Background Neuroimaging Histopathology & Immunohistochemistry

BACKGROUND AND CLINICAL INFORMATION: Head

Summary: The spectrum of congenital rubella syndrome (Gregg's syndrome) includes low birth weight, ocular abnormalities (micropthalmos, cataracts, chorioretinitis), cardiovascular defects, mental retardation, bone lesion, encephalopathy, pneumonitis, hearing defects (peripheral or central) in addition to the overt clinical findings of petechiae and associated thrombocytopenia. True malformation of the CNS is rare. The range of disease in newborns is extremely variable. Norman Gregg is an Australian ophthalmologist who fisrt associated an epidemic of morbilliform rash, characteristic of rubella, with the appearance of cataracts in newborn children in 1941.

Pathogenesis: Rubella virus is an RNA virus that has been classified in the togavirus family. The destructive (inflammatory) effect is far more contributory to the final result than the teratogenic effect. Functional abnormalities are usually found and structural malformation is less common. The gestational age of the conceptus at the time of infection is a critical factor in determining the outcome.

Incidence: It occurs in 15 - 40% of fetus with a history of maternal rubella infection during gestation.

Time of the year: rubella infection usually occurs in late winter and early spring. Babies with congenital rubella are usually seen in late fall. Be careful when findings suggestive of congenital rubella is seen in baby not being born not in this period. The patient may be infected in the southern hemisphere or something other than congenital rubella causes the pathologic changes.

Mortality: 10-20% mortality during the first year of life. At the time of birth, the infant may harbor a large amount of virus and may continue to shed virus for a year.

Delayed manifestations are common. The most significant delayed manifestations include hearing loss (87%), congenital heart disease (46%), mental retardation (39%), cataract or glaucoma (34%). Children thought to have normal hearing when tested early in life have subsequently been found to have hearing loss when they reached school age.

Time of infection:

Prior to the 8th week of gestation, between 50 - 80% of fetus exposed to maternal rubella become infected; by the 2nd trimester no more than 10-20% of the infants become infected, and during the 3rd trimester infection of the fetus is relatively unknown.
The earlier the infection, the more severe the manifestations and more organs are affected in addition to higher rate of malformation. The later the congenital infection, the pathologic change due to the inflammatory effect is more important than the teratogenic effect.

Eye pathology:

Characteristic 'salt and pepper' rubella retinopathy is not included in the description.
Earlier infection will cause more severe malformation of the eye such as microopthalmia and cardiovascular defects. Infection at later time will cause cataract. The pathology of the cataract is a sequelae of the disturbance of the primary lens fibers formation during the fourth to seventh weeks. Histologically, the nucleus of the lens is necrotic.

NEUROIMAGING: Head

Microcephaly (the most common, probably secondary to chronic encephalitis), chronic encephalitis, hydrocephalus, agenesis of corpus callosum, Down's syndrome, epilepsy and spastic syndromes have all been described. True malformation of the CNS is rare and most of the lesions are destructive in nature.

HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY: Head

Neuropathology: Meningoencephalitis, microcephaly, and retarded myelination and cytoarchitecture development.

Vascular abnormality:

About half of the cases have a vascular abnormality, most frequently the capillaries of the basal ganglia are affected. There is focal destruction of the vessel wall, focal disruption of the internal elastic membrane, pericapillary collection of granular material, and endothelial necrosis.
Ischemic damages are present in over half of the cases and are usually adjacent to the vascular lesions.

Progress rubella panencephalitis:

A sequel of congenital and non-congenital rubella infection that involves the cerebrum, cerebellum, brain stem.
Essentially a demyelinating disease of white matter with extensive involvement of the basal ganglion and brain stem. The cortex is relatively intact.
Widespread neuronal destruction with perivascular lymphocytic infiltration and vasculitis
Multinucleated giant cells may be seen.

Ear pathology:

The deafness is due to defective development of the organ of Corti and is seldom total. In most cases, the organ of Corti is partly intact and the patient can perceive some deep frequency. In the inner ear, the cochlear and the vestibule is affected by the teratogenic effect at the time of development and also the inflammatory effect on the cochlear epithelium.
The critical stage for the development of the cochlear is about a month later than that for the lens, so cataract and deafness are rarely found in the same individual.