Malformations of cortical development in children : clinical manifestation, neuroimaging and neuropathology in selected cases

Cerebral cortical development can be divided into three steps: cellular proliferation, neuronal migration and organization. Based on known pathologic, genetic and neuroimaging features a classification for malformations of cortical development was proposed by Barkovich in 2001, and updated in 2005. Malformations of cerebral cortex development (MCCD) often demonstrate epileptic seizures and delay in psychomotor development. About 20-40% of children with epilepsy are drug-resistant and there is a large paediatric population requiring epilepsy surgery operations. In our work we performed clinical analysis of 68 children with MCCD treated in our hospital between 2000 and 2006. In our work to consider the type of MCCD we used the updated classification scheme proposed by Barkovich et al. We analyzed epilepsy, gestational and perinatal history, initial symptoms, time to establishing full diagnosis and neurodevelopmental/IQ status. In our results we found that despite similar clinical manifestation neuropathological basis could be significantly different, and vice versa: children with nearly identical neuropathological findings could have completely different neurological and radiological symptoms. Children with drug-resistant epilepsy are potential candidates for neurosurgical treatment; especially lesionectomies in such cases could be very promising in terms of epilepsy management and quality of life as well

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

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. 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. 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. 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

Polimorfizm C242T genu kodującego cytochrom b-245 alfa nie jest związany z udarem niedokrwiennym mózgu u dzieci : analiza wewnątrzrodzinna i badanie kliniczno-kontrolne

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 in - dividuals: 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 childre

Polimorfizm C242T genu kodującego cytohrom b-245 alfa nie jest związany z udarem niedokrwiennym mózgu u dzieci: analiza wewnątrzrodzinna i badanie kliniczno-kontrolne

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.Wstęp i cel pracy Reaktywne formy tlenu pełnią istotną funkcję zarówno w fizjologii, jak i patologii tętnic mózgowych, także w patogenezie udaru niedokrwiennego mózgu. Gen cytochromu b-245 alfa (gen CYBA) koduje lekki łańcuch cytochromu b-245 (białko p22phox), kluczowy składnik oksydaz NAD(P)H, najważniejszego źródła anionorodnika ponadtlenkowego w obrębie tętnic mózgowych. W niniejszej pracy, poszukując genetycznych czynników ryzyka predysponujących do udaru mózgu u dzieci, oceniano możliwe związki pomiędzy polimorfizmem C242T genu CYBA i chorobą. Materiał i metody W badaniu wzięło udział 238 osób: 70 dzieci z udarem niedokrwiennym mózgu, 118 ich biologicznych rodziców oraz 50 dzieci bez żadnych objawów udaru. Polimorfizm C242T genu CYBA genotypowano metodą polimorfizmu długości fragmentów restrykcyjnych w reakcji łańcuchowej polimerazy. Do oceny możliwych związków pomiędzy polimorfizmem i udarem zastosowano dwie niezależne metody: wewnątrzrodzinny test transmisji i badanie kliniczno-kontrolne. Wyniki Allel C242 był częściej przekazywany chorym dzieciom przez heterozygotycznych rodziców niż allel 242T (62,2% w porównaniu z 37,8%), jednak obserwowane częstości nie odbiegały znamiennie od oczekiwanych (p = 0,10). Nie wykazano także znaczących różnic w rozkładzie alleli i genotypów pomiędzy pacjentami i dziećmi z grupy kontrolnej (pacjenci: CC – 50,0%, CT – 38,6%, TT – 11,4%; grupa kontrolna: CC – 52,0%, CT – 36,0%, TT – 12,0%). Wnioski Wyniki badań nie wykazały, aby polimorfizm C242T genu CYBA był czynnikiem ryzyka udaru niedokrwiennego u dzieci

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

Circadian Profile of Salivary Melatonin Secretion in Hypoxic Ischemic Encephalopathy

Purpose. In the present study, the salivary melatonin secretion in the hypoxic ischemic encephalopathy (HIE) children was measured. The logit model was fitted to the data to obtain the salivary dim light melatonin onsets (DLMOs), and the results were compared with the values estimated from the classic threshold method with a linear interpolation and those previously published for the blood measurements. Materials and Methods. 9 patients suffering from HIE aged from 65 to 80 months were included in the study. The melatonin levels were assessed by a radioimmunoassay (RIA). The diurnal melatonin secretion was estimated using a nonlinear least squares method. Student’s t-test and the Mann–Whitney U test were used for the comparisons of the obtained parameters. Results. The circadian profiles of the melatonin secretion for both calculation methods do not differ statistically. The DLMO parameters obtained in the blood and saliva samples in children with hypoxic is chemic encephalopathy were similar

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

Epilepsy in selected neurometabolic diseases

W grupie chorób neurometabolicznych padaczka stanowi bardzo częsty objaw. Ponad 268 wrodzonych wad metabolizmu w obrazie klinicznym zawiera napady padaczkowe. W przypadku drgawek noworodkowych wrodzone wady metabolizmu (wwm) można zdiagnozować u 1,1–7,4% pacjentów. Według innych autorów częstość występowania padaczki w chorobach neurometabolicznych wynosi około 7%. Wczesna diagnoza poddających się leczeniu wrodzonych wad metabolizmu przebiegających z padaczką jest niezwykle istotna. Autorzy dokonują przeglądu wiedzy na temat wybranych, poddających się leczeniu wwm stanowiących przyczynę padaczki.In the group of neurometabolic diseases epilepsy is a common feature. Over 268 inborn errors of metabolism may cover epileptic seizures in their clinical picture. In the case of newborn seizures, inborn errors of metablism may be diagnosed in 1,1–7,4% of patients. According to other authors, incidence of epilepsy in neurometabolic disorders is around 7%. Early diagnosis of epilepsy in the course of treatable metabolic diseases is crucial. The authors have reviewed the selected treatable metabolic conditions as a cause of epilepsy

Somatic disorders in persons with autism

Zaburzenia autystyczne mogą współwystępować z licznymi zaburze-niami, mogą również towarzyszyć różnorodnym zespołom genetycznym. Autyzm bywa jednym z objawów ciężkiej wrodzonej czy nabytej patologii. Osoby auty-styczne borykają się z licznymi przeszkodami somatycznymi utrudniającymi co-dzienne funkcjonowanie, wśród których należy wymienić: problemy żywieniowe oraz zaburzenia układu odpornościowego. Obraz somatyczny pacjenta wpływa na proces terapeutyczny, jednak nie może stanowić przyczyny rezygnacji z pracy z osobą z autyzmem.Autistic disorders may co-occur with numerous other dysfunctions and accompany various genetic syndromes. Autism may be a symptom of a severe inborn or acquired disorders. Autistic persons have to cope with many somatic obstacles impeding their day-to-day functioning, including nutritional issues and immune deficiencies. A patient’s somatic condition affects the therapeutic process, but it must not be the reason for abandoning work with a person with autism

Neuroimaging of Basal Ganglia in Neurometabolic Diseases in Children

Diseases primarily affecting the basal ganglia in children result in characteristic disturbances of movement and muscle tone. Both experimental and clinical evidence indicates that the basal ganglia also play a role in higher mental states. The basal ganglia can be affected by neurometabolic, degenerative diseases or other conditions from which they must be differentiated. Neuroradiological findings in basal ganglia diseases are also known. However, they may be similar in different diseases. Their assessment in children may require repeated MRI examinations depending on the stage of brain development (mainly the level of myelination). A large spectrum of pathological changes in the basal ganglia in many diseases is caused by their vulnerability to metabolic abnormalities and chemical or ischemic trauma. The diagnosis is usually established by correlation of clinical and radiological findings. Neuroimaging of basal ganglia in neurometabolic diseases is helpful in early diagnosis and monitoring of changes for optimal therapy. This review focuses on neuroimaging of basal ganglia and its role in the differential diagnosis of inborn errors of metabolism