Cortical maldevelopment in congenital cytomegalovirus infection transmitted by a woman with preexisting immunity.

Although cytomegalovirus (CMV) congenital infection is more severe in children born to women with primary infection, neurological symptoms have also been observed in infants born to mothers with preconceptional immunity. The authors describe for the first time a case of severe cortical development disorder associated with multiple abnormalities of the white matter, occurring in the second-born child of a woman found to be positive for anti-CMV immunoglobulin G (IgG) before pregnancy. CMV DNA was detected in the urine and blood of the infant. These findings indicate that the neurological outcome of CMV infection may be severe also in infants born to women with preexisting immunity.

Prenatal and perinatal determinants of neonatal seizures occurring in the first week of life.

To evaluate prenatal and perinatal risk factors for early neonatal seizures, we conducted a case-control study including 100 newborns with neonatal seizures in the first week of life and 204 controls randomly selected from a list of healthy newborns born in the same hospital during the study period. Generalized tonic seizures were the most common seizures observed (29%), although the majority of newborns (71%) experienced more than one type of seizure. The most frequent presumed etiology of neonatal seizures was hypoxic-ischemic encephalopathy (30%). A history of epilepsy in first-degree relatives was found only for cases. Neonatal seizures were found to be associated with maternal disease in the 2 years before pregnancy, mother's weight gain > 14 kg during pregnancy, placental pathology, preeclampsia, low birthweight, low gestational age, and jaundice in the first 3 days of life. The need for cardiopulmonary resuscitation was found only for cases (37%). The causal pathways for neonatal seizures often begin before birth, and some of the factors identified may be preventable.

Teratogenic effects of antiepileptic drugs: use of an International Database on Malformations and Drug Exposure (MADRE).

PURPOSE: The study goal was to assess teratogenic effects of antiepileptic drugs (AEDs) through the use of a surveillance system (MADRE) of infants with malformations. METHODS: Information on all malformed infants (1990-1996) with maternal first-trimester drug exposure was collected by the International Clearinghouse for Birth Defects and Monitoring Systems (ICBDMS). Cases were defined as infants presenting with a specific malformation, and controls were defined as infants presenting with any other birth defect. Exposure was defined by the use of AEDs during the first trimester of pregnancy. The association of AEDs with malformations was then estimated by calculating the odds ratios with 95% confidence intervals and testing their homogeneity among registries. RESULTS: Among 8005 cases of malformations, 299 infants were exposed in utero to AEDs. Of those exposed to monotherapy, 65 were exposed to phenobarbital, 10 to methylphenobarbital, 80 to valproic acid, 46 to carbamazepine, 24 to phenytoin, and 16 to other AEDs. Associations were found for spina bifida with valproic acid. Infants exposed to phenobarbital and to methylphenobarbital showed an increased risk of oral clefts. Cardiac malformations were found to be associated with phenobarbital, methylphenobarbital, valproic acid, and carbamazepine. Hypospadias was associated with valproic acid. Porencephaly and other specified anomalies of brain, anomalies of face, coarctation of aorta, and limb reduction defects were found to be associated with valproic acid. CONCLUSIONS: Using the MADRE system, we confirmed known teratogenic effects of AEDs. We also found increased risks for malformations that had never been reported associated with AEDs or for which the association was suggested by case reports.

Does HHV-8 have a protective role on the development of HIV encephalopathy? Italian HIV-Seroconversion Study.

OBJECTIVE: To evaluate risk factors for HIV encephalopathy and whether Kaposi's sarcoma (KS) and coinfection with human herpesvirus 8 (HHV-8) protect against this disease in a cohort of HIV seroconverters. METHODS: Individuals with known dates of HIV seroconversion belonging to different HIV exposure categories (intravenous drug users, homosexual men, heterosexual contacts) were recruited by 17 clinical centers throughout Italy. Antibodies to HHV-8 lytic antigens were detected in a subgroup of participants using an immunofluorescence assay. Risk factors for HIV encephalopathy were evaluated using Cox proportional models. The association between KS or HHV-8 infection and HIV encephalopathy was evaluated using standard statistical techniques. RESULTS: During the study period, 485 of the 1,520 participants developed acquired immunodeficiency syndrome, 38 of whom developed HIV encephalopathy. HHV-8 serologic status was determined for 390 participants. Male gender, injecting drug use, and low CD4 T-cell count were associated with HIV encephalopathy; none of the 63 participants with KS developed this disease. The risk of HIV encephalopathy did not differ significantly by HHV-8 serologic status. CONCLUSIONS: HIV encephalopathy was found to be associated with male gender and intravenous drug use. The risk increased at lower CD4 T-cell counts. Although HIV encephalopathy occurred less frequently in patients with KS, no association with HHV-8 infection was found.

Prion protein glycotype analysis in familial and sporadic Creutzfeldt-Jakob disease patients.

Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs) are characterised by the accumulation of a pathological conformer of PrP, named PrPsc. Molecular weight and glycosylation of the protease-resistant core of PrPsc (PrP27-30) are heterogeneous in different forms of TSEs. We analysed PrP27-30 glycotypes in a large number of TSE-affected patients: 50 sporadic CJD (sCJD), 1 iatrogenic CJD, 1 Gerstmann-Sträussler-Scheinker syndrome (GSS) with the Pro102Leu mutation of PrP, 3 familial CJD (fCJD) with the Glu200Lys mutation and, for the first time, 7 fCJD with the Val210ll3e mutation. All patients were screened for the polymorphic codon 129 of the PrP gene. PrP27-30 deglycosylation and PrPsc immunohistochemistry were performed in selected cases. We found that two PrP27-30 glycotypes (type 1A and type 2A) are produced in sCJD. Type 1A is more frequently associated with methionine than valine in position 129. Type 1A is also formed in Val210lle fCJD. In Glu200Lys fCJD and GSS patients, we found that PrP27-30 has the same mobility of type 1 but different glycosylation ratios (type 1B). Our findings indicate that the polymorphic residue 129 of PrP has a leading role in determining the proteinase degradation site of PrPsc while mutant residues 102 or 200 influence only the glycosylation pattern.

Differing risk factors for cerebral palsy in the presence of mental retardation and epilepsy.

Whether the combined diagnosis of cerebral palsy with mental retardation or with mental retardation and epilepsy reflects more severe manifestations of the spectrum of cerebral palsy, or whether these conditions reflect overlapping outcomes related to different exposure, remains an open question. At two centers, in Rome and Conegliano, Italy, 51 children with combined cerebral palsy, mental retardation, and epilepsy, 31 children with both cerebral palsy and mental retardation, and 48 with cerebral palsy alone were identified and examined, and their mothers interviewed. The triple diagnosis group was significantly more likely than the other two groups to have a history of neonatal convulsions and a history of epilepsy in first-degree relatives, but less likely to have a mother's age at delivery greater than 33 years, a birthweight less than 1500 g, or gestational age less than 32 weeks. The dual diagnosis group was more likely than the other two groups to have maternal education of less than 8 years. These data suggest the possibility of different etiopathogenetic pathways for various presentations of cerebral palsy.

Congenital malformations in twins: an international study.

Data provided by nine registries based in European and Latin America countries were analyzed to assess whether there is an excess of malformations in twins compared to singletons. Specific congenital malformations were coded according to the ninth revision of the International Classification of Diseases (ICD). Malformation rates and rate ratios (RR) for twins compared to singletons were calculated for each registry, and the homogeneity of the RRs was tested using the test of Breslow and Day. If departure from homogeneity in the different registries was not significant, registry-adjusted RRs with 95% confidence intervals were calculated. Overall, among 260,865 twins, 5,572 malformations were reported. A total of 101 different types of malformations or groups of defects was identified, and a homogeneous estimate of the RRs among registries was found for 91.1% of the malformations. Thirty-nine of the 92 malformations with homogeneous estimates of RRs were more common in twins than in singletons. For the remaining nine malformations, heterogeneous estimates of RRs were obtained. This study confirms the majority of already known associations and further identifies previously unreported malformations associated with twins. In conclusion, there is an excess of malformations in twins compared with singletons, and all anatomical sites are involved. The number of specific malformations associated with twins is higher than that previously reported in smaller studies.

Creutzfeldt-Jakob disease mortality in Italy, 1982-1996.

We report an estimate of Creutzfeldt-Jakob disease (CJD) deaths in Italy from 1982 to 1996 by using mortality data based on a retrospective review of deaths taken from the mortality data base of the Italian Census Bureau (ISTAT, years 1982-1993), and on the prospective surveillance performed by the Italian National Register of CJD (years 1993-1996). One hundred and ninety-five and 154 deaths attributed to CJD were recorded by ISTAT and the CJD register, respectively. The average annual age-adjusted mortality rate was 0. 45 and 0.84 deaths per million for the period 1982-1993 and 1993-1996, respectively. The yearly increase in the number of CJD deaths was mostly due to a rise in the reported deaths among people older than 60 years. The result of the linkage between ISTAT and the CJD register shows that the integrated age-adjusted mortality rate for 1993 was about 1 case per million, similar to the rates observed in other studies and obtained by the CJD register alone in 1996. This study indicates that the data of the CJD register is accurate and therefore important for assessing eventual changes in the characteristics of the disease resulting from bovine spongiform encephalopathy or other new risk factors.

Idiopathic chronic fatigue and chronic fatigue syndrome: a comparison of two case-definitions.

The aim of the study was to compare the signs and symptoms of individuals meeting two different definitions of chronic fatigue syndrome (CFS). Ninety-four patients fitting the eligibility criteria for idiopathic fatigue were enrolled into the study. Of the 94 patients, 48 met the 1988 definition of CFS, 20 the 1994 (but not the 1988) definition of CFS, and 26 met neither definition. The 1994 defined cases were more likely than 1988 defined cases, and non-syndromal individuals to be male, married, and high school educated. The 1994 cases were less likely than 1988 cases to present acute onset, self reported sore throat, mild fever lymphadenopathy, pharyngitis. In conclusion, the 1994 criteria increased the number of patients classified as CFS; however, those who fit only the 1994 criteria were less likely to have an acute symptomatic onset and signs and symptoms suggestive of an infectious process.

Prescription of neuroleptics for children and adolescents in Italy.

The objective of this study was to describe the use of neuroleptics among children and adolescents in the province of Rome. Subjects 5 to 19 years of age who received neuroleptic prescriptions within the National Health Service between 1986 and 1991 were identified. Prevalence and incidence of use were estimated. The yearly prevalence of use during the study period ranged from 1.3 to 1.7 per 1000 inhabitants. The incidence during 1989 was 1.1 per 1000, with a marked increase with age. Haloperidol was the drug most frequently prescribed; 59.2% of the subjects received only one prescription during the year. Among subjects with more than one prescription, 42.3% received neuroleptics in combination. The observed pattern of use suggests that in current practice neuroleptics are also used for the treatment of nonpsychotic conditions. The analysis of data derived from a prescription monitoring system may provide an important contribution to the description of neuroleptic use among children and adolescents.

[Epidemiological study of a primary fibromyalgia in pediatric age]. / Studio epidemiologico sulla fibromialgia primaria in età pediatrica.

BACKGROUND: The aim of the present epidemiological research was to select paediatric subjects who were suspicious of Primary Fibromyalgia (PF) and estimate its incidence in the students of the schools of Castiglione delle Stiviere (Mantova). METHODS: The students had to answer Campbell's questionnaire which was varied and simplified in order to make it comprehensive to everybody even if the key answers were unchanged. The questionnaire was distributed in primary schools (3dr up to 5th class), secondary schools and high schools and its compilation was carried out with a doctor's help. The authors collected and examined 2408 forms. After this evaluation 66 subjects, corresponding to 2.74%, had been considered suspected of PF and had been called to our Paediatric Department to continue the study. In the second phase of the research these 66 students have been submitted to a deep anamnesis, a careful clinical evaluation, a test of tender-points with a digital pressure algometer and some laboratory tests to exclude other rheumatic diseases. The map of the American College of Rheumatology adapted by Wolfe et al. (1990) was used to evaluate tender-points. RESULTS: After this phase 29 students (1.20%) proved to be affected by primary fibromyalgia.

Risk factors for the co-occurrence of partial epilepsy, cerebral palsy and mental retardation.

A case-control study (64 cases and 209 controls) was carried out to identify risk factors for the co-occurrence of early-onset partial epilepsy, cerebral palsy and mental retardation in children with and without cerebral malformations. History of epilepsy in first-degree relatives, maternal diseases in the two years before pregnancy, placental pathologies, low gestational age, being small for dates, neonatal convulsions and the need for cardiopulmonary resuscitation were associated with partial epilepsy, cerebral palsy and mental retardation. A family history of epilepsy in first-degree relatives was surprisingly frequent in both groups, suggesting that genetic factors play an important role for children with and without cerebral malformations.

Use and misuse of antidepressant drugs in a random sample of the population of Rome, Italy.

Prescribing patterns of antidepressant drugs were studied, over a period of 30 months, in a random sample of 8743 residents of the area of Rome, Italy. Data from the regional outpatient drug monitoring system were used. The proportion of subjects receiving, during the study period, at least one prescription of antidepressant drugs, was 5.4%; the female-to-male ratio was 2.1. Consumption prevalence increased with age. The single most prescribed drug was fluoxetine followed by amitriptyline and ademetionine. For a surprisingly high proportion of subjects, the observed length of treatment was shorter than expected on the basis of current knowledge in clinical pharmacology. Inappropriate diagnostic and therapeutic procedures are likely explanations.

Prevalence of chronic fatigue syndrome in Italian patients with persistent fatigue.

Our study was carried out to determine the prevalence of chronic fatigue syndrome (CFS) within a selected population of patients suffering from persistent fatigue. We studied subjects with recurrent or persistent fatigue lasting 6 months and fulfilling at least four minor Center for Disease Control (CDC) criteria for the diagnosis of CFS. Evaluation included both clinical examination and laboratory testing. All subjects filled out a questionnaire specifically designed to gain information about the length and severity of symptoms, and patients with a previously diagnosed illness associated with fatigue were excluded. The study was carried out at the Fatigue Clinic of an internal medicine unit (Clinica Medica I) of the University of Rome "La Sapienza". Sixty-three subjects, residents of the Lazio region (central Italy), completed the diagnostic assessment. Alternative diagnoses were established in 37 (59%) of the 63 patients. A diagnosis of CFS based on the CDC criteria was established in only 6 cases. In 2 subjects, CFS had appeared following infectious mononucleosis, and no definitive diagnosis could be formulated for 18 patients. In Italy, CFS seems to be an infrequent cause of severe and persistent fatigue in a selected population. Numerous morbid conditions may be responsible for a clinical picture closely resembling CFS. We recommend that patients suffering from fatigue be thoroughly evaluated.

Chronic fatigue: a peculiar evolution of eosinophilia myalgia syndrome following treatment with L-tryptophan in four Italian adolescents.

We describe four Italian adolescents in whom a persistent, debilitating fatigue appeared after therapeutic ingestion of products containing L-tryptophan and subsequent to the development of a transient rise in eosinophil count and severe myalgia (Eosinophilia Myalgia Syndrome-EMS). Their clinical picture was indistinguishable from that of the so-called Chronic Fatigue Syndrome. A chronic fatigue may occur after diverse triggering agents and its represents the peculiar clinical evolution of these four paediatric cases of EMS.

Declining prevalence of HIV infection among injecting drug users entering drug treatment in Italy: 1990-1991.

Two surveys were conducted in 1990 and 1991 in order to estimate the prevalence of HIV infection among injecting drug users attending drug treatment centers throughout Italy. Among the 35,073 IDUs attending these facilities in 1990, 32.1% were HIV-positive. In 1991, 29.7% of 41,794 IDUs were HIV-positive. HIV prevalence was higher among prior attendees compared to new entrants (38.0% vs. 20.5% in 1990, and 35.8% vs. 16.6% in 1991); prevalence was also higher among females. These findings suggest that HIV prevalence among Italian drug users is slowly declining.

Toxocara infection and epilepsy in children: a case-control study.

A case-control study of 305 children was done to evaluate the relationship between toxocariasis and seizures and risk factors associated with toxocariasis transmission and seizure onset. A significant association existed between seropositivity for anti-Toxocara canis and seizures (p less than 0.05); the correlation was closest in children aged less than 5 years of age. Among risk factors, pica was more common in children with seizures than in controls but was not associated with toxocariasis. The association between dog ownership and toxocariasis was highly significant (p less than .000001). Our findings suggest that toxocariasis may be involved as a cofactor in the pathogenesis of seizures.