Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Long-Term Clinical and Biological Prognostic Factors of Anti-NMDA Receptor Encephalitis in Children.","authors":"Maxime Mazowiecki, Lorraine Flet-Berliac, Julia Roux, Anne Lépine, Pascale Chretien, Salima Hacein-Bey-Abina, Laetitia Giorgi, Frederic Villega, Emmanuel Cheuret, Marie Benaiteau, Veronique Rogemond, Geraldine Picard, Sarah Baer, Pierre Cleuziou, Elodie Lametery, Isabelle Desguerre, Mélodie Aubart, Mathilde Chevignard, Roger Le Grand, Philippe Horellou, Carole Leroy, Bastien Joubert, Jerome Honnorat, Kumaran Deiva","doi":"10.1212/NXI.0000000000200346","DOIUrl":"10.1212/NXI.0000000000200346","url":null,"abstract":"<p><strong>Background and objectives: </strong>Anti-NMDAR encephalitis (NMDARE) is a severe neurologic condition, and recently, the NMDAR Encephalitis One-Year Functional Status (NEOS) score has emerged as a 1-year prognostic tool. This study aimed to evaluate NEOS score and biomarker (neurofilament light chains [NfL], total-Tau protein, glial fibrillary acidic protein, and serum cytokines) correlation with modified Rankin Scale (mRS), cognitive impairment, and clinical recovery in pediatric NMDARE over 2 years.</p><p><strong>Methods: </strong>In this French multicenter observational study, 104 pediatric patients with NMDARE were followed for a minimum of 2 years. Clinical data and serum/plasma samples were collected. Biomarker levels, measured using electroluminescence mesoscale discovery (MSD) S-PLEX, were compared between patients and controls and assessed for correlations with disease activity, mRS, cognitive/language impairment, and recovery status at 2 years.</p><p><strong>Results: </strong>At a median follow-up of 39.5 months, 68 percent of patients had unfavorable recovery and 54% had significant cognitive impairment. Both outcomes were strongly associated with younger age at diagnosis (OR 6.10 [1.91-27.3] <i>p</i> < 0.01 and 5.69 [1.46-27.7] <i>p</i> = 0.02, respectively). A higher NEOS score was significantly correlated with increased cognitive impairment (OR 2.53 [1.52-4.21], <i>p</i> < 0.001), higher mRS scores (OR 2.12 [1.34-3.57], <i>p</i> < 0.01), and unfavorable recovery at 2 years (OR 2.00 [1.30-3.06], <i>p</i> = 0.015). Elevated NfL levels were significantly associated with unfavorable recovery (OR 3.62 [1.29-10.9] <i>p</i> = 0.012) and severe cognitive impairment (OR 3.77 [1.38-10.9] <i>p</i> = 0.012) at 2 years. The combined area under the curve (AUC) for NfL and NEOS was significantly higher than the AUCs of NEOS and NfL alone <i>(p</i> = 0.01).</p><p><strong>Discussion: </strong>The NEOS score strongly predicts long-term outcomes in NMDARE, with its predictive value extending beyond the first-year mR prediction. NfL levels at disease onset seem to improve accuracy in predicting poor outcomes, providing valuable information for treatment decisions and future clinical trials.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200346"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of the Kynurenine Pathway in Relapsing Remitting Multiple Sclerosis and Its Correlations With Progressive Neurodegeneration.","authors":"Ananda Staats Pires, Shivani Krishnamurthy, Samridhi Sharma, Sharron Chow, Samuel Klistorner, Gilles J Guillemin, Alexander Klistorner, Yuyi You, Benjamin Heng","doi":"10.1212/NXI.0000000000200372","DOIUrl":"10.1212/NXI.0000000000200372","url":null,"abstract":"<p><strong>Background and objectives: </strong>Despite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to progress, and a potential underlying mechanism could be the kynurenine pathway (KP). Prolonged activation of the KP from chronic inflammation is known to exacerbate the progression of neurodegenerative diseases through the production of neurotoxic metabolites. Among the 8 KP metabolites, six of them, namely kynurenine (KYN), 3-hydroxylkynurenine (3HK), anthranilic acid (AA), kynurenic acid (KYNA), and quinolinic acid (QUIN), have been associated with neurodegeneration.</p><p><strong>Methods: </strong>To gain insights into the links between the KP and neurodegeneration in MS, we investigated the KP metabolomics profile of relapsing remitting MS (RRMS) patients and their correlation with parameters of neurodegeneration in brain and retinal. Outpatients with a clinical diagnosis of RRMS (n = 98) or age-matched and sex-matched healthy controls (n = 39) were included. MS participants undertook yearly evaluation of MRI and optical coherence tomography scan to evaluate neuroaxonal loss. Blood samples were collected at the baseline from all participants for the biochemical analysis of KP metabolites.</p><p><strong>Results: </strong>We identified increased plasma levels of AA and 3HAA in the MS group, indicating an anti-inflammatory response alongside active neurodegeneration. By contrast, plasma levels of KYNA and 3HK were lower in the MS group than in healthy controls. Our analysis revealed a higher KYN:tryptophan (TRP) and QUIN:KYNA ratios in the MS cohort, suggesting activation of the pathway toward the production of neurotoxic QUIN. Another important finding was that KP metabolites were correlated with measures of axonal degeneration in patients with MS. Notably, central brain atrophy positively correlated with the TRP levels, but negatively correlated with KYN and level KYN:TRP ratio. Finally, the choroid plexus volume was inversely correlated with KYNA plasma levels.</p><p><strong>Discussion: </strong>These findings highlight changes in the biosynthesis of KP during the progression of RRMS and its correlation with axonal loss. This study underscores the potential of targeting the KP in developing novel treatments for neuroaxonal damage in MS and warrants future research in greater depth.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200372"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenetic Studies in Patients With GAD-Positive Stiff-Person Syndrome Reveal Novel Lymphocytic Genes and <i>KLK10</i>-Gene Variants.","authors":"Popianna Tsiortou, Harry Alexopoulos, Konstantinos Kyriakidis, Michalis Kosmidis, Chrysanthi Barba, Sofia Akrivou, Ioannis Michalopoulos, Panagiotis Politis, Marinos C Dalakas","doi":"10.1212/NXI.0000000000200373","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200373","url":null,"abstract":"<p><strong>Background and objectives: </strong>The aim of this study was to identify genetic markers and immunologic characteristics of glutamic acid decarboxylase (GAD) antibody-positive patients with stiff-person syndrome (SPS).</p><p><strong>Methods: </strong>We conducted systemic immunogenetic studies in 11 GAD-positive patients: 8 with sporadic SPS and 3 from a three-generation family with very high GAD-ab titers but diverse symptomatology (one with GAD-epilepsy and SPS and 2 only with diabetes), by performing complete immunologic profile and whole-exome sequencing analysis.</p><p><strong>Results: </strong>Two genes expressed in immune and neuronal tissues were identified: the <i>ORAI1</i> that codes for a calcium release-activated channel protein with a role in the activation of T lymphocytes and the <i>LILRA4</i> that encodes an IgG-like cell surface protein expressed in plasmacytoid dendritic cells. An important finding was the identification of 7 genetic polymorphisms in the novel <i>Kallikrein 10</i> (<i>KLK10)</i> gene, shared by all 9 typical patients with SPS, as verified by Sanger sequencing, but not in the 2 GAD-positive family members with diabetes or the GAD-negative controls. To further verify these findings, Sanger sequencing was performed in 10 more patients with SPS and 15 autoimmune controls collectively confirmed that among a total of 39 tested samples, 95% of the 19 patients with SPS were homozygous or heterozygous for all 7 KLK10 variants while 90% of the 20 controls had the wild type or were heterozygous. <i>KLK10</i> is a peptidase expressed in the choroid plexus epithelium and neuroendocrine organs and participates in the initiation of systemic inflammatory responses and immune-modulated disorders through proteolytic cascades.</p><p><strong>Discussion: </strong>KLK10 is a novel and potentially key genetic marker in patients with SPS that can contribute to disease pathogenesis by altering protease activity or the expression of neuron-to-immune cell signaling facilitating GAD autoimmunity. Along with the 2 newly identified immune-related genes, KLK10 is likely an interplay between genetic predisposition and immune dysregulation, necessitating the need to explore their significance as susceptibility disease factors and possibly as novel therapeutic targets.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200373"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Manifestations and Treatment Responses in Pediatric Neurofascin 155-IgG4 Autoimmune Nodopathy.","authors":"Hebatallah R Rashed, Naveen Kumar Paramasivan, Duygu Selcen, P James B Dyck, Smathorn Thakolwiboon, Michelle L Mauermann, John Mills, Divyanshu Dubey","doi":"10.1212/NXI.0000000000200368","DOIUrl":"10.1212/NXI.0000000000200368","url":null,"abstract":"<p><strong>Background and objectives: </strong>While it is well characterized in adults, little is known about the clinical features of neurofascin 155-IgG4 autoimmune nodopathy (NF155-IgG4 AN) in the pediatric population. In this study, we aimed to describe the clinical features and treatment outcomes in children diagnosed with neurofascin 155-IgG4 autoimmune nodopathy (NF155-IgG4 AN).</p><p><strong>Methods: </strong>Pediatric and adult patients with NF155-IgG4 AN were identified retrospectively through the Mayo Clinic Neuroimmunology Laboratory database.</p><p><strong>Results: </strong>Eight pediatric and 20 adult patients with NF155-IgG4 AN were included with a median age at onset of 11 and 43 years, respectively. Pediatric patients (3/8) were often diagnosed initially with Guillain-Barre syndrome compared with adults (2/20) (<i>p</i> = 0.123). Six pediatric patients deteriorated beyond 2 months with rapid progression to disease nadir compared with adults (22 vs 52 weeks, <i>p</i> = 0.04). All had distal predominant weakness with paresthesias. Four patients had tremor, and one had cerebellar ataxia. Sensory ataxia was significantly less common in pediatric patients (4/8) compared with adults (18/20) (<i>p</i> = 0.038). Most pediatric patients (6/7) were IVIG refractory and responded to rituximab. Six patients had favorable outcomes after immunotherapy with improvement ≥1 in the Inflammatory Neuropathy Cause and Treatment disability score.</p><p><strong>Discussion: </strong>Pediatric patients with NF155-IgG4 AN display an aggressive disease course with rapid progression to disease nadir compared with adults. Sensory ataxia is less common in children, and they often respond to rituximab. It is crucial to consider autoimmune nodopathies in the differential diagnosis of pediatric patients with suspected inflammatory demyelinating polyneuropathy and to test for NF155-IgG4 antibodies because of their diagnostic and therapeutic implications.</p><p><strong>Classification of evidence: </strong>This study provides Class IV evidence that in pediatric patients with NF155-IgG4 AN who are refractory to IVIG, rituximab treatment provided some benefit.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200368"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conformational Antibodies to Proteolipid Protein-1 and Its Peripheral Isoform DM20 in Patients With CNS Autoimmune Demyelinating Disorders.","authors":"Stefano Masciocchi, Pietro Businaro, Giacomo Greco, Silvia Scaranzin, Antonio Malvaso, Chiara Morandi, Elisabetta Zardini, Mario Risi, Elisa Vegezzi, Luca Diamanti, Paola Bini, Sabrina Siquilini, Maria Pia Giannoccaro, Luana Morelli, Rocco Liguori, Francesco Patti, Valeria De Giuli, Emilio Portaccio, Chiara Zanetta, Stefania Bergamoni, Anna Maria Simone, Roberta Lanzillo, Giorgia Bruno, Antonio Gallo, Alvino Bisecco, Massimiliano Di Filippo, Flavia Pauri, Antonella Toriello, Paolo Barone, Francesco Tazza, Sebastiano Bucello, Paola Banfi, Martina Fabris, Irene Volonghi, Loredana Raciti, Maria Claudia Vigliani, Tommaso Bocci, Matteo Paoletti, Elena Colombo, Massimo Filippi, Anna Pichiecchio, Enrico Marchioni, Diego Franciotta, Matteo Gastaldi","doi":"10.1212/NXI.0000000000200359","DOIUrl":"10.1212/NXI.0000000000200359","url":null,"abstract":"<p><strong>Background and objectives: </strong>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.</p><p><strong>Methods: </strong>We devised a new live cell-based assay (CBA) for PLP1-IgG and used it to test 2 cohorts (retrospective exploratory, n = 284; prospective validation, n = 824) of patients with ADDs and controls (n = 177). Patients were classified as MS, neuromyelitis optica spectrum disorders (NMOSDs), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and other ADDs. PLP1-IgG-positive samples were tested for IgG subclasses, DM20-IgG, and on rat brain tissue-based assay (TBA). Complement-dependent cytotoxicity (CDC) was assessed on a live CBA and antigen specificity and conformational binding through immunoadsorption/colocalization/fixation experiments.</p><p><strong>Results: </strong>PLP1-IgG were found in 0 of 177 controls and 42 of 1104 patients with ADDs mainly diagnosed as other ADDs (19/42) with frequent myelitis/encephalomyelitis (14/19) and coexisting PNS involvement (13/19). Four of 19 patients with other ADDs fulfilled the seronegative NMOSD criteria. PLP1-IgG were also found in patients with MOGAD (11/42), more frequently with PNS involvement (<i>p</i> = 0.01), and in patients with MS (12/42), more frequently with atypical features (<i>p</i> < 0.001). PLP1-IgG-positive MOGAD had higher EDSS scores (<i>p</i> < 0.001) and PLP1-IgG-positive MS had higher severity scores (MSSS, <i>p</i> < 0.001) compared with those PLP1-IgG-negative. Overall, PLP1-IgG were found in 24.1% of patients with CNS+PNS-ADD, 21.2% with atypical MS, 8.3% with MOGAD, 12.0% with seronegative NMOSD, and 1.4% with typical MS. Their frequency within each diagnostic subgroup was consistent between the exploratory and validation cohorts. PLP1-IgG a) colocalized with their target on CBA-TBA, where their binding was abolished after immunoadsorption and fixation-induced conformational epitope alteration; b) mostly pertained to the IgG1/IgG3 subclass (68.3%) and were able to induce CDC; and c) coreacted with DM20 in all 12 patients with PNS involvement tested.</p><p><strong>Discussion: </strong>Conformational PLP1-IgG predominantly identify patients with non-MS ADDs. They should be tested mainly in those with CNS + PNS ADD, coherently with DM20-IgG coreactivity. PLP1-IgG could also be investigated as disease modifiers and prognostic markers in MS and MOGAD. Preliminary evidence supports their pathogenic potential.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200359"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Risk of Relapse After In Vitro Fertilization in Women With Multiple Sclerosis.","authors":"Marie Mainguy, Romain Casey, Sandra Vukusic, Christine Lebrun-Frenay, Eric Berger, Anne Kerbrat, Abdullatif Al Khedr, Bertrand Bourre, Jonathan Ciron, Pierre Clavelou, Jerome De Seze, Gilles Defer, Ines Doghri, Amélie Dos Santos, Karolina Hankiewicz, Pierre M Labauge, Emmanuelle Le Page, Laurent Magy, Elisabeth Maillart, Eric Manchon, Laure Michel, Thibault Moreau, Solène Moulin, Jean Pelletier, Corinne Pottier, Aurélie Ruet, Mariana Sarov, Bruno Stankoff, Eric Thouvenot, Abir Wahab, Helene Zephir, Emmanuelle Leray, David Axel Laplaud","doi":"10.1212/NXI.0000000000200371","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200371","url":null,"abstract":"<p><strong>Background and objectives: </strong>Older studies reported an increased risk of relapse after in vitro fertilization (IVF) in women with multiple sclerosis (MS), which has not been confirmed by more recent works. All these studies had several limitations, such as small sample sizes, absence of a control population, or lack of neurologic validation of the relapses. The aim of this study was to determine the risk of relapse after IVF in women with MS.</p><p><strong>Methods: </strong>This retrospective cohort study included all women with MS who underwent IVF between 2009 and 2019 and a control group of women with MS who did not undergo IVF matched on age, MS duration, number of relapses, and MS-specific treatments in the previous year. Data on MS (disease duration, treatments, and relapses) were from the French MS Registry (OFSEP), whereas data on IVF (number of procedures, stimulation protocol type, and outcomes) were from the French national health insurance database. For this, the 2 databases were linked by indirect matching.</p><p><strong>Results: </strong>In total, 115 women with MS underwent 199 IVF procedures (mean age at first IVF: 33.9 ± 4.0 years; 45.2% had ≥2 IVF procedures), and 175 IVFs (88.0%) could be matched to specific patients. The risk of relapse in the 3 months after index date was the same in both IVF group and control group (0.06 relapse per patient-year), as confirmed also by the before-after analysis in the IVF group (0.06 vs 0.08).</p><p><strong>Discussion: </strong>This study, using a 10-year clinical and administrative dataset, did not find any increased risk of relapse after IVF. The maintenance of disease-modifying therapies until IVF was a determining factor in reducing the risk of relapse.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200371"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast Cancer Specificities of Patients With Anti-Ri Paraneoplastic Neurologic Syndromes.","authors":"Elise Peter, Isabelle Treilleux, Valentin Wucher, Macarena Villagrán-García, Pauline Dumez, Daniel Pissaloux, Sandrine Paindavoine, Valéry Attignon, Geraldine Picard, Veronique Rogemond, Marine Villard, Laurie Tonon, Anthony Ferrari, Alain Viari, Bertrand Dubois, Jerome Honnorat, Virginie Desestret","doi":"10.1212/NXI.0000000000200367","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200367","url":null,"abstract":"<p><strong>Background and objectives: </strong>Breast cancers (BCs) of patients with paraneoplastic neurologic syndromes and anti-Yo antibodies (Yo-PNS) overexpress human epidermal growth factor receptor 2 (HER2) and display genetic alterations and overexpression of the Yo-onconeural antigens. They are infiltrated by an unusual proportion of B cells. We investigated whether these features were also observed in patients with PNS and anti-Ri antibodies (Ri-PNS).</p><p><strong>Methods: </strong>Using clinicopathologic data, DNA sequencing, and whole-transcriptome analysis, 28 BCs associated with Ri-PNS were characterized regarding oncological characteristics. Genetic alteration of the onconeural antigens and differential gene expression profiles were analyzed in the 12 available tumor samples and compared with those of 5 Yo-PNS tumors.</p><p><strong>Results: </strong>Ri-PNS BCs were mainly luminal B invasive carcinomas that did not overexpress HER2 and were a subtype of BCs different from the ones observed in Yo-PNS BCs. They had a low expression of wild-type <i>TP53</i> and deletions of 1p chromosome. Neither overexpression nor genetic alteration of the Ri onconeural antigens was found in Ri-PNS BCs. Conversely, the nature of the antitumor immune reaction in Ri-PNS BCs was similar to the one found in Yo-PNS BCs. Ri-BCs also had a high propension for early nodal regional metastasis.</p><p><strong>Discussion: </strong>BCs associated with Ri-PNS are uncommon and the tumor subtype and their molecular and oncological characteristics are different from those of Yo-PNS and controls. Overexpression or sequence variation in the gene of the onconeural antigen is not mandatory. Conversely, Ri-PNS-associated and Yo-PNS-associated BCs display the same atypical B-cell-mediated intratumoral immune response, and tumor escape in the lymph nodes is frequent.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200367"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive Deficits in Anti-LGI1 Encephalitis Are Linked to Immunotherapy-Resistant White Matter Network Changes.","authors":"Stephan Krohn, Leonie Müller-Jensen, Joseph Kuchling, Amy Romanello, Katharina Wurdack, Sophia Rekers, Thorsten Bartsch, Frank Leypoldt, Friedemann Paul, Christoph J Ploner, Harald Prüss, Carsten Finke","doi":"10.1212/NXI.0000000000200360","DOIUrl":"10.1212/NXI.0000000000200360","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cognitive deficits represent a major long-term complication of anti-leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E). Although severely affecting patient outcomes, the structural brain changes underlying these deficits remain poorly understood. In this study, we hypothesized a link between white matter (WM) networks and cognitive outcomes in LGI1-E.</p><p><strong>Methods: </strong>In this cross-sectional study, we combined clinical assessments, comprehensive neuropsychological testing, diffusion tensor MRI, probabilistic WM tractography, and computational network analysis in patients with LGI1-E referred to Charité-Universitätsmedizin Berlin. Healthy individuals were recruited as control participants and matched to patients for age and sex with logistic regression propensity scores.</p><p><strong>Results: </strong>Twenty-five patients with LGI1-E (mean age = 63 ± 12 years, 76% male) and 25 healthy controls were enrolled. Eighty-eight percent of patients presented persistent cognitive symptoms at postacute follow-up (median: 12 months from onset, interquartile range: 6-23 months)-despite treatment with immunotherapy and good overall recovery (modified Rankin Scale [mRS] score at peak illness vs postacute: <i>z =</i> -4.1, <i>p</i> < 0.001, median mRS score at postacute visit: 1). Neuroimaging revealed that WM networks in LGI1-E are characterized by (1) a systematic reduction in whole-brain connectivity (<i>t =</i> -2.16, <i>p =</i> 0.036, <i>d =</i> -0.61), (2) a cortico-subcortical hypoconnectivity cluster affecting both limbic and extralimbic brain systems, and (3) a \"topological reorganization\" marked by a bidirectional shift in the relative importance of individual brain regions in the WM network. The extent of this WM reorganization was strongly associated with long-term deficits of verbal memory (<i>r =</i> -0.56), attention (<i>r =</i> -0.55), and executive functions (<i>r =</i> -0.60, all <i>p</i>_<i>FDR</i> = 0.017).</p><p><strong>Discussion: </strong>Although traditionally viewed as a form of limbic encephalitis, our study characterizes LGI1-E as a \"network disorder\" that affects the whole brain. Structural reorganization of WM networks was linked to long-term and multidomain cognitive impairment, which was not prevented by immunotherapy. These findings highlight the need for closer monitoring and improved treatment strategies to mitigate long-term cognitive impairment in LGI1-E.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200360"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Paraclinical Characterizations, Management, and Prognosis in DPPX Antibody-Associated Encephalitis: A Systematic Review.","authors":"Er-Chuang Li, Tian-Yi Zhang, Meng-Ting Cai, Sheng-Yao Su, Chun-Hong Shen, Qi-Lun Lai, Yin-Xi Zhang","doi":"10.1212/NXI.0000000000200350","DOIUrl":"10.1212/NXI.0000000000200350","url":null,"abstract":"<p><p>In dipeptidyl-peptidase-like protein 6 (DPPX) antibody-associated encephalitis, DPPX antibodies from serum and CSF target the extracellular subunit of the voltage-gated potassium channel 4.2. This targeting leads to a characteristic clinical triad comprising gastrointestinal symptoms (predominantly diarrhea), cognitive-psychiatric dysfunction, and manifestations of CNS hyperexcitability, with hyperekplexia being a more specific feature. This rare disease typically presents with a subacute or chronic course and often affects middle-aged and older individuals. Patients may have a weak association with certain hematologic malignancies, particularly lymphoma and chronic lymphocytic leukemia. Brain MRI typically shows normal findings or nonspecific white matter changes. DPPX antibody-associated encephalitis responds well to immunotherapy, and most patients ultimately present with a good prognosis. However, relapses can occur. To improve our understanding of this rare but treatable autoimmune encephalitis and avoid misdiagnosis, we conduct a systematic review and summarize the current knowledge of its clinical and paraclinical features, management, and prognosis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200350"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characterization and Prognostic Risk Factors of Susac Syndrome: A Retrospective Multicenter Study.","authors":"Lior Fuchs, Adi Wilf-Yarkoni, Hadar Kolb, Ifat Vigiser, Keren Regev, Dinah Zur, Zohar Habot-Wilner, Yahav Oron, Viktoria Furer, Nitai Shimon, Mark A Hellmann, Itay Lotan, Eitan Auriel, Robert Rennebohm, Ori Elkayam, Arnon Karni","doi":"10.1212/NXI.0000000000200357","DOIUrl":"10.1212/NXI.0000000000200357","url":null,"abstract":"<p><strong>Background and objectives: </strong>Susac syndrome (SuS) is a rare disorder characterized by encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss, often accompanied by vertigo. Recent updates to diagnostic criteria and treatment guidelines have been made. This study examines clinical manifestations; disease activity; and risk factors of disability, dependency, and return to work in patients with SuS.</p><p><strong>Methods: </strong>A retrospective multicenter study was conducted on 20 consecutive patients with SuS with at least 2 years of follow-up. Clinical and paraclinical activities were assessed and rated according to the severity at onset and the end of follow-up. Cognitive function was assessed using the Montreal Cognitive Assessment while disability and dependence in daily activities were measured using the modified Rankin Scale. Employment status was graded.</p><p><strong>Results: </strong>The mean age at onset was 38.9 years, with a mean follow-up of 55.9 months. The female-to-male ratio was 1.86, and 45% of patients had the complete clinical triad. Severe cerebral involvement at onset was associated with a higher risk of cerebral exacerbations within the first year and with an increased long-term disability and dependency. Cognitive function improved in 75% of patients during follow-up. At disease onset, hearing loss excluding low frequencies occurred in 46.7%. Relapse of hearing loss was associated with greater impairment in daily activities. Male sex and elevated CSF protein levels were linked to poorer prognosis. Cerebral and inner ear exacerbations were most common in the first year while retinal exacerbations occurred more frequently, mainly within the first 2 years. Approximately 50% of patients resumed employment while 25% did not return to work.</p><p><strong>Discussion: </strong>Current treatment strategies for SuS do not fully prevent relapses. Severe brain manifestation at onset, male sex, and high CSF protein levels are risk factors of a worse prognosis of disability and dependence, indicating the need for intensive treatment. High-frequency hearing loss does not exclude SuS diagnosis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200357"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}