Computerised patient-specific prediction of the recovery profile of upper limb capacity within stroke services: the next step.

INTRODUCTION: Predicting upper limb capacity recovery is important to set treatment goals, select therapies and plan discharge. We introduce a prediction model of the patient-specific profile of upper limb capacity recovery up to 6 months poststroke by incorporating all serially assessed clinical information from patients. METHODS: Model input was recovery profile of 450 patients with a first-ever ischaemic hemispheric stroke measured using the Action Research Arm Test (ARAT). Subjects received at least three assessment sessions, starting within the first week until 6 months poststroke. We developed mixed-effects models that are able to deal with one or multiple measurements per subject, measured at non-fixed time points. The prediction accuracy of the different models was established by a fivefold cross-validation procedure. RESULTS: A model with only ARAT time course, finger extension and shoulder abduction performed as good as models with more covariates. For the final model, cross-validation prediction errors at 6 months poststroke decreased as the number of measurements per subject increased, from a median error of 8.4 points on the ARAT (Q1-Q3:1.7-28.1) when one measurement early poststroke was used, to 2.3 (Q1-Q3:1-7.2) for seven measurements. An online version of the recovery model was developed that can be linked to data acquisition environments. CONCLUSION: Our innovative dynamic model can predict real-time, patient-specific upper limb capacity recovery profiles up to 6 months poststroke. The model can use all available serially assessed data in a flexible way, creating a prediction at any desired moment poststroke, stand-alone or linked with an electronic health record system.

The association between freezing of gait, fear of falling and anxiety in Parkinson's disease: a longitudinal analysis.

Aim: We studied the longitudinal associations between freezing of gait (FoG), fear of falling (FoF) and anxiety, and how these associations are influenced by confounding factors. Materials & methods: We analyzed longitudinal motor and nonmotor measurements from 153 Parkinson's disease patients. Possible confounding factors were divided into three subgroups: demographics, disease characteristics, medication use and adverse effects of medication. Results: All crude associations between FoG, FoF and anxiety were significant and remained so after adjusting for confounders. When analyzing FoF and anxiety together as independent variables, the association between FoG and FoF remained, and the association between FoG and anxiety diminished. Conclusion: We confirm the complex interactions between motor and nonmotor symptoms in Parkinson's disease, and plead for a multidisciplinary approach.

The effect of cerebellar transcranial direct current stimulation to improve standing balance performance early post-stroke, study protocol of a randomized controlled trial.

RATIONALE: Restoration of adequate standing balance after stroke is of major importance for functional recovery. POstural feedback ThErapy combined with Non-invasive TranscranIAL direct current stimulation (tDCS) in patients with stroke (POTENTIAL) aims to establish if cerebellar tDCS has added value in improving standing balance performance early post-stroke. METHODS: Forty-six patients with a first-ever ischemic stroke will be enrolled in this double-blind controlled trial within five weeks post-stroke. All patients will receive 15 sessions of virtual reality-based postural feedback training (VR-PFT) in addition to usual care. VR-PFT will be given five days per week for 1 h, starting within five weeks post-stroke. During VR-PFT, 23 patients will receive 25 min of cerebellar anodal tDCS (cb_tDCS), and 23 patients will receive sham stimulation. STUDY OUTCOME: Clinical, posturographic, and neurophysiological measurements will be performed at baseline, directly post-intervention, two weeks post-intervention and at 15 weeks post-stroke. The primary outcome measure will be the Berg Balance Scale (BBS) for which a clinical meaningful difference of six points needs to be established between the intervention and control group at 15 weeks post-stroke. DISCUSSION: POTENTIAL will be the first proof-of-concept randomized controlled trial to assess the effects of VR-PFT combined with cerebellar tDCS in terms of standing balance performance in patients early post-stroke. Due to the combined clinical, posturographical and neurophysiological measurements, this trial may give more insights in underlying post-stroke recovery processes and whether these can be influenced by tDCS.

Respiratory muscle training for multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic disease of the central nervous system, affecting approximately 2.5 million people worldwide. People with MS may experience limitations in muscular strength and endurance - including the respiratory muscles, affecting functional performance and exercise capacity. Respiratory muscle weakness can also lead to diminished performance on coughing, which may result in (aspiration) pneumonia or even acute ventilatory failure, complications that frequently cause death in MS. Training of the respiratory muscles might improve respiratory function and cough efficacy. OBJECTIVES: To assess the effects of respiratory muscle training versus any other type of training or no training for respiratory muscle function, pulmonary function and clinical outcomes in people with MS. SEARCH METHODS: We searched the Trials Register of the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group (3 February 2017), which contains trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, LILACS and the trial registry databases ClinicalTrials.gov and WHO International Clinical Trials Registry Platform. Two authors independently screened records yielded by the search, handsearched reference lists of review articles and primary studies, checked trial registers for protocols, and contacted experts in the field to identify further published or unpublished trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that investigated the efficacy of respiratory muscle training versus any control in people with MS. DATA COLLECTION AND ANALYSIS: One reviewer extracted study characteristics and study data from included RCTs, and two other reviewers independently cross-checked all extracted data. Two review authors independently assessed risk of bias with the Cochrane 'Risk of bias' assessment tool. When at least two RCTs provided data for the same type of outcome, we performed meta-analyses. We assessed the certainty of the evidence according to the GRADE approach. MAIN RESULTS: We included six RCTs, comprising 195 participants with MS. Two RCTs investigated inspiratory muscle training with a threshold device; three RCTs, expiratory muscle training with a threshold device; and one RCT, regular breathing exercises. Eighteen participants (˜ 10%) dropped out; trials reported no serious adverse events.We pooled and analyzed data of 5 trials (N=137) for both inspiratory and expiratory muscle training, using a fixed-effect model for all but one outcome. Compared to no active control, meta-analysis showed that inspiratory muscle training resulted in no significant difference in maximal inspiratory pressure (mean difference (MD) 6.50 cmH2O, 95% confidence interval (CI) -7.39 to 20.38, P = 0.36, I2 = 0%) or maximal expiratory pressure (MD -8.22 cmH2O, 95% CI -26.20 to 9.77, P = 0.37, I2 = 0%), but there was a significant benefit on the predicted maximal inspiratory pressure (MD 20.92 cmH2O, 95% CI 6.03 to 35.81, P = 0.006, I2 = 18%). Meta-analysis with a random-effects model failed to show a significant difference in predicted maximal expiratory pressure (MD 5.86 cmH2O, 95% CI -10.63 to 22.35, P = 0.49, I2 = 55%). These studies did not report outcomes for health-related quality of life.Three RCTS compared expiratory muscle training versus no active control or sham training. Under a fixed-effect model, meta-analysis failed to show a significant difference between groups with regard to maximal expiratory pressure (MD 8.33 cmH2O, 95% CI -0.93 to 17.59, P = 0.18, I2 = 42%) or maximal inspiratory pressure (MD 3.54 cmH2O, 95% CI -5.04 to 12.12, P = 0.42, I2 = 41%). One trial assessed quality of life, finding no differences between groups.For all predetermined secondary outcomes, such as forced expiratory volume, forced vital capacity and peak flow pooling was not possible. However, two trials on inspiratory muscle training assessed fatigue using the Fatigue Severity Scale (range of scores 0-56 ), finding no difference between groups (MD, -0.28 points, 95% CI-0.95 to 0.39, P = 0.42, I2 = 0%). Due to the low number of studies included, we could not perform cumulative meta-analysis or subgroup analyses. It was not possible to perform a meta-analysis for adverse events, no serious adverse were mentioned in any of the included trials.The quality of evidence was low for all outcomes because of limitations in design and implementation as well as imprecision of results. AUTHORS' CONCLUSIONS: This review provides low-quality evidence that resistive inspiratory muscle training with a resistive threshold device is moderately effective postintervention for improving predicted maximal inspiratory pressure in people with mild to moderate MS, whereas expiratory muscle training showed no significant effects. The sustainability of the favourable effect of inspiratory muscle training is unclear, as is the impact of the observed effects on quality of life.

Standardized measurement of sensorimotor recovery in stroke trials: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable.

Finding, testing and demonstrating efficacy of new treatments for stroke recovery is a multifaceted challenge. We believe that to advance the field, neurorehabilitation trials need a conceptually rigorous starting framework. An essential first step is to agree on definitions of sensorimotor recovery and on measures consistent with these definitions. Such standardization would allow pooling of participant data across studies and institutions aiding meta-analyses of completed trials, more detailed exploration of recovery profiles of our patients and the generation of new hypotheses. Here, we present the results of a consensus meeting about measurement standards and patient characteristics that we suggest should be collected in all future stroke recovery trials. Recommendations are made considering time post stroke and are aligned with the international classification of functioning and disability. A strong case is made for addition of kinematic and kinetic movement quantification. Further work is being undertaken by our group to form consensus on clinical predictors and pre-stroke clinical data that should be collected, as well as recommendations for additional outcome measurement tools. To improve stroke recovery trials, we urge the research community to consider adopting our recommendations in their trial design.

Caregiver-mediated exercises for improving outcomes after stroke.

BACKGROUND: Stroke is a major cause of long-term disability in adults. Several systematic reviews have shown that a higher intensity of training can lead to better functional outcomes after stroke. Currently, the resources in inpatient settings are not always sufficient and innovative methods are necessary to meet these recommendations without increasing healthcare costs. A resource efficient method to augment intensity of training could be to involve caregivers in exercise training. A caregiver-mediated exercise programme has the potential to improve outcomes in terms of body function, activities, and participation in people with stroke. In addition, caregivers are more actively involved in the rehabilitation process, which may increase feelings of empowerment with reduced levels of caregiver burden and could facilitate the transition from rehabilitation facility (in hospital, rehabilitation centre, or nursing home) to home setting. As a consequence, length of stay might be reduced and early supported discharge could be enhanced. OBJECTIVES: To determine if caregiver-mediated exercises (CME) improve functional ability and health-related quality of life in people with stroke, and to determine the effect on caregiver burden. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (October 2015), CENTRAL (the Cochrane Library, 2015, Issue 10), MEDLINE (1946 to October 2015), Embase (1980 to December 2015), CINAHL (1982 to December 2015), SPORTDiscus (1985 to December 2015), three additional databases (two in October 2015, one in December 2015), and six additional trial registers (October 2015). We also screened reference lists of relevant publications and contacted authors in the field. SELECTION CRITERIA: Randomised controlled trials comparing CME to usual care, no intervention, or another intervention as long as it was not caregiver-mediated, aimed at improving motor function in people who have had a stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials. One review author extracted data, and assessed quality and risk of bias, and a second review author cross-checked these data and assessed quality. We determined the quality of the evidence using GRADE. The small number of included studies limited the pre-planned analyses. MAIN RESULTS: We included nine trials about CME, of which six trials with 333 patient-caregiver couples were included in the meta-analysis. The small number of studies, participants, and a variety of outcome measures rendered summarising and combining of data in meta-analysis difficult. In addition, in some studies, CME was the only intervention (CME-core), whereas in other studies, caregivers provided another, existing intervention, such as constraint-induced movement therapy. For trials in the latter category, it was difficult to separate the effects of CME from the effects of the other intervention.We found no significant effect of CME on basic ADL when pooling all trial data post intervention (4 studies; standardised mean difference (SMD) 0.21, 95% confidence interval (CI) -0.02 to 0.44; P = 0.07; moderate-quality evidence) or at follow-up (2 studies; mean difference (MD) 2.69, 95% CI -8.18 to 13.55; P = 0.63; low-quality evidence). In addition, we found no significant effects of CME on extended ADL at post intervention (two studies; SMD 0.07, 95% CI -0.21 to 0.35; P = 0.64; low-quality evidence) or at follow-up (2 studies; SMD 0.11, 95% CI -0.17 to 0.39; P = 0.45; low-quality evidence).Caregiver burden did not increase at the end of the intervention (2 studies; SMD -0.04, 95% CI -0.45 to 0.37; P = 0.86; moderate-quality evidence) or at follow-up (1 study; MD 0.60, 95% CI -0.71 to 1.91; P = 0.37; very low-quality evidence).At the end of intervention, CME significantly improved the secondary outcomes of standing balance (3 studies; SMD 0.53, 95% CI 0.19 to 0.87; P = 0.002; low-quality evidence) and quality of life (1 study; physical functioning: MD 12.40, 95% CI 1.67 to 23.13; P = 0.02; mobility: MD 18.20, 95% CI 7.54 to 28.86; P = 0.0008; general recovery: MD 15.10, 95% CI 8.44 to 21.76; P < 0.00001; very low-quality evidence). At follow-up, we found a significant effect in favour of CME for Six-Minute Walking Test distance (1 study; MD 109.50 m, 95% CI 17.12 to 201.88; P = 0.02; very low-quality evidence). We also found a significant effect in favour of the control group at the end of intervention, regarding performance time on the Wolf Motor Function test (2 studies; MD -1.72, 95% CI -2.23 to -1.21; P < 0.00001; low-quality evidence). We found no significant effects for the other secondary outcomes (i.e. PATIENT: motor impairment, upper limb function, mood, fatigue, length of stay and adverse events; caregiver: mood and quality of life).In contrast to the primary analysis, sensitivity analysis of CME-core showed a significant effect of CME on basic ADL post intervention (2 studies; MD 9.45, 95% CI 2.11 to 16.78; P = 0.01; moderate-quality evidence).The methodological quality of the included trials and variability in interventions (e.g. content, timing, and duration), affected the validity and generalisability of these observed results. AUTHORS' CONCLUSIONS: There is very low- to moderate-quality evidence that CME may be a valuable intervention to augment the pallet of therapeutic options for stroke rehabilitation. Included studies were small, heterogeneous, and some trials had an unclear or high risk of bias. Future high-quality research should determine whether CME interventions are (cost-)effective.

Interventions for fatigue in Parkinson's disease.

BACKGROUND: Factors contributing to subjective fatigue in people with idiopathic Parkinson's disease (PD) are not well known. This makes it difficult to manage fatigue effectively in PD. OBJECTIVES: To evaluate the effects of pharmacological and non-pharmacological interventions, compared to an inactive control intervention, on subjective fatigue in people with PD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE (via PubMed); Ovid EMBASE; EBSCO CINAHL; Ovid PsycINFO; PEDro; and the WHO International Clinical Trials Registry Platform Search Portal up to April 2015. References of included studies and identified review articles were screened for additional studies. There were no restrictions based on language, date of publication or study setting. SELECTION CRITERIA: Randomised controlled trials (RCTs) that report on subjective fatigue in people with PD. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data collection and risk of bias assessments. MAIN RESULTS: Eleven studies were eligible for this systematic review, with a total of 1817 people. Three studies included only people who experienced clinically relevant fatigue (Fatigue Severity Scale score ≥ 4 out of 7 or Multidimensional Fatigue Inventory total score > 48 out of 100), whereas all other studies did not select participants on the basis of experienced fatigue. Nine studies investigated the effects of medication (i.e. levodopa-carbidopa, memantine, rasagiline, caffeine, methylphenidate, modafinil or doxepin) on subjective fatigue. All studies were placebo controlled. There was insufficient evidence to determine the effect of doxepin on the impact of fatigue on activities in daily life (ADL) or fatigue severity (one study, N = 12, standardised mean difference (SMD) = -1.50, 95% confidence interval (CI) -2.84 to -0.15; low quality evidence). We found high quality evidence that rasagiline reduced or slowed down the progression of physical aspects of fatigue (one study, N = 1176, SMD = -0.27, 95% CI -0.39 to -0.16, I(2) = 0%). None of the other pharmacological interventions affected subjective fatigue in PD. With regard to adverse effects, only levodopa-carbidopa showed an increase for the risk of nausea (one study, N = 361, risk ratio (RR) = 1.85, 95% CI 1.05 to 3.27; high quality evidence). Two studies investigated the effect of exercise on fatigue compared with usual care. We found low quality evidence for the effect of exercise on reducing the impact of fatigue on ADL or fatigue severity (two studies, N = 57, SMD = -0.45, 95% CI -1.21 to 0.32, I(2) = 44%). AUTHORS' CONCLUSIONS: Based on the current evidence, no clear recommendations for the treatment of subjective fatigue in PD can be provided. Doxepin may reduce the impact of fatigue on ADL and fatigue severity; however, this finding has to be confirmed in high quality studies. Rasagiline may be effective in reducing levels of physical fatigue in PD. No evidence was found for the effectiveness of levodopa-carbidopa, memantine, caffeine, methylphenidate, modafinil or exercise. Studies are needed to investigate the effect of exercise intensity on exercise capacity and subjective fatigue. Future studies should focus on interventions that address the maladaptive behavioural or cognitive aspects of fatigue in people with PD. Characteristics, such as severity and nature of perceived fatigue and underlying mood disorders should be considered to identify responders and non-responders when studying interventions for fatigue. The development of a core-set of self-report fatigue questionnaires with established responsiveness and known minimal important difference values will facilitate the interpretation of change in fatigue scores.

Impact of fatigue on health-related quality of life in patients with Parkinson's disease: a prospective study.

OBJECTIVE: To investigate the longitudinal association between the impact of fatigue and health-related quality of life and to determine if potential confounders distorted this association. DESIGN: Baseline, 3-, 6- and 12-week assessments of a randomized clinical trial were used. SETTING: Outpatient rehabilitation centre. SUBJECTS: Patients with idiopathic Parkinson's disease. METHODS: Quality of life was assessed with the Parkinson's Disease Questionnaire-39 and the Multidimensional Fatigue Inventory was used to assess fatigue. Time-independent and time-dependent factors were investigated for their bivariate association with quality of life by applying random coefficient analysis. Candidate confounders were successively added to the longitudinal association model to determine if the relationship between quality of life and fatigue was distorted. A change beyond 15% of found regression coefficient of the Multidimensional Fatigue Inventory was considered significant. RESULTS: One hundred and fifty-three patients were included. Impact of fatigue was significantly associated with poorer quality of life (ß = 0.24, 95% confidence interval = 0.18 to 0.30). This association was significantly distorted by depression (30.0%) and anxiety (24.1%). No distortion was found for other factors. After controlling for confounders, fatigue remained significantly associated with quality of life (ß = 0.12, 95% confidence interval = 0.06 to 0.18, r (2) = 2.3%). CONCLUSIONS: Our results suggest that patients who experience fatigue tend to report lower levels of quality of life. However, this longitudinal relationship is confounded by depression and anxiety and suggests that the unique contribution of fatigue to overall quality of life is rather small.