Joanna Śmigielska-Kuzia

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.

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.

Somatosensory evoked potentials in epileptic children treated with carbamazepine or valproate in monotherapy - a preliminary study.

PURPOSE Data from the literature suggest that long-term therapy with various antiepileptic drugs can be responsible for the functional disturbances within the nervous system e.g. peripheral neuropathy and encephalopathy. Useful and non-invasive instruments for evaluation of even subclinical nerve conduction abnormalities in somatosensory tracts are somatosensory evoked potentials (SEPs). The aim of this study was to assess the potentially drug-induced abnormalities in the SEP parameters in epileptic children, treated chronically in monotherapy with one of the two most often used antiepileptic drugs: valproate (VPA) or carbamazepine (CBZ). MATERIALS AND METHODS SEP from left median nerve stimulation were recorded in twenty children with idiopathic/cryptogenic epilepsy treated in monotherapy with CBZ (9 patients) or VPA (11 patients). The mean age of the patients was 13.4 ± 2.9 years (range 7-17 years). The plasma concentrations of the drugs were consistently within therapeutic range. The mean duration of treatment was eight months. The control group consisted of twenty-four age-matched children with tension type headache. The latencies of the components: N9, N13, N20, P25 and the peripheral conduction time (PCT) and central conduction time (CCT) were analyzed. RESULTS No significant differences in all analyzed SEP parameters between the epileptic and control children were found. CONCLUSIONS Our results indicate that during the first 8 months from the beginning of antiepileptic treatment in children, monotherapy with VPA or CBZ does not induce nerve conduction disturbances within both the peripheral- and the central part of the somatosensory tracts, detected in SEP examination.

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-cm3 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.