Florian Lamblin, Jeroen Kerstens, Sergio Muñiz-Castrillo, Alberto Vogrig, David Goncalves, Veronique Rogemond, Geraldine Picard, Marine Villard, Anne-Laurie Pinto, Marleen H Van Coevorden-Hameete, Marienke A De Bruijn, Juna M De Vries, Marco Schreurs, Louise Tyvaert, Lucie Hopes, Jerome Aupy, Cecile Marchal, Dimitri Psimaras, Laurent Kremer, Veronique Bourg, Jean-Christophe G Antoine, Adrien Wang, Philippe Kahane, Sophie Demeret, Guido Ahle, Vicente Peris Sempere, Noemie Timestit, Mikail Nourredine, Aurelien Maureille, Marie Benaiteau, Bastien Joubert, Emmanuel Mignot, Maarten J Titulaer, Jerome Honnorat
{"title":"Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABA<sub>B</sub>R Antibodies.","authors":"Florian Lamblin, Jeroen Kerstens, Sergio Muñiz-Castrillo, Alberto Vogrig, David Goncalves, Veronique Rogemond, Geraldine Picard, Marine Villard, Anne-Laurie Pinto, Marleen H Van Coevorden-Hameete, Marienke A De Bruijn, Juna M De Vries, Marco Schreurs, Louise Tyvaert, Lucie Hopes, Jerome Aupy, Cecile Marchal, Dimitri Psimaras, Laurent Kremer, Veronique Bourg, Jean-Christophe G Antoine, Adrien Wang, Philippe Kahane, Sophie Demeret, Guido Ahle, Vicente Peris Sempere, Noemie Timestit, Mikail Nourredine, Aurelien Maureille, Marie Benaiteau, Bastien Joubert, Emmanuel Mignot, Maarten J Titulaer, Jerome Honnorat","doi":"10.1212/NXI.0000000000200229","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABA<sub>B</sub>R-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied.</p><p><strong>Methods: </strong>Patients with GABA<sub>B</sub>R-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples.</p><p><strong>Results: </strong>A total of 111 patients (44/111 [40%] women) were enrolled, including 84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases (cancer status was undetermined for 9 patients). Patients presented with seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54 years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, <i>p</i> < 0.001) and showed a different demographic distribution. Nonparaneoplastic patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], <i>p</i> = 0.02), were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], <i>p</i> < 0.001), and were more frequently treated with second-line immunotherapy (11/18 [61%] vs 18/82 [22%], <i>p</i> = 0.003). However, no difference of IgG subclass or HLA association was observed, although sample size was small (10 and 26 patients, respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13 of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases (<i>p</i> = 0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last follow-up (<i>p</i> = 0.008), respectively. Neurologic outcome no longer differed after adjustment for confounding factors but seemed to be negatively associated with increased age and ICU admission. A better survival was associated with nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs.</p><p><strong>Discussion: </strong>Nonparaneoplastic GABA<sub>B</sub>R-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABA<sub>B</sub>R-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":7.8000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087025/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurology® Neuroimmunology & Neuroinflammation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1212/NXI.0000000000200229","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/4/24 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background and objectives: While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABABR-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied.
Methods: Patients with GABABR-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples.
Results: A total of 111 patients (44/111 [40%] women) were enrolled, including 84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases (cancer status was undetermined for 9 patients). Patients presented with seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54 years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, p < 0.001) and showed a different demographic distribution. Nonparaneoplastic patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], p = 0.02), were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], p < 0.001), and were more frequently treated with second-line immunotherapy (11/18 [61%] vs 18/82 [22%], p = 0.003). However, no difference of IgG subclass or HLA association was observed, although sample size was small (10 and 26 patients, respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13 of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases (p = 0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last follow-up (p = 0.008), respectively. Neurologic outcome no longer differed after adjustment for confounding factors but seemed to be negatively associated with increased age and ICU admission. A better survival was associated with nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs.
Discussion: Nonparaneoplastic GABABR-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABABR-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.
期刊介绍：
Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.
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