Cytomegalovirus Encephalopathy Research Articles

Cytomegalovirus Encephalopathy during Brain Tumor Irradiation.

Some patients with brain cancer show extremely short survival postradiochemotherapy treatment for unknown reasons. Recent work shows that this is closely linked to encephalopathy associated with reactivation of latent cytomegalovirus in the host. Importantly, survival can be enhanced by treatment with antiviral drugs.See related article by Goerig et al., p. 3259.

Failure of preventive measures leading to mother-to-child hiv transmission. Case report.

Despite significant advances in antiretroviral treatment (ARV) and HIV infection prevention, about 400 children worldwide are still diagnosed daily with HIV infection, most cases due to perinatal transmission. It is estimated that the knowledge and rigorous application of prophylactic measures to reduce the vertical transmission of infection would significantly reduce this risk to less than 1%. We report the case of a 5 months old infant coming from a pregnancy with HIV risk and multiple risk factors for transmission of the vertical infection, who did not receive postnatal testing and treatment. The diagnosis was established during infancy, falling into the AIDS stage by cytomegalovirus (CMV) disease with retinal sequelae occlusion. ARV treatment was initiated late, but from the moment of diagnosis, requiring further changes due to drug interactions, lack of availability and resistance to TARV. Although the patient’s progression was marked by severe comorbidities: sequelae of CMV disease, mixed HIV and CMV encephalopathy, pulmonary tuberculosis, repetitive respiratory and digestive opportunistic infections, the evolution of immunological parameters was slowly favorable under treatment. Proper implementation of prophylactic measures in the newborn and the pregnant woman could have significantly reduced the risk of HIV transmission to the patient, with a high probability that she would not have been infected. The case reported reflects the failure of strategies to prevent HIV / AIDS infection in pregnant women and newborns; conclusions must be drawn to avoid similar situations.

Frequent occurrence of therapeutically reversible CMV-associated encephalopathy during radiotherapy of the brain.

Neurological decline during radio(chemo)therapy of the brain is often attributed to disease progression or side effects of radiotherapy. Diagnosis of opportunistic neurotropic infections such as cytomegalovirus (CMV) infections is uncommon, even though high-grade gliomas and some brain metastases are known to contain CMV particles. We prospectively examined the frequency of CMV encephalopathy during radiotherapy of the brain. Fifty patients requiring whole-brain radiotherapy for brain metastases (n = 27) or local radio(chemo)therapy of the brain for high-grade gliomas (n = 23) were observed in the prospective observational GLIO-CMV-01 study. MRIs and blood samples were obtained before, halfway through, and at the end of radiotherapy. MRIs were screened for disease progression or increased intracranial pressure. Blood was tested for anti-CMV immunoglobulin (Ig)M, anti-CMV IgG, and CMV DNA. Thirty-two of 50 (64%) patients were positive for anti-CMV IgG before radio(chemo)therapy. Fifteen of those 32 (48%) developed viremia during or up to 28 days after treatment. Thirteen of those 15 (87%) required treatment for CMV-associated encephalopathy. MRIs were negative for disease progression, edema, or bleeding. None of the patients negative for anti-CMV IgG developed viremia, suggesting a reactivation rather than a primary infection.In the group at risk consisting of anti-CMV IgG+ patients, age >65 (P = .004) and the amount of dexamethasone taken during radio(chemo)therapy (P = .004) were associated with an increased risk for CMV-associated encephalopathy. One hundred and fifty days after the start of radio(chemo)therapy, survival was 74% (14/19) (no encephalopathy) versus 54% (7/13) (encephalopathy) (odds ratio, 0.42; 95% CI, 0.03-1.86; P = .25). CMV reactivation frequently causes encephalopathy during radio(chemo)therapy of the brain. The unexpected high incidence of this infection makes it highly clinically relevant for every treating physician.

Severity of disability in patients with cerebral palsy secondary to symptomatic congenital cytomegalovirus encephalopathy

Cytomegalovirus (CMV) is a leading cause of congenital encephalopathy and cerebral palsy (CP). In this study we report the severity of disability in individuals who developed CP secondary to symptomatic congenital CMV encephalopathy. The medical records of patients with CP secondary to symptomatic congenital CMV encephalopathy diagnosed from 1995 to 2011 were retrospectively reviewed. Gross Motor Functional Classification Scale (GMFCS) level, language function, and swallowing function were collected. Twenty-three patients were found. Of those 23 patients, 83% (19/23) were at a GMFCS level IV or V, 9% (2/23) each GMFCS level II or III and none (0%) at GMFCS I. Eighteen patients were non-verbal, 3 had minimal to moderate verbal skills and 2 had no verbal impairment. Eighteen patients also had severe dysphagia requiring gastrostomy tube (GT) feedings, and 5 ate orally. There was a strong correlation between the severity of GMFCS and having a gastrostomy tube (p< 0.0006) and GMFCS and verbal skills (p< 0.0023). This study shows that patients with CP secondary to symptomatic congenital cytomegalovirus encephalopathy have a very high risk of having severe physical and cognitive disabilities. This information can help healthcare providers and caregivers plan for the potential long-term medical, rehabilitation, and financial needs of this group of patients.

Prenatal Diagnosis of Fetal Cytomegalovirus Infection After Primary or Recurrent Maternal Infection

In Brief Objective To determine the reliability of prenatal diagnosis of cytomegalovirus infection in women with primary or recurrent infection. Methods Amniotic fluid (AF) samples from 117 pregnant women were evaluated for cytomegalovirus culture and cytomegalovirus-DNA detection. Neonatal and postnatal samples also were examined to confirm or exclude transmission of maternal-fetal cytomegalovirus infection. Results Of 25 women with primary cytomegalovirus infection, 13 (52%) had cytomegalovirus-positive AF samples by polymerase chain reaction (PCR), nine of which also were diagnosed by culture. All eight neonates born to mothers whose AF was cytomegalovirus-positive by PCR and culture were cytomegalovirus-infected, and three were symptomatic. One aborted fetus had cytomegalovirus-DNAemia. Of four women with cytomegalovirus-positive AF samples by PCR only, two delivered asymptomatic cytomegalovirus-infected neonates and two aborted (one fetus had cytomegalovirus encephalopathy). Of 45 mothers with recurrent infection, two with AF cytomegalovirus-positive by PCR and culture, and another with cytomegalovirus-positive AF samples by PCR only, aborted cytomegalovirus-DNA-positive fetuses. Of the other seven women with cytomegalovirus-positive AF samples by PCR only, two delivered asymptomatic cytomegalovirus-infected neonates, two delivered neonates cytomegalovirus-positive by PCR only (one was symptomatic), and three delivered infants cytomegalovirus-negative by PCR and culture. All 47 mothers with nonactive cytomegalovirus infection and cytomegalovirus-negative AF samples had uninfected neonates. Polymerase chain reaction was superior to viral culture in sensitivity and negative predictive value (100% compared with 57% and 94%, respectively) but was lower in specificity and positive predictive value (97% and 83%, respectively, compared with 100%). Conclusion Prenatal diagnosis of fetal cytomegalovirus infection should include PCR in addition to viral culture, particularly for congenital cytomegalovirus infections following maternal recurrence. Prenatal diagnosis of fetal cytomegalovirus infection should include polymerase chain reaction assay in addition to viral culture, particularly for congenital infections after maternal recurrence.

Prenatal diagnosis of fetal cytomegalovirus infection after primary or recurrent maternal infection

Objective: To determine the reliability of prenatal diagnosis of cytomegalovirus infection in women with primary or recurrent infection. Methods: Amniotic fluid (AF) samples from 117 pregnant women were evaluated for cytomegalovirus culture and cytomegalovirus-DNA detection. Neonatal and postnatal samples also were examined to confirm or exclude transmission of maternal-fetal cytomegalovirus infection. Results: Of 25 women with primary cytomegalovirus infection, 13 (52%) had cytomegalovirus-positive AF samples by polymerase chain reaction (PCR), nine of which also were diagnosed by culture. All eight neonates born to mothers whose AF was cytomegalovirus-positive by PCR and culture were cytomegalovirus-infected, and three were symptomatic. One aborted fetus had cytomegalovirus-DNAemia. Of four women with cytomegalovirus-positive AF samples by PCR only, two delivered asymptomatic cytomegalovirus-infected neonates and two aborted (one fetus had cytomegalovirus encephalopathy). Of 45 mothers with recurrent infection, two with AF cytomegalovirus-positive by PCR and culture, and another with cytomegalovirus-positive AF samples by PCR only, aborted cytomegalovirus-DNA-positive fetuses. Of the other seven women with cytomegalovirus-positive AF samples by PCR only, two delivered asymptomatic cytomegalovirus-infected neonates, two delivered neonates cytomegalovirus-positive by PCR only (one was symptomatic), and three delivered infants cytomegalovirus-negative by PCR and culture. All 47 mothers with nonactive cytomegalovirus infection and cytomegalovirus-negative AF samples had uninfected neonates. Polymerase chain reaction was superior to viral culture in sensitivity and negative predictive value (100% compared with 57% and 94%, respectively) but was lower in specificity and positive predictive value (97% and 83%, respectively, compared with 100%). Conclusion: Prenatal diagnosis of fetal cytomegalovirus infection should include PCR in addition to viral culture, particularly for congenital cytomegalovirus infections following maternal recurrence.

Microglial nodular encephalitis and ventriculoencephalitis due to cytomegalovirus infection in patients with AIDS: two distinct clinical patterns.

In patients with AIDS, cerebral infection due to cytomegalovirus (CMV) results in two distinct neuropathological patterns: microglial nodular encephalitis (MGNE) and ventriculoencephalitis (VE). In order to identify clinical features to facilitate the differential diagnosis of these two forms of CMV encephalopathy in living patients, we retrospectively reviewed the clinical records of 18 patients with MGNE or VE diagnosed at autopsy. We identified the following clinical features as distinguishing the two encephalopathies: (1) MGNE manifests earlier than VE; (2) the onset of MGNE is acute, whereas the onset of VE is insidious; (3) the onset of MGNE is marked by confusion and delirium, which do not occur in VE; (4) VE is frequently associated with radiculopathy, which is absent in MGNE; and (5) VE is associated with more marked alterations in cerebrospinal fluid (high protein levels and pleocytosis). The early neurological manifestations of MGNE should prompt a search for systemic CMV infection, which may lead to earlier treatment.

Cytomegalovirus Encephalopathy in an Infant with Congenital Acquired Immuno-Deficiency Syndrome

A female infant born pre-term to a HIV seropositive mother presented at birth with seropositivity for HIV and CMV viruria. At five months of age she developed an AIDS-related complex. Six months later she died from rapidly progressive diffuse encephalopathy. Post mortem examination revealed generalized CMV infection. Neuropathological examination showed a nodular encephalitis with occasional cytomegalic cells containing characteristic CMV inclusion bodies. There was no evidence of HIV encephalitis; immunostaining for HIV antigen (gp 41) was negative. Opportunistic infections in infants with congenital AIDS are the exception. To our knowledge, only one case of CMV encephalitis in an infant with congenital AIDS has been reported previously. In that case, as in the present one, a reactivation of a congenital CMV infection is likely.

Prenatally Acquired Cytomegalovirus Encephalopathy

A case is reported of congenital cytomegalovirus infection. A baby girl was born at an estimated gestational age of 35 weeks to a 26-year-old Hispanic women. There was maternal cocaine abuse and poor prenatal care, and variable decelerations, abruptio placentae, and meconium-stained fluid occurred in the intrapartum period. Cytomegalovirus was isolated from the urine, with growth occurring in 48 hours, and the neonate had characteristic neurodevelopment handicaps.

Prenatal cytomegalovirus disease and cerebral microgyria: evidence for perfusion failure, not disturbance of histogenesis, as the major cause of fetal cytomegalovirus encephalopathy.

From the study of four personal cases of microgyria related to fetal CMV infection and a review of the literature it is concluded that: 1) Microgyria is a frequent neuropathological finding in this disease - 2) CMV microgyria is the result of an insufficiency of cerebral blood supply and is not due to a disturbance of neurogenesis or histogenesis as a consequence of a direct cytopathic effect of the virus on germinal cells. The way by which the CMV causes cerebral ischemia - angeitis or more probably, transient systemic perfusion failure, - is discussed, but remains obscure. Other viruses may act on the fetal brain by way of circulatory disturbances.