A preterm neonatal male was born at 30 weeks with frequent jerking movements of all extremities and poor responsiveness to stimulation.
Prepared by Andrew West, MD from St. Josephs's Hospital,
A preterm neonatal male was born at 30 weeks gestation with
frequent jerking movements of all extremities and poor
responsiveness to stimulation. Physical exam also demonstrated a
denuded area of skin anterior to the left ear as well as a number
of healed skin lesions on his face. Electroencephalogram (EEG)
revealed a markedly abnormal pattern of generalized voltage
suppression without definable cortical rhythmicity consistent with
marked generalized cortical activity suppression and poor
neurological prognosis. Ophthalmologic consult revealed vitreous
haze, retinal lipid exudation, and multiple areas of retinal
hyperpigmentation. Pertinent laboratory tests revealed the
cerebrospinal fluid (CSF) to be clear yellow with elevated
lymphocytes, low glucose, and elevated protein. Secretion and blood
cultures initially were negative. Additionally, the mother had been
admitted at 18 weeks gestation with fever secondary to suspected
chorioamnionitis and was treated supportively. Later that same
month, the mother described having a nonpruritic rash on her
abdomen, buttocks, and upper legs that resolved spontaneously.
Postinfectious encephalomalacia secondary to herpes simplex type
A neonatal neurosonogram (figure 1) and an MRI of the brain
following delivery (figure 2) were performed. Neonatal cranial
ultrasound performed through the anterior fontanel in the coronal
(figure 1A) and sagittal (figure 1B) planes demonstrate diffuse
parenchymal volume loss with associated ventriculomegaly and large
extra-axial fluid collections. Additionally, cystic parenchymal
changes are evident on the sagittal image.
A coronal T2-weighted image confirms extensive cystic
encephalomalacia with associated volume loss (figure 2A). Also,
note the areas of hyperintensity on the axial T1 image (figure 2B)
within the basal ganglia, which are markedly hypointense on the T2
images (figures 2C and 2D), suggestive of hemorrhage or
Herpes virus is included in the congenital TORCH infections
(toxoplasmosis, other agents, rubella, cytomegalovirus, herpes
simplex), which affect the central nervous system (CNS) in the
fetal or neonatal period. Herpes is a DNA virus with two known
serotypes, types 1 and 2. Approximately 75% or more of neonatal
infections are caused by type 2.
The most common mode of transmission is parturitional, with
infection caused by direct contact of the infants' eyes, skin, or
oral cavity in the cervix or vagina. In these more typical cases,
clinical onset and CNS manifestations are seen 2 to 4 weeks after
birth. Infection in the fetal period is extremely rare with virus
transmission though the hematogenous-transplacental route. The
overall risk of intrauterine infection with herpes virus has been
estimated at 1 in 200,000 pregnancies.
Also, the frequency of viral manifestation with intrauterine
infection has been estimated at 3 for every 100 infected infants
; the protective effects of the placenta mitigate against
transmission of viral agents in most episodes of maternal viremia.
The rarity of infected fetuses carried to term may be secondary to
the severe encephaloclastic destructive effects occurring earlier
in the gestational period, possibly due to defective macrophage
function or impaired production of antiherpes antibody.
Thus, infections that occur within the first half of pregnancy are
associated with an increased frequency of spontaneous abortions and
The neuropathic and radiological findings vary upon the time of
gestation/age of infection. Imaging performed early in the
infection may demonstrate widespread areas of white matter signal
and attenuation abnormality reflecting edema, which eventually
evolves into encephalomalacic change.
Hemorrhagic infarction and meningeal enhancement can be seen in
Further progression reveals cortical gray matter laminar changes
with increased attenuation on CT and shortened T1 and T2 signal on
Regardless of the specific radiologic findings, fetal and neonatal
meningoencephalitis is usually diffuse and overwhelming, resulting
in widespread brain destruction.
Late imaging in the disease process demonstrates volume loss
diffusely throughout the cerebral hemispheres, hydrocephalus, and
Cerebellar involvement is seen in approximately 50% of cases.
Calcifications may be seen in the periventricular white matter and
the basal ganglia.
Occasionally, gyriform-type cortical calcifications are
Pathologically, astrogliosis with multifocal gray and white
matter involvement with cystic infarction and demyelination leads
to cystic encephalomalacia.
Microglial nodules with intranuclear inclusion-bearing cells are
seen under the microscope.
Herpes virus has a predilection for endothelial cells, which
explains the resulting vascular thrombosis and hemorrhagic
The imaging findings in the fetal form of herpes infection
differ from the more commonly described findings seen in the older
child/adult form. The more localized manifestations of the
infection afflicting the frontal and temporal regions are seen in
older children and adults, usually a result of the herpes simplex
type 1 virus.
The parturitional neonatal type of infection is similar to the
fetal form in that there is also a diffuse involvement.
Associated clinical findings can include skin, eye, and mouth
lesions. These are the most common manifestations of herpes
infection. Herpes can cause a chorioretinitis as was seen in this
patient. Disseminated infections have a high mortality rate, as do
the early gestational CNS infections.
Cerebrospinal fluid in these infants typically demonstrates at
least a partial elevation of protein, some pleocytosis, and mild
reduction of glucose.
Cerebrospinal fluid evaluation with PCR to detect the viral DNA has
become a major diagnostic tool.
Electroencephalography findings can help characterize the infection
manifestations by demonstrating characteristic, repetitive
sharp-slow wave complexes or spike activity.
Long-term sequelae of survivors can be markedly debilitating,
with major neurological problems, including mental retardation,
blindness, and spastic quadraparesis.
Congenital type 2 herpes infection in the fetal period is
exceedingly rare in contrast to the more typical neonatal form of
the disease. The radiological/pathological findings reflect the
diffuse, destructive CNS sequelae the virus can manifest as a
result of intrauterine infection. These sequelae typically result
in early fetal demise or long-term neurological impairment. The
patient in this case expired 4 days following delivery.