Migraine Monitoring in the Time of COVID-19: Triggers and Protectors During a Pandemic
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Pain Medicine, 0(0), 2021, 1–11
doi: 10.1093/pm/pnab202
Advance Access Publication Date: 28 June 2021
Original Research Article
Migraine Monitoring in the Time of COVID-19: Triggers and
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Protectors During a Pandemic
Francesca Schiano di Cola, MD, Salvatore Caratozzolo, MD, Marco Di Cesare, MD, Paolo Liberini, MD,
Renata Rao, MD, and Alessandro Padovani, MD, PhD
Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
Correspondence to: Francesca Schiano di Cola, MD, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia,
Piazzale Spedali Civili 1, 25123 Brescia, BS, Italy. Tel: þ39 0303995632; E-mail: francescaschiano@hotmail.it.
Funding sources: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest: There are no conflicts of interest to report.
Abstract
Objective. Aim of the present observational study was to assess the impact of coronavirus disease 2019 (COVID-19)
quarantine on migraine and evaluate potential influencing factors. Previous studies reported mixed results regard-
ing clinical outcome during quarantine in patients with migraine. In particular, data from areas strongly affected by
COVID-19 pandemic are missing. Methods. One hundred and seventy patients, previously assessed at the Headache
Centre—ASST Spedali Civili Brescia, underwent a telephonic interview regarding migraine features and clinical, oc-
cupational, and lifestyle variables. Results. Compared to baseline, during quarantine, we found a significant overall
reduction in migraine days (14.7 6 0.6 vs 12.3 6 0.7, P < .001), with 47.1% patients reporting a clinical improvement.
Outdoor living spaces (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.7–3.07, P ¼ .009), a positive attitude
throughout quarantine (OR 4.12, 95% CI 2.3–7.1, P ¼ 0.03), working full-time (OR 1.03, 95% CI 0.5–1.9, P < .001) and a
baseline diagnosis of chronic migraine (OR 1.4, 95% CI 1.1–2.02, P ¼ 0.002) were associated with an increased chance
of migraine improvement. Being single (OR 1.5, 95% CI 1.1–2.01, P ¼ .05) and physical inactivity (OR 1.3, 95% CI 1.1–
1.6, P ¼ .02) were associated with an increased risk of worsening. Conclusions. Quarantine had an overall positive im-
pact on migraine. Based on our results, we hypothesize the reduction of daily hassles and challenges might be the
main reason for such improvement.
Key Words: Quarantine; COVID-19, SARS-CoV-2, Migraine Triggers; Chronic Migraine; Daily Hassle
Introduction The primary endpoint of the present study was to as-
sess headache frequency and intensity, in patients with a
The role played by migraine triggers has been confirmed by
preexisting diagnosis of migraine, during the quarantine
various studies, with stress, auditory stimuli, fatigue, fasting,
period (March–April 2020), compared to a preset base-
and menses the most commonly implicated [1–4]. What trig-
line period (October–November 2019). The secondary
gers seem to have in common is the alteration of routine
endpoint was to evaluate factors that might have influ-
daily activities, which increases migraine susceptibility [5].
enced migraine during quarantine. Moreover, the epide-
Due to severe acute respiratory syndrome coronavirus
miology of coronavirus disease 2019 (COVID-19)
2 (SARS-CoV-2) contagion, Italy has been in a state of
pathology in our cohort was also assessed.
emergency since late February 2020, undergoing strict
measures to implement social distancing as a measure to
contain the spread of the infection and limit viral trans-
Methods
mission. The Lombardy Region has been the most Study Design and Participants
heavily in the whole of Italy and especially the two dis- The present work is a non-profit observational study,
tricts of Bergamo and Brescia [6]. conducted at the Headache Centre—Neurology Clinic at
C The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.
V
All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 12 Schiano di Cola et al.
the Spedali Civili Hospital of Brescia. All patients previ- October–November 2019 (baseline) and March–April
ously evaluated at our Centre between September 2019 2020 (quarantine): number of headache days, number of
and January 2020 with a diagnosis of migraine [7] were severe headache days, number of moderate headache
contacted over the telephone during June and July 2020. days, mean pain intensity using the Numerical Rating
Patients underwent a telematic semi-structured interview Scale (NRS, ranging 1–10), analgesic consumption.
(see Supplementary Appendix A1). Each patient was Following comparison of headache frequency between
assigned a code containing the patient’s initials, the inter- baseline and quarantine, patients were categorized into
viewer’s initials, and the patient’s year of birth, in order
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three main groups: “unchanged” (no difference in terms
to maintain anonymity. of number of headache days between quarantine and
Inclusion criteria were the following: age 18 years; baseline); “improved” (lower headache frequency during
diagnosis of migraine (with or without aura, episodic or quarantine compared to baseline); “worsened” (higher
chronic) for at least 12 months according to the headache frequency during quarantine compared to base-
International Classification of Headache Disorders -3rd line). Moreover, patients in the “improved” and
Edition (ICHD-3)7; available headache diary between “worsened” groups were further subgrouped according
October 2019 and April 2020. Exclusion criteria were to the degree of improvement/worsening: “improved þ”
the following: refusal to participate to the study; failure (lost up to 50% of headache days during quarantine);
to complete the headache diary; headache diagnosis other “improved þþ” (lost over 50% of headache days during
than migraine according to the International
quarantine); “worsened þ” (gained up to 50% of head-
Classification of Headache Disorders -3rd Edition
ache days during quarantine); “worsened þþ” (gained
(ICHD-3)7.
over 50% of headache days during quarantine).
The study was approved by the Ethical Committee of
the ASST Spedali Civili di Brescia (NP 4176 -
COVID_MIG2020). All participants provided verbal in- COVID-19 Pathology
formed consent during the interview. Patients were asked whether they had experienced any
COVID-19 related symptomatology (fever, cough, sore
Measures throat, dyspnea, anosmia/hyposmia, ageusia/hypogeusia,
The following variables were obtained during the vomiting and diarrhea) and/or diagnosed with COVID-
interview. 19 infection during the March–April 2020 period. If af-
firmative, information about disease duration, hospitali-
Baseline Clinical and Demographical Variables zation, diagnostic tests, pharmacological treatments and
Age, gender, and body mass index (BMI) were recorded oxygen support were obtained. Moreover, the onset of a
for each patient, as well as past medical history, comor- new headache or migraine characteristics/frequency/in-
bidities, and pharmacological treatments. Women were tensity modifications was investigated.
also asked about their menstrual cycle (irregularities, pre-
vious and/or present pregnancies, menopause) and previ- Occupational Variables
ous or ongoing hormonal therapies. Town and place of Education (years), occupation (job type, hours per week),
residence, cohabitants, relationship status (single vs sta- and quarantine modifications (suspension, virtual work-
ble relationship), children (number and age) were also ing from home, unchanged) were recorded for each
recorded. patient.
Headache Assessment
Routine Daily Activities
Migraine subtype (episodic vs chronic, with and/or with-
Patients were inquired about their routine daily activities
out aura) and disease duration were obtained from the
(meals, physical activities, hobbies) and whether they had
Clinic records and confirmed during the interview.
been modified, qualitatively and/or quantitatively, by
Patients with a diagnosis of episodic migraine (EM) were
quarantine.
further classified according to whether they had a low
migraine frequency (EM-LF), that is, 1–7 migraine days
per month, or a high migraine frequency (EM-HF), that COVID-19 Quarantine Qualitative Experience
is, 8–14 migraine days per month. Information about At the end of the interview, patients were asked about
type and number of acute medications consumption per their own personal experience regarding the overall
month, prophylactic treatments (present and previous), COVID-19 pandemic and related quarantine. In particu-
medication overuse and headache characteristics (locali- lar, patients were encouraged to qualitatively express
zation, accompanying symptoms, allodynia) were also their emotions/feelings concerning the unique events of
collected. During the interview patients were asked to re- March–April 2020. These qualitative information were
view their headache diaries and report the following in- then gathered together and organized so that patients
formation, per month, regarding the time periods of could be grouped accordingly.Impact of COVID-19 Quarantine on Migraine Symptoms 3
Statistical Analysis different between the EM-LF, EM-HF, and CM groups
Shapiro-Wilk test and Levene test were used to assess the (P < .001).
normality of the distribution and the homogeneity of var- Notably, 44 (47.3%) patients with a diagnosis of CM
iance. Continuous variables were described as mean and at baseline reverted to an episodic frequency during quar-
standard deviation or median and interquartile range as antine, whereas 13 (16.9%) went from episodic to CM.
appropriate, categorical variables were expressed as fre-
quencies and percentages. The v2 test, or Fisher exact test Baseline Clinical-Demographical Variables
where appropriate, were used to compare the frequency
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Baseline clinical and demographic characteristics of all
of categorical variables within the above mentioned sub- participants are presented in Table 4. The five most fre-
groups, whereas one-way analysis of variance (ANOVA) quent comorbidities were grouped as follows: psychiatric
with Bonferroni post hoc comparisons was performed for (generalized anxiety disorder, panic disorder, cyclothy-
continuous variables (age, BMI, headache baseline fre- mic disorder, persistent depressive disorder), autoim-
quency, education). mune (celiac disease, Hashimoto thyroiditis, Addison’s
Significant variables by v2 and ANOVA were further disease, chronic atrophic gastritis), thyroid (unspecified
analyzed to assess factors associated with quarantine hypo- and hyper-thyroidism, thyroid neoplasms), gyne-
clinical improvement and worsening, using a multivari- cological (endometriosis, benign ovarian cysts, uterine
able logistic regression model. myomas), and cardiovascular disorders (systemic hyper-
For all tests, a significant difference was set to be at tension, dyslipidemia, cardiac arrhythmias, hyperhomo-
P < .05. Statistical analyses were performed with IBM cysteinemia). Data regarding town of residence, personal
SPSS Statistics 25.0 software for Windows (SPSS Inc., and housing characteristics are presented in Table 5.
Chicago, IL, USA). Four variables were found to be significantly different
within the three main groups: current smoking status (v2
Results ¼ 6.6; P ¼ .03), relationship status (v2 ¼ 14.2; P ¼ .001),
outdoor living (v2 ¼ 38.3; P < .001), psychiatric comor-
Out of 253 patients visited between September 2019 and
bidities (v2 ¼ 7.8; P ¼ .02). In particular, being single,
January 2020, 221 patients were diagnosed with mi-
lack of outdoor space and psychiatric comorbidities were
graine. Twenty-seven patients could not be reached due
more frequent in the “worsened” group, whereas current
to incorrect telephone number record/failure to answer,
smoking status, being in a stable relationship and owning
13 patients refused to participate to the present study and
an outdoor living space were more frequent in the
41 could not provide an accurate headache diary.
“improved” group (Figure 3).
Overall, 170 patients were recruited.
COVID-19 Epidemiology
Migraine History and Quarantine Assessment
Considering all participants, only 10 (5.8%) reported
Forty patients (23.5%) did not report any change in their
COVID-19 related symptoms, of whom only 3 had an ac-
migraine frequency during quarantine compared to base-
line, 80 patients (47.1%) reported an improvement, tual COVID-19 diagnosis, by either SARS-CoV-2 naso-
whereas 50 patients (29.4%) reported a worsened fre- phariengeal swab or serology. No patient was hospital-
quency (Figure 1). ized due to COVID-19. Four patients reported a modifi-
During quarantine, compared to baseline, there was a cation of their usual migraine characteristics during the
statistically significant reduction in total migraine days infection. In particular, one patient reported increased
(14.7 6 0.6 vs 12.3 6 0.7, P < .001), severely disabling pain severity whereas the other three reported increased
migraine days (7.3 6 0.4 vs 6.3 6 0.4, P ¼ .03), pain in- migraine frequency—bearing the usual characteristics.
tensity (NRS score; 7.02 6 0.09 vs 6.2 6 0.1, P < 0.001) Of note, the latter three patients were all in the
and analgesics consumption (13.9 6 0.9 vs 11.3 6 0.9, “worsened” group. Full details are presented in Table 6.
P ¼ .01) per month (Table 1). The “improved” group
lost, on average, 9.6 migraine days per month during Occupational Variables
quarantine, compared to the “worsened” group, who Mean years of education were 13.3 (63.2), with no sig-
gained 8.1 migraine days per month (P < .001). nificant differences between groups (P ¼ .72). Job types
Patients’ headache history and characteristics are pre- were grouped as follows: unemployed/not working out-
sented in Table 2. Patients with chronic migraine (CM) side of the home (student, jobless, housewife, retired), of-
were more frequent in the “improved” group, whereas fice workers (including school teaching staff), medical
patients with EM-LF more frequently underwent a clini- staff, laborers, professionals (manager, professor, entre-
cal worsening (P ¼ .003), as presented in Figure 2. Table preneur, lawyer). No significant differences were found
3 presents mean migraine days (MMD) per month at within the three main groups (P ¼ .14). However, when
baseline and quarantine, according to migraine diagnosis. stratifying the “worsened” and “improved” groups
The difference between MMD at quarantine and baseline according to the percentage of migraine improvement/
was also calculated (delta), which was significantly worsening during quarantine (see Methods), the4 Schiano di Cola et al.
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Figure 1. Percentages of migraine outcome during quarantine.
Table 1. Migraine frequency and related variables per month during baseline and quarantine
All Patients Unchanged Improved Worsened
(n ¼ 170) (n ¼ 40) (n ¼ 80) (n ¼ 50) P
MMD baseline, (mean 6 SD) 14.7 6 8.9 15.8 6 10.4 16.8 6 8.5 10.4 6 6.5Impact of COVID-19 Quarantine on Migraine Symptoms 5
Table 2. Migraine history and characteristics of all subjects
All Patients (n ¼ 170) Unchanged (n ¼ 40) Improved (n ¼ 80) Worsened (n ¼ 50) P
• Episodic migraine, LF n (%) • 39 (22.9) • 10 (35) • 9 (11.3) • 20 (40) 0.003†
• Episodic migraine, HF n (%) • 48 (28.2) • 11 (27.5) • 23 (28.7) • 14 (28)
• Chronic migraine, n (%) • 83 (48.9) • 19 (47.5) • 48 (60) • 16 (32)
Disease duration, years (mean 6 SD) 21 6 11.2 23.3 6 13.3 19.1 6 10 22.1 6 11 0.14*
Migraine prevention, n (%) 118 (69.4) 25 (62.5) 55 (68.7) 38 (76) 0.32†
Topiramate, n (%) 10 (5.8) 2 (5) 2 (2.5) 6 (12) 0.4†
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Amitriptiline, n (%) 24 (14.1) 5 (12.5) 11 (13.7) 8 (16) 0.4†
Onabotulinum toxin A, n (%) 42 (24.7) 11 (27.5) 18 (22.5) 13 (26) 0.4†
CGRP mAbs, n (%) 33 (19.4) 6 (15) 16 (20) 11 (22) 0.4†
Flunarizine, n (%) 8 (4.7) 1 (2.5) 6 (7.5) 1 (2) 0.4†
Beta-blocker, n (%) 2 (1.1) 0 (0) 2 (2.5) 0 (0) 0.4†
Medication overuse, n (%) 82 (48.2) 20 (50) 35 (43.7) 27 (54) 0.5†
LF ¼ low frequency; HF ¼ high frequency; n ¼ number; SD ¼ standard deviation; CGRP mAbs ¼ monoclonal antibodies targeting CGRP.
*One-way ANOVA.
† 2
v .
Figure 2. Migraine baseline diagnosis and clinical outcome during quarantine, expressed in percentages and confidence intervals.
following results were found (Figure 4): unemployed Regarding baseline working hours and quarantine
patients were more frequent in the “unchanged” group, modifications, all data are presented in Table 7. Full-time
office workers and professionals were more frequent, re- workers were more frequent in the “improved” group
spectively, in the “improved þ” and “improved þþ” (v2 ¼ 12.9; P ¼ .01) compared to part-time workers.
group, whereas medical staff were more frequent in the Relatively to quarantine job modifications, participants
“worsened þ” group (v2 ¼ 37.9; P ¼ .002). whose migraine improved were more frequently on6 Schiano di Cola et al.
Table 3. MMD and MMD quarantine to baseline delta according to migraine diagnosis
EM-LF (n ¼ 39) EM-HF (n ¼ 48) CM (n ¼ 83) P
MMD baseline, mean 6 SD 3.8 6 1.7 10.2 6 1.9 22.3 6 5.7Impact of COVID-19 Quarantine on Migraine Symptoms 7
Table 5. Residential, housing and personal characteristics of all subjects
All Patients (n ¼ 170) Unchanged (n ¼ 40) Improved (n ¼ 80) Worsened (n ¼ 50) P
Town of residence .54†
0–60.000 inhabitants, n (%) 125 (73.5) 28 (70) 62 (77.5) 35 (70)
>60.000 inhabitants, n (%) 45 (26.5) 12 (30) 18 (22.5) 15 (30)
House rooms .24†
1–2, n (%) 25 (14.8) 5 (12.8) 8 (10) 12 (24)
3–4, (%) 139 (82.2) 33 (84.6) 70 (87.5) 36 (72)
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>4, n (%) 5 (3) 1 (2.6) 2 (2.5) 2 (4)
Cohabitants .19*
n, (mean 6 SD) 1.79 6 1.1 1.8 6 1.2 1.8 6 1.1 1.6 6 1.1
Type .67†
None 22 (12.9) 4 (10) 10 (12.5) 8 (16)
Family 110 (64.7) 28 (70) 55 (68.8) 27 (54)
Children alone 11 (6.5) 2 (5) 4 (5) 5 (10)
Parents 27 (15.9) 6 (15) 11 (13.8) 10 (20)
Ratio rooms cohabitants .51†
1, n (%) 86 (50.9) 18 (46.2) 45 (56.3) 23 (46)
Outdoor, n (%) 111 (65.7) 21 (53.8) 71 (88.8) 19 (38)8 Schiano di Cola et al.
Table 7. Occupational variables of all subjects
All Patients (n ¼ 170) Unchanged (n ¼ 40) Improved (n ¼ 80) Worsened (n ¼ 50) P
Working hours .01*
Full-time, n (%) 122 (71.8) 23 (57.5) 63 (78.8) 36 (72)
Part-time, n (%) 8 (4.7) 0 (0) 4 (5) 4 (8)
Quarantine modifications .04*
Unchanged, n (%) 40 (29.4) 11 (42.3) 13 (18.8) 16 (39)
Virtual working, n (%) 60 (18.3) 12 (46.2) 32 (46.4) 16 (39)
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Suspension, n (%) 36 (26.5) 3 (11.5) 24 (34.8) 9 (22)
Quarantine hrs modification .03*
More hrs, n (%) 45 (26.5) 12 (30) 17 (21.3) 16 (32)
Less hrs, n (%) 61 (35.9) 8 (20) 38 (47.5) 15 (30)
Unchanged, n (%) 64 (37.6) 20 (50) 25 (31.3) 19 (38)
n ¼ number; hrs ¼ hours.
*v2
Figure 3. Baseline clinical and demographical variables significantly associated with migraine outcome during quarantine.
associated with an increased risk of migraine worsening. communication with treating neurologist), occupational
Psychiatric comorbidities, a baseline diagnosis of low- (working during the pandemic) and psychological (e.g.,
frequency EM, increased work-load during quarantine, sleep disturbances, symptoms of anxiety and/or depres-
working as a health professional, and negative feelings sion) variables. Indeed, these latter findings are in agree-
related to the pandemic were all more frequent in the ment with our present results. Mean reported migraine
“worsened” group. frequency was 5.7, in line with a diagnosis of low-
Our findings confirm previous studies [8–10] that frequency EM. Notably, our results also reported a
documented an overall migraine frequency and intensity higher frequency of migraine worsening in this group of
improvement, even in a high COVID-19 prevalence patients.
area like ours. On the contrary, a study performed A plethora of migraine triggers have been described,
in Kuwait [11] found an overall migraine worsening with stress being one of the most frequently reported.
during quarantine, which correlated with a variety of Perceived stress and failure to cope with “change” [12–
healthcare-related (e.g., access to medication, lack of 14] seem to be particularly involved. Various studiesImpact of COVID-19 Quarantine on Migraine Symptoms 9
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Figure 4. Job type and migraine outcome during quarantine, expressed in percentages and confidence intervals.
Figure 5. Qualitative COVID-19 related personal experience and migraine outcome during quarantine, expressed in percentages
and confidence intervals.10 Schiano di Cola et al.
have actually reported migraine to be more closely corre- Conclusion
lated to daily hassles than stressful events [14–15], partic- COVID-19 quarantine was a unique condition to investi-
ularly chronic migraine [16–17]. Accordingly, it has been gate the impact of routine life triggers on migraine. The
reported that patients affected with CM tend to display present pandemic had a sudden and massive impact on
higher levels of perceived stress [18]. Moreover, these daily activities, working conditions, freedom of move-
patients also have to balance family and working life ment, interpersonal relationships and access to health-
with a chronic pain condition, with reported high levels care. In light of such a complex scenario, the present
of presenteeism, considering the disability associated
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findings suggest that the reduction of routine daily has-
with CM [19]. sles, even during a stressful event like a pandemic, to-
The main “benefit” of quarantine, in terms of mi- gether with particular personal and logistic conditions,
graine improvement, could be related to the reduction of had a significant positive impact on migraine.
daily hassles, especially in patients with a baseline highly What is the impact of these findings? On the clinical
stressful environment. Indeed, these patients might actu- level, physicians might continue to educate patients on
ally be those who benefited more from the more stable lifestyle modifications. It also raises questions on our life-
and “unforseenless” daily routine, once acquainted with style in general. Modern humans are becoming more and
quarantine. It has been hypothesized that it is the level of more self-centered, work-centered, “alone-centered”
“surprise,” in terms of rarity and low probability, of a [31]. In 2019,
migraine trigger to actually make it a trigger [20]. Thus, World Health Organization (WHO) declared loneli-
in a routine made of virtual work from home, regular ness a major health concern worldwide [32]. Like many
meals, proximity to the one’s own family, it seems plausi- other primates, humans are intensely social. The higher
ble to witness a migraine improvement rather than a your social capital, the faster you get better if you fall ill
worsening. and the longer you will live [33]. Physical inactivity,
Regarding migraine worsening, this event was more meaningless social relationships, social isolation, poor
frequent in single patients, who reduced their level of quality diets, over-working have all been associated,
physical activity, increased their work load and with psy- from years, to poor physical and mental health [28], and
chiatric comorbidities. These findings are in line with migraine seems not to be excluded.
previous reports regarding the negative impact of quaran-
tine, social isolation and loneliness, especially on psychi-
atric patients, reported during the COVID-19 pandemic Supplementary Data
[21–27]. Migraine worsening, in these patients, might Supplementary data are available at Pain Medicine
just be the tip of the iceberg. Numerous studies [28–30] online.
have proven social isolation and loneliness to have a dra-
matic, negative impact on psychological well-being,
physical health, and even longevity. References
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