The key findings in our study are as follows: (1) 74.0% of attacks in VM were presented in morning hours before 12 o’clock; occurrence of VM peaked in the morning hours between 07:00-07:59, and reached valley between 21:00-21:59; (2) clinical presentations of vestibular symptoms showed variations among four 6-hour quadrants per day; (3) attacks may be influenced by poor sleep, however, the biological circadian cycles may have greater impact of VM than lack of sleep. To our knowledge, this study was the first time to analyze the circadian variations in the occurrence and the clinical presentation of VM.
In our population, the age of onset was 36.00 (29.50, 44.00) years old, consistent other studies(15). But few of our patients had a personal history of alcohol or caffeine, that may due to the gender or local dietary habit and may affect the composition of influence factors.
For all attacks, frequencies of activities at onset differed among four 6-hour quadrants and “rising” (36.5%) was presented most frequently. The onset patterns of vestibular symptoms in each quadrant was related to the regular activity patterns of our population. But on the whole, vestibular symptoms were more often triggered by activities of moving their heads, which perhaps was one trigger unique to VM but not migraine headache(4). The attack of VM presented more frequently between 00:00-12:00 and reached its peak about 7 o'clock in the morning. This finding is similar to previous chronobiological studies that reported an increased frequency of morning headache attacks among migraineurs(16). We also found abnormal upward fluctuations at 14:00 and 20:00, which may correlate to the taking of food and suggesting a role of the sympathetic nervous system(17).
In addition, most of our VM patients experienced more than one accompanying symptom and vestibular symptom. Orthostatic vertigo was reported more frequent in the morning hours while dizziness was reported more frequent in the afternoon hours. Headaches may or may not accompany vestibular symptoms during VM attacks, consistent with previous study(5). The majority reported nausea with or without vomiting, photophobia or phonophobia. Just a few of our patients described tinnitus and visual aura, which is much lower than those data reported in other studies(4, 18).
Through these analyses, we can get a preliminary conclusion about circadian variations of VM attacks. However, what is the possible mechanism in the occurrence and clinical presentation of VM underlying the circadian rhythm? The pathophysiology of VM has not been fully established yet(19, 20). In present hypotheses, as a a variant of migraine, VM is the integral overlap among vestibular pathways, migraine circuit triggers and central mechanisms for premonitory symptom generation(21-23).Hypothalamic activation and circadian variation has been reported during migraine attacks in many recently studies(16, 24, 25). The circadian rhythm is controlled by a complex system of molecular regulation with a master precursor, located in the suprachiasmatic nucleus of the anterior hypothalamus(26, 27). In pathophysiological model of VM by Furman, the hypothalamus was contained within a network of interoceptive circuits for vestibular, visceral sensory, and nociceptive information(28).Therefore, the circadian variations in the occurrence and the clinical presentation of VM may due to the hypothalamic involvement in both nociception and circadian periodicity(28).
Similar to the migraine, peak incidence of VM is usually during sleep or upon awakening(9, 29). A key question is whether the observed temporal pattern represents a true endogenously mediated circadian pattern, or it is just triggered by alteration of the sleep pattern. However, the proportion of attacks induced by abnormal sleep did not increase significantly in VM patients with morning onset. Lack of sleep may indeed be one of the triggers of attacks, but endogenously circadian rhythm of VM maybe dominant.
Our data should be interpreted with some caution due to limitations of the study. These included the relatively small sample size and retrospective bias inherent. Secondly, we enrolled patients with probable VM, who might develop definite VM over time as some studies have shown(30-32). Moreover, we only described the clinical features of VM by a cross-sectional study, further study on the relevant mechanism will be great helpful to identify this entity.