Severe enterovirus 76 associated acute encephalitis syndrome complicated by myocarditis and successfully treated with intravenous immunoglobulins

Acute viral encephalitis is known to be caused by a wide range of viruses including enteroviruses. Here, we describe a case of 2-year-old patient of acute encephalitis syndrome from Japanese encephalitis endemic area, which was provisionally diagnosed as JE viral encephalitis but subsequently worked up for enterovirus due to atypical clinical presentation such as moderate grade fever, hypotonia, and hepatosplenomegaly along with ECG findings suggestive of myocarditis, which was successfully treated with intravenous immunoglobulins.

Keywords: Enterovirus, intravenous immunoglobulins, Japanese encephalitis virus

Acute viral encephalitis is known to be caused by a wide range of viruses including enteroviruses. Here, we describe a case of acute encephalitis syndrome (AES), which was previously diagnosed as JE viral encephalitis but subsequently worked up for enterovirus due to clinical and ECG findings of myocarditis and successfully treated with intravenous immunoglobulins.

A 2-years-old male child was admitted with complaints of fever from last 7 days, which was low grade, convulsions (generalized tonic clonic) from 2 days, and altered sensorium from last 1 day. Examination revealed a febrile child with temperature of 100°F, pulse of 178/min which was feeble, R.R of 64/min, blood pressure of 56/32 mm Hg, and GCS score of 4. Systemic examination revealed hepatosplenomegaly, B/L ronchi in chest, tachypnoea, tachycardia, muffled heart sound extensor planters, and diminished DTR. Investigation of this patient revealed hemoglobin of 11.5 gm%, normal cell count, and platelet counts of 2.8 lacs, SGPT of 329 U/l, Urea of 67 mg%, blood sugar of 88 mg%, normal electrolytes. C.S.F 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 malarial parasite was negative. Widal was negative, viral markers for acute hepatitis were negative, blood cultures were sterile, chest X-ray showed features of pulmonary edema, and CECT of patient was normal. As the heart sound of the patient was muffled, an 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 of 29%, suggesting myocarditis in this patient. Cardiac troponin was done, which was raised (2 ng/dl). As the patient was from endemic zone of Japanese encephalitis, C.S.F and serum for JEV genome was sent, which came out to be negative. However, as clinical and ECG changes suggestive of myocarditis are not reported in JE, an alternative provisional diagnosis of enteroviral encephalitis was considered as in 2006 enterovirus 76 ^[1] was reported from this region. C.S.F of this patient was subjected to reverse transcriptase polymerase chain reaction (RT-PCR) for detection of enterovirus genome, which came out to be positive for enterovirus 76. Therefore, a diagnosis of enterovirus encephalitis with myocarditis was made, and patient was managed conservatively.

Patient was managed symptomatically, shock was treated with ionotropes following which shock improved, and phenytoin was given for seizures. Intravenous immunoglobulin was given to patient for 5 consecutive days at a dose of 400 mg/kg/day. 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 and urea became normal on 12 ^th day of admission. The patient was discharged without any sequelae.

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. ^[2] EVs are also etiological agents of encephalitis outbreaks in humans. ^[3] 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). ^[4] 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. In the European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases, 72% of patients had dyspnea, 32% had chest pain, and 18% had arrhythmias. ^[5] The condition of some patients with acute focal myocarditis mimics a diagnosis of myocardial infarction, with acute onset of chest pain, tachyarrhythmia, or sudden death. ^[6] In our patient, 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 this patient. JE virus is not known to cause myocarditis; therefore, an alternative diagnosis of enterovirus infection was made and confirmed after an isolation of EV-76 in this patient. Intravenous immunoglobulin was given to patient for 5 consecutive days by slow infusion at dosage of 400 mg/kg/day. Such dose schedules of IVIG have been widely used in the therapy of several inflammatory disorders, ^[7] and from various studies it is known that IVIG dosage can enhance the level of endogenous cytokine modulators with anti-inflammatory effects. ^[8] 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. However, larger clinical trials are needed to confirm role of intravenous immunoglobulins in EV-76 associated encephalitis myocarditis syndrome.

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

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1755-6783.102066