Gyrification, cortical and subcortical morphometry in neurofibromatosis type 1: an uneven profile of developmental abnormalities.

Background: Neurofibromatosis type 1 (NF1) is a monogenic disorder associated with cognitive impairments. In order to understand how mutations in the NF1 gene impact brain structure it is essential to characterize in detail the brain structural abnormalities in patients with NF1. Previous studies have reported contradictory findings and have focused only on volumetric measurements. Here, we investigated the volumes of subcortical structures and the composite dimensions of the cortex through analysis of cortical volume, cortical thickness, cortical surface area and gyrification. Methods: We studied 14 children with NF1 and 14 typically developing children matched for age, gender, IQ and right/left-handedness. Regional subcortical volumes and cortical gyral measurements were obtained using the FreeSurfer software. Between-group differences were evaluated while controlling for the increase in total intracranial volume observed in NF1. Results: Subcortical analysis revealed disproportionately larger thalami, right caudate and middle corpus callosum in patients with NF1. Cortical analyses on volume, thickness and surface area were however not indicative of significant alterations in patients. Interestingly, patients with NF1 had significantly lower gyrification indices than typically developing children primarily in the frontal and temporal lobes, but also affecting the insula, cingulate cortex, parietal and occipital regions. Conclusions: The neuroanatomic abnormalities observed were localized to specific brain regions, indicating that particular areas might constitute selective targets for NF1 gene mutations. Furthermore, the lower gyrification indices were accompanied by a disproportionate increase in brain size without the corresponding increase in folding in patients with NF1. Taken together these findings suggest that specific neurodevelopmental processes, such as gyrification, are more vulnerable to NF1 dysfunction than others. The identified changes in brain organization are consistent with the patterns of cognitive dysfunction in the NF1 phenotype. © 2013 Violante et al

Langerhans Cell Histiocytosis in the Occipital Condyle: A Case Study and a Brief Review of the Literature

We present a case study of a 5-year-old patient, who presented with left-sided torticollis. Due to persistence of problems, a CT and an MRI were made showing a single osteolytic lesion centred on right occipital condyle. After an open biopsy, histology confirmed it to be Langerhans cell histiocytosis (LCH). Torticollis or restricted range of motion is a presenting feature in 76% of children with LCH with cervical involvement. There remains much debate on the best treatment strategy. The clinical and radiological outcomes of the case study presented on this article support the treatment of LCH with chemotherapy in cases with solitary involvement of the occipital condyle.info:eu-repo/semantics/publishedVersio

Prognosis following acute coronary syndromes according to prior coronary artery bypass grafting: Meta-analysis

PURPOSE: Conduct a meta-analysis to study the prognostic influence of a previous coronary artery bypass grafting (CABG) in patients admitted for an acute coronary syndrome (ACS). METHODS: A systematic review of the literature was performed using electronic reference databases through January 2013 (MEDLINE, Cochrane Library, Web of Knowledge, Google Scholar and references cited in other studies). Studies in which ACS outcomes with a previous history of CABG were compared with ACS outcomes with no history of previous CABG were considered for inclusion. The main endpoints of interest were mortality and non-fatal acute myocardial infarction. Data was aggregated at three follow-up times using random-effects meta-analysis models. RESULTS: Twenty-four studies were included which provided 387,181 patients for analysis. Previous CABG ACS patients were older, more diabetic and had a more frequent history of a previous myocardial infarction. Pooled in-hospital mortality was higher for the previous CABG ACS patients (OR 1.22 [1.04-1.44], p<0.01, I(2) 88%). The pooled adjusted OR showed no significant differences for the two groups (adjusted OR 1.13 [0.93-1.37], p=0.22, I(2) 92%). Previous CABG ACS patient had a higher pooled 30-day mortality (OR 1.28 [1.05-1.55], p=0.02, I(2) 74%); a higher non-adjusted (OR 1.61 [1.38-1.88], p<0.01, I(2) 70%) and adjusted (adjusted OR 1.37 [1.15-1.65], p<0.01, I(2) 0%) long-term mortality. Both the in-hospital and the long-term re-infarction rates were higher for the previous CABG ACS patients. CONCLUSIONS: According to our data, ACS patients with previous CABG history had a higher risk for short- and long-term adverse events

Probable acute disseminated encephalomyelitis due to Haemophilus influenzae meningitis

We report the case of a 17-year-old male on long-term steroid therapy for minimal lesion glomerulopathy who, after an upper respiratory infection, presented with Haemophilus influenzae type b meningitis. Twenty-four hours later he developed depression of consciousness which progressed to coma and left hemiparesis. Brain magnetic resonance imaging (MRI) revealed multiple lesions (hyperintense on T2 and slightly hypointense on Tl) involving mainly white matter suggestive of inflammation. MRI features were compatible with acute disseminated encephalomyelitis (ADEM), although a differential diagnosis included cerebritis or vasculitis, secondary to bacterial meningitis. The patient was treated with high-dose steroids which resulted in a gradual improvement followed by complete clinical recovery. We propose a diagnosis of ADEM was the best diagnosis because of the radiological features and response to steroids. The occurrence of ADEM associated with acute meningitis, however rare, represents an important diagnostic challenge for the clinician

Use (or Misuse) of Drugs in Pediatrics

Introdução e Objectivos: A exposição a fármacos na idade pediátrica pode ser nociva. A utilização elevada de medicamentos não aprovados em Pediatria, bem como o uso para sintomas em que a sua eficácia não foi comprovada, tem sido descrita de forma preocupante. Foi objectivo deste estudo avaliar o padrão de consumo de fármacos numa população pediátrica portuguesa. Métodos: Estudo transversal, com recrutamento prospectivo dos casos e amostra de conveniência; recolha de dados por inquérito; incluídas crianças, sem doença crónica, que recorreram ao serviço de urgência de um hospital na área da Grande Lisboa, num período de dois meses. Resultados: Foram incluídas 189 crianças com idade média de 5,8 anos. A proporção de crianças com consumo de fármacos, nos trêsmeses precedentes, foi de 120/189 (63,5%) – superior entre os seis e 24 meses (74%vs 58,5%; p=0,038).Os fármacos mais prescritos foram os analgésicos/antipiréticos e anti-inflamatórios (83/202, 41,1%), os antibióticos (52/202, 25,8%) e os anti-histamínicos (14/202, 7%). Em 96/202 casos (47,5%) eram medicamentos não sujeitos a receita médica e em 33/174 (19,1%) “automedicações”. Verificou-se utilização de anti-histamínicos, expectorantes, analgésicos e anti-inflamatórios não recomendados para a faixa etária. O consumo de antibióticos foi mais elevado entre os seis e 24 meses (36%vs 18,5%; p=0,012), com predomínio da associação amoxicilina/ácido clavulânico (21/52, 40,4%). Em seis casos foram relatados possíveis efeitos secundários. Conclusões: De acordo com o nosso conhecimento este é o primeiro estudo em Portugal a avaliar o padrão de utilização de fármacos em Pediatria. Este consumo foi elevado, sobretudo na infância precoce, evidenciando a necessidade de vigilância e regulamentação adequadas. Os medicamentos não sujeitos a receita médica, amplamente utilizados, poderão associar-se a riscos acrescidos, pela facilidade no seu acesso. O uso frequente de antibióticos, sobretudo de largo espectro, poderá vir a associar-se ao desenvolvimento de resistências

Amiloidose. Caracterização Epidemiológica, Clínica e Morfológica

Introdução: A amiloidose é uma doença sistémica, cujo diagnóstico cabe frequentemente ao nefrologista. O tipo de amiloidose varia de acordo com o grau de desenvolvimento do país, com maior prevalência de amiloidose AL nos países ricos. Material e métodos: Revisão retrospectiva de todas as biopsias de rim nativo avaliadas no serviço entre 1981 e 2008. Caracterização clínica dos doentes à data da biópsia. Avaliação morfológica qualitativa do tipo de substância amiloíde por imunofluorescência e imunoperoxidase. Avaliação semi-quantitativa do grau de depósitos de acordo com a sua localização; grau de glomeruloesclerose e fibrose tubulo -interstical. Resultados: Neste período de 28 anos, observámos 202 biópsias positivas para substância amiloíde (3,5% de 5797) num total de 197 doentes (54,4% homens vs 45,5 mulheres), com idade mediana de 59,5 ± 15,6 anos. A maioria (68%) dos doentes foi biopsada por síndrome nefrótico. A insuficiência renal e as alterações assintomáticas urinárias foram os outros principais motivos de biopsia em 15 % e 7% dos casos, respectivamente. Os doentes na altura da biopsia apresentavam proteinúria mediana de 5 g/dia ± 5,4 (n=144) e creatinina mediana de 1,3 ± 1,7 mg/dl (n=150). As amiloidoses foram classificadas como AA em 51% dos casos, AL em 31,6% (25,5% lambda e 5,9% kappa) e Polineuropatia Amiloidótica Familiar em 3,5%. Não foi possível a caracterização do tipo de amilóide, por dificuldade técnica, em 12,8% das biópsias. A amiloidose revelou-se a terceira causa de síndrome nefrótico nos doentes com mais de 65 anos. Os doentes com amiloidose primária são significativamente mais velhos do que aqueles com amiloidose secundária ou PAF (65,2 vs 53,7 vs 52,7 respectivamente, p <0,05).Verificámos uma diminuição da incidência das amiloidoses AA com aumento das AL, com inversão do predomínio das AA em relação as AL a partir de 1995. Em termos morfológicos, a maioria das biópsias caracteriza-se por deposição marcada de amilóide no glomérulo (30% com +++) e nos vasos (40% com +++), com escassa deposição a nível intersticial cortical (60% sem depósitos) e medular (50% sem depósitos). Estudámos as possíveis relações entre manifestações clínicas e morfologia renal. Verificámos uma correlação positiva entre creatinina e grau de fibrose e/ou grau de deposição intersticial. Não encontrámos relação entre proteinúria e grau/local de deposição de amilóide. Conclusões: Actualmente, em Portugal, predomina a amiloidose AL, que surge em doentes mais idosos e se manifesta mais frequentemente por sindrome nefrótico. A função renal a data da biópsia correlaciona-se com o grau de fibrose tubulo-interstical renal

CSF Tau proteins reduce misdiagnosis of sporadic Creutzfeldt-Jakob disease suspected cases with inconclusive 14-3-3 result

Cerebrospinal fluid (CSF) 14-3-3 protein supports sporadic Creutzfeldt-Jakob (sCJD) diagnosis, but often leads to weak-positive results and lacks standardization. In this study, we explored the added diagnostic value of Total Tau (t-Tau) and phosphorylated Tau (p-Tau) in sCJD diagnosis, particularly in the cases with inconclusive 14-3-3 result. 95 definite sCJD and 287 patients without prion disease (non-CJD) were included in this study. CSF samples were collected in routine clinical diagnosis and analysed for 14-3-3 detection by Western blot (WB). CSF t-Tau and p-Tau were quantified by commercial ELISA kits and PRNP and APOE genotyping assessed by PCR-RFLP. In a regression analysis of the whole cohort, 14-3-3 protein revealed an overall accuracy of 82 % (sensitivity = 96.7 %; specificity = 75.6 %) for sCJD. Regarding 14-3-3 clear positive results, we observed no added value either of t-Tau alone or p-Tau/t-Tau ratio in the model. On the other hand, considering 14-3-3 weak-positive cases, t-Tau protein increased the overall accuracy of 14-3-3 alone from 91 to 94 % and specificity from 74 to 93 % (p < 0.05), with no sensitivity improvement. However, inclusion of p-Tau/t-Tau ratio did not significantly improve the first model (p = 0.0595). Globally, t-Tau protein allowed a further discrimination of 65 % within 14-3-3 inconclusive results. Furthermore, PRNP MV genotype showed a trend to decrease 14-3-3 sensitivity (p = 0.051), but such effect was not seen on t-Tau protein. In light of these results, we suggest that t-Tau protein assay is of significant importance as a second marker in identifying 14-3-3 false-positive results among sCJD probable cases

Anti-inflammatory activity of Blutaparon portulacoides ethanolic extract against the inflammatory reaction induced by Bothrops jararacussu venom and isolated myotoxins BthTX-I and II

This article reports the anti-inflammatory effect of Blutaparon portulacoides (B. portulacoides), specifically the ethanolic extract of its aerial parts, on the edema formation and leukocyte influx caused by Bothrops jararacussu (B. jararacussu) snake venom and Bothropstoxin-I and II (BthTX-I and II) isolated from this venom as an alternative treatment for Bothrops snakebites. The anti-inflammatory effect of B. portulacoides ethanolic extract was compared with an animal group pretreated with dexamethasone. B. portulacoides ethanolic extract significantly inhibited paw edema induced by B. jararacussu venom and by BthTX-I and II. Also, results demonstrated that the extract caused a reduction of the leukocyte influx induced by BthTX-I. However, the extract was not capable of inhibiting the leukocyte influx induced by the venom and by BthTX-II. In conclusion, these results suggest that the ethanolic extract of this plant possess components able to inhibit or inactivate toxins present in B. jararacussu venom, including its myotoxins, responsible for the edema formation. However, the leukocyte migration caused by the venom and BthTX-II was not inhibited by the plant, probably due to the different mechanisms involved in the edema formation and leukocyte influx. This is the first report of B. portulacoides extract as anti-inflammatory against snake venoms and isolated toxins