Clinical features and magnesium levels: Novel insights in 15q11.2 BP1-BP2 copy number variants.

BACKGROUND: Investigating copy number variations (CNVs) such as microdeletions or microduplications can significantly contribute to discover the aetiology of neurodevelopmental disorders. 15q11.2 genomic region, including NIPA1 and NIPA2 genes, contains a recurrent but rare CNV, flanked by the break points BP1 and BP2. Both BP1-BP2 microdeletion and microduplication have been associated with intellectual disability (ID), neuropsychiatric/behavioural disturbances and mild clinical features, even if with incomplete penetrance and variable expressivity. The pathogenic role of this CNV is quite unclear though. Unknown variants in other DNA regions and parent-of-origin effect (POE) are some of the mechanisms that have been proposed as an explanation of the wide phenotypic variability. As NIPA1 and NIPA2 encode for proteins that mediate magnesium (Mg2+ ) metabolism, it has been suggested that urinary Mg2+ levels could potentially represent informative and affordable biomarkers for a rapid screening of 15q11.2 duplications or deletions. Furthermore, magnesium supplementation has been proposed as possible therapeutic strategy. METHODS: Thirty one children with ID and/or other neurodevelopmental disorders carrying either a duplication or a deletion in 15q11.2 BP1-BP2 region have been recruited. When available, blood samples from parents have been analysed to identify the CNV origin. All participants underwent family and medical data collection, physical examination and neuropsychiatric assessment. Electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) scan were performed in 15 children. In addition, 11 families agreed to participate to the assessment of blood and urinary Mg2+ levels. RESULTS: We observed a highly variable phenotypic spectrum of developmental issues encompassing ID in most subjects as well as a variety of behavioural disorders such as autism and attention-deficit disorder/attention-deficit hyperactivity disorder. Dysmorphic traits and malformations were detected only in a minority of the participants, and no clear association with growth anomalies was found. Abnormal brain MRI and/or EEG were reported respectively in 64% and 92% of the subjects. Inheritance assessment highlighted an excess of duplication of maternal origin, while cardiac alterations were detected only in children with 15q11.2 CNV inherited from the father. We found great variability in Mg2+ urinary values, without correlation with 15q11.2 copy numbers. However, the variance of urinary Mg2+ levels largely increases in individuals with 15q11.2 deletion/duplication. CONCLUSIONS: This study provides further evidence that 15q11.2 BP1-BP2 CNV is associated with a broad spectrum of neurodevelopmental disorders and POE might be an explanation for clinical variability. However, some issues may question the real impact of 15q11.2 CNV on the phenotype in the carriers: DNA sequencing could be useful to exclude other pathogenic gene mutations. Our results do not support the possibility that urinary Mg2+ levels can be used as biomarkers to screen children with neurodevelopmental disorders for 15q11.2 duplication/deletion. However, there are evidences of correlations between 15q11.2 BP1-BP2 CNV and Mg2+ metabolism and future studies may pave the way to new therapeutic options.

Cholelithiasis management in a third-level pediatric center: case series and literature review.

Pediatric cholelithiasis is being increasingly diagnosed owing to the widespread use of ultrasonography, raised pediatric obesity and use of long-time parenteral nutrition. Clinical presentation is variable and complicated onset could lead to severe consequences. The aim of this study is to present a 15-years-experience of a pediatric third-level-center in treating cholelithiasis. A retrospective study collecting children with gallstone operated on between 2006 and 2020 is presented. Demographic data, clinical presentation, sonographic findings, risk factors, surgery, complications, follow-up were evaluated. 199 patients were included. Twenty-nine patients (14.5%) with cholelithiasis had a complicated onset. Patients with cholelithiasis older than 10 years had a higher rate of symptomatic/complicated onset. Hemolytic disease was the most frequent co-morbidity (16.1%). Laparoscopic cholecystectomy was performed in 192 cases (96.5%) with a conversion rate of 1.6%. Nearly 1% showed a major post-operative complication after cholecystectomy. Cholelithiasis in patients older than 10 years can be safely treated with laparoscopic cholecystectomy, especially if one or more co-morbidities are present. Laparoscopic splenectomy can be easily associated in the same procedure depending on medical indication. Definition of pediatric surgical timing guidelines would be of quite interest in the field.

Different renal manifestations associated with very early onset pediatric inflammatory bowel disease: case report and review of literature.

BACKGROUND: Inflammatory bowel diseases are characterized by chronic inflammation of the gastrointestinal tract. In particular, Crohn disease and ulcerative colitis represent the two most common types of clinical manifestations. Extraintestinal manifestations of inflammatory bowel diseases represent a common complications, probably reflecting the systemic inflammation. Renal involvement is reported in 4-23% of cases. However, available data are limited to few case series and retrospective analysis, therefore the real impact of renal involvement is not well defined. CASE PRESENTATION: We report the case of a 10-years old male affected by very early onset unclassified-Inflammatory bowel diseases since he was 1-year old, presenting with a flare of inflammatory bowel diseases associated with acute kidney injury due to granulomatous interstitial nephritis. Of interest, at 7-year-old, he was treated for IgA nephropathy. To our knowledge, no previous reports have described a relapse of renal manifestation in inflammatory bowel diseases, characterized by two different clinical and histological phenotypes. CONCLUSIONS: The link between the onset of kidney injuries with flares of intestinal inflammation suggest that nephritis maybe considered an extra-intestinal manifestation correlated with active inflammatory bowel disease. However, if granulomatous interstitial nephritis represents a cell-mediated hypersensitivity reaction than a true extraintestinal manifestation of inflammatory bowel diseases is still not clarified. We suggest as these renal manifestations here described may be interpreted as extraintestinal disorder and also considered as systemic signal of under treatment of the intestinal disease.

Disease Activity Patterns in the First 5 Years After Diagnosis in Children With Ulcerative Colitis: A Population-Based Study.

BACKGROUND: The aim of this study was to define clusters of activity in a population-based cohort during the first 5 years after diagnosis in children with ulcerative colitis [UC] and to identify early prognostic risk factors. METHODS: All UC patients from the SIGENP IBD registry with a complete follow-up of at least 5 years were included. Active disease was defined every 6 months in the presence of at least one of the following: clinical activity [Paediatric Ulcerative Colitis Activity Index ≥ 35]; endoscopic activity [Mayo score ≥ 1]; faecal calprotectin > 250 µg/g; hospitalization; surgery; or treatment escalation. Formula-based clusters were generated based on four published questionnaire-based activity patterns in adults, plus one additional cluster. RESULTS: In total, 226 patients were identified. Forty-two [19%] had moderate-severe chronically active disease, 31 [14%] chronic-intermittent, 75 [33%] quiescent, 54 [24%] active disease in the first 2 years after the diagnosis, then sustained remission, and 24 [11%] a remission in the first 2 years then an active disease. Mild disease onset along with a lower clinical severity not requiring the use of corticosteroids at 6 months were related to a quiescent disease course at the next follow-up (logistic model area under the curve 0.86 [95% confidence interval 0.78-0.94]; positive predictive value 67%; negative predictive value 70%). Eight per cent of patients needed surgery, none in the quiescent group [p = 0.04]. CONCLUSIONS: More than one-third of children with UC present with a chronically active or intermittent course during the first 5 years of follow-up. A significant group of patients has active disease in the first 2 years and then sustained remission. Interestingly, after initial treatment, one-third of patients have well-controlled disease throughout.

Comprehensive molecular screening strategy of OCLN in band-like calcification with simplified gyration and polymicrogyria.

Occludin (OCLN) is an important component of the tight junction complex, providing apical intercellular connections between adjacent cells in endothelial and epithelial tissue. In 2010 O'Driscoll et al reported mutations in OCLN to cause band-like calcification with simplified gyration and polymicrogyria (BLC-PMG). BLC-PMG is a rare autosomal recessive syndrome, characterized by early onset seizures, progressive microcephaly, severe developmental delay and deep cortical gray matter and basal ganglia calcification with symmetrical, predominantly fronto-parietal, polymicrogyria. Here we report 4 additional cases of BLC-PMG with novel OCLN mutations, and provide a summary of the published mutational spectrum. More generally, we describe a comprehensive molecular screening strategy taking into account the technical challenges associated with the genetic architecture of OCLN, which include the presence of a pseudo-gene and copy number variants.

The effect of whole-brain radiation (WBI) and Karnofsky performance status (KPS) on survival of patients receiving stereotactic radiosurgery (SRS) for second brain metastatic event.

OBJECTIVE: The objective of the present study is to analyze prognostic factors affecting survival of patients receiving stereotactic radiosurgery (SRS) for second brain metastatic event (SBME) following initial treatment with whole brain irradiation (WBI), surgical resection, or previous SRS. METHODS: The 88 patients treated with SRS for SBME at Philadelphia CyberKnife between January 2006 and October 2013 were included in the study group. Cox proportional-hazards regression was used to identify prognostic factors that significantly impacted survival from the time of SRS for SBME. Independent variables considered in survival analysis included primary disease, first brain metastatic event (FBME) treatment type, age, gender, number of brain metastases at SBME, Karnofsky performance status (KPS), recursive partitioning analysis (RPA), and presence of extracranial metastasis. RESULTS: The median survival for all patients was 7.31 months. Log-rank comparison of Kaplan-Meier survival curves revealed significant impact by Karnofsky performance status (p = 0.003), RPA class (p = 0.008), age (p = 0.014), and FBME treatment type (p = 0.010). Median survival was longer for patients who had not previously received WBI (14.7 months). Median survival was further increased in patients who had not received previous WBI and demonstrated KPS scores of 70-100 (19.5 months). Patients who received WBI prior to SBME treatment experienced a pronounced decrement in median survival (5.7 months), yet patients in this group who demonstrated strong KPS scores (80-100) experienced significantly increased survival (15.5 months). CONCLUSIONS: The outcomes of SRS for SBME are most favorable for patients who have not received previous WBI or who have maintained higher performance status despite previous WBI.

Paediatric ulcerative colitis surgery: Italian survey.

BACKGROUND AND AIMS: Recent epidemiological studies showed an increase in ulcerative colitis among children, especially in its aggressive form, requiring surgical treatment. Although medical therapeutic strategies are standardized, there is still no consensus regarding indications, timing and kind of surgery. This study aimed to define the surgical management of paediatric ulcerative colitis and describe attitudes to it among paediatric surgeons. METHODS: This was a retrospective cohort study. All national gastroenterology units were invited to participate. From January 2009 to December 2013, data on paediatric patients diagnosed with ulcerative colitis that required surgery were collected. RESULTS: Seven units participated in the study. Seventy-one colectomies were performed (77.3% laparoscopically). Main surgical indications were a severe ulcerative colitis attack (33.8%) and no response to medical therapies (56.3%). A three-stage strategy was chosen in 71% of cases. Straight anastomosis was performed in 14% and J-pouch anastomosis in 86% of cases. A reconstructive laparoscopic approach was used in 58% of patients. Ileo-anal anastomosis was performed by the Knight-Griffen technique in 85.4% and by the pull-through technique in 9.1% of patients. Complications after colectomy, after reconstruction and after stoma closure were reported in 12.7, 19.3 and 35% of cases, respectively. CONCLUSIONS: This study shows that there is general consensus regarding indications for surgery. The ideal surgical technique remains under debate. Laparoscopy is a procedure widely adopted for colectomy but its use in reconstructive surgery remains limited. Longer follow-up must be planned to define the quality of life of these patients.

Management of oxygen and carbon dioxide pressure after cardiac arrest.

Experimental evidence shows that derangements of arterial partial pressures of either oxygen (PaO2) and carbon dioxide (PaCO2) immediately after resuscitation from cardiac arrest may increase the severity of organ dysfunction due to whole body ischemia and subsequent reperfusion. Hyperoxia is believed to increase reperfusion injury, especially to mitochondrial membrane due to increased production of reactive oxygen species. Two large observational studies in human adults showed that hyperoxia (defined as a PaO2≥300 mmHg) in the first 24 h after hospital admission was associated with increased mortality or lower likelihood of independent functional status at hospital discharge. Evidence of the effects of hyperoxia in children were less consistent. A reduction of PaCO2 below normal values may cause cerebral vasoconstriction and increase the severity of delayed brain hypopefusion which usually occurs within 24h from resuscitation. Cerebrovascular reactivity to CO2 is preserved during therapeutic hypothermia. According to recent clinical studies, a low PaCO2 after resuscitation is associated with increased mortality and higher rates of poor neurological outcome both in children and in adults, while the effects of a PaCO2 above 45 mmHg are less clear. The PaCO2 derangements are very common in resuscitated patients. Maintaining normal levels of both PaO2 and PaCO2 and in particular avoiding both hyperoxia and hypocapnia may reduce morbidity and improve survival of cardiac arrest survivors. Available clinical evidence is however almost exclusively limited to observational studies which may be biased by potential uncontrolled confounders.

Supratentorial and pontine MRI abnormalities characterize recessive spastic ataxia of Charlevoix-Saguenay. A comprehensive study of an Italian series.

BACKGROUND AND PURPOSE: The autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disorder caused by mutations in the SACS gene. The disease, first described in Canadian families from Québec, is characterized by cerebellar ataxia, pyramidal tract involvement and peripheral neuropathy. METHODS: Analysis of SACS gene allowed the identification of 14 patients with ARSACS from 13 unrelated Italian families. Clinical phenotype, gene mutations and magnetic resonance imaging (MRI) findings were analysed. RESULTS: We found 16 novel SACS gene mutations, including a large in-frame deletion. The age at onset was in infancy, but one patient presented the first symptoms at age 32. Progression of the disease was variable, and increased muscle tone was mostly recognized in later stages. Structural MRI showed atrophy of the superior cerebellar vermis, a bulky pons exhibiting T2-hypointense stripes, identified as the corticospinal tract (CST), thinning of the corpus callosum and a rim of T2-hyperintensity around the thalami in 100% of cases. The presence of iron or other paramagnetic substances was excluded. Diffusion tensor imaging (DTI) revealed grossly over-represented transverse pontine fibres (TPF), which prevented reconstruction of the CST at this level (100% of cases). In all patients, significant microstructural alterations were found in the supratentorial white matter of forceps, cingulum and superior longitudinal fasciculus. CONCLUSIONS: Our findings further enlarge the genetic spectrum of SACS mutations and widen the study of clinical phenotype. MRI characteristics indicate that pontine changes and supratentorial abnormalities are diagnostic. The over-representation of TPF on DTI suggests a developmental component in the pathogenesis of the disease.

A validated HPLC method for the monitoring of thiopurine metabolites in whole blood in paediatric patients with inflammatory bowel disease.

Therapeutic drug monitoring (TDM) of major metabolites of thiopurine drugs is a widely used tool for assessing treatment efficacy and toxicity in patients with inflammatory bowel disease (IBD). We report the laboratory and clinical validation of a simple and reliable high performance liquid chromatography (HPLC) method for the measurement of 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) on paediatric patients with IBD. The aim of this paper is to develop and validate a method for the measurement of 6-TGN and 6-MMP applicable to routine practice and to evaluate the usefulness of the TDM of thiopurine drugs in children with IBD attending our Gastroenterology Unit. The HPLC method was validated following international guidelines starting from red blood cells (RBC) and whole blood (WB). A comparison between RBC and WB was assessed. The usefulness of TDM was then evaluated using the new method from WB in 47 paediatric patients with IBD treated with thiopurine drugs. WB and RBC resulted in interchangeable matrices. The majority of patients had the metabolite levels inside the therapeutic ranges. A moderate correlation was found between 6-MMP concentration and the dose of thiopurines. A higher percentage of non responders was found among patients with lower levels of 6-TGN. Toxicity was found in eight patients and was evaluated in respect to the metabolite concentration. The described HPLC method is applicable to routine practice and it is suitable for its use in multicentric studies. Our results of TDM on paediatric IBD patients can contribute to clarify its role in their therapeutic management.

Novel POMGNT1 point mutations and intragenic rearrangements associated with muscle-eye-brain disease.

Congenital muscular dystrophies due to defects in genes encoding proteins involved in α-dystroglycan (α-DG) glycosylation are a heterogeneous group of muscle disorders variably associated with central nervous system and eye abnormalities. One of the more severe is muscle-eye-brain disease (MEB). Mutations in genes coding for proven or putative glycosyltransferases (POMT1, POMT2, POMGnT1, fukutin, FKRP, and LARGE), the DPM3 gene encoding a DOL-P-Man synthase subunit, and the DAG1 gene encoding α-dystroglycan, have been associated with altered α-DG glycosylation. We report new POMGnT1 mutations and evaluate protein expression in 3 patients and 2 foetuses with variably severe MEB features. We identify two new point mutations (c.643C>T, c.1863delC), one new intragenic rearrangement (deletion of exons 2-8), and a new intron retention (between exons 21 and 22) resulting from a known point mutation c.1895+1G>T. Our study provides further evidence that rearrangements of the POMGnT1 gene are relatively common. Importantly, if heterozygous, they can be missed on standard genomic DNA sequencing. POMGNT1 protein analysis in 3 patients showed that the severity of the phenotype does not correlate with protein expression. Cerebral MRI is important for identifying MEB and α-dystroglycanopathy phenotypes in children and foetuses, and hence for directing the genetic analysis.

The "eye-of-the-tiger" sign may be absent in the early stages of classic pantothenate kinase associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disorder associated with brain iron accumulation. The brain MRI abnormality consists of T2 hypointensity in the globus pallidus with a small hyperintensity in its medial part, called the "eye-of-the-tiger" sign. We report on 2 patients affected by PKAN, in whom MRI examination did not demonstrate the "eye-of-the-tiger" sign in the early stages; the typical abnormalities were detected only in the following examinations. Case 1 is a 4-year-old boy first studied at age 2 years for psychomotor delay. The brain MRI was normal. In the following 2 years, the motor impairment progressed. The second brain MRI at age 4 years demonstrated the "eye-of-the-tiger" sign. Molecular analysis of the PANK2 gene revealed a missense mutation F228S in exon 2 in homozygosis. Case 2 is a 6-year-old boy first studied at age 2 years because of psychomotor delay. His brain MRI did not demonstrate abnormalities in the globus pallidus. In the following years spastic-dystonic tetraparesis became evident. A brain MRI at age 4 years demonstrated the "eye-of-the-tiger" sign. Molecular analysis of the PANK2 gene revealed a missense mutation in exon 5 (N501I). Our 2 cases demonstrate that the observation of a normal globus pallidus in the early stage of the disease does not exclude the diagnosis of classic PKAN.

Oxidative stress in resuscitation and in ventilation of newborns.

The lungs of newborns are especially prone to oxidative damage induced by both reactive oxygen and reactive nitrogen species. Yet, these infants are often 1) exposed to high oxygen concentrations, 2) have infections or inflammation, 3) have reduced antioxidant defense, and 4) have high free iron levels which enhance toxic radical generation. Oxidative stress has been postulated to be implicated in several newborn conditions with the phrase "oxygen radical diseases of neonatology" having been coined. There is, however, reason to believe that oxidative stress is increased more when resuscitation is performed with pure oxygen compared with ambient air and that the most effective ventilatory strategy is the avoidance of mechanical ventilation with the use of nasopharyngeal continuous positive airway pressure whenever possible. Multiple ventilation strategies have been attempted to reduce injury and improve outcomes in newborn infants. In this review, the authors summarise the scientific evidence concerning oxidative stress as it relates to resuscitation in the delivery room and to the various modalities of ventilation.

Esophageal impedance and esophagitis in children: any correlation?

AIM: : The aim of this study was to correlate the data obtained with multiple intraluminal esophageal impedance and pH (MII-pH) recordings in infants and children referred for suspected gastroesophageal reflux disease with esophageal histology. MATERIALS AND METHODS: : In a prospective study, results of esophageal biopsies and MII-pH recording obtained in 45 children (mean age +/- SD: 69 +/- 55 months) were analyzed. Regarding the MII-pH data, an automatic (Autoscan Bioview Analysis Software, version 5.3.4, Sandhill Scientific Inc, Highlands Ranch, CO) and a manual reading were performed; an automatic pH analysis (meal included) was also performed. RESULTS: : Acidic, weakly acidic, and alkaline reflux episodes accounted, respectively, for 48.7%, 49.5%, and 1.8% of the total number of reflux episodes detected by MII-pH. Esophagitis was present in 25 (56%) children. Concordance between classic pH-study analysis (alone) and esophageal histology was found in 19 of 45 (42%) children. According to the MII-pH analysis, the mean and median value of the pH were significantly higher in the group with esophagitis than in the group with normal esophageal histology. A longer clearance time was found in the group with esophagitis than in subjects with normal histology. Gas reflux episodes represented 21% of the total reflux episodes and were comparable in both groups. CONCLUSIONS: : Multiple intraluminal esophageal impedance and pH analysis does not provide a distinct parameter to predict esophageal mucosal injury in children. In our population, MII-pH shows comparable acidic, weakly acidic, alkaline, and gas reflux in children with and without esophagitis. Further research is needed to analyze clearance parameters.

Band-like intracranial calcification with simplified gyration and polymicrogyria: a distinct "pseudo-TORCH" phenotype.

The combination of intracranial calcification and polymicrogyria is usually seen in the context of intrauterine infection, most frequently due to cytomegalovirus. Rare familial occurrences have been reported. We describe five patients-two male-female sibling pairs, one pair born to consanguineous parents, and an unrelated female-with a distinct pattern of band-like intracranial calcification associated with simplified gyration and polymicrogyria. Clinical features include severe post-natal microcephaly, seizures and profound developmental arrest. Testing for infectious agents was negative. We consider that these children have the same recognizable "pseudo-TORCH" phenotype inherited as an autosomal recessive trait.

[Probiotics, prebiotics and zinc in the therapy and prevention of acute infectious diarrhoea in children: state of the art]. / Probiotici, prebiotici e zinco nella terapia e prevenzione della diarrea acuta infettiva in età pediatrica: qual' è l'attuale evidenza?

Selected probiotics (mainly Lactobacilli, and particularly LGG, and Saccharomyces boulardii) have recently demonstrated a therapeutic efficacy in acute diarrhoea, if used in the early phase of infection and at high concentration. Further data are needed to clarify their effect for prevention and travellers' diarrhoea. The mechanisms of action of probiotics need to be fully elucidated but seem to include a complex interaction of epithelial, molecular, metabolic and immune responses. There is an increasing evidence that different micro-organisms show different properties and efficacy. An accurate identification and selection of the strains, the dose and the patients are thus crucial for a correct therapeutic approach. Prebiotics can modify the intestinal flora and interact with the immune system of the host against specific pathogens. However, clinical trials are currently limited and a beneficial effect of prebiotics in acute diarrhoea is still lacking. In developing countries zinc supplementation demonstrated a significant reduction of fecal excretion, duration, severity and persistency of diarrhoea. Moreover, zinc may improve immune status, intestinal permeability, epithelial and enzymatic functions, and transport of electrolytes. The use of zinc in addition to oral rehydration solution (ORS) could thus theoretically improve the treatment and reduce the complications of diarrhoea worldwide. However, in developed countries, no trial using zinc supplementation in patients with acute diarrhoea has been published yet and the cost-benefit ratio of zinc supplementation needs to be assessed.

The effectiveness of hospitalization in the treatment of paediatric idiopathic headache patients.

BACKGROUND: Headache is a disease that has a high social impact in the paediatric as well as in the adult population, often resulting in a significant reduction in the young patient's quality of life, reflected primarily in a greater number of days off school and increasingly frequent recourse to symptomatic drugs. The idea for this study came from the clinical impression that some paediatric headache patients might benefit more from inpatient than outpatient care. AIM: The aim of our study was to compare the effectiveness of hospitalization to outpatient care of patients with newly diagnosed frequent and disabling headache. METHODS: A pragmatic randomized open-label trial was conducted at the Child Neurology Clinic of the University of Pavia, Italy. Children and adolescents with a 2- to 6-month moderate-to-severe migraine or tension-type headache history were randomized to hospital admission or outpatient assessment and followed for 6 months. The efficacy of the two therapeutic strategies was measured by counting the number of responders in each arm. Other end points included the mean frequency and duration of attacks, the number of drug prescriptions taken to control pain, and the number of patients and physicians expressing satisfaction with treatment. RESULTS: The study population included 27 girls and 23 boys aged 8 through 18 years with migraine (23 cases) or tension-type headache (27 cases). Compared to outpatient assessment, hospital admission was correlated to a significant increase in the number of responders: 0 vs. 44% (1 month), 0 vs. 68% (3 months), and 12 vs. 68% (6 months). The mean frequency and duration of attacks were significantly lower in hospitalized patients (p < 0.0001). Hospitalization was correlated with a significant reduction of patients with severe headache (p < 0.005), a reduction of drug use, and a higher number of satisfied patients and physicians (p < 0.05). Logistic regression analysis confirmed the higher responder rate among hospitalized patients after adjusting for age, sex, diagnosis, and headache characteristics or admission. CONCLUSIONS: We think hospitalization reduces the emotional mechanisms that provoke stress in children and often induce or favour headache attacks. If these mechanisms can be interrupted, the management of disease may become easier and with enduring benefits.

Cognitive and behavioural effects of migraine in childhood and adolescence.

Since cognitive and behavioural characteristics of paediatric migraine sufferers have yet to be adequately defined, in this study we assessed the effect of migraine on the interictal functioning of children and adolescents by comparing the performance of two patient groups, 17 migraine sufferers with aura (MA) and 31 without aura (MoA) and by correlating the duration of the disorder, the frequency of attacks and interictal period with neuropsychological and behavioural findings. Both patient groups had cognitive performance within normal range except for a significant delay in the reaction time (RT) task. Both MA and MoA revealed a behavioural phenotype characterized by internalizing problems on Child Behaviour Check List (CBCL) scales. Slower RT to simple visual stimuli may be an early sign of a subclinical neuropsychological dysfunction, significantly correlated with the frequency of headache attacks and interictal period. The lack of a control group and other methodological limitations, such as patient selection bias and unadjusted P-value for multiple testing, make it difficult to give this finding a clearcut meaning. Further studies are needed on larger samples compared with a control group.

Unilateral frontal lobe epilepsy affects executive functions in children.

Very few studies to date have investigated the neuropsychological changes detectable in children suffering from frontal lobe epilepsy (FLE). The aim of the present study was to assess the effects of FLE on cognitive and executive functions in childhood. The sample includes 17 children with a frontal epileptogenic focus (10 right and 7 left), with no evidence of anatomical brain damage. These subjects were assessed by means of a battery of tests to investigate executive functioning. The results emphasised the presence of selective impairments of frontal lobe functions without evidence of deficits in global intellectual functioning. No side-specific deficits were detected, while an earlier onset of epilepsy and the duration of the disorder, but not the seizures frequency, were found to correspond with more severe deficits in some specific frontal lobe functions.

The natural history of Aicardi-Goutières syndrome: follow-up of 11 Italian patients.

Described are the outcomes of 11 Italian patients with Aicardi-Goutières syndrome. Neurologic symptoms progressed in the first year of life and stabilized by the end of the second year in 10 patients. White matter abnormalities remained stable; cerebral atrophy was stable in four patients and progressive in two. Calcifications increased (in number and size) in two of six patients. Serial CSF and serum interferon-alpha measurements (three patients) showed reduced CSF interferon-alpha levels.