Review ArticleThe multiple faces of encephalitis: Antibody profile in a case series of autoimmune encephalitis in Bogotá, Colombia
Introduction
Encephalitis is defined as a parenchymal brain inflammation that leads to neurological dysfunction (Dalmau and Graus, 2018). The most common cause is viral infection followed by acute disseminated encephalomyelitis and antibody-mediated encephalitis (Dubey et al., 2018). This last etiology is the scope of the article being an increasingly recognized entity in the last 15 years.
There is a lack of population based studies about the epidemiological profile of this disease, initially because of under-recognized antibodies and also because testing is not accessible in many institutions (Graus et al., 2016).
The estimated incidence of AE in high-income countries is approximately 5–10 per 100,000 inhabitants per year and in Northern Europe it is 2–3 per 100,000 inhabitants (Dalmau and Graus, 2018). Dubey et al. report a prevalence of 0.8/100.000 and an incidence of 1.2/100,000 persons per year in Olmsted County-Minnesota (Dubey et al., 2018). Among all encephalitis, 20% are immune mediated, principally by NMDA, LGI1 and CASPR2 antibodies. Anti-NMDA encephalitis is the most frequent, followed by LGI1 with an incidence of 0.83 cases per 1 million (Dalmau and Graus, 2018). AE affects patients of all ages and represents a significant burden on patients, families and society.
The first antibody discovered was the Anti-R-NMDA by Josep Dalmau in 2005. Since then the role of antibodies are still elucidating, and the process may involve an autoimmune response against some membrane surface antigens (as in NMDAR or LGI1), or toward intracellular proteins such as Hu, Ma2 and CRMP5. In the second case, the CD8+ T cell mediated mechanism is predominantly involved (Dalmau and Graus, 2018). The distinction between both types is becoming a key feature as it has implications on prognosis and treatment response (Vogrig et al., 2019).
Symptoms are usually subacute, with a wide range of manifestations that include: decreased level of consciousness, changes in behavior, cognitive impairment, seizures and abnormal movements. While definitive diagnosis is mainly achievable with antibody testing, waiting for results delay an early initiation of the immunotherapy which impacts outcome (Graus et al., 2016; Titulaer et al., 2013; Dalmau et al., 2019).
In Latin America the largest series including antibody testing that have been published includes 372 patients in Brazil, as a preliminary report (Toso et al., 2020). The rest of the case series include between 10 and 13 individuals (Melamud et al., 2020; Nóbrega et al., 2019). In Colombia to our knowledge there are few case series with no more than 6 patients most of them without antibody testing (Torres-Ballesteros et al., 2020).
The aim of this study is to describe the demographic, clinical and antibodies profile of patients with AE managed in three centers in Bogotá-Colombia. We also included paraneoplastic and Hashimoto encephalopathy (HE) associated with autoimmune thyroiditis, entities that can also present as a sub-acute neuropsychiatric syndrome.
Section snippets
Methodology
It is a retrospective case-series study, conducted at three tertiary medical centers in Bogotá-Colombia. We included 9 individuals with definitive AE treated between 2015 and 2019. The diagnosis was made according to Francesc Graus et al. criteria (Graus et al., 2016). The collected data included: demographic information, clinical features, imaging studies, cerebrospinal fluid (CSF) analysis, presence of antibodies, treatment and outcome.
The method for the antibody testing was a cell-based
Demographic and clinical characteristics
Nine patients from Bogotá-Colombia were included in the study. The most prevalent antibody was anti-NMDAR (3/9 individuals) followed by anti-LGI1 (2/9 individuals). The youngest patients had anti-NMDAR and HE. Patients with anti-LGI1 were older and had associated cardiovascular risk factors primarily: coronary heart disease, arterial hypertension and obesity. Two patients had an infection preceding the neurological dysfunction: herpes virus type 1 for anti-NMDAR encephalitis (Armangue et al.,
Discussion
All patients presented with a subacute neurological disorder, and after excluding other etiologies (vascular, infectious, degenerative and metabolic) a diagnosis of a possible AE was made. Even though there are established syndromes such as limbic encephalitis and anti-NMDAR encephalitis, there were some clinical differences even in patients with the presence of the same antibody. These heterogeneous findings conform to a spectrum of the disease and make the diagnosis especially challenging.
Conclusions
Our results in a cohort of patients from three hospitals in Bogota with AE, are concordant with previous studies. The main limitation was the small sample that correlates with the lack of available antibody testing in Countries of Latin America. As early recognition is crucial, larger series are needed for characterizing our population to estimate the incidence and prevalence of AE in Colombia. This is the basis for future research that will probably involve a personalized approach based on
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of Competing Interest
The Authors declare that there is no conflict of interest.
Acknowledgements
We would like to thank Orlando Oliveros-Pasión and Milena Rodríguez-López, for providing us help with the methodology design.
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These authors contributed equally to the manuscript.