Language 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 difficulties of scanning at this severe end of the spectrum, insights from MRI are scarce. Here we used manual deterministic tractography to investigate, for the first time, the integrity of the core white matter tracts defining 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 effect of group consisting in a reduction in fractional anisotropy (FA) in the IFOF in nvASD relative to TD; (ii) a main effect of group revealing lower values of radial diffusivity (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 differences of the dorsal language route previously observed in nvASD, and instead point to a disruption of the ventral language pathway, in line with semantic deficits observed behaviourally in this group.
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.
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).
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.
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.
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.
•This is the 1st estimation of the CT scan use in 0-20 year old Spanish population•>17,400 CT scans were used to reliably estimate the organ-doses•Chest-to-pelvis CTs conferred the highest lifetime risks•The 2013 CT scanning activity would increase 0.43% the lifetime risk of cancer
The number of genes implicated in neurodevelopmental conditions is rapidly growing. Recently, variants in PPP2R1A have been associated with syndromic intellectual disability and a consistent, but ...still expanding, phenotype. The PPP2R1A gene encodes a protein subunit of the serine/threonine protein phosphatase 2A enzyme, which plays a critical role in cellular function. We report an individual showing pontocerebellar hypoplasia (PCH), microcephaly, optic and peripheral nerve abnormalities, and an absence of typical features like epilepsy and an abnormal corpus callosum. He bears an unreported variant in an atypical region of PPP2R1A. In silico studies, functional analysis using immunofluorescence, and super-resolution microscopy techniques were performed to investigate the pathogenicity of the variant. This analysis involved a comparative analysis of the patient’s fibroblasts with both healthy control cells and cells from an individual with the previously described phenotype. The results showed reduced expression of PPP2R1A and the presence of aberrant protein aggregates in the patient’s fibroblasts, supporting the pathogenicity of the variant. These findings suggest a potential association between PPP2R1A variants and PCH, expanding the clinical spectrum of PPP2R1A-related neurodevelopmental disorder. Further studies and descriptions of additional patients are needed to fully understand the genotype–phenotype correlation and the underlying mechanisms of this novel phenotype.
To describe experience with bronchial artery embolization (BAE) in a cohort of patients with cancer.
All consecutive patients with cancer and at least one episode of hemoptysis that required BAE ...during a 14-year period were included in this observational retrospective review. The endpoints of the study were immediate success, recurrence of hemoptysis, mortality resulting from hemoptysis, and all-cause mortality.
Immediate control of bleeding was achieved in 31 of 40 patients (77.5%). Recurrence requiring BAE occurred in eight patients (20%). Cumulative hemoptysis control rate was 0.90 (95% confidence interval CI, 0.80-1.0) at 1 month and 0.65 (95% CI, 0.44-0.86) at 6 months. Probability of survival was 0.75 (95% CI, 0.62-0.88) at 1 month, 0.42 (95% CI, 0.27-0.57) at 6 months, 0.36 (95% CI, 0.21-0.51) at 12 months, and 0.08 (95% CI, 0.0-0.18) at 3 years.
BAE is an effective and safe technique in the treatment of hemoptysis in patients with cancer. Nevertheless, mortality resulting from hemoptysis and recurrence rate are high among these patients secondary to progression of the underlying disease.
The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse.
We ...report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive basal ganglia disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature.
At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10-40 mg/kg/day) and biotin (1-2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring.
ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.
Okur‐Chung neurodevelopmental syndrome (OCNS, MIM#617062) is a rare autosomal dominant syndrome related to CSNK2A1 mutations. It is characterized by intellectual disability, hypotonia, feeding and ...speech difficulties, dysmorphic features, and multisystem involvement. To date, less than 30 patients with OCNS have been described in detail in the literature, primarily in Asian populations. Here, we report a 5‐year‐old Spanish female with OCNS arising from a novel CSNK2A1 mutation c.149A>G, p.Tyr50Cys. Although her clinical features were compatible with OCNS syndrome, magnetic resonance imaging unexpectedly showed a duplication of the pituitary gland, a clinical finding not previously related to any known genetic condition. Other novel signs were an absence of the olfactory bulbs and multiple duplications of cervical vertebrae. We suggest that the midline abnormalities may be a significant part of this condition and lead to diagnostic suspicion. However, further descriptions are needed.
In this study, we present our experience with 1.5-T high-field intraoperative magnetic resonance imaging (ioMRI) for different neuro-oncological procedures in a pediatric population, and we discuss ...the safety, utility, and challenges of this intraoperative imaging technology.
A pediatric consecutive-case series of neuro-oncological surgeries performed between February 2020 and May 2022 was analyzed from a prospective ioMRI registry. Patients were divided into four groups according to the surgical procedure: intracranial tumors (group 1), intraspinal tumors (group 2), stereotactic biopsy for unresectable tumors (group 3), and catheter placement for cystic tumors (group 4). The goal of surgery, the volume of residual tumor, preoperative and discharge neurological status, and postoperative complications related to ioMRI were evaluated.
A total of 146 procedures with ioMRI were performed during this period. Of these, 62 were oncology surgeries: 45 in group 1, two in group 2, 10 in group 3, and five in group 4. The mean age of our patients was 8.91 years, with the youngest being 12 months. ioMRI identified residual tumors and prompted further resection in 14% of the cases. The mean time for intraoperative image processing was 54 ± 6 min. There were no intra- or postoperative security incidents related to the use of ioMRI. The reoperation rate in the early postoperative period was 0%.
ioMRI in pediatric neuro-oncology surgery is a safe and reliable tool. Its routine use maximized the extent of tumor resection and did not result in increased neurological deficits or complications in our series. The main limitations included the need for strict safety protocols in a highly complex surgical environment as well as the inherent limitations on certain patient positions with available MR-compatible headrests.
Phosphomannomutase-2 deficiency (PMM2-CDG) is associated with a recognisable facial pattern. There are no early severity predictors for this disorder and no phenotype-genotype correlation. We ...performed a detailed dysmorphology evaluation to describe facial gestalt and its changes over time, to train digital recognition facial analysis tools and to identify early severity predictors.
Paediatric PMM2-CDG patients were evaluated and compared with controls. A computer-assisted recognition tool was trained. Through the evaluation of dysmorphic features (DFs), a simple categorisation was created and correlated with clinical and neurological scores, and neuroimaging.
Dysmorphology analysis of 31 patients (4-19 years of age) identified eight major DFs (strabismus, upslanted eyes, long fingers, lipodystrophy, wide mouth, inverted nipples, long philtrum and joint laxity) with predictive value using receiver operating characteristic (ROC) curveanalysis (p<0.001). Dysmorphology categorisation using lipodystrophy and inverted nipples was employed to divide patients into three groups that are correlated with global clinical and neurological scores, and neuroimaging (p=0.005, 0.003 and 0.002, respectively). After Face2Gene training, PMM2-CDG patients were correctly identified at different ages.
PMM2-CDG patients' DFs are consistent and inform about clinical severity when no clear phenotype-genotype correlation is known. We propose a classification of DFs into major and minor with diagnostic risk implications. At present, Face2Gene is useful to suggest PMM2-CDG. Regarding the prognostic value of DFs, we elaborated a simple severity dysmorphology categorisation with predictive value, and we identified five major DFs associated with clinical severity. Both dysmorphology and digital analysis may help physicians to diagnose PMM2-CDG sooner.
The CACNA1A gene encodes the pore-forming α1A subunit of the voltage-gated CaV2.1 Ca2+ channel, essential in neurotransmission, especially in Purkinje cells. Mutations in CACNA1A result in great ...clinical heterogeneity with progressive symptoms, paroxysmal events or both. During infancy, clinical and neuroimaging findings may be unspecific, and no dysmorphic features have been reported. We present the clinical, radiological and evolutionary features of three patients with congenital ataxia, one of them carrying a new variant. We report the structural localization of variants and their expected functional consequences. There was an improvement in cerebellar syndrome over time despite a cerebellar atrophy progression, inconsistent response to acetazolamide and positive response to methylphenidate. The patients shared distinctive facial gestalt: oval face, prominent forehead, hypertelorism, downslanting palpebral fissures and narrow nasal bridge. The two α1A affected residues are fully conserved throughout evolution and among the whole human CaV channel family. They contribute to the channel pore and the voltage sensor segment. According to structural data analysis and available functional characterization, they are expected to exert gain- (F1394L) and loss-of-function (R1664Q/R1669Q) effect, respectively. Among the CACNA1A-related phenotypes, our results suggest that non-progressive congenital ataxia is associated with developmental delay and dysmorphic features, constituting a recognizable syndromic neurodevelopmental disorder.
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