Unilateral Cerebral Palsy (UCP), the most frequent form of Cerebral Palsy, usually affects more the upper limb (UL) than the lower limb. Rehabilitation programs are addressed to improve manual ...abilities and UL use. In recent years, Information and Communication Technology (ICT) has been introduced in rehabilitation to increase treatment opportunities for patients, and also in home-based intervention. Moreover, the discovery of the Mirror Neuron System allowed to insert a new paradigm of treatment that is the Action Observation Training (AOT). The aim of the present study was to investigate the feasibility of a new rehabilitative home-based approach, called Tele-UPCAT (Tele-monitored UPper Limb Children Action Observation Training), based on the principles of AOT, in a group of Italian children and adolescents with UCP. This investigation was to provide information about the possibility of introducing ICT in telerehabilitation field. Twenty-nine children aged 11.73 ± 3.65 years (range 6.00-18.75) with a diagnosis of UCP participated in the study. They carried out 15 days of training based on the AOT paradigm with Tele-UPCAT system while wearing Actigraphs on both wrists. The feasibility of both training and study design and procedures was assessed through nine criteria taken from existent literature and from a questionnaire designed and realized
for the purpose, based on standard items of usability and acceptability. All feasibility criteria were met: 80% of training sessions were completed in the planned time and no significant technical issues were found. From the questionnaire, total scores were all above 82.15%, while the four sections obtained the following scores: (i) customization of exercises 80.00%; (ii) acceptability at home, 77.50%; (iii) required effort 80.00%; and (iv) suitability of manual and software 95.00%. No differences were found for age and sex. Tele-UPCAT demonstrated to be feasible as a home-based AOT for children and adolescents with UCP. Trial registration NCT03094455.
A protocol named Outwalk was developed to easily measure the thorax-pelvis and lower-limb 3D kinematics on children with cerebral palsy (CP) and amputees during gait in free-living conditions, by ...means of an Inertial and Magnetic Measurement System (IMMS). Outwalk defines the anatomical/functional coordinate systems (CS) for each body segment through three steps: (1) positioning the sensing units (SUs) of the IMMS on the subjects' thorax, pelvis, thighs, shanks and feet, following simple rules; (2) computing the orientation of the mean flexion-extension axis of the knees; (3) measuring the SUs' orientation while the subject's body is oriented in a predefined posture, either upright or supine. If the supine posture is chosen, e.g. when spasticity does not allow to maintain the upright posture, hips and knees static flexion angles must be measured through a standard goniometer and input into the equations that define Outwalk anatomical CSs. In order to test for the inter-rater measurement reliability of these angles, a study was carried out involving nine healthy children (7.9 ± 2 years old) and two physical therapists as raters. Results showed RMS error of 1.4° and 1.8° and a negligible worst-case standard error of measurement of 2.0° and 2.5° for hip and knee angles, respectively. Results were thus smaller than those reported for the same measures when performed through an optoelectronic system with the CAST protocol and support the beginning of clinical trials of Outwalk with children with CP.
The study’s aim was two-fold: to describe the trend of hip subluxation in the largest sample of Italian nonambulatory cerebral palsy (CP) children ever published; to investigate its determinants. ...This single-centre retrospective cohort study included patients with spastic or dyskinetic CP, Gross Motor Function Classification System (GMFCS) level IV or V, age 0–18 years, having been referred to our unit before March 2020. The hip subluxation was measured by means of the migration percentage (MP). Other data were gathered such as sex, CP subtype, GMFCS level, presence of drug-resistant epilepsy, age, use of walkers with weight relief or standing devices, previous botulinum injection or hip surgery, oral or intrathecal baclofen and hip pain. Multiple linear stepwise regression was performed and descriptive statistics are provided. Spastic CP had MP maximum increase in early ages, with GMFCS level V values persistently higher than level IV. The dyskinetic subtype showed a slower increase of the MP, with GMFCS level IV presenting similar or higher values, compared to level V. Age, CP severity and spastic subtype are the main determinants. The stepwise multiple regression analysis demonstrated that weight relief walking and standing assistive devices, combined with botulinum contributed to reduce the MP progression. Dyskinetic CP showed overall lower MP values and a more variable behaviour relative to age and GMFCS level, compared to the spastic subtype. Standing and walking assistive devices, with partial or total weight relief, combined with individually targeted botulinum injections, should be considered in the management of bilateral nonambulatory CP patients, to prevent hip subluxation or its recurrence after surgery.
Human dental pulp is a promising alternative source of stem cells for cell-based tissue engineering in regenerative medicine, for the easily recruitment with low invasivity for the patient and for ...the self-renewal and differentiation potential of cells. So far, in vitro culture of mesenchymal stem cells is usually based on supplementing culture and differentiation media with foetal calf serum (FCS). FCS is known to contain a great quantity of growth factors, and thus to promote cell attachment on plastic surface as well as expansion and differentiation. Nevertheless, FCS as an animal origin supplement may represent a potential means for disease transmission besides leading to a xenogenic immune response. Therefore, a significant interest is focused on investigating alternative supplements, in order to obtain a sufficient cell number for clinical application, avoiding the inconvenients of FCS use. In our study we have demonstrated that human serum (HS) is a suitable alternative to FCS, indeed its addition to culture medium induces a high hDPSCs proliferation rate and improves the in vitro osteogenic differentiation. Furthermore, hDPSCs-collagen constructs, pre-differentiated with HS-medium in vitro for 10 days, when implanted in immunocompromised rats, are able to restore critical size parietal bone defects. Therefore these data indicate that HS is a valid substitute for FCS to culture and differentiate in vitro hDPSCs in order to obtain a successful bone regeneration in vivo.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Lesion of subcortical structures is more frequent in patients with synergic hand.•Sparing of subcortical white matter connections predicts hand impairment.•Children with ...semi-functional hand exhibit bilateral activations during grasping execution.•Patients with synergic hand show activations lateralized to the damaged hemisphere.•Lesion localization, rather than type (timing), predicts the manipulation level.
Brain damage in children with unilateral cerebral palsy (UCP) affects motor function, with varying severity, making it difficult the performance of daily actions. Recently, qualitative and semi-quantitative methods have been developed for lesion classification, but studies on mild to moderate hand impairment are lacking. The present study aimed to characterize lesion topography and preserved brain areas in UCP children with specific patterns of hand manipulation. A homogeneous sample of 16 UCP children, aged 9 to 14 years, was enrolled in the study. Motor assessment included the characterization of the specific pattern of hand manipulation, by means of unimanual and bimanual measures (Kinematic Hand Classification, KHC; Manual Ability Classification System, MACS; House Functional Classification System, HFCS; Melbourne Unilateral Upper Limb Assessment, MUUL; Assisting Hand Assessment, AHA). The MRI morphological study included multiple methods: (a) qualitative lesion classification, (b) semi-quantitative classification (sq-MRI), (c) voxel-based morphometry comparing UCP and typically developed children (VBM-DARTEL), and (d) quantitative brain tissue segmentation (q-BTS). In addition, functional MRI was used to assess spared functional activations and cluster lateralization in the ipsilesional and contralesional hemispheres of UCP children during the execution of simple movements and grasping actions with the more affected hand. Lesions most frequently involved the periventricular white matter, corpus callosum, posterior limb of the internal capsule, thalamus, basal ganglia and brainstem. VMB-DARTEL analysis allowed to detect mainly white matter lesions. Both sq-MRI classification and q-BTS identified lesions of thalamus, brainstem, and basal ganglia. In particular, UCP patients with synergic hand pattern showed larger involvement of subcortical structures, as compared to those with semi-functional hand. Furthermore, sparing of gray matter in basal ganglia and thalamus was positively correlated with MUUL and AHA scores. Concerning white matter, q-BTS revealed a larger damage of fronto-striatal connections in patients with synergic hand, as compared to those with semi-functional hand. The volume of these connections was correlated to unimanual function (MUUL score). The fMRI results showed that all patients, but one, including those with cortical lesions, had activation in ipsilesional areas, regardless of lesion timing. Children with synergic hand showed more lateralized activation in the ipsilesional hemisphere both during grasping and simple movements, while children with semi-functional hand exhibited more bilateral activation during grasping. The study demonstrates that lesion localization, rather than lesion type based on the timing of their occurrence, is more associated with the functional level of hand manipulation. Overall, the preservation of subcortical structures and white matter can predict a better functional outcome. Future studies integrating different techniques (structural and functional imaging, TMS) could provide further evidence on the relation between brain reorganization and specific pattern of manipulation in UCP children.
Evidence regarding the management of several aspects of cerebral palsy improved in recent years. Still, discrepancies are reported in clinical practice. Italian professionals and stakeholders ...expressed the need of setting up updated, evidenced-based, shared statements, to address clinical practice in cerebral palsy rehabilitation. The objective of the present study was to provide an updated overview of the state of knowledge, regarding the management and motor rehabilitation of children and young people with cerebral palsy, as the framework to develop evidence-based recommendations on this topic.
Guidelines and systematic reviews were searched, relative to evidence-based management and motor treatment, aimed at improving gross motor and manual function and activities, in subjects with cerebral palsy, aged 2-18 years. A systematic search according to the Patients Intervention Control Outcome framework was executed on multiple sites. Independent evaluators provided selection and quality assessment of the studies and extraction of data.
Four guidelines, 43 systematic reviews, and three primary studies were included. Agreement among guidelines was reported relative to the general requirements of management and motor treatment. Considering the subject's multidimensional profile, age and developmentally appropriate activities were recommended to set individual goals and interventions. Only a few approaches were supported by high-level evidence (i.e., bimanual therapy and constraint-induced movement therapy to enhance manual performance). Several task-specific active approaches, to improve gross motor function and gait, were reported (mobility and gait training, cycling, backward gait, and treadmill), based on low-level evidence. Increasing daily physical activity and countering sedentary behavior were advised. Based on the available evidence, non-invasive brain stimulation, virtual reality, action-observation therapy, hydrotherapy, and hippotherapy might be complementary to task or goal-oriented physical therapy programs.
A multiple-disciplinary family-centered evidence-based management is recommended. All motor rehabilitation approaches to minors affected by cerebral palsy must share the following fundamental characteristics: engaging active involvement of the subject, individualized, age and developmentally appropriate, goal-directed, skill-based, and preferably intensive and time-limited, but suitable for the needs and preferences of the child or young person and their family, and feasible considering the implications for themselves and possible contextual limitations.
The main aim of this study was the comparative evaluation of fibroin scaffolds combined with human stem cells, such as dental pulp stem cells (hDPSCs) and amniotic fluid stem cells (hAFSCs), used to ...repair critical-size cranial bone defects in immunocompromised rats. Two symmetric full-thickness cranial defects on each parietal region of rats have been replenished with silk fibroin scaffolds with or without preseeded stem cells addressed toward osteogenic lineage in vitro. Animals were euthanized after 4 weeks postoperatively and cranial tissue samples were taken for histological analysis. The presence of human cells in the new-formed bone was confirmed by confocal analysis with an antibody directed to a human mitochondrial protein. Fibroin scaffolds induced mature bone formation and defect correction, with higher bone amount produced by hAFSC-seeded scaffolds. Our findings demonstrated the strong potential of stem cells/fibroin bioengineered constructs for correcting large cranial defects in animal model and is likely a promising approach for the reconstruction of human large skeletal defects in craniofacial surgery.
Motor Imagery (MI) refers to mental simulation of a motor action without producing any overt movement. Previous studies showed that children with Unilateral Cerebral Palsy (UCP) are impaired in ...implicit MI, as demonstrated by the performance of Hand Laterality Judgment tasks. The aim of this study was to examine the specificity of explicit MI deficits in UCP children.
A group of UCP children (
= 10; aged 9-14) performed a mental chronometry task consisting in grasping an object and placing it into a container, or in imagining to perform the same action. As control, a group of typically developing (TD) children, matched by age, performed the same task. Movement durations for executed and imagined trials were recorded. A subgroup of 7 UCP children and 10 TD children also underwent a session of functional MRI to examine the activation of parieto-frontal areas typically associated to MI processes, during the imagination of reaching-grasping actions performed with the paretic hand.
Behavioral results revealed the existence of a correlation between executed and imagined movement durations both in TD and UCP groups. Moreover, the regression analysis in TD children showed that higher scores in mental chronometry tasks were positively correlated to increased bilateral activation of the intraparietal sulcus (IPS), superior parietal lobule (SPL), and dorsal premotor (PMd) cortex. A similar analysis revealed in the UCP group a positive correlation between a higher score in the mental chronometry task and bilateral activations of IPS, and to activation of contralesional, right PMd, and putamen during imagination of grasping movements.
These results provide new insights on the relationship between MI capacity and motor deficits in UCP children, suggesting the possibility of the use of explicit MI training to improve patient's upper limb motor functions.
The interpretation of cerebral palsy (CP) is closely linked to points of view that are no longer acceptable: 1) the idea that it is primarily a motor problem (posture and movement disorder); 2) the ...idea that it is only a central (cerebral) pathology; 3) the idea that it is a non-progressive disease (fixed encephalopathy). Actually, the problems that contribute to producing the CP clinical picture are several and complex. First of all, building of the action, starting from subject motivation, through motor imagery and subsequent project elaboration. Sequentially, executive planning, disorder often hidden under the most remarkable alteration of motor patterns and muscle tone. Finally, realization, conditioned by the idea that the locomotor apparatus is only and always the victim of an incapable central nervous system. Little known and very neglected perceptive components can contribute to compromising subject motor control. The influences that primitive changes of musculoskeletal system, often depending on site, nature, size and time of the lesion, exert on the possible choices of the central nervous system are often overlooked. Peripheral structures can in fact modify considerably the expression of palsy (understood as the form of adaptive functions) primitively. At least six different sources of error can be identified in the cerebral palsied child. For a rehabilitative intervention with greater possibilities of effectiveness, it is necessary to recognize and evaluate each of them. Especially as regards the prevention of secondary deformities, the responsibility attributed to physiotherapy must be re-evaluated.
Duchenne muscular dystrophy (DMD), caused by a lack of the functional structural protein dystrophin, leads to severe muscle degeneration where the patients are typically wheelchair-bound and die in ...their mid-twenties from cardiac or respiratory failure or both. The aim of this study was to investigate the potential of human dental pulp stem cells (hDPSCs) and human amniotic fluid stem cells (hAFSCs) to differentiate toward a skeletal myogenic lineage using several different protocols in order to determine the optimal conditions for achieving myogenic commitment and to subsequently evaluate their contribution in the improvement of the pathological features associated with dystrophic skeletal muscle when intramuscularly injected into mdx/SCID mice, an immune-compromised animal model of DMD.
Human DPSCs and AFSCs were differentiated toward myogenic lineage in vitro through the direct co-culture with a myogenic cell line (C2C12 cells) and through a preliminary demethylation treatment with 5-Aza-2'-deoxycytidine (5-Aza), respectively. The commitment and differentiation of both hDPSCs and hAFSCs were evaluated by immunofluorescence and Western blot analysis. Subsequently, hDPSCs and hAFSCs, preliminarily demethylated and pre-differentiated toward a myogenic lineage for 2 weeks, were injected into the dystrophic gastrocnemius muscles of mdx/SCID mice. After 1, 2, and 4 weeks, the gastrocnemius muscles were taken for immunofluorescence and histological analyses.
Both populations of cells engrafted within the host muscle of mdx/SCID mice and through a paracrine effect promoted angiogenesis and reduced fibrosis, which eventually led to an improvement of the histopathology of the dystrophic muscle.
This study shows that hAFSCs and hDPSCs represent potential sources of stem cells for translational strategies to improve the histopathology and potentially alleviate the muscle weakness in patients with DMD.
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