ABSTRACT
BACKGROUND: Fluoro-D-deoxyglucose positron emission tomography (FDG-PET) is a standard procedure for interictal assessment and accurate pre-surgical evaluation of presumed epileptogenic zone localization. Profound sedation or general anesthesia is frequently required to reduce movement artefacts in young or cognitively impaired patients during image acquisition. This study compares the impact of propofol and sevoflurane anesthesia on overall quality of PET images, detectability of a hypometabolic lesion and demarcation of the detected lesion in pediatric patients suffering from focal epilepsia. METHODS: Pediatric patients with focal epilepsia were anesthesized using propofol (N.=37) or sevoflurane (N.=43). Two independent blinded investigators rated the PET-scans on a 3-point Likert scale with respect to overall quality of PET images, detectability of a hypometabolic lesion and demarcation of the detected lesion. Mann-Whitney-U-Test was conducted to compare the rating results between the two anesthesia regimes. Inter-rater reliability was calculated using Cohen's Kappa. RESULTS: Anesthesia was throughout uneventful and there was no clinical evidence for peridiagnostic seizures. Differences in neither single dimension ratings nor in sum scores (mean 5.8 ± SD 1.5 for propofol, and 5.7 ± SD 1.5 for sevoflurane; P=0.567) were statistically significant. Cohen's Kappa was between 0.428 and 0.499. CONCLUSION: For surgical planning in patients with epilepsy, FDG-PET imaging is an indispensable functional imaging technique to detect hypometabolism. We conclude that both, sevoflurane and propofol based anesthetic regimes are suitable to detect hypometabolic cerebral lesions during FDG-PET.
Subject(s)
Anesthesia, General , Anesthetics, Inhalation , Anesthetics, Intravenous , Epilepsies, Partial/diagnostic imaging , Methyl Ethers , Positron-Emission Tomography , Propofol , Child , Humans , Sevoflurane , Single-Blind MethodABSTRACT
The purpose of this study was to assess the effect of epilepsy surgery on seizure outcome in children and adolescents under 18 years with intractable epilepsy due to focal cortical dysplasia. We analysed clinical data, such as age at seizure onset, epilepsy course, localisation of focus from presurgical evaluation, MRI, tissue pathology and seizure outcome in 68 patients 6 months to 9 years after epilepsy surgery. Seizure outcome was classified according to the Engel classification. Mean age at seizure onset was 7 months, ranging from the first days of life to 7 years. All patients had medically intractable epilepsy. Localisation of the lesion was predominantly extratemporal: posterior (uni- or multilobar) 43 %, frontal without central region 26 %, multilobar involving central area 19 % and temporal in 12 %. MRI signs typically seen in cortical dysplasia (FCD) such as localised blurring of gray-white matter junction was found in 68 %, dysgyria in 62 %, thickening of the cortical ribbon in 46 % and T2 signal elongation of the subcortical white matter in 40 % of the patients' MRI. Age at surgery ranged from 5 months to 16 years; 14 patients were under 2 years when operated on. In 34 patients (6 patients under 3 years) subdural grid electrode evaluation was performed prior to surgery. Pathology revealed focal cortical dysplasia without balloon cells (type I) in 60 %, FCD of the balloon cell subtype (type II) in 40 % of the specimens. Postoperative complications were subdural hygroma in 5 and an increased motor deficit in 2 patients. Up to two years after epilepsy surgery 50 % of the children were seizure free (Engel class I), 10 % Engel class II, 33 % Engel class III and 7 % unchanged (Engel class IV). Long-term seizure outcome (> 3 years post surgery) in 32 patients showed similar results (class I 50 %, class II 19 %, class III 28 %, class IV 3 %). Complete resection of the dysplastic lesion was significantly correlated with favorable seizure outcome, whereas seizure outcome was not significantly different in patients with mild (type I) or balloon cell (type II) FCD. Children operated after 6 years of age had no better outcome than children operated in infancy or at preschool age. Epilepsy surgery resulted in good (class I and II) seizure control in 60 % of children with intractable epilepsy due to focal cortical dysplasia.
Subject(s)
Cerebral Cortex/abnormalities , Cerebral Cortex/surgery , Epilepsy/congenital , Epilepsy/surgery , Adolescent , Cerebral Cortex/pathology , Child , Child, Preschool , Epilepsy/pathology , Female , Humans , Infant , Longitudinal Studies , Magnetic Resonance Imaging , Male , Prognosis , Prospective Studies , Retrospective Studies , Time FactorsABSTRACT
Ruthenium(III) complexes of the general formula HL[RuCl4L2], with two trans-standing heterocyclic ligands L bound to ruthenium via nitrogen, show remarkable activity in different tumor models. To obtain a deeper insight into the mode of action of this class of anticancer compounds, we investigated the interaction of HIm trans-[RuC14(im)2] (im, imidazole) and HInd trans-[RuCl4(ind)2] (ind, indazole) with all four nucleoside monophosphates in buffered solution by means of capillary electrophoresis. A preference for GMP- and AMP-coordination was found. A decrease of the pH resulted in a significantly increased amount of bound nucleotide. This feature seems to be interesting with regard to the lower pH values in solid tumors.
Subject(s)
Antineoplastic Agents/chemistry , Electrophoresis, Capillary/methods , Nucleotides/chemistry , Ruthenium Compounds/chemistry , Adenosine Monophosphate/chemistry , Guanosine Monophosphate/chemistry , Hydrogen-Ion ConcentrationABSTRACT
Functional magnetic resonance imaging (fMRI) was performed in a 6-year-old boy with a complex malformation of the right hemisphere who suffered from pharmaco-refractory epilepsy. Clinical examination revealed left-sided hemiparesis and marked mirror movements of the opposite hand both during paretic and non-paretic hand movements. Functional MRI of repetitive unimanual grasping demonstrated that the two hands share a common cortical representation located in the central motor region of the unaffected left hemisphere. The affected right hemisphere did not show any activation during either task. This case study demonstrates the feasibility and usefulness of motor fMRI in young children before they undergo epilepsy surgery.
Subject(s)
Cerebral Cortex/abnormalities , Dominance, Cerebral/physiology , Epilepsy/congenital , Functional Laterality/physiology , Hemiplegia/congenital , Magnetic Resonance Imaging , Brain Mapping , Cerebral Cortex/pathology , Child , Epilepsy/diagnosis , Epilepsy/pathology , Hemiplegia/diagnosis , Hemiplegia/pathology , Humans , Image Enhancement , Male , Motor Activity/physiology , Motor Cortex/abnormalities , Motor Cortex/pathologyABSTRACT
High performance capillary electrophoresis (HPCE) as well as high performance liquid chromatography-mass spectrometry (HPLC-MS) have been applied to the separation, identification and quantification of the tumor-inhibiting ruthenium compounds HIm trans-[RuCl4(im)2] (im = imidazole) and HInd trans-[RuCl4(ind)2] (ind = indazole) and their hydrolysis products. The half-lives for the hydrolytic decomposition of the Ru(III) compounds were determined by monitoring the relative decrease of the original complex anion under different conditions by means of capillary electrophoresis. The decomposition follows pseudo-first-order kinetics. The rate constants in water at 25 degrees C are 1.102 +/- 0.091 x 10(-5) s-1 for HIm trans-[RuCl4(im)2] and 0.395 +/- 0.014 x 10(-5) s-1 for HInd trans-[RuCl4(ind)2]. About 8% of HIm trans-[RuCl4(im)2] but only about 2% of HInd trans-[RuCl4(ind)2] were hydrolyzed after 1 h at room temperature. Whereas the hydrolysis rate of the imidazole complex is independent of the pH value, the indazole complex hydrolyzes much faster at higher pH. The half-life of HInd trans-[RuCl4(ind)2] in phosphate buffer at pH 6.0 and 37 degrees C is 5.4 h, whereas it is less than 0.5 h at pH 7.4. In contrast to the imidazole complex, where no dependence on the buffer system was observed, hydrolysis of the indazole complex is even faster if a buffer containing hydrogen carbonate is used. The formation of [RuCl2(H2O)2(im)2]+ could be demonstrated by HPLC-MS measurements. In the case of the indazole complex, a release of the indazole ligands results in the formation of [RuCl4(H2O)2]-.
Subject(s)
Antineoplastic Agents/chemistry , Imidazoles/chemistry , Organometallic Compounds/chemistry , Buffers , Chromatography, High Pressure Liquid/methods , Drug Stability , Electrophoresis, Capillary/methods , Hydrogen-Ion Concentration , Hydrolysis , Kinetics , TemperatureABSTRACT
PURPOSE: We sought to analyze semiology of seizure onset and evolution in young children with frontal lobe epilepsy (FLE), compare this with adult reports, and assess age-related differences. METHODS: We analyzed 111 videotaped seizures from 14 patients with FLE based on focal cortical dysplasia aged 3-81 months (mean, 30 months). Ictal events were categorized into behavioral, consciousness, autonomic, and sensory features, as well as motor patterns, which included tonic, clonic, epileptic spasm, and myoclonic seizure components. We developed a time-scaled datasheet to record each epileptic event as onset, very early, early, or late manifestation. RESULTS: Patients had a high seizure frequency with up to 40 attacks/day; half of them showed a cluster tendency. Forty-seven percent of the seizures started in sleep. Mean duration of seizures was short (29 s). Most common seizure components were motor manifestations, mostly tonic-clonic seizures, and epileptic spasms. Behavioral change was frequent, and hypermotor seizures were not seen. In five patients, the motor features were contralateral to the epileptic focus, including two children with asymmetric epileptic spasms. Secondarily generalized tonic-clonic seizures (SGTCSs) were not recorded, but had been reported in the history of two patients. Complex motor automatisms were not seen, whereas oral automatism appeared in three children. CONCLUSIONS: Motor features are common in young children with FLE, as reported in adults. The characteristics, however, differ. Epileptic spasms and subtle behavioral change were frequent. Hypermotor seizures and complex motor automatisms were not seen, and SGTCSs were unusual. Our results suggest that FLE in young children shows age-related features differing from those of adults.
Subject(s)
Epilepsy, Frontal Lobe/diagnosis , Adult , Age Factors , Automatism/diagnosis , Automatism/epidemiology , Behavioral Symptoms/diagnosis , Behavioral Symptoms/epidemiology , Child , Child, Preschool , Circadian Rhythm , Confusion/diagnosis , Confusion/epidemiology , Diagnosis, Differential , Epilepsy, Frontal Lobe/epidemiology , Epilepsy, Frontal Lobe/psychology , Female , Humans , Infant , Male , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/epidemiology , Videotape RecordingABSTRACT
BACKGROUND: Endotoxemia after injury has been a controversial issue. Endotoxins stimulate the innate and adaptive immune system. OBJECTIVE: To investigate endotoxemia and its effects on the production of antiendotoxin antibodies of cultured mononuclear cells of patients with multiple injuries. METHODS: Blood samples of 20 patients with multiple injuries were collected up to 12 days after trauma. The endotoxin concentration was measured in the plasma, and mononuclear cells were isolated and cultured. Specific antibodies against two lipopolysaccharides, one lipid A preparation, and alpha-hemolysin of Staphylococcus aureus were measured in the cell culture supernatant by an enzyme-linked immunosorbent assay. RESULTS: Endotoxemia peaked at admission of the patients, decreasing thereafter to almost normal values within 5 days. Isolated mononuclear cells synthesized antibodies against all tested antigens with a peak at or between day 5 and day 7. The increase was significant for immunoglobulin (Ig)A and IgM specific to all endotoxins tested and for IgA specific to alpha-hemolysin. However, there were no significant changes of the concentrations of total IgM, IgA, and IgG. All specific IgG remained unaffected. CONCLUSION: Patients with multiple injuries initially have temporary endotoxemia. Endotoxin may be suggested as a stimulator of the synthesis of antiendotoxin antibodies, in particular of the IgA and IgM class in patients with multiple injuries.
Subject(s)
Antibodies, Bacterial/blood , Endotoxemia/etiology , Endotoxemia/immunology , Endotoxins/immunology , Immunoglobulin A/blood , Immunoglobulin M/blood , Lipid A/immunology , Multiple Trauma/complications , Staphylococcal Infections/etiology , Staphylococcal Infections/immunology , Staphylococcus aureus/immunology , Adult , Bacterial Translocation , Cells, Cultured , Endotoxemia/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Linear Models , Male , Middle Aged , Staphylococcal Infections/blood , Time FactorsABSTRACT
The ruthenium(III) complex Hlnd trans-[RuCl(4),(ind)(2)], with two trans-standing indazole (ind) ligands bound to ruthenium via nitrogen, shows remarkable activity in different tumor models in vitro and in vivo. The solvolysis of the complex trans-[RuCl(4),(ind)(2)](-) has been investigated by means of spectroscopic techniques (UV/vis, NMR)in different solvents. We investigated the indazolium as well as the sodium salt, the latter showing improved solubility in water. In aqueous acetonitrile and ethanol the solvolysis results in one main solvento complex. The hydrolysis of the complex is more complicated and depends on the pH of the solution as well as on the buffer system.
ABSTRACT
Case reports of four patients with therapy-resistant lesional partial epilepsies and additional foci of benign epileptic discharges of childhood, in addition to the usual electroencephalogram (EEG) changes, are presented. A family history of epileptic or febrile seizures in childhood was reported in all four patients. A distant relative of one patient, not manifesting seizures, demonstrated rolandic spikes on EEG. An abnormal pregnancy (polyhydramnion, premature pains, induced labor because of an abnormal CTG , placenta insufficiency) was reported in one patient, risk factors during birth (birth 14 days after term, placenta insufficiency) were reported in one, and bacterial meningitis at 4 weeks of age was reported in one. All patients manifested a retarded, partly severe, unfavorable infantile psychomotor development. An early seizure onset was observed in all patients (in three patients during the first year of life and in one patient during the second year). A hemifacial seizure symptomatology was seen, in addition to other symptoms, in two patients, possibly indicating the seizure pattern indicative of benign partial seizures; seizures occurred exclusively in sleep in one patient. The benign focus was never located in the lesional area. It was recorded over the same hemisphere in two patients and over the other hemisphere in the other two.