Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-27T07:02:25.795Z Has data issue: false hasContentIssue false

A scoping review on paraneoplastic autoimmune limbic encephalitis (PALE) psychiatric manifestations

Published online by Cambridge University Press:  30 October 2020

João Costa Fernandes
Affiliation:
Clínica Universitária de Psiquiatria e Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
João Gama Marques*
Affiliation:
Clínica Universitária de Psiquiatria e Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal Clínica de Psiquiatria Geral e Transcultural, Hospital Júlio de Matos, Centro Hospitalar Psiquiátrico de Lisboa, Lisboa, Portugal
*
*Author for correspondence: João Gama Marques, Email: [email protected]

Abstract

The term limbic encephalitis has been used with an oncological precedent for over 50 years and, since then, has been applied in relation to multiple antibodies found in its etiological process. Over the last decade, the psychiatric community has brought paraneoplastic autoimmune limbic encephalitis (PALE) to a new light, scattering the once known relationships between said screened antibodies responsible for causing limbic encephalitis. Due to the fact that some individuals with this condition have a psychiatric syndrome as an initial manifestation, the aim of this updated scoping review is to reestablish a causal relationship between the onconeuronal autoantibodies, both intracellular and extracellular, possible underlying malignancies and subsequent neuropsychiatric syndrome. In pair with it, there is the idea of sketching a cleaner thorough picture of what poses as psychiatric symptoms as well as possible therapeutics. Even though the always evolving epistemology of the neurosciences achieved a significant unveiling of what includes PALE in its relevant pathological subgroups, the amount of gray literature still is much superior, appealing to a further research with more randomized controlled trials, with larger populations, so that the results corroborate the small amount of data that already exist and posteriorly be applied in the general population.

Type
Review
Copyright
© The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Denny–Brown, D. Primary sensory neuropathy with muscular changes associated with carcinoma. J Neurol Neurosurg Psychiatry. 1948;11(2):7387.10.1136/jnnp.11.2.73CrossRefGoogle ScholarPubMed
Gultekin, SH, Rosenfeld, MR, Voltz, R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumor association in 50 patients. Brain. 2000;123:14811494.10.1093/brain/123.7.1481CrossRefGoogle ScholarPubMed
Budhram, A, Leung, A, Nicolle, MW, Burneo, JG. Diagnosing autoimmune limbic encephalitis. CMAJ. 2019;191(19):E529E534.10.1503/cmaj.181548CrossRefGoogle ScholarPubMed
Brierley, JB, Corsellis, JAN, Hierons, R, et al. Subacute encephalitis of later adult life mainly affecting the limbic areas. Brain. 1960;83:357368.10.1093/brain/83.3.357CrossRefGoogle Scholar
Corsellis, JA, Goldberg, GJ, Norton, AR. "Limbic encephalitis" and its association with carcinoma. Brain. 1968;91(3):481496.10.1093/brain/91.3.481CrossRefGoogle ScholarPubMed
Bakheit, AM, Kennedy, PG, Behan, PO. Paraneoplastic limbic encephalitis: clinico–pathological correlations. J Neurol Neurosurg Psychiatry. 1990;53(12):10841088.10.1136/jnnp.53.12.1084CrossRefGoogle ScholarPubMed
Benros, ME, Laursen, TM, Dalton, SO, Mortensen, PB. Psychiatric disorder as a first manifestation of cancer: a 10–year population–based study. Int J Cancer. 2009;124(12):29172922.10.1002/ijc.24274CrossRefGoogle ScholarPubMed
Tricco, AC, Lillie, E, Zarin, W, et al. PRISMA extension for scoping reviews (PRISMA–ScR): checklist and explanation. Ann Intern Med. 2018;169(7):467473.10.7326/M18-0850CrossRefGoogle ScholarPubMed
Dalmau, J, Bataller, L. Clinical and immunological diversity of limbic encephalitis: a model for paraneoplastic neurologic disorders. Hematol Oncol Clin North Am. 2006;20(6):13191335.10.1016/j.hoc.2006.09.011CrossRefGoogle Scholar
Dalmau, J, Graus, F. Antibody–mediated encephalitis. N Engl J Med. 2018;378(9):840851.10.1056/NEJMra1708712CrossRefGoogle ScholarPubMed
Mori, M, Kuwabara, S, Yoshiyama, M, Kanesaka, T, Ogata, T, Hattori, T. Successful immune treatment for non–paraneoplastic limbic encephalitis. J Neurol Sci. 2002;201(1–2):8588.10.1016/S0022-510X(02)00188-0CrossRefGoogle ScholarPubMed
Dubey, D, Pittock, SJ, Kelly, CR, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 2018;83(1):166177.10.1002/ana.25131CrossRefGoogle Scholar
Endres, D, Leypoldt, F, Bechter, K, et al. Autoimmune encephalitis as a differential diagnosis of schizophreniform psychosis: clinical symptomatology, pathophysiology, diagnostic approach, and therapeutic considerations. Eur Arch Psychiatry Clin Neurosci. 2020;270:803818.10.1007/s00406-020-01113-2CrossRefGoogle ScholarPubMed
Graus, F, Saiz, A. Encefalitis límbica: un síndrome probablemente infradiagnosticado. Neurologia. 2005;20(1):2430.Google Scholar
Graus, F, Titulaer, MJ, Balu, R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391404.10.1016/S1474-4422(15)00401-9CrossRefGoogle ScholarPubMed
Alexopoulos, H, Dalakas, MC. The immunobiology of autoimmune encephalitides. J Autoimmun. 2019;104:102339.10.1016/j.jaut.2019.102339CrossRefGoogle ScholarPubMed
Galli, J, Greenlee, J. Paraneoplastic diseases of the central nervous system. F1000Res. 2020;9:F1000 Faculty Rev–167.10.12688/f1000research.21309.1CrossRefGoogle ScholarPubMed
Marinas, JE, Matveychuk, D, Dursun, SM, Baker, GB. Neuroimmunological antibody–mediated encephalitis and implications for diagnosis and therapy in neuropsychiatry. Acta Neuropsychiatr. 2019;3:19.Google Scholar
Ibrahim Ismail, I, John, JK, Ibrahim, M, Al–Hashel, JY. Paraneoplastic limbic encephalitis associated with anti–CV2/CRMP5 antibodies secondary to thymoma in an adolescent. Case Rep Neurol. 2020;12(1):5055.10.1159/000505232CrossRefGoogle Scholar
Al-Diwani, A, Handel, A, Townsend, L, et al. The psychopathology of NMDAR-antibody encephalitis in adults: a systematic review and phenotypic analysis of individual patient data. Lancet Psychiatry. 2019;6(3):235246.10.1016/S2215-0366(19)30001-XCrossRefGoogle ScholarPubMed
Joubert, B, Kerschen, P, Zekeridou, A, et al. Clinical spectrum of encephalitis associated with antibodies against the aamino–3–hydroxy–5–methyl–4–isoxazolepropionic acid receptor: case series and review of the literature. JAMA Neurol 2015;72:11631169.10.1001/jamaneurol.2015.1715CrossRefGoogle ScholarPubMed
Chen, C, Sigurdsson, HP, Pépés, SE, et al. Activation induced changes in GABA: Functional MRS at 7T with MEGA–sLASER. Neuroimage. 2017;156:207213.CrossRefGoogle ScholarPubMed
Alcantara, M, Bennani, O, Verdure, P, Leprêtre, S, Tilly, H, Jardin, F. Voltage–gated potassium channel antibody paraneoplastic limbic encephalitis associated with acute myeloid leukemia. Case Rep Oncol. 2013;6(2):289292.10.1159/000351835CrossRefGoogle ScholarPubMed
Sharma, A, Dubey, D, Sawhney, A, Janga, K. GAD65 positive autoimmune limbic encephalitis: a case report and review of literature. J Clin Med Res. 2012;4(6):424428.Google ScholarPubMed
Spatola, M, Sabater, L, Planagumà, J, et al. Encephalitis with mGluR5 antibodies: symptoms and antibody effects. Neurology. 2018;90(22):e1964e1972.10.1212/WNL.0000000000005614CrossRefGoogle ScholarPubMed
Kayser, MS, Kohler, CG, Dalmau, J. Psychiatric manifestations of paraneoplastic disorders. Am J Psychiatry. 2010;167(9):10391050.10.1176/appi.ajp.2010.09101547CrossRefGoogle ScholarPubMed
Sillevis Smitt, P, Grefkens, J, de Leeuw, B, et al. Survival and outcome in 73 anti–Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy. J Neurol. 2002;249(6):745753.10.1007/s00415-002-0706-4CrossRefGoogle ScholarPubMed
Ortega Suero, G, Sola–Valls, N, Escudero, D, Saiz, A, Graus, F. Síndromes neurológicos paraneoplásicos asociados a anticuerpos anti–Ma y anti–Ma2. Neurología. 2018;33(1):1827.10.1016/j.nrl.2016.05.010CrossRefGoogle Scholar
Roberts, WK, Darnell, RB. Neuroimmunology of the paraneoplastic neurological degenerations. Curr Opin Immunol. 2004;16(5):616622.10.1016/j.coi.2004.07.009CrossRefGoogle ScholarPubMed
Dalmau, J, Graus, F, Villarejo, A, et al. Clinical analysis of anti–Ma2–associated encephalitis. Brain. 2004;127(Pt 8):18311844.10.1093/brain/awh203CrossRefGoogle ScholarPubMed
Fukada, M, Watakabe, I, Yuasa–Kawada, J, et al. Molecular characterization of CRMP5, a novel member of the collapsin response mediator protein family. J Biol Chem. 2000;275(48):3795737965.10.1074/jbc.M003277200CrossRefGoogle ScholarPubMed
Yu, Z, Kryzer, TJ, Griesmann, GE, Kim, K, Benarroch, EE, Lennon, VA. CRMP–5 neuronal autoantibody: marker of lung cancer and thymoma–related autoimmunity. Ann Neurol. 2001;49(2):146154.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
Warren, N, Swayne, A, Siskind, D, et al. Antibody testing in psychiatry. J Neuropsychiatry Clin Neurosci. 2020;32(2):154160.CrossRefGoogle Scholar
Tüzün, E, Dalmau, J. Limbic encephalitis and variants: classification, diagnosis and treatment. Neurologist. 2007;13(5):261271.CrossRefGoogle Scholar
Dalmau, J, Geis, C, Graus, F. Autoantibodies to synaptic receptors and neuronal cell surface proteins in autoimmune diseases of the central nervous system. Physiol Rev. 2017;97(2):839887.10.1152/physrev.00010.2016CrossRefGoogle ScholarPubMed
Galli, J, Greenlee, J. Paraneoplastic diseases of the central nervous system. F1000Res. 2020;9:F1000 Faculty Rev-167.CrossRefGoogle ScholarPubMed
Titulaer, MJ, McCracken, L, Gabilondo, I, et al. Treatment and prognostic factors for long–term outcome in patients with anti–NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12:157165.CrossRefGoogle ScholarPubMed
Wong, D, Fries, B. Anti–NMDAR encephalitis, a mimicker of acute infectious encephalitis and a review of the literature. IDCases. 2014;1(4):6667.10.1016/j.idcr.2014.08.003CrossRefGoogle Scholar
Jeraiby, M, Depincé–Berger, A, Bossy, V, Antoine, JC, Paul, S. A case of anti–NMDA receptor encephalitis in a woman with a NMDA–R(+) small cell lung carcinoma (SCLC). Clin Immunol. 2016;166–167:9699.10.1016/j.clim.2016.03.011CrossRefGoogle Scholar
Marques Macedo, I, Gama Marques, J. Catatonia secondary to anti–N–methyl–D–aspartate receptor (NMDAr) encephalitis: a review. CNS Spectr. 2019;30:118.Google Scholar
Stone, JM, Dietrich, C, Edden, R, et al. Ketamine effects on brain GABA and glutamate levels with 1H–MRS: relationship to ketamine–induced psychopathology. Mol Psychiatry. 2012;17:664665.CrossRefGoogle ScholarPubMed
Höftberger, R, van Sonderen, A, Leypoldt, F, et al. Encephalitis and AMPA receptor antibodies: novel findings in a case series of 22 patients. Neurology. 2015;84(24):24032412.CrossRefGoogle Scholar
Lai, M, Hughes, EG, Peng, X, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol. 2009;65(4):424434.10.1002/ana.21589CrossRefGoogle ScholarPubMed
Graus, F, Boronat, A, Xifró, X, et al. The expanding clinical profile of anti–AMPA receptor encephalitis. Neurology. 2010;74(10):857859.10.1212/WNL.0b013e3181d3e404CrossRefGoogle ScholarPubMed
Wei, YC, Liu, CH, Lin, JJ, et al. Rapid progression and brain atrophy in anti–AMPA receptor encephalitis. J Neuroimmunol. 2013;261(1–2):129133.10.1016/j.jneuroim.2013.05.011CrossRefGoogle ScholarPubMed
Jeffery, OJ, Lennon, VA, Pittock, SJ, Gregory, JK, Britton, JW, McKeon, A. GABAB receptor autoantibody frequency in service serologic evaluation. Neurology. 2013;81(10):882887.10.1212/WNL.0b013e3182a35271CrossRefGoogle ScholarPubMed
Kim, TJ, Lee, ST, Shin, JW, et al. Clinical manifestations and outcomes of the treatment of patients with GABAB encephalitis. J Neuroimmunol. 2014;270(1–2):4550.10.1016/j.jneuroim.2014.02.011CrossRefGoogle ScholarPubMed
Guan, HZ, Ren, HT, Yang, XZ, et al. Limbic encephalitis associated with anti–γ–aminobutyric acid B receptor antibodies: a case series from China. Chin Med J (Engl). 2015;128(22):30233028.CrossRefGoogle ScholarPubMed
Zhang, YX, Yang, HL, Wu, YY, et al. [Clinical analysis of 9 cases with Anti–leucine–rich glioma inactivated 1 protein antibody associated limbic encephalitis]. Zhonghua Yi Xue Za Zhi. 2017;97(17):12951298.Google Scholar
Alexopoulos, H, Akrivou, S, Dalakas, MC. Glycine receptor antibodies in stiff–person syndrome and other GAD–positive CNS disorders. Neurology. 2013;81:19621964.10.1212/01.wnl.0000436617.40779.65CrossRefGoogle ScholarPubMed
Gagnon, MM, Savard, M. Limbic encephalitis associated with GAD65 antibodies: brief review of the relevant literature. Can J Neurol Sci. 2016;43(4):486493.10.1017/cjn.2016.13CrossRefGoogle ScholarPubMed
Soto–Rincón, CA, Castillo–Torres, SA, Cantú–García, DA, Estrada–Bellmann, I, Chávez–Luévanos, B, Marfil, A. The poor insane Ophelia: reconsidering Ophelia syndrome. Arq Neuropsiquiatr. 2019;77(11):828831.CrossRefGoogle ScholarPubMed
Lancaster, E, Martinez–Hernandez, E, Titulaer, MJ, et al. Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology. 2011;77(18):16981701.10.1212/WNL.0b013e3182364a44CrossRefGoogle ScholarPubMed
Spatola, M, Sabater, L, Planagumà, J, et al. Encephalitis with mGluR5 antibodies: symptoms and antibody effects. Neurology. 2018;90(22):e1964e1972.10.1212/WNL.0000000000005614CrossRefGoogle ScholarPubMed
Shen, K, Xu, Y, Guan, H, et al. Paraneoplastic limbic encephalitis associated with lung cancer. Sci Rep. 2018;8(1):679.Google ScholarPubMed
Klausner, JD. The great imitator revealed: syphilis. Top Antivir Med. 2019;27(2):7174.Google ScholarPubMed
Jetley, S, Jairajpuri, ZS, Pujani, M, Khan, S, Rana, S. Tuberculosis ‘The Great Imitator’: a usual disease with unusual presentations. Indian J Tuberc. 2017;64(1):5459.10.1016/j.ijtb.2016.01.001CrossRefGoogle ScholarPubMed
Gama Marques, J. Organic psychosis causing secondary schizophrenia in one–fourth of a cohort of 200 patients previously diagnosed with primary schizophrenia. Prim Care Companion CNS Disord. 2020;22(2):19m02549.Google Scholar
Ponte, A, Brito, A, Nóbrega, C, Pinheiro, S, Gama Marques, J. Catatonia in anti–N–methyl–D–aspartate (NMDA) receptor encephalitis misdiagnosed as schizophrenia. Acta Med Port. 2020;33(3):208211.10.20344/amp.11077CrossRefGoogle ScholarPubMed
Marinas, JE, Matveychuk, D, Dursun, SM, Baker, GB. Neuroimmunological antibody–mediated encephalitis and implications for diagnosis and therapy in neuropsychiatry. Acta Neuropsychiatr. 2019;3:19.Google Scholar
Graus, F, Escudero, D, Oleaga, L, et al. Syndrome and outcome of antibody-negative limbic encephalitis. Eur J Neurol. 2018;25(8):10111016.10.1111/ene.13661CrossRefGoogle ScholarPubMed