Agenesis of the internal carotid artery: a family pathology?

The internal carotid artery agenesis is a rare malformation disorder. We report the case of a 12-year-old boy suffering migraine, who had presented an episode featuring amaurosis fugax, spontaneously regressed. CT angiography images show hypoplasia of the left common carotid artery with loss of opacification of the left internal carotid artery consistent to agenesis. Moreover CT scans through the skull base demonstrate absence of left petrous carotid canal and an hypertrophic left middle cerebral artery originating from an aberrant artery arising from the right cavernous carotid. All diagnostic examinations confirmed the presence of the internal carotid artery agenesis, as Lie's type IV. We started an annual follow up that over the next 7 years did not reveal any change in magnetic resonance angiography images.

Is it possible a new definition of metabolic syndrome in childhood?

OBJECTIVE: To investigate whether a group of Italian children and adolescents who were diagnosed to have metabolic syndrome (MS) according to a new ethnic age and gender specific definition had, in comparison with a control group, other signs and metabolic risk factors which are commonly associated with MS. PATIENTS AND METHODS: The cross-sectional study population included 300 subjects (51% boys, age range 6-14 years), who were divided into 2 groups according to the presence of MS, diagnosed on the basis of 3/5 factors derived from the age and gender specific quantile distribution of MS components in a large regional Italian population survey (Calabrian Sierras Community Study, CSCS). In all subjects the following data were collected: anthropometric measures, blood pressure, liver function, C-reactive protein (hsCRP), uric acid blood levels, lipid and glucose profile. Triglycerides/HDL-cholesterol (TG/HDL-C) ratio was calculated. RESULTS: There were 38 subjects (13%) with MS, who had higher indices of growth and fat distribution and higher blood levels of uric acid, alanine aminotransferase and gamma-glutamyltransferase. TG/HDL ratio was higher (median 3.11 vs. 1.14, p = 0.00001) in MS subjects who had lower apolipoprotein A and higher apolipoprotein B and non-HDL-C levels. hsCRP was not different between groups. CONCLUSIONS: Our ethnic age and gender specific definition of MS in Italian children and adolescents was able to identify in a youth group different cardiometabolic risk factors related to insulin resistance, endothelial damage and nonalcoholic fatty liver disease, which are commonly associated with MS diagnosis.

Morphological and molecular assessment of apoptotic mechanisms in peripheral neuroblastic tumours.

Multiple defects in apoptotic pathways have been described in peripheral neuroblastic tumours (NTs). Mitosis-karyorrhexis index (MKI) is a reliable morphological marker identifying favourable and unfavourable NTs. The extent to which apoptotic processes contribute to determine the clinical significance of MKI is still undefined. Apoptosis was investigated in a series of 110 peripheral NTs by comparing MKI to immunohistochemical and molecular apoptotic features. High MKI was found in 55 out of 110 NTs (50%) and was associated with advanced stage (P = 0.007), neuroblastoma (NB) histological category (P = 0.024), MYCN amplification (P < 0.001), and poor outcome (P = 0.011). Overall survival probability was 45% in patients with high MKI compared to 73% in patients with low MKI. In the same 110 NTs, the expression of Bcl-2, Bcl-XL, Bax and Mcl-1 was studied by immunohistochemistry, but no significant associations were found with clinicohistological features. Microarray analysis of apoptotic genes was performed in 40 out of 110 representative tumours. No significant association was found between the expression of apoptotic genes and MKI or clinicohistological features. Proliferative activity was assessed in 60 out of 110 representative tumours using Ki67 immunostaining, but no significant correlations with MKI or clinicobiological features were found. In NTs, the combination of apoptosis and proliferation as expressed by MKI is a significant prognostic parameter, although neither of them is per se indicative of the clinicobiological behaviour and outcome.

Functional neuroradiologic investigations in band heterotopia.

Band heterotopias are an example of genetic generalized neuronal migration disorders that may be present in patients with mild epilepsy and normal or slightly impaired intellect, as well as in patients with intractable epilepsy and mental retardation. The case of a 17-year-old left-handed female patient with epilepsy and normal cognitive development is reported in whom single-photon emission computed tomography (SPECT), proton magnetic resonance spectroscopy, and functional magnetic resonance imaging (fMRI) were performed. MRI revealed the presence of bilateral asymmetric band heterotopia. SPECT revealed a left frontoparietal and occipital hypoperfusion, demonstrating a good correlation with the electroencephalogram abnormalities. Because of the appearance of new types of seizures, the patient underwent a second MRI investigation together with a proton magnetic resonance spectroscopy (MRS) study. MRI confirmed bilateral band heterotopia characterized by greater thickness in the left hemisphere at the frontal and occipital level. MRI and SPECT findings were in agreement with left occipital electroencephalogram abnormalities and with occipital seizure type. Qualitative results of proton MRS revealed normal spectra profiles in the examined left frontal and occipital heterotopic area and in the normal overlying cortex. Later, fMRI was performed. The finger-tapping test of the right hand yielded the activation of both normal left sensory-motor cortex and the facing band heterotopia. In the right hemisphere, only the activation of the sensory-motor neocortex was observed; no involvement of the right misplaced brain tissue was present. This functional behavior could be considered the consequence of poor neuronal representation. On the contrary, the involvement of both band heterotopia and normal cortex observed in the left hemisphere could be the result of many synaptic interconnections. Functional investigations may have an important role in defining the activity of band heterotopia per se and in relation to the overlying neocortex.

Visual field constriction in children with epilepsy on vigabatrin treatment.

Vigabatrin is considered the drug of choice for infantile spasms and simple and complex partial epilepsy in childhood. Its mechanism of action relies on the irreversible inhibition of gamma-aminobutyric acid (GABA) transaminase. Since June 1997 several articles have been published reporting visual field constriction in adult patients on vigabatrin therapy. Recently, 7 pediatric patients, 1 on vigabatrin monotherapy and 6 on add-on therapy with visual field constriction have been described. We have observed 30 pediatric patients with epilepsy (14 boys and 16 girls), ages ranging from 4 to 20 years (mean: 11 years and 2 months) treated with vigabatrin for infantile spasms, simple and complex partial epilepsy, who had never complained of ophthalmologic disturbances. Twenty-one patients underwent complete routine ophthalmologic examination (fundus oculi, visual acuity, intraocular pressure, and visual field tests); 9 children (<6 years old) underwent only fundus examination, because collaboration was lacking. We report on 4 children showing constriction of visual field, prevailing in nasal hemifield. In 1 child, visual abnormalities were stable even 10 months after vigabatrin discontinuation, while in another a greater improvement was observed 5 months after discontinuation. The possible mechanisms have been discussed and the cone dysfunction, connected with GABA augmentation in the outer retina, has been outlined. We suggest a possible protocol to control visual abnormalities in epileptic children.

Superoxide release by human polymorphonuclear leukocytes in the presence of deferoxamine.

BACKGROUND AND OBJECTIVE: Anecdotal reports in patients with acute and chronic iron overload have recently indicated that the efficacy and safety of an alternative chelation program including intravenous and/or continuous delivery of deferoxamine (DFO) may be in contrast with the risk of developing lung injury. Production of oxygen radicals has been postulated to be an important mechanism by which polymorphonuclear leukocytes (PMNs) could cause tissue injury in patients undergoing this alternative treatment method. METHODS: PMNs obtained from healthy donors were incubated at 37 degrees C for 30 min with DFO (across the drug concentration 0.125 to 10 mg/mL). Superoxide (O2) production was measured by superoxide inhibitable cytochrome c reduction as well as by an NBT densitometric kinetic test. In the same run the effect of lipid peroxidation was demonstrated by means of a malonyl-dialdehyde (MDA) assay. RESULTS: Preincubation of PMNs with any study concentration of DFO significantly enhanced O2 release as well as MDA production upon PMA stimulation. Maximal intracellular and extracellular O2-release as well as MDA production occurred at certain drug concentrations. INTERPRETATION AND CONCLUSIONS: Our in vitro findings suggest that O2-release may be an additional detrimental contribution to tissue injury in some patients who develop pulmonary toxic effects while on intravenous and/or continuous DFO administration.

Superoxide production by neutrophils in children with malignant tumors treated with recombinant human granulocyte colony-stimulating factor.

BACKGROUND: Human recombinant granulocyte colony-stimulating factor (rhG-CSF), widely used to combat chemotherapy-induced neutropenia, stimulates both in vivo and in vitro intra- and extra-cellular O2- production in human polymorphonuclear cells (PMNs). PATIENTS AND METHODS: Twelve patients with solid tumors or acute lymphoblastic leukemia were treated during induced aplasia with rhG-CSF (5 micrograms/kg/day). Intra- and extracellular O2- production by PMNs isolated from these patients after 5 days of rhG-CSF therapy was assessed following both fMLP and PMA stimulation. RESULTS: All patients showed a rise in PMN count; administration of rhG-CSF enhanced intra- and extracellular O2- release after fMLP but not after PMA stimulation. CONCLUSIONS: rhG-CSF potentiates in vivo O2- production by PMNs stimulated with receptor-mediated agonists via G-protein (e.g. fMLP), but not by those stimulated with agonists that bypass receptors via protein kinase C (e.g. PMA).