Autoimmune encephalitis in a resource-limited public health setting: a case series analysis

Abstract

Background Autoimmune encephalitis (AE) consists of a group of acquired diseases that affect the central nervous system. A myriad of phenotypes may be present at the onset. Due to the heterogeneity of clinical presentations, it is difficult to achieve uniformity for the diagnostic and therapeutic processes and follow-up strategies.

Objective To describe a series of patients diagnosed with AE in a resource-limited public hospital in southern Brazil and to analyze therapeutics and outcomes.

Methods We retrospectively reviewed the electronic medical records of patients diagnosed with AE at the Hospital de Clínicas de Porto Alegre from 2014 to 2022. Data collected included clinical presentation, neuroimaging, cerebrospinal fluid testings, electroencephalogram, autoantibodies, treatments, outcomes, follow-up time, degree of neurological impairment, and mortality.

Results Data from 17 patients were retrieved. Eleven cases were classified as definite AE and 6 as possible AE. Autoantibodies were identified in 9 patients. Timing for diagnosis was impacted by the high costs associated with autoantibody testing. Most patients became functionally dependent (82.4%) and most survivors remained with autoimmune-associated epilepsy (75%). Five patients died during hospitalization, and one after a 26-month of follow-up.

Conclusion In this resource-limited hospital, patients with AE had a worse clinical outcome than that previously described in the literature. Development of epilepsy during follow-up and mortality were greater, whilst functional outcome was inferior. Autoantibody testing was initially denied in most patients, which impacted the definitive diagnosis and the use of second-line therapies.

Resumo

Antecedentes A encefalite autoimune (EA) consiste em um grupo de doenças adquiridas que afetam o sistema nervoso central.

Objetivo Descrever uma série de pacientes diagnosticados com EA em um contexto de atenção terciária à saúde com recursos limitados e analisar a terapêutica e os resultados.

Métodos Revisamos retrospectivamente os prontuários eletrônicos de pacientes diagnosticados com EA no Hospital de Clínicas de Porto Alegre de 2014 a 2022. Os dados coletados incluíram apresentação clínica, neuroimagem, exames de líquido cefalorraquidiano, eletroencefalograma, autoanticorpos, tratamentos, resultados, tempo de acompanhamento, grau de comprometimento neurológico e mortalidade.

Resultados Dados de 17 pacientes foram coletados. Onze casos foram classificados como EA definitivo e seis como EA possível. Autoanticorpos foram identificados em nove pacientes. O tempo para o diagnóstico foi afetado pelos altos custos associados ao teste de autoanticorpos. A maioria dos pacientes tornou-se funcionalmente dependente (82,4%), e a maioria dos sobreviventes permaneceu com epilepsia autoimune associada (75%). Cinco pacientes faleceram durante a internação, e um após 26 meses de seguimento.

Conclusão No hospital em questão, os pacientes com EA tiveram um desfecho clínico pior do que o previamente descrito na literatura. O desenvolvimento de epilepsia durante o acompanhamento e a mortalidade foram maiores, enquanto o desfecho funcional foi inferior. Os testes de autoanticorpos foram inicialmente negados para a maioria dos pacientes, o que impactou o diagnóstico definitivo e o uso de terapias de segunda linha.

Keywords

Autoantibodies - Seizures - Paraneoplastic Syndromes, Nervous System - Limbic Encephalitis

Palavras-chave

Autoanticorpos - Convulsões - Síndromes Paraneoplásicas do Sistema Nervoso - Encefalite Límbica

Authors' Contributions

CMT, MBM: conceived the study; MBM: collected and analyzed data, and wrote the first draft of the manuscript; CMT, WVB, GN, CDP, MBL, AF, MMB, RMC: provided a substantial contribution to development of the study, analysis and interpretation of data, and discussion of content; CDP, WVB: designed the figures. All authors reviewed, commented, and edited the manuscript. All authors read and approved the final manuscript.

Support

WVB is funded by the Alzheimer's Association (AACSFD-22-928689) and National Council for Scientific and Technological Development (CNPq) (PDJ scholarship). CDP is funded by CNPq (PIBIC scholarship). RMC is funded by the Alzheimer's Association (AARG-D 21-846545).

Publikationsverlauf

Eingereicht: 02. Juli 2023

Angenommen: 22. Oktober 2023

Artikel online veröffentlicht:
07. Februar 2024

• References

• 1 Abboud H, Probasco JC, Irani S. et al; Autoimmune Encephalitis Alliance Clinicians Network. Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry 2021; 92 (07) 757-768
• 2 Dubey D, Pittock SJ, Kelly CR. et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol 2018; 83 (01) 166-177
• 3 Endres D, Lüngen E, Hasan A. et al. Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany. Mol Psychiatry 2022; 27 (03) 1479-1489
• 4 Turcano P, Day GS. Life after autoantibody-mediated encephalitis: optimizing follow-up and management in recovering patients. Curr Opin Neurol 2022; 35 (03) 415-422
• 5 Graus F, Titulaer MJ, Balu R. et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15 (04) 391-404
• 6 Ruiz-García R, Muñoz-Sánchez G, Naranjo L. et al. Limitations of a Commercial Assay as Diagnostic Test of Autoimmune Encephalitis. Front Immunol 2021; 12: 691536
• 7 Pagaling GT, Turalde CWR, Jamora RDG. Autoimmune Encephalitis in the Philippines: A Scoping Review on the Treatment Gaps, Challenges, and Current State of Care. Front Neurol 2022; 13: 788309
• 8 Bygbjerg IC. Double burden of noncommunicable and infectious diseases in developing countries. Science 2012; 337 (6101) 1499-1501
• 9 Wingfield T, McHugh C, Vas A. et al. Autoimmune encephalitis: a case series and comprehensive review of the literature. QJM 2011; 104 (11) 921-931
• 10 Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D. CARE Group. The CARE guidelines: consensus-based clinical case reporting guideline development. J Med Case Rep 2013; 7: 223
• 11 Titulaer MJ, McCracken L, Gabilondo I. et al. Late-onset anti-NMDA receptor encephalitis. Neurology 2013; 81 (12) 1058-1063
• 12 Xu X, Lu Q, Huang Y. et al. Anti-NMDAR encephalitis: A single-center, longitudinal study in China. Neurol Neuroimmunol Neuroinflamm 2019; 7 (01) e633
• 13 Ball C, Fisicaro R, Morris III L. et al. Brain on fire: an imaging-based review of autoimmune encephalitis. Clin Imaging 2022; 84: 1-30
• 14 Chi X, Zhou D. Risk factors for mortality in patients with anti-NMDA receptor encephalitis: Reply to comment on data sparsity. Acta Neurol Scand 2017; 136 (06) 738
• 15 Datta AK, Pandit A, Biswas S, Biswas A, Roy BK, Gangopaddhyay G. Spectrum of Anti-NMDA Receptor Antibody Encephalitis: Clinical Profile, Management and Outcomes. Ann Indian Acad Neurol 2021; 24 (03) 383-389
• 16 Broadley J, Seneviratne U, Beech P. et al. Prognosticating autoimmune encephalitis: A systematic review. J Autoimmun 2019; 96: 24-34
• 17 Herard K, Khanni JL, Alusma-Hibbert K, Samuels CR, Espinosa PS. Neurological Disorders Associated with Glutamic Acid Decarboxylase Antibodies. Cureus 2019; 11 (05) e4738
• 18 Morena J, Elsheikh B, Hoyle JC. Recurrent Miller Fisher: A Case Report Along With a Literature and an EMG/NCS Review. Neurohospitalist 2021; 11 (03) 263-266
• 19 Dade M, Berzero G, Izquierdo C. et al. Neurological Syndromes Associated with Anti-GAD Antibodies. Int J Mol Sci 2020; 21 (10) 3701
• 20 Vasconcelos GA, Barreira RM, Antoniollo KENT. et al. Autoimmune Encephalitis in Latin America: A Critical Review. Front Neurol 2021; 11: 606350
• 21 Dalmau J, Graus F, Villarejo A. et al. Clinical analysis of anti-Ma2-associated encephalitis. Brain 2004; 127 (Pt 8): 1831-1844
• 22 Sechi E, Flanagan EP. Antibody-Mediated Autoimmune Diseases of the CNS: Challenges and Approaches to Diagnosis and Management. Front Neurol 2021; 12: 673339
• 23 Steriade C, Britton J, Dale RC. et al. Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmune-associated epilepsy: Conceptual definitions. Epilepsia 2020; 61 (07) 1341-1351
• 24 Zhang W, Wang X, Shao N, Ma R, Meng H. Seizure characteristics, treatment, and outcome in autoimmune synaptic encephalitis: A long-term study. Epilepsy Behav 2019; 94: 198-203
• 25 Liu X, Yan B, Wang R. et al. Seizure outcomes in patients with anti-NMDAR encephalitis: A follow-up study. Epilepsia 2017; 58 (12) 2104-2111
• 26 Schubert J, Brämer D, Huttner HB. et al; GENERATE and IGNITE network. Management and prognostic markers in patients with autoimmune encephalitis requiring ICU treatment. Neurol Neuroimmunol Neuroinflamm 2018; 6 (01) e514
• 27 Wang B, Wang C, Feng J, Hao M, Guo S. Clinical Features, Treatment, and Prognostic Factors in Neuronal Surface Antibody-Mediated Severe Autoimmune Encephalitis. Front Immunol 2022; 13: 890656
• 28 Byun J-I, Lee S-T, Jung K-H. et al. Effect of Immunotherapy on Seizure Outcome in Patients with Autoimmune Encephalitis: A Prospective Observational Registry Study. PLoS One 2016; 11 (01) e0146455
• 29 Zhang Y, Deng C, Zhu L, Ling L. Predisposing factors and prognosis of status epilepticus in patients with autoimmune encephalitis. Medicine (Baltimore) 2020; 99 (13) e19601
• 30 Joubert B, Belbezier A, Haesebaert J. et al. Long-term outcomes in temporal lobe epilepsy with glutamate decarboxylase antibodies. J Neurol 2020; 267 (07) 2083-2089
• 31 Falip M, Jaraba S, Rodríguez-Bel L. et al. Seizures and epilepsy of autoimmune origin: A long-term prospective study. Seizure 2020; 81: 157-165
• 32 von Rhein B, Wagner J, Widman G, Malter MP, Elger CE, Helmstaedter C. Suspected antibody negative autoimmune limbic encephalitis: outcome of immunotherapy. Acta Neurol Scand 2017; 135 (01) 134-141
• 33 Bataller L, Kleopa KA, Wu GF, Rossi JE, Rosenfeld MR, Dalmau J. Autoimmune limbic encephalitis in 39 patients: immunophenotypes and outcomes. J Neurol Neurosurg Psychiatry 2007; 78 (04) 381-385
• 34 Dalmau J, Gleichman AJ, Hughes EG. et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7 (12) 1091-1098
• 35 Aurangzeb S, Symmonds M, Knight RK, Kennett R, Wehner T, Irani SR. LGI1-antibody encephalitis is characterised by frequent, multifocal clinical and subclinical seizures. Seizure 2017; 50: 14-17
• 36 Byun JI, Lee ST, Moon J. et al. Cardiac sympathetic dysfunction in anti-NMDA receptor encephalitis. Auton Neurosci 2015; 193: 142-146
• 37 DeSena AD, Noland DK, Matevosyan K. et al. Intravenous methylprednisolone versus therapeutic plasma exchange for treatment of anti-N-methyl-D-aspartate receptor antibody encephalitis: A retrospective review. J Clin Apher 2015; 30 (04) 212-216
• 38 Waitzberg R, Quentin W, Webb E, Glied S. The Structure and Financing of Health Care Systems Affected How Providers Coped With COVID-19. Milbank Q 2021; 99 (02) 542-564