Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid.

Not every neonate with congenital Zika virus (ZIKV) infection (CZI) is born with microcephaly. We compared inflammation mediators in CSF (cerebrospinal fluid obtained from lumbar puncture) between ZIKV-exposed neonates with/without microcephaly (cases) and controls. In Brazil, in the same laboratory, we identified 14 ZIKV-exposed neonates during the ZIKV epidemic (2015-2016), 7(50%) with and 7(50%) without microcephaly, without any other congenital infection, and 14 neonates (2017-2018) eligible to be controls and to match cases. 29 inflammation mediators were measured using Luminex immunoassay and multidimensional analyses were employed. Neonates with ZIKV-associated microcephaly presented substantially higher degree of inflammatory perturbation, associated with uncoupled inflammatory response and decreased correlations between concentrations of inflammatory biomarkers. The groups of microcephalic and non-microcephalic ZIKV-exposed neonates were distinguished from the control group (area under curve [AUC] = 1; P < 0.0001). Between controls and those non-microcephalic exposed to ZIKV, IL-1ß, IL-3, IL-4, IL-7 and EOTAXIN were the top CSF markers. By comparing the microcephalic cases with controls, the top discriminant scores were for IL-1ß, IL-3, EOTAXIN and IL-12p70. The degree of inflammatory imbalance may be associated with microcephaly in CZI and it may aid additional investigations in experimental pre-clinical models testing immune modulators in preventing extensive damage of the Central Nervous System.

Utility of Surface and Blood Polymerase Chain Reaction Assays in Identifying Infants With Neonatal Herpes Simplex Virus Infection.

Of 27 neonates with herpes simplex virus, DNAemia was observed in 100% with disseminated disease, 57% with central nervous system disease and 28% with skin, eye, mouth disease, suggesting DNAemia occurs frequently in these infants. Herpes simplex virus culture and polymerase chain reaction were performed on surface specimens from 13/27 infants, and ~50% tested positive only by polymerase chain reaction, suggesting the superiority of this technique.

Association of Herpes Simplex Virus Testing with Hospital Length of Stay for Infants ≤60 Days of Age Undergoing Evaluation for Meningitis.

Although neonatal herpes simplex virus (HSV) causes significant morbidity, utilization of the cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) test remains variable. Our objective was to examine the association of CSF HSV PCR testing with length of stay (LOS) in a 20-center retrospective cohort of hospitalized infants aged ≤60 days undergoing evaluation for meningitis after adjustment for patient-level factors and clustering by center. Of 20,496 eligible infants, 7,399 (36.1%) had a CSF HSV PCR test performed, and 46 (0.6% of those tested) had a positive test. Infants who had a CSF HSV PCR test performed had a 23% longer hospital LOS (incident rate ratio 1.23; 95% CI: 1.14-1.33). Targeted CSF HSV PCR testing may mitigate the impact on LOS for low-risk infants.

Plasma and cerebrospinal fluid herpes simplex virus levels at diagnosis and outcome of neonatal infection.

OBJECTIVE: To evaluate the utility of quantitative herpes simplex virus (HSV) polymerase chain reaction (PCR) levels for prognosis and management of neonatal HSV disease. STUDY DESIGN: Clinical and virologic data were abstracted by medical record review from neonatal HSV cases treated at Seattle Children's Hospital between 1993 and 2012. HSV PCR results from plasma (n = 47), cerebrospinal fluid (n = 56), or both (n = 40) at the time of diagnosis were available from 63 infants; 26 with skin-eye-mouth (SEM), 18 with central nervous system (CNS), and 19 with disseminated (DIS) disease. RESULTS: Plasma HSV PCR was positive in 78% of the infants with SEM, 64% with CNS and 100% with DIS disease. Mean plasma viral level was 2.8 log10 copies/mL in SEM, 2.2 log10 copies/mL in CNS, and 7.2 log10 copies/mL in DIS infants. The HSV levels were higher among infants who died compared with surviving infants, 8.1 log10 copies/mL (range 7.7-8.6) vs 3.8 log10 copies/mL (range 0.0-8.6), P = .001, however, level of HSV DNA in the cerebrospinal fluid or in plasma did not correlate with neurologic outcome. Dynamics of HSV clearance from plasma during high-dose acyclovir treatment showed single-phase exponential decay with a median viral half-life of 1.26 days (range: 0.8-1.51). CONCLUSIONS: Plasma HSV levels correlate with clinical presentation of neonatal HSV disease and mortality, but not neurologic outcome.

Management of HSV-1 encephalitis due to reactivation of HSV-1 during late pregnancy.

A previously healthy 31-year-old G4P2 woman at 33 weeks of gestation was admitted as an emergency with a pyrexia of 39°C, vomiting, headache and neck stiffness associated with photophobia, phonophobia and visual and auditory symptoms. There were no heraldic signs of eclampsia. Polymerase chain reaction and testing for herpes simplex virus in the cerebrospinal fluid diagnosed herpes simplex-1 meningoencephalitis. Following acyclovir, the clinical course improved. Spontaneous vaginal delivery occurred at 39 weeks of gestation with epidural analgesia using ropivacaine. Mother and child were neurologically normal and healthy 15 months later. Early administration of acyclovir is essential to reduce the risk of neurological complications. After treatment and a negative polymerase chain reaction for herpes simplex virus in the cerebrospinal fluid, epidural analgesia with local anesthetic and sufentanil is possible.

Two rare cases of central nervous system opportunistic mycoses.

This article presents two cases of opportunistic mycoses (OMs) of the central nervous system (CNS) caused by Cryptococcus neoformans and Aspergillus nidulans, respectively. The patients were hospitalised in local hospitals between 2009 and 2011 because of unspecific symptoms (fever, headache, and/or weight lost). Duration of symptoms varied from 4 days to over 2 weeks. The patients were treated with antibiotics and symptomatically. OM was not suspected in any of them. The patients became critically ill with symptoms of CNS involvement and were transferred to the Intensive Care Unit (ICU) of the University Hospital for Infectious diseases (UHID) in Zagreb. None of the patients belonged to the high-risk population for developing OMs. They were not HIV-infected, had no transplantation of bone marrow or solid organ, and were not on severe immunosuppressive chemotherapy. Fungi were isolated from cerebrospinal fluid (CSF) samples and, in one patient, from aspirate of cerebral abscess. Isolation and mycological identification of all fungal isolates and in vitro antifungal susceptibility testing of these isolates were done at the Reference Centre for Mycological Diagnostics of Systemic and Disseminated Infections (RCMDSDI) in Zagreb. The patient with cryptococcal meningitis was treated with amphotericin B and fluconazole and the patient with cerebral aspergilloma with voriconazole.

Tuberculous meningitis in pregnancy--implications for mother and fetus: case report and literature review.

The objective of this article is to report an illustrative case of tuberculous meningitis in pregnancy and review the recent literature outlining management and outcome of this devastating disease. A MEDLINE database search for English and French language articles dating back to 1966 was conducted and supplemented by reviewing the references of key articles and textbooks. An article was included if it described a case of tuberculous meningitis during pregnancy or explained the management of this disease. The search yielded a total of 17 articles, case reports, and reviews relating to tuberculous meningitis and/or pregnancy. Six authors describe cases and outcomes of tuberculous meningitis during pregnancy to give a total of 55 cases. Twenty-one patients died of their disease (38.2%), while 15 fetal or neonatal deaths have been reported (36.6%). Tuberculous meningitis is an insidious disease presenting a diagnostic challenge to even an astute practitioner. When recognized early and treated effectively with modern antituberculous medication, prognosis for mother and child is greatly improved.

Herpes simplex virus encephalitis in pregnancy.

BACKGROUND: Although polymerase chain reaction (PCR) can detect herpes simplex virus (HSV) in the cerebrospinal fluid (CSF), HSV encephalitis remains a significant cause of neurologic impairment in pregnant women. Assessment of fetal contamination also remains a problem. CASES: We report two cases in which HSV encephalitis initially was not suspected and led to significant maternal neurologic impairment. In both cases, HSV PCR of CSF confirmed the diagnosis. In one case, fetal serum HSV PCR excluded fetal contamination. CONCLUSION: As soon as encephalitis in pregnancy is suspected, a combination of acyclovir and penicillin is recommended because the potential benefits far outweigh the risks. Using the HSV PCR, HSV infection in the fetus can be diagnosed.

Maternal brain death during pregnancy.

A case of a 36-year-old woman diagnosed brain dead secondary to pneumococcal meningitis at 27 weeks of gestation is presented. In spite of aggressive therapy, supportive intensive care was possible for only 36 h. Signs of fetal distress appeared and a cesarean section was performed. The complexity of supportive care and its ethical implications are discussed.

Transfer of specific IgG and IgG subclasses to herpes simplex virus across the blood-brain barrier and placenta in preterm and term newborns.

The kinetics of virus-specific IgG subclasses (IgG 1-4) among newborns and their mothers has not yet been determined. In this report, we examined anti-herpes simplex virus IgG activities (HSV-IgG) and its subclasses in CSF and serum of premature or term newborns without HSV infection and in the serum of their mothers using ELISA. We found that CSF/serum ratios of HSV-IgG and IgG subclasses (IgG 1-4) in newborns with a gestational age less than 38 weeks were higher than those of term newborns. These findings indicate that the blood-brain barrier against HSV-IgG and IgG subclasses is insufficient in newborns. Furthermore, we found that HSV-IgG subclasses, which were transferred across the placenta and later transferred across the blood-brain barrier had a tendency to be proportional to each of the maternal HSV-IgG subclasses.

[Herpes simplex virus infection in pregnancy: epidemiologic, diagnostic and therapeutic data. An unusual case of HSV-1 in monozygotic twins]. / L'infezione da herpes simplex virus in gravidanza: rilievi epidemiologici, diagnostici e terapeutici. A proposito di un caso insolito di HSV-1 in gemelli monocoriali.

The Authors report a case of two pre-term monocorial twins affected by HSV-1 infection (Herpes Simplex Virus type 1), with generalized sepsis and involvement of the central nervous system (CNS), born by mother with primary infection who presented a typical vesicular eruption a week before delivery. As the HSV-1 was a disseminated type and the CNS was involved in both the twins, the diagnosis was based on clinical and laboratory findings (specific IgM and IgG) and on the use of Delpech-Lichtblau antibody liquoral index, a significant results both in the first and the second twin. Intensive care and early specific treatment with Acyclovir allowed a slow but progressive improvement of the twins' clinical picture. The antibody liquoral index may therapy of the viral sepsis cases involving the CNS, more than the cultural or antigen isolation of the treated virus.

A prospective study of the polymerase chain reaction for detection of herpes simplex virus in cerebrospinal fluid submitted to the clinical virology laboratory.

Polymerase chain reaction (PCR) was prospectively performed with cerebrospinal fluid (CSF) from 51 patients whose CSF was available for analysis and was submitted for viral culture and/or herpes simplex virus (HSV) serology and 20 patients whose CSF was submitted exclusively to the Clinical Biochemistry Laboratory. Primers were used that flanked a 92 bp segment of the HSV DNA polymerase gene (35 cycles). Amplified products were electrophoresed on agarose gel, blotted onto nylon membrane, and probed with a 32P-labelled sequence internal to the primers. For nested PCR, 1 microliter of PCR product was amplified for an additional 35 cycles before electrophoresis and Southern blot analysis. Review of the clinical records revealed that 15 patients had central nervous system (CNS) infections. Specific HSV DNA sequences were detected in CSF specimens of three of the individuals [PCR(2), nested PCR(1)]. Two of these patients had disseminated HSV infection including encephalitis and one patient had aseptic meningitis. The diagnoses of the 12 patients with CNS infection who did not have HSV DNA detected in CSF included encephalitis [varicella-zoster virus (1), cytomegalovirus (1), Mycoplasma pneumoniae (1)], meningitis [Neisseria meningitidis (1), Coccidioides immitis (1), Enterovirus (1), aseptic meningitis (1)], varicella-zoster radiculitis (2), human immunodeficiency virus dementia (2), and transverse myelitis due to Epstein-Barr virus (1). Importantly, HSV DNA was also not detected in the CSF of the 36 patients who did not have CNS infection and 20 samples submitted exclusively to the Clinical Biochemistry Laboratory. Our findings demonstrate the utility of PCR as a rapid, non-invasive method for the routine laboratory diagnosis of CNS infection due to HSV.

Coccidiodal meningitis and pregnancy: a case report.

A woman with coccidiodal meningitis had two successive pregnancies and was treated with intrathecal amphotericin B. The outcome was successful.

Cerebrospinal fluid eosinophilia and ataxia in five llamas.

Cerebrospinal fluid eosinophilia was associated with ataxia in five llamas. A presumptive diagnosis of cerebrospinal parasitism was made, and a response to combined anthelmintic and anti-inflammatory therapy was seen in each animal. The results demonstrate the value of an examination of cerebrospinal fluid in the evaluation of neurological disease in llamas.