Will Lymphocytic Choriomeningitis Virus (Lcmv) Affect the Baby in the First Four Weeks of Pregnancy

Congenital Lymphocytic Choriomeningitis Virus (LCMV) infection:

ane-week-former male with hydrocephalus and bilateral chorioretinitis

Built Lymphocytic Choriomeningitis Virus (LCMV) infection:

i-calendar week-old male with hydrocephalus and bilateral chorioretinitis

Lucas J. A. Wendel Medico, Lauren Jensen BA, and Susannah Q. Longmuir MD

February ii, 2009

Chief Complaint: i-calendar week-onetime male person infant in the Neonatal Intensive Care Unit referred for center test for possible TORCH infection.

History of Nowadays Affliction: The patient was built-in at 39 ⁴/_seven weeks gestation with a birth weight of 3498 gm to a 24-year-one-time G2P0 (now P1) mother. A pre-natal ultrasound revealed large lateral ventricles and a prominent third ventricle; in that location were no other abnormalities seen at that fourth dimension. The pregnancy was also complicated by gestational diabetes and maternal cigarette smoking. The commitment was complicated by maternal fever, fetal tachycardia, and respiratory distress secondary to meconium aspiration. The patient was initially intubated but was weaned to room air after stabilization in the NICU.

Because of the abnormal findings on the pre-natal ultrasound, an MRI of the head was performed on the first day of life (Figure 1). This revealed marked hydrocephalus and bilateral intraventricular hemorrhage. Due to concern for intracerebral calcification, a CT scan was afterward performed which demonstrated periventricular calcification suggestive of an intrauterine "TORCH" infection (Toxoplasmosis, Other, Rubella, Cytomegalovirus (CMV), Canker Simplex Virus (HSV) (Figure 2). An ophthalmology consult was requested to evaluate for ocular findings consistent with a TORCH infection.

**Figure 1:** MRI of brain demonstrating marked hydrocephalus of the lateral ventricles.

**Figure 2:** CT scan of brain demonstrating subependymal periventricular calcifications (circled).

Past Ocular History: This was the patient's first eye exam.

Medical History: In add-on to the history to a higher place, the patient had failed a hearing screening in his left ear the day before ophthalmologic evaluation.

Family unit History: No family unit history of neurologic or ocular disorders. The mother denied a history of sexually transmitted illness or whatsoever disease during pregnancy. She reported some close contact with cats merely denied handling litter boxes or being exposed to their excrement.

Social History: Noncontributory.

Newborn Ocular Exam:

Visual Vigil: Winces to calorie-free, OD and Bone.
Movement: Move full OU.
Exterior and Anterior Segment Exam: Lids, conjunctiva, cornea, anterior chamber, iris, and lens were normal OU.
Dilated Fundus Exam: Extensive areas of chorioretinal scarring and atrophy with associated hyperpigmentation. These lesions were documented at the bedside with the RetCam Wide Field Digital Imaging System (effigy iii).

**Figure 3:** Fundus photos revealing bilateral chorioretinal scarring and atrophy.

Course:

Neurosurgery was consulted for evaluation of the child's hydrocephalus and found no indication for emergent shunting.

With regards to the ophthalmologic findings, information technology was felt that the lesions most likely represented chorioretinal scarring from inflammation or infection. Due to the fact that the abnormalities were bilateral, an inherited etiology was considered but felt to exist unlikely.

The Communicable diseases service was consulted. Due to the constellation of findings that included chorioretinitis, hydrocephalus, intracerebral calcification, and hearing loss, intrauterine TORCH infection was felt to be the best unifying diagnosis. The classic TORCH infections, namely Toxoplasmosis, Rubella, Cytomegalovirus (CMV), and Herpes Simplex Virus (HSV), were initially considered. Still, workup including urine culture for CMV and serum Toxoplasma IgM and IgG titers were negative. As well, the mother was Rubella immune, had a negative VDRL, and had no history or signs of HSV.

Later, attention was turned towards testing for bottom known, just increasingly recognized infectious agents. The patient'due south serum was drawn for antibody titers to Lymphocytic Choriomeningitis Virus (LCMV). Serum IgG was significantly elevated (>1:256) and IgM was within normal limits, which was felt to be consistent with prior infection.

The patient did eventually undergo a shunting procedure for his hydrocephalus. He has been discharged home. His retinal findings take been stable on serial exam.

Word:

Based on the appearance of the retinal findings, inflammatory or infectious causes were at the pinnacle of our differential diagnosis. Even so, inherited disorders were also considered. Aicardi syndrome, and X-linked disorder associated with peripapillary retinal "lacunae" and brain malformations seemed to be a potential fit, yet, this syndrome is fatal in males. Other genetic diseases such as choroideremia and gyrate atrophy would be unlikely to present and then early in life and with coincident primal nervous organisation pathology. Finally, the lack of neurologic and ocular disorders in the patient's family history, forth with the hydrocephalus, intracerebral calcifications, and hearing loss pointed to intrauterine infection as the most likely cause of the findings.

"TORCH"pathogens, a group of pathogens capable of crossing the placenta during maternal infection, have been identified worldwide as causes of significant perinatal morbidity and mortality. TORCH infections include Toxoplasmosis, Rubella, Cytomegalovirus (CMV), Herpes Simplex Virus (HSV), and other infections such as Syphilis, VZV, EBV, HIV, West Nile Virus, parvovirus, and LCMV. When these cross the placenta from infected mother to fetus, the result may range from pocket-size rash to spontaneous ballgame. A brief explanation of each of the TORCH infections follows.

Toxoplasmosis is an infection from the protozoan Toxoplasma gondii, whose only definitive host is the domestic true cat. It is for this reason that significant women are routinely brash against handling litter boxes that harbor cat waste during pregnancy. The majority of infants infected with Toxoplasmosis are asymptomatic at birth, but the archetype triad of symptoms includes chorioretinitis, hydrocephalus, and intracranial calcifications. Serum testing for anti-Toxoplasma gondii IgM and IgG antibodies usually facilitates a diagnosis. Pyrimethamine plus sulfadiazine tin can be effective as drug treatment for astute infection or for recurrences. Unfortunately, the damage to the fetus that may have already occurred is irreversible.

Rubella is a viral illness as well known as "German Measles," which has been nigh eliminated in the U.s.a. due to gimmicky vaccination practices. While the disease may be mild in children, information technology tin can cause serious fetal abnormalities if contracted during the offset trimester of pregnancy. Fetal abnormalities may include mental retardation, heart disease, deafness, and eye defects such every bit cataracts, glaucoma, and retinal damage. Some other classic sign of Rubella is the "blueberry muffin" rash. Handling for congenital infection is primarily supportive. A mother's immunity against Rubella is routinely tested for in the United States.

Cytomegalovirus (CMV) is a common and widespread infectious amanuensis, which affects approximately 40,000 infants built-in in the United States each yr. CMV has a bloodshed rate of 20%, simply survivors usually suffer from pregnant neurologic morbidities. Chorioretinitis occurs in fifteen-20% of cases. Diagnosis of CMV infection in the newborn is commonly fabricated via urine culture. Even though CMV is the virtually common viral infection in infants, there is no cure. Treatment is primarily supportive. Ganciclovir and foscarnet may accept some utility in selected cases.

Congenital Herpes Simplex Virus (HSV) is frequently contracted from the infected mother's genital tract during delivery. Equally such, signs and symptoms are usually not evident in the newborn until 5-15 days mail-birth. Common findings include intracranial calcifications, respiratory distress, conjunctivitis, keratitis, chorioretinitis, and microphthalmia. Diagnosis can be fabricated via viral culture or PCR.

Other. As our diagnostic abilities improve, the list of pathogens that are known to cause intrauterine infection grows longer. Syphilis, VZV, EBV, HIV, West Nile Virus, parvovirus, and Lymphocytic Choriomeningitis Virus (LCMV) have all been identified equally pathogens that can crusade intrauterine infections.

LCMV is a virus that is becoming increasingly recognized equally a dangerous pathogen. LCMV has been isolated from several clusters of patients that died all of a sudden after solid organ transplant, and reports of its ability to cross the placenta and crusade serious intrauterine infection are arable. This has led to increased awareness of LCMV among physicians specializing in transplant medicine, obstetrics, and infectious disease.

LCMV was get-go reported to crusade built infection in 1955. Its natural hosts are rodents, primarily mice and hamsters. Humans can be infected when they come into contact with the droppings or saliva of infected animals. In congenital infection it is idea that the virus accesses the CNS through the choroid plexus and replicates in ependymal cells and meninges. Necrotizing ependymitis causes aqueductal obstruction and hydrocephalus, and the immunologic response causes chorioretinitis. In a review of built LCMV infections, conducted at the University of Iowa (three), there was a 35% infant mortality associated with congenital infection. 88% of the children had chorioretinitis; 76% of these cases were bilateral. A bulk of the survivors had severe neurologic sequelae. It is very likely that our patient may have permanent visual and neurologic deficits.

Serologic testing for anti-LCMV IgM and IgG antibodies is available for diagnosis. In our case, it was felt that the clinical findings forth with the elevated IgG antibodies were indicative of intrauterine LCMV infection. There is no proven treatment for LCMV and treatment is primarily supportive. Antivirals such every bit ribavirin and acyclovir have been used in transplant patients without demonstrable effectiveness.

Differential Diagnosis:

Infectious (TORCH infections)
- Toxoplasmosis
- Other (i.due east. Syphilis, VZV, EBV, HIV, W Nile Virus)
- Rubella
- Cytomegalovirus (CMV)
- Canker Simplex Virus (HSV)
Inherited
- Aicardi Syndrome (lethal in males)
- Choroideremia
- Gyrate Atrophy

Diagnosis: Lymphocytic Choriomeningitis Virus (LCMV, categorized every bit "Other" in TORCH infections)

EPIDEMIOLOGY

Carried past rodents such as hamsters, guinea pigs, and mice.
Transmitted past exposure to urine, droppings, saliva, or nesting material of infected rodents.
Person-to-person transmission is rare but can occur betwixt infected female parent and fetus and through organ transplantation from infected donors.

SIGNS

Signs of chief maternal LCMV infection are rare.
Affected infants may have hydrocephalus, intracerebral calcification, macro- or microcephaly, and chorioretinitis.

SYMPTOMS

Symptoms of primary infection are similar to flu symptoms and include fever, stiff neck, loss of appetite, muscular aches, headache, and nausea and vomiting.
Symptoms occur ane-2 weeks post-obit exposure to an infected rodent and may be more severe in pregnant women and people with weakened immune systems.

TREATMENT

Currently, no specific handling for LCMV is available.
Women who either are pregnant or intend to become pregnant are advised to speak with their physicians recommended screenings and routine healthcare maintenance during pregnancy.
Pregnant women and those intending to go pregnant should avoid contact with rodents and their excreta.

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Source: https://webeye.ophth.uiowa.edu/eyeforum/cases/91-LCMV.htm