Influence of the physical pressure of an ultrasound probe on shear-wave elastography measurements of the gastrocnemius muscle in a paediatric population: a non-interventional cohort study.

Purpose: The aim of our study is to evaluate the impact of ultrasound probe mechanical pressure on the stiffness of the gastrocnemius muscle in a healthy paediatric population. As far as we know, there has been no previous qualitative in vivo study on the impact of probe pressure on muscle shear-wave elastography results with objective evaluation of compression in the paediatric population. Material and methods: In this cohort study, a group of 22 children (mean age 8.99 years, SD 2.74, 11 males) underwent elastography of the gastrocnemius muscle of the dominant leg. A custom-made, 3-dimensional printed probe cover was used to measure the mechanical pressure of the probe on tissues. Results: The obtained results were related to the age, sex, BMI, and calf circumference of the subjects. We observed a significant difference in the stiffness parameter at a pressure of 1 N, with a further increase if force was increased (p < 0.001). A significant, very weak positive correlation of age and stiffness was observed (p < 0.001, r2 = 0.022). There was no significant correlation of stiffness, BMI, and calf circumference. Conclusions: The use of compression during muscle elastography in children causes a significant bias in results, regardless of age, sex, BMI, or calf size.

Study of 52 Pediatric Patients Who Required 78 Hospital Admissions for Cerebral Venous Sinus Thrombosis from 2013 to 2020 Using Data from the Polish National Health Fund Registry.

BACKGROUND Cerebral venous sinus thrombosis (CVST) in children is a rare disease with a complex, multifactorial etiopathogenesis. The Polish National Health Fund (NHF) Registry [Narodowy Fundusz Zdrowia (NFZ)], contains health insurance data from all 16 national provinces, or voivodeships. This study used data from the Polish NHF Registry to evaluate 52 pediatric patients who required 78 hospital admissions for CVST from 2013 to 2020. MATERIAL AND METHODS The data in the Polish NHF Registry were acquired based on the disease code I67.6 from the International Classification of Diseases, Tenth Revision (ICD-10), and the patients' age (up to 18 years old). RESULTS We identified 78 hospitalizations of 52 pediatric patients due to CVST in Poland from 2013 to 2020 (63.5% boys and 36.5% girls, mean age 9.7±5.8 years old). The mean duration of hospitalization was 10.5±11.7 days, the mean cost of hospitalization was 3273±2191 Polish zloty (PLN). The most common age subgroup was adolescents (27%). Ten percent of patients were hospitalized in a region other than their region of residence. The duration and cost of hospitalization were positively correlated with each other (r=0.512, P<0.001). The most common type of admission was an emergency (51%), and the most common discharge was referral for further outpatient treatment (50%). CONCLUSIONS Polish registry data showed that from 2013 to 2020, CVST was more commonly diagnosed in male adolescents from 15 to 18 years of age who presented as emergency hospital admissions. There were regional differences in incidence and duration of hospital stay and healthcare costs between patients.

Polish recommendations for diagnosis and therapy of paediatric stroke.

Stroke remains one of the greatest health challenges worldwide, due to a high mortality rate and, despite great progress in its treatment, the significant disability that it causes. Studies conducted around the world show that the diagnosis of stroke in children is often significantly delayed. Paediatric ischaemic arterial stroke (PAIS) is not only a problem that varies greatly in frequency compared to the adult population, it is also completely different in terms of its risk factors, clinical course and outcome. The main reason for the lack of a rapid diagnosis of PAIS is a lack of access to neuroimaging under general anaesthesia. The insufficient knowledge regarding PAIS in society as a whole is also of great importance. Parents and carers of children should always bear in mind that paediatric age is not a factor that excludes a diagnosis of stroke. The aim of this article was to develop recommendations for the management of children with acute neurological symptoms suspected of ischaemic stroke and further treatment after confirmation of the ischaemic aetiology of the problem. These recommendations are based on current global recommendations for the management of children with stroke, but our goal was also to match them as closely as possible to the needs and technical diagnostic and therapeutic possibilities encountered in Poland. Due to the multifactorial problem of stroke in children, not only paediatric neurologists but also a neurologist, a paediatric cardiologist, a paediatric haematologist and a radiologist took part in the preparation of these recommendations.

International Prevalence and Mechanisms of SARS-CoV-2 in Childhood Arterial Ischemic Stroke During the COVID-19 Pandemic.

BACKGROUND: Data from the early pandemic revealed that 0.62% of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had an acute arterial ischemic stroke (AIS). In a larger cohort from June 2020 to December 2020, we sought to determine whether our initial point estimate was stable as the pandemic continued and to understand radiographic and laboratory data that may clarify mechanisms of pediatric AIS in the setting of SARS-CoV-2. METHODS: We surveyed international sites with pediatric stroke expertise to determine numbers of hospitalized SARS-CoV-2 patients <18 years, numbers of incident AIS cases among children (29 days to <18 years), frequency of SARS-CoV-2 testing for children with AIS, and numbers of childhood AIS cases positive for SARS-CoV-2 June 1 to December 31, 2020. Two stroke neurologists with 1 neuroradiologist determined whether SARS-CoV-2 was the main stroke risk factor, contributory, or incidental. RESULTS: Sixty-one centers from 21 countries provided AIS data. Forty-eight centers (78.7%) provided SARS-CoV-2 hospitalization data. SARS-CoV-2 testing was performed in 335/373 acute AIS cases (89.8%) compared with 99/166 (59.6%) in March to May 2020, P<0.0001. Twenty-three of 335 AIS cases tested (6.9%) were positive for SARS-CoV-2 compared with 6/99 tested (6.1%) in March to May 2020, P=0.78. Of the 22 of 23 AIS cases with SARS-CoV-2 in whom we could collect additional data, SARS-CoV-2 was the main stroke risk factor in 6 (3 with arteritis/vasculitis, 3 with focal cerebral arteriopathy), a contributory factor in 13, and incidental in 3. Elevated inflammatory markers were common, occurring in 17 (77.3%). From centers with SARS-CoV-2 hospitalization data, of 7231 pediatric patients hospitalized with SARS-CoV-2, 23 had AIS (0.32%) compared with 6/971 (0.62%) from March to May 2020, P=0.14. CONCLUSIONS: The risk of AIS among children hospitalized with SARS-CoV-2 appeared stable compared with our earlier estimate. Among children in whom SARS-CoV-2 was considered the main stroke risk factor, inflammatory arteriopathies were the stroke mechanism.

Nusinersen treatment of Spinal Muscular Atrophy Type 1 - results of expanded access programme in Poland.

AIM OF THE STUDY: This study aimed to evaluate the effects of nusinersen therapy in Polish children with SMA type 1. CLINICAL RATIONALE OF STUDY: Spinal muscular atrophy (SMA) is a neuromuscular disorder that is characterised by the loss of motor neurons, progressive muscle weakness and atrophy, leading to increased disability and mortality. Nusinersen, an antisense oligonucleotide that promotes production of the functional survival motor neuron protein is approved for the treatment of SMA 5q in the European Union. In 2017, an early access programme (EAP) for nusinersen was launched in Poland. In this study, we present the results of nusinersen treatment in Polish patients participating in the EAP. MATERIALS AND METHODS: We collected prospectively clinical data including mutational analysis of SMN1 and SMN2 genes, motor function outcomes as measured on a standardized scales, ventilatory and nutritional status, on SMA type 1 patients receiving nusinersen in three EAP centres in Poland. Scores on the CHOP-INTEND scale after 18-26 months of treatment were compared to baseline. RESULTS: We analysed data from 26 patients with SMA type 1, mean age 4.79 (2-15) years. The mutational analysis revealed two SMN2 gene copies in the majority of patients (61.54%). Three and four copies were found in 34.62% and 3.84%, respectively. Median disease duration was 21 months. Half (n = 13) of the patients required mechanical ventilation at baseline and 57.69% (n = 15) were fed by nasogastric tube or percutaneous endoscopic gastrostomy. No patient worsened during the follow-up. Mean improvement in CHOP-INTEND from baseline to the last follow-up was 7.38 points (p < 0.001). CHOP-INTEND scores did not decline for any patient. Patients with three or more SMN2 gene copies had higher scores than did the patients with two copies (p = 0.013), and they tended to show greater improvement over time, but the difference was not significant (p = 0.324). Shorter disease duration and higher CHOP-INTEND baseline score were associated with a better response (p = 0.015). Patients with a CHOP-INTEND score above the median had higher scores overall than the rest (p < 0.0013), and they improved significantly more than the rest (p = 0.037). Nusinersen was well tolerated, no new safety findings were identified. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our data indicates that nusinersen treatment might be effective in SMA type 1 patients, regardless of their age and functional status.

Upstream Stimulating Factor 1 (USF-1) Gene Polymorphisms and the Risk, Symptoms, and Outcome of Pediatric Ischemic Stroke.

BACKGROUND: Pediatric ischemic stroke is an important cause of morbidity and mortality. As previous studies of children after stroke showed, dyslipidemias were very common in Polish and other European populations. Thus, looking for genetic factors predisposing to pediatric stroke, its symptoms, and outcome, we have analyzed 2 polymorphisms of the upstream stimulating factor 1 (USF-1) gene. MATERIALS AND METHODS: The study group consisted of 82 children with stroke, 156 parents, and 146 controls. We used 2 alternative methods: the case-control model and the analysis of families using the transmission disequilibrium test. The 2 polymorphisms, rs2516839 and rs3737787, were genotyped using the TaqMan Pre-Designed SNP Genotyping Assay. The Statistica 10.0 software was used in all statistical analyses. RESULTS: We did not observe any statistical differences in genotype and allele frequencies between patients and controls. There were also no significant differences in the transmission of alleles from the parents to the affected children. However, we have observed that the TT genotype of the rs2516839 polymorphism was more common in patients with epilepsy and dysarthria, whereas the TT genotype of the rs3737787 polymorphism was more frequent in the group of patients with a decrease in intellectual functioning. CONCLUSIONS: Our study did not show any associations between the 2 analyzed polymorphisms of the USF-1 gene and pediatric ischemic stroke. However, we have observed an influence of specific genotypes on the outcome of stroke, including epilepsy, dysarthria, and a decrease in intellectual functioning.

Neurodegenerative changes detected by neuroimaging in a patient with contiguous X-chromosome deletion syndrome encompassing BTK and TIMM8A genes.

INTRODUCTION: In this study we describe a patient with gross deletion containing the BTK and TIMM8A genes. Mutations in these genes are responsible for X-linked agammaglobulinemia and Mohr-Tranebjaerg syndrome, respectively. X linked agammaglobulinemia is a rare primary immunodeficiency characterized by low levels of B lymphocytes and recurrent microbial infections, whereas, Mohr-Tranebjaerg syndrome is a progressive neurodegenerative disorder with early onset of sensorineural deafness. MATERIAL AND METHODS: For neuroimaging, the magnetic resonance imaging and magnetic resonance spectroscopy of the brain were performed. Microarray analysis was performed to establish the extent of deletion. RESULTS: The first clinical symptoms observed in our patient at the age of 6 months were connected with primary humoral immunodeficiency, whereas clinical signs of MTS emerged in the third year of live. Interestingly, the loss of speech ability was not accompanied by hearing failure. Neuroimaging of the brain suggested leukodystrophy. Molecular tests revealed contiguous X-chromosome deletion syndrome encompassing BTK (from exons 6 through 19) and TIMM8A genes. The loss of the patient's DNA fragment was accurately localized from 100 601 727 to 100 617 576 bp on chromosome's loci Xq22.1. CONCLUSIONS: We diagnosed XLA-MTS in the first Polish patient on the basis of particular molecular methods. We detected neurodegenerative changes in MRI and MR spectroscopy in this patient. Our results provide further insight into this rare syndrome.

The rs10757278 Polymorphism of the 9p21.3 Locus in Children with Arterial Ischemic Stroke: A Family-Based and Case-Control Study.

BACKGROUND: The association of 9p21.3 locus single nucleotide polymorphisms with arterial ischemic stroke in adults was demonstrated in many studies, but there are no studies in pediatric arterial ischemic stroke patients. We investigated whether the 9p21.3 locus polymorphism, namely rs10757278, is associated with the arterial ischemic stroke risk in children. METHODS: The study group consisted of 335 individuals: 80 children with arterial ischemic stroke, their biological parents (n = 122), and 133 children (age and sex matched) without any symptoms of arterial ischemic stroke as a control group. The rs10757278 polymorphism was genotyped using the TaqMan® Pre-designed SNP Genotyping Assay (Applied Biosystems). Two different study design models were used: family-based association test (transmission-disequilibrium test) and case-control model. RESULTS: There were no statistically significant differences in the distribution of genotypes and alleles of the rs10757278 polymorphism between groups of children with arterial ischemic stroke and controls. The frequency of both transmitted alleles in transmission-disequilibrium test analysis was identical (50%). The A allele carrier state (AA+AG genotype) was more frequent in arterial ischemic stroke children with hemiparesis than in patients without this symptom (94.5% versus 68.0%, P = .004). CONCLUSIONS: There is no evidence to consider the 9p21.3 locus polymorphism as a risk factor for childhood arterial ischemic stroke.

Retracted: Post-stroke epilepsy in Polish paediatric patients.

The above article, published online on 5 October 2013 in Wiley Online Library Early View (http://onlinelibrary.wiley.com/), has been retracted by agreement between the authors, the journal Editor in Chief, Dr Peter Baxter, and John Wiley & Sons Ltd. The retraction has been agreed due to several errors in the statistics. These errors make interpretation of the data difficult and the validity of the conclusions questionable.

Post-stroke epilepsy in Polish paediatric patients.

AIM: The aim of this study was to characterize a group of children with early and late remote seizures, which occurred after arterial ischaemic stroke (AIS), and to find predictors of post-stroke seizures. METHOD: The study group, recruited in the Department of Neuropediatrics (Medical University of Silesia, Katowice, Poland), comprised 78 individuals (range 1-18y) who had suffered a stroke: 13 participants had early seizures, occurring up to 7 days after AIS, seven participants had late remote seizures, occurring more than 7 days after AIS, and 58 participants had no seizures. RESULTS: Post-stroke epilepsy occurred in 10 patients having post-stroke seizures. Participants affected by late remote seizures were younger, on average, than participants unaffected by seizures. The frequencies of total anterior circulation infarct (TACI) stroke subtype and focal cerebral arteriopathy (FCA) were significantly higher in the late seizure subgroup than in the subgroup without seizures (71% vs 26%, p=0.014, OR 7.17, and 100% vs 51%, p=0.015 respectively). Multivariable Cox analysis showed that age at time of stroke (p=0.027), FCA (p=0.010), and the number of infarct foci (p<0.001) were significant predictors of post-stroke seizures. INTERPRETATION: Age at time of stroke, presence of FCA, and number of infarct foci are predictors of post-stroke seizures in Polish paediatric patients.

The role of biochemical risk factors in the etiology of AIS in children and adults.

Stroke is an abrupt onset of both focal and global neurological deficits secondary to a vascular event lasting more than 24 h and with a vascular background as its only cause. It can be triggered by a rupture of a blood vessel, aneurysm (hemorrhagic stroke, HS), thrombosis or embolisms (ischemic stroke, IS). In developed countries, it is the third most common cause of death in the adult population. Stroke in children is a rare disorder with a reported frequency of about 3 cases per 100,000 children per year. The history of acute brain ischemia is burdened with neurological complications such as motor impairment, speech impairment and intellectual delay. Moreover, in children after AIS seizures and epilepsy are also quite common. Stroke is a heterogeneous disorder; its risk factors in adults are well known, however, in pediatrics, in more than 20% cases, the cause of stroke is impossible to determine. Due to the fact that stroke usually arises as a consequence of the cerebral thrombosis, many of the mechanisms responsible for its occurrence can be considered as risk factors. We have reviewed the recent case-control studies conducted on pediatric patients regarding biochemical risk factors such as elevated levels of homocysteine, fibrinogen, protein C, protein S, antithrombin III, lipoprotein(a), cholesterol and its fractions, and compared them with the results obtained from adult patients.

Methylenetetrahydrofolate reductase gene A1298C polymorphism in pediatric stroke--case-control and family-based study.

Moderate hyperhomocysteinemia is one of the risk factors of pediatric stroke. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme, which regulates homocysteine metabolism, and some polymorphisms of gene encoding this enzyme are associated with a decreased activity of the enzyme. The aim of the study was to assess an association between the A1298C polymorphism and pediatric stroke. We also evaluated a possible synergistic effect of A1298C and C677T polymorphisms of this gene. The study group consisted of 88 children after ischemic stroke, 142 of their parents and 111 controls. The A1298C polymorphism was genotyped using the restriction fragment length polymorphism method. We used 2 study designs: a case-control model and a family-based association test. The Statistica 7.1 and EpiInfo 6 softwares were used in all analyses. We did not observe any statistically significant differences either in the transmission of the A allele in the family-based test or in the frequency of the A allele in the patients group compared with the controls. We also did not notice any significant additive or synergistic effects between the A1298C and C677T polymorphisms. An analysis of the results obtained in this study and a critical review of previously published studies indicate that the A1298C polymorphism of the MTHFR gene is not related to ischemic stroke in children.

The role of genetic risk factors in arterial ischemic stroke in pediatric and adult patients: a critical review.

The incidence of arterial ischemic stroke (AIS) in childhood (about 2-13 per 100,000 children a year) is much lower than the incidence in the adult population. Still, adverse outcomes of acute brain ischemia in childhood include death (10% of AIS children), neurological sequel, epileptic seizures (over 50%) and recurrence (over 20%). The knowledge of childhood stroke etiopathogenesis is still insufficient and the diagnostic and therapeutic procedures--controversial. Risk factors for childhood stroke differ from those observed in adults due to differing exposure to external risk factors. The most frequently reported risk factors for pediatric ischemic stroke are cerebral arteriopathies and vascular malformations, cardiac diseases, infections, traumas and metabolic diseases. Because of its multifactorial etiology pediatric AIS probably has a multigenic inheritance pattern. The genetic susceptibility to AIS may be determined by specific polymorphic variants encoding markers of hemostasis regulation and they are some of the most important targets in searching for genetic determinants in pediatric AIS. The authors have reviewed the recent literature on risk factors of childhood ischemic stroke with the focus on genetic factors like polymorphisms of genes encoding coagulation factors II, V, VII and XIII, MTHFR, fibrinogen beta, and compared them with the results performed in adult patients.

Analysis of 622 paediatric hospitalisations due to arterial ischaemic stroke in Poland - National Health Fund registry-based study from 2011 to 2020.

Introduction: The present study aimed to evaluate the prevalence of arterial ischaemic stroke (AIS) in Polish children, as well as to analyse the parameters related to AIS hospitalisation, including age, gender, region, month and season of the year at admission, duration, and costs, based on data from National Health Fund (NHF) registry in 2011-2020. Material and methods: Data from the NHF were analysed statistically. The disease was identified according to the codes I63 and I64 of the International Classification of Diseases, 10th Revision (ICD-10), and patients included only individuals up to 18 years of age. Results: We identified 622 hospitalisations due to paediatric AIS in Poland in the study period. The most frequent age subgroups were adolescents, followed by toddlers or pre-school children (34.73% and 24.12%, respectively), while the least frequent were neonates or infants (9.81%). ICD-10 procedures did significantly affect the duration and costs of hospitalisation (p < 0.001). The highest costs of hospitalisations concerned the I63.1 procedure (cerebral infarction due to embolism of precerebral arteries), which included thrombectomy. The duration and costs of hospitalisation were positively correlated with each other (r = 0.525, p < 0.001). Age correlated negatively with duration of hospitalisation (r = -0.154, p < 0.001) and positively with costs of hospitalisation (r = 0.133, p = 0.008). Conclusions: Data from the NHF registry proved that AIS occurs more often in boys than in girls and is more common in adolescents (15-18 years) than in younger children.

The TT genotype of methylenetetrahydrofolate reductase 677C>T polymorphism increases the susceptibility to pediatric ischemic stroke: meta-analysis of the 822 cases and 1,552 controls.

The 677C>T polymorphism within methylenetetrahydrofolate reductase (MTHFR) gene is related to an elevated level of homocysteine. Thus it may be considered as a genetic risk factor in ischemic stroke. Apparently studies of this type of polymorphism in childhood stroke have shown conflicting results. We performed meta-analysis of all the data that are available in relation with MTHFR polymorphism and the risk of ischemic stroke in children. We searched PubMed (last search dated December 2010) using "MTHFR polymorphism", "ischemic stroke" "child", "children", "pediatric stroke" as keywords and reference lists of studies and reviews on the topic. Finally, 15 case-control studies corresponded to the inclusion criteria for meta-analysis. These studies involved the total number of 822 children and adolescents after ischemic stroke and 1,552 control subjects. Fixed or random effects models were used depending on the heterogeneity between the studies. The association between ischemic stroke and 677C>T polymorphism within MTHFR gene was observed in three of the studies. The pooled analysis showed that TT genotype of MTHFR gene is more common in stroke patients than in controls (p = 0.0402, odds ratio = 1.57, 95 % confidence interval 1.02-2.41). The Egger's test did not reveal presence of a publication bias. The results based on a sizeable group of cases and controls have proved that the 677C>T polymorphism in MTHFR gene is associated with the development of ischemic stroke in children.

Introduction to the Special Issue on Ischemic Stroke in Children.

The occurrence of arterial ischemic stroke (AIS) is a serious medical problem due to the deleterious neurological consequences that affect the daily functioning of the patient as well as the costs of medical care and rehabilitation [...].

Serum Levels of Lipids and Selected Aminothiols in Epileptic Children-A Pilot Case-Control Study.

BACKGROUND: Standard treatment of epileptic seizures involves the use of antiepileptic drugs (AEDs). Both AEDs themselves and treatment duration may influence the levels of biochemical parameters, e.g., lipids or homocysteine (HCys), that may increase the risk of cardiovascular diseases. The aim of the present study was to compare the levels of lipid parameters, as well as the concentrations of selected aminothiols (i.e., HCys, cysteine, and glutathione) between epileptic children treated with multiple AEDs and children without epilepsy. METHODS: In the study, 21 children with epilepsy treated with two or more AEDs for at least 6 months (8 girls and 13 boys, mean age 7.03 ± 4.51) and 23 children without epilepsy (7 girls and 16 boys, mean age 7.54 ± 3.90) were prospectively analyzed. Lipid parameters, i.e., total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL), and levels of selected aminothiols were determined in the blood serum. RESULTS: No differences in the mean levels of lipid parameters and in the mean values of lipid ratios (TC/HDL, TG/HDL, LDL/HDL) were observed between the total groups as well as in the sex subgroups. HCys and cysteine levels did not differ between the patients and controls. We observed significantly lower levels of glutathione in children with epilepsy than in children without epilepsy (1.49 ± 0.35 µmol/L vs. 2.39 ± 1.17 µmol/L, respectively) (p < 0.001). Glutathione level was also lower in boys with epilepsy than in boys without epilepsy (p = 0.007). Similarly, epileptic girls had statistically decreased levels of glutathione when compared to girls without epilepsy (p = 0.006). CONCLUSIONS: A lower level of glutathione is observed in pediatric patients with epilepsy treated with two or more AEDs for at least 6 months. This indicates the oxidative stress of the patients treated with AEDs, which in turn may affect their well-being, and in the case of chronic occurrence resulting from long-term treatment, also on the function of the liver and the condition of the cardiovascular system.

Medico-legal analysis of cases of children who died suddenly due to pneumonia undiagnosed in their lifetime. / Sadowo-lekarska analiza przypadków dzieci zmarlych nagle z powodu nierozpoznanego za zycia zapalenia pluc.

Pneumonia is one of the most common causes of children's hospitalization and death. The aim of the study was a medico-legal analysis of children who died suddenly due to pneumonia undiagnosed in their lifetime. The research was of a retrospective character and consisted in an analysis of prosecution files. The study included 47 children who died between 2011-2018 in whom pneumonia after post-mortem examination was indicated as the cause of death, as well as children in whom the cause of death, despite additional post-mortem examinations, including histopathological tests, was not established. In some cases, under additional post-mortem examinations, additional targeted immunohistochemical staining of selected lung sections was performed to establish the diagnosis. In children with prodromal symptoms, histopathological examination showed significantly more frequent atelectasis than in children without prodromal symptoms. Pneumonia is a significant clinical problem. Especially in young children, it may proceed with- out any symptoms that would cause such a diagnosis to be made. A properly conducted post-mortem diagnosis supplemented by immunohistochemical examinations allows to reduce the number of unexplained deaths in children.

Do Antiepileptic Drugs Change the Levels of Arginine Derivatives in Epileptic Children Treated with Polytherapy? The Results of a Case-Control Study.

Previously, a relation between therapy with antiepileptic drugs (AEDs) and the levels of biochemical parameters was observed in adult patients suffering from epilepsy. Among these biochemical factors, arginine derivatives are often analyzed, i.e., asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and homoarginine (hArg) as they may be linked with increased risk for cardiovascular disease (CVD). Since the levels of arginine derivatives may increase during therapy, and the treatment of epilepsy often lasts many years, patients may experience CVD faster. The aim of the present study was to analyze the levels of arginine derivatives in children with epilepsy who were treated with multiple AEDs to answer the question whether pediatric patients may be at increased risk of CVD in the future. We prospectively analyzed 21 children suffering from epilepsy who took ≥2 AEDs for at least 6 months and 22 children without epilepsy (reference group). The levels of the arginine derivatives, e.g., ADMA, SDMA, and hArg, were determined in the blood serum using the HPLC method. No differences in both the mean levels of ADMA and SDMA, as well as in the mean values of the arginine derivative ratios, were observed between the groups. The tendency toward a lower level of hArg was found in epileptic patients more than in the reference group (p = 0.091). Epileptic children receiving three or more AEDs had significantly lower concentrations of hArg and values of the hArg/ADMA ratio than the reference group (p = 0.023 and p = 0.006, respectively). In turn, the mean hArg/ADMA ratio was lower in children receiving three or more AEDs compared to children receiving two AEDs (p = 0.002). There was also a positive correlation between the hArg and ADMA concentrations in children with epilepsy taking two AEDs; the higher the level of hArg, the greater the level of ADMA on average (r = 0.650, p = 0.022). Taking three or more AEDs by epileptic children resulted in lower levels of both hArg and the value of the hArg/ADMA ratio.

Selected Factors of Vascular Changes: The Potential Pathological Processes Underlying Primary Headaches in Children.

BACKGROUND: The prevalence, social consequences and complicated pathogenesis make headaches in children a significant clinical issue. Studies in adults suggest that primary headaches could be the first sign of atherosclerosis and platelet aggregation. AIM: To analyze the blood levels of selected biomarkers of vascular changes potentially associated with a higher risk of atherosclerosis in children with primary headaches. METHODS: The medical family history, brain-derived neurotrophic factor (BDNF), soluble CD40 ligands (sCD40L), endothelial plasminogen activator inhibitor (PAI I), vascular endothelial growth factor (VEGF) and intima-media thickness (IMT) measurements were performed in the 83 children (52 with primary headaches, 31 controls). Selected factors were compared with basic laboratory parameters that are potentially related to atherosclerosis: C-reactive protein (CRP) and lipid concentration. RESULTS: There were no significant differences in biomarkers of vascular changes in the study group and controls in general. In the study group, boys had a higher BDNF level than girls (p = 0.046). Normal-weight migraine patients had significantly higher PAI-I levels than controls (p = 0.034). A positive correlation between PAI-1 and triglycerides (TG) was observed. IMT did not differ between children with primary headaches and controls; however, IMT showed a positive correlation with BMI z-score and TG. Children with headaches had, more often, a positive family history of cardiovascular disease (p = 0.049). CONCLUSIONS: There were no clear clinical changes indicative of atherosclerosis in the study population. However, some trends are visible. Primary headaches are more often related to a family history of cardiovascular diseases. IMT is associated with TG levels and BMI z-score. The measured biomarkers of vascular changes show mutual relations.