Impact of the COVID-19 pandemic on migraine in Japan: a multicentre cross-sectional study

In this multicentre study, we studied the effects of social distancing during the first wave of the COVID-19 pandemic on headache-related disability, daily life and other various clinical symptoms using clinical information, headache diaries, and questionnaires at multiple headache centres. We found that a significant number of patients reported increased stress, a negative impact of the first wave of the COVID-19 pandemic on their daily lives, concerns about COVID-19 and changes in mood and sleep. A higher migraine risk in healthcare workers than in the general population was reported in a nationwide population-based cohort study [19]. In our study, 98.3 % of the participants were on acute medication, and 63.4 % were on preventive medication; 30.7 % reported increased acute headache treatment, and 15.5 % reported additions to or changes in headache-prevention medication.

Based on the total MIDAS and A and B scores in this study, headache-related disability, the number of headache days and headache intensity did not change during the first wave of the COVID-19 pandemic. This result was contrary to the research hypothesis that increased stress worsens headache and negatively impacts headache-related disability in patients with migraine. In a web survey of 1,018 patients with migraine during the lockdown period, 60 % reported an increase in migraine frequency, 16 % reported a decrease in migraine frequency and 10 % reported progression to chronic migraine. Migraine severity was increased in 64 % of patients [20]. An observational cross-sectional study from Italy including 433 migraine patients found that migraine frequency and intensity were significantly reduced during quarantine compared to the pre-quarantine period and were correlated with an increased number of days at home [21]. In contrast, similar to the results of our study, Verhagen et al. [22] performed a study in 592 migraine patients who used headache e-diaries and showed that the number of migraine days did not change, the daily use of acute medication decreased and well-being scores improved after lockdown due to the COVID-19 outbreak. We agree with speculation made by Verhagen et al. [22] that the combined effects of working from home, reductions in demanding social lives, and the freedom to choose how to organise one’s time contributed to the lack of change in headache status during the COVID-19 pandemic. However, we could not determine the factors that contributed to the lack of a significant change in the MIDAS score before and during the first wave of the COVID-19 pandemic in this study.

In our study, we found that 56.8 % of the patients with migraine reported increased stress, and increased stress was one of determinants of the development of new-onset headaches during the first wave of the COVID-19 pandemic. In a study from China performed during the COVID-19 outbreak, patients with migraine had significantly higher levels of stress than the controls [23]. In a 90-day prospective daily-diary cohort study involving adults with episodic migraine, increased levels of stress were associated with the risk of migraine the next day [24]. During the COVID-19 pandemic, perceived stress was more strongly associated with brooding and COVID-related rumination among patients with migraine than healthy controls [25]. Also, perceived stress has been found to be associated with chronic migraine, depression and anxiety [26]. The utilization of coping strategies to manage stressful life events has been reported to have a substantial impact on migraines in social situations and at work in patients with migraine without aura [27]. Therefore, differences in the strategies for coping with stress during periods of social restrictions, limited access to hospitals and medication shortages may be associated with the number of headache days and nature of headaches in various studies. In our study, we did not assess how the patients coped with their stress; however, low proportions of participants had difficulty accessing a hospital (15.7 %) and reported a medication shortage (7.1 %), which could be factors that would increase stress.

According to the stepwise linear regression analysis, among the many clinical and social characteristics of patients with migraine, the worsening of sleep, increased use of acute medications, increased stress, medication shortages, the presence of comorbidities, the absence of aura and new-onset headache were significant contributors to increased headache-related disability during the first wave of the COVID-19 pandemic. During the COVID-19 pandemic, patients with migraine were more likely than patients with other neurological conditions to report worsened anxiety and sleep problems [28]. Other studies addressed changes in headache intensity or migraine days during the COVID-19 pandemic [22], but changes in disability related to headache in patients with migraine have not been well studied.

Other noteworthy findings in our study include the fact that 15.7 % of the patients developed new-onset headache during the pandemic, the nature of which differed from that of their pre-existing migraine headaches. In a study of 158 healthcare workers (64.6 % nurses, 32.3 % physicians, and 3.2 % paramedical staff), pre-existing primary headache was present in 29.1 %, and 81 % had complaints of headache related to wearing PPE. New PPE-associated headaches were associated with the presence of pre-existing primary headaches and combined PPE usage > 4 h/day [29]. Additionally, a study consisting of 383 Italian healthcare providers found that 44 (26.5 %) developed de novo facemask-associated headache [30]. In our study, 31.8 % were involved in frontline work, and 12.5 % were healthcare providers. The increased duration of mask usage (h/d) was significantly longer in patients with new-onset headache than in patients without new-onset headache; however, in the logistic regression analysis, it did not remain a significant factor for new-onset headache. Worsened sleep and mood significantly contributed to new-onset headache in our study after adjustment for clinical factors. However, since the location and presentation of the new headaches were diverse and overlapped, we could not determine their characteristics. In healthcare workers, headaches related to PPE use were associated with photophobia, phonophobia and nausea [29]; however, these factors were not determinants of new-onset headache in our study.

In this study, we asked patients to complete a MIDAS assessment of their condition reflecting the 3-month period before and after the first state of emergency declaration. One limitation is that the state of emergency declaration issued between April and May 2020 was a recommendation, with no enforcement until December, the period of the research. Thus, social distancing in our study setting was based on the premise of voluntary cooperation by the population. Second, although the study period was limited to 7 months and we adjusted for the evaluation period after the end of the first declaration of the state of emergency in the linear regression analysis predicting changes in the total MIDAS score, our study was subject to recall bias. Third, 73.6 % of the patients who kept a headache diary reported the number of headache days on the MIDAS based on their diary. However, the number of days reported on the MIDAS in the remaining patients was self-reported. Fourth, we did not include healthy controls in our study because we intended to focus on changes in clinical symptoms in patients with migraine. Fifth, we identified new-onset headache in several patients; however, the presence of photo/phono/osmophobia, nausea, vomiting, symptom worsening due to physical activity, cranial autonomic symptoms and relief after using triptans were not assessed. The relationships between new-onset headache and wearing a mask and the type of mask worn were unclear. Therefore the association between mask-related headache and new-onset headache was not investigated. Sixth, the PGIC scale is not specifically designed to assess changes in mood or sleep, so the use of this assessment method may have influenced the results of this study. Seventh, we did not have baseline data for our participants in this study, and all the data were collected at the same assessment. Last, in our multicentre study, 83.5 % of the patients received triptans, suggesting a possible selection bias towards migraine patients treated by headache specialists at headache centres. In addition, our study was conducted at multiple major headache centres, but it may not be representative of all migraine patients in Japan.

In conclusion, our study identified several clinical factors contributing to headache-related disability and helped clarify the changes in clinical symptoms in migraine patients during the COVID-19 pandemic, which may contribute to improving the future management of migraine patients. In patients with migraine, new-onset headache, stress and sleep disturbances should be carefully monitored and adequately addressed during the COVID-19 pandemic. Our study is also clinically significant because it reveals the impact of the social conditions associated with COVID-19 infection control measures on migraine, a major neurological disease.