The prevalence of the restless legs Syndrome/Willis-Ekbom disease among teenagers, its clinical characteristics and impact on everyday functioning.

BACKGROUND AND AIMS: The data on the prevalence of the Restless Legs Syndrome/Willis -Ekbom disease (RLS/WED) in the population of teenagers is scarce. The aim of this study was to determine RLS/WED occurrence in adolescents, its diagnostic accuracy, family history, clinical characteristics and impact on everyday functioning. MATERIAL AND METHODS: A group of 2379 pupils (aged 13-18 y.o.) from 6 randomly selected secondary schools in Gdansk, Poland were screened for RLS/WED with the use of a questionnaire. In order to verify the diagnosis and perform additional tests (neurological examination, psychological evaluation, biochemical blood tests, demographic questionnaire, International RLS rating scale/IRLSS, Epworth daytime sleepiness scale). all of the respondents with RLS/WED suspicion and their parents were asked for a consultation by a child neurologist. Both children and parents with RLS/WED diagnosis were tested with actigraphy at home for at least two consecutive nights. RESULTS: Two thousand and ninety seven students (88,15%) filled the questionnaire correctly (1171 girls and 926 boys, 56% and 44%). Sixty four respondents were suspected of having RLS/WED (3,1%), however, 36 of them were diagnosed as RLS/WED-mimics (mainly positional discomfort). Finally, 21 (1%) were diagnosed with definite idiopathic RLS/WED. The average age of symptom onset was 10.96 years. The severity was moderate in the most of the cases (61.9%) and the course of the disease was intermittent in all of them. Family history was positive in 80%. Abnormal actigraphy (PLMS index >5/h) was present in 80%. Blood level of ferritin was low (<50 ng/ml) in 85%. Excessive daytime sleepiness and school problems affected almost half of them. The presence of RLS/WED symptoms was associated with disrupted sleep, behavioral problems (irritability, aggression, hyperactivity), attention deficit and lowered mood. No correlation between RLS/WED and attention deficit hyperactivity disorder (ADHD), nocturnal enuresis or primary headaches was found. Thirty eight percent of the patients sought medical help, but none of them obtained proper diagnosis nor treatment of RLS/WED. CONCLUSIONS: In this study restless legs syndrome affected 1% of Polish teenagers, in the majority of cases was idiopathic and associated with positive family history. It affected sleep and everyday functioning. Neurological consultation is essential to avoid false positive diagnoses of RLS/WED in teenagers.

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.

Long-Term Follow-Up with Video of a Patient with Deafness-Dystonia Syndrome Treated with DBS-GPi.

BACKGROUND: The prevalence of deafness-dystonia syndrome (DDS) is relatively low. To our knowledge, only 2 cases of this syndrome treated with deep brain stimulation (DBS) have been reported. OBJECTIVES: We present a patient with DDS of unknown cause, refractory to medical treatment, who has been successfully treated with DBS of the internal globus pallidus (DBS-GPi) and followed up for 4 years. METHODS: A 21-year-old male, with progressive bilateral sensorineural hearing loss since the age of 3, developed dystonic movements at the age of 12. The patient presented with progressive segmental craniocervical dystonia with jaw-opening, tongue protrusion, retrocollis and gradual overflow including upper limb dystonia. Pharmacological therapy was ineffective. At the age of 17, the patient's condition deteriorated with the risk of developing a dystonic state. RESULTS: DBS-GPi implantation resulted in a striking improvement. The Burke-Marsden-Fahn Dystonia Rating Scale (BMFDRS) score improved from 75 points before the surgery to 10 points at 3 months after DBS-GPi implantation. Neurological examination at the age of 21 showed mild dystonic movements, mainly oromandibular dystonia (BMFDRS: 15 points). The clinical phenotype of our patient was consistent with Mohr-Tranebjaerg syndrome (MTS). We performed genetic analysis of the TIMM8A gene (the only gene in which mutations are known to cause MTS), but the result was negative; however, other potentially new mutations have to be considered. CONCLUSIONS: Based on our case with the longest reported follow-up of 4 years and 2 earlier reports, we advise to consider DBS-GPi in patients with DDS with unsatisfactory effect of pharmacological treatment.

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 syndrome of deafness-dystonia: clinical and genetic heterogeneity.

The syndrome of deafness-dystonia is rare and refers to the association of hearing impairment and dystonia when these are dominant features of a disease. Known genetic causes include Mohr-Tranebjaerg syndrome, Woodhouse-Sakati syndrome, and mitochondrial disorders, but the cause frequently remains unidentified. The aim of the current study was to better characterize etiological and clinical aspects of deafness-dystonia syndrome. We evaluated 20 patients with deafness-dystonia syndrome who were seen during the period between 1994 and 2011. The cause was identified in only 7 patients and included methylmalonic aciduria, meningoencephalitis, perinatal hypoxic-ischemic injury, large genomic deletion on chromosome 7q21, translocase of inner mitochondrial membrane 8 homolog A (TIMM8A) mutation (Mohr-Tranebjaerg syndrome), and chromosome 2 open reading frame 37 (C2orf37) mutation (Woodhouse-Sakati syndrome). The age of onset and clinical characteristics in these patients varied, depending on the etiology. In 13 patients, the cause remained unexplained despite extensive work-up. In the group of patients who had unknown etiology, a family history for deafness and/or dystonia was present the majority of patients, suggesting a strong genetic component. Sensory-neural deafness always preceded dystonia. Two clinical patterns of deafness-dystonia syndrome were observed: patients who had an onset in childhood had generalized dystonia (10 of 13 patients) with frequent bulbar involvement, whereas patients who had a dystonia onset in adulthood had segmental dystonia (3 of 13 patients) with the invariable presence of laryngeal dystonia. Deafness-dystonia syndrome is etiologically and clinically heterogeneous, and most patients have an unknown cause. The different age at onset and variable family history suggest a heterogeneous genetic background, possibly including currently unidentified genetic conditions.

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.

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.

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.

Association analysis of the E-selectin 98G > T polymorphism and the risk of childhood ischemic stroke.

Genes related to platelet and arterial endothelial function have been recently considered as independent risk factors for stroke. We aimed to analyze a relationship between the E-selectin 98G > T polymorphism and stroke in children and to observe the transmission of E-selectin alleles from heterozygous parents to their affected children. We studied 59 children after stroke, 112 parents, and 87 healthy children. The E-selectin 98G > T polymorphism was analyzed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The frequency of the 98T allele in patients was almost twofold lower than in controls (5.1% vs. 9.8%, p = 0.145, odds ratios (OR) = 0.49) as well as carriers of the 98T allele (19.5% in controls vs. 8.5% in cases, p = 0.067, OR = 0.38). The G allele of the E-selectin 98G > T polymorphism was more frequently transmitted to the children after stroke compared to the T allele (68% vs. 32%). In conclusion, we did not confirm the relationship between the 98G > T polymorphism of the E-selectin gene and childhood ischemic stroke. There is still a need for further studies.

APOE gene epsilon 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.

[Restless legs syndrome - an underestimated health problem in children]. / Zespol Niespokojnych NOG-niedoceniany Problem Zdrowotny U Dzieci.

Restless legs syndrome (RLS) is one of the most common neurological diseases. Even though there is a large progress in its diagnosis, pathophysiology and treatment, it still remains recognised too rarely. It is elderly people who mostly suffer from restless legs syndrome, but it is established that the disease may begin in childhood. The aim of this study is to present the diagnostic criteria and differential diagnosis in cases of this syndrome, in children. Correct diagnosis of restless legs syndrome is a starting point for epidemiological studies on the incidence of RLS in children.

[Sporadic hemiplegic migraine in a 14-year-old boy--a case report]. / Sporadyczna migrena polowiczoporazna u 14-letniego chlopca--opis przypadku.

Hemiplegic migraine is a specific form of migraine with aura including hemiparesis. It is a rare condition of unclear aetiology. The authors present a case of a 14-year-old boy with persistent foramen ovale, suffering from sporadic hemiplegic migraine. The authors broadly describe the symptoms and types of hemiplegic migraine as well as underlining diagnostic and therapeutic difficulties of the attacks. The patient suffered from recurrent severe headaches, vomiting and co-existing focal neurological symptoms, including alternant hemiparesis. On the basis of the history, thorough clinical observation and numerous accessory investigations a diagnosis of sporadic hemiplegic migraine was established. However, the last attack, with prolonged neurological deficits, was treated as a complication of migraine and defined as persistent aura without infarction. The authors also broadly discuss a differential diagnosis, including other stroke-like incidents, vascular diseases, immunological and mitochondrial disorders that mimic the symptoms and clinical course of sporadic hemiplegic migraine.