{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:19:45Z","timestamp":1790129985239,"version":"4.0.1"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare but debilitating disease within the stiff person syndrome (SPS) spectrum characterised by muscle rigidity, spasms, myoclonus, dysautonomia, and brainstem dysfunction. The exact pathogenetic mechanism is unclear, although there is an association with the presence of glycine receptor antibodies in serum and cerebrospinal fluid, and some cases are paraneoplastic. Here, we report a case of paraneoplastic, glycine receptor antibody-positive PERM associated with an otherwise subclinical monoclonal B-cell lymphocytosis (MBL) of the non-CLL phenotype, which may be, in turn, likely secondary to long-term methotrexate use [i.e., methotrexate-associated lymphoproliferative disorder (MTX-LPD)] or an underlying autoimmune disease. Treatment with multiple lines of initial induction immunomodulatory therapies, followed by maintenance rituximab, achieved long-term remission of the neurologic, haematological, and rheumatologic disease. This is, to our knowledge, the first reported association between PERM and MBL, or between PERM and MTX-LPD.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1436733","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T05:26:25Z","timestamp":1729056385000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Paraneoplastic progressive encephalomyelitis with rigidity and myoclonus associated with monoclonal B-cell lymphocytosis in the setting of longstanding methotrexate use: case report"],"prefix":"10.3389","volume":"15","author":[{"given":"Fangzhi (Frank)","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Ruhul","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gi Tae","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Mousapasandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jed","family":"Kitson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Selim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Ip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/brain\/99.1.27","article-title":"Progressive encephalomyelitis with rigidity: its relation to \u201cSubacute myoclonic spinal neuronitis\u201d and to the \u201cStiff man syndrome","volume":"99","author":"Whiteley","year":"1976","journal-title":"Brain"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1177\/17562864211003486","article-title":"GAD antibody-spectrum disorders: progress in clinical phenotypes, immunopathogenesis and therapeutic interventions","volume":"14","author":"Tsiortou","year":"2021","journal-title":"Ther Adv Neurological Disord"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1209302","article-title":"An update on Malignant tumor-related stiff person syndrome spectrum disorders: clinical mechanism, treatment, and outcomes","volume":"14","author":"Peng","year":"2023","journal-title":"Front Neurol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000327606.50322.f0","article-title":"Progressive encephalomyelitis, rigidity, and myoclonus: A novel glycine receptor antibody","volume":"71","author":"Hutchinson","year":"2008","journal-title":"Neurology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2009.12.025","article-title":"Progressive encephalomyelitis with rigidity and myoclonus preceding otherwise asymptomatic hodgkin\u2019s lymphoma","volume":"291","author":"Schmidt","year":"2010","journal-title":"J Neurological Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu142","article-title":"Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes","volume":"137","author":"Carvajal-Gonz\u00e1lez","year":"2014","journal-title":"Brain"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00401","article-title":"Progressive encephalomyelitis with rigidity and myoclonus associated with anti-glyR antibodies and hodgkin\u2019s lymphoma: A case report","volume":"8","author":"Borellini","year":"2017","journal-title":"Front Neurol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.01017","article-title":"Progressive encephalomyelitis with rigidity and myoclonus with thymoma: A case report and literature review","volume":"11","author":"Su","year":"2020","journal-title":"Front Neurol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/589154","article-title":"Anti-glycine receptor antibody mediated progressive encephalomyelitis with rigidity and myoclonus associated with breast cancer","volume":"2013","author":"De Blauwe","year":"2013","journal-title":"Case Rep Neurological Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1590\/S0004-282X2004000300033","article-title":"Progressive encephalomyelitis with rigidity: A paraneoplastic presentation of oat cell carcinoma of the lung. Case report","volume":"62","author":"Spitz","year":"2004","journal-title":"Arquivos Neuro-Psiquiatria"},{"key":"B11","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1186\/s13256-023-04059-w","article-title":"Progressive encephalomyelitis with rigidity and myoclonus (PERM) associated with anti-glycine receptor antibodies and urothelial carcinoma: A case report","volume":"17","author":"Ali","year":"2023","journal-title":"J Med Case Rep"},{"key":"B12","doi-asserted-by":"publisher","first-page":"4168","DOI":"10.1182\/blood.V130.Suppl_1.4168.4168","article-title":"Clinicopathological study of methotrexate-associated lymphoproliferative disorders in rheumatoid arthritis patients: histological classification and predictive factors for disease progression","volume":"130","author":"Kurita","year":"2017","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the world health organization classification of haematolymphoid tumours: lymphoid neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-643569","article-title":"The 2016 revision of the world health organization classification of lymphoid neoplasms","volume":"127","author":"Swerdlow","year":"2016","journal-title":"Blood"},{"key":"B15","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.beha.2016.08.028","article-title":"Clonal B-cell lymphocytosis of marginal zone origin","volume":"30","author":"Xochelli","year":"2017","journal-title":"Best Pract Res Clin Haematology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000438","article-title":"Glycine receptor modulating antibody predicting treatable stiff-person spectrum disorders","volume":"5","author":"Hinson","year":"2018","journal-title":"Neurol Neuroimmunology Neuroinflamm"},{"key":"B17","first-page":"ECR59","article-title":"Paraneoplastic stiff-person syndrome, heterotopic soft tissue ossification and gonarthritis in a HLA B27-positive woman preceding the diagnosis of Hodgkin\u2019s lymphoma","volume":"9","author":"Gutmann","year":"2006","journal-title":"Haematologica"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.26300\/cd20-cq84","article-title":"Progressive encephalomyelitis with rigidity and myoclonus treated with rituximab: case report and review of the literature","volume":"1","author":"Chuck","year":"2022","journal-title":"Brown Hosp Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1436733\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T05:26:29Z","timestamp":1729056389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1436733\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,16]]},"references-count":18,"alternative-id":["10.3389\/fimmu.2024.1436733"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1436733","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,16]]},"article-number":"1436733"}}