The neural correlates of upper limb motor blocks in Parkinson's disease and their relation to freezing of gait.

Due to basal ganglia dysfunction, bimanual motor performance in Parkinson patients reportedly relies on compensatory brain activation in premotor-parietal-cerebellar circuitries. A subgroup of Parkinson's disease (PD) patients with freezing of gait (FOG) may exhibit greater bimanual impairments up to the point that motor blocks occur. This study investigated the neural mechanisms of upper limb motor blocks and explored their relation with FOG. Brain activation was measured using functional magnetic resonance imaging during bilateral finger movements in 16 PD with FOG, 16 without FOG (PD + FOG and PD - FOG), and 16 controls. During successful movement, PD + FOG showed decreased activation in right dorsolateral prefrontal cortex (PFC), left dorsal premotor cortex (PMd), as well as left M1 and bilaterally increased activation in dorsal putamen, pallidum, as well as subthalamic nucleus compared with PD - FOG and controls. On the contrary, upper limb motor blocks were associated with increased activation in right M1, PMd, supplementary motor area, and left PFC compared with successful movement, whereas bilateral pallidum and putamen activity was decreased. Complex striatofrontal activation changes may be involved in the difficulties of PD + FOG to perform bimanual movements, or sequential movements in general. These novel results suggest that, whatever the exact underlying cause, PD + FOG seem to have reached a saturation point of normal neural compensation and respond belatedly to actual movement breakdown.

Effects of deep brain stimulation of the subthalamic nucleus on freezing of gait in Parkinson's disease: a prospective controlled study.

BACKGROUND: Freezing of gait (FOG) is a debilitating gait disorder in Parkinson's disease (PD) with partial responsiveness to dopaminergic medication. To date, notions about the effects of subthalamic deep brain stimulation (STN-DBS) on FOG remain controversial. OBJECTIVES: To compare the effects of bilateral STN-DBS and continued best medical treatment (BMT) on FOG occurrence, FOG severity and clinical outcomes in PD patients at 6 and 12 months follow-up. METHODS: In this prospective, controlled study, 41 PD patients with at least 5 years disease duration participated. Twenty-four subjects (20 with FOG) were treated with STN-DBS and seventeen (15 with FOG) continued BMT. The primary outcome was the New Freezing of Gait Questionnaire (NFOGQ) at 6 months postsurgery. Other outcomes were the NFOGQ at 12 months and clinical outcomes (Unified Parkinson's Disease Rating Scale III (UPDRS III), timed gait, falls and quality of life) at both time points. RESULTS: STN-DBS increased the likelihood to convert from being a freezer to a non-freezer at 6 and 12 months follow-up (relative risk reduction=0.4). However, 45% of baseline freezers still experienced FOG 6 and 12 months postsurgery although with reduced severity. Three baseline non-freezers (1/2 BMT-treated, 2/4 STN-DBS-treated) developed FOG during follow-up. STN-DBS-induced benefits on FOG were mostly mediated by baseline levodopa equivalent dose, altered medication-intake and reduced motor fluctuations. CONCLUSIONS: In contrast to continued BMT, STN-DBS reduced FOG occurrence and severity at 6 months postsurgery with largely sustained effects at 12 months follow-up. Longer follow-up periods are needed to test whether FOG improvements after STN-DBS persist with disease progression.

Cognitive aspects of freezing of gait in Parkinson's disease: a challenge for rehabilitation.

Freezing of gait (FOG) is a very disabling symptom affecting up to half of the patients with Parkinson's disease (PD). Evidence is accumulating that FOG is caused by a complex interplay between motor, cognitive and affective factors, rather than being a pure motor phenomenon. In the current paper, we review the evidence on the specific role of cognitive factors in FOG. Results from behavioral studies show that patients with FOG experience impairments in executive functioning and response selection which predict that motor learning may be compromised. Brain imaging studies strengthen the neural basis of a potential association between FOG and cognitive impairment, but do not clarify whether it is a primary or secondary determinant of FOG. A FOG-related reduction of cognitive resources implies that adaptation of rehabilitation interventions is indicated for patients with FOG to promote the consolidation of learning.

Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease.

OBJECTIVE: To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. METHODS: For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. RESULTS AND CONCLUSIONS: For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence.

'PDSAFE' - a multi-dimensional model of falls-rehabilitation for people with Parkinson's. A mixed methods analysis of therapists' delivery and experience.

OBJECTIVE: To explore the clinical reasoning of physiotherapists using PDSAFE; according to disease severity and their experiences of treatment delivery in a large fall-prevention trial for people with Parkinson's (PwP). DESIGN: A descriptive study of delivering PDSAFE. Semi-structured interviews explored therapists' experiences. SETTING: A two-group, home-based, multi-centred, single-blinded, randomised controlled trial showed no overall effect on fall reduction between groups but demonstrated a significant secondary effect relating to disease severity with benefits to balance, falls efficacy and near-falls for all. PARTICIPANTS: Physiotherapists with a background in neurology and older-person rehabilitation were trained in the delivery of PDSAFE INTERVENTION: A multi-dimensional, individually tailored and progressive, home-based programme. RESULTS: Fifteen physiotherapists contributed to the 2587 intervention sessions from the PDSAFE trial and six of those physiotherapists took part in the interviews. The personalised intervention was reflected in the range of strategies and exercises prescribed. Most commonly prescribed fall-avoidance strategies were 'Avoiding tripping', 'Turning' and 'Freezing Cues' and all possible combinations of balance and strength training within the programme were selected. PwP with greater disease severity were more likely to have received less challenging strategies, balance and strengthening exercises than those with lower disease severity. Therapists considered the focus on fall events and fall avoidance strategies an improvement on 'impairment only' treatment. The presence of cognitive deficits, co-morbidities and dyskinesia were the most challenging aspects of delivering the intervention. CONCLUSION: Falls management for PwP is complex and compounded by the progressive nature of the condition. Physiotherapists both delivered and positively received PDSAFE. (248 words) The trial registration number is ISRCTN 48152791.

Everyday walking with Parkinson's disease: understanding personal challenges and strategies.

PURPOSE: This qualitative study was designed to explore the personal experience of everyday walking with Parkinson's disease (PD), the challenges and the strategies employed to compensate for difficulties, to help contextualise the scientific knowledge base. METHODS: Semi-structured interviews were undertaken with a sample of 20 people with idiopathic PD (12 male, 8 female; mean age 65 years (range 50 - 80); mean disease duration 10 years (range 2.5 - 26). Verbatim interview transcripts were analyzed thematically using NUD*IST N6 qualitative data analysis software. RESULTS: Walking was invariably performed as an integral part of a purposeful activity within a specific context, termed walking 'plus', with challenges encountered by people with PD in three main areas: Undertaking tasks; negotiating environments; and making transitions to walking. The two key strategies to compensate for difficulties experienced were monitoring through the use of concentration, and correcting through generating rhythm and size of steps. Carers supported monitoring and correcting. CONCLUSION: People with PD need to constantly assess and drive their walking performance. Attentional resources, which can themselves be compromised in PD, were used to accomplish what is normally a largely automatic activity. Personal accounts support scientific hypotheses. Rehabilitation interventions and measurements in PD need to reflect both the physical and psychosocial context of everyday walking.

The challenge of evaluating freezing of gait in patients with Parkinson's disease.

Freezing of gait (FOG) poses difficulties for measurement as it is highly sensitive to environmental triggers, cognitive input and medication. To ensure valid and reliable measurement of FOG, a combined methodology is recommended relying on tests of complex gait during the off-period together with a FOG-questionnaire, addressing severity and impact of freezing on daily life.

Balancing between the two: Are freezing of gait and postural instability in Parkinson's disease connected?

Postural instability and freezing of gait (FoG) are key features of Parkinson's disease (PD) closely related to falls. Growing evidence suggests that co-existing postural deficits could influence the occurrence and severity of FoG. To date, the exact nature of this interrelationship remains largely unknown. We analyzed the complex interaction between postural instability and gait disturbance by comparing the findings available in the posturographic literature between patients with and without FoG. Results showed that FoG and postural instability are intertwined, can influence each other behaviorally and may coincide neurologically. The most common FoG-related postural deficits included weight-shifting impairments, and inadequate scaling and timing of postural responses most apparent at forthcoming postural changes under time constraints. Most likely, a negative cycle of combined and more severe postural deficits in people with FoG will enhance postural stability breakdown. As such, the wide brain network deficiencies involved in FoG may also concurrently influence postural stability. Future work needs to examine whether training interventions targeting both symptoms will have extra clinical benefits on fall frequency.

Cueing training in the home improves gait-related mobility in Parkinson's disease: the RESCUE trial.

OBJECTIVES: Gait and mobility problems are difficult to treat in people with Parkinson's disease. The Rehabilitation in Parkinson's Disease: Strategies for Cueing (RESCUE) trial investigated the effects of a home physiotherapy programme based on rhythmical cueing on gait and gait-related activity. METHODS: A single-blind randomised crossover trial was set up, including 153 patients with Parkinson's disease aged between 41 and 80 years and in Hoehn and Yahr stage II-IV. Subjects allocated to early intervention (n = 76) received a 3-week home cueing programme using a prototype cueing device, followed by 3 weeks without training. Patients allocated to late intervention (n = 77) underwent the same intervention and control period in reverse order. After the initial 6 weeks, both groups had a 6-week follow-up without training. Posture and gait scores (PG scores) measured at 3, 6 and 12 weeks by blinded testers were the primary outcome measure. Secondary outcomes included specific measures on gait, freezing and balance, functional activities, quality of life and carer strain. RESULTS: Small but significant improvements were found after intervention of 4.2% on the PG scores (p = 0.005). Severity of freezing was reduced by 5.5% in freezers only (p = 0.007). Gait speed (p = 0.005), step length (p<0.001) and timed balance tests (p = 0.003) improved in the full cohort. Other than a greater confidence to carry out functional activities (Falls Efficacy Scale, p = 0.04), no carry-over effects were observed in functional and quality of life domains. Effects of intervention had reduced considerably at 6-week follow-up. CONCLUSIONS: Cueing training in the home has specific effects on gait, freezing and balance. The decline in effectiveness of intervention effects underscores the need for permanent cueing devices and follow-up treatment. Cueing training may be a useful therapeutic adjunct to the overall management of gait disturbance in Parkinson's disease.

The effect of rhythmic somatosensory cueing on gait in patients with Parkinson's disease.

BACKGROUND AND AIMS: Gait and gait related activities in patients with Parkinson's disease (PD) can be improved with rhythmic auditory cueing (e.g. a metronome). In the context of a large European study, a portable prototype cueing device was developed to provide an alternative for rhythmic auditory cueing: rhythmic somatosensory cueing (RSC, a miniature vibrating cylinder attached to the wrist). We investigated whether PD patients could adapt their walking pattern using RSC under conditions of changing walking speed and the presence of potentially distracting visual flow while walking on a treadmill. METHODS: A total of 17 patients with PD participated (mean age 63.4+/-10.3 years; Hoehn-Yahr score 2.5+/-0.9, mean Unified Parkinson's Disease Rating Scale score 49.8+/-13.7, mean disease duration 7.7+/-5.1 years). They performed systematic walking speed manipulations under 4 conditions in a random order: (1) no cue, no visual flow, (2) no cue, visual flow, (3) cue, no visual flow and (4) cue, visual flow. Visual flow in the form of a virtual corridor that moved at the current walking speed was projected on a 2 x 2 m rear-projection screen. The cueing rhythm was set at -10% of preferred stride frequency at each speed. Stride frequency was assessed using peaks in the trajectories of thigh sagittal plane segmental angles. RESULTS: Walking with RSC resulted in lower stride frequencies, and thus larger step lengths (p-values <0.05), regardless of walking speed. The presence of visual flow did not impair the use of RSC, as evidenced by the lack of differences between conditions 3 and 4 (p>0.05). CONCLUSION: Rhythmic somatosensory cueing may be a viable alternative for auditory cueing and is robust to changes in walking speed and visual distractors.

The effects of visual rhythms and optic flow on stride patterns of patients with Parkinson's disease.

This study was aimed at determining the effects of rhythmic visual cueing under changing visual conditions on stride frequency in patients with Parkinson's disease (PD; n = 21) and healthy age matched controls (n = 7) while walking at different speeds on a treadmill. Stride frequency and stride length in patients with PD as well as controls were not rigidly coupled to walking speed and could be manipulated with walking speed as well as by using spatial and temporal rhythmic visual cues.

The use of rhythmic auditory cues to influence gait in patients with Parkinson's disease, the differential effect for freezers and non-freezers, an explorative study.

PURPOSE: To study the effect of rhythmic auditory cues on gait in Parkinson's disease subjects with and without freezing and in controls. METHOD: A volunteer sample of 20 patients (10 freezers, 10 non-freezers) and 10 age-matched controls performed five randomized cued walking conditions in a gait-laboratory. Auditory cues were administered at baseline frequency, at an increased step frequency of 10 and 20% above baseline and at a decreased step frequency of 10 and 20% below baseline. Mean step frequency, walking speed, stride length and double support duration were collected. RESULTS: Rhythmical auditory cueing induced speed changes in all subjects. Stride length was not influenced by rhythmical auditory cues in controls, whereas patients showed a larger stride length in the -10% condition (p < 0.01). Freezers and non-freezers showed the same response to rhythmical auditory cues. Within group analysis for stride length showed different cueing effects. Stride length decreased at the +10% condition for freezers (p < 0.05), whereas it increased for non-freezers. CONCLUSIONS: This study points to fact that physiotherapists might need to carefully adjust the cueing frequency to the needs of patients with and without freezing. On the basis of the present results we recommend to lower the frequency setting for freezers, whereas for non-freezers an increase of up to +10% may have potential therapeutic use.

Dual-task-related neural connectivity changes in patients with Parkinson' disease.

BACKGROUND AND OBJECTIVES: Dual-task (DT) gait impairment in people with Parkinson's disease (PD) and specifically in those with freezing of gait (FOG), reflects attentional dependency of movement. This study aimed to elucidate resting-state brain connectivity alterations related to DT gait abnormalities in PD with and without FOG. METHODS: PD patients (n=73) and healthy age-matched controls (n=20) underwent DT gait analysis and resting-state functional Magnetic Resonance Imaging (rs-MRI) while 'off' medication. Patients were classified as freezer (n=13) or non-freezer (n=60). Functional connectivity (FC) alterations between PD and controls and between patient subgroups were assessed in regions of interest (ROIs) within the fronto-parietal and motor network. RESULTS: PD had longer stance times, shorter swing times and more step length asymmetry during DT gait and needed more time and steps during DT turning compared to controls. Additionally, freezers showed similar impairments and longer double support times compared to non-freezers during DT gait. PD demonstrated hyper-connectivity between the inferior parietal lobule and premotor cortex (PMC) and between the cerebellum and the PMC and M1. FOG-specific hypo-connectivity within the striatum and between the caudate and superior temporal lobe and hyper-connectivity between the dorsal putamen and precuneus was correlated with worse DT performance. CONCLUSION: PD showed FC alterations in DT-related networks, which were not correlated to DT performance. However, FOG-specific FC alterations in DT-related regions involving the precuneus and striatum were correlated to worse DT performance, suggesting that the balance between cognitive and motor networks is altered.

Center of mass trajectories during turning in patients with Parkinson's disease with and without freezing of gait.

BACKGROUND: Despite the strong relationship between freezing of gait (FOG) and turning in Parkinson's disease (PD), few studies have addressed specific postural characteristics during turning that might contribute to freezing. METHODS: Thirty participants with PD (16 freezers, 14 non-freezers) (all tested OFF medication) and 14 healthy controls walked 5 meters and turned 180° in a 3D gait laboratory. COM behavior was analyzed during four turning quadrants of 40° between 10° and 170° pelvic rotation and during 40° before actual FOG episodes. These pre-FOG segments were compared with similar turning sections in turns of freezers without FOG. Outcome parameters were turn time, COM distance, COM velocity, step width and the medial- and anterior COM position. RESULTS: Turn time was increased in freezers compared to non-freezers (p=.000). No differences were found regarding COM distance and velocity during turning quadrants between groups and between freezers' pre-FOG segments and similar turning segments without FOG. Medial COM deviation was reduced in PD patients compared to controls (p=.004), but no differences were found between freezers and non-freezers. In turns with freezing, turn time increased (p=.005) and step width decreased (p=.025) pre-FOG. Freezers also showed a less medial (p=.020) and more anterior (p=.016) COM position pre-FOG compared to turning sections without FOG. CONCLUSIONS: Our results revealed no subgroup differences in COM behavior during uninterrupted turning. However, we found a reduced medial deviation, a forward COM shift and a decreased step width in freezers just before FOG episodes. These abnormalities may play a causal role, as they could hamper stability and fluent weight shifting necessary for continued stepping during turning.

Measuring gait and gait-related activities in Parkinson's patients own home environment: a reliability, responsiveness and feasibility study.

The aim of this study was to assess reliability, responsiveness and feasibility of gait and gait related tests in the home of patients with Parkinson's disease (PD). The Unified Parkinson's Disease Rating Scale, a timed walking test, the Timed Get Up and Go test the Berg Balance Scale and the Functional Reach test were applied by three independent observers on 26 PD patients. Moderate to high Intraclass Correlation Coefficients were found, ranging from 0.74 to 0.88 and 0.64 to 0.87 for the intra- and inter-observer reliability, respectively. All test showed Reliable Change Indexes under 11% and the whole test battery was applicable within 30 min.

Discriminant ability of the Trunk Impairment Scale: A comparison between stroke patients and healthy individuals.

PURPOSE: The Trunk Impairment Scale (TIS) is a standardized scale to evaluate the trunk function in stroke patients. It was the aim of this study to determine the discriminant ability of the TIS by comparing stroke patients with healthy individuals. Further, the variables that had an influence on obtaining a high score on the TIS in healthy subjects were examined. METHOD: Forty stroke patients and 40 age- and sex-matched healthy individuals were included in the study. TIS scores from the stroke patients and healthy individuals were compared using the Wilcoxon ranked sum test. RESULTS: Sub-scale and total TIS scores showed significant differences between stroke patients and healthy individuals (P < 0.0001). Univariate analysis and logistic regression analysis further revealed that younger persons, women and people who are more active in daily life have a higher chance of obtaining a high score on the TIS. CONCLUSIONS: The TIS discriminates between stroke patients and healthy individuals. A submaximal score on the TIS was found in 45% of the healthy subjects suggesting that a lower score on the TIS still indicates normal trunk function and full participation in daily life.

Walking ability after implantation of a pallidal stimulator: analysis of plantar force distribution in patients with Parkinson's disease.

This preliminary study aimed to analyse the roll-off of the foot during gait before and after implantation of a unilateral pallidal electrode in severely affected patients with Parkinson's disease (PD). Five subjects were tested in a gait laboratory during the "on" phase of the medication cycle. Spatiotemporal variables demonstrated a pronounced increase of stride length and gait speed in three patients. Plantar force distribution and roll-off was considerably improved in one patient, which was not replicated in others. Gait analysis highlighted the variable effects found after surgery with a pallidal stimulator and might contribute to future studies into the effect of surgical procedures in PD.

Development of an activity scale for individuals with advanced Parkinson disease: reliability and "on-off" variability.

BACKGROUND AND PURPOSE: Functional mobility in people with advanced Parkinson disease, some of whom have a variable response to drug treatment, is often difficult to evaluate. The objectives of this study were to investigate the interrater reliability of measurements obtained with a scale designed to measure mobility and to determine the impact of self-rated dyskinesias and fluctuations on the measure. SSUBJECTS: Twenty-nine people with Parkinson disease and with disability and considerable disease duration (mean=11.7 years, SD=4.9, range=6-22) took part in the study. METHODS: The subjects' performance on a 10-item scale was videotaped. The videotapes were then scored by 2 independent raters, and the scores were used to determine interrater reliability. The stability of 6 repeated measurements was examined in the home situation, taking into account self-rated fluctuations of motor performance. RESULTS: Weighted Kappa values of agreement (.86-.98) confirmed the reliability between testers. Measurement during the "on" phase (when medication was working optimally) and the "off" phase (when the action of medication was strongly decreased or absent) led to different measurements. Measuring frequently within "on" and "off" phases gave relatively stable measurements for total function, bed transfers, and gait akinesia, the latter during the "off" phase only (intraclass correlation coefficients [ICCs]=.70-.93). However, more modest repeatability applied to transfers from a chair (ICC=.65-.67). CONCLUSION AND DISCUSSION: To ensure valid results in future effect studies, clinical differentiation between "on" and "off" phase measurements is proposed on the basis of patients' own perception of their medication status.