Krzysztof Sendrowski

Hippocampus, hippocampal sclerosis and epilepsy

Hippocampal sclerosis (HS) is considered one of the major pathogenic factors of drug-resistant temporal lobe epilepsy. HS is characterized by selective loss of pyramidal neurons - especially of sectors CA1 and CA3 of the hippocampus - pathological proliferation of interneuron networks, and severe glia reaction. These changes occur in the course of long-term and complex epileptogenesis. The authors, on the basis of a review of the literature and own experience, present the pathomechanisms leading to hippocampal sclerosis and epileptogenesis, including various morphological and functional elements of this structure of the brain and pharmacological possibilities of preventing these processes.

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

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.

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.

Study of the protective effect of calcium channel blockers against neuronal damage induced by glutamate in cultured hippocampal neurons

BACKGROUND The aim of this study was to examine the putative protective effect of calcium channel blockers on hippocampal neurons in the experimental model of excitotoxic damage. METHODS Seven-day old primary dissociated cultures of rat hippocampal neural cells containing one of the following calcium channel blockers: cinnarizine, flunarizine or nimodipine were exposed to glutamate-induced injury. Quantitative assessments of neuronal injury were accomplished by measuring lactate dehydrogenase (LDH) activity in the media 24 h after exposure to glutamate and by counting and establishing the apoptotic and necrotic cells in flow cytometry with Annexin V-FITC/PI staining. RESULTS In our experiment, glutamate induced a 339% elevation of apoptotic cells and a 289% increase of necrotic cells in hippocampal neurons as compared to control cultures without drugs. In cultures containing flunarizine, glutamate-induced cell apoptosis was suppressed by 62% while necrosis showed no significant alternation. Cinnarizine exerted no anti-apoptotic effects on glutamate-injured cultured hippocampal neurons, while nimodipine intensified the apoptotic pathway of cell death and promoted an increase in the number of apoptotic neurons by 26%. When cinnarizine or nimodipine were used, the percentage of necrotic cells was significantly lower when compared with glutamate-injured cultures and it amounted to 44% and 24% for cinnarizine and nimodipine, respectively. CONCLUSIONS The obtained results suggest the beneficial anti-apoptotic potential of flunarizine and the anti-necrotic potential of cinnarizine against glutamate-induced death of cultured hippocampal neurons. Nimodipine can protect neurons against necrosis, but has an intensified adverse pro-apoptotic effect on cultured neurons in the experimental model of excitotoxic injury.

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 manufacturers 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.

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.