Establishment of a Biorepository for Down Syndrome: Experience of the Inter-Institutional Multidisciplinary BioBank - BioBIM.

BACKGROUND: Down syndrome, or Trisomy 21, is the leading genetic cause of cognitive disability in children and is associated with a high risk of several comorbidities, particularly congenital heart defects, early onset Alzheimer's disease, leukaemia, and autoimmune disorders. OBJECTIVE: This study describes the design, methods, and operational procedures employed to establish a biobank dedicated to Down syndrome that can support research projects investigating the effects of various genetic and environmental factors on this complex disease. METHODS: Blood was collected from all recruited subjects, processed, aliquoted and immediately frozen at -80 °C in the Interinstitutional Multidisciplinary BioBank (BioBIM) facilities. A small aliquot of the sample was used to perform blood tests for which analysis would not be feasible at a later date, such as blood cell counts. Each biological sample was coded, assigned a Standard PREanalytical Code, and registered in the oloBIOBANK software connected to a medical card containing all the donor's anamnestic data. All samples were stored under continuous real-time temperature recording using a freezer connected to a T-GUARD alarm system. In addition, a radiofrequency identification tracking system strictly monitored each cryopreservation operation performed throughout the sample lifecycle. RESULTS: Biological samples were collected from 454 individuals with Down syndrome from 2007 to 2023. A total of 2233 biological samples were available for research purposes, including whole blood in different anticoagulants, serum, plasma, and frozen peripheral blood mononuclear cells. The quality of the nucleic acids obtained through specific standard operating procedures demonstrated that these samples were appropriate for clinical and basic research. CONCLUSION: By establishing this biobank, we have gathered a significant number of biological samples and clinical data from individuals with Down syndrome, thereby fostering collaboration between different research groups in an open and transparent manner. Sharing expertise and resources among scientists will ultimately facilitate the transfer of knowledge to clinical practice, leading to the development of more effective therapeutic treatments to improve the outcomes and quality of life of patients with Down syndrome.

Corrigendum to "Energy analysis of gait in patients with down syndrome" [Heliyon 8 (11) (November 2022) Article e11702].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e11702.].

Influence of Foot Morphology on the Center of Pressure Pattern in Patients with Down Syndrome.

BACKGROUND: The primary aim of this study was to assess how different conformations of the foot in individuals with Down syndrome affected the CoP during walking, and the secondary aim was to evaluate the effect of an excess of mass in young adults and children with Down syndrome and flat foot. The greater investigation of these aspects will allow for more targeted rehabilitation treatments to improve a patient's quality of life. METHODS: The tests were carried out on 217 subjects with Down syndrome, 65 children and 152 young adults, and on 30 healthy individuals, 19 children and 11 young adults. All subjects underwent gait analysis, and the group with Down syndrome was also assessed with baropodometric tests to evaluate foot morphology. RESULTS: The statistical analysis showed that within both the young adult and child groups, the CoP pattern in the anterior-posterior direction reflected a difficulty in proceeding in the walking direction compensated by a medio-lateral swing. The gait of children with Down syndrome was more impaired than that of young adults. In both young adults and children, a higher severity of impairment was found in overweight and obese female individuals. CONCLUSIONS: These results suggest that the sensory deficits and the development of hypotonic muscles and lax ligaments of the syndrome lead to morphological alterations of the foot that, combined with the physical characteristics of short stature and obesity, negatively impact the CoP pattern of people with Down syndrome during walking.

Energy analysis of gait in patients with down syndrome.

Background: the primary aim of this study is to analyse the energy parameters of patients with Down syndrome compared to a control group and secondly to verify whether the sport activity leads to differences in energy expenditure. Methods: 3 groups of subjects were identified: 8 healthy subjects and 147 subjects with Down syndrome, of whom 14 played sports at least once a week. An energy index was calculated, given by the ratio between potential and kinetic energy. Next, kinetic ad potential energy parameters were extrapolated at 60% of the gait cycle (propulsion phase). Findings: Down syndrome group was compared with the control group and emerged that the energy index was higher in the first one. No changes were found between Down syndrome and Down syndrome Sport groups. The analysis of the energy parameters showed that all parameters, except the medio-lateral kinetic energy, were higher in the control than in the Down syndrome groups. The potential energy, medio-lateral kinetic energy, and vertical were higher in the Down syndrome Sport group than in the Down syndrome group. The kinetic energy and the mean velocity were higher in the control group than in Down syndrome Sport group while the medio-lateral kinetic energy was lower. Interpretation: sport modified the parameter of potential energy but not that of kinetic energy, which continued to be different compared to the healthy group and increased the oscillations in the medio-lateral plane, which were double compared to Down syndrome group. The increase in potential energy, found to be almost equal to that of control group, indicates an increase in vertical oscillations. This could be because subjects who practise sports have stronger muscles that allow a greater push-off ability, which therefore increases their potential energy.

Quantification of the effects of robotic-assisted gait training on upper and lower body strategy during gait in diplegic children with Cerebral Palsy using summary parameters.

The effects of robotic-assisted gait training on upper and lower body strategy during gait in diplegic children with Cerebral Palsy (CP) were quantified using summary parameters (Upper Body Profile Score (UBPS) and Gait Profile Score (GPS)). Firstly, the upper body strategy during gait was assessed in 73 children with CP and 15 healthy children (Control Group: CG): patients with CP exhibited higher values of most of the summary parameters of the upper body position than the CG. Then, the effects of a robotic-assisted gait training in a sub-group of 35 children by means of UBPS were evaluated. After robotic-assisted gait training program, no significant differences as for the summary parameters (UBPS and GPS). However, considering the specific variables scores, significant improvements are displayed as for the upper body parameter on the sagittal plane (Upper Body Ant/Pst index) and the lower limbs, in particular pelvis (Pelvic Ant/Pst and Pelvic Int/Ext indices) and as for walking velocity. A sort of reorganization of full-body kinematics, especially at upper body and proximal level (pelvis) seems to appear, with a new gait approach, characterised by a better strategy of the upper body associated with a significant improvement of the pelvis movement.

Multi-segmental postural control patterns in down syndrome.

BACKGROUND: Patients with Down Syndrome (DS) exhibit less efficient and unstable standing postural control. The specificities of somatosensorial deficits might result in a different utilization of resources and in distinct whole-body kinematic patterns, to date still unexplored. In this paper we aim at addressing multi-segmental coordination patterns in people with DS while maintaining standing balance under different visual conditions (open and closed eyes). METHODS: This cross-sectional observational cohort study involved two groups of 23 patients with DS and 12 healthy controls. A 30-s standing balance test allowed to extract (i) the length of the trajectory of the center-of-pressure sway and 95% confidence ellipse area from Ground Reaction forces, and (ii) Principal Movement (PM) components from full-body motion kinematics; the latter were obtained exploiting a Principal Component Analysis-based approach, also embracing a motor-control perspective through the evaluation of the number of modifications applied by the neuromuscular controller on segments' acceleration. FINDINGS: Trajectory length was significantly higher in patients; 95% ellipse confidence area did not differ between groups/condition. Postural movement components differed in people with DS from healthy controls not only in the "observable", behavioural phenotype (PM3 and PM8), but also in the amount of activation of the associated control (PM1 to PM8, over-activated in DS) in all spatial directions. INTERPRETATION: Results reinforced the prevalence of a medio-lateral hip strategy (instead of an ankle strategy) in maintaining postural stability. Most important, they revealed a less frequent activation of postural patterns in all spatial directions.

Quantification of upper body strategy during gait in children with spastic diplegia using a summary parameter.

A summary measure for quantification of the upper body position (Upper Body Profile Score [UBPS]) during gait was proposed and used in 38 children with Cerebral Palsy (CP) and 15 healthy children (Control Group: CG). Patients with CP exhibited higher values of most of the summary parameters of the upper body position than the CG. The higher influence on UBPS is by the upper body position in sagittal and transversal plane. A significant and fair correlation between UBPS and Gait Profile Score (a summary measure to quantify the lower limb gait pattern) suggests that altered upper body movements during walking could be associated with the presence of lower limb impairments.

Bilateral Foot Orthoses Elicit Changes in Gait Kinematics of Adolescents with Down Syndrome with Flatfoot.

Background: Subjects with Down Syndrome (DS) are characterized by specific physiological alterations, including musculoskeletal abnormalities. Flat Foot (FF), caused by hypotonia and ligament laxity, represents one of the most common disabling disorders in this population. Conservative treatments promote the use of orthopaedic insoles and plantar supports. The aim of this study was to evaluate the impact of Foot Orthoses (FOs) on the gait pattern of subjects with DS, assessing the biomechanical effects associated with their use. Methods: Twenty-nine subjects were screened under two conditions-walking barefoot (WB); with shoes and insoles (WSI), during three trials for each. Assessments were performed through the 3D gait analysis, using an optoelectronic system, force platforms, and video recording. Specifically, synthetic indices of gait kinematics, i.e., gait profile score (GPS) and gait variable score (GVS) were calculated and compared with Wilcoxon signed-rank test, to evaluate between-conditions. Results: Significant variations were found in GVS foot progression index, representative of foot rotation during walking, in adolescents only. Conclusions: Bilateral FOs has a positive immediate impact on gait quality in adolescents with DS, as confirmed by quantitative analysis. FOs prescription is an evidence-based early approach to slow down biomechanical abnormalities and prevent relative symptoms.

Gait and postural control patterns and rehabilitation in Down syndrome: a systematic review.

[Purpose] To describe (1) the current knowledge on gait and postural control in individuals with Down syndrome in terms of spatiotemporal, kinematics and kinetics, and (2) relevant rehabilitation strategies. [Methods] Randomized and non-randomized clinical trials published between January 1997 and October 2019 were selected by searching four scientific databases. We included studies on patients with Down syndrome involving gait analysis or postural control. A custom data-extraction and appraisal form was developed to collect the key features of each article. The PEDro Scale was used to evaluate the methodological quality of the studies. [Results] A total of 37 out of 146 cross-sectional and longitudinal studies were included in the review. The main abnormalities included: reduction of gait velocity and step length, poor static balance with increased anteroposterior and mediolateral oscillations and a larger step width. [Conclusion] A number of compensatory patterns during movement was observed, with a direct influence on improvements in stability and postural control throughout daily life. Intensive gait training at an early age appears to produce long-term improvements in this population. Future research should focus on the interaction between the motor and cognitive function, and on the functional effects due to the exposure to an enriched environment.

A novel summary kinematic index for postural characterization in subjects with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a progressive neurological disorder characterized, among other symptoms, by a significant modified posture. Although a detailed assessment of postural abnormalities can be performed using quantitative movement analysis, the output of such procedure might be not suitable for a routine clinical use due to its intrinsic complexity. However, synthetic measures may facilitate the interpretation of kinematic data for physicians and thus make such tools fully exploitable in daily practice. AIM: According to these considerations, the aim of the present study is to propose a new summary index, the Postural Profile Score (PPS, together with its constituent variables: Postural Variable Scores [PVSs]), which can characterize the postural kinematic biomechanical profile of an individual; this approach was then applied to a cohort of individuals with PD. DESIGN: Controlled observational study. SETTING: Movement Analysis Laboratory of Hospital. POPULATION: Forty-five individuals with PD in mild to severe disability stage, of mean age 65.9 (SD 8.3) years and 21 healthy control age-matched (CG) were tested using an optoelectronic system during bipedal quiet standing. METHODS: Twelve joint angles of trunk and of lower limbs, considered representative of the whole-body posture according to Davis protocol, were acquired and the root mean square (RMS) difference between them and those of the unaffected participants (PVSs) were computed. Then, the PPS was calculated as a combination of the selected PVSs. The existence of possible differences between people with PD and controls for PPS and PVSs was assessed using MANOVA test. UPDRS III score was also considered in order to assess existence of correlation between synthetic indexes and Clinical scales values. RESULTS: Significant differences in PPS were detected between PD and CG (8.59° vs. 6.11°, P<0.001) and in some of the considered PVS (Trunk Sagittal, Trunk Frontal, Trunk Transversal, Hip flexion-extension, Hip abdo-adduction and Knee flexion-extension). Significant positive correlations were found between Clinical scales Vs trunk and ankle orientation. CONCLUSIONS: PPS could represent a reliable summary index of global postural abnormalities in people with PD, and in particular some PVSs appear more suitable to describe the deviation from a physiologic postural pattern. The results demonstrate that the posture in the patient with PD is modified compared to the control group. In particular, the trunk is the body district which mainly characterizes the alteration of the posture as documented by its PVSs values and their correlation with clinical evaluation scales. In conclusion, this study evidences the interest to measure the position of the trunk in order to characterize the postural kinematic position in individuals with PD. CLINICAL REHABILITATION IMPACT: PPS could be a useful tool for the characterization of postural phenotype in subjects with Parkinson's disease and could provide indications for specific rehabilitation protocols.

Down Syndrome: Gait Pattern Alterations in Posture Space Kinematics.

Gait characteristics in Down syndrome (DS) are documented in terms of discrete kinematic variables. However, such features are strictly interrelated and reflect neurological and developmental delays. A phenotypical, quantitative assessment of how multi-joint walking patterns are activated and controlled during gait would enhance the understanding of locomotor mechanisms in such patients. We adopted an analysis framework based on principal component analysis: the gait kinematics of 221 patients aged 6-45 were expressed in terms of a reduced set of one-dimensional movement components. Their time course during the gait cycle was described by score vectors, here called principal positions; its second time derivative, called principal acceleration, characterized the activity of the neuromuscular controller on each component. Outcomes were compared to an age-matched group of 49 healthy individuals. After controlling for the effect of walking speed, we observed that the main alterations in gait patterns emerged in the fourth component which is mostly devoted to stability management (group differences, p < 0.001). Rather, the main sagittal-plane locomotor patterns showed only subtle differences from the control group. Using statistical parametrical mapping, we found when (step-to-step transitions) and how (interrelated joints motion) the fourth movement deviated from normal: in particular, an excessive hip adduction and trunk inclination during the transition between single and double support phases. These findings match the neurological and sensorimotor trait of DS and suggest the promotion of targeted rehabilitative interventions. Furthermore, this paper opens to the adoption of principal positions and principal accelerations to investigate the neuromuscular control of movement patterns during locomotion.

Kinetic-based indexes for the functional evaluation of gait in diplegic children: a preliminary report.

We evaluated the feasibility of a set of indexes based on ground reaction forces to discriminate between the degree of severity of spastic diplegia, identified via Gross Motor Function Classification System (GMFCS). A stepwise discriminant ordinal regression analysis performed on a sample of 58 children returned a subset of variables related to the ratio between braking and propulsive vertical forces and anteroposterior timings. Rather, parameters concerning bilateral symmetry were poorly discriminating. The relative simplicity of the selected indexes allows for their easy implementation on existing gait analysis applications for screening purposes.

A biomechanical study of gait initiation in Down syndrome.

BACKGROUND: Gait Initiation (GI) is a functional task that challenges the balance control requiring weight shift and a transition from standing to walking. Individuals with Down Syndrome (DS) walk with low velocity, prolonged stance and shorter steps beside an increased support base. However, no studies performed GI analysis on this population. The aim of this study is to quantitatively characterize the GI task in subjects with DS compared with a typically developed control group. METHODS: Seventeen individuals with DS (17 to 40 years) and 19 healthy subjects (17 to 40 years) were enrolled in the study. Data were acquired using an optoelectronic motion capture system and force plates in order to measure the displacement and velocity of Center of Mass (CoM) and the trajectory of Center Of Pressure (CoP). All participants were asked to stand barefoot on the first force platform and received a verbal cue to begin walking for 6 gait initiation trials (three starting with each foot). The CoP duration, velocity, length and excursion were calculated during the anticipatory postural adjustments phases (APAs) and the locomotor (LOC) phase. For the analysis of the CoM, its displacements in antero-posterior (AP) and medio-lateral (ML) during the APAs and LOC phases. Statistical analysis was conducted to compare the two groups. RESULTS: Regarding CoP measures, when compared to control group, individuals with DS presented higher durations, lower velocities, longer lengths during the second APA and total phases, and shorter lengths during the first APA and LOC phases. The group with DS also presented longer CoP excursion during the second APA, whereas a shorter excursion was present during the first APA and LOC phases. The AP excursion in CoM is reduced in the participants with DS. CONCLUSIONS: Our results could be useful in the rehabilitation of individuals with DS as they suggest to reinforce exercise programs to improve balance in AP and ML directions, which is demonstrated to be impaired in these subjects.

Quantitative assessment of drawing tests in children with dyslexia and dysgraphia.

Drawing tests in children diagnosed with dyslexia and dysgraphia were quantitatively compared. Fourteen children with dysgraphia, 19 with dyslexia and 13 normally developing were asked to copy 3 figures: a circle, a square and a cross. An optoelectronic system allowed the acquisition of the drawing track in three-dimensions. The participants' head position and upper limb movements were measured as well. A set of parameters including movement duration, velocity, length of the trace, Range of Motion of the upper limb, was computed and compared among the 3 groups. Children with dyslexia traced the circle faster than the other groups. In the cross test, dyslexic participants showed a reduced execution time and increased velocity while drawing the horizontal line. Children with dyslexia were also faster in drawing certain sides of square with respect to the other groups.

Use of 3D gait analysis as predictor of Achilles tendon lengthening surgery outcomes in children with cerebral palsy.

BACKGROUND: In children with spastic cerebral palsy (CP), the treatment of equinus foot with Achilles tendon lengthening (ATL) surgery is associated with high incidence of overcorrection, which may result in crouch gait. AIM: We aimed to assess if gait pattern in preoperative time could be a predictor of the surgery outcome. DESIGN: Cross-sectional retrospective study. SETTING: Movement Analysis Lab of IRCCS San Raffaele Pisana Hospital in Rome (Italy). POPULATION: Eighteen children (mean age 9.6±4.7 years) with spastic diplegia CP who underwent bilateral ATL surgery to correct equinus foot were involved. METHODS: Participants underwent 3D gait analysis before and approximately 12 months after surgery. Primary measures were spatiotemporal, kinematic (summarized by Gait Variable Scores, GVSs) and kinetic parameters. The gait patterns for each leg was defined from kinematic data, using a quantitative classification: plantar flexor knee extension (PFKE) index. The CP group was split into true equinus and jump gait. RESULTS: The equinus foot was successfully corrected as demonstrated by the improvement of GVS ankle dorsi-plantarflexion. However, there was a high rate of overcorrection in the true equinus, characterized by increases in knee flexion-extension GVS (8.7° pre vs. 16.7° post P<0.05) and knee flexion angle at initial contact (5.2° vs. 20.6° P<0.05) and by a decrease in the maximum ankle power generated at push-off (1.49 vs. 0.83 W/kg P<0.05). CONCLUSIONS: Assessment of motor phenotype in preoperative time are good predictors of the results of ATL surgery. In children with true equinus gait, the increase of knee flexion subsequent to ATL is an early indicator that this technique will lead to crouch gait. These results show the influence of true equinus and jump gait patterns on the outcomes of the ATL. CLINICAL REHABILITATION IMPACT: Therefore, we propose that this approach could have clinical value to evaluate and prescribe rehabilitation in children with CP disease, proposing different solutions depending on motor phenotype.

A proposal for a kinetic summary measure: the Gait Kinetic Index.

A new summary index for kinetic gait data is proposed (Gait Kinetic Index - GKI), BASED on six kinetic selected variables: hip, knee and ankle moments and powers on the sagittal plane. This method was applied on a control group (CG) of 18 subjects and on 57 patients with diplegic Cerebral Palsy (CP). CP showed statistical different GKI value in comparison with CG. The same is for the sub GKI with the exclusion of GKI Knee Power. The GKI seems to be a promising tool useful to measure extensively the gait pathology taking into consideration kinetic aspects of gait pattern.

Sex differences in the gait kinematics of patients with Down syndrome: A preliminary report.

OBJECTIVE: Sex-specific medicine requires understanding of the specific therapeutic needs and patho-physiology of men and women. In these terms, we investigated sex-related differences in the gait kinematics of patients with Down syndrome. DESIGN: Retrospective observational cohort study. SUBJECTS: A sample of 230 patients (103 females) aged 7-50 years underwent a standard gait-analysis test from 2000 to 2015. METHODS: Spatiotemporal gait parameters and synthetic indexes were computed as Gait Profile Score (GPS) and pelvis/lower limbs as Gait Variable Scores. RESULTS: Although speed, normalized step width, %stance and %swing were similar, in female patients step length was shorter and GPS was higher than in male patients, with no significant effect of age, speed and body mass index. Sex-specific features were found at the pelvis, hip and knee level (sagittal plane), and at the ankle level (transverse plane). CONCLUSION: Overall, in people with Down syndrome, the gait function of females tends to be more impaired than in males, with the exception of foot progression. Therapists should consider these differences when evaluating the severity of gait impairment and designing rehabilitation strategies.

An examination of the relationship between dynamic knee joint stiffness and gait pattern of children with cerebral palsy.

Dynamic joint stiffness represents the resistance that a joint opposes to an applied moment. Stiffness arises in conditions of joint laxity, instability and increased co-contraction and is commonly utilized as a means to stabilize the joint. The knee joint seems to be crucial for determining the walking pattern. The aim of this study was to investigate the association between the gait pattern, globally quantified by the Gait Profile Score (GPS), which indicates the 'quality' of a particular walking strategy, and knee dynamic joint stiffness (Kk) in children with diplegia. Kk is expressed by plotting the values of the knee flexion-extension moment versus the knee flexion-extension angle during weight acceptance. In this interval, the linear regression was fitted. The angular coefficient of the linear regression corresponded to the joint stiffness index. Sixty-one children with diplegia and 18 healthy individuals took part in this study. From their gait analysis data, the GPS (with its Gait Variable Scores-GVSs) and the Kk were calculated. Data showed that GPS (p = 2.73 × 10-21) and GVSs values for the patients with diplegia were higher in comparison to healthy controls. The Kk values for patients were not statistically different from those of controls. The correlation between Kk and GPS did not show the presence of any significant relationship (r = -0.04; p > 0.05). Thus, the functional limitation in diplegic children does not seems to be strictly related to Kk.

Gait evaluation using inertial measurement units in subjects with Parkinson's disease.

We investigated whether a wearable system based on a commercial Inertial Measurement Unit (IMU) can reliably provide the main spatiotemporal gait parameters in subjects with Parkinson's disease (PD), compared to a gold-standard optoelectronic motion capture system. The gait of 22 subjects with PD (Age: 69.4 (6.1) years; UPDRS-III: 28.0 (9.2)) was recorded simultaneously with an optoelectronic system and a commercial IMU-based wearable system. Eight spatiotemporal parameters describing the step cycle (cadence, velocity, stride length, stride duration, step length, stance, swing and double support duration) were compared between the two systems. The IMU and the optical system reported comparable gait parameters, with the exception of walking velocity (optical system, 0.72 (0.27) m∙s-1 vs. IMU: 0.86 (0.26) m∙s-1, p < 0.05). Although most parameters detected by the two systems were not statistically different, some of them like stride length, double support and step duration showed notable root mean square and mean absolute errors. In conclusion, the algorithm embedded in the current release of the commercial IMU requires further improvements to be properly used with subjects with PD. Overall, the IMU system was sufficiently accurate in the assessment of fundamental gait spatiotemporal parameters. The fast and simplified data recording process allowed by wearables makes this technology appealing and represents a possible solution for the quantification of gait in the clinical context, especially when using a traditional 3D optoelectronic gait analysis is not possible, and when subjects are not fully cooperative.

Slip avoidance strategies in children with bilateral spastic cerebral palsy and crouch gait.

BACKGROUND: A slip occurs when the required friction (RCOF) to prevent slipping at the foot/floor interfaces exceeds the available friction. The RCOF is dependent upon the biomechanics features of individuals and their gait. On the other hand, the available friction depends on environmental features. Once individuals with crouch gait have their biomechanics of gait completely altered, how do they interact with a supporting surface? The aim was to quantify the RCOF in children with bilateral spastic cerebral palsy (BSCP) and crouch gait. METHODS: 11 children with crouch gait and 11 healthy age-matched children were instructed to walk barefoot at self-selected speed over a force platform. The RCOF curve was obtained as the ratio between the tangential forces (FT), and the vertical ground reaction force (FZ). Three points were extracted by the RCOF, FT and FZ curves at the loading response, midstance and push-off phases. FINDINGS: Children with BSCP presented higher values of RCOF in all support phase and lower gait velocity relative to the healthy controls. For BSCP group no correlation between FT and FZ were found, indicating that this group is not able to negotiate the forces during the support phase. INTERPRETATION: Children with BSCP and crouch gait are not able to negotiate the forces applied on the ground in support phase, so to avoid the fall, their strategy is to reduce the gait velocity.