Bed rest impairs the vestibular control of balance.

Prolonged bed rest impairs standing balance but the underlying mechanisms are uncertain. Previous research suggests strength loss is not the cause, leaving impaired sensorimotor control as an alternative. Here we examine vestibular control of posture in 18 male volunteers before and after 60 days of bed rest. Stochastic vestibular stimulation (SVS) was used to evoke sway responses before, 1 and 6 days after bed rest under different head yaw orientations. The directional accuracy and precision of these responses were calculated from ground reaction force vectors. Bed rest caused up to 63% increases in spontaneous standing sway and 31% reductions in leg strength, changes which were uncorrelated. The increase in sway was exacerbated when the eyes were closed. Mean directions of SVS-evoked sway responses were unaffected, being directed towards the anodal ear and rotating in line with head orientation in the same way before and after bed rest. However, individual trial analysis revealed 25%-30% increases in directional variability, which were significantly correlated with the increase in spontaneous sway (r = 0.48-0.71; P ≤ 0.044) and were still elevated on day 6 post-bed rest. This reveals that individual sway responses may be inappropriately oriented, a finding masked by the averaging process. Our results confirm that impaired balance following prolonged bedrest is not related to loss of strength. Rather, they demonstrate that the sensorimotor transformation process which converts vestibular feedback into appropriately directed balance responses is impaired. KEY POINTS: Prolonged inactivity impairs balance but previous research suggests this is not caused by loss of strength. Here we investigated vestibular control of balance before and after 60 days of bed rest using electrical vestibular stimulation (EVS) to evoke sway responses. Spontaneous sway significantly increased and muscle strength reduced following bed rest, but, in keeping with previous research, these two effects were not correlated. While the overall accuracy of EVS-evoked sway responses was unaffected, their directional variability significantly increased following bed rest, and this was correlated with the increases in spontaneous sway. We have shown that the ability to transform head-centred vestibular feedback into an appropriately directed body sway response is negatively affected by prolonged inactivity; this may contribute to the impaired balance commonly observed following bed rest.

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.

Altered visual and haptic verticality perception in posterior cortical atrophy and Alzheimer's disease.

There is increasing theoretical and empirical support for the brain combining multisensory information to determine the direction of gravity and hence uprightness. A fundamental part of the process is the spatial transformation of sensory signals between reference frames: eye-centred, head-centred, body-centred, etc. The question 'Am I the right way up?' posed by a patient with posterior cortical atrophy (PCA) suggests disturbances in upright perception, subsequently investigated in PCA and typical Alzheimer's disease (tAD) based on what looks or feels upright. Participants repeatedly aligned to vertical a rod presented either visually (visual-vertical) or haptically (haptic-vertical). Visual-vertical involved orienting a projected rod presented without or with a visual orientation cue (circle, tilted square (±18°)). Haptic-vertical involved orientating a grasped rod with eyes closed using a combination of side (left, right) and hand (unimanual, bimanual) configurations. Intraindividual uncertainty and bias defined verticality perception. Uncertainty was consistently greater in both patient groups than in control groups, and greater in PCA than tAD. Bias in the frontal plane was strongly directionally affected by visual cue tilt (visual-vertical) and grip side (haptic-vertical). A model was developed that assumed verticality information from multiple sources is combined in a statistically optimal way to produce observed uncertainties and biases. Model results suggest the mechanism that spatially transforms graviceptive information between body parts is disturbed in both patient groups. Despite visual dysfunction being typically considered the primary feature of PCA, disturbances were greater in PCA than tAD particularly for haptic-vertical, and are considered in light of posterior parietal vulnerability. KEY POINTS: The perception of upright requires accurate and precise estimates of orientation based on multiple noisy sensory signals. The question 'Am I the right way up?' posed by a patient with posterior cortical atrophy (PCA; purported 'visual variant Alzheimer's') suggests disturbances in the perception of upright. What looks or feels upright in PCA and typical Alzheimer's disease (tAD) was investigated by asking participants to repeatedly align to vertical a rod presented visually (visual-vertical) or haptically (haptic-vertical). PCA and tAD groups exhibited not only greater perceptual uncertainty than controls, but also exaggerated bias induced by tilted visual orientation cues (visual-vertical) and grip side (haptic-vertical). When modelled, these abnormalities, which were particularly evident in PCA haptic-vertical performance, were compatible with disruption of a mechanism that spatially transforms verticality information between body parts. The findings suggest an important role of posterior parietal cortex in verticality perception, and have implications for understanding spatial disorientation in dementia.

Stepping in circles: how locomotor signals of rotation adapt over time.

KEY POINTS: While it has been well described that prolonged rotational stepping will adapt the podokinetic sense of rotation, the mechanisms involved are not clearly understood. By studying podokinetic after-rotations following conditioning rotations not previously reported we have shown that slower rotational velocities are more readily adapted than faster velocities and adaptation occurs more quickly than previously thought. We propose a dynamic feedback model of vestibular and podokinetic adaptation that can fit rotation trajectories across multiple conditions and data sets. Two adaptation processes were identified that may reflect central and peripheral processes and the discussion unifies prior findings in the podokinetic literature under this new framework. The findings show the technique is feasible for people with locomotor turning problems. ABSTRACT: After a prolonged period stepping in circles, people walk with a curved trajectory when attempting to walk in a straight line without vision. Podokinetic adaptation shows promise in clinical populations to improve locomotor turning; however, the adaptive mechanisms involved are poorly understood. The first phase of this study asks: how does the podokinetic conditioning velocity affect the response velocity and how quickly can adaptation occur? The second phase of the study asks: can a mathematical feedback model account for the rotation trajectories across different conditioning parameters and different datasets? Twelve healthy participants stepped in place on the axis of a rotating surface ranging from 4 to 20 deg s-1 for durations of 1-10 min, while using visual cues to maintain a constant heading direction. Afterward on solid ground, participants were blindfolded and attempted to step without rotating. Participants unknowingly stepped in circles opposite to the direction of the prior platform rotation for all conditions. The angular velocity of this response peaked within 1 min and the ratio of the stimulus-to-response peak velocity fitted a decreasing power function. The response then decayed exponentially. The feedback model of podokinetic and vestibular adaptive processes had a good fit with the data and suggested that podokinetic adaptation is explained by a short (141 s) and a long (27 min) time constant. The podokinetic system adapts more quickly than previously thought and subjects adapt more readily to slower rotation than to faster rotation. These findings will have implications for clinical applications of the technique.

Visual field motion during a body pull affects compensatory standing and stepping responses.

KEY POINTS: It is unclear whether the visual input that accompanies a perturbation of a standing person can affect whether a recovery step is taken. Visual motion speeds were manipulated during unexpected forward and backward shoulder pulls. Visual motion that appeared slower than actual body motion reduced the initial in-place resistance to the perturbation. As a result of the modulation of the in-place response, less pull force was needed to trigger a step when visual velocity appeared slower than normal. The visuomotor postural response occurred earlier and was larger when the full-field visual input was paired with a mechanical perturbation. ABSTRACT: The present study aimed to determine how visual motion evoked by an upper body perturbation during standing affects compensatory postural responses. This was investigated by rotating the visual field forwards or backwards about the ankle, time-locked to a forwards or backwards shoulder pull. Kinematic, kinetic and electromyographic responses were recorded to a range of pull forces over 160 trials in 12 healthy adults (mean ± SD = 31 ± 5.8 years). Stepping threshold forces and in-place postural responses were compared between conditions. When the visual field moved in the same direction as the pull, so that the apparent velocity of the body was reduced (SLOW condition), the pull-force required to induce a step was less than when the visual field either rotated in the opposite direction (FAST) or was unaltered (NATURAL). For in-place responses, the body was displaced further in the direction of the pull in the SLOW condition. This was the result of a reduction in the resistive force from lower leg muscles 130 ms after the visual motion onset. In trials with no pull, the visual motion induced postural responses that were later (290 ms) and had smaller amplitudes compared to when visual motion is paired with an unexpected perturbation of the body. The results suggest that the apparent speed of the visual environment during a perturbation does influence whether a compensatory step is taken, not via a direct effect on the decision to step but by modulating the initial in-place response.

Variance based weighting of multisensory head rotation signals for verticality perception.

We tested the hypothesis that the brain uses a variance-based weighting of multisensory cues to estimate head rotation to perceive which way is up. The hypothesis predicts that the known bias in perceived vertical, which occurs when the visual environment is rotated in a vertical-plane, will be reduced by the addition of visual noise. Ten healthy participants sat head-fixed in front of a vertical screen presenting an annulus filled with coloured dots, which could rotate clockwise or counter-clockwise at six angular velocities (1, 2, 4, 6, 8, 16°/s) and with six levels of noise (0, 25, 50, 60, 75, 80%). Participants were required to keep a central bar vertical by rotating a hand-held dial. Continuous adjustments of the bar were required to counteract low-amplitude low-frequency noise that was added to the bar's angular position. During visual rotation, the bias in verticality perception increased over time to reach an asymptotic value. Increases in visual rotation velocity significantly increased this bias, while the addition of visual noise significantly reduced it, but did not affect perception of visual rotation velocity. The biasing phenomena were reproduced by a model that uses a multisensory variance-weighted estimate of head rotation velocity combined with a gravito-inertial acceleration signal (GIA) from the vestibular otoliths. The time-dependent asymptotic behaviour depends on internal feedback loops that act to pull the brain's estimate of gravity direction towards the GIA signal. The model's prediction of our experimental data furthers our understanding of the neural processes underlying human verticality perception.

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.

Sensory trick efficacy in cervical dystonia is linked to processing of neck proprioception.

BACKGROUND: Muscle vibration activates muscle spindles and when applied over posterior neck muscles during stance modulates global body orientation. This is characterised by a tonic forward sway response that is reportedly diminished or absent in patients with idiopathic cervical dystonia. OBJECTIVE: To investigating the impact of the sensory trick on vibration-induced postural responses. METHODS: 20 patients with idiopathic cervical dystonia and a sensory trick, 15 patients without a trick, and 16 healthy controls were recruited. Neck muscle vibration was applied bilaterally over the upper trapezius under three different conditions: 1) Quiet standing; 2) standing while performing the trick (or trick-like movement in non-responders); 3) standing while elevating the flexed arm without touching any part of the body. Centre of pressure position and whole-body orientation in the sagittal plane were analysed. RESULTS: Patients with a sensory trick responded similarly to healthy controls: neck muscle vibration led to an initial forward sway of the body that slowly increased during the prolonged vibration for all three conditions. This response was mainly mediated by ankle flexion. In patients without a trick, the initial sagittal sway was significantly reduced in all three conditions and the later slow increase was absent. Performance of the trick did not have an effect on any aspect of the response in either cervical dystonia group. CONCLUSIONS: The whole-body response to neck vibration in cervical dystonia differs depending on the effectiveness of the sensory trick to alleviate the dystonic neck posture. Variable pathophysiology of proprioceptive processing may be the common factor.

Cerebellar Degeneration Increases Visual Influence on Dynamic Estimates of Verticality.

Our perception of verticality relies on combining sensory information from multiple sources. Neuronal recordings in animals implicate the cerebellum in the process, yet disease of the human cerebellum was not found to affect this perception. Here we show that a perceptual disturbance of verticality is indeed present in people with a genetically determined and pure form of cerebellar degeneration (spinocerebellar ataxia type 6; SCA 6), but is only revealed under dynamic visual conditions. Participants were required to continuously orient a visually displayed bar to vertical while the bar angle was perturbed by a low-frequency random signal and a random dot pattern rotated in their visual periphery. The random dot pattern was rotated at one of two velocities (4°/s and 16°/s), traveling with either coherent or noisy motion. Perceived vertical was biased by visual rotation in healthy participants, particularly in a more elderly group, but SCA 6 participants were biased more than both groups. The bias was reduced by visual noise, but more so for SCA 6 participants than young controls. Distortion of verticality by visual rotation stems from the stimulus creating an illusion of self-rotation. We modeled this process using a maximum-likelihood sensory cue-combination model operating on noisy visual- and vestibular-rotation signals. The observed effects of visual rotation and visual noise could be compellingly explained by cerebellar degeneration, and to a lesser extent aging, causing an increase in central vestibular noise. This is consistent with the human cerebellum operating on dynamic vestibular signals to inform the process that estimates which way is up.

Voluntary steps and gait initiation.

This chapter explores mechanisms that control goal-directed steps for the purpose of reorienting the body or initiating gait. A key issue concerns the control of balance. We argue that standing balance is relinquished while the stepping foot is in the air thus allowing the body to fall under gravity. The falling body's trajectory is largely controlled by motor activity that occurs before the stepping foot leaves the ground (the throw), and is finely tuned to where and when the foot is planned to land (the catch). This close coupling between the throw and catch is paramount for achieving the stepping goal while simultaneously ensuring balance is regained at the end of the step. Nonetheless, there is some scope for making midstep adjustments by modifying the body's trajectory and/or the stepping leg's movement. The magnitude of midstep adjustment is severely limited by mechanical and balance constraints, but can occur at remarkably short latency in response to new visual information, possibly controlled by subcortical neural networks. We conclude that taking a step is a highly predictive and coordinated action that is vulnerable to errors leading to falls, particularly in the face of neural and muscular degeneration associated with aging or neurologic disease.

Dual processing of visual rotation for bipedal stance control.

KEY POINTS: When standing, the gain of the body-movement response to a sinusoidally moving visual scene has been shown to get smaller with faster stimuli, possibly through changes in the apportioning of visual flow to self-motion or environment motion. We investigated whether visual-flow speed similarly influences the postural response to a discrete, unidirectional rotation of the visual scene in the frontal plane. Contrary to expectation, the evoked postural response consisted of two sequential components with opposite relationships to visual motion speed. With faster visual rotation the early component became smaller, not through a change in gain but by changes in its temporal structure, while the later component grew larger. We propose that the early component arises from the balance control system minimising apparent self-motion, while the later component stems from the postural system realigning the body with gravity. ABSTRACT: The source of visual motion is inherently ambiguous such that movement of objects in the environment can evoke self-motion illusions and postural adjustments. Theoretically, the brain can mitigate this problem by combining visual signals with other types of information. A Bayesian model that achieves this was previously proposed and predicts a decreasing gain of postural response with increasing visual motion speed. Here we test this prediction for discrete, unidirectional, full-field visual rotations in the frontal plane of standing subjects. The speed (0.75-48 deg s(-1) ) and direction of visual rotation was pseudo-randomly varied and mediolateral responses were measured from displacements of the trunk and horizontal ground reaction forces. The behaviour evoked by this visual rotation was more complex than has hitherto been reported, consisting broadly of two consecutive components with respective latencies of ∼190 ms and >0.7 s. Both components were sensitive to visual rotation speed, but with diametrically opposite relationships. Thus, the early component decreased with faster visual rotation, while the later component increased. Furthermore, the decrease in size of the early component was not achieved by a simple attenuation of gain, but by a change in its temporal structure. We conclude that the two components represent expressions of different motor functions, both pertinent to the control of bipedal stance. We propose that the early response stems from the balance control system attempting to minimise unintended body motion, while the later response arises from the postural control system attempting to align the body with gravity.

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.

The Throw-and-Catch Model of Human Gait: Evidence from Coupling of Pre-Step Postural Activity and Step Location.

Postural activity normally precedes the lift of a foot from the ground when taking a step, but its function is unclear. The throw-and-catch hypothesis of human gait proposes that the pre-step activity is organized to generate momentum for the body to fall ballistically along a specific trajectory during the step. The trajectory is appropriate for the stepping foot to land at its intended location while at the same time being optimally placed to catch the body and regain balance. The hypothesis therefore predicts a strong coupling between the pre-step activity and step location. Here we examine this coupling when stepping to visually-presented targets at different locations. Ten healthy, young subjects were instructed to step as accurately as possible onto targets placed in five locations that required either different step directions or different step lengths. In 75% of trials, the target location remained constant throughout the step. In the remaining 25% of trials, the intended step location was changed by making the target jump to a new location 96 ms ± 43 ms after initiation of the pre-step activity, long before foot lift. As predicted by the throw-and-catch hypothesis, when the target location remained constant, the pre-step activity led to body momentum at foot lift that was coupled to the intended step location. When the target location jumped, the pre-step activity was adjusted (median latency 223 ms) and prolonged (on average by 69 ms), which altered the body's momentum at foot lift according to where the target had moved. We conclude that whenever possible the coupling between the pre-step activity and the step location is maintained. This provides further support for the throw-and-catch hypothesis of human gait.

Effect of head pitch and roll orientations on magnetically induced vertigo.

KEY POINTS: Lying supine in a strong magnetic field, such as in magnetic resonance imaging scanners, can induce a perception of whole-body rotation. The leading hypothesis to explain this invokes a Lorentz force mechanism acting on vestibular endolymph that acts to stimulate semicircular canals. The hypothesis predicts that the perception of whole-body rotation will depend on head orientation in the field. Results showed that the direction and magnitude of apparent whole-body rotation while stationary in a 7 T magnetic field is influenced by head orientation. The data are compatible with the Lorentz force hypothesis of magnetic vestibular stimulation and furthermore demonstrate the operation of a spatial transformation process from head-referenced vestibular signals to Earth-referenced body motion. ABSTRACT: High strength static magnetic fields are known to induce vertigo, believed to be via stimulation of the vestibular system. The leading hypothesis (Lorentz forces) predicts that the induced vertigo should depend on the orientation of the magnetic field relative to the head. In this study we examined the effect of static head pitch (-80 to +40 deg; 12 participants) and roll (-40 to +40 deg; 11 participants) on qualitative and quantitative aspects of vertigo experienced in the dark by healthy humans when exposed to the static uniform magnetic field inside a 7 T MRI scanner. Three participants were additionally examined at 180 deg pitch and roll orientations. The effect of roll orientation on horizontal and vertical nystagmus was also measured and was found to affect only the vertical component. Vertigo was most discomforting when head pitch was around 60 deg extension and was mildest when it was around 20 deg flexion. Quantitative analysis of vertigo focused on the induced perception of horizontal-plane rotation reported online with the aid of hand-held switches. Head orientation had effects on both the magnitude and the direction of this perceived rotation. The data suggest sinusoidal relationships between head orientation and perception with spatial periods of 180 deg for pitch and 360 deg for roll, which we explain is consistent with the Lorentz force hypothesis. The effects of head pitch on vertigo and previously reported nystagmus are consistent with both effects being driven by a common vestibular signal. To explain all the observed effects, this common signal requires contributions from multiple semicircular canals.

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.

Sensorimotor processing for balance in spinocerebellar ataxia type 6.

BACKGROUND: We investigated whether balance impairments caused by cerebellar disease are associated with specific sensorimotor processing deficits that generalize across all sensory modalities. Experiments focused on the putative cerebellar functions of scaling and coordinate transformation of balance responses evoked by stimulation of single sensory channels. METHODS: Vestibular, visual, and proprioceptive sensory channels were stimulated in isolation using galvanic vestibular stimulation, moving visual scenery, and muscle vibration, respectively, in 16 subjects with spinocerebellar ataxia type 6 (SCA6) and 16 matched healthy controls. Two polarities of each stimulus type evoked postural responses of similar form in the forward and backward directions. Disease severity was assessed using the Scale for Assessment and Rating of Ataxia. RESULTS: Impaired balance of SCA6 subjects during unperturbed stance was reflected in faster than normal body sway (P = 0.009), which correlated with disease severity (r = 0.705, P < 0.001). Sensory perturbations revealed a sensorimotor processing abnormality that was specific to response scaling for the visual channel. This manifested as visually evoked postural responses that were approximately three times larger than normal (backward, P < 0.001; forward P = 0.005) and correlated with disease severity (r = 0.543, P = 0.03). Response direction and habituation properties were no different from controls for all three sensory modalities. CONCLUSION: Cerebellar degeneration disturbs the scaling of postural responses evoked by visual motion, possibly through disinhibition of extracerebellar visuomotor centers. The excessively high gain of the visuomotor channel without compensatory decreases in gains of other sensorimotor channels provides a potential mechanism for instability of the balance control system in cerebellar disease.

Training balance with opto-kinetic stimuli in the home: a randomized controlled feasibility study in people with pure cerebellar disease.

OBJECTIVE: To investigate the feasibility of a randomized controlled trial of a home-based balance intervention for people with cerebellar ataxia. DESIGN: A randomized controlled trial design. SETTING: Intervention and assessment took place in the home environment. PARTICIPANTS: A total of 12 people with spinocerebellar ataxia type 6 were randomized into a therapy or control group. Both groups received identical assessments at baseline, four and eight weeks. INTERVENTIONS: Therapy group participants undertook balance exercises in front of optokinetic stimuli during weeks 4-8, while control group participants received no intervention. MAIN MEASURES: Test-retest reliability was analysed from outcome measures collected twice at baseline and four weeks later. Feasibility issues were evaluated using daily diaries and end trial exit interviews. RESULTS: The home-based training intervention with opto-kinetic stimuli was feasible for people with pure ataxia, with one drop-out. Test-retest reliability is strong (intraclass correlation coefficient >0.7) for selected outcome measures evaluating balance at impairment and activity levels. Some measures reveal trends towards improvement for those in the therapy group. Sample size estimations indicate that Bal-SARA scores could detect a clinically significant change of 0.8 points in this functional balance score if 80 people per group were analysed in future trials. CONCLUSIONS: Home-based targeted training of functional balance for people with pure cerebellar ataxia is feasible and the outcome measures employed are reliable.