A randomised double-blind, cross-over trial of 4-aminopyridine for downbeat nystagmus--effects on slowphase eye velocity, postural stability, locomotion and symptoms.

OBJECTIVE: The effects of 4-aminopyridine (4-AP) on downbeat nystagmus (DBN) were analysed in terms of slow-phase velocity (SPV), stance, locomotion, visual acuity (VA), patient satisfaction and side effects using standardised questionnaires. METHODS: Twenty-seven patients with DBN received 5 mg 4-AP four times a day or placebo for 3 days and 10 mg 4-AP four times a day or placebo for 4 days. Recordings were done before the first, 60 min after the first and 60 min after the last drug administration. RESULTS: SPV decreased from 2.42 deg/s at baseline to 1.38 deg/s with 5 mg 4-AP and to 2.03 deg/s with 10 mg 4-AP (p<0.05; post hoc: 5 mg 4-AP: p=0.04). The rate of responders was 57%. Increasing age correlated with a 4-AP-related decrease in SPV (p<0.05). Patients improved in the 'get-up-and-go test' with 4-AP (p<0.001; post hoc: 5 mg: p=0.025; 10 mg: p<0.001). Tandem-walk time (both p<0.01) and tandem-walk error (4-AP: p=0.054; placebo: p=0.059) improved under 4-AP and placebo. Posturography showed that some patients improved with the 5 mg 4-AP dose, particularly older patients. Near VA increased from 0.59 at baseline to 0.66 with 5 mg 4-AP (p<0.05). Patients with idiopathic DBN had the greatest benefit from 4-AP. There were no differences between 4-AP and placebo regarding patient satisfaction and side effects. CONCLUSIONS: 4-AP reduced SPV of DBN, improved near VA and some locomotor parameters. 4-AP is a useful medication for DBN syndrome, older patients in particular benefit from the effects of 5 mg 4-AP on nystagmus and postural stability.

Accessing escalators: a central vestibular disorder after posterior fossa tumor removal.

About 20% of childhood tumors originate within the central nervous system. Progress in assessment and treatment of these lesions has led to improved survival rates. We describe a patient with a posterior fossa ependymoma who despite a remarkable recovery following treatment has been frustrated by difficulty in using escalators. Such symptom selectivity is explained by specific vertical visuomotor and high-frequency vestibular deficits disrupting the execution of this complex motor act.

The effect of repeated visual motion stimuli on visual dependence and postural control in normal subjects.

Patients with vestibular dysfunction, migraine and/or anxiety may experience visual vertigo (VV), whereby symptoms are provoked by disorienting visual environments (e.g. supermarkets). Patients with VV over rely on vision for balance (i.e. visually dependent). Visual vertigo significantly improves when vestibular rehabilitation incorporates exposure to optokinetic stimulation (OKS). However, whether OKS exposure induces a reduction in visual dependency is unknown. This study investigated this issue by measuring visual dependency before and after repeated OKS exposure. Twenty-six healthy subjects (10 males; mean age 29.8 years, range 20-42 years) were randomly allocated into an OKS group who underwent graded OKS exposure for five consecutive days, or a no intervention control group. Assessment included the 'Rod and Frame' and 'Rod and Disc' tests where subjects set the subjective visual vertical in darkness, facing a tilted luminous frame or luminous rotating disc, respectively. Postural sway measures were obtained with eyes open, closed and facing the rotating disc. Results showed significant reductions in subjective vertical tilt with the frame and rotating disc for the OKS group only (p≤0.01). Total sway path and mean deviation induced by the rotating stimulus decreased significantly only for the OKS group (p<0.01), as did the Kinetic Quotient (disc rotation/eyes open sway path ratio; p=0.04). The Romberg Quotient (eyes closed/eyes open ratio) showed no change. Findings suggest visual dependency, both at a perceptual and a postural level, can be reduced with short-term graded OKS exposure in healthy subjects. This has important implications for treatment of patients with VV and balance disorders.

Adaptation of ventilation to 'buffeting' in vehicles.

OBJECTIVES: Short exposures to buffeting in a vehicle driving over rough terrain induce an increase in the frequency of respiration resulting in hyperpnoea and hypocapnia. The present study investigates the adaptation to buffeting-induced hyperpnoea. METHODS: We monitored ventilation and cardiovascular function in nine healthy young adults prior to, throughout and post a 30 minute simulation of buffeting. RESULTS: All subjects had a consistent elevation of respiratory frequency throughout motion. End-tidal CO(2) decreased during the first 5 minutes of buffeting due to a transient increase in minute ventilation. Elevation of respiratory frequency was facilitated by shortening of inspiration without change in expiratory time. Tidal volume was maintained which resulted in an increase in mean inspiratory flow during buffeting. At later stages of motion there was a partial return to normal for mean inspiratory flow, minute ventilation and end-tidal CO(2)because of a slight reduction in tidal volume whilst inspiratory time remained shortened. Salivary cortisol levels were unaffected by motion, suggesting that the hyperpnoea was not secondary to non-specific stress. INTERPRETATION: The cause of elevated respiratory frequency during buffeting could be due to mechanical action on the torso, vestibular-respiratory drive or a protective reinforcement of the torso.

Reduced self-motion perception in patients with midline cerebellar lesions.

Vestibular input to the cerebellum mediates balance and eye movement control. Recent functional MRI studies, however, show midline cerebellar activation during visually induced illusions of self-rotation, thus suggesting that the cerebellum may also contribute to self-motion perception. Here, we investigate self-motion perception directly in patients with vermal (or midline) cerebellar ataxia. Participants were rotated in the dark (90 degrees /s velocity steps) and the time constant of decay of the postrotational angular velocity sensation was measured. The perceptual vestibular time constant in patients was considerably reduced (7.8 s) with respect to control values in this (25.6 s) and several previous studies. In addition to the processing of vestibular signals for motor control, the cerebellar vermis is involved in vestibular processing of self-motion perception.

Influence of target size on vertical gaze palsy in a pathologically proven case of progressive supranuclear palsy.

We document a new oculomotor phenomenon in a patient with pathologically proven progressive supranuclear gaze palsy (PSP), namely that vertical gaze excursion improves with larger pursuit targets. We used computerised video-oculography during vertical smooth pursuit eye movements (SPEM) of circular targets of diameter 0.16 degrees and 16 degrees, sinusoidally oscillating at 0.08 Hz (peak-to-peak amplitude 49 degrees). Increasing target size improved vertical gaze excursion from 10 degrees to 25 degrees. There was no concomitant increase in slow phase eye velocity. The findings could be explained by a potentiation of the position control mechanism of pursuit by target size due to increased activation of brainstem pursuit-optokinetic pathways and to higher order attentional mechanisms. This observation may be useful in the clinical assessment of PSP patients with severe neck rigidity in whom the doll's head-eye manoeuvre cannot be performed by comparing the degree of vertical gaze palsy during smooth pursuit testing between at least two differently sized targets and observing whether there is a larger excursion in response to a large target such as a newspaper.

Effect of semicircular canal stimulation on the perception of the visual vertical.

UNLABELLED: The subjective visual vertical (SVV) is usually considered a measure of otolith function. Herewith we investigate the influence of semicircular canal (SCC) stimulation on the SVV by rotating normal subjects in yaw about an earth-vertical axis, with velocity steps of +/- 90 degrees /s, for 60 s. SVV was assessed by setting an illuminated line to perceived earth vertical in darkness, during a per- and postrotary period. Four head positions were tested: upright, 30 degrees backward (chin up) or forward, and approximately 40 degrees forward from upright. During head upright/backward conditions, a significant SVV tilt (P < 0.01) in the direction opposite to rotation was found that reversed during postrotary responses. The rotationally induced SVV tilt had a time constant of decay of approximately 30 s. Rotation with the head 30 degrees forward did not affect SVV, whereas the 40 degrees forward tilt caused a direction reversal of SVV responses compared with head upright/backward. Spearman correlation values (Rho) between individual SCC efficiencies in different head positions and mean SVV tilts were 0.79 for posterior, 0.34 for anterior, and - 0.80 for horizontal SCCs. Three-dimensional video-oculography showed that SVV and torsional eye position measurements were highly correlated (0.83) and in the direction opposite to the slow phase torsional vestibuloocular reflex. IN CONCLUSION: 1) during yaw axis rotation without reorientation of the head with respect to gravity, the SVV is influenced by SCC stimulation; 2) this effect is mediated by the vertical SCCs, particularly the posterior SCCs; 3) rotationally induced SVV changes are due to torsional ocular tilt; 4) SVV and ocular tilts occur in the "anticompensatory," fast phase direction of the torsional nystagmus; and 5) clinically, abnormal SVV tilts cannot be considered a specific indication of otolith system dysfunction.

Short-latency eye movements evoked by near-threshold galvanic vestibular stimulation.

To investigate whether the primary planes of eye and body responses to galvanic vestibular stimulation (GVS) are congruent, we have measured the binocular, three-dimensional eye movements (scleral coil technique) to bilateral bipolar GVS in six normal human subjects. Stimulation intensities were kept deliberately low in order to characterize the response to near-threshold intensities of stimulation (0.1-0.9 mA) that had been used previously to characterise body postural responses. Stimuli were applied for 4 s, but only the early responses that occurred within the initial 300 ms of turning the current on or off were measured. At intensities of 0.1-0.7 mA the 'on' response consisted almost exclusively of a torsional slow phase eye movement in which the top of the eyes rotated towards the anode. The latency of the torsional response was ca. 46 ms. A weak polarity-dependent disconjugate response was also observed in which the intorting eye elevated and the extorting eye depressed ('skew eye deviation'). When the current was turned off similar responses occurred in the reverse direction. Removal of the visual fixation light-emitting diode (LED) had no consistent effect on the short-latency ocular responses. The direction of the ocular response was similar to that of the postural response and is compatible with GVS inducing an apparent dynamic roll-tilt of the head towards the cathode. However, weak horizontal eye movements, which became more prominent as the stimulus intensity was increased to 0.9 mA, were also observed. This suggests that an additional weak rotational component about the yaw axis, or a component of lateral translation in the frontal plane, is contained in the GVS-evoked signal. The overall pattern of eye movement suggests that semicircular canal afferents contribute to these low-intensity GVS responses.