Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Racial and Ethnic Disparities in the Incidence of Anti-NMDA Receptor Encephalitis.","authors":"Samir Alsalek, Kathryn B Schwarzmann, Sakar Budhathoki, Viridiana Hernandez-Lopez, Jessica B Smith, Bonnie H Li, Annette Langer-Gould","doi":"10.1212/NXI.0000000000200255","DOIUrl":"10.1212/NXI.0000000000200255","url":null,"abstract":"<p><strong>Objectives: </strong>To estimate the incidence of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of >10 million person-years of observation from members of Kaiser Permanente Southern California, 2011-2022. The electronic health record of individuals with text-string mention of <i>NMDA</i> and <i>encephalitis</i> were reviewed to identify persons who met diagnostic criteria for anti-NMDAR encephalitis. Age-standardized and sex-standardized incidences stratified by race and ethnicity were estimated according to the 2020 US Census population.</p><p><strong>Results: </strong>We identified 70 patients who met diagnostic criteria for anti-NMDAR encephalitis. The median age at onset was 23.7 years (IQR = 14.2-31.0 years), and 45 (64%) were female patients. The age-standardized and sex-standardized incidence of anti-NMDAR encephalitis per 1 million person-years was significantly higher in Black (2.94, 95% CI 1.27-4.61), Hispanic (2.17, 95% CI 1.51-2.83), and Asian/Pacific Island persons (2.02, 95% CI 0.77-3.28) compared with White persons (0.40, 95% CI 0.08-0.72). Ovarian teratomas were found in 58.3% of Black female individuals and 10%-28.6% in other groups.</p><p><strong>Discussion: </strong>Anti-NMDA receptor encephalitis disproportionately affected Black, Hispanic, or Asian/Pacific Island persons. Ovarian teratomas were a particularly common trigger in Black female individuals. Future research should seek to identify environmental and biological risk factors that disproportionately affect minoritized individuals residing in the United States.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200255"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904825","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":"Synaptic Protein Loss in Extracellular Vesicles Reflects Brain and Retinal Atrophy in People With Multiple Sclerosis.","authors":"Dimitrios C Ladakis, Michael Vreones, Joseph Blommer, Kimystian L Harrison, Matthew D Smith, Eleni S Vasileiou, Hussein Moussa, Gelareh Ahmadi, Omar Ezzedin, Anna L DuVal, Blake E Dewey, Jerry L Prince, Kathryn C Fitzgerald, Elias S Sotirchos, Shiv Saidha, Peter A Calabresi, Dimitrios Kapogiannis, Pavan Bhargava","doi":"10.1212/NXI.0000000000200257","DOIUrl":"10.1212/NXI.0000000000200257","url":null,"abstract":"<p><strong>Objectives: </strong>To assess whether the rate of change in synaptic proteins isolated from neuronally enriched extracellular vesicles (NEVs) is associated with brain and retinal atrophy in people with multiple sclerosis (MS).</p><p><strong>Methods: </strong>People with MS were followed with serial blood draws, MRI (MRI), and optical coherence tomography (OCT) scans. NEVs were immunocaptured from plasma, and synaptopodin and synaptophysin proteins were measured using ELISA. Subject-specific rates of change in synaptic proteins, as well as brain and retinal atrophy, were determined and correlated.</p><p><strong>Results: </strong>A total of 50 people with MS were included, 46 of whom had MRI and 45 had OCT serially. The rate of change in NEV synaptopodin was associated with whole brain (rho = 0.31; <i>p</i> = 0.04), cortical gray matter (rho = 0.34; <i>p</i> = 0.03), peripapillary retinal nerve fiber layer (rho = 0.37; <i>p</i> = 0.01), and ganglion cell/inner plexiform layer (rho = 0.41; <i>p</i> = 0.006) atrophy. The rate of change in NEV synaptophysin was also correlated with whole brain (rho = 0.31; <i>p</i> = 0.04) and cortical gray matter (rho = 0.31; <i>p</i> = 0.049) atrophy.</p><p><strong>Discussion: </strong>NEV-derived synaptic proteins likely reflect neurodegeneration and may provide additional circulating biomarkers for disease progression in MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200257"},"PeriodicalIF":8.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956892","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":"Primary Angiitis of the CNS: Differences in the Profile Between Subtypes and Outcomes From an Indian Cohort.","authors":"Naveen K Paramasivan, Dev P Sharma, S M Krishna Mohan, Soumya Sundaram, Sapna E Sreedharan, P Sankara Sarma, P N Sylaja","doi":"10.1212/NXI.0000000000200262","DOIUrl":"10.1212/NXI.0000000000200262","url":null,"abstract":"<p><strong>Background and objectives: </strong>Primary angiitis of the CNS (PACNS) is a rare disease that has significant morbidity and mortality. Subtypes of PACNS can have different presentations that could be missed with certain diagnostic modalities, further increasing diagnostic complexity. We sought to distinguish the subtypes of PACNS and describe their outcomes in an Indian cohort.</p><p><strong>Methods: </strong>Adult patients in this retrospective single-center cohort study were reviewed from the PACNS database between 2000 and 2019. Diagnosis was made as per Calabrese and Malleck criteria. Small and medium vessel vasculitis was defined, and their clinical and radiologic profile, treatment, and outcomes were compared. Functional outcomes were noted at 6-month, 1-year, and at last follow-up, while relapses were noted at last follow-up. A poor outcome was defined as modified Rankin Scale >2.</p><p><strong>Results: </strong>Seventy-two patients fulfilled the inclusion criteria of whom 50 (69.4%) were male. The small vessel vasculitis subtype had a younger age at onset (30.5 vs 40.5 years, <i>p</i> = 0.014), presented less often as a stroke (22% vs 62%, <i>p</i> = 0.001), and had greater delay in diagnosis and treatment initiation (median of 620 days vs 118 days, <i>p</i> = 0.001) compared with medium vessel vasculitis subtype. Although no difference was noted at 6 months, the small vessel vasculitis group had poor outcomes at 1-year and last follow-up (57% vs 20%, <i>p</i> = 0.011 and 72% vs 34%, <i>p</i> = 0.005, respectively) and had more relapses at last follow-up (89% vs 30%, <i>p</i> < 0.001) when compared with the medium vessel vasculitis group. On analyzing the entire cohort, 50 of 72 (69%) and 37 of 53 (69.8%) patients had a good outcome at 6 months and 1 year, respectively. Relapse was noted in 35 of 72 (49%) at final follow-up. The choice of the treatment regimen did not predict outcomes or relapses.</p><p><strong>Discussion: </strong>The small vessel vasculitis subtype of PACNS is a distinct entity that has diagnostic and treatment delays with poor long-term outcomes and more relapses. Recognizing the different subtypes of PACNS may help to expedite diagnosis and plan treatment.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200262"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11197987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301109","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":"Cerebrospinal Fluid-In Gradient of Cortical and Deep Gray Matter Damage in Multiple Sclerosis.","authors":"Martina Rubin, Elisabetta Pagani, Paolo Preziosa, Alessandro Meani, Loredana Storelli, Monica Margoni, Massimo Filippi, Maria A Rocca","doi":"10.1212/NXI.0000000000200271","DOIUrl":"10.1212/NXI.0000000000200271","url":null,"abstract":"<p><strong>Background and objectives: </strong>A CSF-in gradient in cortical and thalamic gray matter (GM) damage has been found in multiple sclerosis (MS). We concomitantly explored the patterns of cortical, thalamic, and caudate microstructural abnormalities at progressive distances from CSF using a multiparametric MRI approach.</p><p><strong>Methods: </strong>For this cross-sectional study, from 3T 3D T1-weighted scans, we sampled cortical layers at 25%-50%-75% depths from pial surface and thalamic and caudate bands at 2-3-4 voxels from the ventricular-GM interface. Using linear mixed models, we tested between-group comparisons of magnetization transfer ratio (MTR) and R2* layer-specific z-scores, CSF-in across-layer z-score changes, and their correlations with clinical (disease duration and disability) and structural (focal lesions, brain, and choroid plexus volume) MRI measures.</p><p><strong>Results: </strong>We enrolled 52 patients with MS (33 relapsing-remitting [RRMS], 19 progressive [PMS], mean age: 46.4 years, median disease duration: 15.1 years, median: EDSS 2.0) and 70 controls (mean age 41.5 ± 12.8). Compared with controls, RRMS showed lower MTR values in the outer and middle cortical layers (false-discovery rate [FDR]-<i>p</i> ≤ 0.025) and lower R2* values in all 3 cortical layers (FDR-<i>p</i> ≤ 0.016). PMS had lower MTR values in the outer and middle cortical (FDR-<i>p</i> ≤ 0.016) and thalamic (FDR-<i>p</i> ≤ 0.048) layers, and in the outer caudate layer (FDR-<i>p</i> = 0.024). They showed lower R2* values in the outer cortical layer (FDR-<i>p</i> = 0.003) and in the outer thalamic layer (FDR-<i>p</i> = 0.046) and higher R2* values in all 3 caudate layers (FDR-<i>p</i> ≤ 0.031). Both RRMS and PMS had a gradient of damage, with lower values closer to the CSF, for cortical (FDR-<i>p</i> ≤ 0.002) and thalamic (FDR-<i>p</i> ≤ 0.042) MTR. PMS showed a gradient of damage for cortical R2* (FDR-<i>p</i> = 0.005), thalamic R2* (FDR-<i>p</i> = 0.004), and caudate MTR (FDR-<i>p</i> ≤ 0.013). Lower MTR and R2* of outer cortical, thalamic, and caudate layers and steeper gradient of damage toward the CSF were significantly associated with older age, higher T2-hyperintense white matter lesion volume, higher thalamic lesion volume, and lower brain volume (β ≥ 0.08, all FDR-<i>p</i> ≤ 0.040). Lower MTR of outer caudate layer was associated with more severe disability (β = -0.26, FDR-<i>p</i> = 0.040). No correlations with choroid plexus volume were found.</p><p><strong>Discussion: </strong>CSF-in damage gradients are heterogeneous among different GM regions and through MS course, possibly reflecting different dynamics of demyelination and iron loss/accumulation.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200271"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11197989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427375","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":"Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis.","authors":"Jan D Lunemann, Harald Hegen, Luisa María Villar, Konrad Rejdak, Augusto Sao-Aviles, Pere Carbonell-Mirabent, Jaume Sastre-Garriga, Neus Mongay-Ochoa, Klaus Berek, Sergio Martínez-Yélamos, Francisco Pérez-Miralles, Ahmed Abdelhak, Franziska Bachhuber, Hayrettin Tumani, Jan N Lycke, Igal Rosenstein, Roberto Alvarez-Lafuente, Tamara Castillo-Trivino, David Otaegui, Sara Llufriu, Yolanda Blanco, Antonio J Sánchez López, Juan Antonio Garcia Merino, Nicolas Fissolo, Lucia Gutierrez, Javier Villacieros-Álvarez, Enric Monreal, Adrián Valls-Carbó, Heinz Wiendl, Xavier Montalban, Manuel Comabella","doi":"10.1212/NXI.0000000000200270","DOIUrl":"10.1212/NXI.0000000000200270","url":null,"abstract":"<p><strong>Background and objectives: </strong>The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS).</p><p><strong>Methods: </strong>Sixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up).</p><p><strong>Results: </strong>In short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; <i>p</i> = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; <i>p</i> = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; <i>p</i> = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; <i>p</i> = 0.025).</p><p><strong>Discussion: </strong>Proteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200270"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443132","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":"Management of Autoimmune Encephalitis in a 7-Year-Old Child With CTLA-4 Haploinsufficiency and AMPA Receptor Antibodies: A Case Report.","authors":"Marjolijn S W Quaak, Michiel S J S Buijze, Virginie J M Verhoeven, Clementien Vermont, Emmeline P Buddingh, Maud Heredia, Janneke N Samsom, Maarten J Titulaer, Annemarie M van Rossum, Sylvia Kamphuis, Rinze F Neuteboom","doi":"10.1212/NXI.0000000000200254","DOIUrl":"10.1212/NXI.0000000000200254","url":null,"abstract":"<p><strong>Objectives: </strong>We report on the therapeutic management of early-onset severe neurologic symptoms in cytotoxic T lymphocyte antigen-4 haploinsufficiency (CTLA-4h) and the presence of antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) as an important finding.</p><p><strong>Methods: </strong>This is a case report from a Dutch academic hospital. Repeated clinical examinations, repeated brain MRI and extended diagnostics on serum and CSF were performed. We used the CARE checklist.</p><p><strong>Results: </strong>A 7-year-old boy was diagnosed with CTLA-4h based on family screening. On diagnosis, he had mild chronic diarrhea and autism spectrum disorder, but no abnormalities in extensive laboratory screening. Six months later, he presented with sudden-onset autoimmune encephalitis. Repeated brain MRI revealed no abnormalities, but immunohistochemistry analysis on serum and CSF showed the presence of AMPAR antibodies. Treatment was initially focused on immunomodulation and targeted CTLA-4 replacement therapy. Because of the persistent fluctuating cerebellar and neuropsychiatric symptoms and the potential clinical significance of the AMPAR antibodies, treatment was intensified with repetition of first-line immunomodulation and rituximab. This combined therapy resulted in sustained clinical improvement and served as a bridge to curative hematopoietic stem cell transplantation.</p><p><strong>Discussion: </strong>This case illustrates the rare early onset of autoimmune encephalitis and presence of AMPAR antibodies in CTLA-4h. Targeted CTLA-4 replacement therapy resulted in a partial response. However, awaiting its optimal therapeutic effect, refractory CNS symptoms required intensification of immunomodulation. The identification of AMPAR antibodies guided our treatment decisions.</p><p><strong>Classification of evidence: </strong>This provides Class IV evidence. It is a single observational study without controls.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200254"},"PeriodicalIF":8.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904798","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":"PET Study of Microglial Activation in Kleine-Levin Syndrome.","authors":"Lucie Barateau, Anis Krache, Alexandre Da Costa, Michel Lecendreux, Sofiene Chenini, Nicolas Arlicot, Patrick Vourc'h, Mathieu Alonso, Anne-Sophie Salabert, Séverine Beziat, Isabelle Jaussent, Denis Mariano-Goulart, Pierre Payoux, Yves Dauvilliers","doi":"10.1212/NXI.0000000000200263","DOIUrl":"10.1212/NXI.0000000000200263","url":null,"abstract":"<p><strong>Objectives: </strong>Kleine-Levin syndrome (KLS) is a rare recurrent hypersomnolence disorder associated with cognitive and behavioral disturbances, of unknown origin, but inflammatory mechanisms could be involved. We aimed to explore in vivo microglia activation using [¹⁸F]DPA-714 PET imaging in patients with KLS compared with controls, and during symptomatic vs asymptomatic periods.</p><p><strong>Methods: </strong>Patients with KLS and controls underwent a standardized clinical evaluation and PET imaging, using a radiolabeled ligand specific to the 18 kDa translocator protein. Images were processed on the PMOD (peripheral module) interface using a standard uptake value (SUV). Five regions of interest (ROIs) were analyzed: hypothalamus, thalamus, frontal area, cerebellum, and whole brain. SUV ratios (SUVr) were calculated by normalizing SUV with cerebellum uptake.</p><p><strong>Results: </strong>Images of 17 consecutive patients with KLS (7 during episodes, 10 out of episodes) and 14 controls were analyzed. We found no SUV/SUVr difference between KLS and controls, between patients in and out episodes in all ROIs, and no correlation between SUVr and episode duration at the time of PET scan. No association was found between SUVr and sex, disease duration, or orexin levels.</p><p><strong>Discussion: </strong>Our findings do not support the presence of neuroinflammation in KLS. Further research is needed to identify relevant biomarkers in KLS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200263"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420150","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":"Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE).","authors":"Aurélie Hanin, Le Zhang, Anita J Huttner, Isabelle Plu, Bertrand Mathon, Franck Bielle, Vincent Navarro, Lawrence J Hirsch, David A Hafler","doi":"10.1212/NXI.0000000000200259","DOIUrl":"10.1212/NXI.0000000000200259","url":null,"abstract":"<p><strong>Background and objectives: </strong>New-onset refractory status epilepticus (NORSE) occurs in previously healthy children or adults, often followed by refractory epilepsy and poor outcomes. The mechanisms that transform a normal brain into an epileptic one capable of seizing for prolonged periods despite treatment remain unclear. Nonetheless, several pieces of evidence suggest that immune dysregulation could contribute to hyperexcitability and modulate NORSE sequelae.</p><p><strong>Methods: </strong>We used single-nucleus RNA sequencing to delineate the composition and phenotypic states of the CNS of 4 patients with NORSE, to better understand the relationship between hyperexcitability and immune disturbances. We compared them with 4 patients with chronic temporal lobe epilepsy (TLE) and 2 controls with no known neurologic disorder.</p><p><strong>Results: </strong>Patients with NORSE and TLE exhibited a significantly higher proportion of excitatory neurons compared with controls, with no discernible difference in inhibitory GABAergic neurons. When examining the ratio between excitatory neurons and GABAergic neurons for each patient individually, we observed a higher ratio in patients with acute NORSE or TLE compared with controls. Furthermore, a negative correlation was found between the ratio of excitatory to GABAergic neurons and the proportion of GABAergic neurons. The ratio between excitatory neurons and GABAergic neurons correlated with the proportion of resident or infiltrating macrophages, suggesting the influence of microglial reactivity on neuronal excitability. Both patients with NORSE and TLE exhibited increased expression of genes associated with microglia activation, phagocytic activity, and NLRP3 inflammasome activation. However, patients with NORSE had decreased expression of genes related to the downregulation of the inflammatory response, potentially explaining the severity of their presentation. Microglial activation in patients with NORSE also correlated with astrocyte reactivity, possibly leading to higher degrees of demyelination.</p><p><strong>Discussion: </strong>Our study sheds light on the complex cellular dynamics in NORSE, revealing the potential roles of microglia, infiltrating macrophages, and astrocytes in hyperexcitability and demyelination, offering potential avenues for future research targeting the identified pathways.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200259"},"PeriodicalIF":8.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11139018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175911","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":"Acute Paresthesia and Ataxia in a Child: \"Tick\" Outside the Box!","authors":"Federico G Seifarth, Rachel Desimone","doi":"10.1212/NXI.0000000000200232","DOIUrl":"10.1212/NXI.0000000000200232","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200232"},"PeriodicalIF":8.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11065324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867794","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":"MOG Antibody-Associated Disease in the Setting of Metastatic Melanoma Complicated by Immune Checkpoint Inhibitor Use.","authors":"Stephanie B Syc-Mazurek, Hannah Zhao-Fleming, Yong Guo, Nanthaya Tisavipat, John J Chen, Anastasia Zekeridou, Ioannis Kournoutas, Jacob J Orme, Matthew S Block, Claudia F Lucchinetti, Rafid Mustafa, Eoin P Flanagan","doi":"10.1212/NXI.0000000000200249","DOIUrl":"10.1212/NXI.0000000000200249","url":null,"abstract":"<p><strong>Objectives: </strong>Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune demyelinating disease rarely associated with malignancy. We report the clinical, MRI, immunopathology, and treatment response in a person with MOGAD and melanoma.</p><p><strong>Methods: </strong>This is a case report of a person with a multidisciplinary evaluation at a tertiary referral center.</p><p><strong>Results: </strong>A 52-year-old man presented with progressive encephalomyelitis that led to identification of metastatic melanoma. Investigations revealed positive MOG-IgG at high titers in serum (1:1,000; normal, <1:20) and CSF (1:4,096; normal, <1:2). MRI demonstrated multifocal T2 lesions with enhancement in the brain and spine. Brain biopsy showed demyelination and inflammation. MOG immunostaining was not present in the tumor tissue. He initially improved with methylprednisolone, plasmapheresis, prolonged oral steroid taper, and cancer-directed treatment with BRAF and MEK 1/2 inhibitors, but then developed bilateral optic neuritis. IV immunoglobulin (IVIG) was initiated. Five months later, he developed metastases and immune checkpoint inhibitor (ICI) treatment was started, which precipitated optic neuritis and myelitis despite IVIG and prednisone. Tocilizumab, an interleukin-6 receptor blocker, was started with excellent and sustained clinical and radiologic response.</p><p><strong>Discussion: </strong>This case revealed a presentation of MOGAD concurrent with melanoma without tumor MOG immunostaining. We highlight tocilizumab as a dual-purpose treatment of MOGAD and the neurologic immune-related adverse effect of ICI.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200249"},"PeriodicalIF":8.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11068306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867795","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}