Benign epilepsy with centro-temporal spikes (BECTS): relationship between unilateral or bilateral localization of interictal stereotyped focal spikes on EEG and the effectiveness of anti-epileptic medication.

BACKGROUND AND AIM: Benign epilepsy with centro-temporal spikes (BECTS) is one of the most frequent epileptic syndromes in children. It is placed among the idiopathic localization-related epilepsies. However, the relationship between unilateral or bilateral localization of interictal stereotyped focal spikes on electroencephalogram (EEG) and the effectiveness of anti-epileptic drugs has not been studied yet. PATIENTS AND METHODS: We studied 55 neurodevelopmentally normal children who had been diagnosed with BECTS. Children were subdivided into two groups, based on EEG findings: Group A comprised 30 children with unilateral findings on EEG and Group B 25 children with bilateral findings on EEG. All patients in the present study were started on an anti-epileptic medication after the third seizure (Sodium Valproate, Carbamazepine, Oxcarbazepine) and we studied the response to medications. RESULTS: Children with bilateral findings on EEG had the same response to treatment with either Sodium Valproate or Carbamazepine or Oxcarbazepine. Other side, children with unilateral findings on EEG corresponded best to Carbamazepine or Oxcarbazepine. CONCLUSIONS: Children diagnosed with BECTS and bilateral discharges on EEG have good response to treatment with either Sodium Valproate or Carbamazepine or Oxcarbazepine.

Idiopathic acute transverse myelitis: Complete recovery after intravenous immunoglobulin.

Idiopathic acute transverse myelitis is a focal inflammatory disorder of the spinal cord of unknown etiology diagnosed according to established criteria. As it occurs rarely in children herein we report a case of a 4 year old boy who developed clinical and radiological manifestations of myelitis, 10 days after a recent respiratory tract infection. Diagnostic workup failed to reveal a causative factor. After the administration of corticosteroids a clinical deterioration was observed and intravenous immunoglobulin was administered. Symptoms resolved within a 48-hour period, suggesting an immune-mediated pathogenetic mechanism.

Evaluation of thyroid gland function in children with obstructive apnea hypopnea syndrome.

Patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and thyroid function abnormalities, such as hypothyroidism and Hashimoto's thyroiditis, usually have closely resembling clinical features. Differentiation between these disorders is made more difficult because hypothyroid patients are also at risk for secondary sleep-disordered breathing. The aim of our study is to evaluate the prevalence of thyroid function abnormalities in children with OSAHS. Forty-four children (15 females: 29 males), 2.5-14.5 (7.43±2.98) years old were studied with overnight polysomnography. Biochemical screening of thyroid gland function was also carried out. Patients were judged to have OSAHS based mainly on the evaluation of Apnea Hypopnea index per hour of sleep (AHI). 15/44 (34.1%) children had mild OSAHS, 17/44 (38.6%) moderate and 12/44 (27.3%) severe OSAHS. Hypothyroidism was recorded only in 5/44 (11.4%) and Hashimoto's thyroiditis in 3/44 (6.8%) of OSAHS patients. Two patients with hypothyroidism showed mild and three severe OSAHS, while from the 3 children with Hashimoto's thyroiditis one presented mild, one moderate and one severe degree of OSAHS. Although the majority of studies in bibliography worldwide do not consider necessary the systemic evaluation of thyroid gland function in patients with breathing disorders during sleep, it seems that in children this type of screening is required for the differential diagnosis between primary sleep apnea and hypothyroid sleep-disordered breathing in order to differentiate these two conditions. Therefore, the laboratory investigation of thyroid gland function could be considered necessary.

Alterations of bone mineral metabolism of children with different cell lineage types of acute lymphoblastic leukaemia under chemotherapy.

BACKGROUND: Children with haematological malignancies such as acute lymphoblastic leukaemia (ALL) may have alteration of bone mineral metabolism therefore increased risk for osteopenia and osteoporosis. PATIENTS AND METHODS: The purpose of this study was to examine the alterations of bone mineral metabolism in two groups of children (n=42) according to immunophenotyping (B-cell type, T-cell type) both quantitative (bone mineral density z-scores) and qualitative (serum osteocalcin - OC and carboxyl-terminal telopeptide of human type I collagen - ICTP) during diagnosis (T=0), after the intensified chemotherapy period (T=0.5) and the consolidation period (T=1). RESULTS: According to our results 15 patients had osteopenia and 1 child developed osteoporosis at T=0.5 and 13 patients had osteopenia at T=1. Mean BMD z-score was significantly decreased in both groups during chemotherapy and especially statistically significant decline of T-cell type ALL group compared with B-cell type ALL patients. OC mean level remains in low levels for both groups reaching in plateau during chemotherapy and ICTP level was increased in T-cell type ALL group of patients compared with B-cell type in both periods of chemotherapy. CONCLUSIONS: It seems that not only the combination of chemotherapeutic agents but also the cell lineage of ALL are important parameters of altering bone mineral metabolism.

Maternal smoking during pregnancy and childhood lymphoma: a meta-analysis.

Results from epidemiological studies exploring the association between childhood lymphoma and maternal smoking during pregnancy have been contradictory. This meta-analysis included all published cohort (n = 2) and case-control (n = 10) articles; among the latter, the data of the Greek Nationwide Registry for Childhood Hematological Malignancies study were updated to include all recently available cases (-2008). Odds ratios (ORs), relative risks and hazard ratios were appropriately pooled in three separate analyses concerning non-Hodgkin lymphoma (NHL, n = 1,072 cases), Hodgkin lymphoma (HL, n = 538 cases) and any lymphoma (n = 1,591 cases), according to data availability in the included studies. An additional metaregression analysis was conducted to explore dose-response relationships. A statistically significant association between maternal smoking (any vs. no) during pregnancy and risk for childhood NHL was observed (OR = 1.22, 95% confidence interval, CI: 1.03-1.45, fixed effects model), whereas the risk for childhood HL was not statistically significant (OR = 0.90, 95% CI: 0.66-1.21, fixed effects model). The analysis on any lymphoma did not reach statistical significance (OR = 1.10, 95% CI = 0.96-1.27, fixed effects model), possibly because of the case-mix of NHL to HL. No dose-response association was revealed in the metaregression analysis. In conclusion, this meta-analysis points to a modest increase in the risk for childhood NHL, but not HL, among children born by mothers smoking during pregnancy. Further investigation of dose-response phenomena in the NHL association, however, warrants accumulation of additional data.

Delayed exposure to infections and childhood lymphomas: a case-control study.

OBJECTIVES: Delayed exposure to common infections during childhood, have been implied to cause strong immunological response to a single infectious agent that eventually triggers leukemogenesis. The aim of the present study was to investigate whether decreased exposure to infections, as reflected in a more seronegative spectrum to several common infectious agents, is associated with increased risk for the development of childhood lymphomas. METHODS: All 125 children (up to 14 years old), with Hodgkin (HL, n = 52) and non-Hodgkin lymphomas (NHL, n = 73) diagnosed through the national network of childhood Hematology-Oncology units during an 8-year period were enrolled in the study along with 125 age- and gender-matched controls. Past exposure to nine common infections [respiratory syncytial virus (RSV), influenza A and B, parainfluenza type 1, adenovirus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV6), Bartonella henselae] was assessed using serological markers. RESULTS: After controlling for possible confounding factors, the overall seronegativity status upon diagnosis was statistically significantly associated with NHL [odds ratio; 95% CI: 1.45 (1.10-1.93), p = 0.01] and less so with HL risk [odds ratio; 95% CI: 1.30 (0.83-2.05), p = 0.25]. A statistically significant association of seronegativity with the development of NHL was evident for RSV [odds ratio; 95% CI: 7.27 (1.59-33.28), p = 0.01], EBV [odds ratio; 95% CI: 6.73 (1.45-31.20), p = 0.01] and suggestive association for influenza B [odds ratio; 95% CI: 2.60 (0.90-7.55), p = 0.08] and influenza A [odds ratio; 95% CI: 2.35 (0.81-6.80), p = 0.11]. In contrast, there was no evidence for association of HL with negative serology for any of the infectious agents tested. CONCLUSIONS: The risk of lymphomas, especially NHL, might be higher when, due to lower exposure to several infectious agents, the relatively unmodulated immune system of a child is challenged by environmental stimuli that can trigger development of lymphomas. The results, however, need further confirmation, through more pertinent methodological designs.

MR spectroscopy and serial magnetic resonance imaging in a patient with mitochondrial cystic leukoencephalopathy due to complex I deficiency and NDUFV1 mutations and mild clinical course.

We present clinical, magnetic resonance imaging and MR spectroscopic findings of a female patient, first admitted at the age of 9 months for regression of motor milestones and signs of mild spastic diplegia. Magnetic resonance imaging (MRI) demonstrated periventricular white matter abnormalities with sparing of the subcortical white matter. Subsequent MRIs, performed at the ages of 13 and 16 months, demonstrated progression of the white matter changes, progressive white matter rarefaction and cystic degeneration, and additional involvement of the corpus callosum; only the subcortical white matter remained spared. Proton MR spectroscopy revealed lactate elevation in the white matter. Blood lactate and lactate/pyruvate ratio were mildly elevated. Subsequent analysis of mitochondrial function in muscle tissue showed decreases in substrate oxidation and in ATP and CrP production rates. Complex I activity was seriously decreased, whereas mild decreases of complex II and IV activities were also noted. Analysis of the NDUFV1 gene revealed compound heterozygosity for two point mutations, each of them carried by one parent. The further clinical course of the patient was uphill; she slowly regained all previously lost motor milestones. In conclusion, diffuse white matter changes on MRI are compatible with mitochondrial encephalopathy and not necessarily associated with a severe clinical course.

Childhood leukaemias and lymphomas in Greece (1996-2006): a nationwide registration study.

BACKGROUND: Monitoring time trends in the incidence of childhood leukaemias and lymphomas requires efficient and continuous data collecting systems. In countries without official cancer registries, such as Greece, ad hoc nationwide registration of incident childhood leukaemias and lymphomas could help elucidate the underlying aetiology and monitor socioeconomic differentials in health care delivery. METHODS: We registered all cases and produced age, gender, type and immunophenotype specific figures and overall crude and age adjusted annual incidence rates and secular trends for 863 leukaemia and 311 lymphoma incident cases diagnosed in children <15 years of age across Greece during 1996-2006, namely the first 11 years of the Nationwide Registry for Childhood Hematological Malignancies. RESULTS: The epidemiological profiles of leukaemias/lymphomas in Greece are similar to those in industrialised countries. No secular trends are observed for either malignancy during the studied period. However, the calculated incidence for leukaemia (46.60 cases per 1 million children annually) is among the highest in the EU-27 (19% higher than average; p<0.001), whereas that for lymphoma (16.8 cases per 1 million children annually) is around the EU-27 average. CONCLUSIONS: Minimal secular changes in childhood leukaemias/lymphomas have been noted recently in the EU-27, which cannot be easily explained in countries with small populations. Therefore, centralised EU databases such as the Automated Childhood Cancer Information System (ACCIS) should be enlarged to generate sufficient statistical power for monitoring time trends. It would be interesting to explore whether different lifestyle patterns across the EU might be responsible for the observed excess leukaemia incidence in countries such as Greece.

An integrated evaluation of socioeconomic and clinical factors in the survival from childhood acute lymphoblastic leukaemia: a study in Greece.

An evaluation of the role of socioeconomic factors in the survival of children with leukaemia, controlling for major clinical prognostic indicators, has been attempted in very few studies and the role of these factors may be different in various cultural settings. Our investigation aims to study the independent role of socioeconomic factors on the prognosis of childhood acute lymphoblastic leukaemia (ALL) in Greece. During a 7-year period (1996-2002) 293 cases of incident ALL were diagnosed and followed up in four Childhood Haematology-Oncology Units, which covered over half of all childhood ALL cases nationwide. At the time of diagnosis, information concerning age, gender, maternal schooling, maternal marital status, sibship size, distance of residence from the treating centre, attendance of day care centre and clinical information was recorded. The influence of these factors on survival was studied by modelling the data through Cox's proportional-hazards regression. After adjustment for clinical prognostic factors, children of mothers who were not currently married, were of low educational level or were living far from the treating centre tended to have lower survival (P-values 0.02, 0.14 and 0.08, respectively). There was also evidence that two factors that are predictive of disease occurrence, that is sibship size and attendance of day care centre, may also predict survival (P-values 0.04 and 0.26, respectively). In conclusion, socioeconomic factors are likely to influence survival from ALL at least in some sociocultural contexts. Moreover, there is evidence that factors that could affect incidence of ALL through modulation of herd immunity may also have prognostic implications for this disease.

Insulin-like growth factor-I and binding protein-3 in relation to childhood leukaemia.

The aetiology of most cases of childhood leukaemia remains unknown, but several studies have indicated that increased birthweight and height are risk factors for the disease. Since insulin-like growth factor-I (IGF-I) mediates the effect of growth hormone and has been positively associated with prostate cancer, we have evaluated the role of this hormone and its principal binding protein, IGFBP-3, in the aetiology of childhood leukaemia. Incident cases of childhood leukaemia from those recorded by a national network of childhood oncologists were enrolled in our study. Controls were children hospitalised for acute conditions of no more than moderate severity with matching for gender, age and maternal place of residence. Blood measurements of IGF-I and IGFBP-3 were undertaken using commercially available radioimmunoassays. Serum IGF-I values decreased by about 1.7% per month, and the rate of decline was higher, though not significantly so, among cases (2.1% per month) than among controls (1.4%). There was no significant association between IGF-I and the likelihood of childhood leukaemia, but an increment of 1 microg/ml of IGFBP-3 was associated with a substantial and statistically significant reduction of childhood leukaemia by 28% (95% confidence interval 7% to 45%). Because IGFBP-3 is essentially a binding protein, we interpret our findings as indicating that bioavailable IGF-I may play an important role in the aetiology of childhood leukaemia. The much smaller quantities and the inherent instability of IGF-I in the blood in comparison to those of IGFBP-3 are likely to hinder documentation of an underlying positive association of IGF-I with the disease.

Electrical power lines and childhood leukemia: a study from Greece.

Residential proximity to electrical power lines of different voltage in relation to childhood leukemia was investigated through a case-control study undertaken in Greece during 1993-1994. The study comprised 117 incident cases of childhood leukemia and 202 age-, gender- and place-of-residence-matched controls. Four measures of exposure to magnetic fields were developed, using data provided by the Public Power Corporation of Greece: Voltage (V) divided by the distance (d), V/d2, V/d3 and an adaptation of the Wertheimer-Leeper code. Conditional-logistic-regression modeling was used to adjust for potential confounding influences of 18 variables. No significant trends of childhood leukemia risk with increasing exposure levels were noted, nor were there statistically significant elevations of disease risk at the higher exposure levels in each measure of exposure. These results do not support a causal link between residential proximity to electrical high-voltage wires and childhood leukemia risk, but in themselves do not refute a weak empirical association.

Aggregation of childhood leukemia in geographic areas of Greece.

A total of 872 children aged up to 14 years, who were diagnosed with leukemia in Greece during the decade 1980-89, were allocated by place of residence to the 601 administrative districts of the country. Evaluation of spatial clustering was done using the Potthoff-Whittinghill method, which validly assesses heterogeneity of leukemia risk among districts with variable expected numbers of cases. There was highly significant evidence for spatial clustering occurring particularly among children living in urban and, to a lesser extent, semi-urban areas. The evidence was stronger for children younger than 10 years old, applied also to children in different five-year age groups, and persisted when cases of acute lymphoblastic leukemia were analyzed separately. These findings provide support to the hypothesis that localized environmental exposures could contribute to the etiology of childhood leukemia, but they cannot distinguish between exposures of physical or chemical nature, nor can they exclude socially conditioned patterns of exposure to infectious agents.

The risk profile of childhood leukaemia in Greece: a nationwide case-control study.

The risk profile of childhood leukaemia in Greece was studied through a case-control investigation that included all 153 incident cases of the disease, ascertained throughout the country during 1993 and 1994, and two hospital controls for every case matched for gender, age and place of residence. The data were analysed using conditional logistic regression and the associations are expressed in terms of adjusted odds ratios (OR) and their 95% confidence intervals. Cases were born to mothers of a higher standard education, the OR for an increment of four schooling years being 1.48 (1.17-1.87) and had higher birth weight, the OR for an increment of 500g being 1.36 (1.04-1.77). Pet ownership and birth after a pregnancy with anaemia were associated with increased risk, the ORs being 2.18 (1.14-4.16) and 2.60 (1.39-4.86) respectively. From the frequency analyses, indicative inverse associations were found with birth order, household crowding and previous hospitalization with allergic diseases, whereas indicative positive associations were found with diabetes mellitus during pregnancy and with neonatal jaundice. Substantial or significant elevations were not found with respect to maternal smoking and coffee drinking during pregnancy, diagnostic radiography and ultrasonographic examinations or blood transfusions. A significant inverse association with maternal consumption of alcohol could be due to multiple comparisons, but a detrimental effect can probably be excluded. A non-significant positive association with total shots of viral vaccinations and a weak non-significant inverse association with breast feeding were also found. We interpret the findings of this study as being compatible with acute childhood leukaemia being linked with delayed development of herd immunity to fairly common infectious agents, in conjunction with accelerated perinatal and early post-natal growth.

Infant leukaemia after in utero exposure to radiation from Chernobyl.

There has been no documented increase in childhood leukaemia following the Chernobyl accident. However, different forms of childhood leukaemia may not be equally susceptible to radiation carcinogenesis. Infant leukaemia is a distinct form associated with a specific genetic abnormality. Outside the former Soviet Union, contamination resulting from the Chernobyl accident has been highest in Greece and Austria and high also in the Scandinavian countries. All childhood leukaemia cases diagnosed throughout Greece since 1 January 1980 have been recorded. Here we report that infants exposed in utero to ionizing radiation from the Chernobyl accident had 2.6 times the incidence of leukaemia compared to unexposed children (95% confidence interval, 1.4 to 5.1; P approximately 0.003), and those born to mothers residing in regions with high radioactive fallout were at higher risk of developing infant leukaemia. No significant difference in leukaemia incidence was found among children aged 12 to 47 months. Preconceptional irradiation had no demonstrable effect on leukaemia risk at any of the studied age groups.

Space-time clustering of childhood leukaemia in Greece: evidence supporting a viral aetiology.

The method introduced by Knox for evaluation of space-time clustering has been applied to 872 cases of childhood (0-14 year old) leukaemia diagnosed in Greece over the 10 year period 1980-89. Greek towns are characterised by substantial population mixing due to internal migration, whereas there is relative isolation in mountainous rural areas. Predetermined space (5 km) and time (1 year) limits were used on the basis of previous reports in order to define the clustering cell. There is highly significant evidence for clustering of childhood leukaemia in Greece as a whole, the observed number of pairs that are close in both spaces and time exceeding the expected number by 5.2% (P = 0.004). The excess is particularly evident for leukaemia cases in 0 to 4-year-old children, among whom the observed number of pairs that are close in both space and time exceeded the expected number by 9.4% (P = 0.004). There is no evidence of space-time clustering for leukaemia cases older than 5 years. The overall pattern is descriptively similar in urban and semiurban areas and is especially marked for acute lymphoblastic leukaemia at the childhood peak ages (2-4 years) with an excess of 19% (P = 0.0006). In the rural population there is evidence for clustering of cases belonging to older and broader age groups, a phenomenon compatible with a delay in the development of herd immunity against putative infectious aetiological agents. The findings of the present study provide support for the hypothesis that a substantial proportion of cases of childhood leukaemia may arise as a rare sequel to exposure to an agent or agents, most probably viral in nature.

Trends and geographical distribution of childhood leukemia in Greece in relation to the Chernobyl accident.

Parts of Greece have been exposed to fallout radiation from the Chernobyl accident as much as any of the countries boardering with the former Soviet Union, because of the direction of the prevailing winds after the accident. Although fallout radiation did not reach levels expected to be associated with measurable effects, there is widespread concern in Greece that the incidence of childhood leukemia may be rising in the more heavily affected parts of Greece. Patient discharge data from all Greek hospitals treating childhood leukemia were used to calculate the annual incidence of the disease from January 1980 to June 1986 (preaccident period), from July 1986 to June 1988 (immediate postaccident period) and from July 1988 to June 1991 ("relevant" post-accident period, that accommodates the presumed latent period of the disease). Fallout radiation measurements (in Bq/kg Cs-137) were used to create 17 regions of similar (within regions) but highly variable (between regions) levels of fallout deposition. Background radiation (in Bq/kg Ra-226) and annual incidence of childhood leukemia by region were also estimated. There was no evidence of increased incidence of childhood leukemia during the immediate or the "relevant" post-Chernobyl period in any part of the country. Furthermore, regression analyses did not show any significant or suggestive association of childhood leukemia by region with either background or fallout radiation. These results indicate that the Chernobyl accident did not affect noticeably the incidence of childhood leukemia in Greece during the five-year post accident period.

Hepatitis B vaccination in children with thalassemia in northern Greece.

Sera from 101 children with thalassemia, aged between 6 months to 15 years, were examined for detection of HBV infection. Of these 101 children, 18 negative for all HBV markers were vaccinated against HB with "Hevac B" vaccine from the Pasteur Institute. Our results show that 3 inocculations at one-month intervals have induced an excellent antibody (anti-HBs) response in all vaccinated children, affording full protection against HBV infection. There were no noticeable local or general reactions to "Hevac B" vaccine. Our results, in accordance with other reports, have revealed that hepatitis B vaccine is highly immunogenic for children with thalassemia and is particularly well tolerated.