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Patients with sternotomy are advised to follow sternal precautions to avoid the risk of sternal complications. However, there are no standard recommendations, in particular to perform the supine-to-sitting postural change, where sternal asymmetrical force may be applied. The aim of this study was to compare the rotational movement and the use of a tied rope (individual device for supine-to-sitting, "IDSS") to perform the supine-to-sitting postural change. A total of 92 patients (26% female) admitted to a rehabilitative post-surgery ward with sternotomy were assessed for sternal instability. Levels of pain and perceived effort during the two modalities of postural change and at rest were assessed. Patients reported higher values of pain and perceived effort (both p < 0.0005) during rotational movement with respect to the use of the IDSS. Moreover, patients with sternal instability (14%) and female patients with macromastia (25%) reported higher pain than those stable or without macromastia (both p < 0.05). No other risk factors were associated with pain. Thus, the IDSS seems to reduce the levels of pain and perceived effort during the supine-to-sitting postural change. Future studies with quantitative assessments are required to suggest the adoption of this technique, mostly in patients with high levels of pain or with sternal instability.

Many clinical practice recommendations indicate rehabilitation as essential for patients with sequelae of severe or critical COVID-19 and suggest the prompt initiation of a multicomponent rehabilitation program focused on aerobic and endurance training. However, randomized controlled trials (RCTs) regarding aerobic exercise are lacking. Therefore, we aimed to assess the feasibility and effectiveness of the addition of aerobic training to standard rehabilitation in subjects with subacute COVID-19. Participants were 32/214 patients with the sequelae of severe or critical COVID-19 in the acute phase who were eligible and agreed to participate in the study (eligibility = 15%, recruitment = 100%). After randomization and assessment with functional and strength tests, all the participants underwent an inpatient-tailored rehabilitation program (50 min/day, 5 days/week, 10 sessions); in addition, the experimental group performed a low- to moderate-intensity aerobic exercise (30 min/day, 10 sessions). No dropouts or severe adverse events were reported, with an attendance rate of 95.6%. Most of the secondary outcomes significantly improved in both groups, but the improvement in the Functional Independence Measure and Cumulated Ambulation Score-Italian version was significantly greater in the experimental group (at least, p < 0.05). This RCT showed that aerobic exercise is feasible and safe in subacute COVID-19. Moreover, it appears to be beneficial and useful in improving patients' independence and mobility.

Recent studies suggest that also the non-critical form of COVID-19 infection may be associated with executive function impairments. However, it is not clear if they result from cognitive impairments or by COVID-19 infection per se. We aimed to investigate if patients in the post-acute stage of severe COVID-19 (PwCOVID), without manifest cognitive deficits, reveal impairments in performing dual-task (DT) activities compared to healthy controls (HS). We assessed balance in 31 PwCOVID vs. 30 age-matched HS by stabilometry and the Timed Up and Go (TUG) test with/without a cognitive DT. The DT cost (DTC), TUG test time and sway oscillations were recorded; correct cognitive responses (CCR) were calculated to evaluate cognitive performance. Results show a significant difference in overall DT performance between PwCOVID and HS in both stabilometry ( p < 0.01) and the TUG test ( p < 0.0005), although with similar DTCs. The main difference in the DTs between groups emerged in the CCR (effect size > 0.8). Substantially, PwCOVID gave priority to the motor task, leaving out the cognitive one, while HS performed both tasks simultaneously. Our findings suggest that PwCOVID, even without a manifest cognitive impairment, may present a deficit in executive function during DTs. These results encourage the use of DTs and CCR in PwCOVID.

Background and Purpose: The Mini-BESTest is a balance measure with robust psychometric properties widely used in people with Parkinson disease. The aim of this study was to examine-with advanced psychometric techniques-some key properties of the Mini-BESTest (including unidimensionality, functioning of rating categories, internal construct validity, reliability indexes) in a consecutive sample of individuals with Parkinson disease admitted for balance rehabilitation., Methods: Confirmatory factor analysis and Rasch analysis (partial credit model) were performed on 193 individual raw scores of the Mini-BESTest items., Results: Confirmatory factor analysis fit indices and principal component analysis of the residuals confirmed the scale's unidimensionality. At Rasch analysis, the 3-level rating scale demonstrated appropriate functioning. All items fitted the Rasch model. Item response dependence was negligible. No differential item functioning was found across gender and age groups., Discussion and Conclusions: We confirmed and extended the evidence (demonstrated in different populations) on the general psychometric soundness of the Mini-BESTest, even when tested with rigorous statistical methods. In addition, 2 forms were created: (i) to transform raw scores into linear estimates of dynamic balance; and (ii) to compare the individual's item responses with those expected by the Rasch model (thus providing an aid for tailored interventions) and manage missing responses. Further independent studies using advanced psychometric techniques are warranted, also in people with balance disturbances of different etiology. Our study further increases the confidence in using the Mini-BESTest to assess dynamic balance in people with Parkinson disease and provides some useful additional clinical aids for interpreting the results and calculating more precise change scores.See the Supplementary Video, available at: http://links.lww.com/JNPT/A384., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Academy of Neurologic Physical Therapy, APTA.)

COVID-19 leaves important sequelae in patients, not only in those who had the experience of a critical illness but also in patients with severe form. Understanding the impairments allows us to target rehabilitation to patients' real needs; balance impairments are an assumed sequela of COVID-19, but no study has specifically evaluated balance performance in these patients. Their performance was compared to that of patients with a pulmonary disease that leads to systemic diseases, such as patients with an acute exacerbation of chronic obstructive pulmonary disease (PwAECOPD), and of healthy subjects. A total of 75 subjects were assessed: 25 patients with COVID-19 (PwCOVID) with a severe form in the acute phase, 25 PwAECOPD and 25 healthy subjects sex- and age-matched. A stabilometric platform was used to evaluate static balance, both with eyes open and closed, while the dynamic balance was assessed with the Mini-BESTest and the Timed Up and Go test. When compared to healthy subjects, results showed that PwCOVID had worse performance in both static (P < 0.005) and dynamic (P < 0.0001) balance, with a large effect size in all measures (>0.8). Moreover, PwCOVID showed similar results to those of PwAECOPD. In conclusion, PwCOVID showed a balance deficit in both dynamic and static conditions. Therefore, as for PwAECOPD, they should require not only respiratory rehabilitation but also balance and mobility physiotherapy to prevent today's PwCOVID from becoming tomorrow's fallers., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Various conceptual gait models have been created with exploratory factor analysis to assess gait performance in healthy individuals or patients with orthopaedic or neurological diseases. However, a direct comparison between these models, to determine which is best for assessing gait in healthy elderly subjects, has never been performed. Confirmatory factor analysis is a statistical technique which allows to compare the structure of these models and to evaluate their validity and reliability., Research Question: Which of the current models for evaluating gait shows the best construct, convergent and discriminant validity and reliability when replicated in a sample of healthy elderly subjects?, Methods: 92 healthy elderly subjects (aged 73.3 ± 6.8 years) were enrolled. Participants were instructed to walk on a baropodometric walkway; gait variables were then extracted and analyzed according to 8 different gait models (published between 2007 and 2019). Correlation between variables of each model were investigated. The number of factors to include for each model was assessed with different criteria of principal component analysis. The construct validity of the gait models was assessed in terms of goodness of fit indexes through confirmatory factor analysis. Convergent and discriminant validity and reliability of the models were also assessed., Results: Of the models considered, only our model previously created for patients with Parkinson's Disease reached convergence, with an excellent fit in all indexes (χ 2  = 18.34, df = 13, p = 0.15, RMSEA = 0.06 (95%CI = 0.00-0.13), CFI = 0.98, TLI = 0.96, SRMR = 0.05). The model showed an acceptable convergent validity. The three factors resulted to be mutually independent (correlations among factors <0.85) and reliable. Most of the other seven considered models presented a high number (12.5-65%) of highly inter-related variables and more factors than necessary., Significance: Future studies can use our gait model as a framework for clinical practice or research., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Locomotion in people with Parkinson' disease (pwPD) worsens with the progression of disease, affecting independence and quality of life. At present, clinical practice guidelines recommend a basic evaluation of gait, even though the variables (gait speed, cadence, step length) may not be satisfactory for assessing the evolution of locomotion over the course of the disease. Collecting variables into factors of a conceptual model enhances the clinical assessment of disease severity. Our aim is to evaluate if factors highlight gait differences between pwPD and healthy subjects (HS) and do it at earlier stages of disease compared to single variables. Gait characteristics of 298 pwPD and 84 HS able to walk without assistance were assessed using a baropodometric walkway (GAITRite®). According to the structure of a model previously validated in pwPD, eight spatiotemporal variables were grouped in three factors: pace/rhythm, variability and asymmetry. The model, created from the combination of three factor scores, proved to outperform the single variables or the factors in discriminating pwPD from HS. When considering the pwPD split into the different Hoehn and Yahr (H&Y) stages, the spatiotemporal variables, factor scores and the model showed that multiple impairments of gait appear at H&Y stage 2.5, with the greatest difference from HS at stage 4. A contrasting behavior was found for the asymmetry variables and factor, which showed differences from the HS already in the early stages of PD. Our findings support the use of factor scores and of the model with respect to the single variables in gait staging in PD., (© 2021. The Author(s).)

Objective: The Mini-Balance Evaluation Systems Test (Mini-BESTest) is a balance scale common to clinical practice, but different scoring has been proposed, that is, total score and/or subsections. This study aimed to investigate Mini-BESTest validity by comparing 6 structural models and to establish the best model for discriminating fallers from nonfallers, that is, those who did or did not report at least 2 falls in the 6 months before evaluation., Methods: In this cross-sectional validation study, data from 709 individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1-3) were analyzed. Individuals were evaluated with the Mini-BESTest, and fall history was recorded. Construct, convergent, and discriminant validity and reliability of the 6 models were analyzed. The ability of the models to adequately identify individuals with or without a history of falls was tested with receiving operating characteristic curves., Results: Confirmatory factor analysis showed that the unidimensional models and the 4-factor solutions showed the best fit indexes. Conversely, second-order models, which allowed reporting of both total and subsections, did not converge. Most models and factors showed a low convergent validity (average variance extracted values <0.5). Correlations among the anticipatory postural adjustments factor with both the sensory orientation and the dynamic gait factors of multidimensional models were high (r ≥ 0.85). Unidimensional model reliability was good, whereas low values were found in one-half of the subsections. Finally, both unidimensional models showed a large area under the receiving operating characteristic curve (0.81)., Conclusion: The original unidimensional Mini-BESTest model-with a total score of 28-showed the highest validity and reliability and was best at discriminating fallers from nonfallers. Conversely, its 4 subsections should not be reported separately, because they were highly correlated and had low reliability; therefore, they are not actually capable of measuring different aspects of balance., Impact: This study shows that the Mini-BESTest should be used only with the original unidimensional scoring system in people with Parkinson disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Eye-tracking technology is advancing rapidly, becoming cheaper and easier to use and more robust. This has fueled an increase in its implementation for Augmentative and Alternative Communication (AAC). Nowadays, Eye-Tracking Communication Devices (ETCDs) can be an effective aid for people with disabilities and communication problems. However, it is not clear what level of performance is attainable with these devices or how to optimize them for AAC use. The objective of this observational study was to provide data on non-disabled adults' performance with ETCD regarding (a) range of eye-typing ability in terms of speed and errors for different age groups and (b) relationship between ETCD performance and bimanual writing with a conventional PC keyboard and (c) to suggest a method for a correct implementation of ETCD for AAC. Sixty-seven healthy adult volunteers (aged 20-79 years) were asked to type a sample sentence using, first, a commercial ETCD and then a standard PC keyboard; we recorded the typing speed and error rate. We repeated the test 11 times in order to assess performance changes due to learning. Performances differed between young (20-39 years), middle-aged (40-59 years), and elderly (60-79 years) participants. Age had a negative impact on performance: as age increased, typing speed decreased and the error rate increased. There was a clear learning effect, i.e., repetition of the exercise produced an improvement of performance in all subjects. Bimanual and ETCD typing speed showed a linear relationship, with a Pearson's correlation coefficient of 0.73. The assessment of the effect of age on eye-typing performance can be useful to evaluate the effectiveness of man-machine interaction for use of ETCDs for AAC. Based on our findings, we outline a potential method (obviously requiring further verification) for the setup and tuning of ETCDs for AAC in people with disabilities and communication problems., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Marco Caligari et al.)

Background: Hip fractures should not be considered as a single, homogeneous condition. Various determinants of functional recovery of patients with hip fracture have been proposed, such as age or type of fracture. The aim of this study was to determine if patients with an intertrochanteric fracture (ITF) had lower functional recovery characteristics with respect to those with a femoral neck fracture (FNF)., Methods: A retrospective study was carried out on 531 elderly patients with hip fracture, surgically treated, admitted to a rehabilitation institute between December 1, 2014, and December 31, 2017. Patients underwent an individualized rehabilitation program for improving their physical function. The outcome measures of this study were the length of stay (LOS) in the rehabilitation institute, the Functional Independence Measure (FIM) gain, i.e. the difference in FIM score between discharge and admission, and the FIM efficiency, which represents the daily gain. Patients were also stratified by age categories and by different levels of functional independence, as evaluated with the FIM total score at baseline., Results: Age (p<0.05), LOS (p<0.005) and rehabilitation outcomes (FIM score and efficiency; p<0.05) differed significantly between patients with FNF and ITF. In particular, patients with ITF were older and more dependent at baseline. Moreover, they showed a lower FIM efficiency with respect to patients with FNF (p<0.05), which obtained a similar improvement in FIM total score of about 26 points but were discharged on average 3 days before. With aging, FIM efficiency decreased, while LOS increased. Patients highly dependent at baseline (FIM total score <40) had the lowest FIM gain and efficiency and the longest LOS respect to the more independent patients. Moreover, in older (85+ years) and in higher dependent patients the differences in the outcome measures between ITF and FNF were reduced., Conclusions: The type of hip fracture could affect the LOS and FIM efficiency of younger and more independent patients with hip fracture during inpatient rehabilitation. In particular, patients with ITF require a longer rehabilitation period to achieve a similar functional gain as those with FNF., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Evidence about the psychological functioning in individuals who survived the COVID-19 infectious is still rare in the literature. In this paper, we investigated fearful facial expressions recognition, as a behavioural means to assess psychological functioning. From May 15th, 2020 to January 30th, 2021, we enrolled sixty Italian individuals admitted in multiple Italian COVID-19 post-intensive care units. The detection and recognition of fearful facial expressions were assessed through an experimental task grounded on an attentional mechanism (i.e., the redundant target effect). According to the results, our participants showed an altered behaviour in detecting and recognizing fearful expressions. Specifically, their performance was in disagreement with the expected behavioural effect. Our study suggested altered processing of fearful expressions in individuals who survived the COVID-19 infectious. Such a difficulty might represent a crucial sign of psychological distress and it should be addressed in tailored psychological interventions in rehabilitative settings and after discharge., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To determine the feasibility and safety of aerobic training with an arm crank ergometer and its effectiveness in improving functional capacity and gait in patients with recent hip fracture., Design: Randomized, controlled, assessor-blinded pilot study, with intention-to-treat analysis., Setting: Inpatients, rehabilitation department., Subjects: 40 patients with hip fracture surgically treated., Interventions: Training group performed aerobic exercise with an arm crank ergometer (15 sessions, 30 minutes/day) at an intensity of 64% to 76% of maximum heart rate, in addition to conventional inpatient rehabilitation., Main Measures: Primary outcome was the feasibility (including eligibility rate, recruitment rate, number of drop-outs and adverse events, adherence). Secondary measures were the Timed Up and Go test, ability to walk independently, muscle torque of knee extensors of fractured and non-fractured leg, Functional Independence Measure., Results: Mostly due to pre-existing disability and fracture type, only 40/301 (13%) patients were eligible (age 84.6 ± 7.6 years, 75% female); all agreed to participate and 90% completed the trial, without adverse events. Adherence to aerobic exercise was good, with high attendance at sessions (93%), a strong compliance to exercise duration (95%) but lower compliance to the prescribed intensity (73%). After the program, more patients were able to walk independently in the training group ( n  = 18) compared to control ( n  = 13) ( P  < 0.05). Also the muscle torque of fractured leg knee extensors was higher in the training group ( P  < 0.05)., Conclusion: Aerobic training in addition to conventional rehabilitation after a hip fracture is feasible and safe and it was effective in improving gait performance and strength of fractured leg., Trial Registration: NCT04025866.

Objective: The aim of this experiential review is to explore the state of the art of the literature regarding the evaluation tools available for assessment of patient motivation and satisfaction during technology-assisted rehabilitation (robot rehabilitation, virtual reality rehabilitation, and serious games rehabilitation). Materials and Methods: A systematic search of the peer-reviewed literature published from January 1990 to August 2019 was conducted. The protocol for this review was registered in PROSPERO and carried out in accordance with the PRISMA recommendations. Results: The search of PubMed, PsycINFO, Scopus, and Web of Science databases identified a total of 333 records. After adjusting for duplicates and other inclusion criteria, 69 studies were selected for inclusion in the review. We found that authors used a wide range of dedicated questionnaires and, in about 50% of studies, a few validated tools to assess motivation and satisfaction during technology-assisted rehabilitation. The instruments most used were the Intrinsic Motivation Inventory (IMI), Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST 2.0), and the Usefulness, Satisfaction, and Ease of use (USE) scale. Motivation and satisfaction were generally portrayed as multidimensional concepts; overall, 29 domains were assessed by 9 different tools. Conclusion: The tools used in the current literature to assess patient motivation and satisfaction during technology-assisted rehabilitation are quite variegated, but we would recommend use of the IMI and USE questionnaires based on their widespread diffusion. However, the choice of domains explored and number of items calls for harmonization. Ideally, this should be a joint task for the whole scientific community.

Background: Balance problems in Parkinson's Disease (PD) require appropriate evaluation. While the Mini-BESTest is commonly used to assess dynamic balance, some of its psychometric properties have not yet been addressed., Research Question: What is the responsiveness and the Minimal Clinically Important Difference (MCID) of the Mini-BESTest in patients with PD?, Methods: One-hundred forty-eight patients with PD underwent a treatment specific for balance skills (1-h session, three times/week for four weeks). All patients were initially evaluated with the Mini-BESTest and Activities-Specific Balance Confidence scale 5-levels (ABC-5L). Post-treatment, patients were assessed with the Mini-BESTest, ABC-5L and Global Rating of Change (GRC, both patient- and physiotherapist-rated). Responsiveness to treatment and MCID were calculated with distribution and anchor-based methods: effect size, area under the curve (AUC) of receiver operating characteristics (ROC), and correlations between evaluations (change in score of Mini-BESTest, ABC-5L, GRC). Eleven a priori hypotheses were formulated for testing responsiveness., Results: The effect size of treatment measured with the Mini-BESTest was 0.44, revealing moderate responsiveness. AUCs were 0.75, 0.82 and 0.59 for the patient-rated GRC, physiotherapist-rated GRC and ABC-5L, respectively. There was a moderate correlation between changes in the Mini-BESTest and patient-rated (r s = 0.42) or physiotherapist-rated (r s = 0.62) GRC scores. Conversely, a low correlation (r s = 0.17) was found between changes in the Mini-BESTest and ABC-5L. Consequently, 72.7% of hypotheses were met. The Mini-BESTest MCID was between 3.4 and 4.0 when calculated with distribution and anchor-based methods, respectively., Significance: The Mini-BESTest showed moderate responsiveness for detecting treatment-related improvement in dynamic balance. A 4.0-point MCID value is useful to identify clinical effects of balance rehabilitation in a single patient with PD. Values ranging from 3.4 and 4.0 are recommended for interpretation of results at a group level., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The Brief Balance Evaluation Systems Test (Brief-BESTest) could be a useful tool for balance assessment. Although some psychometric characteristics have been examined, others still need to be clarified., Objective: The objective was to assess the structural validity, convergent validity, discriminant validity, and internal consistency of the Brief-BESTest in neurological patients., Design: This was a cross-sectional study., Methods: Data were from 416 patients with neurological disease and related balance disorders. Patients were assessed with the 5-levels Activities-Specific Balance Confidence Scale (ABC 5-levels), Brief-BESTest, and some simple balance tests (ie, 1-leg stance, Timed "Up & Go" test, functional reach, and a fall history questionnaire). Three Brief-BESTest models were examined through confirmatory factor analysis, and the following indexes were calculated: Comparative Fit Index, Tucker-Lewis Index, and root-mean-square error of approximation. Convergent validity was assessed by calculating the correlation between Brief-BESTest and ABC 5-levels total scores. Receiver operating characteristics assessed the ability of each model to differentiate between people with falls and those without falls. Internal consistency was measured with Cronbach α and coefficient ω., Results: Confirmatory factor analysis showed model 3 (Comparative Fit Index = 0.97; Tucker-Lewis Index = 0.95; root-mean-square error of approximation = 0.05), with item 1 removed and error covariance between items 3 and 4 and between items 5 and 6, to have a significantly better structure than models 1 and 2. The correlation between Brief-BESTest and ABC 5-levels was 0.61 (Spearman ρ) for all 3 models. The area under the curve of the receiver operating characteristics showed an acceptable accuracy (0.72) in distinguishing patients with a history of falls from those without a history of falls (95% confidence interval = 0.66-0.78) for all models and was superior to the areas under the curve of other simple balance tests (1-leg stance, Timed "Up & Go" test, functional reach). Cronbach α was good for Brief-BESTest models 1 (0.92) and 3 (0.92), but ω was greater than 0.80 only for model 3., Limitations: The sample was heterogeneous., Conclusions: The Brief-BESTest, after some changes, shows good validity and internal consistency in patients affected by different balance disorders., (© 2019 American Physical Therapy Association.)

It was highlighted that the original article [1] had an omission in the Abstract. This Correction article shows the omitted sentence: "This article [1] was awarded the SIAMOC Best Methodological Paper 2018".

Background: Gait impairment is a risk factor for falls in patients with Parkinson's disease (PD). Gait can be conveniently assessed by electronic walkways, but there is need to select which spatiotemporal gait variables are useful for assessing gait in PD. Existing models for gait variables developed in healthy subjects and patients with PD show some methodological shortcomings in their validation through exploratory factor analysis (EFA), and were never confirmed by confirmatory factor analysis (CFA). The aims of this study were (1) to create a new model of gait for PD through EFA, (2) to analyze the factorial structure of our new model and compare it with existing models through CFA., Results: From the 37 variables initially considered in 250 patients with PD, 10 did not show good-to-excellent reliability and were eliminated, while further 19 were eliminated after correlation matrix and Kaiser-Meyer-Olkin measure. The remaining eight variables underwent EFA and three factors emerged: pace/rhythm, variability, and asymmetry. Structural validity of our new model was then examined with CFA, using the structural equation modeling. After some modifications, suggested by the Modification Indices, we obtained a final model that showed an excellent fit. In contrast, when the structure of previous models of gait was analyzed, no model achieved convergence with our sample of patients., Conclusions: Our model for spatiotemporal gait variables of patients with PD is the first to be developed through an accurate EFA and confirmed by CFA. It contains eight gait variables divided into three factors and shows an excellent fit. Reasons for the non-convergence of other models could be their inclusion of highly inter-correlated or low-reliability variables or could be possibly due to the fact that they did not use more recent methods for determining the number of factors to extract.

In this review, we briefly recall the fundamental processes allowing us to change locomotion trajectory and keep walking along a curved path and provide a review of contemporary literature on turning in older adults and people with Parkinson's Disease (PD). The first part briefly summarizes the way the body exploits the physical laws to produce a curved walking trajectory. Then, the changes in muscle and brain activation underpinning this task, and the promoting role of proprioception, are briefly considered. Another section is devoted to the gait changes occurring in curved walking and steering with aging. Further, freezing during turning and rehabilitation of curved walking in patients with PD is mentioned in the last part. Obviously, as the research on body steering while walking or turning has boomed in the last 10 years, the relevant critical issues have been tackled and ways to improve this locomotor task proposed. Rationale and evidences for successful training procedures are available, to potentially reduce the risk of falling in both older adults and patients with PD. A better understanding of the pathophysiology of steering, of the subtle but vital interaction between posture, balance, and progression along non-linear trajectories, and of the residual motor learning capacities in these cohorts may provide solid bases for new rehabilitative approaches.

Background: Several patients with Parkinson´s disease (PD) can walk normally along straight trajectories, and impairment in their stride length and cadence may not be easily discernible. Do obvious abnormalities occur in these high-functioning patients when more challenging trajectories are travelled, such as circular paths, which normally implicate a graded modulation in the duration of the interlimb gait cycle phases?, Methods: We compared a cohort of well-treated mildly to moderately affected PD patients to a group of age-matched healthy subjects (HS), by deliberately including HS spontaneously walking at the same speed of the patients with PD. All participants performed, in random order: linear and circular walking (clockwise and counter-clockwise) at self-selected speed. By means of pressure-sensitive insoles, we recorded walking speed, cadence, duration of single support, double support, swing phase, and stride time. Stride length-cadence relationships were built for linear and curved walking. Stride-to-stride variability of temporal gait parameters was also estimated., Results: Walking speed, cadence or stride length were not different between PD and HS during linear walking. Speed, cadence and stride length diminished during curved walking in both groups, stride length more in PD than HS. In PD compared to HS, the stride length-cadence relationship was altered during curved walking. Duration of the double-support phase was also increased during curved walking, as was variability of the single support, swing phase and double support phase., Conclusion: The spatio-temporal gait pattern and variability are significantly modified in well-treated, high-functioning patients with PD walking along circular trajectories, even when they exhibit no changes in speed in straight-line walking. The increased variability of the gait phases during curved walking is an identifying characteristic of PD. We discuss our findings in term of interplay between control of balance and of locomotor progression: the former is challenged by curved trajectories even in high-functioning patients, while the latter may not be critically affected.

We hypothesised that rehabilitation specifically addressing balance in Parkinson's disease patients might improve not only balance but locomotion as well. Two balance-training protocols (standing on a moving platform and traditional balance exercises) were assessed by assigning patients to two groups (Platform, n = 15, and Exercises, n = 17). The platform moved periodically in the anteroposterior, laterolateral, and oblique direction, with and without vision in different trials. Balance exercises were based on the Otago Exercise Program. Both platform and exercise sessions were administered from easy to difficult. Outcome measures were (a) balancing behaviour, assessed by both Index of Stability (IS) on platform and Mini-BESTest, and (b) gait, assessed by both baropodometry and Timed Up and Go (TUG) test. Falls Efficacy Scale-International (FES-I) and Parkinson's Disease Questionnaire (PDQ-8) were administered. Both groups exhibited better balance control, as assessed both by IS and by Mini-BESTest. Gait speed at baropodometry also improved in both groups, while TUG was less sensitive to improvement. Scores of FES-I and PDQ-8 showed a marginal improvement. A four-week treatment featuring no gait training but focused on challenging balance tasks produces considerable gait enhancement in mildly to moderately affected patients. Walking problems in PD depend on postural instability and are successfully relieved by appropriate balance rehabilitation. This trial is registered with ClinicalTrials.gov NCT03314597.

Training subjects to step-in-place eyes open on a rotating platform while maintaining a fixed body orientation in space [podokinetic stimulation (PKS)] produces a posteffect consisting in inadvertent turning around while stepping-in-place eyes closed [podokinetic after-rotation (PKAR)]. Since the rationale for rehabilitation of curved walking in Parkinson's disease is not fully known, we tested the hypothesis that repeated PKS favors the production of curved walking in these patients, who are uneasy with turning, even when straight walking is little affected. Fifteen patients participated in 10 training sessions distributed in 3 weeks. Both counterclockwise and clockwise PKS were randomly administered in each session. PKS velocity and duration were gradually increased over sessions. The velocity and duration of the following PKAR were assessed. All patients showed PKAR, which increased progressively in peak velocity and duration. In addition, before and at the end of the treatment, all patients walked overground along linear and circular trajectories. Post-training, the velocity of walking bouts increased, more so for the circular than the linear trajectory. Cadence was not affected. This study has shown that parkinsonian patients learn to produce turning while stepping when faced with appropriate training and that this capacity translates into improved overground curved walking.

Background: The Brief Balance Evaluation Systems Test (Brief-BESTest) was recently proposed as a clinical tool for quickly measuring balance disorders, but its measurement properties warrant investigation., Objective: The study objective was to perform a detailed analysis of the psychometric properties of the Brief-BESTest by means of Classical Test Theory and Rasch analysis., Design: This was an observational measurement study., Methods: Brief-BESTest data were collected from a sample of 244 participants. Internal consistency was analyzed with the Cronbach α and item-to-total correlations. Test-retest reliability and interrater reliability were investigated in a subgroup of 21 participants. The minimum detectable change at the 95% confidence level was calculated. Scale dimensionality was examined through Horn parallel analysis; this step was followed by exploratory factor analysis for ordinal data. Finally, data were examined using Rasch analysis (rating scale model)., Results: The Cronbach α was .89, and all item-to-total correlations were greater than .40. Test-retest reliability had an intraclass correlation coefficient (ICC) (2,1) of .94, and interrater reliability had an ICC (2,1) of .90. The minimum detectable change at the 95% confidence level was 4.30 points. The unidimensionality of the test was confirmed, but 1 item showed low communality. Rasch analysis revealed the inadequacy of response categories, 5 misfitting items, minor mistargeting, moderate person reliability (.80), and 2 pairs of locally dependent items., Limitations: The sample was a cross-section of people who had balance disorders from different neurological etiologies and were recruited consecutively at a single rehabilitation facility., Conclusions: The Brief-BESTest was confirmed to have some acceptable-to-good reliability indexes when calculated according to Classical Test Theory, but the scale showed fairly limited sensitivity to change. Rasch analysis indicated that item selection should be improved from a psychometric point of view. Item redundancy needs to be reduced, and the metric coverage of the measured construct needs to be improved with new items., (© 2016 American Physical Therapy Association.)

Purpose: Cycle ergometer training improves gait in the elderly, but its effect in patients with Parkinson's disease (PD) is not completely known., Methods: Twenty-nine PD inpatients were randomized to treadmill (n = 13, PD-T) or cycle ergometer (n = 16, PD-C) training for 3 weeks, 1 hour/day. Outcome measures were distance travelled during the 6-min walking test (6MWT), spatio-temporal variables of gait assessed by baropodometry, the Timed Up and Go (TUG) duration, the balance score through the Mini-BESTest, and the score of the Unified Parkinson's Disease Rating Scale (UPDRS)., Results: Sex, age, body mass index, disease duration, Hoehn-Yahr staging, comorbidity and medication did not differ between groups. At end of training, ANCOVA showed significant improvement, of similar degree, in both groups for 6MWT, speed, step length and cadence of gait, TUG, Mini-BESTest and UPDRS., Conclusions: This pilot study shows that cycle ergometer training improves walking parameters and reduces clinical signs of PD, as much as treadmill training does. Gait velocity is accompanied by step lengthening, making the gait pattern close to that of healthy subjects. Cycle ergometer is a valid alternative to treadmill for improving gait in short term in patients with PD.

Background: Recently, a new balance scale, the Mini-BESTest, was introduced. This scale can be administered in about 15 min, and focuses on "dynamic balance". In spite of the recently increased use of this scale, further psychometric studies seem called for to enhance confidence in its use in different fields of clinical practice and research., Aim: To re-examine through Rasch analysis the metric properties of the Mini-BESTest and provide a nomogram that allow to quickly transform raw scores of the scale into linear estimates of dynamic balance., Design: Observational cross-sectional study., Setting: Rehabilitation hospital., Population: A total of 234 patients were consecutively admitted with a variety of neurological diseases causing balance impairment., Methods: Internal construct validity was assessed by determining how well data fit the Rasch model. Reliability was estimated for both persons and items. Scale unidimensionality and local independence of items were analysed performing a principal component analysis (PCA) on the standardized residuals. Also, a differential item functioning (DIF) analysis was run to assess the stability of item calibration across subsamples of patients., Results: All 14 items of Mini-BESTest fitted the "dynamic balance" construct, i.e., the mean of the squared residuals for both the infit and outfit was between 0.8 and 1.2. The person abilities-item difficulty matching was very good. The reliability indices of the Mini-BESTest were as follows: person separation index=3.24 and person reliability=0.91; item separation index=12.00 and item reliability=0.99. The PCA of standardized residuals showed that the variance attributable to the Rasch factor was good (68%) and the eigenvalue of the unexplained variance in the first contrast was just 1.9, thus confirming the unidimensionality of the scale. No DIF was found across gender and age groups., Conclusion: The reliability indexes confirmed their high values, giving a high degree of confidence in the consistency of both person-ability and item-difficulty estimates. Results allowed to transform the ordinal summed raw scores of the Mini-BESTest into interval-level measurements using a nomogram. Since no significant local dependence between items was found, this means that each Mini-BESTest item is appropriate for measuring the variable of interest (dynamic balance) and not redundant. DIF analysis showed the stability of item hierarchy and difficulty among subsamples of patients of different gender and age., Clinical Rehabilitation Impact: This study further increases confidence in use of the Mini-BESTest for clinical assessment of dynamic balance in patients undergoing rehabilitation.

Background: Turning involves complex reorientation of the body and is accompanied by asymmetric motion of the lower limbs. We investigated the distribution of the forces under the two feet, and its relation to the trajectory features and body medio-lateral displacement during curved walking., Methods: Twenty-six healthy young participants walked under three different randomized conditions: in a straight line (LIN), in a circular clockwise path and in a circular counter-clockwise path. Both feet were instrumented with Pedar-X insoles. An accelerometer was fixed to the trunk to measure the medio-lateral inclination of the body. We analyzed walking speed, stance duration as a percent of gait cycle (%GC), the vertical component of the ground reaction force (vGRF) of both feet during the entire stance, and trunk inclination., Results: Gait speed was faster during LIN than curved walking, but not affected by the direction of the curved trajectory. Trunk inclination was negligible during LIN, while the trunk was inclined toward the center of the path during curved trajectories. Stance duration of LIN foot and foot inside the curved trajectory (Foot-In) was longer than for foot outside the trajectory (Foot-Out). vGRF at heel strike was larger in LIN than in curved walking. At mid-stance, vGRF for both Foot-In and Foot-Out was higher than for LIN foot. At toe off, vGRF for both Foot-In and Foot-Out was lower than for LIN foot; in addition, Foot-In had lower vGRF than Foot-Out. During curved walking, a greater loading of the lateral heel occurred for Foot-Out than Foot-In and LIN foot. On the contrary, a smaller lateral loading of the heel was found for Foot-In than LIN foot. At the metatarsal heads, an opposite behaviour was seen, since lateral loading decreased for Foot-Out and increased for Foot-In., Conclusions: The lower gait speed during curved walking is shaped by the control of trunk inclination and the production of asymmetric loading of heel and metatarsal heads, hence by the different contribution of the feet in producing the body inclination towards the centre of the trajectory.

Background: Previous studies have assessed reliability of insole technology for evaluating foot pressure distribution during linear walking. Since in natural motion straight walking is intermingled with turns, we determined the test-retest reliability of insole assessment for curved as well as linear trajectories, and estimated the minimum number of steps required to obtain excellent reliability for each output variable., Methods: Sixteen young healthy participants were recruited. Each performed, two days apart, two sessions of three walking conditions: linear (LIN) and curved, clockwise (CW) and counter-clockwise (CCW). The Pedar-X system was used to collect pressure distribution. Foot print was analyzed both as a whole and as subdivided into eight regions: medial and lateral heel, medial and lateral arch, I metatarsal head, II-V metatarsal heads, hallux, lateral toes. Reliability was assessed by using intraclass correlation coefficient (ICC) for clinically relevant variables from analysis of 50 steps per trajectory: Peak Force (PF); Peak Pressure (PP); Contact Area (CA); Stance Duration (S)., Results: When considering whole-foot, all variables showed an ICC >0.80, therefore highly reliable. This was true for both LIN and curved trajectories. There was no difference in ICC of the four variables between left and right foot. When collapsing foot and trajectories, S had a lower ICC than PP and CA, and PP lower than CA. Mean percent error between the values of first and second session was <5%. When separately considering the eight foot regions, ICCs of PF, PP and CA for all regions and trajectories were generally >0.90, indicating excellent reliability. In curved trajectories, S showed smaller ICCs. Since the least ICC value for S was 0.60 in LIN trajectory, we estimated that to achieve an ICC ≥0.90 more than 200 steps should be collected., Conclusions: High reliability of insole dynamic variables (PF, PP, CA) is obtained with 50 steps using the Pedar-X system. On the contrary, high reliability of temporal variable (S) requires a larger step number. The negligible differences in ICC between LIN and curved trajectory allow use of this device for gait assessment along mixed trajectories in both clinical and research setting.

People with amyotrophic lateral sclerosis (PwALS) show progressive loss of voluntary muscle strength. In advanced disease, motor and phonatory impairments seriously hinder the patient's interpersonal communication. High-tech devices such as eye tracking communication devices (ETCDs) are used to aid communication in the later stages of ALS. We sought to evaluate the effect of ETCDs on patient disability, quality of life (QoL), and user satisfaction, in a group of 35 regular ETCD users in late-stage ALS with tetraplegia and anarthria. The following scales were administered: 1) the Individually Prioritized Problem Assessment (IPPA) scale, in three conditions: without device, with ETCD and, when applicable, with an Eye Transfer (ETRAN) board; 2) the Psychosocial Impact of Assistive Devices Scale (PIADS); and 3) the Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST 2.0). With ETRAN, IPPA showed an increase in communicative abilities with respect to the condition without device, but ETCD produced a further significant increase. PIADS evidenced a large increase of QoL, and QUEST 2.0 showed high user satisfaction with ETCD use. In conclusion, ETCDs should be considered in late-stage ALS with tetraplegia and anarthria, since in these patients they can reduce communication disability and improve QoL.

Background: Recently, a new tool for assessing dynamic balance impairments has been presented: the 14-item Mini-BESTest., Objective: The aim of this study was to compare the psychometric performance of the Mini-BESTest and the Berg Balance Scale (BBS)., Design: A prospective, single-group, observational design was used in the study., Methods: Ninety-three participants (mean age=66.2 years, SD=13.2; 53 women, 40 men) with balance deficits were recruited. Interrater (3 raters) and test-retest (1-3 days) reliability were calculated using intraclass correlation coefficients (ICCs). Responsiveness and minimal important change were assessed (after 10 sessions of physical therapy) using both distribution-based and anchor-based methods (external criterion: the 15-point Global Rating of Change [GRC] scale)., Results: At baseline, neither floor effects nor ceiling effects were found in either the Mini-BESTest or the BBS. After treatment, the maximum score was found in 12 participants (12.9%) with BBS and in 2 participants (2.1%) with Mini-BESTest. Test-retest reliability for total scores was significantly higher for the Mini-BESTest (ICC=.96) than for the BBS (ICC=.92), whereas interrater reliability was similar (ICC=.98 versus .97, respectively). The standard error of measurement (SEM) was 1.26 and the minimum detectable change at the 95% confidence level (MDC(95)) was 3.5 points for Mini-BESTest, whereas the SEM was 2.18 and the MDC(95) was 6.2 points for the BBS. In receiver operating characteristic curves, the area under the curve was 0.92 for the Mini-BESTest and 0.91 for the BBS. The best minimal important change (MIC) was 4 points for the Mini-BESTest and 7 points for the BBS. After treatment, 38 participants evaluated with the Mini-BESTest and only 23 participants evaluated with the BBS (out of the 40 participants who had a GRC score of ≥ 3.5) showed a score change equal to or greater than the MIC values., Limitations: The consecutive sampling method drawn from a single rehabilitation facility and the intrinsic weakness of the GRC for calculating MIC values were limitations of the study., Conclusions: The 2 scales behave similarly, but the Mini-BESTest appears to have a lower ceiling effect, slightly higher reliability levels, and greater accuracy in classifying individual patients who show significant improvement in balance function.

TREX1 (DNase III) is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients) and SS (58 patients), to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients) because it shares similarities with SLE (presence of antinuclear antibodies and connective tissue damage). We observed 7 variations; two of these are novel nonsynonymous variants (p.Glu198Lys and p.Met232Val). They were detected in one SS and in one SSc patient, respectively, and in none of the 200 healthy controls typed in this study and of the 1712 published controls. In silico analysis predicts a possibly damaging role on protein function for both variants. The other 5 variations are synonymous and only one of them is novel (p.Pro48Pro). This study contributes to the demonstration that TREX1 is involved in autoimmune diseases and proposes that the spectrum of involved autoimmune diseases can be broader and includes SSc. We do not confirm a role of TREX1 variants in SLE.

It has recently been suggested that short expansions of CAG repeat in the gene ATXN-2 causing SCA2 (spinocerebellar ataxia type 2) are associated with an increased risk of amyotrophic lateral sclerosis (ALS) in the populations of the USA and northern Europe. In this study, we investigated the role of ATXN-2 in Italian patients clinically diagnosed with ALS and characterized the molecular structure of ATXN-2 expansions. We assessed the size of the CAG repeat in ATXN-2 exon 1 in 232 Italian ALS patients and 395 matched controls. ATXN-2 expanded alleles containing > 30 repeats have been observed in seven sporadic ALS patients (3.0%), while being absent in the controls (p = 0.00089). Four out of the seven patients had an ATXN-2 allele in the intermediate-fully pathological range: one with 32 repeats, 2 with 33 repeats and 1 with 37 repeats, accounting for 1.7% of the ALS cohort. Sequencing of expanded (> 32) alleles showed that they were all interrupted with at least one CAA triplet. ATXN-2 alleles with the same length and structure have been reported in SCA2 patients with parkinsonism or in familial and sporadic Parkinson. Conversely, the phenotype of the present patients was typically ALS with no signs or symptoms of ataxia or parkinsonism. In conclusion, the findings of ATXN-2 expansions in pure ALS cases suggest that ALS may be a third phenotype (alongside ataxia/parkinsonism and pure Parkinson) associated with ATXN-2 interrupted alleles.

Objective: Mutations in HESX1 represent a rare cause of GH deficiency (GHD) associated with a broad spectrum of other anomalies. We searched for causative mutations in a cohort of 244 Italian patients affected by combined and isolated GHD (IGHD)., Methods: The HESX1 gene-coding region and exon-intron boundaries were screened by denaturing HPLC scanning., Results: A novel mutation adjacent to the invariant donor splice site of intron 2 (c.357+3G>A) was identified at the heterozygous state in an IGHD patient. The in vitro and in vivo mRNA analysis of the wild-type HESX1 allele revealed the presence of the whole cDNA and two isoforms lacking exon 2 and exons 2-3 respectively. The mutant HESX1 allele yielded only two splicing products, the whole cDNA and the cDNA missing exons 2-3, whereas the mRNA lacking exon 2 was absent. An in vitro assay demonstrated that the exon 2-deleted mRNA, predicting a prematurely truncated protein, is subjected to nonsense-mediated mRNA decay (NMD)., Conclusions: The c.357+3G>A mutation prevents the generation of one of the alternative isoforms normally produced by the wild-type allele, predicting a truncated HESX1 protein. The mutation is likely to cause IGHD in the heterozygous patient by interfering with the downregulation of HESX1 expression mediated by alternative splicing and NMD. Our results open new insight into the mechanism of HESX1 regulation suggesting that the coupling of alternative splicing and NMD might play a fundamental role in directing the HESX1 expression, and that the alteration of this process might lead to severe consequences.

Motor neurons in amyotrophic lateral sclerosis (ALS) are characterized by the presence of inclusion bodies composed of intermediate filament (IF) proteins. Peripherin protein is as components of these inclusions and rare mutations in peripherin gene (PRPH) were identified in sporadic ALS cases. The aim of this study was to further define the spectrum of PRPH mutations in a cohort of 122 Italian ALS patients. We screened the coding sequence, the exon/intron boundaries, and the 5'-3' un-translated regions (UTRs) in 122 ALS patients. Eighteen sequence variations were detected. Seven variants were not identified in a panel of at least 245 matched controls, including 2 missense variations, namely p.R133P and p.D141Y, each identified in one heterozygous patient. p.R133P was newly identified whereas p.D141Y was previously described in one homozygous sporadic ALS patient. These 2 variants were predicted to have a deleterious effect on protein structure or function. This work contributes to determine the role of PRPH gene variants in ALS. Further studies are necessary to define the mechanisms through which the mutant peripherin could cause ALS phenotype., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To assess the efficacy of a balance rehabilitation treatment by using both a powered platform on which subjects stand and specific physical exercises (EXs)., Design: Crossover trial., Setting: Physical and rehabilitation medicine department in Italy., Participants: Patients (N=33) with balance disorders (14 vestibular origin, 19 peripheral neuropathy origin)., Interventions: Patients underwent powered platform then EX treatment (n=17); the other 16 received the same treatments in reverse order. powered platform consisted of balancing on a sinusoidally oscillating powered platform (in anteroposterior and laterolateral directions in separate trials) with eyes open and closed. A physical therapist administered Cawthorne-Cooksey EXs for patients with vestibular disorders and modified Frenkel EXs for patients with neuropathy. Treatment lasted 1 hour a day for 10 consecutive days, except for the weekend., Main Outcome Measures: Body sway area, subjective score of stability, balance and gait scores, and amplitude of head displacement while balancing on the oscillating powered platform were recorded before, (t0) after the first (t1), and after the second treatment (t2), regardless of the powered platform or EX order., Results: On average, all participants improved balance regardless of the order of treatments, and more so at t2 than t1. Improvement was observed by using instrumental evaluations and balance and gait scales. In both patient groups, powered platform treatment proved to be as effective as EX in improving balance. This effect was stronger in patients with vestibular disorders, independently of order of treatment., Conclusions: Balance rehabilitation with either EX or powered platform is effective in patients with balance disorders of vestibular or neuropathic origin. These findings point to the value of either or both physical EXs and powered platform in increasing stability and potentially decrease the risk of falling in patients with neuropathy, for whom few results are documented in the literature., (Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Curved walking requires complex adaptations, including shift of body weight to counteract the ensuing centrifugal force, and the production of strides of different length between legs. We hypothesized that gait capacities would be more stressed in hemiparetic patients than in healthy subjects when walking along curved, compared with straight, trajectories., Methods: Twenty chronic, stabilized stroke patients and 20 healthy subjects walked along straight or curved trajectories. Mean cadence and gait velocity were off-line computed from video recordings. An electronic walkway detected asymmetry of single support and degree of foot yaw angle at mid-stance. Centre of pressure during standing was recorded by posturography., Results: Compared with linear walking, the velocity of curved walking was not significantly smaller in patients, and was independent of affected body side or direction of rotation. It was inversely correlated with paretic limb weakness, asymmetry of single support, and shift of centre of pressure toward the healthy side. External rotation of the paretic foot relatively favoured curved walking toward the paretic side., Conclusion: Curved locomotion is defective in stabilized stroke patients, but impairment is not dependent on direction of rotation, indicating a shared task between legs or occurrence of effective functional adaptation. These findings advocate rehabilitation exercises targeting complex gait adaptations, including curved walking.

An autosomal dominant form of isolated GH deficiency (IGHD II) can result from heterozygous splice site mutations that weaken recognition of exon 3 leading to aberrant splicing of GH-1 transcripts and production of a dominant-negative 17.5-kDa GH isoform. Previous studies suggested that the extent of missplicing varies with different mutations and the level of GH expression and/or secretion. To study this, wt-hGH and/or different hGH-splice site mutants (GH-IVS+2, GH-IVS+6, GH-ISE+28) were transfected in rat pituitary cells expressing human GHRH receptor (GC-GHRHR). Upon GHRH stimulation, GC-GHRHR cells coexpressing wt-hGH and each of the mutants displayed reduced hGH secretion and intracellular GH content when compared with cells expressing only wt-hGH, confirming the dominant-negative effect of 17.5-kDa isoform on the secretion of 22-kDa GH. Furthermore, increased amount of 17.5-kDa isoform produced after GHRH stimulation in cells expressing GH-splice site mutants reduced production of endogenous rat GH, which was not observed after GHRH-induced increase in wt-hGH. In conclusion, our results support the hypothesis that after GHRH stimulation, the severity of IGHD II depends on the position of splice site mutation leading to the production of increasing amounts of 17.5-kDa protein, which reduces the storage and secretion of wt-GH in the most severely affected cases. Due to the absence of GH and IGF-I-negative feedback in IGHD II, a chronic up-regulation of GHRH would lead to an increased stimulatory drive to somatotrophs to produce more 17.5-kDa GH from the severest mutant alleles, thereby accelerating autodestruction of somatotrophs in a vicious cycle.

Objective: During the administration of timed bilateral alternate vibration to homonymous leg or trunk muscles during quiet upright stance, Parkinsonian (PD) patients undergo cyclic antero-posterior and medio-lateral transfers of the centre of foot pressure. This event might be potentially exploited for improving gait in these patients. Here, we tested this hypothesis by applying alternate muscle vibration during walking in PD., Methods: Fifteen patients and 15 healthy subjects walked on an instrumented walkway under four conditions: no vibration (no-Vib), and vibration of tibialis anterior (TA-Vib), soleus (Sol-Vib) and erector spinae (ES-Vib) muscles of both sides. Trains of vibration (internal frequency 100 Hz) were delivered to right and left side at alternating frequency of 10% above preferred step cadence., Results: During vibration, stride length, cadence and velocity increased in both patients and healthy subjects, significantly so for ES-Vib. Stance and swing time tended to decrease. Width of support base increased with Sol-Vib or TA-Vib, but was unaffected by ES-Vib., Conclusions: Alternate ES vibration enhances gait velocity in PD. The stronger effect of ES over leg muscle vibration might depend on the relevance of the proprioceptive inflow from the trunk muscles and on the absence of adverse effects on the support base width., Significance: Trunk control is defective in PD. The effect of timed vibratory stimulation on gait suggests the potential use of trunk proprioceptive stimulation for tuning the central pattern generators for locomotion in PD., (Copyright (c) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Context and Objective: Main features of the autosomal dominant form of GH deficiency (IGHD II) include markedly reduced secretion of GH combined with low concentrations of IGF-I leading to short stature., Design, Setting, and Patients: A female patient presented with short stature (height -6.0 sd score) and a delayed bone age of 2 yr at the chronological age of 5 yr. Later, at the age of 9 yr, GHD was confirmed by standard GH provocation test, which revealed subnormal concentrations of GH and a very low IGF-I. Genetic analysis of the GH-1 gene revealed the presence of a heterozygous R178H mutation., Interventions and Results: AtT-20 cells coexpressing both wt-GH and GH-R178H showed a reduced GH secretion after forskolin stimulation compared with the cells expressing only wt-GH, supporting the diagnosis of IGHD II. Because reduced GH concentrations found in the circulation of our untreated patient could not totally explain her severe short stature, functional characterization of the GH-R178H performed by studies of GH receptor binding and activation of the Janus kinase-2/signal transducer and activator of transcription-5 pathway revealed a reduced binding affinity of GH-R178H for GH receptor and signaling compared with the wt-GH., Conclusion: This is the first report of a patient suffering from short stature caused by a GH-1 gene alteration affecting not only GH secretion (IGHD II) but also GH binding and signaling, highlighting the necessity of functional analysis of any GH variant, even in the alleged situation of IGHD II.

Context: Mutations in the GHRH receptor (GHRHR) have been detected in the familial type-IB isolated GH deficiency (IGHD-IB) inherited as an autosomal recessive disorder and characterized by a low but detectable serum GH level and good response to substitutive GH therapy., Objective: The aim of our study was the identification of mutations in sporadic patients with a IGHD-IB phenotype., Subjects and Methods: The GHRHR gene was systematically screened by DHPLC in 134 IGHD patients with no family history of the disorder or declared parental consanguinity., Results: We identified a novel variation, Val10Gly, within the signal peptide at the heterozygous state in three patients and in one of 1084 controls (P = 0.004), suggesting that it might contribute to IGHD. The functional analysis showed that the signal peptide is not cleaved from the mutant GHRHR, which in turn is not translocated to the cellular surface, demonstrating that 10Gly drastically affects the receptor correct processing. Because 10Gly was also present in normal-stature relatives of the patients as well as in a control, it is likely that it exerts its effects in the context of other genetic and environmental susceptibility factors., Conclusion: At difference from previous papers reporting GHRHR mutations in familial cases with a clear recessive mode of inheritance, our study was conducted on a large sample of sporadic patients and allowed to discover a novel mechanism of the disease caused by a recurrent dominant mutation in the GHRHR signal peptide associated with incomplete penetrance.

In patients with spastic hemiparesis, centre of foot pressure (CoP) is shifted toward the unaffected limb during quiet stance. We hypothesised that abnormal gait features would correlate with the degree of asymmetry during stance. In 15 patients and 17 normals we recorded CoP and body sway by a force platform and measured spatial-temporal variables of gait with pedobarography. In patients CoP was shifted toward the unaffected limb and sway was larger than in normals. CoP position was associated with the decrease in strength of the affected lower-limb muscles. Spatio-temporal variables of gait were also affected by the disease. Cadence and velocity were decreased, duration of single support on the unaffected limb and of double support were increased with respect to normals. The degree of impairment of gait variables correlated with CoP. We found a negative relationship between velocity or cadence and CoP, and a positive relationship between duration of single support and CoP in the unaffected but not in the affected limb. Duration of double support correlated positively with CoP. CoP asymmetry during both standing and walking suggests that postural and gait problems share some common neural origin in hemiparetic patients. This asymmetry affects gait performance by increasing the time and effort needed to shift body weight toward the affected limb. The degree of postural asymmetry measured by stabilometry is associated with the level of impairment of gait variables.

We hypothesized that gait capacities would be more stressed in patients with Parkinson's disease (PD) when walking along curved than straight trajectories, owing to the complex adaptations required for this walking task. Twenty on-phase patients with PD and 20 healthy subjects walked eyes-open along straight and curved trajectories for 1 minute at self-paced cadence and velocity. Step frequency along straight and curved trajectories was computed from video-recordings of the lower limbs. Step frequency was not affected by trajectory shape in either patients with PD or healthy subjects. Distances run by the patients were shorter than normal under both conditions. However, in PD, distances were relatively shorter during curved than straight walking; therefore, decreased distances in PD were connected with decreased mean step length (as the ratio between distance and step number). No correlation was found between the above mentioned variables and the severity or duration of the disease or the frequency of falls. Walking along curved trajectories can highlight impaired gait control in on-phase patients with PD, and can be suitable for the routine evaluation of possible walking disorders when straight walking is not significantly affected.

Context: Causal mutations have been detected only in a minority of isolated GH deficiency (IGHD) patients. Idiopathic IGHD might be the result of the interaction between several low-penetrance genetic factors and the environment., Objective: The aim of this study was to test the contribution to IGHD of genetic variations in the GH1 gene regulatory regions., Design and Patients: A case-control association study was performed including 118 sporadic IGHD patients with a nonsevere phenotype (height -4/-1 sd score and partial GH deficiency) and two control groups, normal stature (n=200) and short-stature individuals with normal GH secretion (n=113). Seven single-nucleotide polymorphisms in the GH1 promoter, one in the IVS4 region, and two in the locus control region were analyzed., Results: The -57T allele within the vitamin D-responsive element showed a positive significant association when comparing patients with normal (P=0.006) or short stature (P=0.0011) controls. The genotype -57TT showed an odds ratio of 2.93 (1.44-5.99) and 2.99 (1.42-6.31), respectively. The functional relevance of the -57 variation was demonstrated by the luciferase assay in the presence of vitamin D. The vitamin D-induced inhibition of luciferase activity was significantly (P=0.012) stronger for the promoter haplotype carrying the associated variation -57T [haplotype #1 (hp#1)] with respect to hp#2, bearing -57G. Replacement of the T with a G at -57 on hp#1 abolished the repression, demonstrating that the T at position -57 is necessary to determine the greater vitamin D-induced inhibitory effect of hp#1. EMSA experiments showed a different band-shift pattern of the T and G sequences., Conclusion: The common -57G-->T polymorphism contributes to IGHD susceptibility, indicating that it may have a multifactorial etiology.

The aim of this report is to provide an update on the natural history of the Cri du Chat Syndrome by means of the Italian Register (I.R.). Two hundred twenty patients were diagnosed by standard cytogenetic methods and 112 of these were also characterised by molecular-cytogenetic investigation (FISH). FISH analysis showed interstitial deletions, short terminal deletions and other rare rearrangements not previously correctly diagnosed by standard cytogenetics. The diagnosis was made in the first month of life in 42% and within first year in 82% of cases. The remaining 18% were diagnosed at an age ranging from 13 months to 47 years. At the last follow-up, patient age ranged from 8 months to 61 years. Mortality, already low, has decreased over time as it is lower between 1984-2002 compared to 1965-1983. Mortality was higher in patients with unbalanced translocations resulting in 5p deletions. Our data confirm that the cat-like cry and peculiar timbre of voice are the most typical signs of the syndrome, not only at birth but also later and these are the only signs which might suggest the diagnosis in patients with small deletions and mild clinical picture. A cytogenetic and clinical variability must be underlined. Cardiac, cerebral, renal and gastrointestinal malformations were more frequent in the patients with unbalanced translocations resulting in 5p deletions. Sucking and feeding difficulties and respiratory infections are frequent in the first months or years of life. Intubation difficulties linked to larynx anomalies must be considered. Psychomotor development is delayed in all patients but there is a variability related to deletion size and type as well as other genetic and environmental factors. However, the results showed an improvement in the acquisition of the development skills and progress in social introduction which should encourage caregivers and parents to work together in carrying out the rehabilitative and educational interventions.