Functional resources to increase gait speed in people with stroke: strategies adopted compared to healthy controls.

Thirty-nine adult individuals with stroke in the stable phase were asked to walk at their preferred speed and then as fast as possible. A set of gait indexes were computed, including spatial temporal parameters, ankle and hip mechanical work, and timing of ankle push-off onset, for comparison with normal velocity-dependent profiles. Algorithms were used to classify the resulting gait patterns when the patients walked at their preferred speed and fast and to identify the patients' strategies to maximise speed. Patients' strategies were characterised by a variation in the parameters, which were reduced, equal or increased, in relation to normal patterns. At both speeds, stroke individuals tended to walk at higher cadence and with shorter stride length. At the preferred speed the investigated parameters for all patients were mostly within the normal profile (71.8-94.9%). The exception was the finding of positive work at the ankle where 64% of the stroke individuals showed reduced work production. At fast speed (increments to 36%BH/s) fewer patients presented values within the normal profile for all the parameters (17.9-74.4%), with the exception of negative work at the ankle and hip. The parameter variations showed a more consistently abnormal picture. The results indicate that, in order to increase gait speed, patients with hemiparesis have different functional resources on which to draw, and these vary from individual to individual. Thus, gait analysis at different gait speed should be adopted to develop individualised programs that will improve quality of life for the patients.

Disruption of friend of GATA 2 gene (FOG-2) by a de novo t(8;10) chromosomal translocation is associated with heart defects and gonadal dysgenesis.

FOG-2 (Friend of GATA 2) is a transcriptional cofactor able to differentially regulate the expression of GATA-target genes in different promoter contexts. Mouse models evidenced that FOG-2 plays a role in congenital heart disease and normal testis development. In human, while FOG-2 mutations have been identified in sporadic cases of tetralogy of Fallot, no mutations are described to be associated with impaired gonadal function. We here describe a young boy with a balanced t(8;10)(q23.1;q21.1) translocation who was born with congenital secundum-type atrial septal defect and gonadal dysgenesis. Fluorescence in situ hybridization mapped the chromosome 8 translocation breakpoint (bkp) to within the IVS4 of the FOG-2 gene, whereas the chromosome 10 bkp was found to lie in a desert gene region. Quantitative analysis of FOG-2 expression revealed the presence of a truncated transcript but there was no detectable change in the expression of the genes flanking the 10q bkp, thus making it possible to assign the observed clinical phenotype to altered FOG-2 expression. Genetic and clinical analyses provide insights into the signaling pathways by which FOG-2 affects not only cardiac development but also gonadal function and its preservation.

Molecular and genomic characterisation of cryptic chromosomal alterations leading to paternal duplication of the 11p15.5 Beckwith-Wiedemann region.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder with increased risk of paediatric tumours. The aetiology involves epigenetic and genetic alterations affecting the 11p15 region, methylation of the differentially methylated DMR2 region being the most common defect, while less frequent aetiologies include mosaic paternal 11p uniparental disomy (11patUPD), maternally inherited mutations of the CDKN1C gene, and hypermethylation of DMR1. A few patients have cytogenetic abnormalities involving 11p15.5. METHODS: Screening of 70 trios of BWS probands for 11p mosaic paternal UPD and for cryptic cytogenetic rearrangements using microsatellite segregation analysis identified a profile compatible with paternal 11p15 duplication in two patients. RESULTS: Fluorescence in situ hybridisation analysis revealed in one case the unbalanced translocation der(21)t(11;21)(p15.4;q22.3) originated from missegregation of a cryptic paternal balanced translocation. The second patient, trisomic for D11S1318, carried a small de novo dup(11)(p15.5p15.5), resulting from unequal recombination at paternal meiosis I. The duplicated region involves only IC1 and spares IC2/LIT1, as shown by fluorescent in situ hybridisation (FISH) mapping of the proximal duplication breakpoint within the amino-terminal part of KvLQT1. CONCLUSIONS: An additional patient with Wolf-Hirschorn syndrome was shown by FISH studies to carry a der(4)t(4;11)(p16.3;p15.4), contributed by a balanced translocation father. Interestingly, refined breakpoint mapping on 11p and the critical regions on the partner 21q and 4p chromosomal regions suggested that both translocations affecting 11p15.4 are mediated by segmental duplications. These findings of chromosomal rearrangements affecting 11p15.5-15.4 provide a tool to further dissect the genomics of the BWS region and the pathogenesis of this imprinting disorder.

Trans-femoral amputee gait: socket-pelvis constraints and compensation strategies.

The paper deals with the identification of motor strategies adopted by trans-femoral amputees to compensate for the constraints of hip motion induced by the interference of the socket with the pelvis and, particularly, with the ischial tuberosity. A group of 11 subjects with trans-femoral amputation, three of whom wore two different prostheses, giving a sample size of 14 cases, were studied by gait-analysis protocols: the present paper focuses on the pelvis-thigh kinematics at foot strike. The results showed that, at the prosthetic side, the hip is significantly less flexed and less extended, respectively, at the ipsilateral and contralateral foot strike. Moreover, the pelvis is significantly more anterior tilted at sound foot strike. The anterior step length showed a decreased sound limb anterior step in 12 out of 14 cases. The authors interpret these results as a combination of mechanical constraints and compensatory actions: the reduced prosthetic hip extension is determined by the mechanical constraint involved in the pelvis-socket interference; and the increased pelvis tilt and sound hip flexion occurring at the same time are compensating strategies, adopted by the amputees, in order to obtain a functional step length and symmetrical thigh inclinations. Those factors determine a gait pattern which is functional, only slightly slower than normal gait, and without any perceivable alterations. On the other hand, the authors show that the increased pelvis tilting necessarily overloads the lumbar tract of the spine and may be related to the frequent occurrence of low-back pain in amputee subjects, despite the positive functional gait recovery.

Effects of bilateral subthalamic stimulation on gait kinematics and kinetics in Parkinson's disease.

Subthalamic nucleus (STN) stimulation, a recent surgical approach to Parkinson's disease (PD), has been shown to be effective in relieving motor symptoms. The present study carried out a full body gait analysis, during overground walking, on ten PD patients with bilaterally implanted STN stimulation devices. Walking performance was analyzed on the same day, in four conditions (Stim Off-Med Off, Stim On-Med Off, Stim Off-Med On, Stim On-Med On). The results showed that, on average, STN stimulation alone (S+M-) and L-dopa alone (S-M+), significantly increased gait speed, stride length and the lower limb joint Range of Motion (ROM) with respect to the basal condition (S-M-); also cadence was found to play a role in velocity increase, particularly when L-dopa was administered. Both treatments improved pelvis and trunk kinematics, and power production at the ankle and hip joints. The combination of the two treatments (S+M+) produced an additional effect on gait speed, stride length, ROM of knee and ankle joints, pelvis obliquity and trunk inclination. Given the additive and synergistic effects, it can be hypothesized that the two treatments have different mechanisms of action. Our results confirm the findings of earlier studies that employed treadmill walking.

Effects of subthalamic nucleus stimulation and L-dopa in trunk kinematics of patients with Parkinson's disease.

In the advanced phase of Parkinson's disease (PD), high frequency electrical stimulation (HFS) of the subthalamic nucleus (STN) can represent a good therapeutic option, whose effects on walking have been recently quantified by kinematic and dynamic gait analysis. The goal of the present study was to compare, in a group of PD patients, the effects of STN stimulation and of L-dopa on trunk kinematics during walking. The additive effect of these two treatments was investigated as well. Ten idiopathic PD patients implanted bilaterally with a STN stimulation system and ten age-matched controls were studied using a three dimensional motion analyser. Four conditions were considered: with (s+) and without (s-) STN stimulation and with (m+) and without (m-) L-dopa administration. The results showed that both stimulation alone and L-dopa alone significantly increased the stride length and the gait speed, with an additional effect if applied simultaneously. Cadence was more influenced by L-dopa. The range of lateral bending and torsion of the trunk, which were reduced in s-/m-, increased similarly in s-/m+ and in s+/m- conditions. The exaggerated forward inclination of the trunk reduced towards control values in all therapeutic conditions. There was a tendency for L-dopa to increase trunk movements in the frontal plane, similar to events seen in quiet stance. Due to the presence of additive and synergistic effects, we concluded that the mechanisms of action of the two treatments are likely to be different.

Quantitative analysis of gait in Parkinson's disease: a pilot study on the effects of bilateral sub-thalamic stimulation.

Four patients with Parkinson's disease who had a Subthalamic Nucleus (STN) stimulator implanted and four age-matched controls underwent gait analysis using a three-dimensional system. STN stimulation substantially improved most of the key variables in the patients, without producing inefficient compensatory movements of the trunk. A reduction of ankle power production during push off was the most persistent abnormality seen when the patients were stimulated. We also found a reduction of trunk lateral bending and torsion when the patients were not stimulated when compared with controls.

High-frequency electrical stimulation of the subthalamic nucleus in Parkinson's disease: kinetic and kinematic gait analysis.

In the advanced phase of Parkinson's disease (PD), gait disturbances represent one of the main causes of disability. Several studies demonstrated that high-frequency electrical stimulation (HFS) of the subthalamic nucleus (STN) significantly improves the motor symptoms of PD. This study was finalised to quantitatively analyze the effect of STN HFS on gait of PD patients, through a three-dimensional gait analysis system. Ten PD patients were studied, with and without STN HFS. The results demonstrated that STN HFS significantly improves all the main gait parameters in PD patients.