Family-centred care for children and young people with cerebral palsy: results from an Italian multicenter observational study.

Background: Family­centred care (FCC) is recognized as the model of best practice for the provision of services for children who have physical disabilities and their families. Objective: To assess the overall perception of FCC provided in an Italian network of 17 rehabilitation services, as perceived by parents of children with cerebral palsy and professionals, and to explore whether children, families, service providers and service­related characteristics influence parent satisfaction regarding service provision in an FCC practice. Methods: The Measure of Processes of Care (MPOC­20) for parents/caregivers and the Measure of Processes of Care for Service Providers (MPOC­SP) for healthcare providers were used. For the purposes of the study, an ad hoc information form was developed to collect information concerning children, families, service providers and services. Results: A total of 382 parents/caregivers and 269 healthcare providers completed the MPOC questionnaires. Parents and service providers both identified the domains for enabling partnerships and interpersonal sensitivity as a strength, while the domain relating to general information was always scored the lowest. An advanced maternal age, being a single parent, being unemployed and having lower socio­economic status were factors identified as individually predictive of lower FCC scores on the MPOC­20. Higher intensity treatment, inpatient services, primary healthcare settings and settings identified with limited financial resources and reduced space/time for each family were other variables significantly associated with less favourable MPOC­20 ratings. Conclusions: The perception of FCC provided was fairly positive, with some areas of improvement, such as the domain of provision of information. Professionals should, therefore, provide better communication and take more time in giving information and attention to parents. Potential sources of variation in parent perceptions of FCC based on family characteristics and the organization of services highlight the importance the need to support services through the provision of greater financial and human resources.

CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis.

BACKGROUND: The international Inherited Neuropathy Consortium (INC) was created with the goal of obtaining much needed natural history data for patients with Charcot-Marie-Tooth (CMT) disease. We analysed clinical and genetic data from patients in the INC to determine the distribution of CMT subtypes and the clinical impairment associated with them. METHODS: We analysed data from 1652 patients evaluated at 13 INC centres. The distribution of CMT subtypes and pathogenic genetic mutations were determined. The disease burden of all the mutations was assessed by the CMT Neuropathy Score (CMTNS) and CMT Examination Score (CMTES). RESULTS: 997 of the 1652 patients (60.4%) received a genetic diagnosis. The most common CMT subtypes were CMT1A/PMP22 duplication, CMT1X/GJB1 mutation, CMT2A/MFN2 mutation, CMT1B/MPZ mutation, and hereditary neuropathy with liability to pressure palsy/PMP22 deletion. These five subtypes of CMT accounted for 89.2% of all genetically confirmed mutations. Mean CMTNS for some but not all subtypes were similar to those previously reported. CONCLUSIONS: Our findings confirm that large numbers of patients with a representative variety of CMT subtypes have been enrolled and that the frequency of achieving a molecular diagnosis and distribution of the CMT subtypes reflects those previously reported. Measures of severity are similar, though not identical, to results from smaller series. This study confirms that it is possible to assess patients in a uniform way between international centres, which is critical for the planned natural history study and future clinical trials. These data will provide a representative baseline for longitudinal studies of CMT. CLINICAL TRIAL REGISTRATION: ID number NCT01193075.

A new scale for the assessment of performance and capacity of hand function in children with hemiplegic cerebral palsy: reliability and validity studies.

BACKGROUND: In hemiplegic children, the recognition of the activity limitation pattern and the possibility of grading its severity are relevant for clinicians while planning interventions, monitoring results, predicting outcomes. OBJECTIVE: Aim of the study is to examine the reliability and validity of Besta Scale, an instrument used to measure in hemiplegic children from 18 months to 12 years of age both grasp on request (capacity) and spontaneous use of upper limb (performance) in bimanual play activities and in ADL. DESIGN: Psychometric analysis of reliability and of validity of the Besta scale was performed. SETTING: Outpatient study sample METHODS: Reliability study: A sample of 39 patients was enrolled. The administration of Besta scale was video-recorded in a standardized manner. All videos were scored by 20 independent raters on subsequent viewing. 3 raters randomly selected from the 20-raters group rescored the same video two years later for intra-rater reliability. Intra and inter-rater reliability were calculated using Intraclass Correlation Coefficient (ICC) and Kendall's coefficient (K), respectively. Internal consistency reliability was assessed using Alpha's Chronbach coefficient. Validity study: a sample of 105 children was assessed 5 times (at t0 and 2, 3, 6 and 12 months later) by 20 independent raters. Each patient underwent at the same time to QUEST and Besta scale administration and assessment. Criterion validity was calculated using rho-Pearson coefficient. RESULTS: Reliability study: The inter-rater reliability calculated with Kendall's coefficient resulted moderate K=0.47. The intra-rater (or test-retest) reliability for 3 raters was excellent (ICC=0.927). The Cronbach's alpha for internal consistency was 0.972. Validity study: Besta scale showed a good criterion validity compared to QUEST increasing by age and severity of impairment. Rho Pearson's correlation coefficient r was 0.81 (P<0.0001). Limitations. Besta scales in infants finds hard to distinguish between mild to moderately impaired hand function. CONCLUSIONS: Besta scale scoring system is a valid and reliable tool, utilizable in a clinical setting to monitor evolution of unimanual and bimanual manipulation and to distinguish hand's capacity from performance.

Gait pattern classification in children with Charcot-Marie-Tooth disease type 1A.

Gait pattern classification may assist in clinical decision making and cluster analysis (CA) has been often adopted to this aim. The goal of this study was to identify, through CA, typical walking patterns in a group of 21 young subjects with CMT1A, a hereditary progressive neuropathy, and to study possible correlation with the disease's clinical status. The protocol included kinematic/kinetic analysis of natural walking and more demanding locomotor tasks, i.e. toe- and heel-walking. Hierarchical cluster analysis was carried out on parameters related to primary signs (foot-drop and push-off deficit) and, separately, to compensatory mechanisms at proximal (pelvis, hip and knee) or distal (ankle) level. CA on primary signs during natural walking identified three clusters: (1) pseudo-normal patients (PN), not significantly different from controls; (2) patients showing only foot-drop (FD); (3) patients with foot-drop and push-off deficit (FD&POD). Patients belonging to the PN subgroup showed distal abnormalities during heel-walking. The FD&POD subgroup was associated to a significantly worse clinical score (CMTES, p<0.05). The main compensatory strategies, which occurred independently from primary clusterization, included augmented hip/knee flexion in swing (steppage) and early ankle plantarflexion at mid stance (vaulting). We concluded that, although a number of young CMT1A patients do not show typical primary deviations during natural walking, they do show significant abnormalities in more demanding locomotor tasks that should be therefore considered. It is also hypothesized that progression of this degenerative condition may be associated to the migration of patients to more severe clusters, with possible appearance of compensatory strategies.

Quantification of nitrite and nitrate in seawater by triethyloxonium tetrafluoroborate derivatization-headspace SPME GC-MS.

Triethyloxonium tetrafluoroborate derivatization combined with direct headspace (HS) or SPME-gas chromatography-mass spectrometry (GC-MS) is proposed here for the simultaneous determination of nitrite and nitrate in seawater at micromolar level after conversion to their corresponding volatile ethyl-esters (EtO-NO and EtO-NO(2)). Isotopically enriched nitrite [(15)N] and nitrate [(15)N] are employed as internal standards and for quantification purposes. HS-GC-MS provided instrumental detection limits of 0.07 µM NO(2)(-) and 2 µM NO(3)(-). Validation of the methodology was achieved by determination of nitrite and nitrate in MOOS-1 (Seawater Certified Reference Material for Nutrients, NRC Canada), yielding results in excellent agreement with certified values. All critical aspects connected with the potential inter-conversion between nitrite and nitrate (less than 10%) were evaluated and corrected for by the use of the isotopically enriched internal standard.

Reliability of instrumented movement analysis as outcome measure in Charcot-Marie-Tooth disease: results from a multitask locomotor protocol.

Some neurodegenerative diseases at early stage may not drastically affect basic gait ability, whereas more demanding locomotor tasks are more prone to disease-induced abnormalities. In this study, we evaluated the interday test-retest reliability, 4-6 weeks apart, of instrumented movement analysis on a group of 20 subjects with Charcot-Marie-Tooth (CMT) disease considering a set of kinematic and kinetic curves and related parameters obtained during natural walking (NW) and faster walking, heel and toe-walking, step ascending and descending. Results showed that the reliability was good for NW, with the exception of trunk curves, pelvic tilt and EMG profiles (moderate reliability), and trunk ROM in sagittal/transverse plane (poor reliability). Comparing our results with literature, CMT patients did not present a greater variability during NW than healthy subjects or patients with diseases of CNS. Additional locomotor tasks showed a slight reduction of reliability, although the moderate-to-good level shown in NW was almost never reduced to poor. Most of SEM values (absolute measurement errors) were smaller than 5°, a clinically acceptable threshold. In particular THS, an ankle joint related parameter computed across heel and toe-walking tasks, showed an optimal reliability (ICC=0.95, SEM=2.7°) and correlation with CMT clinical scores. Toe and heel-walking and step ascending tasks maximised the number of parameters with a moderate-to-good correlation with patients' clinical status. We concluded that, in addition to natural walking, more challenging locomotor tasks are good candidates to provide reliable and sensitive outcome measures for CMT patients.

Evolution of upper limb function in children with congenital hemiplegia.

Hand function deficits in hemiplegic children are a major cause of disability, but there is a lack of appropriate instruments for evaluating the evolution of this deficit over time and for verifying the efficacy of its treatment. We evaluated changes in upper limb function in relation to age and the course of individual rehabilitation treatment in 20 children (13 males and 7 females) who were first seen within the first four years of life and subsequently followed until a mean age of 13 years and four months (range, 11-17 years) in accordance with a diagnostic/rehabilitation program initiated in our division in 1989. All of the children were treated by us; those whose paretic upper limb functioned well were not treated in any specific or directed manner. The protocol involved a qualitative evaluation of the spontaneous use of the paretic hand and a quantitative evaluation of grip. Analysis of the results revealed an age-related global improvement over time, occurring within the first five years of life and more pronounced in terms of grip than spontaneous use. This finding makes our protocol more specific than those currently used because it more reliably establishes the real capacity to use the paretic hand in different situations of everyday life. The most important changes concerned the children with more impaired functional capacity, whereas the children who presented with good functional skill retained this capacity over time, thus confirming the initial decision not to treat them.

Developmental sequence of postural control in prone position in children with spastic diplegia.

The aim of this study was to assess the development of postural control in the prone position in children with spastic diplegia and triplegia, and determine the influence of clinical characteristics, visual acuity and cognitive performance on that development. We also analysed the relation between these early motor achievements in the prone position and the subsequent acquisition of motor competence in the sitting position. We followed 24 diplegic and triplegic children from before age 2 years (mean age 12 months) to mean age 41 months, videorecording motor behaviour every six months and abstracting acquisitions in alignment and balance using a standardised procedure. We confirm a developmental sequence of all the acquired movements in the prone position. 83.3% of the children completed the uprighting sequence in the sagittal plane, acquired good balance, and ability to rotate the head and trunk. 70.8% of the children (all but one of the diplegic children and none among triplegic children) acquired symmetric posture in the frontal plane and 83.3% reduced leg hyperextension. Development was not uniform, and at 12-18 months two groups began to emerge: diplegic children who rapidly achieved all or most of the steps in the sequence and had a favourable prognosis for subsequent motor development; and triplegic children who achieved these steps at a much slower rate or in some cases not at all and had a less favourable prognosis for future development. Diplegic children with normal visual acuity, and general quotient GQ>70 did better than triplegic children with compromised visual acuity and GQ<70. Acquisition of the full uprighting sequence in the prone position before the age of two related to the later acquisition of autonomous sitting.

Predictors of independent walking in children with spastic diplegia.

A prospective study was carried out to identify predictors of independent walking in 31 children with either spastic diplegia or triplegia, observed from the age of 9 to 18 months (mean, 11 months) and followed for a mean period of 30 months (range, 24 to 36 months). Mean age at most recent examination was 41 months (range, 36 to 54 months). We used an 18-item scheme to chart the acquisition, from the prone position, of prelocomotor, sitting, and locomotor skills. Examinations were conducted every 6 months and videotaped according to a standardized procedure. At latest assessment 18 (58%) of the 31 children had achieved walking, 7 (23%) independently and 11 (35%) with assistance; 13 (42%) did not achieve walking. Ambulatory status was related to developmental quotient and visual acuity: all the children who became independent walkers had normal visual acuity and in 86% of cases a normal general development quotient. Moreover, we found a significant correlation between the number of gross motor skills achieved and the rate of achievement before 2 years of age and ambulatory status at 3 to 5 years of age. Ability to put weight on the hands while prone and to roll from supine to prone position by 18 months of age were significantly related to independent walking, while ability to sit without support was predictive only at around 24 months of age.

Sex steroid binding protein receptor (SBP-R) is related to a reduced proliferation rate in human breast cancer.

In the last years, an increasing amount of studies described a membrane receptor for the Sex Steroid Binding Protein (SBP) on several androgen-estrogen dependent tissues. One of the suggested biological roles of the interaction between SBP and its receptor seems to be a negative control of the E2 induced proliferation of human breast cancer cells through the cAMP pathway. In the present work, SBP membrane receptor was evaluated on human breast cancer specimens with a radio-binding assay. Each tissue sample was also evaluated for ER and PGR status. Cytosol Thymidine Kinase levels were measured in tissue samples in order to evaluate cell proliferation rate. SBP binding to membranes of ER +/PGR + samples was time and temperature dependent, specific and at high affinity. In addition, SBP recognized on breast cancer membranes two sites at different affinity, as previously described for other human tissues and cultured cells. Membrane SBP-R was detected in a significantly higher number of samples positive for both ER and PGR than in negative samples. SBP-R positive samples showed a significantly lower proliferation rate than SBP-R negative samples as demonstrated by TK activity. The present study contains evidences for the existence of a specific membrane receptor for SBP in breast cancer sample membranes and the presence of SBP-R seems to be strictly related to a lower proliferation rate of the sample.

Ring chromosome 9: an atypical case.

A new case of ring chromosome 9 in a 36-month-old child is presented. In addition to the pathognomonic features of this rare disorder (only 21 cases reported), our patient presents some peculiarities, such as corpus callosum hypoplasia and epileptic seizures (infantile periodic spasms). We also observed a reduced level of leukocyte interferon alpha whose synthesis is controlled by a gene on chromosome 9 and which could be responsible for the recurrent respiratory tract infections, typical and sometimes fatal in these patients.

Mild phenotype associated with inv dup 8 (q21.2-q22.3) of maternal origin.

We report on a girl with a de novo inverted duplication of chromosome 8 (q21.2-q22.3) associated with a mild phenotype. We were able to establish the maternal origin of the rearranged chromosome. We discuss the correlation between genotype and phenotype on the basis of a review of the findings from individuals with partial dup(8q).

Biological relevance of the interaction between sex steroid binding protein and its specific receptor of MCF-7 cells: effect on the estradiol-induced cell proliferation.

The human breast cancer cells MCF-7 were shown to bind sex steroid binding protein (SBP) at a receptor site. The binding to whole cells was specific, time-dependent, saturable, and at high affinity. Estradiol, bound to SBP, induced a significant inhibition of SBP-cell binding at a dose of 10(-9) M. The presence of SBP, bound either to estradiol, or to cells, did not alter the amount of estradiol entering cells, but it "captured" an additional quantity of the hormone at the outer surface of cells. Furthermore, the effect of SBP on estradiol-induced MCF-7 cell proliferation was evaluated. While estradiol is an effective proliferating agent on MCF-7 cells, SBP itself did not produce any significant cell proliferation; the growth of MCF-7 cells in the presence of the complex SBP-estradiol was not different from the growth in the presence of estradiol alone; SBP bound to its receptor produced a significant reduction of the estradiol-induced cell proliferation. In summary, the present study provides evidence that the interaction of SBP with its receptor on MCF-7 cells is not involved in the uptake of estradiol, but it can modify the effect of estradiol at target site by a mechanism which is not likely to be a simple sequestration of the hormone at the outer surface of cells.