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Background: Aicardi–Goutières syndrome (AGS) is a genetically determined disorder with a variable phenotype. Since the original description of AGS, advances in gene sequencing techniques have resulted in a significant broadening of the phenotypic spectrum associated with AGS genes, and new clinical pictures have emerged beyond the classic presentation. The aim of this review is to provide a comprehensive analysis of the clinical spectrum of AGS and report currently available treatments and new immunosuppressive strategies. Data sources: Literature reviews and original research articles were collected from databases, including PubMed and ClinicalTrials.gov. Relevant articles about AGS were included. Results: The involvement of the nervous system certainly represents the major cause of mortality and morbidity in AGS patients. However, other clinical manifestations, such as chilblains, hepatosplenomegaly, and hematological disturbances, may lead to the diagnosis and considerably impact the prognosis and overall quality of life of these patients. Therapeutic approaches of AGS are limited to interventions aimed at specific symptoms and the management of multiple comorbidities. However, advances in understanding the pathogenesis of AGS could open new and more effective therapies. Conclusions: The over-activation of innate immunity due to upregulated interferon production plays a critical role in AGS, leading to multi-organ damage with the main involvement of the central nervous system. To date, there is no specific and effective treatment for AGS. New drugs specifically targeting the interferon pathway may bring new hope to AGS patients. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea syndrome (OSAS) in childhood is a complex disease primarily due both to adenotonsillar hypertrophy and pediatric obesity. Notably, inflammation has been recognized as one of the most important shared pathogenic factor between obesity and OSAS resulting in an increased cardiometabolic risk for these patients. To date, evidence is still limited in non-obese population with OSAS. We aimed to evaluate the cardiometabolic risk profile of a pediatric population of non-obese subjects affected by OSAS. A total of 128 school-aged children (mean age 9.70 ± 3.43) diagnosed with OSAS and 213 non-OSAS children (mean age 9.52 ± 3.35) as control group were enrolled. All subjects underwent a complete clinical and biochemical assessment (including white blood cell count (WBC), platelet count (PLT), mean platelet volume (MPV), % of neutrophils (NEU%), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), uric acid, fasting insulin, iron, ferritin, and transferrin levels). A significant association between inflammation markers (including WBC, PLT, MPV, NEU%, ferritin, CPR, and ESR) and OSAS was found (all p < 0.001). Children with OSAS also showed increased transaminase, glucose, uric acid, and insulin levels (all p < 0.001) compared to healthy controls.Conclusion: Taken together, these findings suggested a worse cardiometabolic profile in non-obese children with OSAS. Given the pivotal pathogenic role of inflammation both for hypoxiemia and metabolic derangements, therapeutic strategies for OSAS might also counteract the increased cardiometabolic risk of these patients, by improving their long-term quality of life.What Is Known: • Pediatric OSAS has shown a close relationship with obesity and its cardiometabolic comorbidities. • Inflammation represents the hallmark of both obesity and OSAS.What Is New: • Non obese children with OSAS presented with a worse cardiometabolic risk profile. • OSAS treatment might serve as an effective approach also for the increased cardiometabolic risk of these children. [ABSTRACT FROM AUTHOR]

The last 50 years has seen the introduction of a great number of antiepileptic drugs, relieving the burden of seizures for many patients. However, some conditions remain a challenge for epileptologists, especially Dravet syndrome and Lennox–Gastaut syndrome, which are severe epileptic and developmental encephalopathies characterized by multiple seizure types and electroencephalographic abnormalities that are often unresponsive to combinations of antiepileptic drugs. The re-purposing of an old drug such as fenfluramine could provide an indispensable tool for clinicians, especially because only a few drugs have been tested in relatively homogeneous populations, like Dravet syndrome. It could also provide insights into precision medicine approaches to the treatment of epileptic syndromes. We searched for relevant papers within MEDLINE, EMBASE, and the Clinical Trial Database, considering publications through July 2020. Pre-clinical studies show a mechanism of action for fenfluramine that goes beyond its pro-serotoninergic activity and that is at the intersection of several pathways involved in excitation/inhibition balance. From the ongoing clinical trial data, it is evident that fenfluramine is proving to be a promising antiepileptic drug with very favorable pharmacokinetics and with a good overall safety profile when used at a lower dosage (0.2–0.7 mg/kg/day), despite its previously link to major cardiac adverse events that prompted its withdrawal from the market in 1997. Here, we review the experimental and clinical evidence of the efficacy of fenfluramine, including the latest results from ongoing clinical trials, and critically discuss the future potential of fenfluramine in terms of safety and precision medicine. Available data from the literature suggest a very good efficacy for both epileptic syndromes with a reduction in seizure burden and a longer seizure-free interval. We note the higher prevalence of evidence in patients with Dravet syndrome. Fenfluramine has been used in association with both first- and second-line medications, while its use in monotherapy still needs to be assessed. [ABSTRACT FROM AUTHOR]

Selecting the most appropriate antiepileptic drug (AED) or combination of drugs for each patient and identifying the most suitable therapeutic regimen for their needs is increasingly challenging, especially among pediatric populations. In fact, the pharmacokinetics of several drugs vary widely in children with epilepsy because of age-related factors, which can influence the absorption, distribution, metabolism, and elimination of the pharmacological agent. In addition, individual factors, such as seizure type, associated comorbidities, individual pharmacokinetics, and potential drug interactions, may contribute to large fluctuations in serum drug concentrations and, therefore, clinical response. Therapeutic drug concentration monitoring (TDM) is an essential tool to deal with this complexity, enabling the definition of individual therapeutic concentrations and adaptive control of dosing to minimize drug interactions and prevent loss of efficacy or toxicity. Moreover, pharmacokinetic/pharmacodynamic modelling integrated with dashboard systems have recently been tested in antiepileptic therapy, although more clinical trials are required to support their use in clinical practice. We review the mechanism of action, pharmacokinetics, drug-drug interactions, and safety/tolerability profiles of the main AEDs currently used in children and adolescents, paying particular regard to issues of relevance when treating this patient population. Indications for TDM are provided for each AED as useful support to the clinical management of pediatric patients with epilepsy by optimizing pharmacological therapy. [ABSTRACT FROM AUTHOR]

Background: In the treatment of pediatric epilepsy, there is a critical demand for effective and safe therapeutic options to address patients' unmet clinical needs. Eslicarbazepine acetate is a novel once-daily antiepileptic drug and a third-generation single enantiomer member of the dibenzazepine family.Objective: The objective of this study was to evaluate the efficacy and safety of eslicarbazepine acetate as add-on treatment for focal-onset seizures in pediatric patients using meta-analytical techniques.Methods: Randomized, placebo-controlled, single- or double-blinded add-on trials of eslicarbazepine acetate in patients < 18 years of age with focal-onset seizures uncontrolled by concomitant stable antiepileptic drug regimens were identified through a systematic literature search. The assessed outcomes included the mean relative change and ≥ 50% reduction in the baseline seizure frequency, the incidence of treatment withdrawal, serious adverse events, and treatment-emergent adverse events. Risk ratio and weighted mean difference with 95% confidence intervals were estimated for dichotomous/continuous outcomes.Results: Two trials were included involving 386 participants (age range 2-18 years), 217 for eslicarbazepine acetate and 169 for placebo groups, respectively. At the dosage of 30 mg/kg/day, eslicarbazepine acetate-treated patients had a significantly greater reduction in baseline seizure frequency (weighted mean difference - 21.67, 95% confidence interval - 40.87 to - 2.46; p = 0.027) and 58 patients (44.6%) were seizure responders compared with 27 controls (29.7%) [risk ratio 1.48, 95% confidence interval 0.99-2.20; p = 0.055]. There were no differences in treatment withdrawal (risk ratio 1.24, 95% confidence interval 0.65-2.37; p = 0.513), serious adverse events (risk ratio 1.40, 95% confidence interval 0.69-2.86; p = 0.350), and treatment-emergent adverse events (risk ratio 1.07, 95% confidence interval 0.94-1.22; p = 0.313).Conclusions: Adjunctive eslicarbazepine acetate could be an effective well-tolerated option in children and adolescents with focal-onset seizures uncontrolled by one or more concomitant anti-epileptic drugs. [ABSTRACT FROM AUTHOR]

Epilepsy is common in children and adolescents where its prevalence is 3.2-5.5/1000. About one-third of patients also have attention deficit hyperactivity/impulsivity disorder (ADHD). The possible relationship between epilepsy and ADHD is still unclear, and ADHD symptoms (such as inattention, hyperactivity, behavioral disturbances) are frequently considered as adverse effects of antiepileptic drugs (AEDs). The literature was searched for data on the behavioral effects of AEDs. Phenobarbital is the most frequently reported medication to induce symptoms of ADHD, followed by topiramate and valproic acid. Phenytoin seems to exert modest effects, while for levetiracetam there are contrasting data. Lacosamide induces some beneficial effects on behavior; carbamazepine and lamotrigine exert favorable effects on attention and behavior. Gabapentin and vigabatrin have limited adverse effects on cognition. Oxcarbazepine, rufinamide, and eslicarbazepine do not seem to aggravate or induce ADHD symptoms, whereas perampanel can lead to a high incidence of hostile/aggressive behavior, which increases with higher dosages. Information about the behavioral effects of ethosuximide, zonisamide, tiagabine, pregabalin, stiripentol, and retigabine is still limited. Because ADHD significantly affects the quality of life of epilepsy patients, the clinical management of this neuropsychiatric disorder should be a priority. Methylphenidate is effective most children and adolescents with ADHD symptoms and comorbid epilepsy, without a significant increase of seizure risk, although data are still limited with few controlled trials. [ABSTRACT FROM AUTHOR]

Macrophage activation syndrome (MAS) is a reactive form of hemophagocytic lymphohistiocytosis, complicating Still's disease, both in paediatric and adult patients. In this work, we aimed to investigate clinical picture and outcome of Still's disease patients developing MAS. We performed a retrospective analysis of patients, both paediatrics and adults, affected by Still's disease attending our department . During the follow-up, each patient was investigated for MAS occurrence and possible predictors, clinical and laboratory factors, were analysed. We evaluated 50 patients affected by Still's disease, 21 paediatric and 29 adult patients. Ten patients experienced MAS (five adult and five paediatric patients) and its development significantly reduced the survival rate when compared with patients without this complication ( p < 0.0001). The analysis of possible predictors showed that high-value systemic score ( p = 0.03) and high levels of serum ferritin ( p = 0.002) were independently associated with an increased likelihood of MAS. MAS occurrence significantly reduced survival rate in both paediatric and adult patients affected by Still's disease. The high levels of serum ferritin and an elevated systemic score, at the time of diagnosis, were significantly associated with MAS. [ABSTRACT FROM AUTHOR]

Purpose: Red reflex is a test that can detect potentially life-threatening ocular abnormalities. In 2012, a red reflex screening campaign was started in Umbria, central Italy. In this study, we report the results of the first 3 years (2012-2014) of screening. Methods: Red reflex screening was carried out in the 11 regional birth centres. On the first level, the test was performed on all newborns within the third day of life. A pathologic test was an indication for referral to the nearest Ophthalmology Hospital Department (II level). Patients were referred to the Perugia University Ophthalmology Hospital Department if an ulterior evaluation or if treatment was necessary (III level). Results: Between 1 January 2012 and 31 December 2014, 22,884 children were born in Umbria and of these, 22,272 (97.3%) were tested with the red reflex. Four hundred and sixty-one (4.83%) neonates resulted having a positive or equivocal test and were sent to II level. Three of these cases (0.01%) were affected by an important eye disease, in particular two patients (0.009%) presented congenital cataract and one patient (0.005%) presented retinoblastoma. Conclusion: Our results are consistent with the previous findings, although reports on red reflex screening are sporadic in the literature. Despite the high number of false positives, the red reflex test has proven to be a useful, easy to perform and low cost test for the early detection of congenital low vision diseases, and our data confirm that it must become part of normal neonatal assessments. [ABSTRACT FROM AUTHOR]

Clomiphene citrate (CC) is the oldest drug used to regulate the process of ovulation. Considering the great use of CC over the last 40 years, it is important to understand the possible risks associated with its use. The aim of this review was to evaluate the possible teratogenic effects of CC, analyzing results obtained from animal and human studies. The pharmacokinetics of CC and possible mechanisms involved in teratogenesis are examined. Fetal exposure to CC is possible due to the long half-life of CC and its metabolites. Alarming data have emerged from animal studies, although controversial results come from human studies. There is some evidence regarding a possible association of CC exposure and fetal malformations, mainly neural tube defects and hypospadias, which would require further investigation in order to allow safer use of this useful drug. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown a possible coexistence of absence seizures with other forms of epilepsy. The purpose of this study was to ascertain the possible contemporary or subsequent presence of childhood absence epilepsy (CAE) and benign epilepsy with centro-temporal spikes (BECTS) in pediatric epileptic patients. Data sources: A PubMed systematic search indexed for MEDLINE, PubMed and EMBASE was undertaken to identify studies in children including articles written between 1996 and 2015. Retrospective studies, meta-analysis and case reports were included. The list of references of all the relevant articles was also studied. The date of our last search was December 2015. Results: Review of the literature revealed 19 cases, 8 females and 11 males, reporting a consecutive or contemporary coexistence of CAE and BECTS within the same patients. Patient's age ranged between 4 and 12 years. Three out of 19 patients presented concomitant features of both syndromes, whereas 16 patients experienced the two syndromes at different times. Conclusions: BECTS and CAE may be pathophysiologically related, and the two epileptic phenotypes may indicate a neurobiological continuum. Further studies are needed to elucidate a probable genetic or functional link between partial and primarily generalized electro-clinical patterns in idiopathic childhood epilepsies. [ABSTRACT FROM AUTHOR]

Corpus callosum abnormality (CCA) outcomes are quite unpredictable and variable, from asymptomatic forms to mild or severe neurodevelopment disorders. The aim of this study was to examine clinical outcomes in CCA patients. The study included 61 children and adolescents in whom brain magnetic resonance imaging (MRI) scans showed CCA, isolated or associated to other central nervous system lesions. All patients underwent anamnesis, physical and neurological examination, routine laboratory tests, electroencephalogram (EEG), and MRI scans. In all participants, the intelligence quotient (IQ) was determined. We divided the participants into two subgroups: the first subgroup included patients with an isolated CCA, and the second subgroup included patients with CCA associated with extra-callosal brain lesions (complex CCA). We found that CCA were associated with elevated frequency to intellectual disability (ID), other neurodevelopment disorders, epilepsy, and isolated EEG anomalies. Mild ID ( p = 0.003) was more frequent in the isolated subgroup, while epilepsy ( p = 0.036) and pre-perinatal risk factors ( p = 0.023) were more frequent in the complex CCA subgroup. Although the role of the CC in the interhemispheric communication is known, neurological and neurodevelopment outcomes of CCA are extremely variable and unpredictable. The presence of extra-callosal brain anomalies is one of the major prognostic factor, and probably, they have an important impact on the clinical outcome. [ABSTRACT FROM AUTHOR]

Cannabis is one of the oldest psychotropic drugs and its anticonvulsant properties have been known since the last century. The aim of this reveiw was to analyze the efficacy of cannabis in the treatment of epilepsy in adults and children. In addition, a description of the involvement of the endocannabinoid system in epilepsy is given in order to provide a biochemical background to the effects of endogenous cannabinoids in our body. General tolerability and adverse events associated with cannabis treatment are also investigated. Several anecdotal reports and clinical trials suggest that in the human population cannabis has anticonvulsant properties and could be effective in treating partial epilepsies and generalized tonic-clonic seizures, still known as 'grand mal.' They are based, among other factors, on the observation that in individuals who smoke marijuana to treat epilepsy, cessation of cannabis use precipitates the re-emergence of convulsive seizures, whereas resuming consumption of this psychotropic drug controls epilepsy in a reproducible manner. In conclusion, there is some anecdotal evidence for the potential efficacy of cannabis in treating epilepsy. Though there has been an increased effort by patients with epilepsy, their caregivers, growers, and legislators to legalize various forms of cannabis, there is still concern about its efficacy, relative potency, availability of medication-grade preparations, dosing, and potential short- and long-term side effects, including those on prenatal and childhood development. [ABSTRACT FROM AUTHOR]

Background and Objective: Concerns that antiepileptic brand-to-generic interchange results in disruption of seizure control are widespread. The objective of this study was to evaluate the safety and tolerability of the brand-to-generic levetiracetam switch in patients with focal or generalized epilepsy. Methods: A prospective study in patients with primary, cryptogenic or symptomatic epilepsy, who were taking branded levetiracetam and were switched to generic levetiracetam. Patients were consecutively recruited from January 2013 to January 2015. We evaluated efficacy, tolerability and compliance before switching (T0) and after 6 months of therapy (T1). Evaluations were scheduled as follows: baseline, 7 and 15 days, 1, 3 and 6 months. At each visit clinical diary seizures, physical and neurological examination, laboratory parameters and electroencephalogram were evaluated. Results: Fifty-nine patients, equally mixed by sex, were included in the study. Mean age was 26.1 years. Forty-seven per cent of the patients enrolled received levetiracetam as monotherapy. One patient was lost during the follow-up: so at T1 we had 58 patients (28 monotherapy and 30 polytherapy). At T0 and at T1, there was no statistically significant difference in terms of seizure frequency and intensity, occurrence of adverse events, laboratory parameters and electroencephalographic features. Two patients stopped treatment with the generic (both at 3 months after the switch) and restarted therapy with brand levetiracetam because of seizure increase. At the end of the study, the switchback rate was 3.4 %. Conclusions: No increase of seizures and adverse effects were observed when branded levetiracetam was interchanged to a generic equivalent. More studies should be conducted with a larger series of patients to confirm these results. [ABSTRACT FROM AUTHOR]

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, but potentially fatal, adverse reaction that occurs in patients, including children, who are treated with anticonvulsants. During metabolism of the anticonvulsant, toxic arene-oxide compounds are produced. AHS is associated with both cutaneous and systemic symptoms and is associated with multiorgan involvement. Liver damage, in particular, seems to be associated with fatal outcomes. The pathophysiology of AHS is still uncertain but it may be linked to a genetically determined inability to detoxify reactive drug metabolites. The prompt recognition of the first clinical signs of AHS, and the rapid withdrawal of the anticonvulsant, often avoids the progression of symptoms. Pharmacological treatment is essentially based on systemic corticosteroids in association with enteral nutrition, intravenous fluid augmentation, pain relief and ocular care. Intravenous immunoglobulins may also have a possible therapeutic role in some cases. Diagnostic tests, such as patch tests or in vitro assays, for AHS could help to identify patients at risk of developing the syndrome and could represent a first step of primary prevention when applied to relatives of patients. [ABSTRACT FROM AUTHOR]

In epilepsy trials a substantial proportion of patients receiving placebo has some improvement or experience adverse events (AEs) which match those related to active drug. The characterization of factors influencing these responses is crucial for a better comprehension of study results and to improve design of new trials. Seventy-one placebo-controlled, double-blind trials in drug-resistant focal epilepsies has been selected. The effect of multiple factors on some outcome measures were explored using a meta-regression model. For subjective and objective AEs, risk difference (RD) was calculated and entered in an inverse variance-weighted linear meta-regression model as independent variable to evaluate the relationship with data reported in placebo-treated patients. The number of study arms influence the percentage of patients withdrawing because of AEs and the highest dose of the experimental drug used in each RCT correlates with withdrawal because of AEs and with subjective AEs. Higher titration speed is associated with lower percentages of responders and higher reporting of both objective and subjective AEs. The correlation between proportions of placebo-treated patients with subjective and objective neurological AEs and relative RD, was significant ( P = 0.002 r = 0.364 and P < 0.001 r = 0.650, respectively). Efficacy and tolerability outcomes of the placebo groups are intrinsically tied to the trial methodology and to the outcomes observed in patients treated with the active drug. The correlation for objective and subjective AEs between RD and the placebo-treated patients suggest that investigators are influenced by factors which operate within each specific trial. [ABSTRACT FROM AUTHOR]

Stickler syndrome is a genetically heterogeneous collagenopathy characterized by auditory, ocular, musculoskeletal, and orofacial abnormalities. Stickler syndrome type 1 typically presents ophthalmologic involvement and is due to heterozygous defects of the COL2A1 gene, that have been also identified as the molecular cause of a continuous spectrum of different disorders mainly affecting the cartilage and bone (i.e., Kniest dysplasia, achondrogenesis type II, Legg-Calvè-Perthes disease). We report three Caucasian children with: (a) ocular, oral, facial, auditory, and musculoskeletal manifestations of Stickler syndrome type 1; (b) history of generalized and/or partial seizures coupled with abnormal electroencephalographic records; and (c) pathogenic heterozygous mutations of the COL2A1 gene. Epilepsy has been never reported so far in literature as a possible feature of Stickler syndrome, although neurological presentations, including epilepsy and brain abnormalities, have been occasionally described in other COL2A1-related phenotypes (e.g., Legg-Calvè-Perthes disease). Conclusions: This report raises the possibility of a potential occurrence of seizures among the clinical manifestations of Stickler syndrome type 1, suggesting the presence of a continuous neurological spectrum in some individuals harboring heterozygous mutations in COL2A1. [ABSTRACT FROM AUTHOR]

Health-related quality of life of patients with epilepsy is heavily influenced by antiepileptic drug (AED) tolerability. However, an accepted method for precise assessment of AED-induced adverse events (AEs) has not yet been established. Assessment of tolerability and of the frequency of predefined AEs among drug-resistant epilepsy patients through an analysis of placebo-treated patients from randomized controlled studies (RCTs) performed in patients with partial onset epilepsies (POS) and evaluation of factors which may influence the occurrence of AEs in these patients are the objectives of this study. We searched all double-blind, placebo-controlled trials investigating any AED on adult patients with POS and extracted both for patients treated with placebo and for those treated with the active drug, number of patients, number of responders, number of patients withdrawing because of AEs, number of patients with AEs, and number of patients with 11 predefined AEs. We also explored the effect of multiple factors on AEs reporting. Seventy-nine RCTs were included in our study with 12,594 patients, 6,793 of whom randomized to placebo. In placebo-treated patients, overall responder rate was 15.2 %, proportion of placebo-treated patients withdrawing because of AEs was 3.9 %, and proportion of patients with AE was 60.3 %. The four most frequently reported AEs were headache (12.4 %) somnolence (8.6 %), dizziness (8.2 %), and fatigue (7.9 %). Several factors were found to influence these outcomes. Several factors influence AEs' appearance in RCTs. Among the most important, we found the expectations of patients and doctors and their attitudes on the positive or negative effect of a drug. [ABSTRACT FROM AUTHOR]

Purpose: To monitor weight regain after therapy discontinuation in patients with migraine experiencing weight loss during topiramate (TPM) treatment. Methods: Patients with migraine without aura were enrolled in this observational prospective study. Weight, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, leptin, and ghrelin, and homeostatic model assessment of insulin resistance (HOMA-IR) were evaluated before starting TPM (T1), at 3 (T2) and 6 (T3) months of treatment and 6 months after withdrawal of TPM (T4). Weight loss/regain was considered as a change of 5 % of pre-TPM body weight. Results: A total of 241 patients were analyzed. Of these, 87 (36 %) patients experienced weight loss on TPM medication. During TPM therapy significant reductions in mean values of weight ( p < 0.001), BMI ( p < 0.001), waist circumference ( p < 0.01), HOMA-IR ( p < 0.01), and leptin ( p < 0.01) were observed. After TPM discontinuation, all of these parameters showed a clear trend to increase at T4, achieving pre-TPM values in 27 patients. Among potential predictors, only HOMA-IR before starting TPM (parameter estimate = 1.36, effect size = 0.75; p = 0.006) was significantly associated with weight regain after therapy discontinuation. Conclusions: Loss of body weight is a reversible effect, which at 6 months after TPM discontinuation shows a clear trend to return to baseline values. HOMA-IR is the only predictive factor of weight regain. [ABSTRACT FROM AUTHOR]

Prader-Willi syndrome is a multisystemic genetic disorder that can be associated with epilepsy. There is insufficient information concerning the clinical and electroencephalographic characteristics of epilepsy and the long-term outcome of these patients. The aim of this study is to describe seizure types, electroencephalographic patterns and long-term seizure outcome in Prader-Willi syndrome patients suffering from epilepsy. We retrospectively studied 38 patients with Prader-Willi syndrome and seizures. Results of neuroimaging studies were obtained for 35 individuals. We subdivided these patients into two groups: group A, 24 patients, without brain lesions; and group B, 11 patients, with brain abnormalities. All patients were re-evaluated after a period of at least 10 years. Twenty-one patients (55.2 %) were affected by generalized epilepsy and 17 patients (44.8 %) presented focal epilepsy. The most common seizure type was generalized tonic-clonic seizure. The mean age at seizure onset was 4.5 years (ranged from 1 month to 14 years). In the follow-up period, seizure freedom was achieved in 32 patients (84.2 %). Seizure freedom was associated with electroencephalographic normalization, while the six children presenting drug-resistant epilepsy showed persistence of electroencephalographic abnormalities. Group B patients showed a higher prevalence of drug-resistant epilepsy. Patients with Prader-Willi syndrome were frequently affected by generalized seizures. Most of the patients had a favorable evolution, although, patients with brain abnormalities presented a worse outcome, suggesting that the presence of these lesions can influence the response to antiepileptic therapy. [ABSTRACT FROM AUTHOR]

Background: The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool is a validated questionnaire used to assess the methodological quality of clinical guidelines (CGs). We used the AGREE II tool to assess the development process, the methodological quality, and the quality of reporting of available pediatric CGs for the management of headache in children. We also studied the variability in responses related to the characteristics of eleven Italian neuropediatric centers, showing similarities and differences in the main recommendations reported in CGs. Methods: A systematic literature search was conducted from January 2002 to June 2013 on Mediline, the Cochrane database, the National Guideline Clearinghouse website and the NHS evidence search tool, using the following terms: headache, cephalalgia, guidelines and children (MESH or text words). Six CGs providing information on the diagnosis and management of headache and specific recommendations for children were selected. Eleven neuropediatric centers assessed the overall quality and the appropriateness of all available CGs using of the AGREE II instrument. Results: Six CGs meeting the inclusion and exclusion criteria were identified and assessed by 11 reviewers. Our study showed that the NICE CGs was “strongly recommended” while the French and Danish CGs were mainly “not recommended”. The comparison between the overall quality score of the French CGs and the NICE CGs was statistically significant (6.54 ± 0.69 vs 4.18 ± 1.08; p =0.001). The correlation analysis between quality domain score and guideline publication date showed a statistically significant association only for the “editorial independence” domain (r = 0.842 p = 0.035). The intra-class coefficients showed that the 11 reviewers had the highest agreement for the Lewis CGs (r = 0.857), and the lowest one for the NICE CGs (r = 0.656). Statistical analyses showed that professionals from outpatient services dedicated pediatric headache assigned a higher overall quality score to the NICE CGs as compared to professionals from non-outpatient services (6.86 ± 0.38 vs 6.0 ± 0.82; p = 0.038). Conclusions: CGs resulted definitely of low-moderate quality and non “homogeneous”. Further major efforts are needed to update the existing CGs according to the principles of evidence based medicine. [ABSTRACT FROM AUTHOR]

Many antiepileptic drugs (AEDs) are associated with hematological disorders that range from mild thrombocytopenia or neutropenia to anemia, red cell aplasia, until bone marrow failure. Fortunately, potentially fatal hematological disorders such as aplastic anemia are very rare. This review investigates hematological effects associated with classic and newer AEDs: a PubMed search indexed for MEDLINE was undertaken to identify studies in adults, children and animals using the name of all anticonvulsant drugs combined with the terms 'hematological disease' and 'hematological abnormalities' as key words. The most common hematological alterations occur with older AEDs than newer. Indeed, careful hematological monitoring is needed especially using carbamazepine, phenytoin and valproic acid. The pathogenetic mechanisms are still unknown: they seem to be related to an immunological mechanism, but drugs pharmacokinetics and pharmacodynamics interactions may also play an important role. Further research is needed to assess the real pathogenetic mechanism at the basis of hematological complications caused by AEDs. [ABSTRACT FROM AUTHOR]

Background: Epilepsy associated with Prader-Willi syndrome (PWS) represents an early and important complication, often not clearly reported and described in the literature. Consequently, there are controversial data about the clinical characteristics of epilepsy and electroencephalographic (EEG) abnormalities found in these patients. Data sources: Based on recent original publications, we have reviewed the different types of seizures and EEG findings in PWS patients, the response to antiepileptic treatment, and the prognosis of epilepsy. Results: The frequency of epilepsy in PWS patients ranges from 4% to 26%. The types of seizure include generalized tonic-clonic seizures, complex partial seizures, atypical absence, staring spells, and myoclonic, tonic and hemiclonic seizures, but the most frequent type is focal epilepsy. Status epilepticus has never been reported. EEG abnormalities are not typical but variable in different patients. However, generalized and focal discharges are the most frequently reported findings. There is no evidence of relationship between the course of epilepsy and frequency, morphology and spread of EEG discharges. However, epilepsy in PWS patients is usually responsive to antiepileptic monotherapy with rapid seizure control and a good outcome. Conclusions: The frequency of epilepsy is higher in PWS patients than in general populations and this complication can be a challenge for the clinicians of these patients. Prospective studies are needed to confirm the good long-term prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Epilepsy and migraine frequently show a clinical overlap. An increase in number of electroencephalographic abnormalities, such as centro-temporal spikes (CTS), may be observed in patients suffering from migraine, epileptic abnormalities that are typically in benign epilepsy of childhood with CTS (BECTS). The aim of this study is to better define the role of CTS in children with migraine compared to children with BECTS, in relation with their neuropsychological profile. Methods: Thirty-two children were enrolled and divided into three groups on the basis of their diagnosis: 16 children (eight males and eight females, aged 12.3 ± 2.58 years) affected by BECTS, 8 patients (four males and four females, aged 11.8 ± 3.47 years) affected by BECTS and migraine, and 8 children (four males and four females, aged 13.5 ± 1.79 years) affected by migraine showing CTS abnormalities. A cognitive and neuropsychological assessment was performed, using Wechsler Intelligence Scale for Children-third edition and NEPSY II, in all patients. Results and conclusions: A similar neuropsychological impairment was found in patients affected by BECTS and in those affected by BECTS and migraine; a significant deficit in short- and long-term verbal memory was evident in patients affected by migraine and CTS. CTS in patients with migraine can influence the neuropsychological tests, with a possible negative impact on language and learning development. [ABSTRACT FROM AUTHOR]

Migraine without aura (MoA) could be considered the most frequent form of primary headache in children, associated with many known comorbidities, but only the recent literature has begun to consider the importance of motor impairment linked to the attacks. The developmental coordination disorder (DCD) is a very common problem among children, with a prevalence ranging up to 19 %. The aim of this study was to evaluate the presence of motor coordination impairment in a population of children affected by MoA, and its role as putative risk factor for motor skills impairment. This observational study was performed in the Clinic of Child and Adolescent Neuropsychiatry of the Second University of Naples. MoA was diagnosed according to the International Classification of Headache Disorders (IHS-2) criteria. The study population consisted of 27 patients affected by MoA (16 females, 11 males) (mean age: 8.7 ± 2.15 years) and 59 typically developing children (34 females, 25 males) (mean age: 8.0 ± 2.1 years). The whole population underwent a clinical evaluation in order to assess the total IQ level, the visual motor integration skills, and the presence of DCD. Our results showed that MoA children had more impairments in motor coordination ( p < 0.001) and visual motor integration ( p < 0.001) than control group. To our knowledge, this is the first study to assess the association of poor motor coordination and MoA in children using objective measurements. These findings suggest a new perspective in the management of migraine disease in children, pinpointing that the relationship between DCD and migraine could represent a not yet understood or identified comorbidity, even if further reports are necessary, and that migraine probably could be considered not only a painful syndrome in future. [ABSTRACT FROM AUTHOR]

Several techniques have been used to diagnose gastroesophageal reflux (GER) in children, but no single test is sufficiently accurate to completely investigate the problem. Gastroesophageal US has been described as a widely available, noninvasive and sensitive method. It provides morphological and functional information, but its role in the diagnosis of GER in children is still debated. In this paper we review diagnostic approaches to GER in children. We focus on current use of US in the management of children with suspected GER. Reports suggest that US allows exclusion of several non-GER causes of symptoms and that it provides morphological and functional data with high sensitivity and positive predictive value for the diagnosis of GER. Sonographic assessment of findings such as abdominal esophageal length, esophageal diameter, esophageal wall thickness and gastroesophageal angle provide important diagnostic indicators of reflux and related to the degree of GER. There is a need for standardization of the procedure and for defining diagnostic criteria. [ABSTRACT FROM AUTHOR]

The advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) pathway is a key mediator of glomerular changes in type 1 diabetes. We evaluated endogenous secretory (es)RAGE and soluble (s)RAGE concentrations in 64 pre-pubertal and pubertal normoalbuminuric patients with type 1 diabetes and compared the values with those of 62 controls matched for age, gender and Tanner pubertal stages. We also explored the possible association of their concentrations with early signs of diabetic nephropathy, defined as changes in kidney volume and estimated glomerular filtration rate (eGFR). Significantly lower concentrations of both esRAGE and sRAGE were documented in pre-pubertal ( p = 0.003 and p = 0.001) and pubertal ( p = 0.002 and p = 0.001) subjects with type 1 diabetes than in the controls. In both groups of patients with type 1 diabetes, the eGFR (pre-pubertal p = 0.01 and pubertal p = 0.01) and the mean value of kidney volume adjusted for body surface (pre-pubertal p = 0.003 and pubertal p = 0.002) were higher than those of the controls. The regression analysis showed an inverse relationship between esRAGE and body surface-adjusted mean kidney volume ( p = 0.0004, r = −0.503). esRAGE and sRAGE concentrations were lower in normoalbuminuric youths with type 1 diabetes than in their healthy peers. The inverse association between esRAGE levels and early kidney alterations suggests a potential role of esRAGE in diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Purpose: Headache in epileptic population ranges from 8% to 15%. The aim of this paper was to study the clinical and temporal characteristics of primary headache comorbidity in idiopathic epileptic children. Methods: From June 2006 to June 2009, a cross-sectional multi-center study involving five Italian Child Neurology University Centers (two in Rome, one in Chieti, one in Naples, and one in L'Aquila) was conducted. Among 1,264 consecutively newly diagnosed, idiopathic, partial, or generalized, epileptic children, according to ILAE diagnostic criteria (aged between 5 and 15 years of age), we selected 142 children (11.2%) (130 of whom completed the study) who showed an associated peri-ictal and/or inter-ictal headache diagnosed according to the International Headache Society Criteria. Rare cases of 'ictal epileptic headache', in which headache represents the sole ictal epileptic manifestation, were excluded from this study. Results and conclusions: Post-ictal headaches were most frequent (62%). Pre-ictal headaches were less common (30%). Inter-ictal headaches were described in 57.6%. Clear migrainous features were present in 93% of pre-ictal and 81.4% of post-ictal headaches. Inter-ictal headaches meet criteria for migraines in 87%. The association between partial epilepsy and migraine without aura is most common and reported in 82% of our patients with peri-ictal headache and in 76.5% of patients with post-ictal headache. [ABSTRACT FROM AUTHOR]

Introduction: Subcortical band heterotopia (SBH) or double cortex syndrome is a malformation of cortical development that may be related to intractable epilepsy and severe mental retardation or to mild epilepsy and slight mental delay or normal cognitive functions. Several studies have been performed using neuroradiological or neurophysiological techniques, like SPECT, PET, MRS, fMRI, and MEG, in attempt to better characterize this neuronal migration disorder. Recently, also diffusion tensor imaging (DTI) and fiber tracking (FT) have been used to investigate on white matter anomalies in SBH, adding more information about such gray matter anomaly. Methods: We report on three cases of SBH, evaluated with MRI, DTI, and FT. Conclusions: The data gathered from DTI and TF allow us to hypothesize a new functional role for heterotopic gray matter. [ABSTRACT FROM AUTHOR]

Introduction: The maldevelopment of the midline structures is connected with neurologic disorders. The cavum septum pellucidum (CSP) exists in the fetal period, then it is re-absorbed. The presence of unfused leaflets/fornices may be considered important in the genesis of neurodevelopmental abnormalities inclunding epilepsy. The limbic system includes a group of interconnected gray and white matter structures; in this circuit, the fornix is an important white matter connection with the septum pellucidum. Methods: Five children, 3-10 years of age, with epilepsy and an unfused septum pellucidum and fornices on MRI, were evaluated by diffusion tensor imaging-fiber tracking (DTI-FT) in order to explore the integrity of the axonal microenviroment of these structures. Results: The patients had generalized tonic-clonic seizures (GTCS). The electroencephalogram (EEG) showed focal-temporal abnormalities with secondary generalization. Magnetic resonance imaging (MRI) and DTI-FT demonstrated the CSP, and the presence of the fornix's body split into two bundles with the fornices separated. Conclusion: The fornix appears more involved than CSP alone, as suggested by fornix atrophy observed in MTLE. Even if epilepsy is suggested to be a grey matter disorder, changes in the underlying brain connectivity have an important contribution in seizure generation and diffusion. In addition, the interconnections of medial septal area with hyppocampus, amygdala and entorhinal cortex, have led to the hypothesis of functional limbic epilepsy. In our patients, the role of DTI was not conclusive since the definition of the number of unmyelinated fibers responsible for epilepsy could not be demonstrated probably for a limited number of seizures and for a short period of drug administration. [ABSTRACT FROM AUTHOR]

lthough headache and epilepsy have often been associated, the precise electroclinical and pathophysiological interaction between these disorders and in particular its relations with photosensitivity is as yet to be fully understood in adults or children. The association between headache and epilepsy commonly occurs in all types of epilepsy and not only in occipital epilepsy. Generally, peri-ictal headache is often neglected, regardless of its severity, because patients are more concerned about their seizures. Altered cerebral cortex excitability may be the link between these two conditions and photosensitivity shows this. The physician should bear this association in mind when dealing with epileptic and migraine patients so as to be able to offer such patients an accurate diagnosis and appropriate treatment; this should be borne in mind when declaring epileptic patients 'seizure free'. To date neither the International Headache Society nor the International League against Epilepsy mention that headache/migraine may, on occasion, be the sole ictal epileptic manifestation. Lastly, studies designed to investigate the triggering role of photosensitivity in both headache and epilepsy are warranted. [ABSTRACT FROM AUTHOR]

Levetiracetam is an antiepileptic drug that has been shown to be effective in various types of seizures, both partial and generalized. Although it is not yet well established because of the small number of studies, levetiracetam as both add-on therapy and monotherapy can be considered as an alternative to valproic acid in some pediatric patients. We have reviewed the available data on the efficacy, tolerability, and safety of levetiracetam in children with epilepsy. The efficacy of levetiracetam as an adjunctive therapy and as monotherapy for generalized and partial childhood epilepsies and for some types of specific epilepticsyndromes of infancy and childhood (such as juvenile myoclonic epilepsy, benign rolandic epilepsy, and Jeavon syndrome) has been demonstrated in some studies. Moreover, levetiracetam may be a valuable option for children with refractory epilepsy. The reported tolerability of levetiracetam and its safety profile are favorable. Among the side effects reported, behavioral changes and even psychotic reactions seem to occur more frequently in younger patients (under 4 years of age). The onset of signs/symptoms usually occurs early, even during the titration phase, and, in many cases, at a low dosage (<20 mg/kg/day). These side effects were always observed to be reversible after discontinuation of levetiracetam. [ABSTRACT FROM AUTHOR]

We investigated whether children affected by tension-type headache and migraine without aura, compared with a healthy control group that was matched by age, culturally and socioeconomically display a diverse intellectual functioning and have a separate “cognitive profile”. A cross-sectional study was conducted from January 2006 to November 2008 at “Sapienza University” in Rome. A total of 134 children were diagnosed as being affected by either migraine without aura (93) or tension-type headache (41). On the basis of our exclusion/inclusion criteria, we enrolled 82 of these 134 children, 63 of whom were affected by migraine without aura and 19 by tension-type headache. On entry, cognitive functions were assessed in both the affected subjects and the control group by the Wechsler Intelligence Scale for Children-revised. Significant differences were found between the headache and control groups in the mean total intelligence quotient and verbal intelligence quotient scores ( p < 0.001). Significant negative correlations were found between the total intelligence quotient, verbal intelligence quotient, performance intelligence quotient and the frequency of attacks ( r = −0.55 and p < 0.001, r = −0.61 and p < 0.001, r = −0.29 and p < 0.01, respectively), as well as between the total intelligence quotient score and the age at headache onset ( r = 0.234, p < 0.05). Our results suggest that the cognitive profile of children affected by headache should be assessed at the first child neurology outpatient observation. From a therapeutic point of view, although within a normal range, the abilities most likely to be less brilliant in such children are verbal skills. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) is effective for the treatment of many types of epilepsy, but its use can be associated with an increase in body weight. We report a case of nonalcoholic fatty liver disease (NAFLD) arising in a child who developed obesity during VPA treatment. Laboratory data revealed hyperinsulinemia with insulin resistance. After the withdrawal of VPA therapy, our patient showed a significant weight loss, a decrease of body mass index, and normalization of metabolic and endocrine parameters; moreover, ultrasound measurements showed a complete normalization. The present case suggests that obesity, hyperinsulinemia, insulin resistance, and long-term treatment with VPA may be all associated with the development of NAFLD; this side effect is reversible after VPA withdrawal. [ABSTRACT FROM AUTHOR]

A retrospective multicentre study was performed to analyse psychogenic non-epileptic seizures (PNES) in prepubertal and pubertal patients with idiopathic epilepsy and to determine whether have different clinical characteristics. In this study, we reviewed 36 patients from six neurological referral centres: Department of Pediatrics, Chieti (3 patients); Department of Child Neuropsychiatry, Naples (9 patients); Department of Child Neuropsychiatry, Bologna (8 patients); Department of Neuroscience, Tor Vergata University, Rome (3 patients); Department of Pediatrics, La Sapienza University, Rome (5 patients); and Department of Pediatrics, Siena (8 patients). The population was divided according to Tanner’stages into 14 prepubertal (group I) and 22 pubertal (group II) patients. The two groups were compared on several variables examining the differences between them. The most frequent clinical manifestations in group I were unresponsive events, whereas in group II, motor events were exhibited more significantly. Mood disorders, including major depression, appeared more frequently in pubertal group, but this did not reach a significant difference. Among the psychosocial stressors, fear of rejection and need for attention were the predominant types in the prepubertal patients. The findings of this study reveal some similarities and differences between prepubertal and pubertal patients, which might help to identify predictive factors in patients affected by idiopathic epilepsy who can develop PNES. [ABSTRACT FROM AUTHOR]

Panayiotopoulos syndrome is a relatively frequent and benign epileptic syndrome, characterised by predominantly autonomic symptoms and/or simple motor focal seizures followed or not by impairment of consciousness. Interictal EEG shows occipital spikes although multifocal spikes with high amplitude sharp-slow wave complexes at various locations can be present. This syndrome can imitate gastroenteritis, encephalitis, syncope, migraine, sleep disorders or metabolic diseases. The peculiar aspects should be known not only by epileptologists but also by general doctors because a correct diagnosis would avoid aggressive interventions and concerns on account of its benign outcome. This review focuses on the main clinical and EEG features of this epilepsy underlining its typical and atypical symptoms and its management. [ABSTRACT FROM AUTHOR]

We have read the recent article by Vasquez et al. [[1]] on the possibility of using lung ultrasound (US) for detecting pneumothorax in injured children. The purpose of the study was to examine the sensitivity and the specificity of a single-point lung US exam, comparing US to chest radiography or CT scans. In this regard we have to remember that pneumothoraces restricted to the mediastinal area could not be detected [[6]] and, in best conditions, because of the anatomical constraints of the thoracic cage, only 70% of the lung surface can be assessed by US: in this study a complete chest US examination was not performed. [Extracted from the article]

The objective was to evaluate HLA DR/DQ alleles and their risk factor for type 1 diabetes in the Abruzzo region (central Italy). Sixty incident cases from the Abruzzo region were studied together with 120 unrelated control subjects living in the same administrative areas. The relative risk of diabetes associated with the alleles under study was calculated by deriving the odds ratio (OR) maximum likelihood estimates and their 95% confidence intervals (CI) by the exponentiation of the logistic regression beta–parameter. The combination DRB1*03/DQA1*0501/DQB1*0201 was found in 20.0% of patients and 7.1% of the control subjects, conferring an OR of 4.04 and a CI of 1.97–8.49. The combination DRB1*04/DQA1*0301/DQB1*0302 was found in 23.3% of diabetic patients and 6.7% of controls, giving an OR of 5.69 and a CI of 2.77–12.05. DRB1*11/DQA1*0505/DQB1*0301 and DQA1*0505/DQB1*0301 were negatively associated with type 1 diabetes (OR=0.27, CI 0.11–0.57; OR=0.07, CI 0.02–0.19). The DQA1 genotype at risk was found to be DQA1*0301/DQA1*0501: OR=23.80, CI 2.97–190.89, as it occurred with the highest frequency in the patient group. The DQB1 genotype at risk was found to be DQB1*0201/DQB1*0302, which occurred in 13.3% of patients but in only 1.1% of the control group (OR=29.75, CI 5.36–549.25). Our results shed further light on the risk of development of this disease during a specific time period in an area where the overall incidence of type 1 diabetes is known. [ABSTRACT FROM AUTHOR]

To explore the hypothesis that raised anticardiolipin antibodies, glutamic acid decarboxylase, and antinuclear antibodies may be associated with epilepsy and/or pharmacoresistance, we studied titers in 74 epileptic patients and 50 controls. Epileptic patients were divided into two groups according to their response to anticonvulsant therapy. Group I included 52 children (30 females and 22 males with a mean age±SD of 7.0±2.4 years) suffering from different types of epilepsy who were treated with various anticonvulsants. Group II included 22 children (10 females and 12 males with a mean age of 6.2±3.6 years) suffering from therapy resistant epilepsy. We found that the prevalence of anticardiolipin antibodies was significantly higher in epileptic patients than in controls, while there was no significant difference between patients who were seizure free and those with uncontrolled epilepsy. No significant difference was found in glutamic acid decarboxylase antibodies between epileptic children and controls, and between patients who were seizure free and those with uncontrolled epilepsy. A significant difference in the incidence of antinuclear antibodies was found between epileptic children and controls, while no difference was found between well-controlled and drug-resistant epilepsy. In conclusion, the prevalence of anticardiolipin and antinuclear antibodies was higher in patients with epilepsy than in controls. There was no significant difference in serum glutamic acid decarboxylase antibodies between epileptic children and controls, and between patients who were seizure free and those with uncontrolled epilepsy. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) is an effective anticonvulsant useful in many types of epilepsy and, although it is usually well tolerated, it has been associated with many neurological and systemic side effects. Among these, one of the most important is VPA-induced hyperammonemic encephalopathy (VHE): its typical signs are acute onset of impaired consciousness, focal neurologic symptoms, and increased seizure frequency. The pathogenesis of VHE is still unclear, but it has been suggested that hyperammonemia can produce encephalopathy via inhibition of glutamate uptake by astrocytes which may lead to potential neuronal injury and perhaps cerebral edema. Glutamine production is increased, whereas its release is inhibited in astrocytes exposed to ammonia. The elevated glutamine increases intracellular osmolarity, promoting an influx of water with resultant astrocytic swelling. This swelling could compromise astrocyte energy metabolism and result in cerebral edema with increased intracranial pressure. Moreover, VHE seems to be more frequently in patients with carnitine deficiency or with congenital urea cycle enzymatic defects. [ABSTRACT FROM AUTHOR]

In order to evaluate whether treatment with valproic acid or carbamazepine can modify interleukins and monocyte chemoattractant protein-1, we studied 40 epileptic children and adolescents. We evaluated the patients before and after 1 year of therapy. At the end of follow-up, the patients showed a significant increase of the production of interleukin-1α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1; interleukin-2 production was significantly higher only in patients receiving carbamazepine. In conclusion, antiepileptic drugs can influence the immune system by modifying interleukin and chemokine concentrations; these changes seem to be independent of the serum concentrations of these drugs. [ABSTRACT FROM AUTHOR]

We evaluated the final height achieved by 47 patients who had bone marrow transplantation (BMT) for thalassemia major. Subjects were separated into two groups: patients who received BMT before 7 years of age and patients who received BMT after 7 years of age. Parental height and genetic target height (TH) were calculated. Our data indicated a strict correlation between age at time of transplant and final adult height. The patients whose age at transplant was <7 years had a less impaired growth rate than did patients who were >7 years. Moreover, greatest loss in height was observed in subjects who had higher serum levels of transaminase and ferritin and these biochemical parameters were strictly correlated to the final adult height. Mean final adult height, however, did not differ from the genetic target height in subjects who received BMT before 7 years of age and the final height SDS corrected for TH surpasses even the TH. In contrast, the subjects who received BMT after 7 years of age, failed to achieve their full genetic potential. In conclusion, short stature is present in a significant percentage of transplanted thalassemic children. The data in this study indicate a close effect of the age at time of transplant on subsequent growth rate, but the growth impairment in these subjects remain multifactorial. Bone Marrow Transplantation (2001) 28, 201–205. [ABSTRACT FROM AUTHOR]

In order to evaluate if central static perimetry is useful to identify patients at risk of developing diabetic retinopathy, 60 (27 male, 33 female) adolescents and young adults (mean age, 15.9 years) with insulin-dependent diabetes mellitus were studied prospectively. No patient showed fluorescein angiographic signs of retinopathy initially. The patients were evaluated at the beginning of the study and after 8 years. At the beginning of the study, mean defect in the population was −2.34 dB as determined by perimetry; no patient showed significant impairment of foveal threshold (mean, 33.17 dB). After 8 years of follow-up, 7 patients had developed fluorangiographic signs of retinopathy. Life-table analysis showed that the overall probability of retinopathy development was significantly higher in subgroups of patients with mean sensitivity in areas 2 and 3 below the cut-off. These results suggest that central static perimetry is a useful tool in predicting the development of retinopathy in children with insulin-dependent diabetes mellitus who do not have fluorescein angiographic signs of retinopathy. This tool can help the physician to identify those patients at risk of developing fluorangiographic signs of retinopathy. [ABSTRACT FROM AUTHOR]

Diabetic microangiopathy is characterized by increased prorenin concentrations. In the present study, we evaluated plasma prorenin concentrations in a large group of adolescents with onset of diabetes during childhood to determine whether increasing prorenin levels may predict the development of persistent microalbuminuria. Ninety-seven young diabetic patients were studied; they were divided according to the presence of persistent microalbuminuria, at the end of follow-up, into group A and group B (patients who did not develop and who developed persistent microalbuminuria, respectively). One hundred and two healthy subjects, matched for age and sex, were also selected. Patients were followed up for at least 10 years. At the beginning of the study there were no significant differences in prorenin levels between either the two diabetic groups or the healthy controls. During follow-up, an increase in plasma prorenin started at 4 years and became statistically significant (P<0.01) 3 years before the onset of persistent microalbuminuria. No correlation was found between plasma prorenin levels and HbAlc percentages. In conclusion, an increased concentration of prorenin in plasma precedes the elevation of albumin excretion rate (AER) and, therefore, can be useful for identifying patients with onset of diabetes during childhood at risk of developing incipient nephropathy later in life. [ABSTRACT FROM AUTHOR]

The main objectives of type 1 diabetes mellitus (DM) management include keeping glycemia levels within the euglycemic range to prevent complications. Daily self-monitoring is an important problem for many diabetic patients, particularly for adolescents. The aim of this study was to evaluate the determinants of poor daily self-monitoring, focusing on the patients' parents' perception of the problem. In order to evaluate parents' awareness of their children's disease-monitoring status, we carried out a cross-sectional investigation of a sample of children and adolescents from a population-based register, with the corresponding population of parents. To collect our data, we used a 33-item questionnaire, separately administered by diabetologists to both parents and children. We estimated the concordance with respect to patients' and parents' answers. Adolescents followed their overall medical prescriptions more regularly (48.8%) than children (29.7%), but mostly frequently they forgot to use glycemic tests (adolescents 42.4%, children 29,7%). A major duration of disease affected HbA1c levels (values >: 8%) of patients younger than 14 years (pFisher = 0.016). Our results indicate a worse compliance of adolescents with respect to children in attending to daily self-monitoring, not just regarding daily glycemic levels but also the course of daily activities such as going to school, studying, working, and simulating symptoms and signs of hypo-hyperglycemia. Parents mostly ignored their child's self-monitoring status and the related motivations. [ABSTRACT FROM AUTHOR]