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.

Peri-ictal headaches in the paediatric population - prospective study.

INTRODUCTION: The co-occurrence of headache and epilepsy is well-documented in the adult population. The aim of the prospective study was to analyse in the paediatric population the correlations between the types of peri-ictal headaches and types of seizures. Furthermore, an attempt was made to find trends in characteristic features of peri-ictal headaches.Material: A total of 57 children with peri-ictal headache were enrolled in the study. The participants' guardians were asked to keep a diary of the seizure and peri-ictal headache episodes during a 180-day period. During follow-up visits, systematic history regarding peri-ictal headaches was taken. RESULTS: A total of 913 seizure and 325 peri-ictal headache episodes were noted during the study. Post-ictal headaches were most common, occurring in < 1 h after the seizure, lasting minutes to hours and more likely to occur after generalised seizures, whereas pre-ictal headaches occurred 30-240 min before the seizure. In the analysed group, peri-ictal headaches were most often moderate in intensity. Only 30% of patients took analgesic medication, usually to treat post-ictal headaches. CONCLUSION: Peri-ictal headaches are a significant health problem for patients with epilepsy. The most common type are post-ictal headaches, and they are most likely to appear after a generalised seizure.

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.

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.

Lateral petrosectomy with obliteration cavity for spontaneous cerebrospinal otorrhea in children.

PURPOSE: The most common causative factors of CSF otorrhea in children are injuries and congenital abnormalities of the temporal bone. Spontaneous CSF leak as a consequence of congenital temporal bone defects may result in recurrent meningitis. Diagnosis and management of such an entity are particularly difficult in early childhood. MATERIALS AND METHODS: The aim of this study was to investigate clinical features and to discuss possible methods of treatment of spontaneous CSF otorrhea in children. RESULTS: Severe unilateral sensorineural hearing loss or total deafness was found in children with CSF otorrhea. CT and MRI of the temporal bones revealed dehiscences in the walls of the tympanic cavity and defects of the inner ear, which were confirmed intraoperatively. Lateral petrosectomy and closure of the fistula with muscle tissue and fat obliteration cavity were performed. The children remain free of otorrhea and recurrences of meningitis. CONCLUSION: The diagnosis of spontaneous otorrhea in children is based on the severe unilateral sensorineural hearing loss and presence of CSF in the middle ear cavity. It may be successfully treated by means of lateral petrosectomy with obliteration of the vestibule with muscle tissue and tympanic cavity with fat tissue.

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 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.

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.

Thrombomodulin and antibeta2-glycoprotein I in stroke in children.

BACKGROUND: A quantitative systematic review recently discussed the role of thrombomodulin (Thm) and antibeta2-glycoprotein I (beta2-GPI) in cerebral strokes in adults. Little is known about the problem in children. The aim of the study was to see if there is a difference in the values of Thm and beta2-GPI in children with ischemic stroke. MATERIAL/METHODS: Seventy patients were included, comprising 40 children who had had ischemic stroke of unknown etiology hospitalized from January 1995 to December 2005 at the Department of Developmental Neurology, Chair of Neurology Medical University of Gdansk, and 30 healthy volunteers (no autoimmunologic disease or headache in interview). The concentrations of thrombomodulin (Thm) and antibeta2-glycoprotein I (beta2-GPI) in A, M, and G immunoglobulins were determined according to an immunoenzyme method (ELISA). RESULTS: None of the investigated subjects had elevated levels of beta2-GPI. The patients with stroke had significantly higher Thm values than the healthy group. CONCLUSIONS: This finding of elevated levels of thrombomodulin in cases of pediatric cerebral stroke could help in measuring the extent or duration of parenchymal brain injury, or even perhaps response to future therapeutic maneuvers. All these implications may aid not only in the diagnosis and management of acute ischemic stroke, but encourage prophylactic action to prevent probable stroke relapse.

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.

Early intervention and its short-term effect on the temporal organization of fidgety movements.

BACKGROUND: The Prechtl General Movement Assessment (GMA) predicts various neurological and developmental disorders while also documenting therapeutic effects. AIMS: To describe the temporal organization of fidgety general movements in infants with mild to moderate postural asymmetries and/or tonus regulation problems, and to analyze to what extent the temporal organization of fidgety movements will change after physiotherapy. STUDY DESIGN: Repeated measure design. PARTICIPANTS: Twelve infants (five females) with mild to moderate postural asymmetries and/or tonus regulation problems were admitted for an early intervention program. The gestational age ranged from 27 to 40 weeks (Median, 36 weeks; nine infants born preterm) with birth weights ranging from 740 g to 3500 g (Median, 2590 g). MEASURES: Fidgety movements and their temporal organization were measured using the Prechtl GMA at 9 to 19 weeks post term age (Median, 14 weeks) before and after an early motor training procedure. The movements of one of the infants were analysed using a computer-based approach, measuring the mean and standard deviation of quantity of motion, height of motion and width of motion. RESULTS: Seven infants had sporadic fidgety movements, and five had intermittent fidgety movements. None had continual fidgety movements before the intervention was initiated. After intervention, the temporal organization of fidgety movements increased in all infants. The observations of these movements were supported by computer-based analysis. CONCLUSION: The study indicates that early intervention increases the temporal organization of fidgety movements in infants with postural asymmetries and/or tonus regulation problems. The clinical significance of this finding needs to be further evaluated.

[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.

[Antiphospholipid antibodies in children with migraine]. / Przeciwciala antyfosfolipidowe w migrenie u dzieci.

BACKGROUND AND PURPOSE: There are only a few investigations in the literature, that address the occurrence and the role of anticardiolipin antibodies (aCL) in children with migraine. The results of those studies are often contradictory. The aim of the study was to determine if the values of aCL in children with migraine differ from the control group. We tried to assess whether the type of migraine (with aura or without aura) had the influence on those values. MATERIAL AND METHODS: Sixty patients (mean age: 10.9+/-3.3 years), including 30 children with migraine hospitalized from January 2000 to December 2003 in the Department of Developmental Neurology Medical University of Gdansk and 30 healthy children, were studied. The values of aCL in class IgA, IgM and IgG were assessed by the immunoenzymatic method (ELISA test). RESULTS: The values aCL in IgA and IgG class were significantly different between the migraineurs and control group. The mean value of aCL in patients with migraine was 8.7+/-1.27 U/ml, while in the control group--3.81+/-1.74 U/ml. The positive values of aCL in class IgG were found in 11 (37%) children with migraine, and positive values of aCL in class IgM were noted in 6 (20%) cases in the same group. The type of migraine had no influence on the values of aCL. CONCLUSIONS: Children with migraine present with the higher values of aCL than the control group. The mean values of aCL were within the normal range, therefore their role in pathogenesis of migraine remains unclear. The further observation is needed to assess the reliable role of higher values of aCL in pathophysiology of vascular disorders.

[Epileptic seizures in the vascular malformations in children]. / Napady padaczkowe w wadach naczyniowych mózgu u dzieci.

OBJECTIVES: Cerebral vascular anomalies have been rare pathology of the brain in childhood. The most frequent clinical symptoms of them are: intracerebral hemorrhage, subarachnoid hemorrhage, headache, neurological deficits and epilepsy. AIM: Because of very few reports about epilepsy in cerebral vascular anomalies in children the authors continued studies in this subject. MATERIAL AND METHODS: The subject of the study were 20 patients in the age between 5 to 15 years with cerebral vascular anomalies hospitalized in the Department of Developmental Neurology Medical University of Gdansk in the years 1980-2001. The clinical state and CT, MRI, angiography and EEG recordings were evaluated in all the patients. Arteriovenous malformations (AVM) were diagnosed in 13 (65%), in 5--angioma cavernous (25%), in 2--aneurysms (10%). RESULTS: In 4 children epilepsy was the first symptom of cerebrovascular anomalies. Epileptic seizures were observed in 4 patients in the acute stage of the disease. In 6 children epilepsy was the consequence of arteriovenous malformation. CONCLUSION: Epilepsy occurred in 50% of children with vascular malformations. Among cerebrovascular anomalies, arteriovenous malformations are the most frequent cause of epilepsy in the group of examined children.

[Headache occurrence and assessment of regional blood flow after brain concussion in children]. / Wystepowanie bólów glowy oraz zmian regionalnego przeplywu mózgowego krwi po wstrzasnieniu mózgu u dzieci.

BACKGROUND AND PURPOSE: Headaches which can last for many months and even years belong to the most frequent consequences of closed head injuries in children. The method which makes it possible to demonstrate the presence and extent of the nervous tissue damage caused by trauma is the regional cerebral blood flow (rCBF) evaluation with single photon emission computerized tomography (SPECT). In the present study the regional cerebral blood flow (rCBF) was assessed 10-15 days after trauma, 3 months and one year in cases of brain concussion. We tried to establish whether there was a correlation between changes in rCBF and the occurrence of posttraumatic headache. MATERIAL AND METHODS: SPECT was applied in 32 children, aged 6-16, 10-15 days, and then 3 and 12 months after brain concussion. In all children no changes were found in CT and MRI examinations. RESULTS: In the studied group in the early period after trauma, blood flow impairment was found in 21 children, mostly in frontal areas. One year after trauma the rCBF improved in 11 children, in 10 cases the pattern was normal. In a group of 4 children with headache one year after brain concussion, three of them still presented the impairment of blood flow. CONCLUSIONS: SPECT shows a great sensitivity and usefulness in the assessment of consequences of head trauma and it can explain some posttraumatic complaints in children.