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.

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.

Associations between MDR1 C3435T polymorphism and drug-resistant epilepsy in the Polish population.

Epilepsy is a common neurological disorder. About one-third of epileptic patients demonstrate multidrug resistance (MDR) phenotype and develop drug-resistant epilepsy (DRE). Single nucleotide polymorphism (SNP) C3435T (rs1045642), identified in the MDR1 gene, is associated with an increased intestinal expression of P-glycoprotein (P-gp) which affects the levels of anti-epileptic drugs in plasma. The reported study was designed to explore associations between the MDR1-C3435T gene SNP and the risk of DRE in the Polish population. The C3435T polymorphism of MDR1 gene was investigated by the PCR-RFLP technique in 74 patients with DRE and 70 age- and sex-matched non-DRE controls. Blood samples were obtained from patients with drug-resistant epilepsy, treated at the Department of Neurological Surgery, Medical University in Warsaw between the years 2011 and 2012. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for each genotype and allele. Genotype distribution of C3435T polymorphism of MDR1 gene was compared between the DRE patients and controls with significant differences (p < 0.05) between the two investigated groups. A possible association was observed between DRE and the presence of 3435C allele. The 3435C allele was found in 69 % of DRE cases and in 48 % of the used controls. The variant 3435T allele of MDR1 decreased the risk of drug-resistant epilepsy [odds ratio (OR) 0.41; 95 % confidence interval (CI) 0.26-0.67]. The results indicate that the C3435T polymorphism of MDR1 gene may be associated with the incidence of DRE observed in the Polish population.

[The differential diagnosis of asymmetry in infants].

Asymmetry in infants is a clinical condition in which abnormal body shape, posture or mobility is observed. It is characterized by diverse etiology, localization and severity. The most frequently noted kind is idiopathic asymmetry. Symptomatic asymmetry is less frequent and a variety of structural or systemic disorders underlie this disease. The dynamics of child development in the first year of life makes it necessary for clinicians to give an early diagnosis of asymmetry, which has a significant impact on the expected course of its development and intervention strategies. The aim of the study is to present the definitions, classification and differential diagnosis of asymmetry in infants.

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.

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.

Impact of the -174G/C interleukin-6 (IL-6) gene polymorphism on the risk of paediatric ischemic stroke, its symptoms and outcome.

OBJECTIVES: Ischemic stroke remains one of the top ten causes of death in children. There is evidence for the role of pro-inflammatory cytokines, such as IL-6 and the -174G>C promoter polymorphism of the IL-6 gene, in the occurrence and outcome of stroke in adults. The aim of the present study was to determine a possible association between the -174G>C IL-6 polymorphism and occurrence of paediatric stroke, its symptoms and outcome. MATERIAL AND METHODS: The study group consisted of 340 individuals: 80 stroke children, 122 parents of patients and 138 controls. The -174G/C polymorphism was genotyped using the RFLP method. For the analysis of the relationship between genotypes and stroke we used two alternative methods: the case-control model and the transmission test for linkage disequilibrium using data from families. RESULTS: We observed no differences in the transmission of alleles from parents to children. We also did not find any statistical differences in distribution of genotypes and alleles between patients and controls. However, the analysis showed that post-stroke epilepsy was genotype-dependent. All children with epilepsy were G allele carriers and none of them was a CC homozygote whereas about 25% of children without epilepsy had the CC genotype. CONCLUSIONS: Our study did not show any associations between the IL-6 -174 G>C polymorphism and the occurrence of stroke but we observed a relation between post-stroke epilepsy and the G allele carrier-state.

[Hypoxic-ischemic encephalopathy as a special form of head injury complication in battered child syndrome]. / Encefalopatia niedotlenieniowo-niedokrwienna jako szczególna postac powiklania urazu glowy w zespole dziecka maltretowanego.

The battered child syndrome is increasingly more often described in literature. Head injuries experienced by battered children are the main cause of deaths and neurological complications. A special form of damage inflicted in battered children is vessel background brain injury. The objective of the article was to characterize central nervous system injuries and their results in children who were victims of physical violence. Medical records of three patients hospitalized in Department of Neurology of the Polish Mother Health Center Institute in Lodz, in whom the battered child syndrome had been diagnosed, were analyzed. The authors discussed three cases of children with central nervous system injuries caused by physical violence. All the children were treated pharmacologically, placed on parenteral nutrition and rehabilitated. Among typical central nervous system injuries caused by head trauma, particular attention of the authors was focused on hypoxic-ischemic encephalopathy, a complication of a still unclear etiology that occurred in two cases. Battered children are usually treated in surgical departments and the causes of injuries are not always correctly diagnosed. Brain damage is the reason for permanent neurological consequences in children who experienced physical violence. In medico-legal practice, it is essential to describe precisely all the visible injuries (bruises, abrasions, wounds) especially during the initial medical examination.

[Epilepsy and mental retardation. The school's functioning in children with epilepsy]. / Padaczka a uposledzenie umyslowe. Funkcjonowanie szkolne dzieci z padaczka.

BACKGROUND: In 2009 Polish Society of Epileptology have conducted the survey of public opinion over the situation of the children suffering from epilepsy. Intellectual disability is a major indication for children with epilepsy to attend to special schools and learn in integrative classes. Neurodevelopmental disorders including intellectual disability, is associated with 5% of new-diagnosed cases of epilepsies and with 18% of all epilepsy cases in children. METHODS AND RESULTS: Hereby author describes mechanisms that leads to cognitive impairments in the course of epilepsy, including influence of temporal and extratemporal seizures as well as school problems of children with epilepsy. From 5% to 50% of children suffering from epilepsy have problems in school and 30% require attending to special schools. School achievements of children suffering with epilepsy and normal IQ is similar to those without this disorder with IQ ranging from 71 to 85. The influence of biological factors (age of onset, number of seizures or antiepileptic drugs therapy) on school achievements is smaller than described by earlier authors. Nevertheless, even nowadays retardation in acquisition of reading, writing and calculating capacities can be noticed in 60% of children with epilepsy. Described risk can be increased by coexistence of attention deficit and emotional problems. The impairment decreases with age. CONCLUSIONS: Children suffering from epilepsy require constant monitoring of school achievements and psychostimulation even in cases with normal IQ.

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.

[Lentigines as an important of Peutz-Jeghersa Syndrome]. / Plamy soczewicowate jako istotny objaw diagnostyczny zespolu Peutz-Jeghersa.

Peutz-Jeghers syndrome is an autosomal dominant inherited disorder which is characterized by mucocutaneus melanocytic macules and intestinal hamartomatous polypus. The aim of our work is to underline the role of pigmented changes in the diagnostic process. Numerous lentigines should always lead to multiorgan investigations.

[Lentigines in different multiple organ defects syndromes]. / Wystepowanie plam soczewicowatych w róznych zespolach wielonarzadowych.

The aim of our study is to introduce a larger number of doctors to the subject of lentigines. They may be a first syndrome coexistent with very rare multiple organ defects as syndrome Peutz-Jeghers, LEOPARD, LAMB and Carney syndrome.

[Pseudoatrophic macules as a additional skin sign of neurofibromatosis]. / Pseudozanikowe plamy jako dodatkowy objaw skórny nerwiakowlókniakowatosci.

Pseudoatrophic macules are the infrequently mentioned skin symptom of neurofibromatosis. It may be the important diagnostic sign, especially, when other symptoms are absent or puerlly expressed.

[The diagnostic and therapeutic management in the first cerebral attack in childhood]. / Postepowanie diagnostyczno-terapeutyczne po pierwszym napadzie mózgowym u dziecka.

Cerebral attacks are the most frequent neurological problem in childhood. The diagnostic and therapeutic management in the first cerebral attack belongs to subjects often discussed in literature but currently it arouses some controversies concerning especially the notions "cerebral attack", "unprovoked seizures" and also the fact when epilepsy should be diagnosed after the first or the second unprovoked attack of seizures and when to start its treatment. The author presents in detail the principles of the management of cerebral attack and its differentiation in children. In relation to the neurological examinations (EEG, cerebrospinal fluid analysis, neuroimaging examination), the author demonstrates both the indications for their performance as well as limitations due to frequently obtained negative results. Among cerebral attacks, after exclusion of symptomatic attacks and febrile seizures, the first epileptic seizure can be diagnosed in 50% of children. The treatment of epilepsy after the first epileptic seizure decreases effectively the number of seizures within the first three years. However, the percentage of children who achieved 3-5-year remission is in these patients similar to that in the group treated after 2 successive attacks of unprovoked seizures. EEG and neuroimaging examinations (cerebral MR more beneficial than CT) belong to the diagnostic canon in the case of a cerebral attack. Changes in neurological examination and also the changes maintaining after focal attack, the age of children with cerebral attack up to 6 months and changes on EEG and in neuroimaging examinations increase the risk of another attack. The selection of the performed laboratory tests depends on an individual case and should be extended when symptomatic nature of cerebral attack is suspected (i.e. acute or chronic encephalopathies).

[Bickerstaff's brainstem encephalitis -- an analysis of clinical and MRI findings]. / Zapalenie pnia mózgu Bickerstaffa - analiza przebiegu klinicznego i obraz rezonansu magnetycznego.

BACKGROUND AND PURPOSE: Bickerstaff's brainstem encephalitis (BBE) is a very uncommon central nervous system disease. Its etiology remains unknown but it is postulated that BBE has an autoimmunologic origin. BBE is characterized by acute ophtalmoplegia, ataxia, pyramidal paresis and disturbance of consciousness. A special pattern of changes in magnetic resonance imaging (MRI) is characteristic of BBE. Lesions are located mainly in the brainstem. The aim of this paper is to analyze the clinical course and MRI changes in our own cases of BBE. MATERIAL AND METHODS: We have analyzed medical records, clinical findings and MRI images of the patients with BBE diagnosis established in our Department of Neurology in the years 1998-2004. RESULTS: During that period 4 cases of BBE were diagnosed with clinical sings of acute brainstem lesion and MRI imaging suggestive of BBE. In our patients we have observed ophtalmoplegia, ataxia, disturbances of consciousness and pyramidal signs. Two patients had a monophasic and 2 remitting-relapsing course of the disease. In all four cases we have seen on T2-weighted images large, irregular hyperintense lesions in the brainstem, especially in the pons, midbrain and medulla, but also in one case in the thalamus and vermis of the cerebellum. Patients were treated with steroids, plasmapheresis or acyclovir or a combination of these methods. We observed a complete recovery in two cases and significant improvement in the other two lasting more than two years confirming a relatively good prognosis in BBE. CONCLUSIONS: BBE despite severe initial presentation usually has a good prognosis. MRI plays critical role in the diagnosis of BBE.

[Evaluation of brain activation by functional magnetic resonance in offspring of epileptic mothers and their parents in pathogenetic aspects of dyslexia]. / Ocena aktywacji mózgu potomstwa matek chorych na padaczke i ich rodziców za pomoca czynnosciowego rezonansu magnetycznego w aspekcie patogenezy dysleksji.

PRINCIPLE: So far, the assessment of cerebral centres activity during fonological awareness test with functional magnetic resonance (fMRI) of families with dyslexia has not been carried out. The up till now published studies concern insignificant number of children or adults with dyslexia, whose results have not been unequivocal. THE AIM: The general aim of the study is the explanation of the pathogenetic mechanisms of dyslexia in offspring of mothers with epilepsy and their family. Detailed aim is the evaluation of the influence of dyslexia occurrence in this particular population on activation of the brain in fMRI during phonological tests. MATERIAL AND METHOD: Before fMRI, all the patients were subjected to classical cerebral MRI to estimate central nervous system structure excluding organic causes of lesions. Finally, the groups subjected to MRI included 7 children with dyslexia, 7 without dyslexia, 7 mothers with dyslexia, 10 women without dyslexia, 4 fathers with dyslexia, 10 fathers without dyslexia and 15 men without dyslexia. The examination was carried out during fonological awareness test. Mean quantities of activated pixels in the areas of interest--prefrontal cortex (1) and Broca's area (2) were compared in the investigated and control groups. RESULTS: fMRI demonstrated significantly lower activity in both areas in frontal lobe in offspring of epileptic mothers with dyslexia as compared to offspring without dyslexia (p = 0.01, p = 0.02). Activity of Broca's area in epileptic mothers with dyslexia was significantly lower than in women with dyslexia from the control group (p = 0.05). Mothers with epilepsy and dyslexia, whose offspring also had dyslexia, had significantly lower Broca's area activity. The activity of frontal areas of fathers was on fMRI similar to the activity in control groups. CONCLUSIONS: Epilepsy in mothers with coexisting dyslexia has a modifying effect on the activity of cerebral areas in frontal lobes during the fonological awareness test. Lower activity of Broca's area is a fonotypic trait transmitted to offspring with dyslexia.

[Cognitive disturbances in rolandic epilepsy--correlation with electoencephalographic patterns]. / Zaburzenia poznawcze w padaczce rolandycznej - korelacje z zapisem elektroencefalograficznym.

BACKGROUND: Up till now there have been many discussions in the epileptological literature concerning the occurrence of cognitive deficits in children with rolandic epilepsy (RE). THE AIM OF STUDY: The aim of this study is to establish whether there exist any differences in general intelligence quotient or in particular cognitive functions in children with RE as compared to healthy children in the same age and if a correlation can be found between EEG and cognitive function in RE. MATERIAL AND METHODS: The material comprised two groups: 38 children with RE (1-2 years after diagnosis establishing) and 15 children of the same age and sex - the control group. The study group was then subdivided into: 26 children with typical EEG patterns and 12 with atypical EEG acc. to Dalla Bernardina. The results of WICS, Benton, Raven's test, Bender-Koppitz and Bender-Gestalt test and 16-canal standard wake and sleep EEG were taken into account. Statistical analysis included: Student-test and Fisher exact test. RESULTS: IQ of children with RE in all types of scores (full, verbal or non-verbal) did not differ from the control group. Some differences in particular cognitive functions were found: auditory memory (p<0.01), logical thinking (p<0.05). In the group of children with RE and atypical EEG pattern the full and non-verbal score was lower (p< 0.05) and we found in these children statistically significant deficit in analytic-synthetic thinking based on concrete material and hyperactivity (p< 0.05). CONCLUSIONS: In spite of no difference in general IQ among children with RE and the control group, there are some cognitive deficits in this epilepsy particularly concerning auditory memory and logical thinking. The children with atypical changes in EEG are the risk group of lower full and nonverbal score analytic-synthetic thinking based on concrete material and hyperactivity.

[Linear nevus sebaceous syndrome with hemimegalencephaly diagnosed in child in neonatal period]. / Zespól linijnego znamienia lojowego z polowiczym przerostem mózgu rozpoznany u dziecka w okresie noworodkowym.

The aim of this study was to present the case of the child with linear nevus sebaceous syndrome (LNSS) and hemimegalencephaly, diagnosed in neonatal period. It is one of the five epidermal nevus syndromes. Etiology of this multiorgan disease is still unknown. Most often LNSS consists of central nervous system, skeletal and ocular abnormalities. In present case different epileptic non-responsive seizures began in second week of life. In image exams hemimegalencephaly was found. EEG pattern showed generally discharges. The fits responded to vigabatrin. Psychomotor retardation was observed. Sometimes the skin lesion may be only manifestation of the syndrome. It is very important to perform early image and EEG examinations in LNSS.

[Neurocutaneous melanosis and congenital gigantic pigmented nevi in the light of current knowledge]. / Melanoza nerwowoskórna i olbrzymie wrodzone znamiona barwnikowe w swietle obecnej wiecdzy.

The aim of this work is to approach the subject of neurocutaneous melanosis and to point out the necessity and precise neurological diagnosis in each case of gigantic pigmented nevi. It is necessary to remember about early planning of skin changes removal which is the cause of lowering risk of malignant melanoma.

[Photosensitivity in children with idiopathic headaches]. / Fotowrazliwosc u dzieci i mlodziezy z samoistnymi bólami glowy.

The occipital lobe involvement in the pathogenesis of the migraine aura, frequent occurrence of photogenic stimuli as the provoking factors of a migraine attack, still unsatisfactory explanation of the relation between migraine and epilepsy have drawn our attention to the photosensitivity in the idiopathic headaches, particularly in the developmental period. Photosensitivity is detected in EEG as a paroxysmal response to intermittent photic stimulation. This reaction called a photoparoxysmal response (PPR) has to be regarded as genetically determined EEG-symptom and occurs in 1.3-1.4% of healthy individuals aged 6-18. The aim of the study was to compare the frequency and identify the type of PPR in idiopathic headaches in children: with migraine with aura, without aura and with tension-type headache as well as to find the possible correlation between PPR and migraine photogenic triggering factors in children and adolescents aged 7-18. In years 2001-2003 263 EEG records were performed in patients hospitalized because of idiopathic headaches: 77 with the diagnosis of migraine with aura, 112 - migraine without aura, 74--in tension-type headache. The Fisher exact test was used to compare the number of patients with positive PPR and those with photogenic triggering factors of a migraine attack. The frequency of PPR did not differ significantly in three types of idiopathic headaches and accounts for 7.8% in migraine with aura, 8.9%--migraine without aura and 6.7%--in tension-type headache. PPR was most frequent (17.6%) in a group of children under 12 years of age with migraine with aura. In the migraine with aura PPR had the form of the general paroxysmal of the spike, polyspike and wave in 11.8%, localized changes in the temporal-parietal-occipital region only in 5.9%. In 7/17 patients with migraine and PPR, photogenic stimuli were most frequent provoking factors for the migraine attack (in controls without PPR 10/100) (p<0,01). Frequent coexistence of PPR and photogenic provocation of the migraine attack in children and adolescents supports the theory about general cortical hyperexcitability in migraine.