FormalPara Key Summary Points

The relationship between photophobia and visual triggers in vestibular migraine (VM) remains unexplored.

We investigated the correlation of photophobia during the VM attack with interictal photosensitivity and visually triggering dizziness in patients with VM.

Our study highlighted a positive correlation of photophobia during the VM attack with interictal photosensitivity and visually triggering dizziness in patients with VM.

These findings advance our understanding of the complex pathophysiological mechanisms underlying VM and provide crucial evidence for tailoring management and prevention strategies to the visual sensitivity characteristics of patients with VM.

Introduction

Vestibular migraine (VM) is a prevalent vestibular disorder characterized by episodic vertigo and frequently accompanied by vestibular and migraine symptoms [1]. The detailed classification of VM is provided in the International Classification of Headache Disorders, 3rd edition (ICHD-3) appendix; however, notably, its clinical and pathophysiological features parallel those of classical migraine [2, 3]. Vestibular symptoms, qualifying for a diagnosis of VM, encompass spontaneous and triggered vertigo, including positional, visually induced, and head motion-induced vertigo, along with dizziness [4]. Vertigo is characterized by a false sensation of self-motion, while dizziness refers to a sensation of disturbed spatial orientation. Vestibular symptoms can manifest autonomously of headache occurrence, yet photophobia and phonophobia commonly coincide with vestibular attacks [5].

The pathophysiology of VM-related symptoms is intertwined with the shared neural pathways between migraine and the vestibular system [6]. The key neurotransmitter implicated in vasodilation and neurogenic inflammation, calcitonin gene-related peptide, may play a pivotal role in VM [7, 8]. Aberrant brain sensitization disrupts sensory integration, leading to transient vestibular dysfunction and the emergence of migraine features in patients with VM [9, 10]. Despite the documented influence of visual factors, such as intense light and eyestrain, in inducing dizziness among patients with VM, the specific role of visual stimuli in triggering dizziness remains unexplored.

Photophobia, a defining criterion of migraine, affects approximately 80–90% of patients during a migraine attack [11]. Functional imaging studies have elucidated the connection between photophobia and heightened activity in the occipital lobe, especially when exposed to flickering light and glare [12, 13]. The intensity of light stimulation was found to positively correlate with occipital cortex activation, potentially explaining visual discomfort and eyestrain [14]. Such visual discomfort that may precipitate a migraine attack is more conspicuous in patients with vestibular disorders, raising the question of whether similar occurrences transpire in patients with VM, given their heightened visual system sensitization.

Previous studies have delved into the role of increased interictal visual sensitivity in migraine sufferers, particularly those with aura, and unveiled a correlation between light sensitivity, specific visual triggers (flicker, glare, and eyestrain), and photophobia [15, 16]. Nonetheless, these studies primarily focused on the frequency of headaches induced by visual triggers, without exploring the correlation between light sensitivity and susceptibility to visual triggers in patients with VM. In addition, clinical studies have disclosed a noteworthy prevalence of photophobia (44–87%) in patients with VM [17, 18], with 10.7% remaining photosensitive during the interictal period [19]. Furthermore, 29% of patients with VM reported dizziness induced by light stimulation, including glare and flicker [19]. However, research on the association between photophobia and visual triggers for dizziness in patients with VM is lacking.

Given the close association between VM and migraine, a thorough investigation of the association of photophobia with interictal photosensitivity and visually triggering dizziness in patients with VM is critically imperative. Such an investigation might significantly contribute to the enhancement of VM management and prevention strategies, shedding light on the intricate pathophysiological mechanisms that underlie this complex disorder.

In this study, we aimed to meticulously examine interictal photosensitivity and the frequency of dizziness induced by visual triggers in patients with VM, with a specific emphasis on the role of photophobia. Our hypothesis posited that patients with VM and photophobia would exhibit heightened interictal photosensitivity and greater susceptibility to visual triggers compared with those in patients with VM devoid of photophobia and control participants. Additionally, we sought to explore potential correlations between interictal photosensitivity and the frequency of dizziness triggered by visual factors in patients with VM.

Methods

Study Design and Patient Population

In this cross-sectional study conducted between 2018 and 2022, we systematically recruited patients aged > 18 years from seven specialized vertigo and headache clinics in China, all of whom received a diagnosis of VM. Pertinent data regarding the age of onset, classification, duration, and accompanying symptoms of vertigo were meticulously documented. To stratify VM cases on the basis of the presence of photophobia during attacks, patients were categorized into two groups: “photophobia” and “nonphotophobia”. A concurrently established sex- and age-matched control group, comprising healthy individuals undergoing routine medical examinations at our hospital during the same period, ensured comparability. All participants across these three groups completed comprehensive questionnaires. Vertigo intensity was assessed using a visual analog scale (VAS). The study adhered to the principles of the Declaration of Helsinki and was approved by the ethics committees of the Second Affiliated Hospital of Zhejiang University School of Medicine and other participating centers (ClinicalTrial.gov ID NCT04939922). Written informed consent was obtained from all patients.

The selection criteria for VM aligned with well-established diagnostic criteria for definitive VM as defined by the International Bárány Association and International Headache Society [20]. These criteria included (1) ≥ 5 episodes characterized by moderate-to-severe vestibular symptoms lasting between 5 min and 72 h; (2) a history of prior or ongoing migraine episodes, with or without aura, as per the ICHD diagnostic criteria; (3) ≥ 50% of vestibular episodes with ≥ 1 migraine features; and (4) exclusion of alternative vestibular disorders or other ICHD diagnoses. Exclusion criteria were as follows: (1) alternative primary or secondary headache disorders; (2) other vestibular disorders, including Meniere’s disease, benign paroxysmal positional vertigo, functional dizziness, and psychogenic dizziness; (3) ophthalmic conditions, such as cataracts, glaucoma, and inflammatory ocular diseases; (4) the presence of cardiac conditions, such as arrhythmias and coronary heart disease; (5) intracranial structural abnormalities; (6) epilepsy; and (7) concomitant medical conditions, such as hypotension and anemia.

Questionnaire Survey Methods

Photophobia Assessment

Photophobia assessment was performed using a previously developed scale (Table 1) [21]. Patients who responded affirmatively to more than one among items 1–7 were classified into the photophobia group.

Table 1 Photophobia questionnaire for patients with VM
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Frequency of Dizziness Induced by Visual Triggers and Severity of Interictal Light Sensitivity

For assessing the frequency of dizziness induced by visual triggers and severity of interictal light sensitivity, we employed targeted inquiries from the flicker, glare, and eyestrain sections of the Headache Triggers Sensitivity and Avoidance Questionnaire (HTSAQ) [22]. Participants underwent a comprehensive briefing elucidating the specific scenarios alluded to by these triggers before conscientiously completing the questionnaire. Each participant was queried regarding both the frequency and sensitivity. The HTSAQ, chosen for its elevated readability and demonstrated reliability, exhibits robust internal consistency and test–retest reliability, as evidenced by Cronbach’s alpha values exceeding 0.8.

Dizziness triggered by visual factors, including flicker, glare, and eyestrain, was evaluated on a rigorously structured 5-point scale [22]. Participants were prompted to rate the occurrence of dizziness according to the following scale: 1 = never, 2 = rarely, 3 = sometimes, 4 = usually, and 5 = always. Notably, in this context, dizziness pertained to a disturbed sense of spatial orientation and did not include lightheadedness.

Interictal light sensitivity, reflecting the responsiveness of participants to light between episodes, was quantified on a discerning 5-point scale [16, 22]: 1 = not at all sensitive (indicating that exposure, even at high intensities for prolonged periods, would not precipitate dizziness), 2 = slightly sensitive, 3 = moderately sensitive, 4 = highly sensitive, and 5 = very highly sensitive (suggesting that exposure, even at very low intensities for short durations, would precipitate a dizziness response). This scale allowed for a detailed exploration of the spectrum of interictal light sensitivity in the study cohort.

Statistical Analysis

Normally distributed data are presented as the mean ± standard deviation. Comparisons of clinical characteristics between the VM with photophobia and VM without photophobia groups were conducted using t tests. Light sensitivity and frequency scores for dizziness induced by visual triggers between patients with VM with or without photophobia and those in the control group were compared using the chi-square test, followed by Bonferroni multiple comparisons post hoc test. Spearman’s correlation coefficients were used to determine the correlation between light sensitivity and frequency of dizziness induced by visual triggers. Statistical significance was set at P < 0.05. All statistical analyses were performed using the SPSS software version 20 (IBM Corp., Armonk, NY, USA).

Results

Patient Demographics and Clinical Characteristics

Overall, 366 patients with VM were enrolled in this study. Among these patients, 183 exhibited concurrent photophobia. A comprehensive summary of the demographic profiles and clinical presentations of the two cohorts is presented in Table 2. We did not observe any significant difference in age (P = 0.601) or sex (P = 0.822) between the two groups (P = 0.601). The predominantly reported vestibular symptoms included spontaneous vertigo, triggered vertigo, and dizziness. Notably, spontaneous vertigo was prevalent in both VM groups, indicating a comparable distribution (P = 0.167). Importantly, patients in the photophobia group demonstrated a markedly higher prevalence of triggered vertigo (P = 0.001), motion sickness (P < 0.001), and phonophobia (P < 0.001) than those in the nonphotophobia group. We did not observe any significant intergroup disparities in other clinical features.

Table 2 Baseline demographic and clinical characteristics of participants
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Interictal Light Sensitivity and Visual Trigger-Induced Dizziness

Table 3 lists the levels of interictal light sensitivity and frequency of dizziness induced by visual triggers in the three study cohorts. Patients in the photophobia group displayed significantly higher levels of interictal photosensitivity than those in the nonphotophobia and control groups (P < 0.001, Fig. 1). Conversely, we did not detect any statistically significant disparity in light sensitivity between patients in the nonphotophobia and control groups (P = 0.705, Fig. 1). We also noticed that the incidence of dizziness triggered by flicker (P < 0.001), glare (P < 0.001), and eyestrain (P < 0.001) among patients in the photophobia group was significantly higher than that in the nonphotophobia and control groups. Conversely, we did not detect any significant divergence in the incidence of dizziness between the nonphotophobia and control groups (flicker, P = 0.513; glare, P = 0.844; eyestrain, P = 0.989). Specifically, we found that the proportions of individuals who did not experience dizziness in response to flicker, glare, and eyestrain were as follows: 64.48%, 40.43%, and 15.85% for the control; 57.92%, 38.25%, and 16.39% for the nonphotophobia; and 34.43%, 10.93%, and 6.56% for the photophobia groups, respectively.

Table 3 Interictal light sensitivity and frequency scores of visual trigger-induced dizziness in participant groups
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Fig. 1
figure 1

Mean light sensitivity and the frequency scores of visual trigger-induced dizziness. The photosensitivity level of patients in the photophobia group was significantly higher than that of patients in the nonphotophobia and control groups (P < 0.001); however, no significant difference was observed between patients in the nonphotophobia and control groups. The frequency of dizziness induced by flicker, glare, and eyestrain was significantly higher in patients in the photophobia group than in those in the nonphotophobia and control groups (P < 0.001); however, no significant difference was observed between the last two groups. VM vestibular migraine

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Correlation Analysis of Light Sensitivity and Visual Trigger-Induced Dizziness

Quantitative assessments revealed a positive correlation between light sensitivity and the frequency of dizziness induced by flicker (r = 0.828, P < 0.001, Fig. 2a), glare (r = 0.877, P < 0.001, Fig. 2b), and eyestrain (r = 0.840, P < 0.001, Fig. 2c) in patients with VM. In particular, we observed that elevated light sensitivity corresponded with increased frequency scores for dizziness induced by flicker, glare, and eyestrain, as illustrated in Figs. 1 and 2.

Fig. 2
figure 2

Correlation between light sensitivity and visual trigger-induced dizziness. A quantitative correlation was observed between the degree of photosensitivity and frequency of dizziness triggered by flicker (a), glare (b), and eyestrain (c) in patients with VM (P < 0.001). The number of patients is represented by bubble size. As light sensitivity increased, the frequency scores of visual trigger-induced dizziness were also increased, indicating a significant positive correlation. VM vestibular migraine

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Discussion

This study explored the intricate relationships of photophobia during the VM attack with interictal photosensitivity and visually triggering dizziness in patients diagnosed with VM. Our findings elucidated the correlations among these factors, thereby enhancing our comprehension of their clinical implications and potential applications in treatment strategies.

First, our study revealed a robust association between photophobia and interictal light sensitivity. Patients in the photophobia group displayed significantly elevated interictal light sensitivity compared with those without photophobia and control participants. This observation underscored the importance of comprehending the heightened sensitivity to light in patients with VM, particularly those experiencing photophobia during attacks. It also suggested that photophobia extends beyond the vestibular migraine attack itself, signifying increased vulnerability to light even during symptom-free periods.

Furthermore, our study highlighted the link between heightened interictal light sensitivity and an increased propensity for dizziness triggered by visual factors, such as flicker, glare, and eyestrain. Some visual triggers may function as early symptoms, signifying a delicate sensitization of the visual system preceding the onset of a migraine attack. This susceptibility to visual stimuli before the migraine attack may extend to patients with VM, thereby implying a shared phenomenon between VM and classical migraines. Notably, the level of light sensitivity exhibited a significant positive correlation with the frequency of dizziness induced by visual triggers. This result further emphasized the clinical relevance of interictal light sensitivity in patients with VM, suggesting that those with elevated light sensitivity are more prone to experience vestibular symptoms triggered by visual stimuli, and providing valuable insights into potential treatment and management strategies.

Additionally, our study underscored the augmented susceptibility of patients with VM and photophobia to dizziness induced by flicker, glare, and eyestrain. This observation further strengthened the association between photophobia and dizziness induced by visual triggers, highlighting the clinical importance of addressing photophobia in the management of VM.

The mechanisms underpinning photophobia are complex and involve intricate neural pathways, from retinal ganglion cells to the occipital cortex [23]. The findings of our study aligned with those of prior neuroimaging investigations, which have demonstrated increased excitability in the visual cortex of patients with migraine, persisting both during and between attacks [24,25,26]. This heightened excitability was reported to persist interictally, and our findings provided evidence that patients with VM may share this characteristic. The ictally and interictally enhanced sensitivity to photic and auditory stimuli has already been reported in patients with migraine [19, 25]. Ictal photophobia could simply be a marker of decreased sensory threshold to discomfort, and this was also supported by our observation that the incidence of phonophobia was higher in the photophobia group. The convergence of nociceptive and light signals within the posterior thalamus and their subsequent effect on the visual and somatosensory cortex have contributed to our understanding of the neuroanatomical basis of photophobia [27, 28]. The reliability of this study was reinforced by the exclusion of patients with ophthalmic disorders and use of standard photophobia questionnaires from previous studies [21], adding depth to our photophobia-based categorization.

The interconnected neural pathways between the visual and vestibular systems, including the brainstem, cerebellum, thalamus, and cerebral cortex, play a pivotal role in processing multimodal perceptual information [29,30,31]. Functional magnetic resonance imaging has revealed the activation of brain regions associated with integrating visual and vestibular information in patients with VM subjected to visual stimulation during the interictal phase [32]. Our study provided evidence that patients with VM and photophobia exhibit increased susceptibility to flicker, glare, and eyestrain-induced dizziness, potentially attributed to central sensitization lowering the threshold to light stimulation during the interictal phase. Accordingly, the incongruence between vestibular signals and visual stimuli impairs central integration and processing, resulting in dizziness. In addition, patients in the nonphotophobia group exhibited low photosensitivity and incidence of light-induced dizziness compared to those in the control group. We speculate that the excitability of the visual cortex and the sensitization of the visual pathway are related to the light sensitivity and frequency of light-induced dizziness.

This study had some limitations. First, the questionnaire-based evaluation of light-induced factors and photosensitivity may involve some inaccuracies and is inherently subjective. Second, the term “dizziness” triggered by visual stimuli is unspecific and may not necessarily reflect vestibular symptoms. Third, since there is no recognized scale to assess the sensitivity of visually triggering dizziness, we utilized the HTSAQ scale, which is commonly used to assess sensitivity to migraine triggers, to evaluate sensitivity to dizziness triggers in patients with VM. Additionally, it is well established that patients with migraine often have high rates of comorbidity with anxiety and depression, as well as additional functional dizziness triggered by visual stimuli. Although we excluded patients with histories of functional and psychogenic dizziness, we did not utilize a psychiatric scale to make precise distinctions. Future investigations should strive to address these limitations and build on the current insights on the intricate interplay between photophobia and VM.

Conclusions

Our study highlighted a positive correlation of photophobia during the VM attack with interictal photosensitivity and visually triggering dizziness in patients with VM. These findings highlight the potential clinical utility of this relationship in guiding intervention strategies aimed at addressing the visual sensitivity characteristics in the daily lives of patients with VM.