Maintaining balance against force perturbations: impaired mechanisms unresponsive to levodopa in Parkinson's disease.

There is evidence that postural instability associated with Parkinson's disease (PD) is not adequately improved by levodopa, implying involvement of nondopaminergic pathways. However, the mechanisms contributing to postural instability have yet to be fully identified and tested for their levodopa responsiveness. In this report we investigate balance processes that resist external forces to the body when standing. These include in-place responses and the transition to protective stepping. Forward and backward shoulder pulls were delivered using two force-feedback-controlled motors and were randomized for direction, magnitude, and onset. Sixteen patients with PD were tested OFF and ON levodopa, and 16 healthy controls were tested twice. Response behavior was quantified from 3-dimensional ground reaction forces and kinematic measurements of body segments and total body center-of-mass (CoM) motion. In-place responses resisting the pull were significantly smaller in PD as reflected in reduced horizontal anteroposterior ground reaction force and increased CoM displacement. Ankle, knee, and hip moments contributing to this resistance were smaller in PD, with the knee extensor moment to backward pulls being the most affected. The threshold force needed to evoke a step was also smaller for PD in the forward direction. Protective steps evoked by suprathreshold pulls showed deficits in PD in the backward direction, with steps being shorter and more steps being required to arrest the body. Levodopa administration had no significant effect on either in-place or protective stepping deficits. We conclude that processes employed to maintain balance in the face of external forces show impairment in PD consistent with disruption to nondopaminergic systems.

Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis.

Spinal neurodegeneration is an important determinant of disability progression in patients with primary progressive multiple sclerosis. Advanced imaging techniques, such as single-voxel (1)H-magnetic resonance spectroscopy and q-space imaging, have increased pathological specificity for neurodegeneration, but are challenging to implement in the spinal cord and have yet to be applied in early primary progressive multiple sclerosis. By combining these imaging techniques with new clinical measures, which reflect spinal cord pathology more closely than conventional clinical tests, we explored the potential for spinal magnetic resonance spectroscopy and q-space imaging to detect early spinal neurodegeneration that may be responsible for clinical disability. Data from 21 patients with primary progressive multiple sclerosis within 6 years of disease onset, and 24 control subjects were analysed. Patients were clinically assessed on grip strength, vibration perception thresholds and postural stability, in addition to the Expanded Disability Status Scale, Nine Hole Peg Test, Timed 25-Foot Walk Test, Multiple Sclerosis Walking Scale-12, and Modified Ashworth Scale. All subjects underwent magnetic resonance spectroscopy and q-space imaging of the cervical cord and conventional brain and spinal magnetic resonance imaging at 3 T. Multivariate analyses and multiple regression models were used to assess the differences in imaging measures between groups and the relationship between magnetic resonance imaging measures and clinical scores, correcting for age, gender, spinal cord cross-sectional area, brain T2 lesion volume, and brain white matter and grey matter volume fractions. Although patients did not show significant cord atrophy when compared with healthy controls, they had significantly lower total N-acetyl-aspartate (mean 4.01 versus 5.31 mmol/l, P = 0.020) and glutamate-glutamine (mean 4.65 versus 5.93 mmol/l, P = 0.043) than controls. Patients showed an increase in q-space imaging-derived indices of perpendicular diffusivity in both the whole cord and major columns compared with controls (P < 0.05 for all indices). Lower total N-acetyl-aspartate was associated with higher disability, as assessed by the Expanded Disability Status Scale (coefficient = -0.41, 0.01 < P < 0.05), Modified Ashworth Scale (coefficient = -3.78, 0.01 < P < 0.05), vibration perception thresholds (coefficient = -4.37, P = 0.021) and postural sway (P < 0.001). Lower glutamate-glutamine predicted increased postural sway (P = 0.017). Increased perpendicular diffusivity in the whole cord and columns was associated with increased scores on the Modified Ashworth Scale, vibration perception thresholds and postural sway (P < 0.05 in all cases). These imaging findings indicate reduced structural integrity of neurons, demyelination, and abnormalities in the glutamatergic pathways in the cervical cord of early primary progressive multiple sclerosis, in the absence of extensive spinal cord atrophy. The observed relationship between imaging measures and disability suggests that early spinal neurodegeneration may underlie clinical impairment, and should be targeted in future clinical trials with neuroprotective agents to prevent the development of progressive disability.

Ambulatory intracranial pressure in humans: ICP increases during movement between body positions.

Introduction: Positional changes in intracranial pressure (ICP) have been described in humans when measured over minutes or hours in a static posture, with ICP higher when lying supine than when sitting or standing upright. However, humans are often ambulant with frequent changes in position self-generated by active movement. Research question: We explored how ICP changes during movement between body positions. Material and methods: Sixty-two patients undergoing clinical ICP monitoring were recruited. Patients were relatively well, ambulatory and of mixed age, body habitus and pathology. We instructed patients to move back and forth between sitting and standing or lying and sitting positions at 20 s intervals after an initial 60s at rest. We simultaneously measured body position kinematics from inertial measurement units and ICP from an intraparenchymal probe at 100 Hz. Results: ICP increased transiently during movements beyond the level expected by body position alone. The amplitude of the increase varied between participants but was on average ∼5 mmHg during sit-to-stand, stand-to-sit and sit-to-lie movements and 10.8 mmHg [95%CI: 9.3,12.4] during lie-to-sit movements. The amplitude increased slightly with age, was greater in males, and increased with median 24-h ICP. For lie-to-sit and sit-to-lie movements, higher BMI was associated with greater mid-movement increase (ß = 0.99 [0.78,1.20]; ß = 0.49 [0.34,0.64], respectively). Discussion and conclusion: ICP increases during movement between body positions. The amplitude of the increase in ICP varies with type of movement, age, sex, and BMI. This could be a marker of disturbed ICP dynamics and may be particularly relevant for patients with CSF-diverting shunts in situ.

Chronic Subthalamic Nucleus Stimulation in Parkinson's Disease: Optimal Frequency for Gait Depends on Stimulation Site and Axial Symptoms.

Axial symptoms emerge in a significant proportion of patients with Parkinson's disease (PD) within 5 years of deep brain stimulation (STN-DBS). Lowering the stimulation frequency may reduce these symptoms. The objectives of the current study were to establish the relationship between gait performance and STN-DBS frequency in chronically stimulated patients with PD, and to identify factors underlying variability in this relationship. Twenty-four patients treated chronically with STN-DBS (>4 years) were studied off-medication. The effect of stimulation frequency (40-140 Hz, 20 Hz-steps, constant energy) on gait was assessed in 6 sessions spread over 1 day. Half of the trials/session involved walking through a narrow doorway. The influence of stimulation voltage was investigated separately in 10 patients. Gait was measured using 3D motion capture and axial symptoms severity was assessed clinically. A novel statistical method established the optimal frequency(ies) for each patient by operating on frequency-tuning curves for multiple gait parameters. Narrowly-tuned optimal frequencies (20 Hz bandwidth) were found in 79% of patients. Frequency change produced a larger effect on gait performance than voltage change. Optimal frequency varied between patients (between 60 and 140 Hz). Contact site in the right STN and severity of axial symptoms were independent predictors of optimal frequency (P = 0.009), with lower frequencies associated with more dorsal contacts and worse axial symptoms. We conclude that gait performance is sensitive to small changes in STN-DBS frequency. The optimal frequency varies considerably between patients and is associated with electrode contact site and severity of axial symptoms. Between-subject variability of optimal frequency may stem from variable pathology outside the basal ganglia.

Preventing falls in older adults: new interventions to promote more effective change-in-support balance reactions.

"Change-in-support" (CIS) balance-recovery reactions that involve rapid stepping or reaching movements play a critical role in preventing falls; however, age-related deficits in the neuro-musculoskeletal systems may impede ability to execute these reactions effectively. This review describes four new interventions aimed at reducing fall risk in older adults by promoting more effective CIS reactions: (1) balance training, (2) balance-enhancing footwear, (3) safer mobility aids, and (4) handrail cueing systems. The training program uses unpredictable support-surface perturbations to counter specific CIS control problems associated with aging and fall risk. Pilot testing has demonstrated that the program is well-tolerated by balance-impaired older adults, and a randomized controlled trial is now in progress. The balance-enhancing footwear insole improves control of stepping reactions by compensating for age-related loss of plantar cutaneous sensation. In a clinical trial, subjects wore the insole for 12 weeks with no serious problems and no habituation of the balance-enhancing benefits. The mobility-aid intervention involves changes to the design of pickup walkers so as to reduce impediments to lateral stepping. Finally, work is underway to investigate the effectiveness of handrail cueing in attracting attention to the rail and ensuring that the brain registers its location, thereby facilitating more rapid and accurate grasping.

Interventions to promote more effective balance-recovery reactions in industrial settings: new perspectives on footwear and handrails.

"Change-in-support" balance-recovery reactions that involve rapid stepping or reaching movements play a critical role in preventing falls. Recent geriatrics studies have led to new interventions to improve ability to execute these reactions effectively. Some of these interventions have the potential to reduce fall risk for younger persons working in industrial settings. In this paper, we review research pertaining to two such interventions: 1) balance-enhancing footwear insoles designed to improve stepping reactions, and 2) proximity-triggered handrail cueing systems designed to improve reach-to-grasp reactions. The insole has a raised ridge around the perimeter that is intended to improve balance control by providing increased stimulation of sensory receptors on the footsole in situations where loss of balance may be imminent. The cueing system uses flashing lights and/or verbal prompts to attract attention to the handrail and ensure that the brain registers its location, thereby facilitating more rapid and accurate grasping of the rail if and when sudden loss of balance occurs. Results to date support the efficacy of both interventions in geriatric populations. There is also some evidence that these interventions may improve balance control in younger persons; however, further research is needed to confirm their efficacy in preventing falls in industrial settings.

A perturbation-based balance training program for older adults: study protocol for a randomised controlled trial.

BACKGROUND: Previous research investigating exercise as a means of falls prevention in older adults has shown mixed results. Lack of specificity of the intervention may be an important factor contributing to negative results. Change-in-support (CIS) balance reactions, which involve very rapid stepping or grasping movements of the limbs, play a critical role in preventing falls; hence, a training program that improves ability to execute effective CIS reactions could potentially have a profound effect in reducing risk of falling. This paper describes: 1) the development of a perturbation-based balance training program that targets specific previously-reported age-related impairments in CIS reactions, and 2) a study protocol to evaluate the efficacy of this new training program. METHODS/DESIGN: The training program involves use of unpredictable, multi-directional moving-platform perturbations to evoke stepping and grasping reactions. Perturbation magnitude is gradually increased over the course of the 6-week program, and concurrent cognitive and movement tasks are included during later sessions. The program was developed in accordance with well-established principles of motor learning, such as individualisation, specificity, overload, adaptation-progression and variability. Specific goals are to reduce the frequency of multiple-step responses, reduce the frequency of collisions between the stepping foot and stance leg, and increase the speed of grasping reactions. A randomised control trial will be performed to evaluate the efficacy of the training program. A total of 30 community-dwelling older adults (age 64-80) with a recent history of instability or falling will be assigned to either the perturbation-based training or a control group (flexibility/relaxation training), using a stratified randomisation that controls for gender, age and baseline stepping/grasping performance. CIS reactions will be tested immediately before and after the six weeks of training, using platform perturbations as well as a distinctly different method of perturbation (waist pulls) in order to evaluate the generalisability of the training effects. DISCUSSION: This study will determine whether perturbation-based balance training can help to reverse specific age-related impairments in balance-recovery reactions. These results will help to guide the development of more effective falls prevention programs, which may ultimately lead to reduced health-care costs and enhanced mobility, independence and quality of life.

Does the "eyes lead the hand" principle apply to reach-to-grasp movements evoked by unexpected balance perturbations?

A fundamental principle that has emerged from studies of natural gaze behavior is that goal-directed arm movements are typically guided by a saccade to the target. In this study, we evaluated a hypothesis that this principle does not apply to rapid reach-to-grasp movements evoked by sudden unexpected balance perturbations. These perturbations involved forward translation of a large (2 × 6 m) motion platform configured to simulate a "real-life" environment. Subjects performed a common "daily-life" visuo-cognitive task (find a telephone and make a call) that required walking to the end of the platform, which was triggered to move as they approached a handrail mounted alongside the travel path. A deception was used to ensure that the perturbation was truly unexpected. Eleven of 18 healthy young-adult subjects (age 22-30) reached to grasp or touch the rail in response to the balance perturbation. In support of the hypothesis, none of these arm reactions was guided by concurrent visual fixation of the handrail. Seven of the 11 looked at the rail upon first entering the environment, and hence may have used "stored" central-field information about the handrail location to guide the subsequent arm reaction. However, the other four subjects never looked directly at the rail, indicating a complete reliance on peripheral vision. These findings add to previous evidence of distinctions in the CNS control of volitional and perturbation-evoked arm movements. Future studies will determine whether similar visuo-motor behavior occurs when the available handhold is smaller or when subjects are not engaged in a concurrent visuo-cognitive task.

Effect of a perturbation-based balance training program on compensatory stepping and grasping reactions in older adults: a randomized controlled trial.

BACKGROUND: Compensatory stepping and grasping reactions are prevalent responses to sudden loss of balance and play a critical role in preventing falls. The ability to execute these reactions effectively is impaired in older adults. OBJECTIVE: The purpose of this study was to evaluate a perturbation-based balance training program designed to target specific age-related impairments in compensatory stepping and grasping balance recovery reactions. DESIGN: This was a double-blind randomized controlled trial. SETTING: The study was conducted at research laboratories in a large urban hospital. PARTICIPANTS: Thirty community-dwelling older adults (aged 64-80 years) with a recent history of falls or self-reported instability participated in the study. INTERVENTION: Participants were randomly assigned to receive either a 6-week perturbation-based (motion platform) balance training program or a 6-week control program involving flexibility and relaxation training. MEASUREMENTS: Features of balance reactions targeted by the perturbation-based program were: (1) multi-step reactions, (2) extra lateral steps following anteroposterior perturbations, (3) foot collisions following lateral perturbations, and (4) time to complete grasping reactions. The reactions were evoked during testing by highly unpredictable surface translation and cable pull perturbations, both of which differed from the perturbations used during training. RESULTS: /b> Compared with the control program, the perturbation-based training led to greater reductions in frequency of multi-step reactions and foot collisions that were statistically significant for surface translations but not cable pulls. The perturbation group also showed significantly greater reduction in handrail contact time compared with the control group for cable pulls and a possible trend in this direction for surface translations. LIMITATIONS: Further work is needed to determine whether a maintenance program is needed to retain the training benefits and to assess whether these benefits reduce fall risk in daily life. CONCLUSION: Perturbation-based training shows promise as an effective intervention to improve the ability of older adults to prevent themselves from falling when they lose their balance.