Abstract
Background
Creatine (Cr), an amino acid derivative, is one of the most important sources of energy acting as both a spatial and temporal energy buffer through its phosphorylated analogue ...phosphocreatine (PCr) and creatine kinase (CK). Maternal Cr biosynthesis and metabolism seem to play an important role in pregnancy, as shown in preclinical and in healthy human pregnancy studies. Patients with Arginine:Glycine Amidino-Transferase deficiency (AGAT-d), due to the deficit of the first enzyme involved in Cr synthesis, are at a disadvantage due to their failure to synthesize Cr and their dependence on external intake, in contrast to normal subjects, where changes in Cr biosynthesis supply their needs.
We report the outcomes of a pregnancy in an AGAT-d woman, and the challenge we faced in managing her treatment with oral Cr to ensure optimal conditions for her fetus.
Case presentation
A 22-year-old AGAT-d woman referred to our Institute for the management of her first conception at 11 weeks of fetal gestational age. Sonographic monitoring at 20 w GA indicated a reduction of fetal growth, in particular of the head circumference that was below the 3
rd
centile. Biochemical monitoring of Cr in biological fluids of the mother revealed a decline of the Cr concentrations, in particular in the urine sample, requiring prompt correction of the Cr dose. At 35 weeks of gestation the patient delivered a male infant, heterozygous for
GATM
mutation, with normal brain Cr levels; at one year the baby achieved typical developmental milestones.
Conclusions
This rare pregnancy demonstrates that Cr levels in the blood and urine of the mother with AGAT-d decreased since the first months of gestation. The increase of the Cr daily dose administered to the mother seems to have produced beneficial effects also on the fetus.
The Prechtl General Movement Assessment (GMA) has become a cornerstone assessment in early identification of cerebral palsy (CP), particularly during the fidgety movement period at 3–5 months of age. ...Additionally, assessment of motor repertoire, such as antigravity movements and postural patterns, which form the Motor Optimality Score (MOS), may provide insight into an infant’s later motor function. This study aimed to identify early specific markers for ambulation, gross motor function (using the Gross Motor Function Classification System, GMFCS), topography (unilateral, bilateral), and type (spastic, dyskinetic, ataxic, and hypotonic) of CP in a large worldwide cohort of 468 infants. We found that 95% of children with CP did not have fidgety movements, with 100% having non-optimal MOS. GMFCS level was strongly correlated to MOS. An MOS > 14 was most likely associated with GMFCS outcomes I or II, whereas GMFCS outcomes IV or V were hardly ever associated with an MOS > 8. A number of different movement patterns were associated with more severe functional impairment (GMFCS III–V), including atypical arching and persistent cramped-synchronized movements. Asymmetrical segmental movements were strongly associated with unilateral CP. Circular arm movements were associated with dyskinetic CP. This study demonstrated that use of the MOS contributes to understanding later CP prognosis, including early markers for type and severity.
Creatine Transporter Deficiency (CTD) is an inborn error of metabolism presenting with intellectual disability, behavioral disturbances and epilepsy. There is currently no cure for this disorder. ...Here, we employed novel biomarkers for monitoring brain function, together with well-established behavioral readouts for CTD mice, to longitudinally study the therapeutic efficacy of cyclocreatine (cCr) at the preclinical level. Our results show that cCr treatment is able to partially correct hemodynamic responses and EEG abnormalities, improve cognitive deficits, revert autistic-like behaviors and protect against seizures. This study provides encouraging data to support the potential therapeutic benefit of cyclocreatine or other chemically modified lipophilic analogs of Cr.
Understanding development of bimanual upper limb (UL) activities in both typical and atypical conditions in children is important for: i) tailoring rehabilitation programs, ii) monitoring progress, ...iii) determining outcomes and iv) evaluating effectiveness of treatment/rehabilitation. Recent technological advances, such as wearable sensors, offer possibilities to perform standard medical monitoring. Body-worn motion sensors, mainly accelerometers, have shown very promising results but, so far, these studies have mainly focused on adults. The main aim of this review was to report the evidence of UL activity of both typically developing (TD) children and children with neurodevelopmental disorders (NDDs) that are reliably reported and comparable, using a combination of multiple wearable inertial sensors, both in laboratory and natural settings. Articles were selected from three research databases (PubMed, Web of Science and EBSCO). Included studies reported data on children aged 0-20 years old simultaneously wearing at least two inertial sensors on upper extremities. The collected and reported data were relevant in order to describe the amount of physical activity performed by the two ULs separately. A total of 21 articles were selected: 11 including TD, and 10 regarding NDDs. For each article, a review of both clinical and technical data was performed. We considered inertial sensors used for following aims: (i) to establish activity intensity cut-points; (ii) to investigate validity and reliability of specified markers, placement and/or number of inertial sensors; (iii) to evaluate duration and intensity of natural UL movements, defined motor tasks and tremor; and (iv) to assess efficacy of certain rehabilitation protocols. Our conclusions were that inertial sensors are able to detect differences in use between both hands and that all reviewed studies support use of accelerometers as an objective outcome measure, appropriate in assessing UL activity in young children with NDDs and determining intervention effectiveness. Further research on responsiveness to interventions and consistency with use in real-world settings is needed. This information could be useful in planning UL rehabilitation strategies.
In goal-oriented locomotion, healthy adults generate highly stereotyped trajectories and a consistent anticipatory head orienting behaviour, both evidence of top-down, open-loop control. The aim of ...this study is to describe the typical development of anticipatory orienting strategies and trajectory formation. Our hypothesis is that full-blown anticipatory control requires advanced navigational skills. Twenty-six healthy subjects (14 children: 4–11 years; 6 adolescents: 13–17 years; 6 adults) were asked to walk freely towards one of the three visual targets, in a randomised order. Movement was captured via an optoelectronic system, with 15 body markers. The whole-body displacement, yaw orientation of head, trunk and pelvis, heading direction and foot placements were extracted. Head-heading anticipation, trajectory curvature, indexes of variability of trajectories, foot placements and kinematic profiles were studied. The mean head-heading anticipation time and trajectory curvature did not significantly differ among age groups. In children, however, head anticipation was more often lacking (
χ
2
= 9.55,
p
< 0.01), and there were significant intra- and inter-subject variations. Trajectory curvature was often very high in children, while it became consistently lower in adolescence (
χ
2
= 78.59,
p
< 10
−17
). The indexes of spatial and kinematic variability all followed a decreasing developmental trend (
R
2
> 0.5,
p
< 0.0001). In conclusion, children under 11 do not perform curvilinear locomotor trajectories as adolescents and adults do. Anticipatory head orientation and trajectory formation develop in late childhood, well after gait maturation. Navigational skills, such as path planning and shifting from ego- to allocentric spatial reference frames, are proposed as necessary requisites for mature locomotor control.
Children with Special Needs represent a highly heterogeneous group in terms of neurofunctional, behavioral, and socio-cognitive characteristics, but they have in common a frequent impairment of ...Executive Functions. Educational Robotics is generally dedicated to study the effects of constructing and programming robots based on children's learning and academic achievement. Recently, we found that being engaged in progressively more challenging robot planning and monitoring (ER-Lab) promotes visual-spatial working memory and response inhibition in early childhood during typical development, and that an ER-Lab can be a feasible rehabilitative tool for children with Special Needs. The present study aimed to verify the efficacy of the ER-Lab on Executive Functions in children with Special Needs for the first time by using an RCT within their school environment. To pursue these aims, this study reports the results obtained in 42 first-grade children with Special Needs engaged in school Educational Robotics Laboratories (ER-Lab) to promote Executive Functions by means of enjoyable, intensive, and incrementally more challenging activities requiring them to program a bee-shaped robot called Bee-bot
(Campus Store). Several adaptations were done to meet different motor, cognitive, and social needs. All children were evaluated by means of standardized tests performed by each child before and at the end of the ER-Lab activities. Children with Special Needs had significantly improved inhibition skills, and children with attentional impairment had more benefits in their inhibition of motor responses tasks with respect to children with a language deficit. Results of the study and future perspectives on how ER-Lab programs could become a powerful tool in classrooms with children with special needs are discussed.
There is overwhelming evidence that autism spectrum disorder (ASD) is related to altered brain connectivity. While these alterations are starting to be well characterized in subjects where the ...clinical picture is fully expressed, less is known on their earlier developmental course. In the present study we systematically reviewed current knowledge on structural connectivity in ASD infants and toddlers. We searched PubMed and Medline databases for all English language papers, published from year 2000, exploring structural connectivity in populations of infants and toddlers whose mean age was below 30 months. Of the 264 papers extracted, four were found to be eligible and were reviewed. Three of the four selected studies reported higher fractional anisotropy values in subjects with ASD compared to controls within commissural fibers, projections fibers, and association fibers, suggesting brain hyper-connectivity in the earliest phases of the disorder. Similar conclusions emerged from the other diffusion parameters assessed. These findings are reversed to what is generally found in studies exploring older patient groups and suggest a developmental course characterized by a shift toward hypo-connectivity starting at a time between two and four years of age.
Objective
Subjects with severe hemiplegic cerebral palsy have increased ipsilateral corticospinal projections from their noninfarcted cortex. We investigated whether their severe impairment might, in ...part, be caused by activity‐dependent, competitive displacement of surviving contralateral corticospinal projections from the affected cortex by more active ipsilateral corticospinal projections from the nonaffected cortex, thereby compounding the impairment.
Methods
Transcranial magnetic stimulation (TMS) characterized corticospinal tract development from each hemisphere over the first 2 years in 32 healthy children, 14 children with unilateral stroke, and 25 with bilateral lesions. Magnetic resonance imaging and anatomic studies compared corticospinal tract growth in 13 patients with perinatal stroke with 46 healthy subjects.
Results
Infants with unilateral lesions initially had responses after TMS of the affected cortex, which became progressively more abnormal, and seven were eventually lost. There was associated hypertrophy of the ipsilateral corticospinal axons projecting from the noninfarcted cortex. Magnetic resonance imaging and anatomic studies demonstrated hypertrophy of the corticospinal tract from the noninfarcted hemisphere. TMS findings soon after the stroke did not predict impairment; subsequent loss of responses and hypertrophy of ipsilateral corticospinal axons from the noninfarcted cortex predicted severe impairment at 2 years. Infants with bilateral lesions maintained responses to TMS from both hemispheres with a normal pattern of development.
Interpretation
Rather than representing “reparative plasticity,” increased ipsilateral projections from the noninfarcted cortex compound disability by competitively displacing surviving contralateral corticospinal projections from the infarcted cortex. This may provide a pathophysiological explanation for why signs of hemiplegic cerebral palsy appear late and progress over the first 2 years of life. Ann Neurol 2007
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.
To systematically review and analyse the effects of Action Observation Training on adults and children with brain damage.
Seven electronic databases (Cochrane, EBSCO, Embase, Eric, PubMed, Scopus and ...Web of Science) were searched up to 16 September 2018 to select Randomized Controlled Trials focused on adults and children with brain damage that included AOT training on upper and/or lower limb carried out for at least 1 week. Identification of studies and data extraction was conducted with two reviewers working independently. Oxford Centre for Evidence-based Medicine (March2009) - Levels of Evidence and Physiotherapy Evidence Database scale were used to grade studies. The data collected from the articles were analysed using software R, version 3.4.3. Hedge's g values were calculated and effect size estimates were pooled across studies. Separate meta-analyses were carried out for each ICF domain (i.e. body function and activity) for upper and lower limb.
Out of the 210 records identified after removing duplicates, 22 were selected for systematic review and 19 were included in the meta-analysis. Thirteen studies included in the meta-analysis focused on upper limb rehabilitation (4 in children and 9 in adults) and 6 on lower limb rehabilitation (only studies in adults). A total of 626 patients were included in the meta-analysis. An overall statistically significant effect size was found for upper limb body function (0.44, 95% CI: 0.24, 0.64, p < 0.001) and upper limb activity domain (0.47, 95% CI: 0.30, 0.64, p < 0.001). For lower limb, only the activity domain was analysed, revealing a statistically significant overall effect size (0.56, 95% CI: 0.28, 0.84, p < 0.001).
Action Observation Training (AOT) is an innovative rehabilitation tool for individuals with brain damage, which shows promising results in improving the activity domain for upper and lower limbs, and also the body function domain for the upper limb. However, the examined studies lack uniformity and further well-designed, larger controlled trials are necessary to determine the most suitable type of AOT particularly in children.
CRD42019119600.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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