Neurocognitive development of children with congenital unilateral brain lesion and epilepsy.

The aim of this study was to specify the neuropsychological deficits characteristic of children with unilateral non-progressive brain lesion. In order to assess these specific functions, we used a comprehensive model of congenital hemiparesis with partial epilepsy and newly diagnosed partial epilepsy without hemiparesis. The neuropsychological examination was performed using the NEPSY test battery on 44 children aged from 4 to 9 years. The children were divided into three groups: 18 children suffering from congenital hemiparesis with chronic partial epilepsy, 12 children with newly diagnosed partial epilepsy prior to anti-epileptic treatment, and 14 healthy controls matched by sex, age, and socioeconomic status. Children with congenital hemiparesis and epilepsy had a more clearly expressed cognitive dysfunction, especially in language, visuo-perceptual and memory tasks, than children with newly diagnosed partial epilepsy. The profile of cognitive weakness appears to be diffuse and quite similar in both groups, and it did not demonstrate a clear effect of lateralization, according to the side of epileptic electroencephalogram discharges. Children within both groups are likely to have a high risk of developing attention, phonological, visuo-perceptual, and memory deficits in their life. Especially interesting and surprising was the fact that the newly diagnosed epilepsy group demonstrated impairment not only in attention, visuo-perceptual and short-term memory skills, but also in auditory perception, lexical function, and the comprehension of speech. Therefore, it is recommended that children with epilepsy would undergo neuropsychological examination in order to assess their cognitive abilities.

Is the International League against Epilepsy classification of epileptic syndromes applicable to children in Estonia?

The concept of the epileptic syndrome has had a practical and research impact on the management of patients with epilepsy. The aim of the present study was to verify the applicability of the International Classification of Epilepsies and Epileptic Syndromes in children and adolescents in Estonia. A population-based study was performed between January 1995 and December 1997 in seven counties. Only cases involving children between the ages of 1 month and 19 years with at least two unprovoked seizures were included. In all, 560 children and adolescents were referred to the Children's Hospital of the University of Tartu. A syndrome diagnosis was made in 550 (98.2%) cases: (49.4%) were localization-related (6.4% idiopathic, 18.9% symptomatic, 24.1% cryptogenic). Benign childhood epilepsy with centrotemporal spikes was present in 33 (5.9%) and childhood epilepsy with occipital paroxysms in three (0.5%); 48.4% were generalized (28.8% idiopathic, 5.7% cryptogenic or symptomatic, 14% symptomatic). Childhood absence epilepsy was present in 6.4%, juvenile absence in 2.0%, juvenile myoclonic in 0.7% and epilepsy with generalized tonic-clonic seizures on awakening in 17.7%. West syndrome was diagnosed in 1.4%, Lennox-Gastaut syndrome in 2.9% of the cases. In 0.4% of the cases it was undetermined whether seizures were focal or generalized. In 8.8% of the cases there were atypical features so they were classified as 'other symptomatic generalized epileptic syndromes not defined above' and 1.8% of the cases were unclassified. Specific neurological diseases were diagnosed in 5.0% of cases. Thus, the International Classification of Epilepsies and Epileptic Syndromes was very applicable to children and adolescents in Estonia.

Prevalence of childhood epilepsy in Estonia.

PURPOSE: To establish the prevalence rate (PR) and main characteristics of childhood epilepsy in Estonia. METHODS: We performed a population-based case ascertainment of all the possible sources of medical care in seven counties of Estonia from January 1995 to December 1997. Only cases of patients from 1 month to 19 years of age with active epilepsy (i.e., at least one seizure during the last 5 years, regardless of treatment) were included. All patients were examined by a pediatric neurologist. RESULTS: Five hundred sixty cases met the study criteria on the prevalence day, December 31, 1997. The total PR was 3.6 per 1,000 population (boy/girl ratio, 1.2:1.0). The PR was the highest-4.3 per 1,000-in the 5-to-9-year-old age group. The prevalence declined markedly in children age 14 years and on. The correlation between age and PR was negative (-0.542, p < 0.0001) by regression analyses. The most frequent seizure types in the total group were primarily generalized seizures-PR 2. 1/1,000 [rate ratio (RR) 1.4, 95% confidence interval (CI) 1.2, 1.6]. The predominance of generalized seizures was significant in those younger than 10 years. In 14.8% of cases, there was a history of epilepsy among first- and second-degree relatives. Benign rolandic epilepsy-PR 0.2/1,000-was the most frequent among idiopathic syndromes, and Lennox-Gastaut syndrome-PR 0.08/1,000-was the most frequent among cryptogenic ones. Perinatal factors-PR 0.8/1,000 were the most frequently found cause of epilepsy. In 304 cases (54.2%), additional medical problems existed. CONCLUSIONS: The prevalence of childhood epilepsy was comparable with that found in developed countries. Generalized seizures predominated, and the main cause was perinatal factors.

Incidence of childhood epilepsy in Estonia.

The aim of this study has been to establish the incidence rate (IR) and main characteristics of childhood epilepsy in Estonia. A population-based prospective study was performed from January 1st 1995 to December 31st 1997 in seven counties (population of children 161202). Only cases occurring in the age range of 1 month to 19 years with active epilepsy were included. Two hundred and sixteen cases met the study criteria. The total age-adjusted IR was 45/100000. The IR was the highest, 73/100000, in the age group from 1 month to 4 years. The IR declined markedly after the age of 15 years. Primarily generalized seizures demonstrated a higher IR, 25/100000, than partial seizures, the IR of which was 20/100000. The IR of symptomatic epileptic syndromes was 16/100000, that of cryptogenic, 15.5/100000 and that of idiopathic, 13/100000. The cumulative incidence of epilepsy through age 19 was 0.13%. A family history of epilepsy was present in 13.9% of cases. In 40.7% of cases the cause of epilepsy was identified. Adverse perinatal events were the most frequent etiological factors: in 25%, IR 11/100000. In 103 cases (47.6%) additional medical problems were disclosed. Strong negative univariate association was noted between partial seizures and idiopathic etiology (OR 0.37, 95%CI 0.18, 0.72; P = 0.002) and between partial seizures and motor disability (OR 0.43, 95%CI 0.24, 0.78; P = 0.003). The incidence of childhood epilepsy in Estonia was comparable with developed countries. Generalized seizures predominated. Perinatal factors were the main causes. The idiopathic etiology and motor disability of cryptogenic and symptomatic cases were associated with generalized seizures.

Five days of antibacterial therapy for bacterial meningitis in children?

We evaluated the effectiveness of 5-day antibacterial therapy for bacterial meningitis in children. The study group included 26 children from 2 months to 15 years of age, admitted with microbiologically confirmed bacterial meningitis in 1990-1993 and treated for 5 days. A historical comparison group of 49 patients treated for 8 to 15 days was used. Penicillin monotherapy (300 mg/kg body weight) was used for meningococcal and pneumococcal meningitis and ampicillin (300 mg/kg body weight) for Haemophilus influenzae b meningitis. On day 5 of therapy the activity of aspartate aminotransferase (AST), lactic dehydrogenase (LDH), creatine phosphokinase (CPK) and gamma-glutamyl-transpeptidase (gamma GT) in the CSF was determined by photocolorimetric assay and the concentration of creatine kinase BB (CK-BB) by ELISA. IL-6 was analysed using EIA technique and a cerebral ultrasound was performed at the time of the termination of the antibacterial therapy. The mean follow-up time was 1.3 years for children in the study group and 3.2 in the control group. The time of hospitalisation was shorter in children treated for 5 days (p < 0.005). Complete clinical recovery was 81% in the study group and 66% in the comparison group at the time of the termination of antibacterial therapy. No relapses occurred. The activity of AST, CPK, LDH, and gamma GT in the CSF had returned to normal by the 5th day of therapy, but almost a 7-fold higher concentration of CK-BB was registered. The concentration of IL-6 in the CSF decreased with the therapy from 1,800 pg/ml to 685 pg/ml but still remained high.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of a truncated PR-1 promoter by endogenous enhancers in transgenic plants.

PR-1 genes are induced by various environmental stimuli such as pathogen attack or exposure of the plants to certain chemicals. To examine the regulation of these genes, the 5' flanking regions of the PR-la gene and of two PR-1 pseudogenes were joined by a transcriptional fusion to the Escherichia coli beta-glucuronidase (GUS) gene. These constructs were stably integrated into the tobacco genome and independent primary transformants were monitored for the expression of the reporter gene. Unexpectedly, out of 55 transformants analysed, four plants exhibited considerable GUS activities without any inductive treatment of the plants. Expression of the endogenous PR-1 genes, however, could not be detected in these plants. Primer extension analyses revealed correct initiation of the PR1/GUS hybrid transcripts from the PR-1a TATA box. When the plants were analysed at the cellular level, clear differences regarding the tissue specificity of expression of the reporter gene were observed. These results strongly suggest that the PR1/GUS hybrid promoter expression cassettes may be activated when integrated in the vicinity of heterologous enhancer elements dispersed in the tobacco genome. In order to support this hypothesis, domain B of the enhancer of the 35S RNA promoter from cauliflower mosaic virus (CaMV) was fused to various PR1/GUS hybrid genes upstream as well as downstream from the RNA start site. These constructs were stably introduced into the tobacco genome. In any primary transformant analysed, strong GUS activities were observed with the PR1/GUS hybrid RNAs originating from the normal transcription start site of the PR-1a gene. The tissue specificity of gene expression was identical to that described previously for the CaMV 35S domain B enhancer element. Thus, modulations of the transcriptional activity of the PR-1 promoter can be achieved by heterologous enhancers in transgenic plants and may be encountered upon random integration of PR-1 promoter constructs into the tobacco genome.

Functional analysis of the pathogenesis-related 1a protein gene minimal promoter region. Comparison of reporter gene expression in transient and in stable transfections.

Pathogenesis-related (PR) proteins are a heterogeneous group of host encoded, low-molecular-mass proteins that are induced in plants by various external stimuli, such as pathogen attack or exposure of the plants to certain chemicals. To examine the regulation of these genes, the 5'-flanking region of the tobacco PR-1a gene [Pfitzner U.M., Pfitzner, A.J.P. & Goodman, H.M. (1988) Mol. Gen. Genet. 211, 290-295] was joined by a transcriptional fusion to the Escherichia coli beta-glucuronidase (GUS) gene. Expression of the reporter gene was monitored in transient expression assays as well as in stable transformants. The PR-1a 5'-flanking sequences from -335, -149 or -71 to +28 are functional promoter elements in tobacco and carrot protoplasts, as determined by transient expression. These constructs direct correct initiation at the normal transcription-start site of the PR-1a gene. The level of gene expression was about twofold less than that obtained with the cauliflower mosaic virus 35S RNA promoter. Regulation of gene expression by acetylsalicylic acid, however, could not be detected in the transient assays. When the same constructs were stably integrated into the tobacco genome, neither constitutive nor induced beta-glucuronidase activity was observed. A comparison of the results from the transient and the stable transfection experiments suggests that expression of the reporter gene may be due to a constitutive transcriptional activity of the PR-1a 5'-flanking regions under the conditions of the transient assays and that the PR-1a promoter may contain at least two functional domains.

Molecular analysis of two PR-1 pseudogenes from tobacco.

Two independent PR-1 lambda genomic clones (W38/1 and W38/3) were isolated and characterized from a tobacco (Nicotiana tabacum cv. Wisconsin 38) library. Neither clone is identical to the previously described PR-1 cDNA clones, and both clones carry mutations within the highly conserved PR-1 protein coding region. For example, clone W38/1 has a GAA Glu codon instead of the translation stop codon thus harbouring an open reading frame extended by 16 additional amino acids. Furthermore, both clones display considerable variations in the genomic flanking sequences when compared to the PR-1a gene. In order to test whether the encoded genes are active, their upstream sequences were fused to the E. coli beta-glucuronidase (GUS) reporter gene. While significant GUS activities as compared to the 35S RNA promoter from cauliflower mosaic virus (CaMV) were obtained with the W38/1 and W38/3 sequences in transient gene expression assays, no transcriptional activities could be observed upon stable transformation of the same constructs. In addition, the protein coding region of W38/1 was joined to the CaMV 35S RNA promoter and transgenic tobacco plants were generated. However, neither transcripts nor a protein could be detected deriving from the W38/1 structural gene with this chimaeric construct in the transformants. Taken together, these data indicate that the genes contained in lambda clones W38/1 and W38/3 are not active in planta.