to pediatric manifestations of NMOSD has grown in recent years, particularly in light of newer information regarding the importance of not only antibodies to aquaporin 4 (AQP4-IgG) but also myelin oligodendrocyte glycoprotein (MOG-IgG) in children manifesting clinically with this syndrome. In this review, we describe the current state of the knowledge related to clinical manifestations, diagnosis, and chronic therapies for children with NMOSD, with emphasis on literature that has been published in the last 5 years. Following the review, we propose recommendations for the assessment/follow up clinical care, and treatment of this population.