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

Abstract

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.

Calcitonin gene-related peptide facilitates sensitization of the vestibular nucleus in a rat model of chronic migraine

“…Medial vestibular nucleus neurons are essential to the maintenance of vestibulo-ocular reflex, especially in stabilizing the images during head movement [58]. Clinical-based studies provide supporting evidence that ocular and perceptual thresholds are significantly increased in migraine patients with vestibular symptoms relative to those without vestibular symptoms, implying that sensitization of the medial vestibular nucleus might be a primary pathophysiological process underlying the vestibular hypersensitivity in migraine patients with vestibular symptoms [10,11]. Clinical trials investigating CGRP antibodies or CGRP receptor antagonists have shown statistically significantly efficacy for migraine treatment [45].…”

“…Whether vestibular symptom is one of clinical manifestations of central sensitization for migraine remains unproven. Clinical data demonstrated that patients with VM exhibited abnormally elevated vestibularocular threshold [10], as well as reduced roll tilt threshold [11] compared to migraine patients without vestibular symptoms and patients with a peripheral inner-ear disorder, indicating that dysfunction of the vestibular nuclei (VN) might be an underlying mechanism for vestibular symptoms in VM. As an important sensorimotor center in brainstem, VN and its direct connection with TNC had been demonstrated in rodents [12].…”

Vestibular migraine — an underdiagnosed cause of vertigo. Diagnosis and treatment

“…So, the cause of VM may be direct central activation of vestibular centres by the trigeminovascular system together with its effects on the inner ear [32]. It seems that vestibular symptoms come from the vestibular nuclei, which are simultaneously suppressed by inhibitory feedback from the cerebellar nodulus and uvula [33]. There is also evidence of otolithic pathway abnormalities in individuals with VM [34].…”

Measuring Vestibular Contributions to Age-Related Balance Impairment: A Review

“…However, compensatory nystagmus and the subjective perception of rotation persist up to 30 s ( 34 , 43 , 203 ); this propagation of behavioral vestibular activity is accomplished through a mechanism called velocity storage [see ( 204 ) for a review on this topic but also see ( 205 , 206 ) for differing perspectives]. A reduced time constant (i.e., faster decay of nystagmus) has been identified in subjects with unilateral and bilateral vestibular loss ( 207 ), in those with central vestibular dysfunction ( 208 ), and in asymptomatic older adults ( 34 , 35 , 203 , 209 ).…”