Original Article

Cephalalgia
2024, Vol. 44(4) 1–10
Physical impairment during and between ! International Headache Society 2024
Article reuse guidelines:
migraine attacks: A daily diary study of sagepub.com/journals-permissions
DOI: 10.1177/03331024241249747
patients with chronic migraine journals.sagepub.com/home/cep

David J Whitaker1 , Gina M Dumkrieger1 , Joseph G Hentz2,

David W Dodick1,3 and Todd J Schwedt1

Abstract
Objective: While a substantial body of research describes the disabling impacts of migraine attacks, less research has
described the impacts of migraine on physical functioning between migraine attacks. The objective of this study is to
describe physical impairment during and between migraine attacks as a dimension of burden experienced by people
living with chronic migraine.
Methods: The physical impairment domain of the Migraine Physical Function Impact Diary was recorded in headache
diaries from the Medication Overuse Treatment Strategy trial. Days with moderate to severe headache were used to
approximate migraine attacks. Factor analysis and regression analysis were used to describe associations between
migraine and physical impairment.
Results: 77,662 headache diary entries from 720 participants were analyzed, including 25,414 days with moderate to
severe headache, 19,149 days with mild headache, and 33,099 days with no headache. Mean physical impairment score
was 41.5 (SD ¼ 26.1) on days with moderate to severe headache, 12.8 (SD ¼ 15.0) on days with mild headache, and
5.2 (SD ¼ 13.1) on days with no headache. Physical impairment on days with mild headache and days with no headache was
significantly associated with days since last moderate to severe headache, physical impairment with last moderate to severe
headache, mild headache (compared to no headache), depression, hypersensitivities and cranial autonomic symptoms.
Conclusions: Physical impairment occurs on migraine and non-migraine days. Study participants with frequent head-
aches, symptoms of depression, hypersensitivities and cranial autonomic symptoms experience physical impairment at a
higher rate on days with no headache and days with mild headache.
Clinical Trial Registration: ClinicalTrials.gov (NCT02764320)

Keywords
Migraine, Physical Impairment, Headache, Disability, Chronic Disease
Date received: 15 December 2023; revised: 9 March 2024; accepted: 27 March 2024

Introduction people with migraine. While there have been numerous

The World Health Organization ranks migraine as the
second leading cause of disability measured in years
lived with disability (YLDs), accounting for 41.1 mil-
lion YLDs in 2019, 4.8% of all YLDs globally (1).
Physical impairment during and between migraine
attacks constitutes a key dimension of migraine-
associated disability (2). While much of the disability
resulting from migraine occurs during migraine
attacks, disability can persist between migraine attacks.
Quantifying disability during migraine attacks without
also considering disability between migraine attacks
underestimates the total burden experienced by
studies reporting migraine-associated disability during
migraine attacks and total migraine-related disability
based on answers to questionnaires requiring patient
Department of Neurology, Mayo Clinic, Phoenix, USA
Department of Quantitative Health Sciences, Mayo Clinic. Scottsdale,
USA
Atria Academy of Science and Medicine, NY, USA
Corresponding author:
Todd J. Schwedt, Mayo Clinic, 5777 East Mayo Blvd, Phoenix, AZ 85054,
USA.
Email: schwedt.todd@mayo.edu

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2 Cephalalgia

recall over a given period (e.g. MIDAS, HIT-6), there

has been a lack of studies quantitatively assessing dis-
ability on migraine and non-migraine days using daily
headache diary data.
The objectives of this study were to describe physical
impairment on migraine days and non-migraine
days and to identify factors associated with physical
impairment.

Methods
Standard protocol approvals, registrations, and
patient consents
The Medication Overuse Treatment Strategy (MOTS)
Trial was approved by the Mayo Clinic Institutional
Review Board and the IRB of record for each enrolling
site, and it was registered at ClinicalTrials.gov
(NCT02764320) with predefined primary and second-
ary outcome measures. All participants underwent an
informed consent process and signed IRB-approved
consent forms.

Study design and population

The present study analyzed data from 720 chronic
migraine patients collected in the MOTS Trial (3).
Participants were recruited in the course of routine clin-
ical care at 34 sites in the United States including six
primary care clinics, 14 general neurology clinics, and
14 headache specialty clinics. Eligibility rules required
participants to be 21 years of age or older and meet
International Classification of Headache Disorders
3 beta (ICHD-3b) (4) diagnostic criteria for chronic
migraine and for medication overuse as defined
within the medication overuse headache diagnostic cri-
teria. ICHD-3b was the most recent ICHD diagnostic
criteria available at the time of study initiation. Nine
hundred and seventy eight individuals were assessed for
eligibility (see Figure 1).
Measures
Headache diary
Participants completed daily electronic headache dia-
ries for up to 20 weeks during their involvement in the
MOTS Trial. Each day in the headache diary, partic-
ipants indicated whether they experienced headache,
peak headache intensity (mild, moderate, or severe),
headache duration, a one-item measure indicating
whether they found the headache disabling on a four-
point scale from “able to function normally” to “not
able to function at all”, migraine medication use, pain
medication use, and the Physical Impairment domain
Figure 1. Flow Diagram
of the Migraine Physical Function Impact Diary
(MPFID-PI), discussed below. Diary entries were
date and time stamped. Compliance with diary keeping
was maximized by allowing access through a mobile
application and a web-based platform, sending auto-
mated e-mail reminders to complete diary entries, and
providing remuneration for diary compliance. In total,
77,662 headache diary entries were recorded. The head-
ache diary employed in MOTS was designed to mea-
sure the primary outcome, frequency of days with
moderate to severe headache (DMoH). The diary did
not collect all information required to formally assess
whether symptoms met criteria for a migraine attack.
In our analysis, self-reported DMoH was used as a
proxy for a migraine attack. In the study population
(diagnosed chronic migraine with medication overuse,
headache days per 28 days mean 22.5 [SD 5.1]), it is
likely that the vast majority of DMoH were attribut-
able to migraine attacks (3). Days were considered
DMoH when patients reported headache that lasted
at least two hours and peaked at moderate or severe
intensity. Days were classified as days with mild head-
ache (DMiH) when patient diary data indicated a head-
ache that did not meet criteria for moderate to severe
headache and days with no headache (DNH) when the
diary indicated no headache. Self-reported DMiH and
DNH were used as a proxy for non-migraine days.
Whitaker et al.
While these proxy definitions may misclassify some
migraine days, we believe they are useful in describing
findings.
Migraine Physical Functioning Impact Diary
In each headache diary entry, participants were
prompted to complete select questions from the
MPFID, a validated instrument measuring migraine
impact on physical functioning over the prior
24 hours (5,6). The selected questions constitute the
physical impairment (PI) domain of the MPFID, five
items, each rated on a five-point scale. Three items ask
about severity of difficulty (e.g., “In the past 24 hours,
were you able to get out of bed?”) rated on a scale from
“without any difficulty” to “unable to do”. Two items
ask about duration of difficulty (e.g., “In the past
24 hours, how much of the time did you have difficulty
moving your head?”) rated on a scale from “none of
the time” to “all of the time”. Sum scores are linearly
transformed to take a range of zero to 100 where higher
score values indicate greater migraine-related physical
impairment.
Covariate measures
Age, sex, race, and ethnicity were collected as demo-
graphic measures. Participants completed a headache
characteristics questionnaire at baseline, constructed
using methodology aligned with the NIH National
Institutes of Neurological Disorders and Stroke
Common Data Elements for headache (7). The ques-
tionnaire included headache frequency, date of chronic
migraine onset, medication use, headache pain charac-
teristics, and an inventory of non-headache migraine
symptoms. Headache pain characteristics included
average headache duration if untreated or inadequately
treated, average headache duration if successfully
treated, pain location (right, left, front, back, and/or
side), whether the pain was typically unilateral, pain
quality (pulsating/throbbing, pressure/aching, stab-
bing, and/or burning), average pain intensity, maxi-
mum pain intensity, and whether headache worsened
with physical activity. Non-headache symptoms includ-
ed nausea, vomiting, sensitivity to light, sensitivity to
sound, conjunctival injection, tearing, nasal conges-
tion/rhinorrhea, eyelid drooping, visual aura, sensory
aura, motor aura, language aura, and other auras.
Participants also completed several validated
questionnaires at baseline: Headache Impact Test 6
(HIT-6), Patient Reported Outcomes Measurement
Information System (PROMIS) Pain Interference
Questionnaire 6b, Generalized Anxiety Disorder 7
(GAD-7), and Patient Health Questionnaire 9 (PHQ-9).
HIT-6 is used to assess the impact of headaches on the
3
respondent’s functioning in vocational, social, and
home settings (8). HIT-6 scores range from 36 to 78,
where 36 to 49 indicates “little or no impact”; 50 to 55,
“some impact”; 56–59, “substantial impact”; and 60 to
78, “severe impact”. PROMIS Pain Interference 6b
measures the extent to which pain has interfered with
social, cognitive, emotional, physical, and recreational
activities over the prior seven days (9). GAD-7 is used
to screen for symptoms of generalized anxiety disorder
(10,11). GAD-7 scores range from 0 to 21, where 0 to
4 indicates “minimal anxiety”; 5 to 9, “mild anxiety”;
10 to 14, “moderate anxiety”; and 15 to 21, “severe
anxiety”. PHQ-9 is used to screen for symptoms of
depressive mood disorders (12). PHQ-9 scores range
from 0 to 27, where 0 to 4 indicates “none-minimal”;
5 to 9, “mild”; 10 to 14, “moderate”; 15 to 19,
“moderately severe”; and 20 to 27 “severe” depression.
Statistical analyses
Variables from the questionnaires and daily diaries
were analyzed individually by frequency and distribu-
tion. MPFID-PI, HIT-6, PROMIS Pain Interference
Questionnaire 6b, GAD-7, and PHQ-9 scales were
scored according to published guidelines and MPFID-
PI was evaluated for internal consistency. In headache
diary data, only entries with complete responses to the
headache diary and MPFID-PI were analyzed.
Exploratory factor analysis and confirmatory factor
analysis were used to extract common factors from the
inventory of non-headache migraine symptoms con-
tained within the headache characteristics questionnaire.
Correlations among headache diary variables, MPFID-
PI, and covariate measures were examined to inform
regression modeling. An initial linear mixed model of
MPFID-PI on DMoH was used to assess the utility of
common factors extracted from non-headache symp-
toms and inform the design of a time series regression
model of MPFID-PI on DMiH and DNH.
Results
Headache diary data
Diary data contained 25,414 DMoH and 52,248 com-
bined DMiH and DNH, including 19,149 DMiH and
33,099 DNH. Headache information and MPFID-PI
were both recorded in 77,381 of 77,662 diary entries
(99.6%). MPFID-PI scores differed by headache
status: Mean on DMoH was 41.5 (SD ¼ 26.1). Mean
on DMiH and DNH combined was 8.0 (SD ¼ 14.3),
including a mean of 12.8 (SD ¼ 15.0, n ¼ 19,149) on
DMiH and 5.2 (SD ¼ 13.1, n ¼ 33,099) on DNH (see
Table 1). Internal consistency of the scores was excel-
lent (a ¼ 0.96) with overall mean 19.0 (SD ¼ 24.7).
4 Cephalalgia

MPFID-PI on DMoH was distributed roughly nor- as a continuous variable. MPFID-PI on DMiH and
mally (median ¼ 40.0, mean ¼ 41.5, skewness ¼ 0.3, DNH was strongly zero-inflated; 63.5% of combined
kurtosis ¼ 2.4; see Figure 2) and conducive to modeling DMiH and DNH entries reported no physical impair-
Table 1. Mean MPFID-PI by Headache Status: Mean MPFID-PI is ment (median ¼ 0, mean ¼ 8.0, skewness ¼ 2.2,
higher DMoH than DMiH and DNH. Among mild and headache kurtosis ¼ 8.2; see Figure 2). MPFID-PI on DMiH
free days, mean MPID-PI is higher on mild headache days than and DNH was not conducive to modeling as a contin-
headache free days. uous variable. However, the relative frequency with
Headache Status n MPFID-PI Mean (SD) which participants reported any physical impairment
(MPFID-PI > 0) varied systematically with respect to
Moderate to severe headache 25,295 41.5 (26.1) migraine characteristics and time (see, e.g., rates of phys-
Mild and headache free 52,086 8.0 (14.3) ical impairment by day since last DMoH in Table 2).
• Mild headache 19,098 12.8 (15.0) Thus, the likelihood of physical impairment (as defined
• Headache free 32,988 5.2 (13.1)
by MPFID-PI > 0) was conducive to modeling, and
n, Sample size; SD, standard deviation. logistic regression was used to model the likelihood of
physical impairment on DMiH and DNH.

Figure 2. MPFID-PI Distribution by Headache Status

Whitaker et al. 5

Covariate measures Hawaiian/Other Pacific Islander (0.0%), 574 White

(81.3%), and 67 other (9.2%), while 10 declined to
Among 706 participants who responded to both the
identify (1.4%). With respect to ethnicity, 94 partici-
demographic questionnaire and patient questionnaires:
pants identified as Hispanic (13.3%), 600 as not
Age ranged from 21 to 83 years with mean 43.9
Hispanic (85.0%), and 12 declined to identify (1.7%).
(SD ¼ 13.0). Six hundred and seventeen participants
were assigned female at birth (87.4%), 88 were assigned Statistics describing HIT-6, PROMIS Pain Interference
male (12.5%), and one declined to identify (0.1%). 6b, GAD-7, and PHQ-9 scores are presented in
With respect to race, two participants identified as Table 3.
American Indian/Alaska Native (0.3%), nine Asian
(1.3%), 44 Black/African American (6.2%), 0 Factor analysis of headache characteristics
Among headache characteristics, non-headache symp-
Table 2. Physical Impairment on Non-Migraine Days: The pro- toms were correlated with MPFID-PI on DMoH (e.g.,
portion of individuals reporting any physical impairment on non- qphotophobia, MPFID-PI ¼ 0.24) and with one another
migraine days decreased as the number of days since last DMoH
increased. (e.g., qnausea, vomiting ¼ 0.73). This prompted factor
analysis of non-headache migraine symptoms to
Days since Reporting any PI relative attempt to extract common factors, such that non-
last DMoH n PI (MPFID-PI > 0) frequency (%) headache symptoms could be retained as explanatory
1 6,633 3,092 46.6 variables in regression without introducing several cor-
2 3,939 1,617 41.1 related, binary regressors. In exploratory factor analy-
3 2,636 1,008 38.2 sis, a model with four factors in geomin rotation
4 1,826 671 36.7 proved to be the most analytically useful, cumulatively
5 1,290 447 34.7 explaining 59% of item variance and organizing symp-
6 927 308 33.2
toms into four common factors:
7 683 211 30.9
8þ 2,734 725 26.5
• F1 (Auras): language aura, motor aura, visual aura,
PI, Physical impairment; n, sample size. and sensory aura;

Table 3. Covariate measures.

Participants* (%) Analytic Sample† (%)

n 706 (100.0) 582 (100.0)

Female 617 (87.4) 512 (88.0)

Male 88 (12.5) 69 (11.9)
Chose not to answer 1 (0.1) 1 (0.2)
American Indian/Alaska Native 2 (0.3) 2 (0.3)
Asian 9 (1.3) 8 (1.4)
Black/African American 44 (6.2) 30 (5.2)
Hawaiian/Other Pacific Islander 0 (0.0) 0 (0.0)
White 574 (81.3) 484 (83.2)
Other 67 (9.5) 52 (8.9)
Chose not to answer 10 (1.4) 6 (1.0)
Hispanic 94 (13.3) 70 (12.0)
Not Hispanic 600 (85.0) 503 (86.4)
Chose not to answer 12 (1.7) 9 (1.5)
Participant Mean (SD) Analytic Sample Mean (SD)

Age 43.8 (13.0) 44.0 (13.0)

HIT-6 60.5 (7.6) 59.9 (7.4)
PROMIS Pain Interference 6 b 61.0 (8.0) 60.5 (7.8)
GAD-7 6.4 (5.6) 6.0 (5.4)
PHQ-9 7.0 (5.9) 6.6 (5.6)
*n ¼ 706 participants completing both demographic information and validated questionnaires.
†
n ¼ 582 participants in the analytic sample of contiguous non-migraine days for time series regression.
n, Sample size; SD, standard deviation.
6 Cephalalgia
• F2 (GI Symptoms): nausea and vomiting;
• F3 (Hypersensitivities): photophobia and phono-
phobia; and
• F4 (Cranial Autonomic Symptoms): tearing, nasal
congestion/rhinorrhea, conjunctival injection, and
drooping eyelid.
Confirmatory factor analysis (CFA) was used to
assess the fit of a model with four factors retaining
factor loadings > 0.3 from EFA (see CFA model as
specified in Figure 3). The CFA model fit well with
Tucker-Lewis fit index (TLI) 0.96.
Regression analysis of physical impairment
on DMoH
To test the utility of the common factor scores, severity
scores were calculated for each common factor and
included in regression analysis of MPFID-PI on
DMoH. Scores were calculated by counting the
number of symptoms assigned to each factor that
were endorsed by the participant. For example, a par-
ticipant who reported no history of auras would be
assigned a score of zero on F1 (Auras), while a partic-
ipant who reported a history of visual auras and sen-
sory auras would be assigned a score of two. Diary
data contained repeated observations of each partici-
pant, which raised the possibility that data were over-
dispersed due to clustering by participant. To test for a
clustering effect and correct for overdispersion, linear
mixed effects regression was employed. We first con-
structed a reference model using headache duration
and peak pain intensity to predict MPFID-PI on
DMoH (n ¼ 25,295). In the reference model, fixed
Figure 3. Confirmatory Factor Analysis Model of Non-Headache Symptoms
effects of headache duration and peak headache inten-
sity explained 27% of the variation in MPFID-PI
(r2model in Table 4) The random intercept parameterizing
individual differences explained an additional 44% of
variation in MPFID-PI (r2complete –r2model ). We then con-
structed a test model using headache duration, head-
ache intensity, and severity scores on the four common
factors. In the test model, fixed effects explained 35%
of variation in MPFID-PI, meaning 8% of variation in
physical impairment was explained by severity scores
on the four common factors.
Regression analysis of physical impairment on DMiH
and DNH
Analyzing physical impairment on DMiH and DNH as
a time series required the calculation of days since last
migraine and days until next migraine (using DMoH as
a proxy). In that calculation, an unlogged DMoH could
render an erroneous count of days since last DMoH or
days until next DMoH. To rule out that possibility,
diary entries were only retained for time series analysis
when each day since the last DMoH and until the next
DMoH was also logged (n ¼ 21,652). The shortest con-
tinuous span of combined DMiH and DNH was one
day and the longest was 80 days (mean ¼ 4.6,
SD ¼ 6.2). The analytic sample was trimmed at the
third standard deviation of days since last DMoH and
days until next DMoH, retaining only diary entries
within 23 days of the last DMoH and 23 days of the
next DMoH, resulting in an analytic sample of 20,658
complete records from 580 participants.
Subsequently, associations between MPFID-PI and
each other variable were tested using univariable
Whitaker et al. 7

Table 4. Regression Analysis of MPFID-PI on DMoH: Fixed effects in the reference model explain 27% of variation in MPFID-PI
(r2model ¼ 0.27), while fixed effects in the test model with common factors explain 35% of variation (r2model ¼ 0.35). All four common
factors are significantly associated with MPFID-PI. The significant random effects describe the clustering effect introduced by repeated
observations of each participant.

Reference Model Test Model

n ¼ 25,294 n ¼ 25,294
Participants ¼ 663 Participants ¼ 663
Random Lower Upper Random Lower Upper
Cluster Effect SD 95% CI 95% CI Cluster Effect SD 95% CI 95% CI

Participant Intercept 16.41 15.51 17.37 Participant Intercept 15.17 14.29 16.01
Lower Upper Lower Upper
Fixed Effect b 95% CI 95% CI Fixed Effect b 95% CI 95% CI

Intercept 42.36 44.18 40.53 Intercept 59.66 64.19 55.14

Intensity 22.19 21.77 22.61 Intensity 22.19 21.77 22.60
Duration 5.39 5.17 5.61 Duration 5.37 5.15 5.59
F1 (Auras) 3.30 2.10 4.49
F2 (GI Symptoms) 3.11 1.34 4.87
F3 (Hypersensitivities) 5.06 2.76 7.36
F4 (Cranial Autonomic Symptoms) 1.50 0.42 2.58
r2model 0.27 r2model 0.35
r2complete 0.71 r2complete 0.72
n, Sample size; SD, standard deviation; CI, confidence interval; b, slope coefficient.

logistic mixed models. Those variables that were signif- Table 5. Logistic Mixed Model of PI on DMiH and DNH:
icantly associated in univariable models were retained Likelihood of physical impairment on DMiH and DNH was sig-
in multivariable modeling (with certain exceptions nificantly associated with mild headache on that diary day, phys-
ical impairment on last DMoH, F3 (hypersensitivities), F4 (cranial
described below). The multivariable model included: autonomic symptoms), days since last DMoH, and PHQ-9.
mild headache on diary day, presence of any physical
impairment on last DMoH, F1 (auras), F3 (hypersen- n ¼ 20,658
sitivities), F4 (cranial autonomic symptoms), days since Participants ¼ 580
last DMoH, duration of last moderate to severe head- Random Lower Upper
Cluster Effect SD 95% CI 95% CI
ache, GAD-7, and PHQ-9. Pain medication and
migraine abortive medication use on a diary day were Participant Intercept 3.55 3.17 3.98
positively associated with physical impairment, which Participant Headache 2.45 2.13 2.82
was interpreted as a confounded relationship (i.e., a Lower Upper
third variable such as headache intensity may have Fixed Effect b 95% CI 95% CI
caused both physical impairment and pain medication
use). Pain medication and migraine abortive medica- Intercept 6.47 7.41 5.53
tion use were excluded from multivariable modeling. Headache 3.91 3.58 4.24
PI w/ migraine 1.50 1.19 1.80
Days since last DMoH and days until next DMoH
F1 (Auras) 0.19 0.05 0.43
are characterized by a determinative algebraic relation-
F3 (Hypersensitivities) 0.44 0.03 0.85
ship; days since last DMoH was advanced to multivar- F4 (cranial autonomic symptoms) 0.30 0.08 0.51
iable modeling for its stronger correlation to physical Days Since Last DMoH 0.06 0.07 0.04
impairment (qDLM, PI ¼ 0.16, qDNM, PI ¼ 0.14). The Last MoH Duration 0.04 0.02 0.10
presence of physical impairment on the last DMoH GAD-7 0.00 0.07 0.07
expressed as an event (event ¼ 1, non-event ¼ 0) had PHQ-9 0.21 0.14 0.28
better explanatory power than MPFID-PI score on r2model 0.33
last DMoH in univariable models and the event vari- r2complete 0.83
able was advanced to multivariable modeling. n, Sample size; SD, standard deviation; CI, confidence interval; b, slope
The final model is presented in Table 5. Mild head- coefficient.
ache, physical impairment on last DMoH, F3 (hyper- since last DMoH, and PHQ-9 were significantly asso-
sensitivities), F4 (cranial autonomic symptoms), days ciated with physical impairment on DNH and DMiH
8 Cephalalgia
(a ¼ 0.05). F1 (auras), duration of last moderate to
severe headache, and GAD-7 were not significantly
associated with physical impairment on DNH and
DMiH. Mild headache was associated with physical
impairment as both a fixed effect, describing the
mean effect among all participants, and a random
effect, describing differences in the effect size among
individual participants. A random intercept term
describing individual differences in likelihood of phys-
ical impairment was also significant. Using odds ratio
estimates to describe the size of fixed effects in the
model of physical impairment on non-migraine days:
• On DMiH, participants were 49.9 times more likely
to report physical impairment compared to DNH
(95% CI 35.9 to 69.4).
• Participants were 4.5 times more likely to report
physical impairment on DMiH and DNH when
they reported physical impairment on their last
DMoH (95% CI 3.3 to 6.0).
• With an additional day since last DMoH, partici-
pants were 5.8% less likely to report physical
impairment (95% CI 3.9% to 6.8%).
While fixed effects explained 33% of the variation in
likelihood of physical impairment on DMiH and
DNH, random effects explained an additional 50% of
the variation.
Discussion
Patterns of physical impairment on DMoH, DMiH,
and DNH suggest that physical impairment: 1) is great-
est on migraine days, but also occurs on non-migraine
days; 2) is less likely to be present as one gets further
from their last migraine; 3) is higher on DMiH than
DNH; 4) is partially explainable by migraine headache
intensity, history of non-headache symptoms, days
since last migraine, occurrence of mild headache, and
depression as measured in PHQ-9; and 5) is character-
ized by individual variation among participants.
Physical impairment and, more broadly, functional
impairment during migraine attacks have been consis-
tently described and thoroughly quantified in the liter-
ature. For example, in Brandes’s study (13) of migraine
in the United Kingdom, France, Germany, Italy, and
the United States, 52.3% of the 516 adult migraine
patients who were interviewed required bed rest to
manage migraine attacks. In Buse and colleagues’ sys-
tematic review (14), they found that impairment related
to migraine incurred enormous indirect costs through
missed work, school absenteeism, and adverse impacts
to family relationships.
While functional impairment on non-migraine days
has been described in the literature, a smaller body of
work has attempted to quantify this dimension of
disease burden. Buse and colleagues’ review (14) fur-
ther describes the nature of burden between migraine
attacks, citing worry, poorer sleep, and lower energy
levels between attacks, with fewer than half of migraine
patients surveyed reporting that they recover fully
between attacks. Dahl€ of and Dimen€as (15) compared
self-report measures from 101 healthy control partici-
pants to those of 103 migraine patients surveyed
between migraine attacks and found migraine patients
reported poorer contentment, vitality, and sleep.
Findings from Mannix and colleagues’ (2) systematic
review and subsequent concept elicitation interviews
with 32 participants elaborated the role of physical
impairment in migraine-associated disability during
and between migraine attacks. Twenty-eight of 32 par-
ticipants (88%) mentioned physical function without
prompting, citing impairments such as needing to lie
down and difficulty moving their heads, bending over,
getting out of bed, or performing activities that required
physical effort both during and between migraine
attacks. Ultimately, Mannix and colleagues (2) found
physical function to be the primary concept of interest
in elicitation from patients, present in ictal and interictal
periods in both episodic migraine and chronic migraine.
Our analysis is unique since it: 1) measured physical
impairment daily using a headache diary, yielding more
detailed information than the use of questionnaires
with weekly, 30 day, or 90 day recall timeframes; 2)
measured physical impairment on DMoH, DMiH,
and DNH; 3) investigated the impact of time since
last migraine on physical impairment; and 4) identified
other factors associated with physical impairment, such
as symptoms that occur during migraine attacks.
The following limitations of the MOTS Trial design
and our analysis should be considered. 1) These find-
ings may not generalize to populations with migraine
diagnoses other than chronic migraine with medication
overuse. 2) While history of non-headache symptoms
was found to be significantly associated with physical
impairment, the occurrence of non-headache symp-
toms was not included in the daily diary. It is unclear
whether the occurrence of these symptoms directly
caused physical impairment. 3) The measurement
point in time for anxiety and depression—years into
chronic migraine for some participants—was not con-
ducive to investigating direction of causation between
depression and physical impairment. 4) Our analysis
did not account for the use of acute migraine medica-
tions. The use of acute migraine medications may par-
tially explain variation in physical impairment on
subsequent days through either the therapeutic effect
or the side effects of those medications. 5) Since data
about non-headache symptoms such as sensitivities and
nausea were not collected in the MOTS Trial headache
diaries, we used DMoH as a proxy to analyze general
Whitaker et al.
trends surrounding migraine attacks. Although we
expect the vast majority of moderate to severe head-
aches lasting at least two hours would meet criteria for
a migraine day in this population, it is possible that
some would not. It is also possible that participants
with mild headache may still fulfill criteria for a
migraine or probable migraine attack on a given day.
Future analyses should describe physical impair-
ment in diverse populations and populations with diag-
noses other than chronic migraine with medication
overuse to investigate the extent to which these findings
are generalizable. Non-headache symptoms should be
included in daily diary entries to analyze the nature of
the relationship between these symptoms and physical
impairment. Prospectively collecting repeated measures
of anxiety and depression would yield data more con-
ducive to meaningful interpretation of the significant
associations among anxiety, depression, and physical
impairment that we observed. Finally, future analyses
should investigate the possible relationship between
Key findings
• People living with chronic migraine experience physical impairment on days with headache and days
without headache.
• Physical impairment on days with mild or no headache is associated with days since last moderate to severe
headache, physical impairment on the last day with moderate to severe headache, currently having a mild
headache (rather than no headache), depression, hypersensitivities, and cranial autonomic symptoms.
Acknowledgement
The authors acknowledge and thank the patient partners who
helped plan and run the The Medication Overuse Treatment
Strategy (MOTS) trial. They also acknowledge the MOTS
investigators, MOTS Steering Committee, and Data Safety
Monitoring Board.
Declaration of conflicting interests
The authors declared the following potential conflicts of
interest with respect to the research, authorship, and/or pub-
lication of this article: DJW reports nothing to disclose.
GMD reports grants from the American Brain Foundation/
American Academy of Neurology and Amgen. JGH reports
grants from the Patient Centered Outcomes Research
Institute (PCORI). DWD reports personal fees from
Amgen, Atria, CapiThera Ltd., Cerecin, Ceruvia
Lifesciences LLC, CoolTech, Ctrl M, Allergan, AbbVie,
Biohaven, GlaxoSmithKline, Lundbeck, Eli Lilly, Novartis,
Impel, Satsuma, Theranica, WL Gore, Genentech, Nocira,
Perfood, Praxis, AYYA Biosciences, Revance, and Pfizer.
He has received speaking fees from from Teva, Amgen, Eli
Lilly, Lundbeck, and Pfizer and honoraria from American
Academy of Neurology, Headache Cooperative of the
Pacific, Canadian Headache Society, MF Med Ed
9
acute migraine medication use and physical impair-
ment between migraine attacks.
Conclusions
Our analysis offers further evidence that physical
impairment on non-migraine days constitutes a sub-
stantive dimension of disease burden among people
living with migraine and advances the quantitative
description of the topic. Physical impairment on
DMoH is associated with headache duration, headache
intensity, and history of aura, GI symptoms, hypersensi-
tivities, and cranial autonomic symptoms. Physical
impairment on DMiH and DNH is partially explainable
by mild headache, days since last DMoH, physical
impairment on last DMoH, depression, history of hyper-
sensitivities, and individual variation among participants.
Study participants with more frequent headaches, more
symptoms of depression, and history of hypersensitivities
and cranial autonomic symptoms experience physical
impairment more often on DMiH and DNH.
Research, Biopharm Communications, CEA Group
Holding Company (Clinical Education Alliance LLC),
Vector Psychometric Group, Clinical Care Solutions, CME
Outfitters, Curry Rockefeller Group, DeepBench, Global
Access Meetings, KLJ Associates, Academy for Continued
Healthcare Learning, Majallin LLC, Medlogix
Communications, Medica Communications LLC, MJH
Lifesciences, Miller Medical Communications, WebMD
Health/Medscape, Wolters Kluwer Health, Oxford
University Press, Cambridge University. He has stock or
stock options in Ctrl M, Aural Analytics, Axon
Therapeutics, ExSano, Palion, Man and Science, Healint,
Theranica, Second Opinion/Mobile Health, Epien, Nocira,
Matterhorn, Ontologics, King-Devick Technologies, Precon
Health, Ayya Biosciences, Cephalgia Group, Atria Health.
He sits on the board of directors for Epien, Matterhorn,
Ontologics, King-Devick Technologies, Precon Health,
Axon Therapeutics, and Cephalgia Group. He has received
research support from United States Department of Defense,
National Institutes of Health, Henry Jackson Foundation,
Sperling Foundation, American Migraine Foundation, and
Patient Centered Outcomes Research Institute (PCORI). He
holds Patent 17189376.1-1466:vTitle: Botulinum Toxin
Dosage Regimen for Chronic Migraine Prophylaxis without
fee and has submitted a patent application for SynaquellVR
10
(Precon Health). TJS reports a grant from PCORI during the
conduct of the MOTS Trial; grants from Amgen, American
Migraine Foundation, United States Department of Defense,
National Institutes of Health, American Heart Association,
Spark Neuro, and Henry Jackson Foundation, personal fees
from Abbvie, Allergan, Amgen, Axsome, Biodelivery Science,
Biohaven, Click Therapeutics, Collegium, Eli Lilly, Ipsen,
Linpharma, Lundbeck, Novartis, Satsuma, Theranica, Tonix,
and Scilex. He has submitted a patent application for predicting
speech outcomes in post-traumatic headache and migraine. He
reports stock options from Aural Analytics and Nocira and
royalties from Up To Date.
Funding
The authors disclosed receipt of the following financial sup-
port for the research, authorship, and/or publication of this
article: Research reported in this article was funded through a
Patient Centered Outcomes Research Institute (PCORI)
award (PCS-1504-30133). The views in this publication are
solely the responsibility of the authors and do not necessarily
represent the view of the PCORI, its Board of Governors, or
its Methodology Committee. Amgen granted free use of the
Migraine Physical Function Impact Diary for the Medication
Overuse Treatment Strategy (MOTS) Trial under a license
agreement with Mayo Clinic.
ORCID iDs
David J. Whitaker https://orcid.org/0009-0000-3414-4350
Gina M. Dumkrieger https://orcid.org/0000-0001-9519-
5370
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