Neuroimaging of herpesvirus infections in children

Abstract

Six members of the herpesvirus family cause well-described neurologic disease in children: herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), varicella-zoster (VZV), Epstein-Barr (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6). When herpesviruses infect the central nervous system (CNS), the clinical presentation is non-specific and often confounding. The clinical urgency is often underscored by progressive neurologic deficits, seizures, or even death, and prompt diagnosis and treatment rely heavily on neuroimaging. This review focuses on the spectrum of cerebral manifestations caused by these viruses, particularly on non-congenital presentations. Recent advances in our understanding of these viruses are discussed, including new polymerase chain reaction techniques that allow parallel detection, which has improved our recognition that the herpesviruses are neurotropic and involve the CNS more often than previously thought. Evolving knowledge has also better elucidated viral neuropathology, particularly the role of VZV vasculitis in the brain, HHV-6 in febrile seizures, and herpesvirus reactivation in immunosuppressed patients. The virology, clinical course, and CNS manifestations of each virus are reviewed, followed by descriptions of neuroimaging findings when these agents infect the brain. Characteristic but often subtle imaging findings are discussed, as well as technical pearls covering appropriate use of MRI and MRI adjuncts to help differentiate viral infection from mimics.

Subcortical cysts in anterior temporal regions: Unusual imaging finding in congenital cytomegalovirus infection

“…4 Common manifestation of congenital CMV infection includes microcephaly, intracranial calcifications, hearing loss, hepatosplenomegaly, low birth weight, pneumonitis, and hematologic abnormalities. 5,6 The degree of neurological impairment varies from mild learning and behavioral problems to mental retardation and impaired physical skills. Neuroimaging findings of congenital CMV infection include intracranial calcification, ventriculomegaly, ventricular adhesions, white matter abnormalities, neuronal migrational disorders, microcephaly, lenticulostriate vasculopathy, and destructive encephalopathy.…”

Bilateral symmetrical basal ganglia and thalamic lesions in children: an update (2015)

“…Varicella Zoster Virus similarly has a relative predisposition to vasculopathy, typically involving the M1 segment of the middle cerebral artery. If the vasculopathy involves the origins of the lenticulostriate arteries, this can result in basal ganglia pathology (usually unilateral) [27]. Cytomegalovirus can affect the bilateral ganglia in the neonatal period but is fairly rare in the older population and is thus outside the scope of this discussion.…”

“…Of all the members of the Herpesviridae family, EBV shows the most characteristic tropism for the deep gray nuclei. T2 hyperintensity in the bilateral basal ganglia and thalami is often identified in EBV encephalitis [25][26][27]. Associated anomalies include the cerebral hemispheres, brainstem, and cerebellum [28].…”

“…However, since the description of several adolescent cases and an association with the nvCJD, interest in these rare, slowly progressive and fatal syndromes has increased among pediatricians and the general public [33]. On MRI, basal ganglia alterations in viral and spongiform encephalopathies are most often characterized by restricted diffusion either from primary viral infection or from secondary to virusrelated small vessel vasculopathy and asymmetric involvement of the gray and white matter structures [26,27,32,34]. Lower NAA/Cr has been described in patients affected by sporadic Creutzfeldt-Jakob disease with basal ganglia involvement showing a rapid course of the disease [35].…”

An Encephalitis Primer

“…Diagnostic work-up should therefore include an LP at least 72 h after the onset of symptoms even if this means a repeat LP for children who presented at < 72 h. An important issue is that a number of children with subsequently proven HSV will have a normal CSF white cell count [15]. Whilst scanning is usually abnormal in HSVE, this may not be the case early in the course of the illness particularly with CT [16]. A wide variety of imaging findings have been described from the classic fronto-temporal lesions through to more diffuse lesions.…”