Although a sporadic disorder in most patients, vestibular migraine can be inherited in an autosomal dominant fashion. A linkage analysis in a four-generation family with 10 affected individuals mapped the locus for vestibular migraine to chromosome 5q35. In a larger study, familial vestibular migraine was found to be genetically heterogenous with a subgroup linking to chromosome 22q12.
The neural mechanisms of vestibular migraine are still obscure. The variability of symptoms and clinical findings both during and between attacks suggests that migraine interacts with the vestibular system at various levels. Spreading depression, which is the presumed mechanism of the migraine aura, may play a role in patients with short attacks. Spreading depression is a cortical mechanism that could produce vestibular symptoms when it reaches the multisensory vestibular cortex, which is mainly located in the posterior insula and at the temporoparietal junction. However, several findings during the acute stage of vestibular migraine, including canal paresis and complex positional nystagmus, cannot be explained by cortical dysfunction.
Some of the neurotransmitters that are involved in the pathogenesis of migraine (calcitonin-gene related peptide, serotonin, noradrenaline, dopamine) are also known to modulate the activity of central and peripheral vestibular neurons and could contribute to the pathogenesis of vestibular migraine. One may speculate that unilateral release of these substances—in analogy with the often unilateral location of headaches—causes a static vestibular imbalance leading to rotatory vertigo, whereas bilateral release would induce a state of altered vestibular excitability leading to a motion sickness type of dizziness. Plasma extravasation from dural vessels causing transient meningeal inflammation is considered to be a key mechanism in migraine. In mice, serotonin-induced plasma extravasation was observed not only in the dura mater, but also in the inner ear. Vestibular and nociceptive pathways show neurochemical similarities and share central pathways for perception, interoception, and affect.
Genetic defects of a voltage-gated calcium channel have been identified as the cause of familial hemiplegic migraine and episodic ataxia type 2 (EA-2). As both of these paroxysmal disorders can have vertigo and migraine headache as prominent symptoms, a defective gene in the same region is a candidate mechanism for vestibular migraine. However, so far no such genetic defect has been identified.
The only hypothesis that is actually based on a human experimental model of vestibular migraine relates to the known reciprocal connections between the trigeminal and vestibular nuclei. Trigeminal activation by painful electrical stimulation of the forehead produced spontaneous nystagmus in migraine patients, but not in controls, indicating that those with migraine have a lowered threshold for crosstalk between these neighboring brainstem structures.