Neurological Involvement in a Portuguese Cohort of IgG4-Related Disease

Authors

  • João Moura *Shared first co-authorship. Neurology Department. Centro Hospitalar Universitário de Santo António. Porto. https://orcid.org/0000-0002-4212-906X
  • Maria João Malaquias *Shared first co-authorship. Neurology Department. Centro Hospitalar Universitário de Santo António. Porto.
  • Firmina Jorge Neurology Department. Centro Hospitalar Universitário de Santo António. Porto.
  • Eduarda Pinto Neurorradiology Department. Centro Hospitalar Universitário de Santo António. Porto.
  • Ana Sardoeira Neurology Department. Centro Hospitalar Universitário de Santo António. Porto.
  • Inês Laranjinha Neurology Department. Centro Hospitalar Universitário de Santo António. Porto.
  • Vanessa Oliveira Neurology Department. Centro Hospitalar Universitário de Santo António. Porto.
  • Ana Paula Sousa Neurophysiology Department. Centro Hospitalar Universitário de Santo António. Porto.
  • Joana Damásio Neurology Department. Centro Hospitalar Universitário de Santo António. Porto; Center for Predictive and Preventive Genetics (CGPP). Institute for Molecular and Cell Biology (IBMC). Instituto de Investigação e Inovação em Saúde (i3S). Universidade do Porto. Porto.
  • Luís Maia Neurology Department. Centro Hospitalar Universitário de Santo António. Porto.
  • Nuno Vila-Chã Neurology Department. Centro Hospitalar Universitário de Santo António. Porto.
  • Raquel Samões Neurology Department. Centro Hospitalar Universitário de Santo António. Porto.
  • Ricardo Taipa Portuguese Brain Bank. Centro Hospitalar Universitário de Santo António. Porto; Unit for Multidisciplinary Research in Biomedicine. Instituto de Ciências Biomédicas Abel Salazar. Universidade do Porto. Porto.
  • Ana Martins da Silva Neurology Department. Centro Hospitalar Universitário de Santo António. Porto; Unit for Multidisciplinary Research in Biomedicine. Instituto de Ciências Biomédicas Abel Salazar. Universidade do Porto. Porto.
  • Ernestina Santos Neurology Department. Centro Hospitalar Universitário de Santo António. Porto; Unit for Multidisciplinary Research in Biomedicine. Instituto de Ciências Biomédicas Abel Salazar. Universidade do Porto. Porto.

DOI:

https://doi.org/10.20344/amp.20767

Keywords:

Immunoglobulin G, Immunoglobulin G4-Related Disease/diagnosis, Nervous System Diseases

Abstract

Introduction: Neurological involvement in immunoglobulin G4-related disease (IgG4-RD) is increasingly recognized. Its diagnosis can be challenging due to clinical mimics and difficulty in obtaining nervous system biopsies. The aim of this study was to describe a cohort of neurological IgG4-RD patients.
Methods: Patients were recruited from a neuroimmunology tertiary center. Clinical, laboratory, neuroimaging and histological data were reviewed.
Results: Fifteen patients (60% women), with a median age of 53 years (48.5 – 65.0) were included: 13 (86.7%) classified as possible IgG4-RD, one (6.7%) as probable and one (6.7%) as definitive. The most common neurological phenotypes were meningoencephalitis (26.7%), orbital pseudotumor (13.3%), cranial neuropathies (13.3%), peripheral neuropathy (13.3%), and longitudinally extensive transverse myelitis (LTEM) (13.3%). Median serum IgG4 concentration was 191.5 (145.0 – 212.0) mg/dL. Seven in 14 patients had CSF pleocytosis (50.0%) and oligoclonal bands restricted to the intrathecal compartment, while most cases presented elevated CSF proteins (64.3%). Magnetic resonance imaging abnormalities included white matter lesions in four (26.7%), hypertrophic pachymeningitis in two (13.3%), and LETM in two (13.3%). Two patients had biopsy-proven IgG4-RD in extra-neurological sites.
Conclusion: This study highlights the phenotypical variability of the neurological IgG4-RD. Biopsy inaccessibility reinforces the importance of new criteria for the diagnosis of this subset of patients.

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References

AbdelRazek MA, Venna N, Stone JH. IgG4-related disease of the central and peripheral nervous systems. Lancet Neurol. 2018;17:183. DOI: https://doi.org/10.1016/S1474-4422(17)30471-4

Martínez-Valle F, Orozco-Gálvez O, Fernández-Codina A. Update in ethiopathogeny, diagnosis and treatment of the IgG4 related disease. Med Clin. 2018;151:18-25. DOI: https://doi.org/10.1016/j.medcle.2018.05.005

AbdelRazek M, Stone JH. Neurologic features of immunoglobulin G4–related disease. Rheum Dis Clin North Am. 2017;43:621-31. DOI: https://doi.org/10.1016/j.rdc.2017.06.010

Baptista B, Casian A, Gunawardena H, D’Cruz D, Rice CM. Neurological manifestations of IgG4-related disease. Curr Treat Options Neurol. 2017;19:14. DOI: https://doi.org/10.1007/s11940-017-0450-9

Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181-92. DOI: https://doi.org/10.1038/modpathol.2012.72

Umehara H, Okazaki K, Kawa S, Takahashi H, Goto H, Matsui S, et al. The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD. Mod Rheumatol. 2021;31:529-33. DOI: https://doi.org/10.1080/14397595.2020.1859710

Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, et al. The 2019 american college of rheumatology/european league against rheumatism classification criteria for IgG4-related disease. Arthritis Rheumatol. 2020;72:7-19. DOI: https://doi.org/10.1002/art.41120

Cação G, Calejo M, Alves JE, Medeiros PB, Vila-Cha N, Mendonça T, et al. Clinical features of hypertrophic pachymeningitis in a center survey. Neurol Sci. 2019;40:543-51. DOI: https://doi.org/10.1007/s10072-018-3689-3

Lu LX, Della-Torre E, Stone JH, Clark SW. IgG4-Related hypertrophic pachymeningitis clinical features, diagnostic criteria, and treatment. JAMA Neurol. 2014;71:785-93. DOI: https://doi.org/10.1001/jamaneurol.2014.243

Lindstrom KM, Cousar JB, Lopes MB. IgG4-related meningeal disease: clinico-pathological features and proposal for diagnostic criteria. Acta Neuropathol. 2010;120:765-76. DOI: https://doi.org/10.1007/s00401-010-0746-2

Levraut M, Cohen M, Bresch S, Giordana C, Burel-Vandenbos F, Mondot L, et al. Immunoglobulin G4-related hypertrophic pachymeningitis: a caseoriented review. Neurol Neuroimmunol NeuroInflammation. 2019;6:568. DOI: https://doi.org/10.1212/NXI.0000000000000568

Melenotte C, Seguier J, Ebbo M, Kaphan E, Bernit E, Saillier L, et al. Clinical presentation, treatment and outcome of IgG4-related pachymeningitis: from a national case registry and literature review. Semin Arthritis Rheum. 2019;49:430-7. DOI: https://doi.org/10.1016/j.semarthrit.2019.05.003

De Virgilio A, de Vincentiis M, Inghilleri M, Fabrini G, Conte M, Gallo A, et al. Idiopathic hypertrophic pachymeningitis: an autoimmune IgG4-related disease. Immunol Res. 2017;65:386-94. DOI: https://doi.org/10.1007/s12026-016-8863-1

Mehta SH, Switzer JA, Biddinger P, Rojiani AM. IgG4-related leptomeningitis: a reversible cause of rapidly progressive cognitive decline. Neurology. 2014;82:540-2.

Regev K, Nussbaum T, Cagnano E, Giladi N, Karni A. Central nervous system manifestation of IgG4-related disease. JAMA Neurol. 2014;71:767-70. DOI: https://doi.org/10.1001/jamaneurol.2014.40

Temmoku J, Sato S, Matsumoto H, Fujita Y, Suzuki E, Yashiro-Furuya M, et al. Igg4-related disease complicated by brain parenchymal lesions successfully treated with corticosteroid therapy: a case report. Tohoku J Exp Med. 2020;251:161-8. DOI: https://doi.org/10.1620/tjem.251.161

Vakrakou AG, Evangelopoulos ME, Boutzios G, Tzanetakos D, Tzartos J, Velonakis G, et al. Recurrent myelitis and asymptomatic hypophysitis in IgG4-related disease: case-based review. Rheumatol Int. 2020;40:337-43. DOI: https://doi.org/10.1007/s00296-019-04502-6

Lin J, Zheng L, Zhou D, Hong Z. Immunoglobulin G4–related disease involving both cerebral parenchyma and spinal cord: a case report. J Neuroimmunol. 2019;335:577018. DOI: https://doi.org/10.1016/j.jneuroim.2019.577018

Oliveira V, Moura J, Pinto E, Santos E. Longitudinal extensive transverse myelitis: a presentation of IgG4‐related disease. Neurol Clin Neurosci.2022;10:172-4. DOI: https://doi.org/10.1111/ncn3.12589

Ohyama K, Koike H, Takahashi M, Kawagashira Y, Iijima M, Watanabe H, et al. Immunoglobulin G4-related pathologic features in inflammatory neuropathies. Neurology. 2015;85:1400-7. DOI: https://doi.org/10.1212/WNL.0000000000002039

Mehta SH, Switzer JA, Biddinger P, Rojiani AM. IgG4-related leptomeningitis: a reversible cause of rapidly progressive cognitive decline. Neurology. 2014;82:540-2. DOI: https://doi.org/10.1212/WNL.0000000000000100

Hiraga A, Ozaki D, Tsuneyama A, Ito S, Koide K, Kuwabara S. Corticosteroid-responsive leptomeningitis with IgG4-positive plasma-cell infiltration. J Neurol Sci. 2015;357:338-40. DOI: https://doi.org/10.1016/j.jns.2015.07.048

Boban J, Ardalı S, Thurnher MM. Leptomeningeal form of Immunoglobulin G4-related hypertrophic meningitis with perivascular spread: a case report and review of the literature. Neuroradiology. 2018;60:769-73. DOI: https://doi.org/10.1007/s00234-018-2028-y

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Published

2024-04-26

How to Cite

1.
Moura J, Malaquias MJ, Jorge F, Pinto E, Sardoeira A, Laranjinha I, Oliveira V, Sousa AP, Damásio J, Maia L, Vila-Chã N, Samões R, Taipa R, Martins da Silva A, Santos E. Neurological Involvement in a Portuguese Cohort of IgG4-Related Disease . Acta Med Port [Internet]. 2024 Apr. 26 [cited 2025 Apr. 3];37(6):429-35. Available from: https://actamedicaportuguesa.com/revista/index.php/amp/article/view/20767

Issue

Vol. 37 No. 6 (2024): June

Section

Original

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