Self-motion perception is sensitized in vestibular migraine: pathophysiologic and clinical implications.

Vestibular migraine (VM) is the most common cause of spontaneous vertigo but remains poorly understood. We investigated the hypothesis that central vestibular pathways are sensitized in VM by measuring self-motion perceptual thresholds in patients and control subjects and by characterizing the vestibulo-ocular reflex (VOR) and vestibular and headache symptom severity. VM patients were abnormally sensitive to roll tilt, which co-modulates semicircular canal and otolith organ activity, but not to motions that activate the canals or otolith organs in isolation, implying sensitization of canal-otolith integration. When tilt thresholds were considered together with vestibular symptom severity or VOR dynamics, VM patients segregated into two clusters. Thresholds in one cluster correlated positively with symptoms and with the VOR time constant; thresholds in the second cluster were uniformly low and independent of symptoms and the time constant. The VM threshold abnormality showed a frequency-dependence that paralleled the brain stem velocity storage mechanism. These results support a pathogenic model where vestibular symptoms emanate from the vestibular nuclei, which are sensitized by migraine-related brainstem regions and simultaneously suppressed by inhibitory feedback from the cerebellar nodulus and uvula, the site of canal-otolith integration. This conceptual framework elucidates VM pathophysiology and could potentially facilitate its diagnosis and treatment.

The Impact of Oral Promethazine on Human Whole-Body Motion Perceptual Thresholds.

Despite the widespread treatment of motion sickness symptoms using drugs and the involvement of the vestibular system in motion sickness, little is known about the effects of anti-motion sickness drugs on vestibular perception. In particular, the impact of oral promethazine, widely used for treating motion sickness, on vestibular perceptual thresholds has not previously been quantified. We examined whether promethazine (25 mg) alters vestibular perceptual thresholds in a counterbalanced, double-blind, within-subject study. Thresholds were determined using a direction recognition task (left vs. right) for whole-body yaw rotation, y-translation (interaural), and roll tilt passive, self-motions. Roll tilt thresholds were 31 % higher after ingestion of promethazine (P = 0.005). There were no statistically significant changes in yaw rotation and y-translation thresholds. This worsening of precision could have functional implications, e.g., during driving, bicycling, and piloting tasks. Differing results from some past studies of promethazine on the vestibulo-ocular reflex emphasize the need to study motion perception in addition to motor responses.

The clinical manifestations of vestibular migraine: A review.

OBJECTIVES: To provide an overview of vestibular migraines presentation, pathology, and diagnosis, as well as an update on current diagnostic criteria. METHODS: A review of the most recent literature on vestibular migraines was performed. RESULTS: Vestibular migraine is a process with significant impact on the quality of life for those afflicted with the disease, with attacks of spontaneous or positional vertigo and migraine symptoms lasting several minutes to 72h. Inner ear disease can co-exist with migraine and the vestibular symptoms occurring with vestibular migraine can mimic inner ear disorders providing a challenge for clinicians in establishing diagnosis. Recent diagnostic criteria for vestibular migraine proposed by a joint committee of the Bárány Society and the International Headache Society provide an important standard for clinical diagnosis and research endeavor. CONCLUSION: Vestibular migraine is a challenging disease process to both diagnose and treat. Proper diagnosis and treatment requires a thorough understanding of the current literature.

Clinical vestibular testing assessed with machine-learning algorithms.

IMPORTANCE: Dizziness and imbalance are common clinical problems, and accurate diagnosis depends on determining whether damage is localized to the peripheral vestibular system. Vestibular testing guides this determination, but the accuracy of the different tests is not known. OBJECTIVE: To determine how well each element of the vestibular test battery segregates patients with normal peripheral vestibular function from those with unilateral reductions in vestibular function. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of vestibular test batteries in 8080 patients. Clinical medical records were reviewed for a subset of individuals with the reviewers blinded to the vestibular test data. INTERVENTIONS: A group of machine-learning classifiers were trained using vestibular test data from persons who were "manually" labeled as having normal vestibular function or unilateral vestibular damage based on a review of their medical records. The optimal trained classifier was then used to categorize patients whose diagnoses were unknown, allowing us to determine the information content of each element of the vestibular test battery. MAIN OUTCOMES AND MEASURES: The information provided by each element of the vestibular test battery to segregate individuals with normal vestibular function from those with unilateral vestibular damage. RESULTS: The time constant calculated from the rotational test ranked first in information content, and measures that were related physiologically to the rotational time constant were 10 of the top 12 highest-ranked variables. The caloric canal paresis ranked eighth, and the other elements of the test battery provided minimal additional information. The sensitivity of the rotational time constant was 77.2%, and the sensitivity of the caloric canal paresis was 59.6%; the specificity of the rotational time constant was 89.0%, and the specificity of the caloric canal paresis was 64.9%. The diagnostic accuracy of the vestibular test battery increased from 72.4% to 93.4% when the data were analyzed with the optimal machine-learning classifier. CONCLUSIONS AND RELEVANCE: Rotational testing should be considered the primary test to diagnose unilateral peripheral vestibular damage in patients with dizziness or imbalance. Most physicians, however, continue to rely on caloric tests to guide their diagnoses. Our results support a significant shift in the approach used to determine diagnoses in patients with vestibular symptoms.

Central Integration of Canal and Otolith Signals is Abnormal in Vestibular Migraine.

Vestibular migraine (VM), a common cause of vestibular symptoms within the general population, is a disabling and poorly understood form of dizziness. We sought to examine the underlying pathophysiology of VM with three studies, which involved the central synthesis of canal and otolith cues, and present preliminary results from each of these studies: (1) VM patients appear to have reduced motion perception thresholds when canal and otolith signals are modulated in a co-planar manner during roll tilt; (2) percepts of roll tilt appear to develop more slowly in VM patients than in control groups during a centrifugation paradigm that presents conflicting, orthogonal canal and otolith cues; and (3) eye movement responses appear to be different in VM patients when studied with a post-rotational tilt paradigm, which also presents a canal-otolith conflict, as the shift of the eye's rotational axis was larger in VM and the relationship between the axis shift and tilt suppression of the vestibulo-ocular reflex differed in VM patients relative to control groups. Based on these preliminary perceptual and eye movement results obtained with three different motion paradigms, we present a hypothesis that the integration of canal and otolith signals by the brain is abnormal in VM and that this abnormality could be cerebellar in origin. We provide potential mechanisms that could underlie these observations, and speculate that one of more of these mechanisms contributes to the vestibular symptoms and motion intolerance that are characteristic of the VM syndrome.

Motion Perception in Patients with Idiopathic Bilateral Vestibular Hypofunction.

We measured vestibular perceptual thresholds in patients with idiopathic bilateral vestibulopathy to assess the distribution of peripheral vestibular damage in this disorder. Thresholds were measured with standard psychometric techniques in 4 patients and compared with thresholds in normal subjects and patients with completely absent peripheral vestibular function. Motion paradigms included yaw rotation (testing the lateral canals), interaural translation (testing the utricles), superior-inferior translation (testing the saccules), and roll tilt (testing the vertical semicircular canals and the otolith organs). We found that perceptual thresholds were abnormally elevated in the patients with idiopathic bilateral vestibulopathy for yaw rotation at all frequencies and for interaural translation at only the lower frequencies. Thresholds were normal for the other 2 motion paradigms. The results demonstrate that the distribution of vestibular dysfunction in this disorder is not uniform but, rather, can affect lateral canal and utricular thresholds while relatively sparing vertical canal and saccular function.

Vestibular labyrinth contributions to human whole-body motion discrimination.

To assess the contributions of the vestibular system to whole-body motion discrimination in the dark, we measured direction recognition thresholds as a function of frequency for yaw rotation, superior-inferior translation ("z-translation"), interaural translation ("y-translation"), and roll tilt for 14 normal subjects and for 3 patients following total bilateral vestibular ablation. The patients had significantly higher average threshold measurements than normal (p < 0.01) for yaw rotation (depending upon frequency, 5.4× to 15.7× greater), z-translation (8.3× to 56.8× greater), y-translation (1.7× to 4.5× greater), and roll tilt (1.3× to 3.0× greater)--establishing the predominant contributions of the vestibular system for these motions in the dark.

Dynamic tilt thresholds are reduced in vestibular migraine.

Vestibular symptoms caused by migraine, referred to as vestibular migraine, are a frequently diagnosed but poorly understood entity. Based on recent evidence that normal subjects generate vestibular-mediated percepts of head motion and reflexive eye movements using different mechanisms, we hypothesized that percepts of head motion may be abnormal in vestibular migraine. We therefore measured motion detection thresholds in patients with vestibular migraine, migraine patients with no history of vestibular symptoms, and normal subjects using the following paradigms: roll rotation while supine (dynamically activating the semicircular canals); quasi-static roll tilt (statically activating the otolith organs); and dynamic roll tilt (dynamically activating the canals and otoliths). Thresholds were determined while patients were asymptomatic using a staircase paradigm, whereby the peak acceleration of the motion was decreased or increased based on correct or incorrect reports of movement direction. We found a dramatic reduction in motion thresholds in vestibular migraine compared to normal and migraine subjects in the dynamic roll tilt paradigm, but normal thresholds in the roll rotation and quasi-static roll tilt paradigms. These results suggest that patients with vestibular migraine may have enhanced perceptual sensitivity (e.g. increased signal-to-noise ratio) for head motions that dynamically modulate canal and otolith inputs together.

Asymmetric responses to rotation at high frequencies in central vestibular neurons of the alert cat.

The horizontal rotatory vestibulo-ocular reflex (VOR) stabilizes gaze by moving the eyes at an angular velocity proportional to head velocity, and can accomplish this for a broad range of frequencies and amplitudes of head motion. Rotation at 5 Hz and above may be processed differently than lower frequencies by the VOR network. We recorded discharges and calculated spike densities of a small sample of vestibular neurons in alert cats during low-velocity rotation at frequencies up to 8 Hz. At high frequencies, we found both vestibular-only (V-only) and eye-movement-sensitive (EM) cells that generated asymmetric output signals. Asymmetry was primarily of the cutoff type, i.e., changes in spike density were smallest for rotation in the inhibitory direction. Most cells were identified as secondary neurons. The mean spike density was 23 sp/s, which was lower than previously reported in vestibular neurons of monkeys. A few neurons had very high sensitivities, associated with phase-locking, to rotation at high frequencies. In general, vestibular neurons carried a high-pass-filtered version of rotational signals. When synaptic inputs from the vestibular commissure were quantified, we found that the immediate change in probability of firing due to commissural vestibular input was inversely correlated with the degree of high-pass filtering. At high frequencies, increased asymmetry and phase-locking occurred in some neurons. A small number of neurons responded with increased probability of firing to both directions of rotation. Together, these observations suggest that high frequencies of rotation may be encoded differently than low frequencies by central vestibular neurons in alert animals.