A volumetric magnetic resonance imaging study of brain structures in children with Down syndrome.

BACKGROUND AND PURPOSE: Down syndrome (DS) is the most common genetic cause of mental retardation with deficits in language and memory. Mental retardation of varying degrees is the most consistent feature of DS. The objective of this study was to use high-resolution magnetic resonance imaging (MRI) techniques to investigate the volumes of the hippocampus, amygdala, and temporal and frontal lobes in children with DS compared with healthy children. MATERIAL AND METHODS: MRI of 49 patients was reviewed prospectively. The study included 23 children with DS (9 girls and 14 boys, mean age 6.7 ± 3.7 years) and 26 healthy children (11 girls and 15 boys, mean age 8.3 ± 2.4 years). Volumes of the right and left hippocampus, the right and left amygdala, temporal and frontal lobes and the total brain volume were measured by a radiologist who was unaware of the diagnosis. RESULTS: Total brain volume in children with DS was significantly lower compared with controls. It was associated with significantly lower volume of the frontal and temporal lobes. Children with DS had a significantly smaller right and left hippocampus volume and a significantly smaller right and left amygdala volume than did the control group. We also found a negative correlation between mental retardation and volume of the right hippocampus. CONCLUSIONS: The presence of these abnormalities from an early age contributes to the specific cognitive and developmental deficits seen in children with DS.

Levetiracetam protects hippocampal neurons in culture against hypoxia-induced injury.

Many experimental studies indicate that some antiepileptic drugs possess neuroprotective properties in varied models of neuronal injury. Levetiracetam is a second-generation antiepileptic drug with a novel mechanism of action. In the present study, we evaluated the putative neuroprotective effect of levetiracetam on primary hippocampal cultures at seven day in vitro. Cell death was induced by incubation of neural cultures in hypoxic conditions over 24 hours. Neuronal injury was assessed by morphometric investigation of death/total ratio of neurons in light microscopy using Trypan blue staining and by evaluation of lactate dehydrogenase (LDH) release in the culture medium. Our results indicate that pre-conditioning of hippocampal cultures with high concentrations of levetiracetam (100 µM and 300 µM) protects neurons against hypoxia-induced death. Two-fold higher number of neurons remained viable as compared to control cultures without drug. Lack of neuroprotective action of the drug on hippocampal neural cultures was observed, when a low concentration (10 µM) of levetiracetam was used.

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.

Somatosensory evoked potentials in children with migraine with aura and without aura.

BACKGROUND: The Interictal abnormalities of cerebral information processing in migraine were found by studying different modality-specific evoked and event related potentials, mostly visual and auditory. In this study we focused on short-latency somatosensory evoked potentials (SEP) in children and adolescents suffering from migraine with and without aura. MATERIAL AND METHODS: The study group consisted 111 of children and adolescents at the age of 7-18 years: 27 of them suffered from migraine with aura, 36 of them suffered from migraine without aura, 48 subjects have episodic tension-type headache. SEPs was performed interictally at least two days after the last headache attack. RESULTS: There were no significant differences in the latency averages of SEP components between all migraneurs and tension-type headache subjects. However, N9 and N13 latency averages were significantly shorter in migraine without aura group compared with migraine with aura and tensiom type headaches. We did not find any significant correlations for either headache type between evoked potentials parametrs and illness duration, unilateral localisation of pain, migraine in family and aura. CONCLUSIONS: In concert with similar studies in adult migraineurs, our findings showed no disturbances of somatosensory information processing in children with migraine with aura and without aura. The diagnosis of migraine in children actually remains predominantly based on medical history. However, electrophysiological techniques allow the study of some of the structures in vivo and enlarge our knowledge on controversial aspects of migraine pathophysiology.

Anti-inflammatory plasma cytokines in children and adolescents with Down syndrome.

Cytokines participate in many physiological processes including the regulation of immune and inflammatory responses. Production of some important cytokines in children with Down syndrome (DS) is depressed or increased. In this study we analysed the selected anti- inflammatory cytokines: interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13) in plasma of children and adolescents with DS. The study group consisted of 20 patients with Down syndrome and 33 healthy subjects at the age of 5-17 years. Levels of: IL-4, IL-10 and IL-13 in plasma samples were determined by specific enzyme- linked immunosorbent assay (ELISA) techniques according to manufacturer's instructions. IL-4 was detectable in 25% subjects with Down syndrome and in 28.6% healthy subjects. IL-13 was detectable in 15% patients with Down syndrome and in 15.2% healthy subjects, respectively. IL-10 was detectable in 1 of 20 patients with Down syndrome and in 2 of 33 healthy subjects only. No significant correlations between measurable cytokine levels and age and gender were found. No significant increased concentration of selected anti- inflammatory cytokines were detected.

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

Down syndrome (DS), or trisomy 21, is one of the most common autosomal mutations. The overexpression of the ß-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 Bialystok. 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.

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.

An age and gender dependency of metabolite concentrations in basal ganglia in children with spastic diplegia: proton magnetic resonance spectroscopy study.

We determined metabolite profile in spastic diplegic children compared to controls in left basal ganglia of brain in using proton magnetic resonance spectroscopy in correlation with age and gender. Twenty-four patients with spastic diplegia and twenty-six healthy children were examined. The relative concentrations of N-acetylaspartate, choline, and myoinositol were measured in relation to creatine and different combinations of metabolites within 8-cm(3) brain voxel. Children with spastic diplegia showed reduced ratios of N-acetylaspartate/creatine, N-acetylaspartate/ choline, and N-acetylaspartate/myoinositol in the basal ganglia compared to the control group. Patients and controls subjects demonstrated a significant age-dependent increase in N-acetylaspartate/creatine, N-acetylaspartate/choline in the basal ganglia. No gender-dependent difference was shown in children with cerebral palsy for all tested metabolite ratios. Gender-related differences because of increased ratio N-acetylaspartate/choline in girls in controls were detected. These results indicate that maturation of brain exists in cerebral palsy and healthy children to a higher degree in healthy children.

Serum and intraerythrocyte antioxidant enzymes and lipid peroxides in children with migraine.

The oxidant-antioxidant balance disorders underlie a number of acute and chronic diseases of the central nervous system (CNS). It is believed that oxidative stress plays a role in the pathogenesis of migraine. The study objective was to assess the processes of lipid peroxidation with malondialdehyde (MDA) as its major indicator and to determine the activities of antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-R) in the serum and erythrocytes of patients at developmental age with migraine with and without aura. The study group consisted of 34 patients at the age of 10-18 years (mean +/- standard deviation: 14.04 +/- 2.29 years), suffering from migraine. The control group included 38 patients, aged 4-17 years (mean age 12.11 +/- 3.46). MDA concentration and activities of SOD, GSH-Px and GSSG-R were determined in serum and erythrocytes of all the patients. In the migraine group, the MDA levels in serum and erythrocytes were statistically significantly lower than in control subjects (p < 0.001). In the migraine group, serum GSH-Px activity was significantly higher (p < 0.05). The GSSG-R activity in the erythrocytes of migraine children was significantly higher compared to controls (p < 0.001). SOD activity was decreased and GSH-Px was increased (non-significantly) in erythrocytes of migraineurs. Our results confirm the disturbances of lipid peroxidation processes in migraine and suggest the activation of antioxidant mechanisms. Its important indicator seems to be the increase in the GSSG-R activity in the erythrocytes and the GSH-Px activity in serum between migraine attacks. Further studies are necessary.

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

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.

Metabolite profile in the basal ganglia of children with cerebral palsy: a proton magnetic resonance spectroscopy study.

This prospective study determined metabolite profile in the left and right basal ganglia of children with spastic cerebral palsy (CP) compared with children without disabilities, by using proton magnetic resonance spectroscopy (1HMRS). Twenty-three patients with spastic CP (12 males, 11 females; mean age 11y 9mo [SD 4y 2mo], range 4-17y) were examined. Twenty children had spastic diplegia and three had quadriplegia. Twenty-four normally developing children (13 females, 11 males; mean age 10y 3mo [SD 4y 8mo], range 4-17y) served as a comparison group. The relative concentrations of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), and gamma-aminobutyric acid (GABA) were measured relative to creatine (Cr) and different combinations of metabolites within 8cm3 brain voxels. Children with CP showed reduced ratios of NAA:Cr, NAA:Cho, NAA:mI, and GABA:Cr in the basal ganglia relative to a matched comparison group. Patients demonstrated a significant age-dependent increase in NAA:Cr and NAA:Cho in the basal ganglia. No sex-dependent difference was shown in children with CP nor in the comparison group for all tested metabolite ratios. Significant correlation between Apgar score and ratio of mI:Cr in the group with CP was found. None of the tested metabolite ratios were correlated with the severity scale of CP in children with CP. NAA:Cr ratios were negatively correlated with learning disability in patients with CP. Results indicate the association of the metabolite ratios in basal ganglia with learning disability.

A comparative study of vigabatrin vs. carbamazepine in monotherapy of newly diagnosed partial seizures in children.

Carbamazepine (CBZ) is a drug of choice for the treatment of simple or complex partial seizures and secondary generalized seizures in adults and children. Vigabatrin (VGB) is a relatively new second line antiepileptic drug and was first registered for use in Poland more than ten years ago. Few reports have been published on the comparison of efficacy of VGB in children with epilepsy. The objective of this study is to evaluate the safety, efficacy and EEG effects of initial VGB monotherapy compared with initial CBZ monotherapy in children with newly diagnosed epilepsy. We present results of a prospective, outpatient and open study carried out in the University Hospital Center in Bialystok. Twenty-six children with partial epilepsy treated with VGB and 28 patients treated with CBZ were studied. The evaluation of the efficacy of the two drugs did not reveal any significant differences. Very good (reduction > 75%) seizure control was achieved in 22 out of 26 patients (84.6%) in the VGB group. One patient had a 50-75% decrease of seizures (good effect), similarly one child had a 25-50% reduction of seizures (mild effect). In two patients, we observed increased seizures (myoclonic jerks). Very good seizure control was achieved in 17 out of 28 patients (60.7%) in the CBZ group. Good seizure control was achieved in 5 out of 28 patients (17.8%) and mild control was seen in two children. No improvement was observed in 4 (14%) of the patients. The EEG background activity was improved in VGB-treated patients. No effect on the EEG background activity was observed in CBZ-treated children. VGB seems to be a safe and effective antiepileptic drug as primary monotherapy for epilepsy in children with similar proportion of side effects as CBZ.

A comparison of spastic diplegic and tetraplegic cerebral palsy.

The aim of this study was to compare spastic diplegic and tetraplegic cerebral palsy. Thirty-eight children had spastic diplegic cerebral palsy and 48 spastic tetraplegic cerebral palsy. Risk factors of cerebral palsy, seizures, severity of cerebral palsy, electroencephalogram, and magnetic resonance imaging findings were analyzed. Gestational history, low birth weight, and perinatal pathologies were present in similar percentages in both groups. Lower values of the Apgar score were recorded more often in the tetraplegic cerebral palsy group than the diplegic group. The children with spastic diplegia were classified more frequently into levels I and II of the Gross Motor Function Classification System, but patients with spastic tetraplegia were classified more frequently into levels IV and V. Similarly, mental retardation was observed more frequently in the patients with spastic tetraplegia. In magnetic resonance imaging, periventricular leukomalacia was detected in a higher proportion of children with spastic diplegia than in patients with tetraplegia. Cerebral atrophy occurred more frequently in the tetraplegic group compared with diplegic patients. Twenty-four (50.0%) children with spastic tetraplegia had epilepsy compared with six children with spastic diplegia. The incidence of intractable epilepsy was higher in the tetraplegic patients than in the children with spastic diplegia.

A multicenter, placebo-controlled, double-blind study of efficacy of a new form of carbamazepine (Carbatrol) in refractory epileptic patients.

Carbatrol (CBR) is a new multiple-unit, sustained-release dosage form of carbamazepine (CBZ) developed by Pharmavene. We present a multicenter, outpatient, randomized, double-blind parallel group study (No PI 101) carried out in two centers in Poland. CBR was evaluated in 47 patients with uncontrolled partial onset seizures. During the 28-day baseline period, patients were required to have at least two seizures and to take CBZ at a therapeutic level, a second antiepileptic drug was allowed but not valproic acid (VPA ). Patients were randomized to VPA or to CBR (dosages 800, 1200, 1600 mg/day). Criteria for escape relative to baseline were: two-fold increase in monthly seizure frequency, two-fold increase in 2-day seizure frequency, two-fold increase in weekly seizure frequency, single generalized tonic-clonic seizure (GTCs) if none occurred during baseline or prolongation of GTCs. The primary efficacy variable was the number of patients escaping in each treatment group. Nineteen patients on VPAand 7 on CBR met escape criteria. CBR adverse experiences were all mild or moderate in severity. CBR therapy was effective in the treatment of partial complex seizures with or without generalization.

[Auditory cognitive event-related potentials in migraine with and without aura in children and adolescents]. / Sluchowe potencjaly zwiazane z wydarzeniem poznawczym w migrenie z aura i bez aury u dzieci i mlodziezy.

BACKGROUND AND PURPOSE: Cognitive Event-Related Potentials (CERP) reflect sensory information processing: cognitive function and early memory. Studies of CERP in adult migraneurs yielded contradictory results. The aim of our study was to evaluate CERP in children and adolescents with migraine with and without aura during the interictal period. MATERIAL AND METHODS: The study was carried out on 111 children aged 7-18 years (mean 12.92 (2.78) with idiopathic attack headaches. In this group migraine with aura (MA) was diagnosed in 27 patients, migraine without aura (MO) in 36 children and episodic tension-type (TH) headaches in 48 patients. RESULTS: The latencies N2 and P3 were significantly longer (p < 0.05 and p < 0.01, respectively) in the group of all migraneurs (MA + MO, n = 63) as compared with the TH group. In the MO group not only N2 and P3 latency, but also P2 latency (p < 0.05) were longer, if particular types of migraine were compared with tension-type headaches. There were no statistically significant differences between mean latencies in MA and TH groups. Analyzing CERP amplitudes, the N1/P2 amplitude was significantly higher in MO patients than in the TH group only. We found longer P2, N2 and P3 latencies and higher N1/P2 amplitude in MO patients in comparison with MA patients. We found correlation between P3 latency and the age of patients with migraine. There were no statistically significant correlations for either headache type between CERP parameters and illness duration, sex of patients and unilateral localisation of headache. CONCLUSIONS: The CERP parameter changes in children with migraine point out the disturbances of cognitive functions also for auditory modalities. It suggests generalized dysfunction of cortical information processing in the interictal period of migraine.

[Current data on interferon therapy of multiple sclerosis in patients at developmental age]. / Aktualne dane na temat zastosowania interferonu w leczeniu stwardnienia rozsianego u pacjentów wieku rozwojowego.

Multiple sclerosis (MS) is a rare disorder of the central nervous system in children. In spite of the investigations of the last decade its etiology has not been established. The authors of the paper presented data on the specific nature of children MS using the current literature. They also demonstrated the role of interferon (INF) and clinical trials of MS treatment in children. The authors described their own experiences in the treatment of a boy with the youth MS using INF. The patient has suffered from MS since he was 15; INF therapy was introduced after two relapses of the disease. The results of the 18-month therapy with INF suggest beneficial immunomodulatory effects of interferon on MS course in children. The presented patient is continuing the therapy while his clinical status is being observed.