Subtle excess in lifetime cancer risk related to CT scanning in Spanish young people

Background: CT scan is a life-saving medical diagnostic tool, entailing higher levels of ionising radiation exposure than conventional radiography, which may result in an increase in cancer risk, particularly in children. Information about the use and potential health effects of CT scan imaging among young people in Spain is scarce. Objective: This paper aims to estimate the number of radiation-related cancer cases which can be expected due to the use of CT scanning in Spanish children and young adults in a single year (2013). Methods: The 2013 distribution of number and types of CT scans performed in young people was obtained for Catalonia and extrapolated to the whole Spain. Organ doses were estimated based on the technical characteristics of 17,406 CT examinations extracted from radiology records. Age and sex-specific data on cancer incidence and life tables were obtained for the Spanish population. Age and sex-specific risk models developed by the Committee on Health Risks of Exposure to Low Levels of Ionizing Radiations (BEIR VII) and Berrington de Gonzalez were used, together, with the dose estimates to derive the lifetime attributable risks of cancer in Spain due to one year of CT scanning and project the number of future cancer cases to be expected. Results: In 2013, 105,802 CT scans were estimated to have been performed in people younger than age 21. It was estimated that a total of 168.6 cancer cases (95% CrI: 30.1-421.1) will arise over life due to the ionising radiation exposure received during these CTs. Lifetime attributable risks per 100,000 exposed patients were highest for breast and lung cancer. The largest proportion of CTs was to the head and neck and hence the highest numbers of projected cancer cases were of thyroid and oral cavity/pharynx. Conclusions: Despite the undeniable medical effectiveness of CT scans, this risk assessment suggests a small excess in cancer cases which underlines the need for justification and optimisation in paediatric scanning. Given the intrinsic uncertainties of these risk projection exercises, care should be taken when interpreting the predicted risks

Agenesis of the corpus callosum in a newborn with Turner mosaicism

The agenesis of the corpus callosum results from a failure in the development of the largest fiber bundle that connects cerebral hemispheres. Patient’s outcome is influenced by etiology and associated central nervous system malformations. We describe a child with Turner syndrome (TS) mosaicism, with particular phenotype features and a complete agenesis of the corpus callosum. To our knowledge, this is the second case report of TS mosaicism associated with complete agenesis of the corpus callosum. Anatomical brain magnetic resonance imaging and diffusion tensor imaging were useful to confirm the complete absence of the corpus callosum, evaluate associated central nervous system malformations, visualize abnormal white matter tracts (Probst bundles) and assess the remaining commissures

Synchronous choroid plexus papilloma and Wilms tumor in a girl, disclosing a Li-Fraumeni syndrome

Background: Li-Fraumeni Syndrome (LFS) is a cancer predisposition syndrome characterized by the early-onset of multiple primary cancers which can occur at different moments (metachronous onset) or, more rarely, coincidentally (synchronous onset). Here we describe a previously unreported patient with presentation of synchronous Wilms tumor and Choroid plexus papilloma, leading to the diagnosis of a Li-Fraumeni Syndrome (LFS). Case presentation: A 6-year-old girl without previous complains presented with abdominal pain. Abdominal US and MRI showed a left renal tumor with subcapsular hematoma. Due to mild headaches, the diagnostic workup included a brain MRI that unexpectedly identified a large left parietal lobe tumor. Histopathological analysis determined the diagnosis of classic Wilms tumor and choroid-plexus papilloma (CPP), respectively. Both neoplasms showed intense nuclear p53 immunostaining associated with the pathogenic TP53 mutation c.844C > T (p.Arg282Trp). Our patient and her father shared the same heterozygous germline TP53 mutation, confirming the diagnosis of familiar Li-Fraumeni syndrome in the girl. The treatment was tailored to simultaneous tumor presentations. Conclusions: LFS has been associated with Choroid plexus carcinoma (CPC), but rarely with CPP as in our patient. That suggests that it may be advisable to consider the possibility of analyzing TP53 mutation, not only in all patients with CPC, but also in some patients with CPP, especially when histological or clinical evidences point out to perform this study. The dissimilar presentation of LFS among our patient's father, not having so far any neoplasia diagnosed, while her daughter presented precociously with two simultaneous different tumors, could be related to possible effects of modifier genes on the underlying mutant p53 genotype

Right Structural and Functional Reorganization in Four-Year-Old Children with Perinatal Arterial Ischemic Stroke Predict Language Production

Brain imaging methods have contributed to shed light on the mechanisms of recovery after early brain insult. The assumption that the unaffected right hemisphere can take over language functions after left perinatal stroke is still under debate. Here, we report how patterns of brain structural and functional reorganization were associated with language outcomes in a group of 4-year-old children with left perinatal arterial ischemic stroke. Specifically, we gathered specific fine-grained developmental measures of receptive and productive aspects of language as well as standardized measures of cognitive development. We also collected structural neuroimaging data as well as functional activations during a passive listening story-telling fMRI task and a resting state session (rs-fMRI). Children with a left perinatal stroke showed larger lateralization indices of both structural and functional connectivity of the dorsal language pathway towards the right hemisphere that, in turn, were associated with better language outcomes. Importantly, the pattern of structural asymmetry was significantly more right-lateralized in children with a left perinatal brain insult than in a group of matched healthy controls. These results strongly suggest that early lesions of the left dorsal pathway and the associated perisylvian regions can induce the inter-hemispheric transfer of language functions to right homolog regions. This study provides combined evidence of structural and functional brain reorganization of language networks after early stroke with strong implications for neurobiological models of language development

Utilitat de la tomografia computada davant la sospita de cel·lulitis orbitària a urgències

Fonament. La cel·lulitis orbitària (CO) és un diagnòstic de sospita clínica que requereix confirmació radiològica. És habitual l'ingrés amb tractament antibiòtic a l'espera de la confirmació diagnòstica. Objectiu. Avaluar el possible impacte de la realització d'una tomografia computada (TC) en el maneig a Urgències del pacient amb sospita de CO. Mètode. Estudi retrospectiu, descriptiu-observacional. Es van revisar les històries clíniques dels pacients atesos a Urgències entre 2011 i 2014 amb diagnòstic de cel·lulitis periorbitària/orbitària. Es van incloure els casos amb sospita de CO. Es van excloure els pacients sense TC. Es defineix CO com la cel·lulitis que afecta més enllà del septe orbitari. Es van considerar criteris d'ingrés: edat <1 any, immunosupressió, vacunació incompleta, triangle d'avaluació pediàtrica (TAP) alterat, mala resposta antibiòtica i presència d'algun dels símptomes o signes oculars següents: dolor amb els moviments oculars, oftalmoplegia, disminució de l'agudesa visual, alteració dels reflexos pupil·lars, edema conjuntival i proptosi. Resultats. Es van incloure 85 pacients. Tots van ser immunocompetents, ben vacunats i presentaven un TAP normal. Vint (23,5%) presentaven un o més signes o símptomes oculars. Vint-i-set (31,8%) tenien un o més criteris d'ingrés. Dels 58 sense criteris d'ingrés, en 38 (65,5%) no es va confirmar CO. A 18 (31%) d'aquests pacients se'ls va fer TC a Urgències; en 13 casos es va indicar maneig ambulatori, ja que l'afectació era només preseptal. Es va confirmar CO en 34 pacients (concordança diagnòstica 40%). Conclusions. En més de la meitat dels pacients amb sospita de CO, aquesta no es confirma radiològicament. Fer una TC a Urgències, en els pacients que no tenen criteris d'ingrés, evitaria hospitalitzacions innecessàries en un nombre significatiu

BCKDK deficiency: a treatable neurodevelopmental disease amenable to newborn screening

There are few causes of treatable neurodevelopmental diseases described to date. Branched-chain ketoacid dehydrogenase kinase (BCKDK) deficiency causes branched-chain amino acid (BCAA) depletion and is linked to a neurodevelopmental disorder characterized by autism, intellectual disability and microcephaly. We report the largest cohort of patients studied, broadening the phenotypic and genotypic spectrum. Moreover, this is the first study to present newborn screening findings and mid-term clinical outcome. In this cross-sectional study, patients with a diagnosis of BCKDK deficiency were recruited via investigators’ practices through a MetabERN initiative. Clinical, biochemical and genetic data were collected. Dried blood spot (DBS) newborn screening (NBS) amino acid profiles were retrieved from collaborating centres and compared to a healthy newborn reference population. Twenty-one patients with BCKDK mutations were included from 13 families. Patients were diagnosed between 8 months and 16 years (mean: 5.8 years, 43% female). At diagnosis, BCAA levels (leucine, valine and isoleucine) were below reference values in plasma and in CSF. All patients had global neurodevelopmental delay; 18/21 had gross motor function (GMF) impairment with GMF III or worse in 5/18, 16/16 intellectual disability, 17/17 language impairment, 12/17 autism spectrum disorder, 9/21 epilepsy, 12/15 clumsiness, 3/21 had sensorineural hearing loss and 4/20 feeding difficulties. No microcephaly was observed at birth, but 17/20 developed microcephaly during follow-up. Regression was reported in six patients. Movement disorder was observed in 3/21 patients: hyperkinetic movements (1), truncal ataxia (1) and dystonia (2). After treatment with a high-protein diet (≥ 2 g/kg/day) and BCAA supplementation (100–250 mg/kg/day), plasma BCAA increased significantly (P < 0.001), motor functions and head circumference stabilized/ improved in 13/13 and in 11/15 patients, respectively. Among cases with follow-up data, none of the three patients starting treatment before 2 years of age developed autism at follow-up. The patient with the earliest age of treatment initiation (8 months) showed normal development at 3 years of age. NBS in DBS identified BCAA levels significantly lower than those of the normal population. This work highlights the potential benefits of dietetic treatment, in particular early introduction of BCAA. Therefore, it is of utmost importance to increase awareness about this treatable disease and consider it as a candidate for early detection by NBS programmes.A.G.C. is supported by FIS P118/00111, FI21/0073 ‘Instituto de Salud Carlos III (ISCIII)’ and ‘Fondo Europeo de desarrollo regional (FEDER)’

Structural connectivity in ventral language pathways characterizes non‑verbal autism

Data de publicació electrónica: 14-03-2022Conté: Suplementary dataLanguage capacities in autism spectrum disorders (ASD) range from normal scores on standardized language tests to absence of functional language in a substantial minority of 30% of individuals with ASD. Due to practical difculties of scanning at this severe end of the spectrum, insights from MRI are scarce. Here we used manual deterministic tractography to investigate, for the frst time, the integrity of the core white matter tracts defning the language connectivity network in non-verbal ASD (nvASD): the three segments of the arcuate (AF), the inferior fronto-occipital (IFOF), the inferior longitudinal (ILF) and the uncinate (UF) fasciculi, and the frontal aslant tract (FAT). A multiple case series of nine individuals with nvASD were compared to matched individuals with verbal ASD (vASD) and typical development (TD). Bonferroni-corrected repeated measure ANOVAs were performed separately for each tract—Hemisphere (2:Left/Right) × Group (3:TD/vASD/ nvASD). Main results revealed (i) a main efect of group consisting in a reduction in fractional anisotropy (FA) in the IFOF in nvASD relative to TD; (ii) a main efect of group revealing lower values of radial difusivity (RD) in the long segment of the AF in nvASD compared to vASD group; and (iii) a reduced volume in the left hemisphere of the UF when compared to the right, in the vASD group only. These results do not replicate volumetric diferences of the dorsal language route previously observed in nvASD, and instead point to a disruption of the ventral language pathway, in line with semantic defcits observed behaviourally in this group.Open Access funding provided thanks to the CRUECSIC agreement with Springer Nature. Supported by an ‘advanced research group’ grant to the Grammar and Cognition Lab (2017 SGR 1265, W.H.), and grants FFI2013-40526P and PID2019-110120RBI00/AEI/10.13039/501100011033 by the Ministerio de Ciencia, Innovación y Universidades (MCIU) and the Agencia Estatal de Brain Structure and Function 1 3 Investigación (AEI) (W.H.), and two predoctoral research grants: one from Generalitat de Catalunya (AGAUR) & European Social Found (2018FI_B_00860, D.S), the other from Government of Andorra: Guillem Olivé Cadena acknowledges the Government of Andorra from a predoctoral grant, (ATC0XX-AND-2020/2021, G.O.). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Utilitat de la tomografia computada davant la sospita de cel·lulitis orbitària a urgències

Fonament. La cel·lulitis orbitària (CO) és un diagnòstic de sospita clínica que requereix confirmació radiològica. És habitual l'ingrés amb tractament antibiòtic a l'espera de la confirmació diagnòstica. Objectiu. Avaluar el possible impacte de la realització d'una tomografia computada (TC) en el maneig a Urgències del pacient amb sospita de CO. Mètode. Estudi retrospectiu, descriptiu-observacional. Es van revisar les històries clíniques dels pacients atesos a Urgències entre 2011 i 2014 amb diagnòstic de cel·lulitis periorbitària/orbitària. Es van incloure els casos amb sospita de CO. Es van excloure els pacients sense TC. Es defineix CO com la cel·lulitis que afecta més enllà del septe orbitari. Es van considerar criteris d'ingrés: edat <1 any, immunosupressió, vacunació incompleta, triangle d'avaluació pediàtrica (TAP) alterat, mala resposta antibiòtica i presència d'algun dels símptomes o signes oculars següents: dolor amb els moviments oculars, oftalmoplegia, disminució de l'agudesa visual, alteració dels reflexos pupil·lars, edema conjuntival i proptosi. Resultats. Es van incloure 85 pacients. Tots van ser immunocompetents, ben vacunats i presentaven un TAP normal. Vint (23,5%) presentaven un o més signes o símptomes oculars. Vint-i-set (31,8%) tenien un o més criteris d'ingrés. Dels 58 sense criteris d'ingrés, en 38 (65,5%) no es va confirmar CO. A 18 (31%) d'aquests pacients se'ls va fer TC a Urgències; en 13 casos es va indicar maneig ambulatori, ja que l'afectació era només preseptal. Es va confirmar CO en 34 pacients (concordança diagnòstica 40%). Conclusions. En més de la meitat dels pacients amb sospita de CO, aquesta no es confirma radiològicament. Fer una TC a Urgències, en els pacients que no tenen criteris d'ingrés, evitaria hospitalitzacions innecessàries en un nombre significatiu

Use of bevacizumab in pediatric low-grade glioma: Ten-year experience in a single center

Purpose: Pediatric low-grade gliomas (PLGG) have an excellent overall survival, but frequently need non-surgical therapy at diagnosis or after progression when located in unresectable sites such as the optic pathway. Chemotherapy side effects have led to the need for better-tolerated regimens with a sustained response. Bevacizumab, a humanized anti-VEGF monoclonal antibody has been used in monotherapy and/or in combination for these entities. Here we present our experience with its use in PLGG. Methods: The authors performed a retrospective, observational, single-institution study, between 2008 and 2018, to evaluate the safety and efficacy of bevacizumab in progressive PLGG. Results: Twenty-six patients with a median age at diagnosis of 3.32 years old [0.12–14.7] and a median age at treatment of 8.11 years old [0.41–16.82] were included in the study. Nineteen had optic pathway gliomas and chiasmatic-hypothalamic gliomas (73.1%), 9 of them (47.4%) associated with neurofibromatosis type 1 (NF1). Fourteen non-NF1 tumors were molecularly studied, disclosing BRAF-KIAA1549 fusion transcript in 9, and BRAF V600E mutation in 2. Bevacizumab was administered in combination with other agent(s) in 16 of the 35 treatment courses. Responses were assessed at 3, 12 months and at the end of treatment. Progression free survival at 12 and 36 months was 91.4% and 31.4%, respectively, and no severe adverse events were observed. Conclusions: In our series, Bevacizumab in PLGG showed clinical efficacy with a favorable toxicity profile. Larger prospective studies may determine whether the response is conditional upon age, tumor location, and different histological and/or molecular characterization

Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND): Case report, pharmacological trial, and literature review

Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND, MIM#604065) is an ultrarare autosomal dominant syndrome related to de novo CACNA1G gain-of-function pathogenic variants. All patients with SCA42ND show cerebellar atrophy and/or hypoplasia on neuroimaging and share common features such as dysmorphic features, global developmental delay, and axial hypotonia, all manifesting within the first year of life. To date, only 10 patients with SCA42ND have been reported with functionally confirmed gain-of-function variants, bearing either of two recurrent pathogenic variants. We describe a girl with congenital ataxia, without epilepsy, and a de novo p.Ala961Thr pathogenic variant in CACNA1G. We review the published subjects with the aim of better characterizing the dysmorphic features that may be crucial for clinical recognition of SCA42ND. Cerebellar atrophy, together with digital anomalies, particularly broad thumbs and/or halluces, should lead to clinical suspicion of this disease. We describe the first pharmacological attempt to treat a patient with SCA42ND using zonisamide, an antiepileptic drug with T-type channel blocker activity, in an off-label indication using an itemized study protocol. No efficacy was observed at the dose tested. However, without pharmacological treatment, she showed a positive evolution in neurodevelopment during the follow-up.This work was supported by a National Grant PI17/00101 from the National R&D&I Plan, cofinanced by the Instituto de Salud Carlos III (Subdirectorate-General for Evaluation and Promotion of Health Research) and FEDER (European Regional Development Fund). M.S. is supported by the Generalitat de Catalunya (PERIS SLT008/18/00194). J.M.F-F. is supported by the Spanish Ministry of Science and Innovation, the State Research Agency (AEI, Agencia Estatal de Investigación), and FEDER Funds (Fondo Europeo de Desarrollo Regional): Grants RTI2018-094809-B-I00, and CEX2018-000792-M through the “María de Maeztu” Programme for Units of Excellence in R&D to “Departament de Ciències Experimentals i de la Salut”