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With the increasing development of medical specialties, an urgent necessity of parallel specialties in the laboratories and nursing fields becomes evident. Immunology is the field of science responsible for the study of defense responses developed by an individual in the face of aggression by microorganisms or foreign particles as well as those coming from the internal environment such as neoplastic cells. Immunology is considered as a young discipline with an spectacular development that took place in the second half of 20th century. From then till date, there have been many important spectacular advances in the area leading to its consolidation as an independent science separate from microbiology. As part of the Immunology Service at the Instituto Nacional de Pediatria (INP), the Short-Stay Immunotherapy Unity (SSI) was established. This unity has been fundamental in ensuring adequate treatment for patients with primary immunodeficiency and autoimmune in the long term. We highlight the roles of the nursing staff of SSI in the area of drug preparation and patient care. [ABSTRACT FROM AUTHOR]

The San Gregorio Formation (Late Oligocene-Early Miocene) is part of the Paleogene and Neogene stratigraphic sequence in La Purísima region, Baja California Sur, Mexico. A borehole from this formation was analyzed with the aim of contributing continental and marine palynomorphs. This paper presents the results concerning to the continental palynomorphs, belonging to bryophyte and pteridophyte spores group. One bryophyte and eight pteridophyte spores were identified to genus level: cf. Camarazonosporites, Cicatricosisporites, Deltoidospora, Granulatisporites, Leptolepidites, Lycopodiacidites, Stereisporites, Undulatisporites and Polypodiisporites. One pteridophyte spore was identified to species level --Lusatisporis dettmannae--, which was the most abundant. We present systematic descriptions of the taxa recorded. These spores are associated to the Cloud Forest vegetation type. [ABSTRACT FROM AUTHOR]

From the San Gregorio Formation (Upper Oligocene-Lower Miocene), Baja California Sur, Mexico, 105.4 meter-deep borehole "B4" was analyzed. Among the continental palynomorphs, four Tubulifloridites taxa, whose botanic affinity is Asteraceae family (Astereae, Eupatorieae and Heliantheae tribes), were recovered and described. The four Tubulifloridites types were classified into three groups according to morphological measures, using k-means cluster analysis. Scanning electron microscope and light photomicrographs were taken. Descriptions complement the contributions made by other authors to this genus, pertaining to the Baja California peninsula during the Paleogene and Neogene and contribute to the geological history of the family. [ABSTRACT FROM AUTHOR]

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. Neural antibody testing to confirm diagnosis of antibody-positive autoimmune encephalitis was done at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic, Barcelona. Patients were classified according to the most probable diagnosis at last follow-up into four prespecified categories. We used multivariable logistic analysis to assess a potential association between immunotherapy and outcome in individuals with probable antibody-negative autoimmune encephalitis. We also did a retrospective analysis of agreement, assessed with the kappa index, between diagnoses made according to the general and paediatric diagnostic algorithms., Findings: Between June 1, 2013, and May 31, 2021, 729 children (mean age 7·1 years [SD 4·9]; 383 boys [53%], 346 girls [47%]) with suspected autoimmune encephalitis were recruited. After a median follow-up of 36 months (IQR 26-60), patients were classified according to their most probable diagnosis: definite autoimmune encephalitis or well defined inflammatory or autoimmune disorders (n=230 [32%]); CNS infections (n=112 [15%]); inflammatory CNS disorders of unknown cause (n=81 [11%], including three (4%) with a novel Klüver-Bucy-like syndrome; and non-inflammatory disorders (n=306 [42%]), which were predominantly epileptic or psychiatric disorders (177 [58%] of 306). Neural antibodies were detected in 150 (65%) of 230 patients who had definite autoimmune encephalitis; 127 (85%) of these 150 individuals had antibodies to the NMDA receptor or myelin oligodendrocyte glycoprotein (MOG). Agreement between algorithms was excellent (kappa index 0·99, 95% CI 0·97-1·00) for the diagnosis of children with antibody-positive autoimmune encephalitis, good (0·59, 0·54-0·65) for recommendations of empiric immunotherapy, and poor (0·29, 0·21-0·37) for the diagnosis of probable antibody-negative autoimmune encephalitis. Compared with the general algorithm, the paediatric algorithm included more patients in the probable antibody-negative autoimmune encephalitis category (173 vs 41). These patients included some of those who had a diagnosis of CNS inflammatory disorder of unknown cause at the last follow-up (80 of 81 with the paediatric algorithm vs 31 of 81 with the general algorithm), who might have benefitted from immunotherapy, and some of those diagnosed with a non-inflammatory disorder at the last follow-up (47 of 306 with the paediatric algorithm vs six of 306 with the general algorithm), who did not need immunotherapy., Interpretation: About a third of children with suspected autoimmune encephalitis eventually had confirmation of this diagnosis, or diagnosis of another well defined inflammatory disorder. Frequent mimics of autoimmune encephalitis were infectious, epileptic, and psychiatric disorders. Both algorithms performed well in the diagnosis of antibody-positive autoimmune encephalitis, but the paediatric algorithm under-recognised definite autoimmune encephalitis that can occur without autoantibodies and might have overdiagnosed patients with probable antibody-negative autoimmune encephalitis. By contrast, the general algorithm might have underdiagnosed patients with probable antibody-negative autoimmune encephalitis. Given that the diagnosis of probable antibody-negative autoimmune encephalitis has treatment implications, inaccuracies on this diagnostic category leads to overuse or underuse of immunotherapy., Funding: Instituto de Salud Carlos III, Fundació Clínic per la Recerca Biomèdica, The Edmond J Safra Foundation, and la Caixa Foundation., Translation: For the Spanish translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests FG holds a patent for anti-IgLON5 as a diagnostic test and receives royalties associated with autoantibody tests from Euroimmun and honoraria for a role as associated editor from Medlink. JD holds patents for the use of Ma2, NMDA receptor, GABAB receptor, GABAA receptor, DPPX, and IgLON5 as autoantibody tests and receives royalties associated with autoantibody tests from Euroimmun. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

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., Methods: A patient in their 70s with severe relapsing CANOMAD, refractory to IVIG, steroids, rituximab and ibrutinib developed severe tetraparesis and respiratory failure. Plasma exchange (PE) improved motor and ventilatory function; however, after 6 weeks, patient remained PE dependent. Intravenous daratumumab was initiated at 16 mg/kg weekly for 3 weeks, every 2 weeks for the second and third month, and monthly afterwards., Results: After 3 weeks of starting daratumumab, PE was discontinued and, since then, the patient evolved to complete recovery. Antidisialosyl antibody titres decreased after PE and remained stable during daratumumab. Serum neurofilament light-chain levels were elevated in the exacerbation phase and normalised after daratumumab. The patient remains in clinical remission under monthly daratumumab, 12 months after initiation., Conclusions: The first patient with aggressive treatment-refractory CANOMAD treated with daratumumab provides proof-of-principle evidence that daratumumab may be an effective treatment in IgM-related neuropathies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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. Patients were excluded if they had an interval of more than 1 year since initial immunotherapy, had pre-existing neurodegenerative or psychiatric disorders, or were unable to travel to Hospital Clínic de Barcelona (Barcelona, Spain). Patients visited Hospital Clínic de Barcelona on three occasions-the first at study entry (visit 1), the second 6 months later (visit 2), and the third 12 months after the initial visit (visit 3). They underwent neuropsychiatric and videopolysomnography assessments at each visit. Healthy participants who were matched for age and sex and recruited from Hospital Clínic de Barcelona underwent the same investigations at study entry and at 12 months. Cross-sectional comparisons of clinical features between groups were done with conditional logistic regression, and binary logistic regression was used to assess associations between cognitive outcomes at 12 months and clinical features before initial immunotherapy and at study entry., Findings: Between May 1, 2019, and Sept 30, 2022, 42 participants agreed to be included in this study. 24 (57%) participants had anti-LGI1 encephalitis (mean age 63 years [SD 12]; 13 [54%] were female and 11 [46%] were male) and 18 (43%) were healthy individuals (mean age 62 years [10]; 11 [61%] were female and seven [39%] were male). At visit 1 (median 88 days [IQR 67-155] from initiation of immunotherapy), all 24 patients had one or more symptoms; 20 (83%) patients had cognitive deficits, 20 (83%) had psychiatric symptoms, 14 (58%) had insomnia, 12 (50%) had rapid eye movement (REM)-sleep behaviour disorder, nine (38%) had faciobrachial dystonic seizures, and seven (29%) had focal onset seizures. Faciobrachial dystonic seizures were unnoticed in four (17%) of 24 patients and focal onset seizures were unnoticed in five (21%) patients. At visit 1, videopolysomnography showed that 19 (79%) patients, but no healthy participants, had disrupted sleep structure (p=0·013); 15 (63%) patients and four (22%) healthy participants had excessive fragmentary myoclonus (p=0·039), and nine (38%) patients, but no healthy participants, had myokymic discharges (p=0·0051). These clinical and videopolysomnographic features led to additional immunotherapy in 15 (63%) of 24 patients, which resulted in improvement of these features in all 15 individuals. However, at visit 3, 13 (65%) of 20 patients continued to have cognitive deficits. Persistent cognitive deficits at visit 3 were associated with no use of rituximab before visit 1 (odds ratio [OR] 4·0, 95% CI 1·5-10·7; p=0·0015), REM sleep without atonia at visit 1 (2·2, 1·2-4·2; p=0·043), and presence of LGI1 antibodies in serum at visit 1 (11·0, 1·1-106·4; p=0·038)., Interpretation: Unsuspected but ongoing clinical and videopolysomnography alterations are common in patients with anti-LGI1 encephalitis during the first year or more after initial immunotherapy. Recognising these alterations is important as they are treatable, can be used as outcome measures in clinical trials, and might influence cognitive outcome., Funding: Fundació La Caixa., Competing Interests: Declaration of interests JD has patents for the use of Ma2, N-methyl-D-aspartate receptors, GABA(B) receptors, GABA(A) receptors, dipeptidyl-peptidase-like protein-6, and IgLON5 as autoantibody tests. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objectives: Although the diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is based on serum MOG antibodies (MOG-Abs) positivity, patients with coexisting or restricted MOG-Abs in the CSF have been reported. The aim of this study is to characterize the relevance of CSF MOG-Abs positivity in clinical practice., Methods: Eleven medical centers retrospectively collected clinical and laboratory data of adult and pediatric patients with suspected inflammatory CNS disease and MOG-Abs positivity in serum and/or CSF using live cell-based assays. Comparisons were performed using parametric or nonparametric tests, as appropriate. Potential factors of unfavorable outcomes were explored by Cox proportional hazard models and logistic regression., Results: The cohort included 255 patients: 139 (55%) women and 132 (52%) children (i.e., <18-year-old). Among them, 145 patients (56.8%) had MOG-Abs in both serum and CSF (MOG-Abs seropositive and CSF positive), 79 (31%) only in serum (MOG-Abs seropositive and CSF negative), and 31 (12%) only in CSF (MOG-Abs seronegative and CSF positive). MOG-Abs seronegative and CSF positive predominated in adults (22% vs 3% of children), presented more commonly with motor (n = 14, 45%) and sensory symptoms (n = 13, 42%), and all but 4 (2 multiple sclerosis, 1 polyradiculoneuritis, and 1 Susac syndrome) had a final diagnosis compatible with MOGAD. When comparing seropositive patients according to MOG-Abs CSF status, MOG-Abs seropositive and CSF positive patients had a higher Expanded Disability Status Scale (EDSS) at nadir during the index event (median 4.5, interquartile range [IQR] 3.0-7.5 vs 3.0, IQR 2.0-6.8, p = 0.007) and presented more commonly with sensory (45.5% vs 24%, p = 0.002), motor (33.6% vs 19%, p = 0.021), and sphincter symptoms (26.9% vs 7.8%, p = 0.001) than MOG-Abs seropositive and CSF negative. At the last follow-up, MOG-Abs seropositive and CSF positive cases had more often persistent sphincter dysfunction (17.3% vs 4.3%, p = 0.008) . Compared with seropositive patients, those MOG-Abs seronegative and CSF positive had higher disability at the last follow-up ( p ≤ 0.001), and MOG-Abs seronegative and CSF positive status were independently associated with an EDSS ≥3.0., Discussion: Paired serum and CSF MOG-Abs positivity are common in MOGAD and are associated with a more severe clinical presentation. CSF-only MOG-Abs positivity can occur in patients with a phenotype suggestive of MOGAD and is associated with a worse outcome. Taken together, these data suggest a clinical interest in assessing CSF MOG-Abs in patients with a phenotype suggestive of MOGAD, regardless of the MOG-Abs serostatus., (© 2022 American Academy of Neurology.)

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. Here, we assessed the clinical performance of a commercial and an in house indirect immunofluorescent cell based assays (IIF-CBA) using paired serum/CSF of 70 patients with suspected anti-LGI1 encephalitis and positive rat brain indirect immunohistochemistry (IIHC). We found that all (100%) patients had CSF antibodies when the in house IIF-CBA was used, but only 88 (83%) were positive if the commercial test was used. In contrast, sera positivity rate was higher with the commercial test (94%) than with the in house assay (86%). If both serum and CSF were examined with the commercial IIFA-CBA, 69/70 (98.5%) patients were positive in at least one of the samples. These findings are clinically important for centers in which rat brain IIHC and in house IIFA-CBA are not available. Moreover, the observation that all patients with anti-LGI1 encephalitis have antibodies in CSF is in line with the concept that these antibodies are pathogenic., Competing Interests: JD receives royalties from Athena Diagnostics for the use of Ma2 as an autoantibody test and from Euroimmun for the use of NMDA, GABA-B receptor, GABA-A receptor, DPPX and IgLON5 as autoantibody tests. FG receives royalties from Euroimmun for the use of (IgLON5) in an autoantibody test and receives honoraria from MedLink Neurology for his role as an associate editor. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Muñoz-Sánchez, Planagumà, Naranjo, Couso, Sabater, Guasp, Martínez-Hernández, Graus, Dalmau and Ruiz-García.)

Background: Anti-NMDA receptor (NMDAR) encephalitis is associated with a post-acute stage that is not well known. We aimed to describe the clinical features of this stage, similarities with schizophrenia spectrum disorders, and the factors that predict cognitive-psychiatric outcomes and could serve as prognostic biomarkers., Methods: In this prospective cohort study, participants (aged 12-60 years) with anti-NMDAR encephalitis during the post-acute stage visited Hospital Clínic de Barcelona (Barcelona, Spain) on three occasions (at study entry [V1], at 6 months [V2], and at 12 months [V3]) and underwent comprehensive neuropsychiatric evaluations. Similar evaluations were done in a group of age-matched participants with schizophrenia spectrum disorders and a group of age-matched and sex-matched healthy participants also recruited from Hospital Clínic de Barcelona. We analysed differences between and within groups in the longitudinal follow-up using multilevel linear mixed-effect models, adjusting for group, age, sex, and socioeconomic status to control for possible confounding., Findings: Between Jan 1, 2017, and Sept 30, 2020, 82 participants were recruited, 28 (34%) with anti-NMDAR encephalitis, 27 (33%) with schizophrenia spectrum disorders, and 27 (33%) healthy participants. Although, by V1 (median 4 months [IQR 3-7] from disease onset), many acute-stage symptoms in participants with anti-NMDAR encephalitis had resolved (acute stage median modified Rankin Scale [mRS] score 5 [IQR 4-5] vs V1 mRS score 2 [1-2]; p<0·0001), 25 (89%) participants showed deficits in at least one cognitive domain. In this group, 15 (68%) of 22 cognitive domain variables were impaired at V1, whereas only eight (36%) were altered at V3 (p=0·016). In participants with schizophrenia spectrum disorders, 11 (50%) of 22 variables (all shared with participants with anti-NMDAR encephalitis) were impaired at V1, without changes at V3. Two acute-stage features of anti-NMDAR encephalitis (ie, decreased consciousness and no improvement within the first 4 weeks of treatment) predicted cognitive domain outcomes, and a visuospatial task (ie, serial biases) at V1 showed potential in predicting learning and memory outcomes. At V1, all psychiatric symptom clusters were similarly altered in participants with anti-NMDAR encephalitis and in those with schizophrenia spectrum disorders, but only those in individuals with anti-NMDAR encephalitis subsequently improved (p=0·031). The greatest cognitive-psychiatric improvement in participants with anti-NMDAR encephalitis occurred between V1 and V2. During this interval, four (14%) participants with anti-NMDAR encephalitis would have met the diagnostic criteria of schizophrenia if CSF antibody findings had not been investigated., Interpretation: The cognitive-psychiatric symptoms of anti-NMDAR encephalitis in the post-acute stage resembled those of stabilised schizophrenia, but only those in participants with anti-NMDAR encephalitis progressively improved, predominantly during V1-V2. These findings are important for clinical trials on anti-NMDAR encephalitis and suggest that prompt cognitive-psychosocial rehabilitation might be a valuable intervention., Funding: Instituto Salud Carlos III, NEURON Network of European Funding for Neuroscience Research, National Alliance for Research in Schizophrenia and Affective Disorders, and la Caixa Health-Research Foundation., Competing Interests: Declaration of interests JD holds patents for the use of NMDAR as autoantibody tests. GS received speaker fees from Angelini Pharma. SL received compensation for consulting services and speaker honoraria from Biogen Idec, Novartis, Teva, Genzyme, Sanofi, and Merck. RS-V served in advisory boards meetings for Wave Lifesciences and Novo Nordisk; and received personal fees for participating in educational activities from Janssen, Roche Diagnostics, and Neuroxpharma, and funding to her institution for research projects from Biogen and Sage Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Neuroleukemia is a rare disorder of the peripheral nervous system due to leukemic cell infiltration., Case Report: We present the case of a 34-year-old patient with history of acute myelomonoblastic leukemia in remission that presented progressive paresis of the right median, bilateral facial, and left peroneal nerves. The electromyogram confirmed the diagnosis of multineuropathy. A PET-CT showed hypermetabolism of both sciatic, facial, and right median nerves. A bone marrow aspirate confirmed the leukemia relapse so a new round of chemotherapy was performed with improvement of the neurological deficit., Conclusion: Peripheral nervous system infiltration by leukemic cells can mimic multiple syndromes depending on the structures involved. The nerve-blood barrier acts as a defense of leukemic cells against chemotherapy and the immune system. Thus, the peripheral nervous system constitutes a reservoir of leukemic cells. Neuroleukemia should be considered in patients with history of acute leukemia who have isolated symptoms of the peripheral nerve.

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. We found that, compared to healthy controls (HC), neuro-COVID patients presented elevated levels of IL-18, IL-6, and IL-8 in both serum and CSF. MCP1 was elevated only in CSF, while IL-10, IL-1RA, IP-10, MIG and NfL were increased only in serum. Patients with COVID-associated encephalitis or encephalopathy had distinct serum and CSF cytokine profiles compared with HC, but no differences were found when both clinical groups were compared to each other. Antibodies against neural antigens were negative in both groups. While the levels of neuroaxonal damage markers, 14-3-3 and NfL, and the proinflammatory cytokines IL-18, IL-1RA and IL-8 significantly associated with acute COVID-19 severity, only the levels of 14-3-3 and NfL in CSF significantly correlated with the degree of neurologic disability in the daily activities at 18 months follow-up. Thus, the inflammatory process promoted by SARS-CoV-2 infection might include blood-brain barrier disruption in patients with neurological involvement. In conclusion, the fact that the levels of pro-inflammatory cytokines do not predict the long-term functional outcome suggests that the prognosis is more related to neuronal damage than to the acute neuroinflammatory process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guasp, Muñoz-Sánchez, Martínez-Hernández, Santana, Carbayo, Naranjo, Bolós, Framil, Saiz, Balasa, Ruiz-García, Sánchez-Valle and The Barcelona Neuro-COVID Study Group.)

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. Here we assessed the performance of neurofilament light chain (NfL) testing in these settings., Methods: In this observational study, NfL levels were determined with single-molecule array in patients with NMDARe, pFEP, herpes simplex encephalitis (HSE), and healthy participants (HC), with the last 2 groups used as controls. Receiver operating characteristic (ROC) analyses were performed to assess the prediction accuracy of serum NfL (sNfL) levels for NMDARe and pFEP and to obtain clinically useful cutoffs., Results: One hundred eighteen patients with NMDARe (33 with isolated psychosis at presentation), 45 with pFEP, 36 with HSE, and 36 HC were studied. Patients with NMDARe with seizures/status epilepticus, intensive care unit admission, and CSF pleocytosis (>20 white blood cells/µL) and without early immunotherapy were more likely to have higher NfL (mainly in CSF) than individuals with NMDARe without these features. NfL levels at diagnosis of NMDARe did not correlate with outcome at 1-year follow-up assessed with the modified Rankin Scale. Patients with NMDARe had significantly higher sNfL than individuals with pFEP and HC and lower sNfL than patients with HSE. ROC analysis of sNfL between NMDARe with isolated psychosis and pFEP provided an area under the curve of 0.93 (95% CI 0.87-0.99) and an sNfL cutoff ≥15 pg/mL to distinguish these disorders (sensitivity 85%, specificity 96%, positive likelihood ratio 19.3). Forty-three of 45 (96%) patients with pFEP had sNfL<15 pg/mL, whereas only 5 of 33 (15%) with NMDARe with isolated psychosis were below this cutoff (risk estimation NMDARe vs pFEP: odds ratio 120.4 [95% CI 21.8-664], p < 0.001). None of the patients with HSE and 35 of 36 (97%) HC had sNfL<15 pg/mL., Discussion: NfL measured at diagnosis of NMDARe associated with features of disease severity but not with long-term outcome. Young patients with FEP and sNfL ≥15 pg/mL had a 120 times higher chance of having NMDARe than those with pFEP. This cutoff correctly classified 96% of patients with pFEP and 85% of patients with NMDARe with isolated psychosis. Patients with FEP of unclear etiology and sNfL ≥15 pg/mL should undergo CSF NMDAR antibody testing., (© 2022 American Academy of Neurology.)

Background: Guillain-Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain-Barré syndrome., Methods: Autoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed., Results: None of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factors., Conclusion: Our study confirms that (1) GBS patients display a heterogeneous repertoire of autoantibodies targeting nerve cells and structures; (2) gangliosides are the most frequent antigens in GBS patients and have a prognostic value; (3) further antigen-discovery experiments may elucidate other potential antigens in GBS., (© 2021. The Author(s).)

Kelch-like 1 (KLHL1) is a neuronal actin-binding protein that modulates voltage-gated calcium channels. The KLHL1 knockout (KO) model displays altered calcium channel expression in various brain regions. We analyzed the electrical behavior of hypothalamic POMC (proopiomelanocortin) neurons and their response to leptin. Leptin's effects on POMC neurons include enhanced gene expression, activation of the ERK1/2 pathway and increased electrical excitability. The latter is initiated by activation of the Jak2-PI3K-PLC pathway, which activates TRPC1/5 (Transient Receptor Potential Cation) channels that in turn recruit T-type channel activity resulting in increased excitability. Here we report over-expression of Ca V 3.1 T-type channels in the hypothalamus of KLHL1 KO mice increased T-type current density and enhanced POMC neuron basal excitability, rendering them electrically unresponsive to leptin. Electrical sensitivity to leptin was restored by partial blockade of T-type channels. The overexpression of hypothalamic T-type channels in POMC neurons may partially contribute to the obese and abnormal feeding phenotypes observed in KLHL1 KO mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Perissinotti, Martínez-Hernández, He, Koob and Piedras-Rentería.)

Objectives: To report the neuropsychiatric features and frequency of NMDA receptor (NMDAR) and other neuronal immunoglobulin G antibodies in patients with first episode psychosis (FEP) and to assess the performance of reported warning signs and criteria for autoimmune psychosis (AP)., Methods: This was a prospective observational study of patients with FEP assessed for neuropsychiatric symptoms, serum and CSF neuronal antibodies (brain immunohistochemistry, cell-based assays, live neurons), and warning signs and criteria of AP. Previous autoimmune FEP series were reviewed., Results: One hundred five patients were included; their median age was 30 (range 14-75) years, and 44 (42%) were female. None had neuronal antibodies. Two of 105 (2%) had CSF pleocytosis, 4 of 100 (4%) had brain MRI abnormalities, and 3 of 73 (4%) EEG alterations. Thirty-four (32%) and 39 (37%) patients fulfilled 2 sets of warning signs of AP, and 21 (20%) fulfilled criteria of possible or probable AP, yet none developed AP. The cause of FEP was psychiatric in 101 (96%) and nonpsychiatric in 4 (4%). During this study, 3 patients with psychosis caused by anti-NMDAR encephalitis were transferred to our center; 2 did not meet criteria for possible AP. Of 1,159 reported patients with FEP, only 7 (1%) had CSF studies; 36 (3%) had serum NMDAR antibodies (without definite diagnosis of AP), and 4 had CSF NMDAR antibodies (3 classic anti-NMDAR encephalitis and 1 with isolated psychiatric features)., Conclusions: NMDAR antibodies were not found in patients with FEP unless they had anti-NMDAR encephalitis. Warning signs and criteria for AP have limited utility when neurologic symptoms are absent or paraclinical tests are normal. A diagnostic algorithm for autoimmune FEP is provided., (© 2021 American Academy of Neurology.)