Elsevier

Journal of Autoimmunity

Volume 96, January 2019, Pages 24-34
Journal of Autoimmunity

Prognosticating autoimmune encephalitis: A systematic review

https://doi.org/10.1016/j.jaut.2018.10.014Get rights and content

Highlights

  • This review examines predictive variables of prognosis in autoimmune encephalitis.

  • Delayed immunotherapy is associated with a wide variety of poor outcomes.

  • Some variables had clear associations with outcomes only in anti-NMDAR encephalitis.

  • The associations of several other variables with outcomes are unclear.

Abstract

Objective

To perform a systematic review of the current scientific literature in order to identify variables associated with patient prognosis in autoimmune encephalitis.

Methods

We performed a systematic literature search using MEDLINE, Embase, PubMed and PsychInfo databases. We selected studies that explored the correlation between early clinical and paraclinical findings, and patient outcomes. Data was extracted, analyzed and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.

Results

Forty four publications detailing 2823 subjects matched our inclusion criteria. There was considerable heterogeneity in methodology, patient profile, investigation results and clinical outcome measures. Findings were often discrepant for cases of anti-NMDAR encephalitis when compared with other causes of autoimmune encephalitis. Delay in immunotherapy contributed to a variety of worse outcomes for patients with different subsets of autoimmune encephalitis. Altered consciousness, ICU admission and no use of immunotherapy were variables associated with poor prognosis in anti-NMDAR encephalitis. Older age, sex, the presence of status epilepticus, CSF abnormalities and MRI changes were unlikely to have significant prognostic value. The influence of antibody titers, autonomic dysfunction and underlying malignancy was unclear.

Conclusions

A number of variables were identified to have potential predictive value for outcomes in autoimmune encephalitis. Heterogeneous study design, size and quality were major limiting factors in this review.

Introduction

Autoimmune encephalitis is a rare, debilitating and potentially treatable condition. There are different sub-types of autoimmune encephalitis characterized by antibodies to intracellular antigens (internal part of the synapse, cytoplasmic or nuclear proteins), or extracellular synaptic proteins and cell surface antigens. A large proportion of presumed autoimmune encephalitis cases do not exhibit the known autoantibodies, and are thus named ‘sero-negative’ autoimmune encephalitis [1]. Some forms of autoimmune encephalitis can start de novo whereas others are associated with an underlying malignancy; the so called paraneoplastic autoimmune encephalitis.

Individuals affected by autoimmune encephalitis usually present with behavioral change, mood alteration, memory and cognitive deficits, seizures as well as movement disorders [1]. During the acute phase of the disease there can be severe disability, and for some the morbidity associated with the illness can persist. Notably, certain subtypes of autoimmune encephalitis have a predilection for younger patients, with otherwise little or no comorbid disease, thus rendering a considerable change in a patient's level of function.

Prognosis is widely variable depending on the subtype, with the best outcomes being reported in patients with cell surface antibodies and poor outcomes are often seen in classic paraneoplastic cases that target intracellular antigens [2]. Even within a subtype, however, there are significant inconsistencies observed in long term morbidity [[3], [4], [5]]. Understanding what factors may influence prognosis is essential in providing an informative perspective to clinicians, patients and families, as well as potentially influencing future treatment decisions.

A number of observational studies have documented associations between the initial clinical and paraclinical findings, and the patients' outcome. Research articles of this nature have diverse designs, with investigators focusing either on cohorts with a specific antibody or with a single syndrome, such as limbic encephalitis or autoimmune epilepsy. Studies that are designed to look at outcome measures such as mortality, seizure control and cognitive deficits are very helpful, not only in improving our current knowledge regarding autoimmune encephalitis sub-types, but also for the future development of clinical guidelines. However such studies are scarce, and even for comparable research articles the results are frequently conflicting. This forms the basis of this systematic review where we attempt to collate and summarize findings from multiple research publications, and interpret it in a meaningful way.

Research focusing on prognosis is underpinned by three critical aspects: (i) case ascertainment, (ii) defining predictors, and (iii) outcome measures of prognosis [6]. In order to identify markers that have been shown to affect prognosis, we reviewed the published literature focusing on all three aspects of prognosis in patients diagnosed with autoimmune encephalitis.

Section snippets

Search strategy

We used the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines as the basis for this review [7]. We identified relevant studies by searching abstracts in MEDLINE, Embase, PsychInfo and PubMed databases from their inception to 30/04/2018. Search terms including autoimmune encephalitis, autoimmune antibody subtypes, outcome and prognosis were combined with Boolean operators (Table 1). Furthermore, we searched the reference lists of included publications to

Search results

Using the search parameters, we found a total of 1411 citations, which adjusted to 753 citations after removing duplicates. After an initial assessment, 497 citations were excluded due to one or more of the following reasons: full text being unavailable, no English translation available or being unrelated to the topic matter. A further 224 studies were excluded after evaluating abstracts as they did not meet our inclusion criteria. A total of 32 studies fulfilled our inclusion criteria through

Discussion

This review presents a qualitative analysis of prognostic factors in autoimmune encephalitis across a wide variety of different studies. Although the results were frequently conflicting, we were able to draw several important conclusions. Firstly, based on the quality and body of evidence in support, delay in immunotherapy commencement remains an important prognostic factor. Studies that did not show this relationship tended to be smaller and of lower quality. Within the constraints of this

Conclusion

We evaluated the current evidence of outcome predictors in patients with autoimmune encephalitis. Results of these studies were often conflicting and the definitions of outcome measures varied greatly, limiting the comparability of the studies. However, delay in the commencement of immunotherapy is clearly an important prognostic factor. This highlights the need for increased awareness, vigilance and early diagnosis. This review also highlights the desperate need for a unified minimum dataset

Funding

This review received no financial support.

Conflicts of interest

The authors declare no conflicts of interest.

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