Discontinuation of anticonvulsant therapy and the electroencephalogram.
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Anticonvulsants↗
Biomedical subjects
Francesco Chiarelli
Publications and source records attributed to Francesco Chiarelli.
Factors associated with poor control in partial complex epilepsy.
To evaluate the predictive factors of response to anticonvulsant therapy in children with complex partial epilepsy, we studied prospectively 74 children and adolescents suffering from this type of epilepsy. All children were prospectively followed for at least 2 years after the beginning of anticonvulsant therapy. At the end of follow-up, the children were subdivided into two groups according to the frequency of seizures: group A, children who were seizure free in the last year, and group B, children with at least six seizures in the previous year. Children with a poor response to anticonvulsant therapy had a more frequent personal history of neonatal seizures, an interval of less than 6 months between the first and the second seizures, and persistent abnormal electroencephalograms than the seizure-free patients and were often treated with polytherapy.
Age of Onset↗
Photosensitivity and epilepsy.
Photosensitive epilepsy is a well-known condition characterized by seizures in patients who show photoparoxysmal responses on electroencephalography (EEG) elicited by intermittent photic stimulation. Photoparoxysmal responses can be defined as epileptiform EEG responses to intermittent photic stimulation or to other visual stimuli of everyday life and are frequently found in nonepileptic children. The modern technologic environment has led to a dramatic increase in exposure to potential trigger stimuli; nowadays, television and video games are among the most common triggers in daily life. There is ample evidence for genetic transmission of photoparoxysmal responses; systematic family studies have provided data for an autosomal dominant mode of inheritance with age-dependent penetrance for photosensitivity. The age of maximum penetrance is between 5 and 15 years. The prognosis for control of seizures induced by visual stimulation is generally very good. The large majority of patients do not need anticonvulsant therapy, but, when needed, the drug of choice is valproate. Stimulus avoidance and stimulus modification can be an effective treatment in some patients and can sometimes be combined with antiepileptic drug treatment.
Adolescent↗
Growth, growth factors and diabetes.
Type 1 diabetes mellitus (T1DM) and other chronic diseases in children are well known to adversely affect linear growth and pubertal development. In the years immediately following the introduction of insulin therapy, short stature was consistently reported in children with T1DM. However, over the past 50 years significant improvement in the prognosis for growth and final height in children with diabetes has been achieved. Although pre-pubertal and post-pubertal growth are important phases in growth, puberty and its related hormonal changes represent a critical phase for growth gain and final height particularly in patients with T1DM. Growth impairment reported in diabetic patients is dependent on abnormalities in physiological bone growth and corresponds to abnormalities of the growth hormone-insulin-like growth-I (GH-IGF-I) axis. These alterations seem to be related to appropriate insulin levels and thereby to glycaemic control as judged by haemoglobin levels. Modern diabetes care, particularly intensified insulin regimens, might improve metabolic control in patients with T1DM, therefore preventing abnormalities of the GH-IGF-I axis and leading to normal growth and final height similar to that of their unaffected peers.
Adolescent↗
Younger age at onset and sex predict celiac disease in children and adolescents with type 1 diabetes: an Italian multicenter study.
OBJECTIVE: To estimate the prevalence of biopsy-confirmed celiac disease in Italian children and adolescents with type 1 diabetes and to assess whether age at onset of type 1 diabetes is independently associated with diagnosis of celiac disease. RESEARCH DESIGN AND METHODS: The study group was a clinic-based cohort of children and adolescents with type 1 diabetes cared for in 25 Italian centers for childhood diabetes. Yearly screening for celiac disease was performed using IgA/IgG anti-gliadin and IgA anti-endomysium antibodies. RESULTS: Of the 4,322 children and adolescents (age 11.8 +/- 4.2 years) identified with type 1 diabetes, biopsy-confirmed celiac disease was diagnosed in 292 (prevalence 6.8%, 95% confidence interval [CI] 6.0-7.6), with a higher risk seen in girls than in boys (odds ratio [OR] 1.93, 1.51-2.47). In 89% of these, diabetes was diagnosed before celiac disease. In logistic regression analyses, being younger at onset of diabetes, being female, and having a diagnosis of a thyroid disorder were independently associated with the risk of having diabetes and celiac disease. In comparison with subjects who were older than 9 years at onset of diabetes, subjects who were younger than 4 years at onset had an OR of 3.27 (2.20-4.85). CONCLUSIONS: We have provided evidence that 1) the prevalence of biopsy-confirmed celiac disease in children and adolescents with type 1 diabetes is high (6.8%); 2) the risk of having both diseases is threefold higher in children diagnosed with type 1 diabetes at age <4 years than in those age >9 years; and 3) girls have a higher risk of having both diseases than boys.
Adolescent↗
Role of camping in the treatment of childhood obesity.
Obesity is constantly increasing among children. Since treatment for obesity on outpatient bases often fails, we evaluated whether camps may help to improve eating habits. Forty-one children, 21 males and 20 females (BMI > 97 degrees percentile, weight excess > 30%, Tanner stage I) agreed to participate to a 8 day camp. After 1-year follow-up, measurements carried out by plicometry, bioelectrical impedance, metabolic and hormonal evaluations, showed a significant reduction of skinfolds, as well as glycemic and insulinemic response to the oral glucose tolerance test. These results suggest that camps may help to improve nutritional and physical education and psychological outcome of obese children.
Adrenocorticotropic Hormone↗
Benign focal epilepsy with onset in infancy in a patient with 18q-syndrome.
CASE REPORT: The 18q-syndrome is sometimes associated with epilepsy. We report a child with a 18q deletion who showed the typical manifestations of the syndrome. In addition, she had benign focal epilepsy with onset in infancy characterized by complex partial seizures with a frequency from 1 to 20 per day. This type of epilepsy is a rare condition and this is the first report of benign focal epilepsy with onset in infancy in a child with 18q-syndrome. The EEGs performed during sleep showed low-voltage spikes over the fronto-central region of the left hemisphere. The magnetic resonance imaging of the brain was normal. CONCLUSION: In conclusion, benign focal epilepsy with onset in infancy could be a condition associated with 18q-syndrome.
Chromosomes, Human, Pair 18↗
The receptor RAGE as a progression factor amplifying arachidonate-dependent inflammatory and proteolytic response in human atherosclerotic plaques: role of glycemic control.
BACKGROUND: RAGE (receptor for advanced glycation end products [AGEs]) plays a role in diabetic atherosclerosis. Recently, we have demonstrated enhanced expression of cyclooxygenase-2 and PGE synthase-1 (COX-2/mPGES-1) in human symptomatic plaques, and provided evidence that it is associated with metalloproteinase (MMP)-induced plaque rupture. However, the specific transmembrane signaling pathway(s) influencing plaque COX-2/mPGES-1 expression is unknown. The aim of this study was to characterize RAGE expression in human plaques and to correlate it with the inflammatory infiltration, COX-2/mPGES-1 and MMP expression, and with clinical evidence of diabetes. METHODS AND RESULTS: Plaques obtained from 60 patients undergoing carotid endarterectomy were divided into diabetic and nondiabetic according to clinical evidence of type 2 diabetes. Plaques were subjected to analysis of RAGE, NF-kappaB, COX-2/mPGES-1, MMP-2 and MMP-9, lipid and oxidized LDL (oxLDL) content, and collagen content by immunohistochemistry and Western blot, whereas zymography was used to detect MMP activity. Immunohistochemistry was used to identify CD68+ macrophages, CD3+ T-lymphocytes, smooth muscle cells (SMCs), and HLA-DR+ inflammatory cells. Diabetic plaques had more (P<0.0001) macrophages, T-lymphocytes, and HLA-DR+ cells, more (P<0.0001) immunoreactivity for RAGE, activated NF-kappaB, COX-2/mPGES-1, and MMPs, increased (P<0.0001) gelatinolytic activity, reduced (P<0.0001) collagen content, and increased (P<0.0001) lipid and oxLDL content. Interestingly, RAGE, COX-2/mPGES-1, and MMP expression was linearly correlated with plasma level of HbA1c. CONCLUSIONS: In conclusion, this study demonstrates in humans that RAGE overexpression is associated with enhanced inflammatory reaction and COX-2/mPGES-1 expression in diabetic plaque macrophages, and this effect may contribute to plaque destabilization by inducing culprit metalloproteinase expression.
Aged↗
Enhanced lipid peroxidation and platelet activation in the early phase of type 1 diabetes mellitus: role of interleukin-6 and disease duration.
BACKGROUND: To investigate early events possibly related to the development of diabetic angiopathy, we examined whether 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) formation, a marker of in vivo oxidant stress, is altered in different stages of type 1 diabetes (T1DM) and whether it correlates with the rate of thromboxane (TX) A2 biosynthesis, a marker of in vivo platelet activation. We also investigated the relationship between inflammatory markers and F2-isoprostane formation in this setting. METHODS AND RESULTS: A cross-sectional study was performed in 23 insulin-treated patients aged <18 years with new-onset T1DM ( 1 year, group B). Urinary 8-iso-PGF2alpha and 11-dehydro-TXB2 were measured in all patients and in age- and gender-matched controls. Circulating interleukin-6 (IL-6), tumor necrosis factor-alpha, and C-reactive protein were also determined as markers of the inflammatory response. Fifteen of the 23 children in group A were reexamined after 12 months. Compared with either controls or group B, diabetic children in group A showed significantly higher levels of 8-iso-PGF2alpha, 11-dehydro-TXB2, IL-6, tumor necrosis factor-alpha, and C-reactive protein. Statistically significant correlations between IL-6 and both 8-iso-PGF2alpha (r=0.63, P<0.001) and 11-dehydro-TXB2 (r=0.51, P<0.01) were observed. The 15 patients reexamined after 1 year showed a significant reduction in lipid peroxidation and platelet activation (P<0.02 and P<0.001, respectively), consistent with reduced levels of IL-6 and tumor necrosis factor-alpha. CONCLUSIONS: These results demonstrate that enhanced lipid peroxidation and platelet activation represent early events in T1DM that are possibly related to an acute inflammatory response. These noninvasive indexes may help in further examining T1DM pathophysiology and monitoring pharmacological interventions to interfere with disease development and progression.
Adolescent↗
Suppression of the functionally coupled cyclooxygenase-2/prostaglandin E synthase as a basis of simvastatin-dependent plaque stabilization in humans.
BACKGROUND: The clinical benefits of statins are attributed to changes in plaque composition that lead to reduced metalloproteinase (MMP) activity and plaque stabilization. However, the molecular mechanism of this effect is unclear. Recently, we demonstrated enhanced expression of isoforms of inducible cyclooxygenase (COX) and PGE synthase (COX-2/mPGES) in human symptomatic plaque and provided evidence that this is associated with MMP-induced plaque rupture. The aim of this study was to characterize the effect of simvastatin on inflammatory infiltration and the expression of COX-2/mPGES and MMPs in human carotid plaques. METHODS AND RESULTS: Seventy patients with symptomatic carotid artery stenosis were randomized to the American Heart Association Step 1 diet plus simvastatin (40 mg/d) or the American Heart Association Step 1 diet alone for 4 months before endarterectomy. Plaques were subjected to analysis of COX-1, COX-2, mPGES, MMP-2 and MMP-9, lipid and oxidized LDL (oxLDL) content, and collagen content by immunocytochemistry, Western blot, and reverse transcription-polymerase chain reaction, whereas zymography was used to detect MMP activity. Immunocytochemistry was also used to identify CD68+ macrophages, CD3+ T-lymphocytes, smooth muscle cells (SMCs), and HLA-DR+ inflammatory cells. Plaques from the simvastatin group had fewer (P<0.0001) macrophages, T-lymphocytes, and HLA-DR+ cells; less (P<0.0001) immunoreactivity for COX-2/mPGES and MMPs; reduced (P<0.0001) gelatinolytic activity; increased (P<0.0001) collagen content; and reduced (P<0.0001) lipid and oxLDL content. Interestingly, COX-2/mPGES inhibition by simvastatin was completely reversed by mevalonate in vitro. CONCLUSIONS: This study demonstrates that simvastatin decreases inflammation and inhibits COX-2/mPGES expression in plaque macrophages, and this effect in turn may contribute to plaque stabilization by inhibition of MMP-induced plaque rupture.
Aged↗
Magnetoencephalography in pediatric neurology and in epileptic syndromes.
In recent years, great advances in the knowledge of neuromagnetism have permitted the application of Superconducting Quantum Interference Devices to the pathophysiologic study of the human brain. In particular, in pediatric neurology, the integration of biomagnetism with magnetic resonance imaging and other techniques for medical imaging have allowed for precise neuromagnetic measurements of the human brain. The more frequently used technique is magnetoencephalography. Recent data have illustrated the usefulness of magnetoencephalography in mapping activity of sensory and motor areas and in studying the spatiotemporal pattern of brain activation specific to somatosensory function. Moreover, magnetoencephalography is an important tool to localize epileptic activity; magnetic source imaging superimposes magnetoencephalographic localizations on the magnetic resonance imaging and yields improved spatial resolution as compared with surface electroencephalography. The role of magnetoencephalography in evaluating patients with epilepsy continues to evolve; in fact, it seems to be very useful in the localization of the epileptogenic zone in patients with partial epilepsy. This application of magnetoencephalography is essential in the selection of epileptic children candidates to surgical treatment of seizures.
Brain Mapping↗
Risk factors for recurrence of epilepsy and withdrawal of antiepileptic therapy: a practical approach.
In epileptic patients, treated with anticonvulsant drugs (AEDs), the question when and how an attempt should be made to withdraw therapy is a crucial point in the management of these patients. In recent years, many studies have identified the main risk factors for seizure recurrence after discontinuation of AEDs. Patients are more likely to have recurrences if there is a definite symptomatic aetiology, two or more different types of seizures, an abnormal neurological examination and a seizure onset at adolescence or later. In contrast, abnormal EEG has not been proved as a risk factor for recurrence. Moreover, the classification of epilepsy syndromes is another important predictor of the outcome for these patients. In practice, most authors suggest that medication is discontinued after a seizure-free period of two years. In this review we analyse data from the literature and we suggest a practical approach for safe anticonvulsant withdrawal, although the decision should always be made individually, weighing risks and benefits.
Age of Onset↗
Serum insulin and leptin levels and valproate-associated obesity.
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Adult↗
Influence of growth hormone therapy on pituitary and lumbar spine astrocytomas. A clinical observation.
We report on a male patient with an inactive pituitary and lumbar astrocytoma. He presented with panhypopituitarism at the age of 16 and received growth hormone replacement therapy for one year. During this period the pituitary mass increased substantially and showed subsequently a consistent shrinkage once treatment was stopped. The lumbar lesion stayed stable for the whole period of observation. The presumable rGH related change of the pituitary astrocytoma underlines the importance of careful follow-up of children with growth hormone deficiency secondary to treatment for brain tumors. Substitution therapy with rGH requires further and longer studies before it can be recommended with absolute reassurance in children with subtotal resection of a pituitary astrocytoma.
Adolescent↗
von Willebrand factor and its propeptide in children with diabetes. Relation between endothelial dysfunction and microalbuminuria.
It has been shown that patients with insulin-dependent diabetes mellitus have elevated von Willebrand factor (vWF) plasma concentrations. Plasma fibrinogen, vWF, and its propeptide concentrations have been evaluated in 102 children with insulin-dependent diabetes mellitus to determine whether an increase of vWF and its propeptide levels precedes and may predict the development of persistent microalbuminuria. The patients have been divided into two groups according to the presence or absence of microalbuminuria at the end of follow-up. They have been followed up for at least 8 y. Control group consisted of 80 age- and sex-matched healthy volunteers. At the beginning of the study there was no significant difference in fibrinogen, vWF, and its propeptide levels between patients and control subjects. During the follow-up, a significant increase of plasma vWF and its propeptide has been observed in the group of patients who later developed microalbuminuria but not in those who remained normoalbuminuric. This increase started 3 y and become statistically significant (p < 0.01) 2 y before the onset of microalbuminuria, persisting until the end of the study. During the entire follow-up plasma values of fibrinogen persisted in the normal range. In conclusion, an increase in plasma concentration of vWF and its propeptide precedes microalbuminuria and, therefore, can be useful to identify children with insulin-dependent diabetes mellitus at risk to develop incipient nephropathy later in life.
Albuminuria↗
A novel insulin-like growth factor (IGF)-independent role for IGF binding protein-3 in mesenchymal chondroprogenitor cell apoptosis.
Chondrogenesis results from the condensation of mesenchymal chondroprogenitor cells (MCC) that proliferate and differentiate into chondrocytes. We have previously shown that IGF binding protein (IGFBP)-3 has an IGF-independent antiproliferative effect in MCC. The current study evaluates the IGF-independent apoptotic effect of IGFBP-3 on MCC to modulate chondrocyte differentiation. We employed the RCJ3.1C5.18 chondrogenic cell line, which in culture progresses from MCC to differentiated chondrocytes; cells do not express IGFs or IGFBP-3. We also used IGFBP-3 mutants with decreased (I56 substituted to G56; L80 and L81 to G80G81) or abolished binding for IGFs (I56, L80, and L81 to G56G80G81). MCC transfected with IGFBP-3 detached, changed their phenotype, and underwent apoptosis. A maximal IGFBP-3 apoptotic effect was observed 24 h after transfection (463 +/- 73% of controls; P < 0.001). Remarkably, IGFBP-3 mutants had similar effects, demonstrating that the IGFBP-3 apoptotic action was clearly IGF independent. In addition, treatment with IGFBP-3 in serum-free conditions resulted in a significant increase of apoptosis (173 +/- 23% of controls; P < 0.05). Moreover, this apoptotic effect was selective for MCC, resulting in a selective reduction of chondrocytic nodules and a significant decrease in type II collagen expression and proteoglycan synthesis. In summary, we have identified a novel IGF-independent role for IGFBP-3 in the modulation of chondrocyte differentiation.
Animals↗
Preventing microvascular diabetic complications in children and adolescents: looking beyond glycaemic control.
Type 1 diabetes mellitus is associated with the development of micro- and macrovascular disease, and diabetic angiopathy in children and adolescents. It is represented mainly by microangiopathy, characterised by structural changes in the eye, renal glomeruli and peripheral nerves. The pathogenesis of the vascular complications of diabetes is controversial, but without any doubt, endothelial dysfunction play an important role in the pathogenesis of glomerulosclerosis and atherosclerosis. Preventive strategies for these three major complications are discussed in this review. Appropriate surveillance for the earliest evidence of microvascular disease should begin at the onset of puberty, and after 3 - 5 years of diabetes. Therapeutic interventions, particularly excellent metabolic control, may be almost effective in preventing complication onset, or significantly retarding the rate of progression.
Adolescent↗
Relationship between metabolic control and quality of life in adolescents with type 1 diabetes. Report from two Italian centres for the management of diabetes in childhood.
This study is aimed at answering the question whether the demands of the intensified diabetes management and good metabolic control may influence the Quality of Life (QOL) of adolescents with Type 1 Diabetes (T1D), and that of their parents. Overall, 153 adolescents were involved (78 males, mean age 15.0 +/- 2.3 median age 14.6 years; average diabetes duration 6.5 +/- 3.5 years) from the Regional Centres of the Universities of Chieti and Parma. HbA1c determination was centralized and the adolescents were tested according to the adolescent version of the questionnaire developed by Ingersoll and Marrero on the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. The burden on the family was assessed following a newly constructed questionnaire. The average HbA1c value was 7.7 +/- 1.4% (boys 8.0 +/- 1.4 and girls 7.5 +/- 1.2%). The impact of diabetes was similar for both boys and girls (average scores: 44.68 vs 45.00) with no effect regarding age or the duration of diabetes, but the influence of HbA1c values was significant (p < 0.001). Compared with boys, girls had an earlier (at about 12 years of age) and more significant increase in worries (p < 0.01). Lower HbA1c values were associated with fewer worries (p < 0.02). Satisfaction deterioration appeared earlier in girls than in boys and was associated with high levels of HbA1c (p < 0.01). Health perception was poorer in girls than in boys and was influenced by HbA1c values (p < 0.005) in both girls and boys. The burden on the family with diabetes decreased with the age of the adolescent. In conclusion, in our group of adolescents with T1D, lower HbA1c was also associated with better QOL and with a lower perception of a burden on the family. These findings justify the efforts to assess QOL perception in adolescents in order to facilitate achieving better metabolic control.
Adolescent↗