This paper introduces a special issue focused on sex and gender (s/g) cognitive/behavioral differences at developmental ages providing an overview of this multifaceted and debated topic. It will ...provide a description of the biological systems that are strongly interconnected to generate s/g differences, that is, genetic determinants, sex hormones, differences in brain structure, organization, and/or function, inherited or modifiable under environmental pressures. Developmental studies are rare. Some addressed whether s/g differences in cognitive/behavioral characteristics are evident early in life and are consistent throughout development, entailing that s/g differences can follow the evolving steps in girls and boys in different domains. The data are far from being homogeneous and consistent about s/g difference in language, social skills, and visuo/spatial abilities. The differences are small, often with overlapping performances, similar to what is seen in adulthood. Given that several variables and the interactions between them are implicated, further longitudinal studies adopting adequate assessment tools, very large size multicultural samples stratified in different, well‐sized and precise age groups, considering biological and sociocultural variables, are needed. Due to the complexity of the issue, there is still the need to support and adopt an s/g difference approach also in cognitive and behavioral studies at developmental ages. Finally, these studies have not only scientific importance and relevant cultural, anthropological, and social implications, but are also useful for pedagogical programming as well as for the study of the different susceptibility to develop CNS diseases and consequently to promote different therapies and treatments.
Neurofibromatosis type-1 (NF1) is a monogenic tumor-predisposition syndrome creating a wide variety of cognitive and behavioral abnormalities, such as decrease in cognitive functioning, deficits in ...visuospatial processing, attention, and social functioning. NF1 patients are at risk to develop neurofibromas and other tumors, such as optic pathway gliomas and other tumors of the central nervous system. Few studies have investigated the impact of an additional diagnosis of brain tumor on the cognitive outcome of children with NF1, showing unclear results and without controlling by the effect of surgery, radio- or chemotherapy. In the present mono-institutional study, we compared the behavioral and cognitive outcomes of 26 children with neurofibromatosis alone (NF1) with two age-matched groups of 26 children diagnosed with NF1 and untreated optic pathway glioma (NF1 + OPG) and 19 children with NF1 and untreated other central nervous system tumors (NF1 + CT). NF1 + CT and NF1 + OPG showed significantly impaired cognitive abilities compared to NF1 group, with weaknesses in visuo-spatial abilities, visual scanning and verbal working memory, while general verbal abilities are preserved. Moreover, NF1 + OPG patients present more frequent internalizing problems and increased oppositional-deviant behaviors. These results suggest that the co-diagnosis of a brain tumor in NF1 children may partially worsen the cognitive and emotional outcome.
Moyamoya disease (MMD) is a slowly progressing steno-occlusive cerebrovascular disease. The typical moyamoya vessels, which originate from an initial stenosis of the internal carotid, highlight that ...increased and/or abnormal angiogenic, vasculogenic and arteriogenic processes are involved in the disease pathophysiology.
Herein, we summarize the current knowledge on the most important signaling pathways involved in MMD vessel formation, particularly focusing on the expression of growth factors and function of endothelial progenitor cells (EPCs).
Higher plasma concentrations of vascular endothelial growth factor, matrix metalloproteinase, hepatocyte growth factor, and interleukin-1β were reported in MMD. A specific higher level of basic fibroblast growth factor was also found in the cerebrospinal fluid of these patients. Finally, the number and the functionality of EPCs were found to be increased. In spite of the available data, the approaches and findings reported so far do not give an evident correlation between the expression levels of the aforementioned growth factors and MMD severity. Furthermore, the controversial results provided by studies on EPCs, do not permit to understand the true involvement of these cells in MMD pathophysiology.
Further studies should thus be implemented to extend our knowledge on processes regulating both the arterial stenosis and the excessive formation of collateral vessels. Moreover, we suggest advances of integrated approaches and functional assays to correlate biological and clinical data, arguing for the development of new therapeutic applications for MMD.
Visual-spatial impairment has long been considered a hallmark feature of neurofibromatosis type 1 (NF1). No study investigating the cognitive and neuropsychological profile of NF1 used the Rey ...Complex Figure Test (RCFT) task as the primary measure of visual-perceptual abilities taking into consideration all functions involved including the strategic processing style. We compared 18 children with NF1, 17 siblings (S), and 18 typically developing children (TD) at intelligence scale and RCFT copy, recall, and recognition trials; we also evaluated the copy strategy as a measure of a visual-processing style. Children with NF1 had normal total IQ, with cognitive weaknesses in the perceptual organization and working memory in line with the existing literature. At the RCFT copy, immediate and delay recall scores are significantly lower in NF1 than S and TD, while recognition is in the normal range in all groups. Copy style was poor and less efficient in children with NF1 and correlated to copy and recall ability, but the effect of the group in the RCFT copy and recall remained significantly controlling for strategic approach. The present study confirms visuospatial impairment in children with NF1, due to a deficit in perceptual analysis of shape and their spatial features, in visuomotor integration efficiency and strategies, in recall memory, while recognition memory is preserved. A more configural/holistic style may facilitate both the visual-perceptual and visuomotor ability and the recall process. Visuoperceptual impairment in NF1 seems to be a unified process from early visual processing to higher order functions (planning, strategy, and executive functioning).
This study aimed at comparing implicit sequence learning in individuals affected by Duchenne Muscular Dystrophy without intellectual disability and age-matched typically developing children. A ...modified version of the Serial Reaction Time task was administered to 32 Duchenne children and 37 controls of comparable chronological age. The Duchenne group showed a reduced rate of implicit learning even if in the absence of global intellectual disability. This finding provides further evidence of the involvement of specific aspects of cognitive function in Duchenne muscular dystrophy and on its possible neurobiological substrate.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With a view to improving the prognosis for patients with metastatic medulloblastoma, we tested the efficacy and toxicity of a hyperfractionated accelerated radiotherapy (HART) regimen delivered after ...intensive sequential chemotherapy.
Between 1998 and 2007, 33 consecutive patients received postoperative methotrexate (8 g/m(2)), etoposide (2.4 g/m(2)), cyclophosphamide (4 g/m(2)), and carboplatin (0.8 g/m(2)) in a 2-month schedule, then HART with a maximal dose to the neuraxis of 39 Gy (1.3 Gy/fraction, 2 fractions/d) and a posterior fossa boost up to 60 Gy (1.5 Gy/fraction,2 fractions/d). Patients with persistent disseminated disease before HART were consolidated with two myeloablative courses and circulating progenitor cell rescue.
Patients were classified as having M1 (n = 9), M2 (n = 6), M3 (n = 17), and M4 (n = 1) disease. Seven patients younger than 10 years old who achieved complete response after chemotherapy received a lower dose to the neuraxis (31.2 Gy). Twenty-two of the 32 assessable patients responded to chemotherapy; disease was stable in five patients and progressed in five patients. One septic death occurred before radiotherapy. Eight patients experienced relapse after a median of 12 months. Fourteen of the 33 patients underwent consolidation therapy after HART. With a median 82-month survivor follow-up, the 5-year event-free, progression-free, and overall survival rates were 70%, 72%, and 73%, respectively. No severe clinical complications of HART have emerged so far.
HART after intensive postoperative chemotherapy, followed by myeloablative chemotherapy in selected cases, proved feasible in children with metastatic medulloblastoma. The results of our treatment compare favorably with other series treated using conventional therapies.
Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause seizures, intracerebral haemorrhages, and focal neurological deficits. Familial form shows an autosomal dominant ...pattern of inheritance with incomplete penetrance and variable clinical expression. Three genes have been identified causing familial CCM: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3. Aim of this study is to report additional PDCD10/CCM3 families poorly described so far which account for 10-15% of hereditary cerebral cavernous malformations. Our group investigated 87 consecutive Italian affected individuals (i.e. positive Magnetic Resonance Imaging) with multiple/familial CCM through direct sequencing and Multiplex Ligation-Dependent Probe Amplification (MLPA) analysis. We identified mutations in over 97.7% of cases, and PDCD10/CCM3 accounts for 13.1%. PDCD10/CCM3 molecular screening revealed four already known mutations and four novel ones. The mutated patients show an earlier onset of clinical manifestations as compared to CCM1/CCM2 mutated patients. The study of further families carrying mutations in PDCD10/CCM3 may help define a possible correlation between genotype and phenotype; an accurate clinical follow up of the subjects would help define more precisely whether mutations in PDCD10/CCM3 lead to a characteristic phenotype.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Many studies based on chromosomal microarray and next-generation sequencing (NGS) have identified hundreds of genes associated with autism spectrum disorder (ASD) risk, demonstrating that there are ...several complex genetic factors that contribute to ASD risk. We performed targeted NGS gene panels for 120 selected genes, in a clinical population of 40 children with well-characterized ASD. The variants identified were annotated and filtered, focusing on rare variants with a minimum allele frequency <1% in GnomAD. We found 147 variants in 39 of the 40 patients. It was possible to perform family segregation analysis in 28 of the 40 patients. We found 4 de novo and 101 inherited variants. For the inherited variants, we observed that all the variants identified in the patients came equally from the paternal and maternal genetic makeup. We identified 9 genes that are more frequently mutated than the others, and upon comparing the mutational frequency of these 9 genes in our cohort and the mutational frequency in the GnomAD population, we found significantly increased frequencies of rare variants in our study population. This study supports the hypothesis that ASD is the result of a combination of rare deleterious variants (low contribution) and many low-risk alleles (genetic background), highlighting the importance of MET and SLIT3 and the potentially stronger involvement of FAT1 and VPS13B in ASD. Taken together, our findings reinforce the importance of using gene panels to understand the contribution of the different genes already associated with ASD in the pathogenesis of the disease.
The present mono-institutional report aimed to describe the cognitive and behavioral outcomes of low-grade central nervous system (CNS) tumors in a cohort of children treated exclusively with ...surgical intervention.
Medical records from 2000-2020 were retrospectively analyzed. We included 38 children (mean age at first evaluation 8 years and 3 months, 16 females) who had undergone presurgical cognitive-behavioral evaluation and/or at least 6 months follow-up. Exclusion criteria were a history of traumatic brain injury, stroke, cerebral palsy or cancer-predisposing syndromes.
The sample presented cognitive abilities and behavioral functioning in the normal range, with weaknesses in verbal working memory and processing speed. The obtained results suggest that cognitive and behavioral functioning is related to pre-treatment variables (younger age at symptoms' onset, glioneuronal histological type, cortical location with preoperative seizures), timing of surgery and seizure control after surgery, and is stable when controlling for a preoperative cognitive and behavioral baseline. Younger age at onset is confirmed as a particular vulnerability in determining cognitive sequelae, and children at older ages or at longer postsurgical follow-up are at higher risk for developing behavioral disturbances.
Timely treatment is an important factor influencing the global outcome and daily functioning of the patients. Preoperative and regular postsurgical cognitive and behavioral assessment, also several years after surgery, should be included in standard clinical practices.
The present study aimed to assess the validity of using a robotic platform (RODDI) to increase and enhance communicative exchanges between educators and children with Autism Spectrum Disorder (ASD) ...and intellectual disability. Nine children with ASD and intellectual disability and their educators took part in the study. Their communicative exchanges were assessed in two different settings: a normal play session and a RODDI play session. RODDI platform did not appear to enhance communicative exchanges in children with ASD. They produced a significantly lower number of vocal productions to the educators in the RODDI play sessions than in the normal ones. Even the educators’ vocal production was significantly lower in quantitative and qualitative terms in the RODDI play sessions. However, analysing children’s gaze direction, RODDI appeared to enhance children’s attention on the task. The benefits of using robotic platforms with children with ASD should be further investigated.
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