Efficacy and safety of intravenous immunoglobulins for the treatment of viral encephalitis: a systematic literature review.

BACKGROUND: For most viral encephalitides, therapy is merely supportive. Intravenous immunoglobulins (IVIG) have been used as a prophylactic and therapeutic approach. We conduct a systematic review on the safety and efficacy of IVIG in viral encephalitis. METHODS: We conducted a systematic review assessing PubMed, Cochrane Database, Biosis Previews and the ClinicalTrials.gov website to identify all reports on patients with viral encephalitis treated with IVIG as of May 31, 2019. The main outcomes assessed were therapeutic efficacy and safety. For an increased homogeneity of the population, atypical viral infections were excluded, as were reports on prophylactic IVIG use, intrathecal application of immunoglobulins, or use of antibody-enriched IVIG-preparations. Data were extracted from published studies. Descriptive statistics were used. RESULTS: We included a total of 44 studies (39 case reports). The case reports cover a total of 53 patients. Our search retrieved two prospective and three retrospective studies. These show heterogeneous results as to the efficacy of IVIG therapy. Only one study reports a significant association between IVIG-use and death (odds ratio 0.032; 95% confidence interval 0.0033-0.3024; p = 0.0027). None of the studies report significant differences in the number of serious adverse events. CONCLUSION: Data on the efficacy of IVIG-therapy is heterogeneous. While it seems generally safe, evident superiority compared to supportive treatment has not been demonstrated so far. Future trials should also investigate the optimal dosing and timing of IVIG and their benefit in the immunosuppressed.

Characteristics and therapy of enteroviral encephalitis: case report and systematic literature review.

OBJECTIVES: Enterovirus (EV) is a frequent cause of encephalitis. The optimal therapeutic approach remains a matter of debate. We present the case of an immunosuppressed patient with EV encephalitis treated successfully with intravenous immunoglobulin (IVIG) and report the results of a systematic review on the characteristics of EV encephalitis, as well as the safety and efficacy of IVIG therapy. METHODS: A systematic review was conducted using the PubMed, Cochrane Database, BIOSIS Previews, and ClinicalTrials.gov databases to identify all reports on patients with EV encephalitis as of December 31, 2020. The main outcomes assessed were the efficacy and safety of the respective therapeutic approach. RESULTS: A total of 73 articles were included: one prospective trial, one retrospective and prospective case series, one purely retrospective case series, and 70 case reports. The case reports included a total of 101 patients. Immunosuppressed patients were at higher risk of contracting EV encephalitis and experiencing a fatal course. Hypogammaglobulinaemia particularly predisposes to EV disease, even with a moderate reduction in serum IgG levels. IVIG therapy in the immunosuppressed may confer a survival advantage. CONCLUSIONS: IVIG therapy is rarely associated with severe adverse events and may be considered in immunosuppressed patients with EV encephalitis. Future trials should investigate the optimal IVIG dosing and route of application, the benefit of antibody-enriched IVIG preparations, and the serum immunoglobulin level that should trigger prophylactic replacement.