Autoimmune diseases related to anti-N-methyl-D-aspartate receptor encephalitis, a descriptive study in a third level center
Keywords:Encephalitis, Autoimmune encephalitis, NMDA, Prevalence, Autoimmune diseases
Background: Epiphenomena in neurological disorders can lead to subsequent autoimmune diseases such as autoimmune encephalitis (AE), but research on this condition is limited. There is a lack of knowledge about the development of autoimmune diseases in AE patients due to its rarity. The objective of this study is to investigate the association between the development of autoimmune diseases and patients with anti-NMDA autoimmune encephalitis.
Methods: A cross-sectional study was conducted from 2015 to 2022 at UMAE La Raza Antonio Fraga Mouret to investigate the relationship between autoimmune diseases and anti-NMDA AE. 194 patients were tested for anti-NMDA antibodies in cerebrospinal fluid (CSF), and 50 were found to meet the criteria for AE based on clinical, laboratory, and imaging tests. Follow-up evaluations assessed for rheumatological diseases and various additional tests were conducted before and after the AE event. The study was approved by the ethical and investigation committee.
Results: Our analysis included 50 patients with autoimmune encephalitis. Of these, 62% were women aged 18-51 years (mean age 31.97 years) and 38% were men aged 19-72 years (mean age 39.2 years). Fifty-two percent of patients had positive antibodies for autoimmune diseases, but only 12% met ACR criteria for autoimmune disease. The CSF was negative for infections. Electroencephelography (EEG) showed abnormalities in 42% of patients, and Magnetic resonance imaging (MRI) showed hyperintensity in the medial temporal lobes, cortico-subcortical regions, and white matter. False positives were excluded.
Conclusions: Among patients with autoimmune encephalitis, 12% had associated autoimmune diseases, most of which developed after the diagnosis of encephalitis. The observed diseases were 3 cases of lupus, 1 of rheumatoid arthritis, 1 of thyroiditis, and 1 of vasculitis. There is an epiphenomenal relationship between autoimmune encephalitis and subsequent development of autoimmune diseases.
Dalmau J, Graus F. Antibody-Mediated Encephalitis. N Engl J Med. 2018;378:840.
Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-89.
Stathopoulos P, Chastre A, Waters P, Irani S, Fichtner ML, Benotti ES, et al. Autoantibodies against Neurologic Antigens in Nonneurologic Autoimmunity. J Immunol. 2019;202(8):2210-9.
McKeon A, Lennon VA, Jacob A, Matiello M, Lucchinetti CF, Kale N, et al. Coexistence of myasthenia gravis and serological markers of neurological autoimmunity in neuromyelitis optica. Muscle Nerve. 2009;39(1):87-90.
Nagarajan M, Maasila AT, Dhanapriya J, Dineshkumar T, Sakthirajan R, Rajasekar D, et al. Systemic Lupus Erythematosus and Myasthenia Gravis: A Rare Association. Indian J Nephrol. 2019;29(1):62-4.
Wingerchuk DM, Weinshenker BG. The emerging relationship between neuromyelitis optica and systemic rheumatologic autoimmune disease. Mult Scler. 2012;18(1):5-10.
Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391-404.
Hara M, Martinez-Hernandez E, Ariño H, Armangué T, Spatola M, Petit-Pedrol M, et al. Clinical and pathogenic significance of IgG, IgA, and IgM antibodies against the NMDA receptor. Neurology. 2018;90(16):e1386-94.
Seki M, Suzuki S, Iizuka T, Shimizu T, Nihei Y, Suzuki N, Dalmau J. Neurological response to early removal of ovarian teratoma in anti-NMDAR encephalitis. J Neurol Neurosurg Psychiatry. 2008;79(3):324-6.
Kayser MS, Titulaer MJ, Gresa-Arribas N, Dalmau J. Frequency and characteristics of isolated psychiatric episodes in anti–N-methyl-d-aspartate receptor encephalitis. JAMA Neurol. 2013;70:1133.
Guasp M, Giné-Servén E, Maudes E, Rosa-Justicia M, Martínez-Hernández E, Boix-Quintana E, et al. Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis. Neurology. 2021;97(1):e61-e75.
Leypoldt F, Buchert R, Kleiter I, Marienhagen J, Gelderblom M, Magnus T, et al. Fluorodeoxyglucose positron emission tomography in anti-N-methyl-D-aspartate receptor encephalitis: distinct pattern of disease. J Neurol Neurosurg Psychiatry. 2012;83(7):681-6.
Thompson J, Bi M, Murchison AG, Makuch M, Bien CG, Chu K, et al. The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain. 2018;141(2):348-56.
Anaya JM, Shoenfeld Y, Correa PA. Garcia Carasco M, Cervera R. Autoimmunity and autoimmune disease. CIB, Medellin, Colombia; 2005.
Sandyk R. Demyelination as an epiphenomenon in multiple sclerosis. Int J Neurosci. 1993;72(3-4):141-8.
Gresa-Arribas N, Titulaer MJ, Torrents A, Aguilar E, McCracken L, Leypoldt F, et al. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol. 2014;13(2):167-77.
Heine J, Prüss H, Bartsch T, Ploner CJ, Paul F, Finke C. Imaging of autoimmune encephalitis — relevance for clinical practice and hippocampal function. Neuroscience. 2015;309:68-83.
Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013;12(2):157-65.
Pittock SJ, Yoshikawa H, Ahlskog JE, Tisch SH, Benarroch EE, Kryzer TJ, et al. Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal, and spinal cord dysfunction. Mayo Clin Proc. 2006;81(9):1207-14.
Byrne S, Walsh C, Hacohen Y, Muscal E, Jankovic J, Stocco A, et al. Earlier treatment of NMDAR antibody encephalitis in children results in a better outcome. Neurol Neuroimmunol Neuroinflamm. 2015;2(4):e130.
Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019;78(9):1151-9.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-81.
Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11.
Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 2014;13(4-5):391-7.