A clinical review on megalencephaly: A large brain as a possible sign of cerebral impairment.

Megalencephaly and macrocephaly present with a head circumference measurement 2 standard deviations above the age-related mean. However, even if pathologic events resulting in both megalencephaly and macrocephaly may coexist, a distinction between these two entities is appropriate, as they represent clinical expression of different disorders with a different approach in clinical work-up, overall prognosis, and treatment. Megalencephaly defines an increased growth of cerebral structures related to dysfunctional anomalies during the various steps of brain development in the neuronal proliferation and/or migration phases or as a consequence of postnatal abnormal events. The disorders associated with megalencephaly are classically defined into 3 groups: idiopathic or benign, metabolic, and anatomic. In this article, we seek to underline the clinical aspect of megalencephaly, emphasizing the main disorders that manifest with this anomaly in an attempt to properly categorize these disorders within the megalencephaly group

Congenital muscular dystrophy: from muscle to brain.

Congenital muscular dystrophies (CMDs) are a wide group of muscular disorders that manifest with very early onset of muscular weakness, sometime associated to severe brain involvement.The histologic pattern of muscle anomalies is typical of dystrophic lesions but quite variable depending on the different stages and on the severity of the disorder.Recent classification of CMDs have been reported most of which based on the combination of clinical, biochemical, molecular and genetic findings, but genotype/phenotype correlation are in constant progression due to more diffuse utilization of the molecular analysis.In this article, the Authors report on CMDs belonging to the group of dystroglycanopathies and in particular on the most severe forms represented by the Fukuyama CMD, Muscle-Eye-Brain disease and Walker Walburg syndrome.Clinical diagnosis of infantile hypotonia is particularly difficult considering the different etiologic factors causing the lesions, the difficulty in localizing the involved CNS area (central vs. peripheral) and the limited role of the diagnostic procedures at this early age.The diagnostic evaluation is not easy mainly in differentiating the various types of CMDs, and represents a challenge for the neonatologists and pediatricians. Suggestions are reported on the way to reach a correct diagnosis with the appropriate use of the diagnostic means

Total Hemi-overgrowth in Pigmentary Mosaicism of the (Hypomelanosis of) Ito Type: Eight Case Reports.

Pigmentary mosaicism of the (hypomelanosis of) Ito type is an umbrella term, which includes phenotypes characterized by mosaic hypopigmentation in the form of streaks, whorls, patchy, or more bizarre skin configurations (running along the lines of Blaschko): these cutaneous patterns can manifest as an isolated skin disorder (pigmentary mosaicism of the Ito type) or as a complex malformation syndrome in association with extracutaneous anomalies (most often of the musculoskeletal and/or nervous systems) (hypomelanosis of Ito). Affected individuals are anecdotally reported to have also partial or total body hemi-overgrowth (HOG), which often causes moderate to severe complications.We studied the occurrence and features of HOG in the 114 children and adults with mosaic pigmentary disorders of the Ito type diagnosed and followed up (from 2 to 22 years; average follow-up 16 years) at our Institutions.Eight patients (5 M, 3 F; aged 4 to 25 years; median age 16 years) out of the 114 analyzed (7%) fulfilled the criteria for unilateral HOG, with differences in diameter ranging from 0.4 to 4.0 cm (upper limbs) and 1.0 to 9.0 cm (lower limbs). Moreover, among these 8 patients, 5/8 filled in the 75th to 90th percentile for height; 6/8 had associated kyphoscoliosis; and 5/8 showed cognitive delays. No tumour complications were recorded. Overall, 6/8 HOG patients presented with additional (extracutaneous) syndromic manifestations, apart from the HOG (ie, with a clinical phenotype of hypomelanosis of Ito).The present study, which includes children and adults with the longest follow-up so far recorded, confirms the association between pigmentary mosaicism of the Ito type and HOG lowering previous estimates (7% vs 16%) for HOG in the context of mosaic hypopigmentation. A careful examination, looking at subtle to moderate asymmetries and associated complications within the spectrum of these mosaic pigmentary disorders, is recommended

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Telangiectasia macularis eruptive perstans (TMEP) in childhood: A case report and literature review

NO ABSTRACT AVAILABL

A retrospective study on standard regimen for vaccination in celiac children

Background: HLA system plays an essential role in the human immune system activity and the expression of some spe-cific HLA antigens could modify the immune response to vaccinations. Celiac Disease is included among the diseases associated to specific HLA profiles, principally characterized by the expression of the HLA DQ2 antigen. Object: Our study was a retrospective study, leaded on a group of celiac children, with the object to evaluate their immunological response to both obligatory and recommended vaccinations in childhood. Materials and methods: It was a retrospec-tive study, including 66 patients affected by celiac disease, between 3 and 15 years of age, and a control group of 50 children of the same age. All patients performed both obligatory and recommended vaccinations as indicated in the Italian standard regimen for vaccinations. The immunologic response to each vaccine was analysed and compared in the two groups. Moreover, authors also studied the immunologic response to vaccines in celiac children comparing patients whose diagnosis was made before 18 months of age with those whose disease was diagnosed after 18 months of age. Results: Our results showed that in celiac patients the immunological response to vaccine is similar to that one found in general population, except for HBV vaccine. Conclusions: the valuation of immunological response to HBV vaccine should be regularly effectuated in celiac children and revaccination should be recommended

Intramuscular versus intradermal route for hepatitis B booster vaccine in celiac children.

AIM: To compare intradermal (ID) and intramuscular (IM) booster doses, which have been used in healthy and high risk subjects, such as healthcare workers, haemodialysis patients, human immunodeficiency virus patients, and renal transplant recipients unresponsive to initial hepatitis B vaccination, in celiac individuals. METHODS: We conducted our study on 58 celiac patients, vaccinated in the first year of life, whose blood analysis had showed the absence of protective hepatitis B virus (HBV) antibodies. All patients had received the last vaccine injection at least one year before study enrolment and they had been on a gluten free diet for at least 1 year. In all patients we randomly performed an HBV vaccine booster dose by ID or IM route. Thirty celiac patients were revaccinated with recombinant hepatitis B vaccine (Engerix B) 2 μg by the ID route, while 28 celiac patients were revaccinated with Engerix B 10 μg by the IM route. Four weeks after every booster dose, the anti-hepatitis B surface (HBs) antibody titer was measured by an enzyme-linked immuneadsorbent assay. We performed a maximum of three booster doses in patients with no anti-HBs antibodies after the first or the second vaccine dose. The cut off value for a negative anti-HBs antibody titer was 10 IU/L. Patients with values between 10 and 100 IU/L were considered "low responders" while patients with an antibody titer higher than 1000 IU/L were considered "high responders". RESULTS: No significant difference in age, gender, duration of illness, and years of gluten intake was found between the two groups. We found a high percentage of "responders" after the first booster dose (ID = 76.7%, IM = 78.6%) and a greater increase after the third dose (ID = 90%, IM = 96.4%) of vaccine in both groups. Moreover we found a significantly higher number of high responders (with an anti-HBs antibody titer > 1000 IU/L) in the ID (40%) than in the IM (7.1%) group, and this difference was evident after the first booster dose of vaccination (P < 0.01). No side effects were recorded in performing delivery of the vaccine by either the ID or IM route. CONCLUSION: Our study suggests that both ID and IM routes are effective and safe options to administer a booster dose of HBV vaccine in celiac patients. However the ID route seems to achieve a greater number of high responders and to have a better cost/benefit ratio. © 2012 Baishideng. All rights reserved

A sudden weight gain in a child as clinical presentation of Chiari Type I Malformation: a case report.

Chiari type I malformation (CM1) is characterised by different symptoms involving cerebellar, cerebral and spinal cord areas. Herein authors report a very uncommon CM1 in an obese child, who suddenly showed a weight gain as clinical presentation of this neurologic disease. Case presentation Since the patient was one-year-old, she had presented a progressive weight gain, with a body weight that maintained between the 90th and 97th percentile for age, but at the age of 6 years she showed a sudden and deep weight gain, associated with recurrent episodes of headache. At admission her weight and height were: 36.2 Kg (&gt;97° pc) and 110 cm (25- 50° pc) respectively, (Body Mass Index = 29.9 kg/m2) with an increase of nearly 5 Kg, during the two months before the admission. Systolic blood pressure was elevated at 140 mmHg. For the recurrence of headache, cerebral magnetic resonance imaging was performed and it revealed a 10 mm herniation of the right cerebellar tonsil, and a 7 mm herniation of the left cerebellar tonsil, compatible with a diagnosis of CM-IConclusions. To our knowledge this is the first case of sudden weight gain as first clinical presentation of CM, even if this sign was associated with headache. This case suggests that a sudden variation of body weight, should be considered a possible sign of disease by pediatricians

Hepatitis B vaccine in celiac disease: Yesterday, today and tomorrow

Some studies showed that in celiac patients the immunological response to vaccination is similar to that one found in general population except for vaccine against hepatitis B virus (HBV). The non-responsiveness to HBV vaccine has also been described in healthy people, nevertheless the number of non-responders has been demonstrated to be higher in celiac disease (CD) patients than in healthy controls. Several hypothesis explaining this higher rate of unresponsiveness to HBV vaccine in CD patients have been described, such as the genetic hypothesis, according with CD patients carrying the disease-specific haplotype HLA-B8, DR3, and DQ2, show a lower response to HBV vaccine both in clinical expressed CD patients and in healthy people carrying the same haplotype. On the other hand, it has been demonstrated that the gluten intake during the vaccination seems to influence the response to the same vaccine. Moreover, it has been demonstrated a possible genetic predisposition to hepatitis B vaccine non-responsiveness likely due to the presence of specific human leukocyte antigen haplotypes and specific single nucleotide polymorphism in genes of cytokine/cytokine receptors and toll like receptors, but the pathogenic mechanism responsible for this low responsiveness still remains unclear. The aim of this review is to focus on the possible pathogenic causes of unresponsiveness to HBV vaccine in CD patients and to propose an alternative vaccination schedule in order to improve the responsiveness to HBV vaccine in this at-risk patients