Search

Dysfunctions in sensory processing are widely described in individuals with autism spectrum disorder (ASD), although little is known about the developmental course and the impact of these difficulties on the learning processes during the preschool and school ages of ASD children. Specifically, as regards the interplay between visual and haptic information in ASD during developmental age, knowledge is very scarce and controversial. In this study, we investigated unimodal (visual and haptic) and cross-modal (visuo-haptic) processing skills aimed at object recognition through a behavioural paradigm already used in children with typical development (TD), with cerebral palsy and with peripheral visual impairments. Thirty-five children with ASD (age range: 5–11 years) and thirty-five age-matched and gender-matched typically developing peers were recruited. The procedure required participants to perform an object-recognition task relying on only the visual modality (black-and-white photographs), only the haptic modality (manipulation of real objects) and visuo-haptic transfer of these two types of information. Results are consistent with the idea that visuo-haptic transfer may be significantly worse in ASD children than in TD peers, leading to significant impairment in multisensory interactions for object recognition facilitation. Furthermore, ASD children tended to show a specific deficit in haptic information processing, while a similar trend of maturation of visual modality between the two groups is reported. This study adds to the current literature by suggesting that ASD differences in multisensory processes also regard visuo-haptic abilities necessary to identify and recognise objects of daily life

Visual Neglect (VN) is a common neuropsychological disorder in adults with unilateral brain lesion (UBL), characterized by the failure to attend and to report sensory events occurring in one side of space, contralateral to an area of brain damage. Less is known about VN expression in children following brain injury. The aim of this systematic review is to evaluate the presence of VN in UBL children and to identify the best neuropsychological assessment’s tool for this population. A comprehensive search of 4 databases (Pubmed, Cochrane Database, SCOPUS, DARE) was undertaken from May 2020 to January 2021. Inclusion criteria were (i) subjects less than 18 years with cerebral lesions and with MRI, (ii) specific neuropsychological assessments for VN, (iii) studies published in English since 2000. A total of 309 articles were found in the initial search but only 10 observational studies met the full inclusion criteria. In these studies, 1051 subjects were evaluated for VN, of them 749 were controls and 302 had brain lesions. The two most common types of neuropsychological tools used in children with unilateral brain damage to assess the presence of VN were target cancellation tests and drawing tests. This review confirms the possibility that children with UBL can develop VN, even if it is not very clear which brain structure’s characteristics can increase this risk. Children with right lesion showed visuo-spatial attention deficits focalized on the contralateral side, compatible with diagnosis of VN, while children with left lesion showed more generalized attention difficulties. The overall level of evidence correlating the presence of VN and different types of UBL in children was low and neuropsychological assessment of VN for children are sparse. Some important limitations of this review must be reported: the limited number of studies included, the administration of various types of tests to evaluate VN, the lack of information regarding the cognitive level of children

Spatial representation is crucial when it comes to everyday interaction with the environment. Different factors influence spatial perception, such as body movements and vision. Accordingly, training strategies that exploit the plasticity of the human brain should be adopted early. In the current study we developed and tested a new training protocol based on the reinforcement of audio-motor associations. It supports spatial development in one hemiplegic child with an important visual field defect (hemianopia) in the same side of the hemiplegic limb. We focused on investigating whether a better representation of the space using the sound can also improve the involvement of the hemiplegic upper limb in daily life activity. The experimental training consists of intensive but entertaining rehabilitation for two weeks, during which a child performed ad-hoc developed audio-motor-spatial exercises with the Audio Bracelet for Blind Interaction (ABBI) for 2 h/day. We administered a battery of tests before and after the training that indicated that the child significantly improved in both the spatial aspects and the involvement of the hemiplegic limb in bimanual tasks. During the assessment, ActiGraph GT3X+ was used to measure asymmetry in the use of the two upper limbs with a standardized clinical tool, the Assisting Hand Assessment (AHA), pre and post-training. Additionally, the study measured and recorded spontaneous daily life activity for at least 2 h/day. These results confirm that one can enhance perceptual development in motor and visual disorders using naturally associated auditory feedback to body movements.

It is well known how early visual experience is critical for the development of multisensory processing abilities, and for this reason an early vision impairment could hinder the transfer of different sensory information during the exploration and recognition of the surrounding environment. Recently, we verified that visuo-haptic transfer for object recognition emerges early in typically developing children but matures slowly during the school-age period. Subsequently we verified the presence of a slower trend of development in unisensory and multisensory skills in children with early abnormal motor and sensory experiences due to brain lesions. Now, we investigated unimodal visual information, unimodal haptic information and visuo-haptic information transfer in children with a diagnosis of low-vision, due to congenital visual impairment. Unimodal and bimodal processes for object recognition were explored in 11 children with low-vision and the results were matched with those of 22 controls. Participants were tested using a clinical protocol involving visual exploration of black-and-white photographs of common objects, haptic exploration of real objects and visuo-haptic transfer of these two types of information. Results show a normal development in haptic unisensory processing in children with low vision and a significant difference in multisensory transfer between the two groups. In children with visual impairment, multisensory processes do not facilitate the recognition of common objects as in typical children, probably because early visual impairment may impact the cross-sensory calibration of vision and touch.

Background: Cerebellar hemorrhage (CBH) represents the main form of direct cerebellar injury in preterm infants. Most CBHs occur bilaterally, while isolated unilateral hemorrhages are less frequent and often associated with focal atrophy. Limited and heterogeneous data exist on preterm birth, unilateral CBH and consequent long-term neurodevelopmental and non-motor outcomes. Case report: This is the case of a six-year-old child, born preterm, diagnosed with a complete atrophy of the right cerebellar hemisphere through brain MRI and presenting mild social atypies, visuo-perceptive and pragmatic language impairment, but only minor neurological signs. Discussion: Despite the large extension of the patient's CBH neurological sequelae were mild, likely due to cerebellar plasticity, and only specific deficits in non-motor, behavioral and social skills were shown. Evidence exists on cerebellar contribution to dynamic visual information processing and to perceptual signals detection and prediction, that might explain the presence of non-motor signs.

The pathophysiological mechanisms of Moyamoya angiopathy (MA), which is a rare cerebrovascular condition characterized by recurrent ischemic/hemorrhagic strokes, are still largely unknown. An imbalance of vasculogenic/angiogenic mechanisms has been proposed as one possible disease aspect. Circulating endothelial progenitor cells (cEPCs) have been hypothesized to contribute to vascular remodeling of MA, but it remains unclear whether they might be considered a disease effect or have a role in disease pathogenesis. The aim of the present study was to provide a morphological, phenotypical, and functional characterization of the cEPCs from MA patients to uncover their role in the disease pathophysiology. cEPCs were identified from whole blood as CD45dimCD34+CD133+ mononuclear cells. Morphological, biochemical, and functional assays were performed to characterize cEPCs. A significant reduced level of cEPCs was found in blood samples collected from a homogeneous group of adult (mean age 46.86 ± 11.7; 86.36% females), Caucasian, non-operated MA patients with respect to healthy donors (HD; p = 0.032). Since no difference in cEPC characteristics and functionality was observed between MA patients and HD, a defective recruitment mechanism could be involved in the disease pathophysiology. Collectively, our results suggest that cEPC level more than endothelial progenitor cell (EPC) functionality seems to be a potential marker of MA. The validation of our results on a larger population and the correlation with clinical data as well as the use of more complex cellular model could help our understanding of EPC role in MA pathophysiology.

Aim: To systematically explore the relationship between type and severity of brain lesion on Magnetic Resonance Imaging (MRI) and visual function in a large cohort of children with periventricular leukomalacia (PVL). Methods: 94 children with bilateral cerebral palsy (CP) and history of PVL were recruited at Stella Maris Scientific Institute in Pisa (Italy). We included data of participants (72) with at least one MRI after the age of three years and an evaluation of visual function including fixation, following, saccades, nystagmus, acuity, visual field, stereopsis and color perception. Brain lesions location and extent were assessed by a semi-quantitative MRI-scale for children with CP. Results: Brain lesion severity strongly correlated with visual function total score (global MRI score p = .000; hemispheric score p = .001 and subcortical score p = .000). Moreover, visual acuity, visual field, stereopsis and colour were compromised when a cortical damage was present, while ocular motricity (and in particular fixation and saccades) were compromised in presence of subcortical brain damage. Interpretation: Structural MRI is valuable for understanding the relationship between brain lesion severity and visual function in children with CP.

Background: Vision is an adaptive function and should be considered a prerequisite for neurodevelopment because it permits the organization and the comprehension of the sensory data collected by the visual system during daily life. For this reason, the influence of visual functions on neuromotor, cognitive, and emotional development has been investigated by several studies that have highlighted how visual functions can drive the organization and maturation of human behavior. Recent studies on animals and human models have indicated that visual functions mature gradually during post-natal life, and its development is closely linked to environment and experience. Discussion: The role of vision in early brain development and some of the neuroplasticity mechanisms that have been described in the presence of cerebral damage during childhood are analyzed in this review, according to a neurorehabilitation prospective.

Object recognition is a complex adaptive process that can be impaired in children with neurodevelopmental disabilities. Recently, we found a significant effect of time on the development of unimodal and crossmodal recognition skills for common objects in typical children and this was a starting point for the study of visuo-haptic object recognition skills in impaired populations. In this study, we investigated unimodal visual information, unimodal haptic information and visuo-haptic information transfer in 30 children, from 4.0 to 10.11 years of age, with bilateral Periventricular Leukomalacia (PVL) and bilateral cerebral palsy. Results were matched with those of 116 controls. Participants were tested using a clinical protocol, adopted in the previous study, involving visual exploration of black-and-white photographs of common objects, haptic exploration of real objects and visuo-haptic transfer of these two types of information. Results show that in the PVL group as in controls, there is an age-dependent development of object recognition abilities for visual, haptic and visuo-haptic modalities, even if PVL children perform worse in all the three conditions, in comparison with the typical group. Furthermore, PVL children have a specific deficit both in visual and haptic information processing, that improves with age, probably thanks to everyday experience, but the visual modality shows a better and more rapid maturation, remaining more salient compared to the haptic one. However, multisensory processes partially facilitate recognition of common objects also in PVL children and this finding could be useful for planning early intervention in children with brain lesion.

Background: Children with Down Syndrome (DS) have a high prevalence of ocular disorders, and even when ophthalmological deficits (i.e. refractive errors or strabismus) are corrected, visual acuity seems to have a different developmental trend compared to typical children. Unfortunately, there is no consensus about the age at which it is fundamental to perform a first comprehensive visual assessment in this population. Aims: We analyzed early visual functions in a sample of 42 Italian children with DS, in order to achieve new insights for early surveillance and intervention. Material and methods: DS children were evaluated with the Early Neurovisual Assessment, including Teller Acuity Cards (at 6, 12 and 18 months of age) and the Pediatric Ophthalmological Examination (within the 36th months of age). Results: Visual acuity in our sample was lower than findings reported in the literature on healthy Italian children, but the values were within the confidence interval reported in previous studies on DS children. Moderate or severe refractive errors (> 3diopters) were present in five children (four had hyperopia and one myopia). Abnormalities in ocular motility were observed in 15 children and pathological findings for fundus oculi or lens were found in another eight. Furthermore, ophthalmological findings correlated with visual acuity at 18 months of age. Conclusion: According to our results, the Early Neurovisual Assessment at 18 months of life is a reliable tool for early detection of visual disorders in children with DS and it is useful for programming early intervention to promote their neurodevelopment.

The term hereditary ataxia (HA) refers to a heterogeneous group of neurological disorders with multiple genetic etiologies and a wide spectrum of ataxia‐dominated phenotypes. Massive gene analysis in next‐generation sequencing has entered the HA scenario, broadening our genetic and clinical knowledge of these conditions. In this study, we employed a targeted resequencing panel (TRP) in a large and highly heterogeneous cohort of 377 patients with a clinical diagnosis of HA, but no molecular diagnosis on routine genetic tests. We obtained a positive result (genetic diagnosis) in 33.2% of the patients, a rate significantly higher than those reported in similar studies employing TRP (average 19.4%), and in line with those performed using exome sequencing (ES, average 34.6%). Moreover, 15.6% of the patients had an uncertain molecular diagnosis. STUB1, PRKCG, and SPG7 were the most common causative genes. A comparison with published literature data showed that our panel would have identified 97% of the positive cases reported in previous TRP‐based studies and 92% of those diagnosed by ES. Proper use of multigene panels, when combined with detailed phenotypic data, seems to be even more efficient than ES in clinical practice.

Object recognition is a long and complex adaptive process and its full maturation requires combination of many different sensory experiences as well as cognitive abilities to manipulate previous experiences in order to develop new percepts and subsequently to learn from the environment. It is well recognized that the transfer of visual and haptic information facilitates object recognition in adults, but less is known about development of this ability. In this study, we explored the developmental course of object recognition capacity in children using unimodal visual information, unimodal haptic information, and visuo-haptic information transfer in children from 4 years to 10 years and 11 months of age. Participants were tested through a clinical protocol, involving visual exploration of black-and-white photographs of common objects, haptic exploration of real objects, and visuo-haptic transfer of these two types of information. Results show an age-dependent development of object recognition abilities for visual, haptic, and visuo-haptic modalities. A significant effect of time on development of unimodal and crossmodal recognition skills was found. Moreover, our data suggest that multisensory processes for common object recognition are active at 4 years of age. They facilitate recognition of common objects, and, although not fully mature, are significant in adaptive behavior from the first years of age. The study of typical development of visuo-haptic processes in childhood is a starting point for future studies regarding object recognition in impaired populations.

Cerebral amyloid angiopathy (CAA) is one of the major types of cerebral small vessel disease, and a leading cause of spontaneous intracerebral hemorrhage and cognitive decline in elderly patients. Although increasingly detected, a number of aspects including the pathophysiology, the clinical and neuroradiological phenotype, and the disease course are still under investigation. The incomplete knowledge of the disease limits the implementation of evidence-based guidelines on patient’s clinical management and the development of treatments able to prevent or reduce disease progression. The SENECA (SEarchiNg biomarkErs of Cerebral Angiopathy) project is the first Italian multicenter cohort study aimed at better defining the disease natural history and identifying clinical and neuroradiological markers of disease progression. By a multidisciplinary approach and the collection of a large and well-phenotyped series and biorepository of CAA patients, the study is ultimately expected to improve the diagnosis and the knowledge of CAA pathophysiological mechanisms.

BACKGROUND: The Early Childhood Attention Battery (ECAB) has been used to assess three different components of attention in preschool children, namely, selective, sustained and attentional control. AIM: The aim of the study was: I) to adapt the ECAB to the Italian language; II) to collect Italian reference data using the translated version and III) to expand the available reference data using 6-month age intervals. STUDY DESIGN: The adaptation of the ECAB to Italian language and the collection of Italian reference data was performed in four phases: translation and identification of the manual and subtests that needed adaptation; interobserver reliability and feasibility of the Italian version; application of the Italian ECAB; statistical analysis. SUBJECTS: The ECAB was performed on a low risk population between 3 and 5 years, 11 months. RESULTS: Statistical analysis was conducted subdividing the cohort in 6-month age groups. The final cohort included 300 low-risk typically developing children. The assessment was well accepted and enjoyed by most of the children except for some in the youngest group who refused to complete all of the tests. Our data showed a progressive improvement in attention across age in seven of the eight subtests of the ECAB. CONCLUSION: The ECAB is a feasible battery in Italian as in the English version, for the assessment of early attention in preschool children, allowing the assessment of the different components of attention and a specific maturation follow up with increasing age.

Multisensory processes permit combinations of several inputs, coming from different sensory systems, allowing for a coherent representation of biological events and facilitating adaptation to environment. For these reasons, their application in neurological and neuropsychological rehabilitation has been enhanced in the last decades. Recent studies on animals and human models have indicated that, on one hand multisensory integration matures gradually during post-natal life and development is closely linked to environment and experience and, on the other hand, that modality-specific information seems to do not benefit by redundancy across multiple sense modalities and is more readily perceived in unimodal than in multimodal stimulation. In this review, multisensory process development is analyzed, highlighting clinical effects in animal and human models of its manipulation for rehabilitation of sensory disorders. In addition, new methods of early intervention based on multisensory-based rehabilitation approach and their applications on different infant populations at risk of neurodevelopmental disabilities are discussed.

Telerehabilitation, defined as the method by which communication technologies are used to provide remote rehabilitation, although still underused, could be as efficient and effective as the conventional clinical rehabilitation practices. In the literature, there are descriptions of the use of telerehabilitation in adult patients with various diseases, whereas it is seldom used in clinical practice with child and adolescent patients. We have developed a new audiovisual telerehabilitation (AVT) system, based on the multisensory capabilities of the human brain, to provide a new tool for adults and children with visual field defects in order to improve ocular movements toward the blind hemifield. The apparatus consists of a semicircular structure in which visual and acoustic stimuli are positioned. A camera is integrated into the mechanical structure in the center of the panel to control eye and head movements. Patients can use this training system with a customized software on a tablet. From hospital, the therapist has complete control over the training process, and the results of the training sessions are automatically available within a few minutes on the hospital website. In this paper, we report the AVT system protocol and the preliminary results on its use by three adult patients. All three showed improvements in visual detection abilities with long-term effects. In the future, we will test this apparatus with children and their families. Since interventions for impairments in the visual field have a substantial cost for individuals and for the welfare system, we expect that our research could have a profound socio-economic impact avoiding prolonged and intensive hospital stays.

The cell microenvironment plays a pivotal role in mediating cell adhesion, survival, and proliferation in physiological and pathological states. The relevance of extracellular matrix (ECM) proteins in cell fate control is an important issue to take into consideration for both tissue engineering and cell biology studies. The glycosylation of ECM proteins remains, however, largely unexplored. In order to investigate the physio-pathological effects of differential ECM glycosylation, the design of affordable chemoselective methods for ECM components glycosylation is desirable. We will describe a new chemoselective glycosylation approach exploitable in aqueous media and on non-protected substrates, allowing rapid access to glyco-functionalized biomaterials.

Results obtained in both animal models and hemianopic patients indicate that sound, spatially and temporally coincident with a visual stimulus, can improve visual perception in the blind hemifield, probably due to activation of multisensory neurons, mainly located in the superior colliculus. In view of this evidence, a new rehabilitation approach, based on audiovisual stimulation of visual field, has been proposed, and applied in adults with visual field reduction due to unilateral brain lesions. So far, results have been very encouraging, with improvements in visual search abilities. Based on these findings, we have investigated the possibility of inducing long-lasting amelioration also in children with a visual deficit due to acquired brain lesions. Our results suggest that, in the absence of spontaneous recovery, audiovisual training can induce activation of visual responsiveness of the oculomotor system also in children and adolescents with acquired lesions and confirm the putatively important role of the superior colliculus (SC) in this process.

Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression. However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment. Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect. In fact, FR054 induces in different breast cancer cells a dramatic decrease in cell proliferation and survival. In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration. Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS. Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.

Background: Down syndrome is a frequent cause of intellectual disability, with severe impact on the quality of life of affected individuals and their families, and high social costs. Intervention programs should start soon after birth but no consensus exists on specific types and timing of early interventions in this population. Aim: This pilot study explores the effects of an early multi-sensory intervention, based on body massage, on the development of visual function in infants with Down syndrome. Method: Infants were randomly allocated to either a massage or a control group. Intervention consisted of only standard care (Control Group) or standard care plus infant massage (Massaged Group). Visual acuity was assessed by Teller Acuity Cards and stereopsis by the Frisby Stereopsis Screening Test at 5, 6, 9 and 12. months. Results: Massaged Group Infants showed a significantly higher visual acuity at 6. months of age and an accelerated development up to at least 12. months; compared to Controls, stereopsis had an earlier onset in the Massaged Group followed by a faster maturation. Conclusion: Environmental enrichment, in the tested form of infant massage, seems to affect maturation of visual functions in human infants, also in the presence of a genetic disability, when applied during a period of high brain plasticity.

Background: Several studies report a high percentage of premature infants presenting perceptual motor difficulties at school age. The new version of the Movement Assessment Battery for Children allows the assessment of perceptual-motor abilities in children from the age of 3. years. Aims: To evaluate early perceptual-motor abilities in prematurely born children below the age of 4. years. Study design: The Movement Assessment Battery for Children 2nd edition was administered to 105 low-risk prematurely born children (< 32 weeks gestation) and in a control group of 105 term-born children matched for age and sex. All children were assessed between the age of 3. years and 3. years-11. months. Results: 63 children (60%) had total scores above the 15th percentile, 15 (14.3%) had scores between the 5th and the 15th percentile, and 13 (12.4%) below the 5th percentile. The remaining 14 children (13.3%) refused to perform or to complete the test. The difference between preterm and control group was significant for total scores, Manual Dexterity and Aiming and Catching scores. In the preterm group there was a correlation between age at testing, total scores and Aiming and Catching subscores. The Movement ABC-2 subscores were significantly lower in children born below 29. weeks. Conclusion: Perceptual-motor difficulties can already be detected on the assessment performed before the age of 4. years. Prematurely born children assessed between 3. years and 3. years-3. months appeared to have more difficulties in performing the test than the older ones or their age matched term-born peers. These findings support the possibility of a delayed maturation in the younger age group. © 2013 Elsevier Ltd.