Nadine Lehnen

Head Impulse Testing Using Video-oculography

Head impulses are a routine clinical test of semicircular canal function. At the bedside, they are used to detect malfunctioning of the horizontal semicircular canals. So far, 3‐D‐search‐coil recording is required to reliably test anterior and posterior canal function and to determine the gain of the vestibulo‐ocular reflex (VOR). Search‐coil recording cannot be done at the bedside. Here we tested whether video‐oculography (VOG) is suitable to assess VOR gain for individual canals at the bedside. We recorded head impulses in healthy subjects using a mobile high‐frame‐rate, head‐mounted VOG‐device and compared the results with those obtained with standard search‐coil recording. Our preliminary results indicate that high‐frame‐rate VOG is a promising tool to measure and quantify individual semicircular canal function not only at the bedside.

4-Aminopyridine improves downbeat nystagmus, smooth pursuit, and VOR gain

Downbeat nystagmus (DBN), the most frequent form of acquired persisting fixation nystagmus, is hypothesized to occur when physiologic, inhibitory cerebellar input to the vestibular nuclei is inhibited. Bilateral cerebellar lesions affecting the vestibulocerebellum or bilateral paramedian brainstem lesions could induce such inhibition.1 GABAergic, glutaminergic, or cholinergic drugs have been used to manage DBN with moderate success.2 3,4-Diaminopyridine (3,4-DAP) was shown recently to effectively suppress DBN.3 In animal experiments, the related 4-aminopyridine (4-AP) increased the excitability of Purkinje cells (PCs).4 Both agents seem to influence DBN by increasing the physiologic, inhibitory influence of the vestibulocerebellum on the vestibular nuclei.3 4-AP penetrates the blood–brain barrier better than 3,4-DAP but has not yet been tested for management of ocular motor disorders. To evaluate how aminopyridines affect DBN and to test whether 4-AP is also effective, we measured DBN, smooth pursuit, gaze holding, and the gain of the vestibular ocular reflex (VOR) with the search coil technique in one patient. A 65-year-old pharmacist had blurred vision for 7 years that increased during lateral gaze. Neurologic examination was normal, except for DBN during fixation, impaired smooth pursuit, and postural imbalance. DBN increased during lateral and downward gaze and convergence. Brain MRI and blood chemistry (including vitamin B12 and Mg2+ …

Evaluation of quantitative head impulse testing using search coils versus video-oculography in older individuals

Objective To evaluate the validity of 2D video-oculography (VOG) compared with scleral search coils for horizontal AVOR gain estimation in older individuals. Study Design Cross-sectional validation study. Setting Tertiary care academic medical center. Patients Six individuals age 70 and older. Interventions Simultaneous eye movement recording with scleral search coil (over right eye) and EyeSeeCam VOG camera (over left eye) during horizontal head impulses. Main Outcome Measures Best estimate search coil and VOG horizontal AVOR gain, presence of compensatory saccades using both eye movement recording techniques. Results We observed a significant correlation between search coil and VOG best estimate horizontal AVOR gain (r = 0.86, p = 0.0002). We evaluated individual head impulses and found that the shapes of the head movement and eye movement traces from the coil and VOG systems were similar. Specific features of eye movements seen in older individuals, including overt and covert corrective saccades and anticompensatory eye movements, were captured by both the search coil and VOG systems. Conclusion These data suggest that VOG is a reasonable proxy for search coil eye movement recording in older subjects to estimate VOR gain and the approximate timing of corrective eye movements. VOG offers advantages over the conventional search coil method; it is portable and easy to use, allowing for quantitative VOR estimation in diverse settings such as a routine office-based practice, at the bedside, and potentially in larger scale population analyses.

Head impulse test reveals residual semicircular canal function after vestibular neurectomy

Meniere disease patients sometimes report vertiginous Meniere attacks after vestibular neurectomy that spares hearing. To determine why, the authors compared postsurgical semicircular canal function in nine patients with preserved hearing with that of a control group with no preservation of hearing. The three-dimensional head impulse test revealed residual posterior canal function in all patients with vertigo attacks (eight). The control patients had no residual canal function. Thus, residual vestibular function on the ipsilesional side may cause vertiginous Meniere attacks.

Covert Anti-Compensatory Quick Eye Movements during Head Impulses

Background Catch-up saccades during passive head movements, which compensate for a deficient vestibulo-ocular reflex (VOR), are a well-known phenomenon. These quick eye movements are directed toward the target in the opposite direction of the head movement. Recently, quick eye movements in the direction of the head movement (covert anti-compensatory quick eye movements, CAQEM) were observed in older individuals. Here, we characterize these quick eye movements, their pathophysiology, and clinical relevance during head impulse testing (HIT). Methods Video head impulse test data from 266 patients of a tertiary vertigo center were retrospectively analyzed. Forty-three of these patients had been diagnosed with vestibular migraine, and 35 with Menière’s disease. Results CAQEM occurred in 38% of the patients. The mean CAQEM occurrence rate (per HIT trial) was 11±10% (mean±SD). Latency was 83±30 ms. CAQEM followed the saccade main sequence characteristics and were compensated by catch-up saccades in the opposite direction. Compensatory saccades did not lead to more false pathological clinical head impulse test assessments (specificity with CAQEM: 87%, and without: 85%). CAQEM on one side were associated with a lower VOR gain on the contralateral side (p<0.004) and helped distinguish Menière’s disease from vestibular migraine (p = 0.01). Conclusion CAQEM are a common phenomenon, most likely caused by a saccadic/quick phase mechanism due to gain asymmetries. They could help differentiate two of the most common causes of recurrent vertigo: vestibular migraine and Menière’s disease.

Optimal Control of Natural Eye-Head Movements Minimizes the Impact of Noise

When shifting gaze to foveate a new target, humans mostly choose a unique set of eye and head movements from an infinite number of possible combinations. This stereotypy suggests that a general principle governs the movement choice. Here, we show that minimizing the impact of uncertainty, i.e., noise affecting motor performance, can account for the choice of combined eye–head movements. This optimization criterion predicts all major features of natural eye–head movements—including the part where gaze is already on target and the eye counter-rotates—such as movement durations, relative eye–head contributions, velocity profiles, and the dependency of gaze shifts on initial eye position. As a critical test of this principle, we show that it also correctly predicts changes in eye and head movement imposed by an experimental increase in the head moment of inertia. This suggests that minimizing the impact of noise is a simple and powerful principle that explains the choice of a unique set of movement profiles and segment coordination in goal-directed action.

Vestibular guidance of active head movements

Vestibular sensors provide precise and timely information about head velocity in space. It is well established that this information is used to stabilize eyes, head and body against movements from outside, i.e., passive movements. Here, we investigate whether vestibular information also helps to monitor and guide active head movements during gaze shifts. We measured head movements during large gaze shifts toward briefly flashed targets in humans with complete vestibular loss (vestibular subjects) and in healthy controls before and after increasing their head moment of inertia. Whereas normally head movements oscillate neither in vestibular subjects nor in controls, the increase in head moment of inertia caused marked head oscillations only in vestibular subjects. We conclude that vestibular information plays an important role in the on-line guidance of active head movements and helps to correct for unexpected changes such as additional torque imposed by an increase in moment of inertia.

Vestibular and cerebellar contribution to gaze optimality

Patients with chronic bilateral vestibular loss have large gaze variability and experience disturbing oscillopsia, which impacts physical and social functioning, and quality of life. Gaze variability and oscillopsia in these patients are attributed to a deficient vestibulo-ocular reflex, i.e. impaired online feedback motor control. Here, we assessed whether the lack of vestibular input also affects feed-forward motor learning, i.e. the ability to choose optimal movement parameters that minimize variability during active movements such as combined eye-head gaze shifts. A failure to learn from practice and reshape feed-forward motor commands in response to sensory error signals to achieve appropriate movements has been proposed to explain dysmetric gaze shifts in patients with cerebellar ataxia. We, therefore, assessed the differential roles of both sensory vestibular information and the cerebellum in choosing optimal movement kinematics. We have previously shown that, in the course of several gaze shifts, healthy subjects adjust the motor command to minimize endpoint variability also when movements are experimentally altered by an increase in the head moment of inertia. Here, we increased the head inertia in five patients with chronic complete bilateral vestibular loss (aged 45.4±7.1 years, mean±standard deviation), nine patients with cerebellar ataxia (aged 56.7±12.6 years), and 10 healthy control subjects (aged 39.7±6.3 years) while they performed large (75° and 80°) horizontal gaze shifts towards briefly flashed targets in darkness and, using our previous optimal control model, compared their gaze shift parameters to the expected optimal movements with increased head inertia. Patients with chronic bilateral vestibular loss failed to update any of the gaze shift parameters to the new optimum with increased head inertia. Consequently, they displayed highly variable, suboptimal gaze shifts. Patients with cerebellar ataxia updated some movement parameters to serve the minimum variance optimality principle but inaccurately undershot the target leading to an average gaze error of 11.4±2.0°. Thus, vestibulopathy leads to gaze variability not only as a result of deficient online gaze control but also a failure in motor learning because of missing error signals. Patients with cerebellar ataxia in our setting can learn from practice-similar to recent findings in reaching movements-and reshape feed-forward motor commands to decrease variability. However, they compromise optimality with inaccurately short movements. The importance of vestibular information for motor learning implies that patients with incomplete bilateral vestibulopathy, and patients with cerebellar ataxia, should be advised to actively move their head whenever appropriate. This way, sensory error signals can be used to shape the motor command and optimize gaze shifts trial-by-trial.

The Intensity of Downbeat Nystagmus during Daytime

On the basis of reports by patients with downbeat nystagmus (DBN) that their symptoms were worse during the morning but better during the daytime, we investigated whether the intensity of DBN changes during the daytime. DBN was measured at 9 am, 11 am, and 1 pm. The mean peak slow phase velocity (MPSPV) of DBN was determined in different eye positions, with and without fixation, as well as in three different body positions: sitting upright, lying supine with the nose up, and lying prone with the nose down. Twelve patients with DBN either due to cerebellar degeneration or of idiopathic etiology were examined. The major findings of this study were as follows. First, the intensity of DBN significantly decreased during the daytime. When measured in the sitting upright position and primary eye position, MPSPV decreased from 4.32 deg/sec (±SEM 1.02) at 9 am to 2.12 deg/sec (± 0.5) at 11 am (P < 0.01) and stayed constant around 1.93 deg/sec (± 0.57) at 1 pm (P < 0.01 from 9 am to 1 pm) and 2.08 deg/sec (± 0.75) at 3 pm (P < 0.01 from 9 am to 3 pm). Second, this change did not depend on fixation during the measurements. Third, this effect was not influenced by the eye position during the measurements (upward, downward, or straight ahead). Our data show that the intensity of DBN decreases during the daytime. This decrease correlates with the symptoms of the patients. This change during daytime did not depend on visual fixation. Another possible mechanism is the modulation of DBN by head position relative to gravity, that is, by otolith input. This should be evaluated in further studies.

The Effect of Vestibulo-Ocular Reflex Deficits and Covert Saccades on Dynamic Vision in Opioid-Induced Vestibular Dysfunction

Patients with bilateral vestibular dysfunction cannot fully compensate passive head rotations with eye movements, and experience disturbing oscillopsia. To compensate for the deficient vestibulo-ocular reflex (VOR), they have to rely on re-fixation saccades. Some can trigger “covert” saccades while the head still moves; others only initiate saccades afterwards. Due to their shorter latency, it has been hypothesized that covert saccades are particularly beneficial to improve dynamic visual acuity, reducing oscillopsia. Here, we investigate the combined effect of covert saccades and the VOR on clear vision, using the Head Impulse Testing Device – Functional Test (HITD-FT), which quantifies reading ability during passive high-acceleration head movements. To reversibly decrease VOR function, fourteen healthy men (median age 26 years, range 21–31) were continuously administrated the opioid remifentanil intravenously (0.15 µg/kg/min). VOR gain was assessed with the video head-impulse test, functional performance (i.e. reading) with the HITD-FT. Before opioid application, VOR and dynamic reading were intact (head-impulse gain: 0.87±0.08, mean±SD; HITD-FT rate of correct answers: 90±9%). Remifentanil induced impairment in dynamic reading (HITD-FT 26±15%) in 12/14 subjects, with transient bilateral vestibular dysfunction (head-impulse gain 0.63±0.19). HITD-FT score correlated with head-impulse gain (R = 0.63, p = 0.03) and with gain difference (before/with remifentanil, R = −0.64, p = 0.02). One subject had a non-pathological head-impulse gain (0.82±0.03) and a high HITD-FT score (92%). One subject triggered covert saccades in 60% of the head movements and could read during passive head movements (HITD-FT 93%) despite a pathological head-impulse gain (0.59±0.03) whereas none of the 12 subjects without covert saccades reached such high performance. In summary, early catch-up saccades may improve dynamic visual function. HITD-FT is an appropriate method to assess the combined gaze stabilization effect of both VOR and covert saccades (overall dynamic vision), e.g., to document performance and progress during vestibular rehabilitation.