Both vertigo and migraine are common clinical symptoms in neurology, and their lifetime prevalence in the general population is 7% and 16%, respectively.1,2 From the end of the 19th century, researchers have studied the relationship between vertigo and migraine.3 Patients with recurrent vertigo accompanied by migraine have been diagnosed with migraine-related vertigo/dizziness,4,5 migraine-associated vertigo,6 and migraine-related vestibular disease.7 In 1999, Dieterich and Brandt7 first advocated the use of the term Vestibular Migraine (VM) as a diagnosis for such patients.

VM is one of the most common paroxysmal vestibular diseases, with an incidence of more than 1% in the population. The International Bárány Society and the International Headache Society jointly developed the diagnostic criteria for VM in 2012. The diagnostic criteria were published in Disorders, 3rd edition (beta version) (ICHD-3β) in 20138 and in the new version, ICHD-3, in 2018.9 In clinical practice, the diagnostic criteria for VM mainly rely on symptoms (vestibular symptoms, migraine/migraine features) and not on evidence from objective evaluation. Therefore, the present study aimed to analyze the types of vestibular symptoms in patients with dVM diagnosed according to the criteria jointly developed by the Bárány Society and the International Headache Society, identify medical history and immune-related indicators that contribute to dVM by using multidimensional objective evaluation based on clinical characteristics, vestibular-related examinations, and immune-related laboratory tests. We hope that our study can help clinicians make early diagnosis of dVM and contribute to better patient management.

This study was approved by the institutional Research Ethics Committee (approval nº 20180314-ST-04). Written informed consent was obtained from each participant prior to recruitment.

There is evidence that the peak incidence of dVM appears in patients at 30–60 years, and is more common in women,7,11,12 with a male-to-female ratio of 1:5. In our study, the male-to-female ratio was 1:4.6, which is consistent with previous studies. Women may be more likely to develop dVM because of changes in female hormone levels.13 Oh et al.14 found that a subgroup of patients with dVM had autosomal dominant inheritance, and the penetrance rate was lower in men than in women, with a correspondingly lower incidence in men than in women.

The onset of migraine often precedes the onset of vestibular symptoms. In our study, the onset of migraine occurred an average of 6 years earlier than vestibular symptoms in patients with dVM, and the onset of migraine preceded vestibular symptoms in 42 (67.7%) patients. Thakar et al.15 and Zhang et al.16 respectively reported that the onset of migraine occurred 8.4 and 6 years earlier than vestibular symptoms in their studied populations. The diagnosis of vestibular symptoms is the core of VM diagnosis. In clinical practice, there is great heterogeneity of vestibular symptoms in patients with VM. Neuhauser et al.3 showed that 67% patients with dVM had spontaneous vertigo, and 24% had positional vertigo. Cho et al.17 reported that head-motion vertigo with nausea is the most common symptom of dVM. Teggi et al.18 found that internal vertigo (73%) is more common than external vertigo (25%) in patients with dVM. Cohen et al.19 showed that unsteadiness (n = 134, 91%) was the most common vestibular symptom in patients with dVM. In our study, spontaneous vertigo (n = 41, 66.1%) was the most common vestibular symptom, and internal vertigo is more common than external vertigo. These findings are consistent with the results of previous studies. The heterogeneities in vestibular symptoms may be partly related to the patients’ subjective symptom description. The occurrence of these vestibular symptoms is speculated to be related to increased sensitivity of the vestibular system.20,21

In clinical practice, there is great heterogeneity in the duration of vestibular symptoms in patients with dVM.10 In our study, the duration of vestibular symptoms was more than 1 h in most patients with dVM (n = 39, 62.9%), which is similar to the results reported in a previous study.22 Teggi et al.18 reported that 55.2% patients had vertigo attacks lasting more than 1 h. Ren et al.23 showed that vertigo attacks generally lasted several hours (37%). There is evidence that the frequency of vestibular symptoms varies greatly. In a study involving 85 patients with Dvm24 reported that 35 (45.5%) patients had episodes of vestibular symptoms once per day to once per week. In our study, most patients with dVM had episodes of vestibular symptoms once per year (61.3%). This variability may be caused by differences in the definition of a single episode among doctors. Morganti et al.24 defined the attack frequency as the number of attacks in the recent onset cycle/the onset cycle, and the frequency in this study was defined as the total number of attacks/ the total course of disease.

In our study, migraine without aura was most common in patients with dVM (n = 44, 71.0%). A previous study16 showed that 53 (79%) patients had migraine without aura, 8 (12%) had migraine with aura, and 6 (9%) had chronic migraine. Cho et al.17 reported that in 65 patients with dVM, the number of patients with migraine without aura was much higher than the number of patients with migraine with aura (66.2% vs. 4.6%).

In our study, among the accompanying migraine features, photophobia/phonophobia (n = 47, 75.8%) was the most common migraine features, followed by migraine-like headache (n = 25, 40.3%) and vision aura (n = 18, 29.0%) during dVM attacks. These results are consistent with those reported by Zhang16 and Xu.25

There is evidence that vestibular symptoms and migraine features do not occur in a specific order at each episode of VM.7,12 Akdal et al.26 found that among patients with migraine with vertigo, 40% did not develop migraine accompanied by vertigo, while 17% developed migraine accompanied by vertigo. Zhang et al.16 showed that migraine-like headache was accompanied by vertigo in 23 (34%) patients. In our study, vestibular symptoms accompanied by migraine features was found in 25 (40.3%) patients. This may be because we investigated the order in which the vestibular symptoms and migraine features occurred during VM attack, and migraine features included not only headache, but also photophobia, phonophobia and visual aura.

We also found that migraine in patients with VM display family aggregation, which is similar to previous studies.27–30 Langhagen et al.31 found that 65.2% patients had a family history of migraine. A study conducted by Teggi et al.18 involved 252 patients with dVM, and found that 177 (70.2%) patients had a family history of migraine.

In our study, approximately 53.2% of patients with dVM had motion sickness. Akdal et al.26 reported that motion sickness was more common in the migraine with vertigo group than in the migraine group (75% vs. 50%). Langhagen et al.31 reported that 51% patients with dVM had a history of motion sickness. Thus, a history of motion sickness can contribute to the diagnosis of dVM in the early stage.

Several studies have shown that patients with dVM exhibit central oculomotor dysfunction, but the incidence differs greatly among studies, ranging from 8.6% to 65.6%.7,32,33 Dieterich and Brandt7 showed that 59 (65.6%) patients with VM developed central oculomotor dysfunction, 43 (48%) had abnormal saccadic pursuit, 24 (27.0%) had gaze-evoked nystagmus, 10 (11%) had positional nystagmus, 10 (11.0%) had spontaneous nystagmus, and 1 (1.1%) had oculomotor nuclear palsy. A study conducted by Radtke et al.34 involving 60 patients with VM reported that 9 (15%) patients had central oculomotor dysfunction, including 7 (12%) of positional nystagmus, 1 (2%) of spontaneous nystagmus, and 1 (2%) of head-shaking nystagmus. They also reported a reduction in the unilateral vestibulo-ocular reflex gain in 1 (2%) patient, but no abnormalities in smooth pursuit eye movement or gaze test were found. In our study, central oculomotor dysfunction occurred in 11 (17.1%) patients, static positional nystagmus occurred in 15 (24.2%) patients, and head-shaking nystagmus occurred in 19 (30.6%) patients. The great variability in central oculomotor dysfunction among studies may be due to that investigator included different testing items of central oculomotor dysfunction. Dieterich and Brandt7 assessed central oculomotor dysfunction with not only the gaze test, saccadic test, smooth pursuit, spontaneous nystagmus, positional nystagmus, but also oculomotor nerve palsy. Radtke et al.34 also included head-shaking nystagmus and unilaterally reduced vestibulo-ocular reflex gain in video head-impulse test.

In clinical practice, patients with VM often have peripheral damage, including hearing or peripheral vestibular function reduction. Here, we found that 35.5% patients had cochlear symptoms, and 16 (25.8%) patients had tinnitus, the results are consistent with previous studies.18,35–37 Patients with VM may have transient or persistent hearing or vestibular dysfunction, which often returns to normal after a period.38 This symptom can be explained by the trigeminovascular theory, this theory indicates that during migraine attacks in VM patients, the trigeminal nerve is stimulated, and substance P, neurokinin A, nitric oxide and calcitonin gene-related peptide are released, resulting in increased labyrinthine blood flow, changes in vascular permeability, and inner ear dysfunction.

In our study, most patients with dVM experienced caloric test intolerance. Previous studies showed that patients with dVM are sensitive to external auditory canal irrigation with cold and warm water.39–43 Patients with dVM developed severe intolerance after external auditory canal irrigation with cold and warm water, including obvious nausea, vomiting, palpitations, numbness of the hands and feet, and even body stiffness. In some patients, those symptoms persisted for several hours after the caloric test was completed. The mechanism underlying the hyperactive response may involve an increase in the time constant of the vestibular ocular reflex caused by heightened sensitivity of the vestibular system.42

It is noteworthy that in our study, serum anti-thyroid antibodies (including TGAb and TPOAb) were positive in 8 (12.9%) patients. TGAb and TPOAb are specific autoantibodies associated with autoimmune thyroid disease, indicating thyroid dysfunction. Wen et al.44 performed a large-sample-size study in a healthy population, and found that TGAb and TPOAb were positive in 8.97% and 9.58% of individuals, respectively. Thus, patients with dVM are positive for TGAb and TPOAb at higher rates than the healthy population, suggesting that dVM may be a secondary/concomitant condition.

Objective evaluation of dVM based on clinical characteristics, vestibular-related examinations, and immune-related laboratory tests offers opportunities for early diagnosis of dVM, however, the sample size in this study is small, and the results are mainly descriptive, further studies with larger sample sizes are needed to confirm our findings.

dVM is more common in women, the onset of migraine precedes that of vestibular symptoms, and vestibular symptoms are often accompanied by photophobia and phonophobia. Most patients develop motion sickness and cannot tolerate the caloric test, which can contribute to dVM diagnosis. Some patients with dVM have abnormal immunological indexes, indicating that the pathogenesis of dVM might involve autoimmune mechanisms.

Data will be made available on request.

The study was supported by Medical and Health Research Project of China Aerospace Science and Industry Corp (2017-LCYL-006).

The authors declare no conflicts of interest.