Human cytomegalovirus DNA in cerebrospinal fluid.

To determine the involvement of human cytomegalovirus (CMV) in conditions of neurological impairment, detection of CMV DNA was attempted in cerebrospinal fluid obtained from 45 neurologically affected children aged from 1 month to 17 years by means of the polymerase chain reaction. Four patients (congenital CMV encephalopathy with West's syndrome, acute encephalitis, chronic epileptic encephalopathy, and lissencephaly) had CMV DNA in their cerebrospinal fluid. CMV DNA was absent in the cerebrospinal fluid of 11 neurologically unaffected controls aged from 1 month to 11 years. Three patients with acute CMV hepatitis had no CMV DNA in their cerebrospinal fluid. Among the four patients who had CMV DNA in their cerebrospinal fluid, two did not excrete CMV DNA or CMV antigen in the urine. The possible pathogenetic significance of CMV DNA in the cerebrospinal fluid is discussed. By applying the polymerase chain reaction to cerebrospinal fluid, the mode of brain invasion by CMV can be clarified further.     

Isolation of cytomegalovirus from cerebrospinal fluid of a congenitally infected infant.

The isolation of cytomegalovirus (CMV) from the CSF of an infant with congenital disease is documented. Samples of urine sediments and CSF were inoculated into tissue cultures of human foreskin fibroblast cells. Cytopathology was evident within 48 hours in those tubes inoculated with CSF. The urine cultures were later positive. All viral isolates were identified by complement fixation tests using known positive CMV antiserum.     

Human herpes virus type 7 DNA in the cerebrospinal fluid of children with central nervous system diseases

Human herpes virus type 7 (HHV-7) has been associated with unspecific febrile syndrome, exanthem subitum (ES), viral rashes and Epstein-Barr virus (EBV) like syndrome. Neurological complications such as hemiplegia or seizures have been described in a few children with ES. Whether HHV-7 may also affect the CNS in the absence of ES is unknown. In this study, we investigated CSF samples from children with different neurological diseases for the presence of HHV-7 specific DNA. A HHV-7 specific nested polymerase chain reaction (PCR) was established amplifying a 478 bp DNA sequence of the glycoprotein U23 of HHV-7 strain SB. 68 children with CNS diseases with inflammatory CSF findings (n=24), CNS diseases without inflammatory CSF findings (n=18) and febrile seizures (n=26) were examined. A total of 26 children with infectious diseases in the absence of neurological disease and 11 children without signs of a peripheral infection and without neurological disease served as controls. The CSF samples of six children from the study groups were HHV-7 PCR positive, but none from the controls. These children were diagnosed with aseptic meningitis (n=1), viral encephalitis/meningoencephalitis (n=2), facial palsy (n=1), vestibular neuritis (n=1) and febrile seizure (n=1). Conclusion These results indicate that human herpes virus type 7 infection is associated with central nervous system disease in children and should be considered in children whether inflammation in the cerebrospinal fluid is present or not. Received: 4 September 2000 and in revised form: 2 December and 23 December 2000 /  Accepted: 27 December 2000     

先天性症状性巨细胞病毒感染脑脊液病毒载量与听力损伤相关性

目的 探讨症状性先天性巨细胞病毒(cytomegalovirus,CMV)感染新生儿脑脊液(cerebrospinal fluid,CSF) CMV DNA载量与感音性听力损伤(sensorineural hearing loss,SNHL)的相关性.方法 36例先天性症状性CMV感染患儿,PCR法检测CSF CMV DNA载量,并于出生1个月内、生后6个月及1年左右行脑干听觉诱发电位检测.结果 (1)36例患儿,其中CSF CMV DNA阳性15例,阳性率41.2％,SNHL17例,SNHL发生率47.2％.(2) CSF CMV DNA阳性组SNHL发生率60.0％(9/15);阴性组SNHL发生率38.1％ (8/21),两组发生率比较差异无统计学意义(P =0.194).(3)CSFCMVDNA阳性组中,SNHL组与听力正常组CSF CMV DNA载量为3.35 ±0.68和3.17±0.56,两组载量比较,差异无统计学意义(P=0.36).结论 先天性症状性CMV感染患儿CSF CMV DNA是否阳性及其载量不是预测SNHL的指标.     

Beta2-microglobulin concentrations in cerebrospinal fluid correlate with neuroimaging findings in newborns with symptomatic congenital cytomegalovirus infection

Overview In newborns with symptomatic congenital cytomegalovirus (CMV) infection, neuroimaging is the best available predictor of neurodevelopmental outcome. Cerebrospinal fluid (CSF) findings in congenital CMV infection have seldom been described. Neonates with central nervous system infections present high CSF Beta₂-microglobulin (β₂-m) levels.Objectives The objectives of this study were: (1) to determine whether CSF β₂-m is increased in newborns with symptomatic congenital CMV infection, and (2) to examine its correlation with neuroimaging findings.Materials and methods Fourteen newborns with symptomatic congenital CMV infection admitted to La Paz Hospital from 1990 through 2004 underwent determination of CSF β₂-m. Ninety-three newborns, constituting the comparison group, underwent CSF β₂-m determination as part of a sepsis or meningo/encephalitis work-up, and at discharge had sterile cultures and normal neurological status. Neuroimaging findings were scored according to a semiquantitative system: (0) no abnormalities; (1) single punctate periventricular (PV) calcification and/or hyperechogenic areas in the thalamus and basal ganglia; (2) multiple discrete PV calcifications and/or ventriculomegaly; and (3) extensive PV calcifications and/or brain atrophy.Discussion and conclusion CSF β₂-m was increased in newborns with CMV infection (median 6.21 mg/L) compared with controls (1.68 mg/L) (P<.001). β₂-m showed a correlation with neuroimaging scores (r _s=0.753, P=.002). β₂-m was higher in patients who scored 2–3 (12.83 mg/L) than in patients who scored 0–1 (5.52 mg/L) (P=.028). CSF β₂-m is increased in newborns with symptomatic congenital CMV infection and correlates with neuroimaging abnormalities. β₂-m appears to be an indicator of the severity of brain involvement in congenital CMV infection.     

Vasopressin in fetal cerebrospinal fluid

Vasopressin concentrations were measured in the cerebrospinal fluid in two hydrocephalic fetuses at 33 and 34 weeks of gestation. The vasopressin concentrations in cerebrospinal fluid were 0.8 and 0.6 pg/ml, and in amniotic fluid 0.4 and 1.0 pg/ml, respectively.Previously measured vasopressin concentrations in amniotic fluid of the normal fetuses have been of the same magnitude.     

Infections in cerebrospinal fluid shunts

Bacterial colonization of cerebrospinal fluid shunts is a cause of significant morbidity, causing not only shunt malfunction and chronic ill-health but has also been implicated in an immune-complex glomerulonephritis. Almost all shunt colonizations involve Staphylococcus albus which gains access to the shunt during surgery and grows in microcolonies inside the shunt. The most reliable means of diagnosis at present is serological surveillance. Medical management is usually ineffective in eradicating colonization and colonized shunts must be replaced. Recent work on the impregnation of Silastic with antimicrobial substances to prevent colonization has provided encouraging results.     

Pump-regulated cerebrospinal fluid drainage

The drainage of cerebrospinal fluid (CSF) from the lumbar subarachnoid space is an effective technique for the treatment of CSF fistula and control of intracranial pressure in children and adults. The use of the lumbar drain poses unique challenges, however, in the pediatric population. We present a safe and effective method of pump-controlled lumbar subarachnoid drainage. This technique allows accurate titration of CSF removal while providing a closed system which is not sensitive to position changes or patient activity. Four case histories are reviewed.     

Neonatal herpes simplex virus infections: HSV DNA in cerebrospinal fluid and serum.

AIM: To investigate the diagnostic potential of herpes simplex virus (HSV) DNA in cerebrospinal fluid and serum; to correlate the findings with outcome in the child and with type of maternal infection. METHODS: Cerebrospinal fluid and serum specimens from 36 children with verified neonatal HSV infections, diagnosed between 1973 and 1996, were examined using the polymerase chain reaction technique (PCR). RESULTS: In 21 children for whom both cerebrospinal fluid and sera were available, HSV DNA was found in one or both specimens in 19 (90%). Overall, HSV DNA was found in the cerebrospinal fluid of 74% of 27 children, and in the sera of 20 out of 30 children (67%). In two children HSV DNA was not demonstrable in either serum or cerebrospinal fluid. In sequential specimens from four children, the persistence of HSV DNA after the end of intravenous treatment was associated with a poor prognosis. CONCLUSIONS: These findings indicate that HSV DNA detection in CSF and serum is highly sensitive for the diagnosis of neonatal HSV infections but does not replace the detection of virus in other locations using virus isolation and antigen detection.     

Malignancy markers in the cerebrospinal fluid

The specificity and sensitivity of malignancy marker determinations in cerebrospinal fluid (CSF) are often insufficient. Even at the subclinical stage of the disease the marker should be present. The effect of therapy should be monitored and relapses noted. Thus high standards of methodology are required. There are many substances that may indicate a malignant process in the central nervous system. However, there are many pitfalls in their determination. Malignant cells may occur in CSF via processes involving leptomeningeal structures such as metastases and leukaemia, but primary brain tumours seldom show cells in CSF. Human chorionic gonadotrophin and alpha-fetoprotein determinations assist in the early detection of cerebral germ cell tumours and of relapses, even in the subclinical stage. Desmosterol may aid in the diagnosis of medulloblastomas and malignant gliomas and in monitoring therapy. Putrescine levels are elevated in CSF of patients with medulloblastoma and correlate with the clinical state, and serial analyses may reveal relapses. Fibronectin, when determined in CSF at the time of diagnosis, appears to be of great significance for the prognosis of acute lymphoblastic leukaemia. Ferritin and beta-2-microglobulin may help in some well-defined conditions. Brain-specific proteins and antibodies to them are non-specific markers whereas tumour-specific antigens and growth factors may be more significant.Abbreviations AAT alpha-1-antitrypsin - AFP alpha fetoprotein - ALL acute lymphoblastic leukaemia - ASAT aspartate aminotransferase - B-2-m peta-2-microglobulin - CEA carcinoembryonic protein - CK creatine kinase - CNS central nervous system - CSF cerebrospinal fluid - FN fibronectin - GFAP glial fibrillary acidic protein - HCG human chorionic gonadotrophin - LD lactate dehydrogenase - MBP myelin basic protein - NGF nerve growth factor - NSE neuronespecific enolase - PA plasminogen activator - PG prostaglandin - TdT terminal deoxynucleotidyl transferase - TX thromboxane     

Endogenous fibrinolysis in neonatal cerebrospinal fluid

Although many infants with intraventricular haemorrhage (IVH) recover without hydrocephalus, little is known about how blood is cleared from the CSF pathways. Fibrinolytic activity was measured by the fibrin plate method in CSF from 11 normal infants and 17 infants with IVH. Normal CSF showed no fibrinolytic activity. All the samples taken less than 17 days from diagnosis of IVH samples taken between 17 and 60 days of IVH showed fibrinolytic activity. In 1 infant where 14 serial samples were taken, there was no detectable fibrinolysis up to 16 days after IVH but from 19 to 52 days there was definite fibrinolytic activity. Delayed endogenous fibrinolysis in the CSF is common after IVH but may, in some cases, be insufficient to prevent hydrocephalus.     

Anti-rotavirus antibody in cerebrospinal fluid.

Ten infants with benign convulsions associated with rotavirus gastroenteritis had no specific antibodies in cerebrospinal fluid by enzyme linked immunosorbent assay (ELISA). On the other hand, eight of 173 patients with other neurological diseases had specific IgG, IgA, or IgM antibodies. The reason for positive ELISA results is discussed.     

Postictal cerebrospinal fluid abnormalities in children

OBJECTIVES: To determine the frequency and characteristics of seizure-induced cerebrospinal fluid (CSF) abnormalities in children and to identify potential alternative causes of these findings. METHODS: Consecutive patients (n = 80) who underwent lumbar puncture within 24 hours after a seizure were studied retrospectively. The presence of CSF abnormalities in total leukocytes, polymorphonuclear cells, and protein was determined by using age-specific reference values. Coexisting conditions that could affect CSF findings, such as traumatic lumbar puncture, concurrent neurologic disease, and undiagnosed meningitis, were identified. RESULTS: Eighteen of the 80 patients were excluded from the final study group because of the presence of another condition that could alter the CSF. More than 50% of the excluded patients had an abnormal CSF leukocyte count or protein level, including 2 patients with initially undiagnosed meningitis, which was subsequently detected by post-hoc polymerase chain reaction testing. In the remaining 62 patients, postictal pleocytosis was detected in only 3 (5%), and increased protein was detected in only 6 (10%). The maximal postictal pleocytosis and protein level were 8 x 10(6) leukocytes/L (8 leukocytes/mm(3)) and 0.52 g/L (52 mg/dL), respectively. CONCLUSIONS: Seizure-induced CSF abnormalities are rare in children, and alternative, often unidentified, disease processes may account for many observed postictal abnormalities. All patients with abnormal CSF after a seizure should be thoroughly evaluated for other causes of the abnormality.     

Epstein-Barr virus DNA in the cerebrospinal fluid of an HIV patient with primary cerebral lymphoma

The case of a 7-month-old boy with vertically acquired immunodeficiency syndrome and multifocal primary cerebral lymphoma is reported. Neither neurological nor neuroradiological findings contributed towards the appropriate diagnosis. Positive Epstein-Barr virus DNA, assessed by means of polymerase chain reaction in cerebrospinal fluid, strongly suggested a diagnosis of primary cerebral lymphoma, which was subsequently confirmed by autopsy. Conclusions The detection of Epstein-Barr virus DNA using the polymerase chain reaction in cerebrospinal fluid is useful for the diagnosis of primary cerebral lymphoma. Received: 18 December 1996 and in revised form: 19 August 1997 / Accepted: 26 August 1997