Congenital Infections

 

·         maternal infection leads to congenital malformations

·         may be acquired transplacental, partruitionally, or by ascending infection (bacteria)

·         manifest as 1)  Malformations (from abnormal neuronal migration); 2)  Destruction (so-called encephaloclastic); 3)  Calcifications

·         Mneumonic

o        To – Toxoplasma

o        R – Rubella

o        C – CMV

o        H – Herpes, HIV

o        E – Enteroviruses

o        S – Syphilis

·         Toxoplasma gondii – an INTRAcellular protozoan acquired via cat feces or infected meat

o        TRANSPLACENTAL infection

o        has a high rate of conversion from fetal infx to symptomatic disease

o        causes CNS necrosis

o        Brain atrophy, microcephaly, hydranencephaly, calcifications in basal ganglia, and periventricular

o        Path show granulomas, eosinophils (think parasites), sometimes organisms.

o        Early (< 26 week) fetal period = highest risk of developing problems

o        Babies present w/ seizures, small heads, and chorioretinitis (eye infections)

o        Calcifications may occur anywhere but mostly in basal ganglia and cortex

o        Hydrocephalus results from aqueductal scarring and subsequent stenosis -> non communicating hydrocephalus

o        TRIAD = calcifications + bilateral chorioretinitis + hydrocephalus

·         Rubella – togavirus, ss RNA virus, causes “German measles” acquired via inhalation

o        baby gets infected via TRANSPLACENTAL route

o        most severe during first 8-12 weeks’ of gestation.  Few effects seen if infected in 3rd trimester

o        affects dividing cells in the GERMINAL MATRIX (periventricular region)

o        loss of dividing neurons leads to small brain, and oligodendroglia loss leads to less myelination, copious calcifications seen

o        causes meningitis, vasculitis, lack of myelination and encephalitis

o        path shows inflammatory cells in meninges, and perivascular spaces w/ necrosis

o        clinically manifests as abortive fetus, still birth, and the following findings if the baby lives:

§         cataracts and other eye abnormalities

§         deafness

§         bone marrow suppression

§         heart malformations

o        US shows subependymal cysts (not specific)

o        CT shows widespread calcifications

o        MRI show perivascular lesions and brain loss

·         CMV – cytomegalovirus, member of herpes family, DNA genome, human reservoir

o        TRANSPLACENTAL infection

o        Affects during 1st and 2nd trimesters

o        Causes porencephaly, microcephaly

o        Path shows NUCLEAR + CYTOPLASMIC inclusions, microglial nodules

o        40% of babies of those who are seropositive are also infected

o        most common cause of TORCH infections (toxo is #2)

o        most common clinical manifestation is neurological

o        neuronal migration abnormalities, necrosis and calcification

o        Diagnosed by a positive culture, seropositivity for IgM, and path showing inclusions

o        CT shows atrophy, ventriculomegaly, and periventricular calcification

o        MRI shows heterotopias, prominent sulci, delayed myelination and cysts

o        Clinically babies are premature w/ hepatosplenomegaly, jaundice, chorioretinitis…later babies have seizures, retardation, hearing loss and hydrocephalus

o        ?active infection?? Treat w/ ganciclovir – but does not reverse abnormalities

·         HERPES – usually HSV-2 (sexually-transmitted), rarely HSV-1 (cold sores), see also Herpes Zoster

o        diffusely affects brain but infection usually occurs during PARTRUITION (down birth canal)

o        intrauterine infection occurs but clinically rarely seen b/c spontaneous abortion usually happens

o        Clinically see hydrocephalus, small heads, chorioretinitis

o        Virus has predilection for endothelial tissue

o        Pathologically see INTRANUCLEAR inclusions, and perivascular anoxic injury (strokes)

o        3 types of lesions:  1) mucosal – skin lesions (drop on rosepetal lesions), eye, mouth; 2) CNS – fever, lethargy, seizures; 3)  Disseminated – full-on sepsis if untreated

o        CT shows hypodense white matter, “falsely dense” cortical matter

o        MRI shows meningeal and cortical enhancement

o        Treat w/ acyclovir

o        **Varicella Zoster – can infect during and trimester, see worse lesions if infected LATER in pregnancy, may see necrotizing encephalitis if infected early.

·         HIV – retrovirus (RNA), sexually transmitted

o        usually perinatal (down birth canal), also sometimes transplacental

o        1/3 mothers pass onto their babies, 80% of childhood infections are from mothers

o        diffuse brain atrophy, basal ganglia calcifications

o        clinically see encephalitis, rarely see opportunistic, wt loss, failure to thrive, may rarely see thrush, may progress to spastic quadriparesis, rarely seizures

o        path shows glial nodules, giant cells, perivascular calcification, also in caudate and putamen, or demyelination

·         Enteroviruses – include coxsackie A + B, Echo, Polioviruses

o        infection is POSTNATAL and seasonal  (not true TORCH)

o        may affect anterior horn cells, cranial nerve nuclei

o        Polio – ssRNA, spreads via cell lysis once consumed, may cause bulbar or myelo symptoms, has affinity for anterior horn cells in spinal cord gray

o        MRI suggest encephalitis

·         Syphilis – treponema pallidum (spirochete), sexually transmitted

o        infection occurs transplacentally, usually from 4-7 months

o        HUTCHINSON’s triad = dental disorders (notched teeth) + bilateral deafness + interstitial keratitis

o        See hydrocephalus, strokes

o        Dx w/ VDRL, FTA-Abs

o        Tx w/ penicillin until CSF has no WBCs, and normal protein