Myoglobin for Detection of High-Risk Patients with Acute Myocarditis.

There is an unmet need for accurate and practical screening to detect myocarditis. We sought to test the hypothesis that the extent of acute myocarditis, measured by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR), can be estimated based on routine blood markers. A total of 44 patients were diagnosed with acute myocarditis and included in this study. There was strong correlation between myoglobin and LGE (rs = 0.73 [95% CI 0.51; 0.87], p < 0.001), while correlation was weak between LGE and TnT-hs (rs = 0.37 [95% CI 0.09; 0.61], p = 0.01). Receiver operating curve (ROC) analysis determined myoglobin ≥ 87 µg/L as cutoff to identify myocarditis (92% sensitivity, 80% specificity). The data were reproduced in an established model of coxsackievirus B3 myocarditis in mice (n = 26). These data suggest that myoglobin is an accurate marker of acute myocarditis. Graphical Abstract Receiver operating curve analysis determined myoglobin ≥ 87 µg/L as cutoff to identify myocarditis and these data were reproduced in an established model of coxsackievirus B3 myocarditis in mice: CMRI, cardiac magnetic resonance imaging; Mb, myoglobin; LGE, late gadolinium enhancement; ROC, receiver operating curve analysis.

Postinfectious Opsoclonus-Myoclonus Syndrome in a 41-Year-Old Patient-Visualizing Hyperactivation in Deep Cerebellar Nuclei by Cerebral [(18) F]-FDG- PET.

A 41-year-old woman presented with acute onset headache, vertigo, nausea, and gait disorder, initially interpreted as a common cold. Within 2 weeks, she developed a severe opsoclonus-myoclonus syndrome with truncal ataxia. Cerebrospinal fluid examination and serological findings suggested a recent infection with Coxsackie B3 virus. [(18) F]-FDG-PET proved to be the only imaging tool to identify the underlying pathology depicting hyperactivation in the vestibulo- and spinocerebellum as well as hyperactivation of the ocular muscles. At the clinical follow-up 4 months later, the patient's symptoms were considerably improved with only intermittent low-frequency opsoclonus. Corresponding PET findings were able to depict the response to therapy in the ocular muscles and the inferior vermis, whereas the deep cerebellar nuclei were still hyperactivated, however, to a lesser extent. This finding highlights the usefulness of functional/metabolic brain imaging to study the pathophysiology of this type of disorder.

Clinical features of coxsackievirus A4, B3 and B4 infections in children.

BACKGROUND: Clinical features of coxsackievirus A4 (CA4), B3 (CB3) and B4 (CB4) infections in children have not been comprehensively described. METHODS/PRINCIPAL FINDINGS: From January 2004 to June 2012, a total of 386 children with culture-proven CA4, CB3 and CB4 infections treated at Chang Gung Memorial Hospital, including 296 inpatients (CA4, 103; CB3, 131; CB4, 62) and 90 outpatients (CA4, 55; CB3, 14; CB4, 21), were included. From outpatients, only demographics were extracted and from inpatients, detailed clinical and laboratory data were collected retrospectively. The mean age was 32.1 ± 30.2 months; male to female ratio was 1.3 ∶ 1. Children with CB3 infection were youngest (76.6% <3 years of age), and had a highest hospitalization rate (90.3%) and a longest duration of hospitalization (mean ± SD, 7.5 ± 6.2 days). Herpangina (74.8%) was the most common presentation for children with CA4 infection, aseptic meningitis (26.7%) and young infant with fever (23.7%) for those with CB3 infection, and herpangina (32.3%) and tonsillitis/pharyngitis (27.4%) for children with CB4 infection. Almost all the inpatients had fever (97.6%). Twelve out of thirteen (92.3%) children with complications and ten of 11 children with long-term sequelae had CB3 infections. Two fatal cases were noted, one due to myocarditis with CA4 infection and CB3 were detected from the other case which had hepatic necrosis with coagulopathy. The remaining 285 children (96.3%) recovered uneventfully. CONCLUSION: CA4, CB3 and CB4 infections in children had different clinical disease spectrums and involved different age groups. Though rare, severe diseases may occur, particularly caused by CB3.

Epidemic pleurodynia caused by coxsackievirus B3 at a medical center in northern Taiwan.

Epidemic pleurodynia is seldom reported in Southeast Asia and there has been no report from Taiwan. We conducted a retrospective chart review of children = 18 years of age in the National Taiwan University Hospital from January 1 to December 31, 2005. Epidemic pleurodynia was defined as an acute illness characterized by sharp localized pain over the chest or upper abdomen. Patients with known heart diseases or pulmonary consolidations were excluded. In total, 28 patients met the case definition of epidemic pleurodynia. Coxsackievirus B3 (CB3) was isolated in 15 (60%) of the 25 throat swab specimens. Four (14%) of the 28 patients presented chest wall tenderness and only one (6%) of the 18 patients tested had an elevated creatinine kinase level. Twenty-one (75%) of the 28 patients described pleuritic chest pains and 10 (45%) of the 22 chest radiographies exhibited pulmonary infiltrates or pleural effusions. Six patients were observed with tonsillar exudates and one was confirmed to have a CB3 urinary tract infection. The clinical features and radiological findings suggest that CB3-associated epidemic pleurodynia might be a disease of the pleura and occasionally spreads to nearby tissues, resulting in chest wall myositis, pulmonary infiltrates and myopericarditis.

99mTc-MIBI myocardial perfusion imaging in myocarditis.

Myocardial perfusion imaging with technetium-99m-labelled methoxyisobutyl isonitrile single photon emission computed tomography (99mTc-MIBI SPECT) has proven to be an important clinical procedure in assessing the severity of myocardial ischaemia. The uptake and clearance of 99mTc-MIBI by the myocardium is affected by cell viability and membrane integrity. Consequently, infectious diseases, such as myocarditis, may also affect myocardial perfusion by inducing local inflammation and necrosis. We compared 99mTc-MIBI myocardial perfusion imaging with other heart monitoring methods in order to assess its value in the diagnosis of children with Coxsackie viral myocarditis. We examined 46 patients (age, 3-12 years) with Coxsackie viral myocarditis using 99mTc-MIBI myocardial perfusion imaging and compared the perfusion data with myocardial enzymes, electrocardiographic findings and echocardiography. Regions of hypoperfusion were found in all 46 patients. Seventeen patients (37%) showed two or more areas of diminished perfusion. Myocardial hypoperfusion was mild-to-moderate (<30%) in 33 (72%) patients and severe (>30%) in 13 (28%) patients. Characteristic creatine-kinase isoenzyme (CK-MB) increases, ST-T segment changes and diminished heart function were significantly correlated with reduced myocardial perfusion (all comparisons P<0.05). The results of this study suggest that the presence of myocardial uptake of 99mTc-MIBI may be a marker of myocardial inflammation and necrosis. All 46 patients with Coxsackie viral myocarditis showed a certain degree of reduced perfusion. When the perfusion findings were compared with other parameters, it was shown that myocardial enzyme levels, ST-T segment changes and left ventricular function correlated well with the 99mTc-MIBI-established perfusion defect severity. 99mTc-MIBI SPECT imaging is therefore helpful in providing additional diagnostic information in patients with Coxsackie viral myocarditis.

SPECT in focal enterovirus encephalitis: evidence for local cerebral vasculitis.

We report a 4-year-old, left-handed male with focal coxsackievirus A3 encephalitis who presented with seizures and acquired aphasia. Electroencephalography exhibited focal spike discharges over the right frontal regions, but cranial magnetic resonance imaging did not reveal any structural abnormalities. However, brain single-photon emission computed tomography performed during the acute phase disclosed focal hypoperfusion in the right frontal lobe, consistent with decreased regional cerebral blood flow in the territory of some branches of the right cerebral anterior artery. Without specific treatment, the patient recovered completely within 1 month, when brain single-photon emission computed tomography images returned to normal and cranial magnetic resonance imaging still demonstrated no abnormalities. The present case suggests the possible role of transient local cerebral vasculitis in the pathogenesis of focal enterovirus encephalitis.

Progressive liver calcifications in neonatal coxsackievirus infection.

Coxsackievirus group B can cause a severe systemic disease in the perinatal period. Severe manifestations like meningitis, encephalitis, hepatitis, and myocarditis have been previously reported. A case of a twin neonate infected by coxsackievirus group B is described, who developed progressive extensive hepatic calcifications demonstrated by ultrasound and computed tomography with follow-up. Hepatic calcifications in coxsackievirus infection have not been previously reported.

[Functional study of the heart valve apparatus by 2-dimensional Doppler echocardiography in rats with experimental endocarditis caused by Coxsackie B3 viruses]. / Issledovanie funktsional'nogo sostoianiia klapannogo apparata serdtsa metodom dvukhmernoi doppler-ékhokardiografii u krys pri éksperimental'nom éndokardite, vyzvannom virusami Koksaki B3.

Eleven neonatal cotton rats were infected with Coxsackie B3 viruses, 9 animals served as controls. The course of the disease was followed for 44 to 154 days. Electro- and phonocardiography, two-dimensional Doppler echocardiography, morphological and histological studies were performed in the experiment. All the histologically examined infected rats were found to develop myocarditis, whereas 75% of the animals had valvulitis. The total number of the afflicted values was 10, out of them the mitral, tricuspid, and pulmonary trunk valves accounted for 40, 40, and 20%, respectively. Doppler echocardiography revealed organic mitral and tricuspid insufficiencies in the outcome of valvulitis induced by Coxsackie B3 viruses due to the impairment of valvular cusp.

Altered distribution of heavy metals and lipids in coxsackievirus B3 infected mice.

This report presents evidence that a micro-organism common in our environment, coxsackievirus B3 (CB3) and the host responses it causes, can change the body distribution of heavy metals and lipids. The present results show that the distributions of intravenously injected 109Cd, 63Ni and 14C-Cholesterol are changed during infection, in a way that is specific for each of the studied compounds. Increased accumulation of 109Cd in the spleen and kidneys, 63Ni in the pancreas and ventricular myocardium, and 14C-Cholesterol in the heart and pancreas was observed during CB3 infection. This may affect the development of inflammatory lesions and subsequently result in altered and/or increased target organ toxicity as well as lipid accumulation. Thus, risk assessment in exposed populations may have to be evaluated depending on individual nutritional and exposure status.

Incessant automatic ventricular tachycardia complicating acute coxsackie B myocarditis.

A 13-year-old girl presented with incessant ventricular tachycardia complicating acute Coxsackie B3 myocarditis. Electrophysiologic assessment revealed that the tachycardia could not be terminated, overdrive suppressed or accelerated by programmed electrical stimulation, but was transiently slowed by intravenous adenosine triphosphate and had marked spontaneous and sympathoautonomic-mediated fluctuation in the tachycardia cycle length. These features were atypical of reentry and triggered automaticity and suggested that abnormal automaticity was the likely tachycardia mechanism. Intravenous amiodarone slowed the ventricular tachycardia, but the patient eventually succumbed from rapidly progressive left ventricular failure. Postmortem pathohistologic examination confirmed the diagnosis of acute myocarditis.

Coxsackie virus-induced acute pancreatitis in a long-term dialysis patient.

This report describes a patient on continuous ambulatory peritoneal dialysis (CAPD) who developed acute pancreatitis with pseudocyst formation and cloudy dialysate with pleocytosis in the absence of bacterial or fungal organisms. To our knowledge, pancreatitis, in the absence of hypertriglyceridemia in a CAPD patient, has not been previously reported. There was a significant increase in Coxsackie B1 and B6 viral titers by complement fixation test, suggesting Coxsackie virus-induced pancreatitis.

Myocardial imaging. Coxsackie myocarditis.

A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

Absence of hepatic uptake of Tc-99m sulfur colloid in an infant with Coxsackie B2 viral infection.

After the intravenous administration of Tc-99m sulfur colloid, there was found homogeneous lung, renal, and splenic uptake with absence of uptake by the liver and bone marrow of a nine-day-old female infant. More than 20 other doses were dispensed from the same Tc-99m sulfur colloid preparation with the expected biodistribution. A necropsy done two days later showed diffuse hepatic hemorrhagic necrosis without evidence of intravascular fibrin deposition in the lungs or kidneys. The underlying cause of the infant's disease was a Coxsackie B2 viral infection, based upon positive postmortem viral cultures of kidney and liver tissues and characteristic histopathologic lesions of the central nervous system and viscera. The altered biodistribution presumably reflected marked impairment of Kupffer cell function and an apparent increase in pulmonary macrophages.