{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:15:42Z","timestamp":1777644942857,"version":"3.51.4"},"reference-count":19,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2025,2,1]]},"abstract":"<jats:sec id=\"ab-nrv240007-4\"><jats:title>Importance<\/jats:title><jats:p>Immunoglobulin G4 (IgG4)\u2013related disease is an increasingly recognized fibroinflammatory condition that can involve multiple organs, including the pachymeninges. The understanding of IgG4-related pachymeningitis (IgG4-RP) remains limited because of its rarity and the predominance of knowledge derived from case reports and case series.<\/jats:p><\/jats:sec><jats:sec id=\"ab-nrv240007-5\"><jats:title>Objective<\/jats:title><jats:p>To systematically review and synthesize the clinical presentation, investigation findings, and prognosis of IgG4-RP to better understand its diagnosis and management.<\/jats:p><\/jats:sec><jats:sec id=\"ab-nrv240007-6\"><jats:title>Evidence Review<\/jats:title><jats:p>A comprehensive systematic review was conducted following guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed\/MEDLINE, Embase, and Scopus were searched from their inception until May 30, 2023, using terms related to IgG4-related disease and pachymeningitis without language or publication restrictions. Case reports and series that met the 2020 Revised Comprehensive Diagnostic Criteria or the 2019 American College of Rheumatology\/European League Against Rheumatism classification criteria were included. Data on clinical presentations, investigation findings, and treatment outcomes were extracted and summarized.<\/jats:p><\/jats:sec><jats:sec id=\"ab-nrv240007-7\"><jats:title>Findings<\/jats:title><jats:p>A total of 148 case reports contributed data from 208 patients. Their median (IQR) age was 52 (39-62) years; 132 patients were male (63.5%) and 76 female (36.5%). Headache and cranial nerve dysfunctions were the most common neurological manifestations. Systemic involvement was identified in nearly half of the patients. Diagnostic imaging often showed preferential involvement of cavernous sinus and middle fossa. Laboratory results highlighted elevated serum IgG4 levels in 97 of 147 patients (65%) of patients and cerebrospinal fluid pleocytosis in 43 of 82 patients (52%). Storiform fibrosis or obliterating phlebitis were uncommon pathological findings. Mortality was below 1% (1\/134; 0.7%), but only a third of patients presented complete clinical improvement, and the recurrence rate was 60 patients (40%) in a median (IQR) follow-up time of 9 (1-20) months. Glucocorticoids were the most commonly prescribed treatment, in 143 of 169 patients (85%); rituximab was prescribed as maintenance therapy in 53 of 169 patients (31%).<\/jats:p><\/jats:sec><jats:sec id=\"ab-nrv240007-8\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>IgG4-RP commonly presents with headaches and cranial nerve dysfunction, posing diagnostic challenges due to the significant absence of systemic manifestations, low IgG4 serum levels, and atypical pathological findings. Current treatment outcomes are limited by incomplete recovery and frequent relapses underscoring the necessity for new treatment strategies.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2024.3947","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T16:32:27Z","timestamp":1731947547000},"page":"193","source":"Crossref","is-referenced-by-count":9,"title":["Clinical Presentation, Investigation Findings, and Outcomes of IgG4-Related Pachymeningitis"],"prefix":"10.1001","volume":"82","author":[{"given":"Sara","family":"Terrim","sequence":"first","affiliation":[{"name":"Division of Neurology, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Vitor","family":"Mahler","sequence":"additional","affiliation":[{"name":"Division of Neurology, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fl\u00e1vio Vieira Marques","family":"Filho","sequence":"additional","affiliation":[{"name":"Division of Neurology, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leandro Tavares","family":"Lucato","sequence":"additional","affiliation":[{"name":"Division of Radiology, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrique Mayrink","family":"Giardini","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarso","family":"Adoni","sequence":"additional","affiliation":[{"name":"Division of Neurology, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guilherme Diogo","family":"Silva","sequence":"additional","affiliation":[{"name":"Division of Neurology, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"10","reference":[{"key":"nrv240007r1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/532612","article-title":"IgG4-related disease.","volume":"2013","author":"Stone","year":"2013","journal-title":"Int J Rheumatol"},{"issue":"1","key":"nrv240007r2","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1136\/annrheumdis-2019-216561","article-title":"The 2019 American College of Rheumatology\/European League Against Rheumatism classification criteria for IgG4-related disease.","volume":"79","author":"Wallace","year":"2020","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"nrv240007r3","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000568","article-title":"Immunoglobulin G4-related hypertrophic pachymeningitis: a case-oriented review.","volume":"6","author":"Levraut","year":"2019","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"6","key":"nrv240007r4","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1001\/jamaneurol.2014.243","article-title":"IgG4-related hypertrophic pachymeningitis: clinical features, diagnostic criteria, and treatment.","volume":"71","author":"Lu","year":"2014","journal-title":"JAMA Neurol"},{"issue":"1","key":"nrv240007r5","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s10067-022-06377-8","article-title":"Bibliometric analysis of IgG4-related disease research from 2003 to 2022 based on Web of Science Core Collection Databases.","volume":"42","author":"Lv","year":"2023","journal-title":"Clin Rheumatol"},{"issue":"1","key":"nrv240007r6","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13643-021-01626-4","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.","volume":"10","author":"Page","year":"2021","journal-title":"Syst Rev"},{"issue":"3","key":"nrv240007r7","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1080\/14397595.2020.1859710","article-title":"The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD.","volume":"31","author":"Umehara","year":"2021","journal-title":"Mod Rheumatol"},{"issue":"1","key":"nrv240007r8","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan: a web and mobile app for systematic reviews.","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst 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Neuroinflamm"},{"issue":"7","key":"nrv240007r12","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1136\/jnnp-2013-306410","article-title":"A nationwide survey of hypertrophic pachymeningitis in Japan.","volume":"85","author":"Yonekawa","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"11","key":"nrv240007r13","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1055\/s-0042-1758645","article-title":"Diagnostic and therapeutic approach to chronic meningitis in Brazil: a narrative review [in English and Portuguese].","volume":"80","author":"Silva","year":"2022","journal-title":"Arq Neuropsiquiatr"},{"issue":"5","key":"nrv240007r14","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1136\/ard-2023-224487","article-title":"Withdrawal of immunosuppressants and low-dose steroids in patients with stable IgG4-RD (WInS IgG4-RD): an investigator-initiated, multicentre, open-label, randomised controlled trial.","volume":"83","author":"Peng","year":"2024","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"nrv240007r15","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1111\/1756-185X.13088","article-title":"Efficacy between high and medium doses of glucocorticoid therapy in remission induction of IgG4-related diseases: a preliminary randomized controlled trial.","volume":"20","author":"Wu","year":"2017","journal-title":"Int J Rheum Dis"},{"issue":"6","key":"nrv240007r16","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1016\/j.semarthrit.2020.01.010","article-title":"Additive effect of leflunomide and glucocorticoids compared with glucocorticoids monotherapy in preventing relapse of IgG4-related disease: a randomized clinical trial.","volume":"50","author":"Wang","year":"2020","journal-title":"Semin Arthritis Rheum"},{"issue":"1","key":"nrv240007r17","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1093\/rheumatology\/key227","article-title":"Efficacy and safety of low dose mycophenolate mofetil treatment for immunoglobulin G4-related disease: a randomized clinical trial.","volume":"58","author":"Yunyun","year":"2019","journal-title":"Rheumatology (Oxford)"},{"issue":"6","key":"nrv240007r18","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1136\/annrheumdis-2014-206605","article-title":"Rituximab for IgG4-related disease: a prospective, open-label trial.","volume":"74","author":"Carruthers","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"nrv240007r19","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.ejim.2019.12.029","article-title":"Long-term efficacy of maintenance therapy with rituximab for IgG4-related disease.","volume":"74","author":"Campochiaro","year":"2020","journal-title":"Eur J Intern Med"}],"container-title":["JAMA 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