Use of Intravenous Immunoglobulin Compared With Standard Therapy is Associated With Improved Clinical Outcomes in Children With Acute Encephalitis Syndrome Complicated by Myocarditis

Abstract

Although an autoimmune mechanism has been postulated for acute encephalitis syndrome (AES) complicated by myocarditis, immunomodulatory treatment strategies are still under investigation. To study the role of intravenous immunoglobulin (IVIG) in AES complicated by myocarditis in children age 2-12 years. This nonrandomized study was conducted in a tertiary care teaching hospital from July 2008 to January 2010. A total of 83 consecutive children with AES complicated by myocarditis were enrolled. Diagnosis of myocarditis was based on clinical, electrocardiogram, and echocardiogram findings. Patients were allocated to the two groups based on the days of the week: Those presenting on Monday and Friday were allocated to IVIG treatment (group I), and those presenting on the other days of the week to standard care (group II). Group I (n = 26) patients received IVIG at a dose of 400 mg/kg/day for 5 days in addition to standard care. All baseline and outcome data were recorded prospectively in a prestructured performa. The primary outcomes were mortality and improvement of left-ventricular dysfunction. A total of 83 children were studied: 26 in group I and 57 in group II. The mean (SD) age of the enrolled children was 4.6 years (3.1). The baseline characteristics were comparable between the two groups. A viral etiology could be established in 14 children, with the 2 most common agents isolated being Coxackie virus and enterovirus. Mortality was lower in the IVIG group [n = 1 (3.8 %)] patients compared with the standard care group [n = 13 (22.8 %)] with a relative risk of 0.17 (95 % CI = 0.02, 1.22). The difference in mortality reached borderline significance (p = 0.05). At discharge, mean (SD) ejection fraction improved from 32.8 % (6.31 %) to 49.5 % (9.04 %) in group I patients, which was significantly greater than that of group II (p = 0.001). Use of IVIG seemed to have a beneficial effect in terms of improved clinical outcomes in children with AES complicated by myocarditis. Our findings need further validation before IVIG can be incorporated into the treatment protocol of these children.

Clinical Features of Acute and Fulminant Myocarditis in Children – 2nd Nationwide Survey by Japanese Society of Pediatric Cardiology and Cardiac Surgery –

“…2 Bhatt et al concluded, based on an unblinded and quasi-randomized study without placebo in India, that 400 mg · kg -1 · day -1 of IVIG for 5 consecutive days compared with standard therapy was associated with improved clinical outcomes in children with acute encephalitis syndrome complicating myocarditis. 15 In contrast, a report of a multi-institutional analysis of pediatric myocarditis in the USA revealed that IVIG did not affect survival; the overall survival rate was as high as 92% despite a 49.1% administration rate for IVIG. 16 A Cochrane review concluded that IVIG should not been given routinely in any cases of pediatric or adult patients with presumed viral myocarditis.…”

Enteroviral encephalitis in children: clinical features, pathophysiology, and treatment advances

“…Intensive care therapies, including mechanical ventilation, ionotropic support, cardiovascular medications, extracorporeal membrane oxygenation, ventricular assist devices, and heart or liver transplants may be required for severely ill patients. 51,56 Prognosis A study in Vietnam concluded that the occurrence of convulsions on admission, the presence of limb weakness, GCS, and age were all significantly associated with fatal outcome, whereas illness day on admission, history of convulsion, and gender were not. 37 The results of a prospective clinical study of nearly 1500 children presenting to one hospital during three EV 71 outbreaks in Sarawak over 7 years showed that neurological involvement was strongly predicted by the presence of at least two of the following: peak temperature of 38.5uC, or more fever for 3 days or longer, and a history of lethargy.…”

“…A prospective quasi-randomized study in a tertiary care center of eastern Uttar Pradesh in 83 consecutive patients of AES complicated by myocarditis found that use of IVIG was associated with decreased mortality and increased left ventricular function. 51 But the major limitation of the study was a low viral yield and lack of follow up data of these patients. Uncertainty remains; however, over whether this expensive human blood product treatment is really effective, and randomized, placebo-controlled, phase 2 trials are needed.…”

A STEMI gone viral

“…[11][12][13] Similar benefits to LVEF were also noted in a randomized control trial of 83 pediatric patients diagnosed with acute viral encephalitis with myocarditis who were treated with IVIG compared to placebo. [14] These studies have led to routine use of IVIG for acute myocarditis at several institutions. Common side effects include headache, fever, and chills.…”