Neurology(R) neuroimmunology & neuroinflammation最新文献

{"title":"GABA-A Receptor Encephalitis After Autologous Hematopoietic Stem Cell Transplant forMultiple Myeloma: Three Cases and Literature Review.","authors":"Yoji Hoshina,&nbsp;Jonathan Galli,&nbsp;Ka-Ho Wong,&nbsp;Tibor Kovacsovics,&nbsp;Mary Steinbach,&nbsp;Karen L Salzman,&nbsp;Joseph Scott McNally,&nbsp;Eric Lancaster,&nbsp;M Mateo Paz Soldán,&nbsp;Stacey L Clardy","doi":"10.1212/NXI.0000000000200024","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200024","url":null,"abstract":"<p><strong>Background and objectives: </strong>The relationship between autologous hematopoietic stem cell transplant (aHSCT) for multiple myeloma (MM) and anti-GABA_A receptor (GABA_AR) encephalitis is unknown. We aimed to describe the clinical features, diagnostic process, and outcome of 3 cases of anti-GABA_AR encephalitis in patients with a history of prior aHSCT for MM.</p><p><strong>Methods: </strong>A case series of 3 patients. Anti-GABA_AR antibody was tested at the University of Pennsylvania Laboratory.</p><p><strong>Results: </strong>The patients were all male, aged 52 (case 1), 61 (case 2), and 62 (case 3) years at encephalitis symptom onset. The duration between completion of aHSCT and the onset of encephalitis was 43, 18, and 9 months, respectively. All 3 patients presented with new seizures and altered cognitive function. Other symptoms included headache and visual obscurations in cases 1 and 2 and intractable vertigo and mania in case 3. Brain MRI demonstrated nonenhancing multifocal T2-weighted/fluid-attenuated inversion recovery cortical and subcortical hyperintensities in all 3 patients. Cases 2 and 3 underwent brain biopsy before initiating immunomodulatory therapy, which demonstrated nonspecific encephalitis with astrogliosis in the white matter; these 2 patients were started on immunotherapy for the treatment of anti-GABA_AR encephalitis after 22 days and 3 months, respectively, from the first presentation. Case 1 was started on empiric immunotherapy within 8 days of presentation without requiring brain biopsy, given characteristic MRI imaging. CSF analysis demonstrated the presence of anti-GABA_AR antibodies in all 3 cases. Cases 1 and 3 also tested positive for anti-GABA_AR antibodies in the serum (serum test was not performed in case 2). Cases 1 and 2 recovered to work full-time within 1 year. Case 3 reported occasional myoclonic-like movement.</p><p><strong>Discussion: </strong>We highlight the importance of considering anti-GABA_AR encephalitis in patients with seizures, multifocal nonenhancing brain lesions, and a history of aHSCT for MM. Awareness in recovered post-aHSCT patients with MM may be crucial because prompt recognition can avoid brain biopsy and delays in treatment. The rapid initiation of immunotherapy while awaiting autoantibody results will likely improve functional outcomes.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/2d/NXI-2022-200030.PMC9417160.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40641945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal T-Cell Responses After a Third SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis on Ocrelizumab or Fingolimod.","authors":"","doi":"10.1212/NXI.0000000000200036","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200036","url":null,"abstract":"","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9417159/pdf/NXI-2022-200042.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40641946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IgG4 Valency Modulates the Pathogenicity of Anti-Neurofascin-155 IgG4 in Autoimmune Nodopathy.","authors":"Alexandre Jentzer,&nbsp;Arthur Attal,&nbsp;Clémence Roué,&nbsp;Julie Raymond,&nbsp;Cinta Lleixà,&nbsp;Isabel Illa,&nbsp;Luis Querol,&nbsp;Guillaume Taieb,&nbsp;Jérôme Devaux","doi":"10.1212/NXI.0000000000200014","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200014","url":null,"abstract":"<p><strong>Background and objectives: </strong>IgG4 autoantibodies to neurofascin-155 (Nfasc155) are associated with a subgroup of patients with chronic inflammatory demyelinating polyneuropathy (CIDP), currently named autoimmune nodopathy. We previously demonstrated that those antibodies alter conduction along myelinated axons by inducing Nfasc155 depletion and paranode destruction. In blood, IgG4 have the potency to exchange their moiety with other unrelated IgG4 through a process called Fab-arm exchange (FAE). This process results in functionally monovalent antibodies and may affect the pathogenicity of autoantibodies. Here, we examined this issue and whether FAE is beneficial or detrimental for Nfasc155 autoimmune nodopathy.</p><p><strong>Methods: </strong>The bivalency and monospecificity of anti-Nfasc155 were examined by sandwich ELISA in 10 reactive patients, 10 unreactive CIDP patients, and 10 healthy controls. FAE was induced in vitro using reduced glutathione and unreactive IgG4, and the ratio of the κ:λ light chain was monitored. To determine the pathogenic potential of bivalent anti-Nfasc155 IgG4, autoantibodies derived from patients were enzymatically cleaved into monovalent Fab and bivalent F(ab')₂ or swapped with unreactive IgG4 and then were injected in neonatal animals.</p><p><strong>Results: </strong>Monospecific bivalent IgG4 against Nfasc155 were detected in the serum of all reactive patients, indicating that a fraction of IgG4 have not undergone FAE in situ. These IgG4 were, nonetheless, capable of engaging into FAE with unreactive IgG4 in vitro, and this decreased the levels of monospecific antibodies and modulated the ratio of the κ:λ light chain. When injected in animals, monovalent anti-Nfasc155 Fab did not alter the formation of paranodes; by contrast, both native anti-Nfasc155 IgG4 and F(ab')₂ fragments strongly impaired paranode formation. The promotion of FAE with unreactive IgG4 also strongly diminished the pathogenic potential of anti-Nfasc155 IgG4 in animals and decreased IgG4 clustering on Schwann cells.</p><p><strong>Discussion: </strong>Our findings demonstrate that monospecific and bivalent anti-Nfasc155 IgG4 are detected in patients and that those autoantibodies are the pathogenic ones. The transformation of anti-Nfasc155 IgG4 into monovalent Fab or functionally monovalent IgG4 through FAE strongly decreases paranodal alterations. Bivalency thus appears crucial for Nfasc155 clustering and paranode destruction.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f8/1c/NXI-2022-200020.PMC9365386.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40597759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebellar Ataxia With Anti-DNER Antibodies: Outcomes and Immunologic Features.","authors":"Elise Peter,&nbsp;Le Duy Do,&nbsp;Salem Hannoun,&nbsp;Sergio Muñiz-Castrillo,&nbsp;Alberto Vogrig,&nbsp;Valentin Wucher,&nbsp;Anne-Laurie Pinto,&nbsp;Naura Chounlamountri,&nbsp;Walaa Zakaria,&nbsp;Veronique Rogemond,&nbsp;Geraldine Picard,&nbsp;Julien-Jacques Hedou,&nbsp;Aditya Ambati,&nbsp;Agusti Alentorn,&nbsp;Alexandra Traverse-Glehen,&nbsp;Mario Manto,&nbsp;Dimitri Psimaras,&nbsp;Emmanuel Mignot,&nbsp;Francois Cotton,&nbsp;Virginie Desestret,&nbsp;Jérôme Honnorat,&nbsp;Bastien Joubert","doi":"10.1212/NXI.0000000000200018","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200018","url":null,"abstract":"<p><strong>Background and objectives: </strong>There is no report on the long-term outcomes of ataxia with antibodies against Delta and Notch-like epidermal growth factor-related (DNER). We aimed to describe the clinical-immunologic features and long-term outcomes of patients with anti-DNER antibodies.</p><p><strong>Methods: </strong>Patients tested positive for anti-DNER antibodies between 2000 and 2020 were identified retrospectively. In those with available samples, immunoglobulin G (IgG) subclass analysis, longitudinal cerebellum volumetry, human leukocyte antigen isotyping, and CSF proteomic analysis were performed. Rodent brain membrane fractionation and organotypic cerebellar slices were used to study DNER cell-surface expression and human IgG binding to the Purkinje cell surface.</p><p><strong>Results: </strong>Twenty-eight patients were included (median age, 52 years, range 19-81): 23 of 28 (82.1%) were male and 23 of 28 (82.1%) had a hematologic malignancy. Most patients (27/28, 96.4%) had cerebellar ataxia; 16 of 28 (57.1%) had noncerebellar symptoms (cognitive impairment, neuropathy, and/or seizures), and 27 of 28 (96.4%) became moderately to severely disabled. Half of the patients (50%) improved, and 32.1% (9/28) had no or slight disability at the last visit (median, 26 months; range, 3-238). Good outcome significantly associated with younger age, milder clinical presentations, and less decrease of cerebellar gray matter volumes at follow-up. No human leukocyte antigen association was identified. Inflammation-related proteins were overexpressed in the patients' CSF. In the rodent brain, DNER was enriched in plasma membrane fractions. Patients' anti-DNER antibodies were predominantly IgG1/3 and bound live Purkinje cells in vitro.</p><p><strong>Discussion: </strong>DNER ataxia is a treatable condition in which nearly a third of patients have a favorable outcome. DNER antibodies bind to the surface of Purkinje cells and are therefore potentially pathogenic, supporting the use of B-cell-targeting treatments.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c8/86/NXI-2022-200024.PMC9359625.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40679247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity of Acetylcholine Receptor Autoantibody-Mediated Complement Activity in Patients With Myasthenia Gravis.","authors":"","doi":"10.1212/NXI.0000000000200017","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200017","url":null,"abstract":"","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352342/pdf/NXI-2022-200023.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40666723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rituximab-Induced Hypogammaglobulinemia and Risk of Infection in Neuromyelitis Optica Spectrum Disorders: A 14-Year Real-Life Experience.","authors":"Su-Hyun Kim,&nbsp;Na Young Park,&nbsp;Ki Hoon Kim,&nbsp;Jae-Won Hyun,&nbsp;Ho Jin Kim","doi":"10.1212/NXI.0000000000001179","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001179","url":null,"abstract":"<p><strong>Background and objectives: </strong>To investigate the frequency and predictors of hypogammaglobulinemia during long-term rituximab (RTX) treatment in patients with neuromyelitis optica spectrum disorder (NMOSD) and its association with infections.</p><p><strong>Methods: </strong>We retrospectively reviewed the data of patients with NMOSD who received RTX through the maintenance regimen based on memory B-cell detection for at least 1 year from 2006 to 2021 at an institutional referral center for NMOSD.</p><p><strong>Results: </strong>A total of 169 patients received a median of 10 courses (range 1-27) of RTX reinfusion after induction over a median of 8 (range, 1-15) years. Their mean serum immunoglobulin (Ig)G level began to decline significantly after 2 years of treatment, steadily declined at a rate of 2%-8% per year for the following 8 years, and then plateaued after 10 years. The proportion of patients with hypo-IgG (<6 g/L) increased from 1.2% after 1 year of treatment to 41% after 14 years of treatment. While being treated with RTX, 58 (34%) patients had 114 infections, of whom 14 (8%) patients had 15 severe infections. Multivariable logistic regression analyses identified duration of RTX treatment in years (odds ratio [OR] 1.234, 95% confidence interval [CI] 1.015-1.502), mean annual RTX dose (OR 0.063, 95% CI 0.009-0.434), history of mitoxantrone (OR 3.318, 95% CI 1.109-9.93), hypo-IgG at baseline (OR 40.552, 95% CI 3.024-543.786), and body mass index >25 kg/m² (OR 4.798, 95% CI 1.468-15.678) as independent predictors of hypo-IgG. The risk of infection during RTX treatment was independently associated with high Expanded Disability Status Scale scores (OR 1.427, 95% CI 1.2-1.697) and relapses during RTX treatment (OR 1.665, 95% CI 1.112-2.492), but not with hypogammaglobulinemia.</p><p><strong>Discussion: </strong>Over 14 years of long-term RTX treatment, IgG levels gradually decreased, and the frequency of hypo-IgG increased to 41% of the patients. Patients with prolonged memory B-cell depletion after RTX, previous mitoxantrone history, hypo-IgG at baseline, or obesity were at risk of developing RTX-induced hypogammaglobulinemia. Nevertheless, infection rates remained low during treatment, and reduced immunoglobulin levels were not associated with an increased incidence of infections.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/74/NEURIMMINFL2022039863.PMC9296048.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40519703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Intrathecal Activity of Follicular Helper T Cells in Patients With Relapsing-Remitting Multiple Sclerosis.","authors":"Rikke Holm Hansen,&nbsp;Jacob Talbot,&nbsp;Helene Højsgaard Chow,&nbsp;Malene Bredahl Hansen,&nbsp;Sophie Buhelt,&nbsp;Sebastian Herich,&nbsp;Nicholas Schwab,&nbsp;Marie Nathalie Nickelsen Hellem,&nbsp;Joergen Erik Nielsen,&nbsp;Finn Sellebjerg,&nbsp;Marina Rode von Essen","doi":"10.1212/NXI.0000000000200009","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200009","url":null,"abstract":"<p><strong>Background and objectives: </strong>Follicular helper T (Tfh) cells play a critical role in protective immunity helping B cells produce antibodies against foreign pathogens and are likely implicated in the pathogenesis of various autoimmune diseases. The purpose of this study was to investigate the role of Tfh cells in the pathogenesis of multiple sclerosis (MS).</p><p><strong>Methods: </strong>Using flow cytometry, we investigated phenotype, prevalence, and function of Tfh cells in blood and CSF from controls and patients with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS). In addition, an in vitro blood-brain barrier coculture assay of primary human astrocytes and brain microvascular endothelial cells grown in a Boyden chamber was used to assess the migratory capacity of peripheral Tfh cells.</p><p><strong>Results: </strong>This study identified 2 phenotypically and functionally distinct Tfh cell populations: CD25^- Tfh cells (Tfh1-like) and CD25^int Tfh cells (Tfh17-like). Whereas minor differences in Tfh cell populations were found in blood between patients with MS and controls, we observed an increased frequency of CD25^- Tfh cells in CSF of patients with RRMS and PPMS and CD25^int Tfh cells in patients with RRMS, compared with controls. Increasing frequencies of CSF CD25^- Tfh cells and the CD25^- Tfh/Tfr ratio scaled with increasing IgG index in patients with RRMS. Despite an increased prevalence of intrathecal Tfh cells in patients with MS, no difference in the migratory capacity of circulating Tfh cells was observed between controls and patients with MS. Instead, CSF concentrations of CXCL13 scaled with total counts of Tfh and Tfr cell subsets in the CSF.</p><p><strong>Discussion: </strong>Our study indicates substantial changes in intrathecal Tfh dynamics, particularly in patients with RRMS, and suggests that the intrathecal inflammatory environment in patients with RRMS promotes recruitment of peripheral Tfh cells rather than the Tfh cells having an increased capacity to migrate to CNS.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/01/70/NXI-2022-200010.PMC9621607.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40591308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Cell-Based Assay for Alpha-3 Nicotinic Receptor Antibodies Detects Antibodies Exclusively in Autoimmune Autonomic Ganglionopathy.","authors":"","doi":"10.1212/NXI.0000000000001177","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001177","url":null,"abstract":"","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278123/pdf/NXI-D-22-00003.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40497163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term Effectiveness of IVIg Maintenance Therapy in 36 Patients With GAD Antibody-Positive Stiff-Person Syndrome.","authors":"Jessica Yi,&nbsp;Marinos C Dalakas","doi":"10.1212/NXI.0000000000200011","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200011","url":null,"abstract":"<p><strong>Background and objectives: </strong>IVIg has been the preferred immunotherapy in stiff-person syndrome (SPS) based on a 3-month controlled trial, but whether it is also effective in inducing long-term benefits or arresting disease progression is unknown. The information is needed because SPS is a progressively disabling disease and IVIg is liberally used as chronic therapy without efficacy data. The present study explores the long-term effects of IVIg in the largest cohort of well-characterized patients with SPS followed by the same clinicians over 10 years.</p><p><strong>Methods: </strong>Data of 36 patients (32 glutamic acid decarboxylase [GAD] positive), diagnosed and treated with monthly maintenance IVIg by the same neurologists, were analyzed. Response was assessed by physician-observed changes, patients' reports of symptom improvement, modified Rankin Scale (mRS) scores, and dependency trials evaluating symptom recurrence after stopping IVIg, prolonging infusion frequency, decreasing monthly dose, or wearing-off effects in between doses. Clinically meaningful long-term response was defined by improved mRS scores, improvement in physician-assessed stiffness, balance and gait, and functional decline with dependency trials.</p><p><strong>Results: </strong>Twenty-four of 36 (67%) patients had clinically meaningful response over a median 40-month period. Patients with improved mRS scores by 1-2 points manifested improved gait, posture, balance and decreased stiffness, spasms, and startle response; some patients using a wheelchair and those ambulating with devices walked unassisted. In 25% of responders, treatment benefit was sustained for a 40-month median period, but in 29.1%, it declined over a 39-month period; 12.5% exhibited a conditioning effect. Three of 5 patients with cerebellar GAD-SPS variant also improved over time. The 12 patients who did not respond the first 3 months remained unresponsive even if IVIg continued for several months.</p><p><strong>Discussion: </strong>This is a large study in 36 patients with SPS demonstrating that monthly maintenance IVIg therapy offers long-term benefits in 67% of patients for a median 3.3-year period. Because 29.1% experienced diminishing benefit over time due to disease progression, the study highlights the need for more effective therapies.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9d/0c/NXI-2022-200017.PMC9262284.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40479092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMPA Receptor Encephalitis in a Patient With Metastatic Breast Cancer Receiving Palbociclib: A Case Report.","authors":"Elizabeth Matthews,&nbsp;Barrie Schmitt,&nbsp;Michlene Passeri,&nbsp;Christopher Mizenko,&nbsp;Karen Orjuela,&nbsp;Amanda Piquet","doi":"10.1212/NXI.0000000000200012","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200012","url":null,"abstract":"<p><strong>Objective: </strong>To report a case of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis (AMPARE) as a potential immune-mediated complication of palbociclib (a cyclin-dependent kinase 4/6 inhibitor).</p><p><strong>Background: </strong>Medication-induced autoimmune encephalitis is an increasingly recognized entity. To date, cases have been reported with immune checkpoint inhibitors (ICIs), typically within 3 months and while cancer is responding to immunotherapy.</p><p><strong>Results: </strong>A 55-year-old woman with metastatic breast cancer presented with new-onset neurologic symptoms. After diagnosis and treatment in 2008, she was in remission from 2010 to 2021. In April 2021, she developed metastatic recurrence. She started palbociclib in June 2021. PET scan in August 2021 showed improved metastases without new lesions. In September 2021, she developed encephalopathy, vertical nystagmus, and ataxia. Workup revealed AMPA-R antibodies. Palbociclib was stopped, and she received steroids, IVIg, and rituximab with marked improvement in her neurologic symptoms.</p><p><strong>Discussion: </strong>AMPARE is a well-described paraneoplastic syndrome. However, it is now understood that paraneoplastic syndromes can be driven by immunomodulatory medications, namely ICIs. Although palbociclib primarily prevents tumor proliferation, emerging data suggest that it may also be immunomodulatory. Given that our patient's AMPARE developed shortly after initiation of palbociclib while her cancer was responding to therapy, we postulate that it may have been unmasked by palbociclib, similarly to what has been reported with ICIs.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/aa/NXI-2022-200018.PMC9258979.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40486364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}