How Does Imaging of Congenital Zika Compare with Imaging of Other TORCH Infections?

The acronym TORCH is used to refer to congenital infections, such as toxoplasmosis, other infections (such as syphillis, varicella-zoster, and parvovirus B19), cytomegalovirus, and herpes simplex virus. The classic findings in patients with TORCH infections include rash in the mother during pregnancy and ocular findings in the newborn. Zika virus has emerged as an important worldwide congenital infection. It fits well with other congenital TORCH infections since there is a rash in the mother and there are commonly ocular abnormalities in the newborn. TORCH infections are recognized to have neurologic effects, such as ventriculomegaly, intraventricular adhesions, subependymal cysts, intracerebral calcifications, and microcephaly; however, the Zika virus is intensely neurotropic. Thus, it targets neural progenitor cells, leading to a more severe spectrum of central nervous system abnormalities than is typically seen in other TORCH infections, while relatively sparing the other organ systems. In this review, nonspecific findings of congenital infections initially will be described, then individual TORCH infections will be described and compared with the imaging findings associated with congenital Zika virus infection. For the radiologist, awareness of imaging features of common congenital infections may facilitate early diagnosis and may, at times, lead to prompt initiation of therapy. Online supplemental material is available for this article.

Noncongenital central nervous system infections in children: radiology review.

Infections of the central nervous system (CNS) are a very common worldwide health problem in childhood with significant morbidity and mortality. In children, viruses are the most common cause of CNS infections, followed by bacterial etiology, and less frequent due to mycosis and other causes. Noncomplicated meningitis is easier to recognize clinically; however, complications of meningitis such as abscesses, infarcts, venous thrombosis, or extra-axial empyemas are difficult to recognize clinically, and imaging plays a very important role on this setting. In addition, it is important to keep in mind that infectious process adjacent to the CNS such as mastoiditis can develop by contiguity in an infectious process within the CNS. We display the most common causes of meningitis and their complications.

Urine viral load and correlation with disease severity in infants with congenital or postnatal cytomegalovirus infection.

BACKGROUND: A correlation between cytomegalovirus (CMV) load in urine and severity of disease in congenitally infected infants has previously been reported. CMV load in postnatally infected infants has not been studied before. OBJECTIVE: To investigate CMV load in urine of infants with postnatal or congenital infection and correlate this with clinical symptoms of CMV disease and cerebral abnormalities. STUDY DESIGN: Infants admitted to our NICU between July 2000 and February 2010, and diagnosed with congenital or postnatal CMV infection were included. Clinical symptoms of CMV infection, cranial ultrasonography (cUS) and magnetic resonance imaging (MRI) findings were evaluated. CMV urine loads of postnatally infected infants were analyzed and compared with CMV urine loads of congenitally infected infants. RESULTS: Seventeen infants with congenital CMV infection and 45 infants with postnatal CMV infection were included. Thirteen/17 (76%) congenitally infected infants had clinical symptoms of CMV infection at birth and 11/17 (65%) had cerebral abnormalities diagnosed by neuro-imaging. None of the four asymptomatic infants had cerebral abnormalities. Of the postnatally infected infants 43/45 (96%) did not develop any clinical symptoms of CMV infection, but in 23/45 (51%) cerebral abnormalities such as lenticulostriate vasculopathy and germinolytic cysts were identified. The median CMV load in postnatally infected infants was significantly lower than in congenitally infected infants (1.0×10(5)copies/ml versus 8.5×10(6)copies/ml, p<0.001, respectively). CONCLUSIONS: CMV load in urine is significantly lower in infants with postnatal CMV infection than in infants with congenital CMV infection irrespective of clinical symptoms of CMV infection or cerebral abnormalities.

Disturbance of cerebral neuronal migration following congenital parvovirus B19 infection.

OBJECTIVE: We describe the clinical course of an infant who presented with severe fetal anemia and fetal hydrops following congenital parvovirus B19 infection before 16 gestational weeks. The fetus was treated by cordocentesis and intrauterine transfusion at 18 weeks. RESULTS: The infant demonstrated mild unilateral ventriculomegaly on antenatal magnetic resonance imaging, and polymicrogyria and heterotopia on postnatal magnetic resonance imaging. CONCLUSION: This adds to the evidence in recent literature of central nervous system damage associated with congenital parvovirus B19 infection.

The neonatal form of Aicardi-Goutières syndrome masquerading as congenital infection.

Aicardi-Goutières syndrome (AGS) is a rare, genetically-determined encephalopathy whose importance from a neonatology perspective is magnified because of the risk of misdiagnosis as the sequelae of congenital infection. Molecular advances have shown that AGS can be caused by mutations in any one of at least five genes (four of which have been identified). A recent genotype-phenotype study has shown that a neonatal form of the disease, highly reminiscent of congenital infection, is seen particularly with TREX1 mutations. It seems likely that the enzymes defective in AGS are involved in digesting endogenous nucleic acids (DNA and RNA) produced during normal cell replication, and that a failure of this removal results in inappropriate triggering of the innate immune system. This hypothesis explains the remarkable phenotypic overlap of AGS with congenital infection, where a similar interferon alpha mediated innate immune response is triggered by viral, as opposed to self, nucleic acids.

Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection.

Aicardi-Goutières syndrome (AGS) is an autosomal recessive neurological disorder, the clinical and immunological features of which parallel those of congenital viral infection. Here we define the composition of the human ribonuclease H2 enzyme complex and show that AGS can result from mutations in the genes encoding any one of its three subunits. Our findings demonstrate a role for ribonuclease H in human neurological disease and suggest an unanticipated relationship between ribonuclease H2 and the antiviral immune response that warrants further investigation.

Infantile spasms in an infant with cytomegalovirus infection treated with ganciclovir.

A 3-month-old male infant with cytomegalovirus infection and intractable partial seizures was treated with ganciclovir for 6 weeks. The drug was well tolerated, and virus shedding in the cerebrospinal fluid and urine was eliminated, although infantile spasms at the age of 6 months appeared. At the age of 12 months, intractable seizures persisted, and the psychomotor development of the infant was markedly delayed. To our knowledge, no previous similar case has been reported. These findings suggest that treatment with ganciclovir of infants with cytomegalovirus infection results only in cessation of virus shedding in the cerebrospinal fluid and urine without having a preventive effect on the future appearance of infantile spasms. This may be due to the irreversibility of previous brain damage from the cytomegalovirus infection and the virostatic nature of the drug.

Central nervous system apoptosis in human herpes simplex virus and cytomegalovirus encephalitis.

Central nervous system (CNS) specimens from 10 immunocompetent patients with herpes simplex encephalitis (HSE) and 3 infants with congenital cytomegalovirus (CMV) encephalitis were analyzed to determine whether apoptosis is a feature of CNS injury in these patients. Apoptotic neurons and glia were detected in significant numbers in acute HSE and CMV encephalitis. Occurring predominantly in areas of productive viral infection, apoptosis appeared to result from direct viral injury to neurons and was not dependent on inflammatory T cell responses. In contrast to patients with acute cases, patients with late sequelae of HSE or CMV had no detectable virus and minimal neuronal or glial apoptosis, regardless of the degree of inflammation. This is the first demonstration of apoptotic neuronal death in humans with HSE. These results suggest that neuronal apoptosis is an important contributing factor to acute CNS injury and may serve as a novel therapeutic target in these patients.

[Neonatal herpetic encephalitis. Current concepts concerning a case]. / Encefalitis herpética neonatal. Conceptos actuales a propósito de un caso.

We describe a newborn patient with herpes simplex infection localized to the central nervous system. The diagnosis was suspected on clinical grounds and it was corroborated by tissue culture isolation of the virus and by herpes simplex glycoprotein B DNA detection by PCR in cerebrospinal fluid. We describe the clinical manifestations of this patient and we present some considerations regarding pathogenesis, diagnosis, prognosis and treatment of this viral infection in the newborn period.

Magnetic resonance imaging of herpes simplex encephalitis.

Eight brain magnetic resonance imagings (MRIs) and one spinal MRI of 7 small infants and children with herpes simplex encephalitis (HSE) were retrospectively studied. Hypointense and hyperintense areas of gray and white matters on T1- and T2- weighted images, respectively, were commonly present, with temporal lobes being the most common lesion sites. Hemorrhagic lesions were found in 4 patients (57%). Early involvement of the white matter, as early as day 4, was a common MRI finding in these patients. One patient had relapsed encephalomyelitis, whose spinal MRI showed diffuse hyperintense T2 signals from the lumbar spinal cord to the conus medullaris. All patients but one survived with major neurological sequelae. Our results indicate that MRI is a sensitive diagnostic modality in cases of HSE, and early involvement of white matter is not an uncommon MRI finding of HSE. Spinal MRI may be helpful in the diagnosis of relapsed herpes encephalomyelitis.

Selected pediatric viral infections.

Viral infections of the central nervous system in infants and children are uncommon but potentially serious illnesses. Common causes have included the enteroviruses (particularly polioviruses and coxsackieviruses), herpes viruses (type 1 and type 2 herpes simplex, varicella, and cytomegalovirus), arboviruses, rubella, mumps, measles (including subacute sclerosing panencephalitis), and human immunodeficiency virus. Several of these viruses, such as cytomegalovirus, herpes simplex, and vertically transmitted human immunodeficiency virus, may cause congenital infections. Others are acquired later in childhood. In recent years, immunization programs have significantly reduced the occurrence of some of these diseases. A brief survey of the clinical and pathological manifestations of these illnesses will be discussed along with current incidence data.