Comparison of two pelvic positioning belt configurations in a pediatric wheelchair.

Maintenance of stability for children in a wheelchair, particularly for those with spasticity, can be achieved through external stabilization components, such as pelvic positioning belts. Different kinds of pelvic belts exist on the market and one of the main characteristics is the different number of attachment points between the seat and the belt. As literature on this topic is limited to qualitative assessments, this study compared quantitatively 4-point versus 2-point pelvic positioning belts for the trunk fixation in 20 young patients with spasticity. Our data showed that 70% of the children required the use of pelvic belts on wheelchairs for stability and a better stability was observed with the 4-point belts than compared to the 2-point. Data generally showed in fact a higher percent of variation in terms of trunk flexion angleand knee joint angle with the 2-point belt than the 4-point belt, indicating increased submarining with the 2-point belt during sitting maintenance if compared to the 4-point belt (p < 0.05). According to our results, the 4-point belts seem to be the most effective configuration for patient stabilization, suggesting that its use prevents the thigh from submarining.

Nitric oxide donor and non steroidal anti inflammatory drugs as a therapy for muscular dystrophies: evidence from a safety study with pilot efficacy measures in adult dystrophic patients.

This open-label, single centre pilot study was designed to evaluate safety and tolerability of the combination of the drugs isosorbide dinitrate, a nitric oxide donor, and ibuprofen, a non steroid anti-inflammatory drug, in a cohort of adult dystrophic patients (Duchenne, Becker and Limb-Girdle Muscular Dystrophy). Seventy-one patients were recruited: 35, treated with the drug combination for 12 months, and 36 untreated. Safety and adverse events were assessed by reported signs and symptoms, physical examinations, blood tests, cardiac and respiratory function tests. Exploratory outcomes measure, such as the motor function measure scale, were also applied. Good safety and tolerability profiles of the long-term co-administration of the drugs were demonstrated. Few and transient side effects (i.e. headache and low blood pressure) were reported. Additionally, exploratory outcomes measures were feasible in all the disease population studied and evidenced a trend towards amelioration that reached statistical significance in one dimension of the MFM scale. Systemic administration of ibuprofen and isosorbide dinitrate provides an adequate safety margin for clinical studies aimed at assessing efficacy.

Constraint-induced movement therapy for children with hemiplegia after traumatic brain injury: a quantitative study.

OBJECTIVE: The aims of this study are to quantify the movement limitation of upper limbs in hemiplegic children with traumatic brain injury (TBI) by using a clinical-functional scale and upper limb kinematics and to evaluate the effectiveness of constraint-induced movement therapy (CIMT) on upper limbs. DESIGN: Pre-post study. SETTING: Clinical rehabilitation research laboratory. PARTICIPANTS: Ten children with TBI. MAIN OUTCOME MEASURES: The participants were evaluated by clinical examinations (Gross Motor Function Measure, Besta scale, Quality of Upper Extremities Skills Test, and Manual Ability Classification System) and 3D kinematic movement analysis of the upper limb before the CIMT program (pretest: 0.7 years after the injury) and at the end of the program (posttest: 10 weeks later). RESULTS: After the CIMT, most of the clinical measures improved significantly. Some significant improvements were present in terms of kinematics, in particular, in the movement duration and the velocity of movement execution of both tasks; the index of curvature and the average jerk improved, respectively, during reaching and hand-to-mouth task, while the adjusting sway parameter decreased during the 2 movements. Significant improvements were found in upper limb joint excursion after the rehabilitative programme too. CONCLUSIONS: Our results suggest that the CIMT program can improve movement efficiency and upper limb function in children after TBI. The integration of the clinical outcomes and upper limb kinematics revealed to be crucial in detecting the effects of the CIMT programme.

Could an Immersive Virtual Reality Training Improve Navigation Skills in Children with Cerebral Palsy? A Pilot Controlled Study.

Children with cerebral palsy (CP) suffer deficits in their motor, sensory, and cognitive abilities, as well as in their visuospatial competences. In the last years, several authors have tried to correlate the visuospatial abilities with the navigational ones. Given their importance in everyday functions, navigation skills have been deeply studied using increasingly cutting-edge techniques such as virtual reality (VR). However, to our knowledge, there are no studies focused on training using immersive VR (IVR) in children with movement disorders. For this reason, we proposed an IVR training to 35 young participants with CP and conceived to improve their navigation skills in a "simil-real" environment while playing on a dynamic platform. A subgroup performed a part of the training which was specifically dedicated to the use of the allocentric strategy (i.e., looking for landmarks) to navigate the virtual environment. We then compared the children's navigation and spatial skills pre- and post-intervention. All the children improved their visual-spatial abilities; particularly, if the IVR activities specifically trained their ability to look for landmarks and use them to navigate. The results of this work highlight the potential of an IVR training program to increase the navigation abilities of patients with CPs.

Learning My Way: A Pilot Study of Navigation Skills in Cerebral Palsy in Immersive Virtual Reality.

Purpose: Human navigation skills are essential for everyday life and rely on several cognitive abilities, among which visual-spatial competences that are impaired in subjects with cerebral palsy (CP). In this work, we proposed navigation tasks in immersive virtual reality (IVR) to 15 children with CP and 13 typically developing (TD) peers in order to assess the individual navigation strategies and their modifiability in a situation resembling real life. Methods: We developed and adapted to IVR an application based on a 5-way maze in a playground that was to be navigated to find a reward. The learning process, navigation strategies, and adaptation to changes were compared between participants with CP and their TD peers and correlated with visual-spatial abilities and cognitive competences. Results: Most participants with CP needed more attempts than TD participants to become proficient in navigation. Furthermore, the learning phase was correlated to visual-spatial memory but not with cognitive competences. Interestingly, navigation skills were comparable between groups after stabilization. While TD participants mainly relied on allocentric strategies based on environmental cues, egocentric (self-centered) strategies based on body motion prevailed in participants with CP. Furthermore, participants with CP had more difficulties in modifying their navigation strategies, caused by difficulties in executive processes beyond the visual-perceptual impairment, with an inefficient shift between implicit and explicit competences. Conclusions: The navigation abilities in participants with CP seem to be different from their TD peers in terms of learning and adaptation to new conditions; this could deeply affect their everyday life and ultimately participation and inclusion. A regular assessing and focused rehabilitative plans could help to better navigate the environment and affect self-perception.

Gait pattern in Duchenne muscular dystrophy.

We investigated the gait pattern of 21 patients with Duchenne muscular dystrophy (DMD), compared to 10 healthy controls through 3D Gait Analysis. An overall observation of gait pattern in our DMD patients when compared to controls confirmed the data previously reported for small dystrophic groups. An excessive anterior tilt of pelvis and abnormal knee pattern in loading response phase were found. Since during the swing phase the DMD foot is too plantarflexed, patients adopt a higher flexion and abduction of the hip in order to advance the swinging limb. Velocity and cadence of DMD patients resulted similar to those calculated for healthy subjects, whereas stride length was reduced and step width was increased. We then divided the DMD patients in to two subgroups (treated with steroids and untreated), and we observed that the only statistically significant differences between the two groups in Gait Analysis parameters were found for the maximum of ankle power. 3D Gait Analysis gives objective and quantitative information about the gait pattern and the deviations due to muscular situation of DMD subjects; being our study a single moment evaluation, it is otherwise unable to unravel changes only detectable through serial analysis during the time course of the disease and, if any, due to the treatment.

A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia.

Mutations in the SPG7 gene encoding a mitochondrial protein termed paraplegin, are responsible for a recessive form of hereditary spastic paraparesis. Only few studies have so far been performed in large groups of hereditary spastic paraplegia (HSP) patients to determine the frequency of SPG7 mutations. Here, we report the result of a mutation screening conducted in a large cohort of 135 Italian HSP patients with the identification of six novel point mutations and one large intragenic deletion. Sequence analysis of the deletion breakpoint, together with secondary structure predictions of the deleted region, indicate that a complex rearrangement, likely caused by extensive secondary structure formation mediated by the short interspersed nuclear element (SINE) retrotransposons, is responsible for the deletion event. Biochemical studies performed on fibroblasts from three mutant patients revealed mild and heterogeneous mitochondrial dysfunctions that would exclude a specific association of a complex I defect with the pathology at the fibroblast level. Overall, our data confirm that SPG7 point mutations are rare causes of HSP, in both sporadic and familial forms, while underlying the puzzling and intriguing aspects of histological and biochemical consequences of paraplegin loss.

Immersive Virtual Reality to Improve Walking Abilities in Cerebral Palsy: A Pilot Study.

Immersive virtual reality (IVR) offers new possibilities to perform treatments in an ecological and interactive environment with multimodal online feedbacks. Sixteen school-aged children (mean age 11 ± 2.4 years) with Bilateral CP-diplegia, attending mainstream schools were recruited for a pilot study in a pre-post treatment experimental design. The intervention was focused on walking competences and endurance and performed by the Gait Real-time Analysis Interactive Lab (GRAIL), an innovative treadmill platform based on IVR. The participants underwent eighteen therapy sessions in 4 weeks. Functional evaluations, instrumental measures including GAIT analysis and parental questionnaire were utilized to assess the treatment effects. Walking pattern (stride length left and right side, respectively p = 0.001 and 0.003; walking speed p = 0.001), endurance (6MWT, p = 0.026), gross motor abilities (GMFM-88, p = 0.041) and most kinematic and kinetic parameters significantly improved after the intervention. The changes were mainly predicted by age and cognitive abilities. The effect could have been due to the possibility of IVR to foster integration of motor/perceptual competences beyond the training of the walking ability, giving a chance of improvement also to older and already treated children.

Are patients with hereditary spastic paraplegia different from patients with spastic diplegia during walking? Gait evaluation using 3D gait analysis.

Patients with hereditary spastic paraplegia (HSP) often resemble patients with mild spastic diplegia (SD), although their motor limitations differ. The aim of this study was to analyse quantitatively the gait of HSP and SD subjects in order to define the gait pattern in HSP and the differences between the two conditions. Fifteen subjects with HSP, 40 patients with SD and 20 healthy subjects underwent gait analysis (GA). The spatio-temporal and kinematic parameters at the proximal joints were found to be similar in HSP and SD, whereas the most significant differences were found at the knee and ankle joints. Both groups displayed a tendency for knee hyperextension in the midstance phase, but the duration of this hyperextension was longer in the HSP patients. This study shows that GA complements traditional clinical evaluations, making it possible to distinguish, clearly, between motor ability in HSP and in SD patients; the duration of the knee hyperextension during midstance was found to discriminate between the two gait patterns.

Effects of dose and duration of Robot-Assisted Gait Training on walking ability of children affected by cerebral palsy.

BACKGROUND: Robot-Assisted Gait Training (RAGT) is a widespread approach for locomotion rehabilitation but information about intervention frequency and duration is still lacking. OBJECTIVE: To evaluate the effect of frequency and duration of a RAGT on motor outcome of children affected by Cerebral Palsy (CP). METHODS: Forty-four CP children (age 4-17) underwent one among four different intensive trainings with equal dose of intervention, combining Task-Oriented Physiotherapy (TOP) and RAGT: 40 sessions (4 sessions/week) over 10 weeks of sole TOP (group1) or RAGT (group2) or RAGT and TOP (2 + 2 sessions/week; group3); 40 sessions in shorter period (4 weeks) of RAGT and TOP (5 + 5 sessions/week; group4). Each child was assessed before, after the training and after 3 months with: Ashworth, gross motor function measure (GMFM)-88, GMFM-66, six minutes walking test and gait analysis. RESULTS: No differences among the 4 protocols were highlighted although both groups with exclusive physiotherapy and RAGT obtained significant improvements in GMFM-88, GMFM-E and GMFM-66 while the mixed approaches did not show significant changes. CONCLUSION: Single-treatment approaches seem to be more effective than mixed approaches, independently from the duration (4 or 10 weeks). RAGT seems to have similar effect with respect to the traditional TOP, at least over 10 weeks.

Early onset, non fluctuating spinocerebellar ataxia and a novel missense mutation in CACNA1A gene.

Mutations in the brain-specific P/Q type Ca2+ channel alpha1 subunit gene, CACNA1A, have been identified in three clinically distinct disorders, spinocerebellar ataxia type 6 (SCA6), episodic ataxia type 2 (EA2), and familial hemiplegic migraine type 1 (FHM1). SCA6 is associated with small expansions of a CAG repeat at the 3' end of the gene, while point mutations are mostly responsible for its two allelic disorders, FHMI and EA2. From the electrophysiological point of view, while FHMI mutations lead to a gain of function [Tottene A, Fellin T, Pagnutti S, Luvisetto S, Striessnig J, Fletcher C, et al. Familial hemiplegic migraine mutations increase Ca2+ influx through single human CaV2.1 channels and decrease maximal CaV2.1 current density in neurons. Proc Natl Acad Sci 99 (20) (2002) 13284-13289.], EA2 mutations usually generate a loss of channel function [Guida S, Trettel F, Pagnutti S, Mantuano E, Tottene A, Veneziano L, et al. Complete loss of P/Q calcium channel activity caused by a CACNA1A missense mutation carried by patients with episodic ataxia type 2. Am J Hum Genet 68 (3) (2001) 759-764, Wappl E, Koschak A, Poteser M, Sinnegger MJ, Walter D, Eberhart A, et al. Functional consequences of P/Q-type Ca2+ channel Cav2.1 missense mutations associated with episodic ataxia type 2 and progressive ataxia. J Biol Chem 277 (9) (2002) 6960-6966.]. In the present study, we describe a child affected by permanent non-fluctuating limb and trunk ataxia with a quite early age of onset. Interestingly, the size of the CACNA1A triplet repeat region in the patient is within the normal range while he carries a novel de novo missense mutation in this gene, p.R1664Q. Although functional data are not available, based on the literature data indicating that severe reductions in P/Q-type channel activity favour episodic and/or progressive ataxic symptoms [Wappl E, Koschak A, Poteser M, Sinnegger MJ, Walter D, Eberhart A, et al. Functional consequences of P/Q-type Ca2+ channel Cav2.1 missense mutations associated with episodic ataxia type 2 and progressive ataxia. J Biol Chem 2002;277(9):6960-6966.], we hypothesize that the functional consequence of the mutation here identified is a partial loss of the Ca channel function. In conclusion, the clinical and molecular findings reported here suggest the opportunity to screen for point mutation in this gene, even patients with a clinical phenotype for some aspects slightly different from the typical picture more commonly associated to SCA6, EA2 or FHM1 diseases.

Kinematic analysis of upper limb during walking in diplegic children with Cerebral Palsy.

Movements of the lower limbs during walking have been widely investigated in literature, while quantification of arm movement during gait is scanty. The aim of the present study was to assess quantitatively the upper limb motion during gait in children with Cerebral Palsy (CP). Sixteen children with diplegic CP were evaluated using a full-body marker set, which allows assessing both the lower and upper limb kinematics. Our results demonstrated that movement of the arms was characterized by an abducted shoulder and a more flexed elbow position at the initial contact of the gait cycle with a quite physiological range of motion if compared to controls. These data showed that gait of children with diplegic CP is generally characterized by abnormal upper limb position which could be considered a strategy to keep balance and posture control during walking.

Dyskinesia caused by ziconotide-baclofen combination in an adolescent affected by cerebral palsy.

OBJECTIVE: To report on the first case of ziconotide-induced dyskinesia. Ziconotide, a synthetic peptide analogue of the ω-conotoxin MVIIA that blocks selectively N-type voltage-sensitive calcium channels, has been used in intrathecal administration for 30 years. Ziconotide is a drug of choice for chronic pain because of its efficacy and flexibility because it can substitute or complement other intrathecal therapies including morphine or baclofen. Whereas substantial information is available regarding its efficacy, systematic data regarding the safety of ziconotide remain scant. The adverse reactions to ziconotide described so far regard only the coordination and execution of intentional movements. CASE REPORT: A 15-year-old male patient developed dyskinesia affecting the head and upper limbs 2 days after administration of ziconotide as an add-on therapy to an established regimen of treatment with baclofen. The strict temporal relationship between ziconotide administration and dyskinesia, together with the absence of any other clinical alteration, led to the hypothesis of a possible adverse drug reaction. Ziconotide was thus withdrawn, and the symptoms disappeared within 2 days. CONCLUSIONS: An analysis of the signaling pathways of baclofen and ziconotide revealed a possible drug interaction that allowed ziconotide to trigger dyskinesia.

Sequence memory skills in Spastic Bilateral Cerebral Palsy are age independent as in normally developing children.

PURPOSE: To study the development of sequence memory skills in a group of participants with Spastic Bilateral Cerebral Palsy (CP) and their matched controls (TD). Sequence memory skills are defined as a blend of implicit and explicit competences that are crucial for the acquisition and consolidation of most adaptive skills along the lifespan. METHOD: A computerized sequence learning task was administered to 51 participants with CP (age range: 4.1-14.7) and their controls. General performance, accuracy and learning strategy were analyzed, as well as cognitive competencies (IQ and explicit visual spatial memory). RESULTS: Explicit learning developed along with age in all participants. Sequence learning skills were age independent and unevenly distributed among CP participants: most TD (96.1%) and only about half (58.8%) of CP participants succeeded in sequence learning, in dynamic relation with cognitive and manipulation abilities. CONCLUSION: Sequence memory skills should be verified to plan therapeutic strategies. Therapeutic plans based on implicit learning (more resistant to disruption and stress) could be effective and highly advantageous for most but not for all CP children. Independently from age, many CP children could fix sequences more efficiently by explicit strategies, a more effortful but probably more effective way.

Unimanual and bimanual intensive training in children with hemiplegic cerebral palsy and persistence in time of hand function improvement: 6-month follow-up results of a multisite clinical trial.

This study aims to compare in hemiplegic children the effectiveness of intensive training (unimanual and bimanual) versus standard treatment in improving hand function, assessing the persistence after 6 months. A multicenter, prospective, cluster-randomized controlled clinical trial was designed comparing 2 groups of children with hemiplegic cerebral palsy, treated for 10 weeks (3 h/d 7 d/wk; first with unimanual constraint-induced movement therapy, second with intensive bimanual training) with a standard treatment group. Children were assessed before and after treatment and at 3 and 6 months postintervention using Quality of Upper Extremity Skills Test (QUEST) and Besta Scales. One hundred five children were recruited (39 constraint-induced movement therapy, 33 intensive bimanual training, 33 standard treatment). Constraint-induced movement therapy and intensive bimanual training groups had significantly improved hand function, showing constant increase in time. Grasp improved immediately and significantly with constraint-induced movement therapy, and with bimanual training grasp improved gradually, reaching the same result. In both, spontaneous hand use increased in long-term assessment.

Specific profiles of neurocognitive and reading functions in a sample of 42 Italian boys with Duchenne Muscular Dystrophy.

A group of 42 Italian boys with Duchenne Muscular Dystrophy was compared with a control group of 10 boys with Spinal Muscular Atrophy and Osteogenesis Imperfecta on tests assessing general intellectual ability, language, neuropsychological functions, and reading skills with the aim of describing a comprehensive profile of the various functions and investigating their interrelationships. The influence of general intellectual level on performance was analyzed. Further, correlations between various neuropsychological measures and language performances were computed for the group with Duchenne Muscular Dystrophy, as well as the correlations between reading scores and other cognitive and linguistic measures. A general lowering in VIQ, PIQ, and FSIQ scores was found to characterize the group with Duchenne Muscular Dystrophy. Expressive language skills were within the normal range, while syntactic and grammatical comprehension were significantly impaired. The presence of below-average reading performances was further confirmed. However, unlike previous studies on irregular orthographies, the present results show that (a) the mild reading difficulties found in the sample essentially concern speed rather than accuracy; (b) they concern word rather than nonword reading; (c) lower reading performances are related to lower scores in general IQ; (d) no correlations emerge with phonological abilities, verbal short-term memory, or working memory, but rather with long-term memory and lexical skills. This may suggest that language-specific effects modulate the cognitive expressions of Duchenne Muscular Dystrophy and raises the possibility that the dysfunctions underlying the reading difficulties observed in affected readers of regular orthographies involve different neurocognitive systems than the cortico-cerebellar circuits usually invoked.

Rib cage deformities alter respiratory muscle action and chest wall function in patients with severe osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is an inherited connective tissue disorder characterized by bone fragility, multiple fractures and significant chest wall deformities. Cardiopulmonary insufficiency is the leading cause of death in these patients. METHODS: Seven patients with severe OI type III, 15 with moderate OI type IV and 26 healthy subjects were studied. In addition to standard spirometry, rib cage geometry, breathing pattern and regional chest wall volume changes at rest in seated and supine position were assessed by opto-electronic plethysmography to investigate if structural modifications of the rib cage in OI have consequences on ventilatory pattern. One-way or two-way analysis of variance was performed to compare the results between the three groups and the two postures. RESULTS: Both OI type III and IV patients showed reduced FVC and FEV(1) compared to predicted values, on condition that updated reference equations are considered. In both positions, ventilation was lower in OI patients than control because of lower tidal volume (p<0.01). In contrast to OI type IV patients, whose chest wall geometry and function was normal, OI type III patients were characterized by reduced (p<0.01) angle at the sternum (pectus carinatum), paradoxical inspiratory inward motion of the pulmonary rib cage, significant thoraco-abdominal asynchronies and rib cage distortions in supine position (p<0.001). CONCLUSIONS: In conclusion, the restrictive respiratory pattern of Osteogenesis Imperfecta is closely related to the severity of the disease and to the sternal deformities. Pectus carinatum characterizes OI type III patients and alters respiratory muscles coordination, leading to chest wall and rib cage distortions and an inefficient ventilator pattern. OI type IV is characterized by lower alterations in the respiratory function. These findings suggest that functional assessment and treatment of OI should be differentiated in these two forms of the disease.

Sequence learning in cerebral palsy.

We investigated sequence-learning skills in 64 children with cerebral palsy (aged 4.01-14.7 years; 49 with bilateral, two with dystonic, and 13 with unilateral cerebral palsy), compared with a matched control group of typically developing children. Participants' motor and handling abilities were classified according to the Gross Motor Function Classification System and the Manual Ability Classification System. General cognitive, visuoperceptual, and constructive abilities were assessed. Participants performed an experimental computerized version of Corsi Span, followed by a normalized Supraspan sequence. Controls outperformed cerebral palsy participants in visual memory and accuracy. Participants with cerebral palsy were likelier to fail the test (cerebral palsy, 37.5%; control subjects, 5%) and obtain overall lower scores. Sequence learning skills were not related to motor and handling impairments. Failure to learn sequences resulted in an overall lower functioning profile regarding visuoperceptual, verbal, and performance abilities. The ability to fix sequences seemed to split the cerebral palsy group into an overall high-functioning group (successful in sequence learning) and low-functioning (failing) group. Results are discussed in light of a specific implicit memory impairment and the abnormal development of white matter frontostriatal and parietal connections.

3D gait analysis in patients with hereditary spastic paraparesis and spastic diplegia: a kinematic, kinetic and EMG comparison.

The predominant clinical feature of patients with Hereditary Spastic Paraparesis (HSP) is gait disturbance owing to spasticity and weakness of the lower limbs; the spasticity in early-onset disease (infancy or childhood) often cannot be distinguished from mild form of spastic diplegia (SD). The aim of this study was to quantify the gait strategy in HSP and SD children, focusing on the differences between groups as concerns functional limitation during gait. 9 HSP and 16 SD children were evaluated using Gait Analysis; kinematic and kinetic parameters and EMG pattern during walking were identified and calculated to compare the two gait strategies. The results revealed that these two pathologies are characterised by different gait strategies. In particular we found that knee joint, in terms of kinematics and kinetics, and rectus femoris pattern represent discriminatory aspects in order to compare and differentiate gait patterns of HSP and SD children. The findings strongly support the issue that HSP and SD patients need individualised therapeutical program, either neurosurgical or pharmacological treatment, based on the quantification of gait deficiencies and in order to address the peculiarity of their motor limitations and to prevent the onset of compensatory strategies.

The effects of femoral derotation osteotomy in cerebral palsy: a kinematic and kinetic study.

We attempted to quantify the effects of isolated femoral derotation osteotomies using clinical evaluation and gait analysis (kinematics and kinetics) in patients with cerebral palsy (CP). Twelve children with CP were evaluated before and 10 months after isolated femoral derotation osteotomy, and 15 healthy children were evaluated as controls. There were significant improvements on clinical examination. A better position of the hip and ankle in the transverse plane was evident and significant changes occurred in terms of hip and ankle kinetics after surgery. Improvements in kinematics and hip and ankle power are very important biomechanically. The correction of lever arm dysfunction and more physiological hip and ankle power generation result in an improvement in terms of energy consumption, leading to a more functional and economic gait pattern.