Wojciech Kułak

Metabolite alterations in autistic children: a 1H MR spectroscopy study

PURPOSE The purpose of this study was to assess the role of proton magnetic resonance spectroscopy (1H MRS) in the detection of changes in cerebral metabolite levels in autistic children. MATERIAL AND METHODS Study group consisted of 12 children, aged 8-15 years, who were under the care of Pediatric Neurology Department and Pediatric Rehabilitation Department of Medical University of Bialystok. The diagnosis of autism was established by neurologist, psychiatrist and psychologist in every case. All patients matched the clinical criteria of the disease according to International Statistical Classification of Diseases and Related Health Problems (ICD-10). The control group included 16 healthy children aged 7-17. 1H MRS was performed with a single-voxel method (TE-36, TR-1500, NEX-192). The volume of interest (VOI) was located in the frontal lobe regions, separately on each side. RESULTS We showed lower N-acetylaspartate/creatine (NAA/Cr), γ-aminobutyric acid /creatine (GABA/Cr) and glutamate/creatine (Glx/Cr) in the frontal lobes in the study group comparing with healthy controls. The ratio of myoinositol/creatine (mI/Cr) was increased in autistic children. No differences in choline/creatine (Cho/Cr) ratio in study group and controls were found. There was a correlation between age and NAA/Cr in autistic children (R=0.593 p=0.041). No significant differences in metabolite ratios between right and left hemisphere in ASD and controls were found. CONCLUSIONS (1)H MRS can provide important information regarding abnormal brain metabolism. Differences in NAA/Cr, GABA/Cr, Glx/Cr and mI/Cr may contribute to the pathogenesis of autism.

Spastic Cerebral Palsy: Clinical Magnetic Resonance Imaging Correlation of 129 Children

A prospective study was undertaken of 129 children with spastic cerebral palsy to clarify the relationship between magnetic resonance imaging (MRI) findings and clinical features of cerebral palsy. Low birth weight, asphyxia, prematurity, seizures, mental development, Gross Motor Function Classification System, and MRI findings were analyzed. Significant abnormalities relevant to the cerebral palsy were evident on imaging in 123 (95.3%). A similar percentage of MRI abnormalities were detected in the groups, 45 (100%) in patients with tetraplegic cerebral palsy, 37 (92.5%) in children with diplegic cerebral palsy, and 42 (95.4%) with hemiplegic cerebral palsy. Periventricular leukomalacia was detected more frequently in the children with spastic diplegia than in the patients with tetraplegia or hemiplegia. Cerebral atrophy was found more often in the tetraplegic group compared to the diplegic patients. Porencephalic cysts were detected more frequently in children with spastic hemiplegia. Congenital brain anomalies were found in a higher proportion in tetraplegic children. Significant correlations between the MRI findings and Gross Motor Function Classification System in the diplegic and tetraplegic patients were found. No correlations between the MRI results and risk factors for cerebral palsy in the tetraplegic patients were noted. Early detection of brain abnormalities in children with cerebral palsy may help in the prognosis and in the initiation of appropriate therapy

Neurophysiologic and neuroimaging studies of brain plasticity in children with spastic cerebral palsy.

Patients with cerebral palsy (CP) may have some problems other than this motor impairment: mental retardation, epilepsy and sensory disturbance. Healthy children and children with CP have an enhanced capacity for learning and memory compared to adults. There are few tools for brain plasticity investigations. The utility of the neurophysiologic and MRI techniques in the determination of brain reorganization and repair in patients with cerebral palsy is described. The authors discuss their results of quantitative EEG and spectroscopy MRI studies in children with CP. Quantitative EEG and spectroscopy MRI can be useful tools in the determination of these processes in children with CP.

Evaluation of the influence of antiepileptic therapy on antioxidant enzyme activity and lipid peroxidation in erythrocytes of children with epilepsy.

The aim of this study was to evaluate the influence of antiepileptic therapy on antioxidant enzyme activity and lipid peroxidation in the erythrocytes of children with epilepsy. For this purpose, the activity of superoxide dismutase, glutathione peroxidase, and glutathione reductase and the malondialdehyde concentration in 61 healthy children and 90 children with epilepsy were measured. The activities of all of these enzymes were insignificantly higher, whereas the malondialdehyde concentration was significantly lower in the patients treated with carbamazepine monotherapy. In patients treated with valproate monotherapy, the activities of all enzymes were insignificantly lower, whereas the malondialdehyde concentration was insignificantly higher. In patients treated with polytherapy, the activity of superoxide dismutase was insignificantly lower, whereas the activity of glutathione peroxidase and glutathione reductase was insignificantly higher and the malondialdehyde concentration was lower. There were differences in glutathione reductase activity between the valproate monotherapy group and both the carbamazepine monotherapy and polytherapy groups and in malondialdehyde concentrations between the carbamazepine and valproate groups. The results indicate that the oxidant-antioxidant balance in children with epilepsy is modified by antiepileptic therapy. (J Child Neurol 2006;21:558–562; DOI 10.2310/7010.2006.00115).

Clinical and EEG Features of Epilepsy in Children and Adolescents in Down Syndrome

Epilepsy is rarely considered as a major component of Down syndrome. We evaluated the prevalence of epileptic seizures in 252 (97 girls and 155 boys) children and adolescents with Down syndrome evaluated at Department of Pediatric Neurology between 1994 and 2007. Results showed that 15 (6%) patients had epileptic seizures: 8 partial seizures; 1 infantile spasms, 1 Lennox-Gastaut syndrome, and 5 generalized tonic-clonic seizures. Electroencephalography was performed on all patients with Down syndrome. Focal changes, spikes, generalized slowing, and hypsarrhythmia were recorded. The electroencephalography was found to be abnormal in Down syndrome with epilepsy in 100%. Almost 60% of patients with Down syndrome and epilepsy had seizures, but 40% of the patients were seizures-free. Quantitative electroencephalography analysis revealed significant differences between children with Down syndrome and the control groups in the alpha, delta, and beta rhythms. Our findings are in accordance with other reports.

Dysphagia in children with infantile cerebral palsy

PURPOSE Dysphagia is a significant health problem in children with infantile cerebral palsy (ICP), but not frequently discussed in the literature. The study objective was to analyse dysphagia symptoms in children with a pyramidal form of ICP, including the oral and pharyngeal phases of deglutition and dysarthria severity. We searched for a correlation between dysphagia severity and ICP type, mental development and occurrence of epilepsy. MATERIAL AND METHODS A total of 67 children with a pyramidal form of infantile cerebral palsy were studied. Data were obtained based on case history elicited from the mothers, analysis of medical and psychological documentation, and logopaedic examination, including an examination of the action of swallowing. RESULTS Dysphagia symptoms were found in 41 (61%) studied children, most frequently referring only to the oral phase (25 children), with concomitant mild and moderate dysarthria. Oral and pharyngeal dysfunctions were observed in 14 children and coexisted with more pronounced dysarthria symptoms. The most severe disorders were mainly found in the pharyngeal phase in 2 children. A statistically significant correlation was noted between the severity of dysphagia symptoms and the ICP type (p<0.044) and mental development (p<0.00002). CONCLUSIONS Swallowing dysfunctions occur in the majority of children (>50%) with ICP. More serious disorders involving the oral and pharyngeal phases mainly affect children with tetraplegia and profound mental impairment. These disorders continue from early infancy through childhood and adolescence and improvement has been mainly observed when only the oral phase of swallowing is affected. These are always accompanied by dysarthria symptoms, which are especially severe when dysphagia involves the oral and pharyngeal phases. Early assessment and stimulation of the swallowing function should be a common element in the rehabilitation and care of children with ICP.

Amino acid metabolic processes in the temporal lobes assessed by proton magnetic resonance spectroscopy (1Η MRS) in children with Down syndrome

Down syndrome (DS), or trisomy 21, is one of the most common autosomal mutations. The overexpression of the β-amyloid precursor protein gene, located on chromosome 21, causes an increased production of the specific amyloid. The current study is a continuation of our earlier investigations relating to the profile of metabolic changes in the frontal lobes of DS patients as assessed by proton magnetic resonance spectroscopy ((1)H MRS). The aims of the study were the morphological assessment of the brain using magnetic resonance imaging (MRI) and the evaluation of metabolic disorders of the temporal lobes using (1)H MRS in DS children. The study group included 20 children with DS aged 3-15 years and treated in the Department of Pediatric Neurology and Rehabilitation, Medical University of Białystok. The control group included healthy children (n = 20). MRI scans of the heads of DS children were performed using a 1.5 T MR scanner under standard conditions. (1)H MRS investigations were also carried out to assess metabolic changes in the temporal lobes. Metabolites, such as N-acetylaspartate (NAA), glutamate-glutamine complex (Glx), choline (Cho), myoinositol (mI) and γ-aminobutyric acid (GABA), were determined in both temporal lobes with reference to the internal marker creatine (Cr). Results were compared with the control group.We found a statistically significant decrease in NAA/Cr, Cho/Cr, mI/Cr and GABA/Cr ratios. The Glx/Cr ratio in both temporal lobes of DS patients did not differ from the control group. Our results indicate metabolic neurotransmitter disorders in the central nervous system in children with DS.

Anti-inflammatory plasma cytokines in children and adolescents with migraine headaches

Studies have shown fluctuations of cytokine levels in patients with migraine headaches; however, further studies are needed to verify these results. Our previous studies suggest increased levels of pro-inflammatory cytokines, such as IL-1alpha, sTNF-RI and TNF-alpha, in children with migraine headaches. In this study, we analyzed anti-inflammatory cytokines interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13) in plasma from children and adolescents with migraine and tension-type headaches during the interictal period. The study group consisted of 35 children and adolescents between 8-18 years old, suffering from migraine headaches with or without aura. The control group consisted of 33 patients suffering from episodic tension-type headaches. IL-4 was detected in 17.1% of patients with migraine headaches and in 28.6% of patients with tension-type headaches. IL-13 was detected in 17.1% of patients with migraine headaches and in 15.2% of patients with tension-type headaches. IL-10 was only detected in 3 of 68 (4.4%) patients. Any significant correlations between measurable cytokine levels and age, gender, aura, duration of disease, frequency and severity of headaches were determined. Any significant fluctuations of selected anti-inflammatory cytokines during the headache-free period in children with migraine and tension-type headaches have been found, immune dysfunction in migraineurs could not be excluded.

Risk factors for cerebral palsy in term birth infants

PURPOSE The aim of this study was to identify the antenatal, intrapartum and neonatal risk factors in term birth infants for cerebral palsy (CP) among babies in a hospital-based study. MATERIALS AND METHODS The medical records of children with cerebral palsy referred to our Pediatric Rehabilitation Department in Bialystok were reviewed. Antenatal, intrapartum, and neonatal events were compared among 213 children with CP and 280 controls in a retrospective study. We studied live births >36 weeks gestation born between January 1, 1990, and December 31, 2005. RESULTS Fifty-seven percent of the infants with CP were male. Spastic tetraplegia 78 (36.61%) and spastic hemiplegia 65 (30.51%) were the dominant types of CP. Factors associated with an increased risk of CP identified as antenatal and intrapartum risk factors were pre-eclampsia, abruptio placenta, and placenta previa. Birth asphyxia occurred significantly more often (p<0.001) in children with CP compared to controls. In the neonatal period, respiratory distress syndrome, meningitis and neonatal seizures were associated with an increased incidence of CP. CONCLUSION Our findings confirm that several antenatal, intrapartum and neonatal risk factors for CP in term birth infants contribute to the etiology of CP.

Duchenne muscular dystrophy: current cell therapies:

Duchenne muscular dystrophy is a genetically determined X-linked disease and the most common, progressive pediatric muscle disorder. For decades, research has been conducted to find an effective therapy. This review presents current therapeutic methods for Duchenne muscular dystrophy, based on scientific articles in English published mainly in the period 2000 to 2014. We used the PubMed database to identify and review the most important studies. An analysis of contemporary studies of stem cell therapy and the use of granulocyte colony-stimulating factor (G-CSF) in muscular dystrophy was performed.