Ilona Kopyta

The T Allele of the 677C>T Polymorphism of Methylenetetrahydrofolate Reductase Gene is Associated With an Increased Risk of Ischemic Stroke in Polish Children

Ischemic stroke is a very rare and multifactorial disease in children. The aim of the study was to analyze the relationship between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and stroke in Polish children and to observe whether there is any significant transmission of MTHFR alleles from heterozygous parents to their affected offspring. We analyzed 64 patients with stroke, 122 parents, and 59 healthy children. The MTHFR polymorphism was genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism. The T allele was more frequent in the stroke group (38%) than in controls (25%, P = .029, odds ratio = 1.84). We also found higher frequency of T allele in male patients compared to male controls (46% vs. 25%, P = .009, odds ratio = 2.53). The number of T allele carriers was again more prevalent in boys with stroke (71%) than in healthy boys (45%, P = .023, odds ratio = 3.09). The T allele was significantly transmitted in male patients (P < .019). We conclude that the MTHFR 677C>T polymorphism may be considered as a genetic risk factor of childhood stroke, especially in boys.

Angelman syndrome revisited.

Objectives:Angelman syndrome (AS) is characterized by severe mental retardation, epilepsy, absent speech, dysmorphic facial features, and a characteristic behavioral phenotype. It is caused by deficiency of gene expression from maternally derived chromosome 15q11-q13. Study Design:The authors present the clinical picture of 9 children (median age, 4.9 years; range, 1 to 10 years) with confirmed Angelman syndrome. The patients complied with the international consensus criteria for AS and were consecutively investigated for psychomotor development, epilepsy, and electroencephalogram (EEG) profiles. Results:The median age at diagnosis was 3.9 years. The motor milestones were delayed. Median developmental quotient level was 26. All patients but 1 experienced predominantly polymorphic seizures. In 4 cases, the epilepsy was refractory to treatment. The EEG of all patients displayed an abnormal sleep pattern and generalized abnormalities, with a maximum over the posterior areas. Conclusions:Milder or less typical phenotypes of AS may remain undiagnosed, leading to an overall underdiagnosis of the disease. The EEG shows no clear relation to genotype, clinical picture, or to the presence and severity of epilepsy. AS should be considered in the differential diagnosis of children with severe cryptogenic epilepsy and a characteristic configuration of clinical features.

APOE Gene ε Polymorphism Does Not Determine Predisposition to Ischemic Stroke in Children

Ischemic stroke in children is relatively rare, but it remains an important medical problem. Previous studies on Polish children have implicated dyslipidemias as significant risk factors in stroke. To search for genetic factors associated with the disease, the possible association between apolipoprotein E gene epsilon polymorphism and childhood stroke was evaluated. The study population consisted of 243 individuals: 72 children with ischemic stroke and 100 of their biological parents and 71 children without any symptoms of stroke. The apolipoprotein E gene epsilon polymorphism was genotyped using restriction fragment length polymorphism methodology. To analyze the possible association between this polymorphism and stroke, the transmission disequilibrium test and the case-control model were used. No preferential distribution of any allele from parents to the affected children was observed. There were also no significant differences in genotype and allele distribution between patients and control subjects. Study findings did not confirm that epsilon polymorphism of the apolipoprotein E gene is a risk factor of ischemic stroke in children.

The C242T polymorphism of the gene encoding cytochrome b-245 alpha is not associated with paediatric ischaemic stroke: family-based and case-control study.

BACKGROUND AND PURPOSE Reactive oxygen species play an important role in the physiology and pathology of cerebral arteries, including ischaemic stroke. The cytochrome b-245 alpha gene (CYBA) encodes cytochrome b-245 alpha light chain (p22phox peptide), a critical element of NAD(P)H oxidases, the most important source of superoxide anion in the cerebral arteries. To search for genetic factors associated with paediatric ischaemic stroke, the possible association between CYBA gene C242T polymorphism and the disease was evaluated. MATERIAL AND METHODS The study group consisted of 238 individuals: children with ischaemic stroke (n = 70), their biological parents (n = 118) and children without any symptoms of stroke (n = 50). The C242T polymorphism was genotyped using polymerase chain reaction - restriction fragment length methodology. To evaluate the possible association between polymorphism and stroke, the transmission disequilibrium test and the case-control method were applied. RESULTS The C242 allele was transmitted more frequently than 242T (62.2% vs. 37.8%) but observed frequencies did not differ significantly from expected (p = 0.10). There were also no significant differences in allele and genotype distribution between patients and control subjects (patients: CC - 50.0%, CT - 38.6%, TT - 11.4% vs. controls: CC - 52.0%, CT - 36.0%, TT - 12.0%). CONCLUSIONS The study did not show that the C242T polymorphism of the CYBA gene is a risk factor of ischaemic stroke in children.

Application of Gait Index Assessment to Monitor the Treatment Progress in Patients with Cerebral Palsy

A three-dimensional analysis of movement is more and more often applied to assess locomotive functions of patients with cerebral palsy (CP). For the past few years there has been a growing interest in gait index methods which enable the evaluation of the patient’s gait with the use of a single numerical value. This research aimed at the assessment of the gait of patients with CP at different stages of treatment on the basis of gait indices Gillette Gait Index (defined by Shutte) and Gait Deviation Index (definied by Schwartz and Rozumalski) as well as finding dependencies between the determined indices values. The studied group consisted of 56 healthy participants and 16 patients with cerebral palsy treated using botulinum toxin. On the grounds of the determined indexes, the improvement of gait was observed in the case of 75 % of patients with CP. Statistically significant differences were found between GGI and GDI values obtained in the initial investigation and after 6 months following the administration of botulinum (PRE and POST). There was a strong linear dependence observed between the GDI and GGI* (\(GGI^*=\ln (\sqrt{GGI})\)) values. No significant dependence was observed between the percentage indices of improvement determined on the basis of the GGI and GDI results obtained (in the PRE and POST examination).

Polymorphisms of genes encoding coagulation factors II, V, VII, and XIII in relation to pediatric ischemic stroke: family-based and case-control study.

Background:The investigation of a possible association between the FII, FV, FVII, and FXIII genes polymorphisms and pediatric ischemic stroke (IS). Methods:The study group consisted of 392 individuals, including 81 children with IS, their biological parents (n=162), and 149 control children. The polymorphisms were genotyped using polymerase chain reaction-restriction fragments length polymorphism method. The relation between analyzed polymorphisms and the disease was tested by 2 independent methods: family-based association test—transmission/disequilibrium test (TDT) and classic case-control model. Results:We did not observe any preferential distribution of any analyzed allele from parents to the affected children. For the FVII gene polymorphism, there was a trend toward a higher frequency of the R allele. In a case-control model, the differences between the patients and controls in the frequency of the Q allele, Q allele carriers, and RR homozygotes lay close to the border of statistical significance (P=0.08). There were no significant differences in genotype and allele distribution between patients and controls in case of other polymorphisms. Conclusions:Analyzed polymorphisms of coagulation factors are not significant determinants of pediatric IS in the studied population; however, these findings require a confirmation in a larger group of participants.

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.

Headaches as somatoform disorders in children and adolescents

Somatoform disorders are often the main cause for seeking professional advice and performing a number of specialist checks. The aim of the study was to determine the frequency of somatoform disorders in the form of headaches in children and adolescents neurologically diagnosed and the risk factors thereof. Analysis of the biological and situational risk factors were established. Somatoform disorders were diagnosed in 27 out of 276 children with headaches. We concluded that in the differential diagnosis of headaches, somatoform headaches should not be omitted as every 10th patient in the developmental age diagnosed on the neurological ward because of headache shows signs of somatoform headaches. In diagnostically difficult cases it is recommended that analysis of biological and situational risk factors be performed with special attention paid to chronic disease of the patient and/or in his immediate family, the patient’s psychological disorders and dysfunctional or low social status families. The creation of separate criteria for somatoform disorders of the developmental age should be considered.

Post-stroke epilepsy in Polish paediatric patients.

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.

The assessment of awareness of child abuse among certain social groups

Child abuse is an act of doing something or failing to do something that result in harm to a child or puts a child at risk of harm. Although the occurrence of child abuse in our society is a serious problem, the statistics often remain unreliable. The purpose of our research was an assessment of the knowledge, attitudes and experiences among physicians, medical students and teachers of reporting child abuse and neglect. The questionnaire containing questions about the demographic data of our respondents and questions regarding the analysed subject was created. The resultswerestatisticallyanalyzed using the Chi-square Test. Theinvestigatedgroup consisted of139 teachers, 131 medical studentsand53 physicians. Amongthephysicians, specialists with more than 10 yr of experience constituted 83% with a predomination of pediatricians. Among the teachers, those with more than 10 yr of experience constituted 67%. Medical journals and professional trainings were the main source of knowledge for the physicians, while television and radio were the source of knowledge for teachers significantly more often than with others groups. The majority of respondents encountered cases of child abuse (physicians 74%, students 29%, and teachers 58%). In spite of their declared knowledge about child abuse the majority of physicians and medical students claim that low social status and uneducated families are the risk factors of child maltreatment, while the majority of teachers are aware there is no difference ( P< 0.000001). The majority of respondents encountered cases of child abuse but their knowledge of child maltreatment still remains insufficient. It is considered reasonable to extend the range of obligatory professional trainings.