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Year : 2012  |  Volume : 5  |  Issue : 6  |  Page : 594-596
Severe enterovirus 76-associated acute encephalitis syndrome complicated by myocarditis and successfully treated with intravenous immunoglobulins

1 Department of Pediatrics, PGIMER and Associated Dr RML Hospital, New Delhi, India
2 Department of Pathology UCMS, GTB Hospital, New Delhi, India
3 Department of Pediatrics, B.R.D Medical College, Gorakhpur, U.P, India

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Date of Web Publication20-Mar-2013


Acute viral encephalitis is known to be caused by a wide range of viruses including enteroviruses. Here, we describe two cases of acute encephalitis syndrome (AES) from Japanese encephalitis endemic area diagnosed as enteroviral (EV 76) encephalitis with myocarditis. Intravenous immunoglobulin was given, following which, ejection fraction improved in both of them.

Keywords: Encephalitis, enterovirus 76, intravenous immunoglobulins, myocarditis

How to cite this article:
Bhatt GC, Sharma T, Kushwaha KP. Severe enterovirus 76-associated acute encephalitis syndrome complicated by myocarditis and successfully treated with intravenous immunoglobulins. Ann Trop Med Public Health 2012;5:594-6

How to cite this URL:
Bhatt GC, Sharma T, Kushwaha KP. Severe enterovirus 76-associated acute encephalitis syndrome complicated by myocarditis and successfully treated with intravenous immunoglobulins. Ann Trop Med Public Health [serial online] 2012 [cited 2020 Feb 27];5:594-6. Available from:

   Introduction Top

Acute viral encephalitis is known to be caused by a wide range of viruses either in sporadic or in outbreak forms. Globally identified viral etiological agents include herpes, enteroviruses, alpha, influenza A, rabies, and flaviviruses. During recent years, many reports have suggested enteroviruses emerging as a common cause of acute viral encephalitis, especially in South East Asia. [1],[2],[3],[4] Enteroviruses (EV) are known to be responsible for 25% to 35% of the cases of myocarditis. [5] Although an immune-mediated mechanism is postulated for encephalitis and myocarditis, therapy with intravenous immunoglobulin is still under investigation. We report two cases of EV-76-associated encephalitis complicated by myocarditis and successfully treated with intravenous immunoglobulin (IVIG).

   Case reports Top

Case 1

A 2-year-old male child was admitted with complaints of low grade fever for 7 days, convulsions (generalized tonic clonic) for 2 days, and altered sensorium for 1 day. Examination revealed a febrile child with temperature of 100 0 F, pulse rate of 178/min, which was feeble, R.R of 64/min, blood pressure of 56/32 mm Hg (< 5 th centile), and GCS score of 4. Systemic examination revealed hepatosplenomegaly (liver 3.5 cm, spleen 2 cm below subcostal margin) along with bilateral rhonchi, tachycardia, muffled heart sound with diminished deep tendon reflexes, and extensor plantar reflex. Investigations showed: Hemoglobin of 11.5 gm%, normal cell counts, platelet counts of 2.8 lacs/mm 3 , SGPT of 329 U/l, Urea of 67 mg%, blood sugar of 88 mg% and normal electrolytes. Cerebrospinal fluid (CSF) study showed total cell count of 46 cells/mm 3 with 92% lymphocytes and C.S.F protein of 38 mg% with normal sugar level. Rapid antigen test and peripheral smear for malaria parasite was negative. Widal, viral markers were negative, and blood cultures were sterile. Chest X-ray showed features of pulmonary edema .CECT head of the patient was normal. As the heart sounds of the patient were muffled, electrocardiography (ECG) was done, which showed rsr' pattern. Echocardiography was done to rule out any congenital and structural heart disease, but it only showed ejection fraction (EF) of 29%, suggesting myocarditis in this patient. Cardiac troponin was done, which was raised (2 ng/dl). As clinical, ECG changes, and echocardiographic changes were suggestive of myocarditis along with CSF pleocytosis, a diagnosis of enteroviral encephalitis with myocarditis was considered, and C.S.F of this patient was subjected to reverse transcriptase polymerase chain reaction (RT-PCR) for detection of EV genome, which came out to be positive for EV 76. Patient was managed symptomatically, shock was treated with ionotropes, following which shock improved, and phenytoin was given for seizures. IVIG was given to patient for 5 consecutive days at a dose of 400 mg/kg. Repeat C.S.F PCR for enterovirus was sent on completion of 5 days of intravenous immunoglobulin, which came out to be negative. The child started improving, and by 6 th day, fever subsided, urea became normal, and GCS increased to 15 on 12 th day of admission. At discharge (Day 20 th ), the ejection fraction improved to 38%. The patient was discharged without any sequelae and is well on follow-up.

Case 2

A 4-year-old female child presented with fever for 5 days, seizures for 2 days, and altered sensorium for 1 day.

General examination showed heart rate of 148/min, respiratory rate of 62/min, blood pressure of 62/30, and pedal edema. Systemic examination showed hepatomegaly (liver 4 cm below subcostal margin), bilateral crepts in chest, gallop rhythm with absent DTR, and inellicitable plantar reflex. Investigations revealed hemoglobin of 12.4 g%, total leukocyte count of 9,500/mm 3 (48% polymorphs, 50% lymphocytes, and 2% eosinophils), SGOT of 356 IU/l, SGPT 178 IU/L, urea of 36 mg/dl, normal creatinine, and trponin T of 2.3 ng/dl. CSF was done, which showed raised counts of 124 cells/mm 3 (with 60% lymphocytes) and normal protein and sugars. Echocardiography further showed EF of 23%. CSF PCR was negative for EV 76, but stool PCR showed EV 76. A diagnosis of EV 76-associated encephalitis with myocarditis was made, and patient was treated with IVIG along with management of shock and seizures. Patient's GCS improved to 12 in next 48 hrs after IVIG; SGOT reduced to 76 IU/l over next 5 days after IVIG, and EF increased to 28%. Finally, patient was discharged on 18 th day of admission when her EF increased to 42%, GCS improved to 15, and liver enzymes became normal. Patient had sequelae in form of behavior problem (irreverent talks) only.

   Discussion Top

Enteroviruses (EVs) cause a wide variety of diseases that range from non-specific viral illness to mild infections of herpangina and hand, foot, and mouth disease to potentially serious diseases such as myopericarditis, meningitis, myelitis, and neonatal sepsis. [6]. EVs are also etiological agents of encephalitis outbreaks in humans. [7] The viral RNA detected in CSF samples from our patient had close identity with the EV-89 and EV-76 that recently were reported as an unusual group classified genetically as group A EV (EV-A). [8] The clinical presentation of viral myocarditis varies from non-specific electrocardiographic abnormalities and mild viral illness to acute hemodynamic compromise or sudden cardiac death. However, most patients are asymptomatic. The condition of some patients with acute focal myocarditis mimics a diagnosis of myocardial infarction, with an acute onset of chest pain, tachyarrhythmia, or sudden death. [9] In our patients, initially a provisional diagnosis of Japanese encephalitis was made as this is the endemic zone for JEV encephalitis. However, raised cardiac enzymes, ECG findings suggestive of myocarditis, and low ejection fraction suggested myocarditis along with encephalitis in these patients. A diagnosis of enterovirus infection was made and confirmed after isolation of EV 76 in both cases. Intravenous immunoglobulin was given to patient for 5 consecutive days by slow infusion at dosage of 400 mg/kg/day. Such dose schedule of IVIG have been widely used in the therapy of several inflammatory disorders, [10] and from various studies, it is known that IVIG dosage can enhance the level of endogenous cytokine modulators with anti-inflammatory effects. [11] In our patient, the C.S.F PCR for enterovirus 76 was sent on 6 th day after completion of intravenous immunoglobulins, which came out to be negative, thus suggesting a possible role in treatment of enterovirus 76 infections. Recently, some of the studies had shown improved outcomes with IVIG in patients of encephalitis. [12] However, larger clinical trials are needed to confirm role of intravenous immunoglobulins in EV 76-associated encephalitis myocarditis syndrome.

   Conclusion Top

In a case of AES with atypical presentation and multiorgan involvement, enterovirus encephalitis must be considered in differential diagnosis. An early treatment with intravenous immunoglobulin is associated with better outcome.

   References Top

1.Ooi MH, Solomon T, Podin Y, Mohan A, Akin W, Yusuf MA, et al. Evaluation of different clinical sample types in diagnosis of human enterovirus 71-associated hand-foot-and-mouth disease. J Clin Microbiol 2007;45:1858-66.   Back to cited text no. 1
2.Karmarkar SA, Aneja S, Khare S, Saini A, Seth A, Chauhan BK. A study of acute febrile encephalopathy with special reference to viral etiology. Indian J Pediatr 2008;75:801-5.   Back to cited text no. 2
3.Sapkal GN, Bondre VP, Fulmali PV, Patil P, Gopalkrishna V, Dadhania V, et al. Enteroviruses in patients with acute encephalitis, Uttar Pradesh, India. Emerg Infect Dis 2009;15:295-8.  Back to cited text no. 3
4.Beig FK, Malik A, Rizvi M, Acharya D, Khare S. Etiology and clinico-epidemiological profile of acute viral encephalitis in children of western Uttar Pradesh, India . Int J Infect Dis 2010;14:e141-6.   Back to cited text no. 4
5.Martino TA, Liu P, Petric M, Sole MJ. Enteroviral myocarditis and dilated cardiomyopathy: A review of clinical and experimental studies. In: Rotbart HA, editor. Human enterovirus infections. Washington, DC: American Society for Microbiology Press; 1995. p. 291-352.  Back to cited text no. 5
6.Abzug MJ. Presentation, diagnosis, and management of enterovirus infections in neonates. Paediatr Drugs 2004;6:1-10.   Back to cited text no. 6
7.Pallansch MA, Roos RP Enteroviruses: Polioviruses, coxsackieviruses, echoviruses, and newer enteroviruses. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, et al, editors. Fields virology. 5 th ed. Philadelphia: Lippincott Williams and Wilkins; 2006. p. 839-94.  Back to cited text no. 7
8.Oberste MS, Maher K, Michele SM, Bellot G, Uddin M, Pallansch MA Enteroviruses 76, 89, 90 and 91 represent a novel group within the species Human enterovirus A. J Gen Virol 2005;86:445-51   Back to cited text no. 8
9.Dec GW Jr, Waldman H, Southern J, Fallon JT, Hutter AM Jr, Palacios I. Viral myocarditis mimicking acute myocardial infarction. J Am Coll Cardiol 1992;20:85-9.  Back to cited text no. 9
10.Mobini N, Sarela A, Ahmed AR. Intravenous immunoglobulin in the therapy of autoimmune and systemic inflammatory disorders. Ann Allergy Asthma Immunol 1995;74:119-28.  Back to cited text no. 10
11.Aukrust P, Frøland SS, Liabakk NB, Müller F, Nordøy I, Haug C, et al. Release of cytokines, soluble cytokine receptors and interleukin-1 receptor antagonist after intravenous immunoglobulin administration in vivo. Blood 1994;84:2136-43.  Back to cited text no. 11
12.Cheng MF, Chen BC, Huang TS, Hsieh KS, Chen SN, Liu YC. Clinical application of reverse-transcription polymerase chain reaction and intravenous immunoglobulin for enterovirus encephalitis. Jpn J Infect Dis 2008;61:18-24.  Back to cited text no. 12

Correspondence Address:
Girish C Bhatt
20/19, Second Floor, Old Rajendra Nagar, New Delhi-60
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1755-6783.109294

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