Original Article

Cephalalgia
0(0) 1–16
Clinical description of attack-related ! International Headache Society 2017
Reprints and permissions:

cognitive symptoms in migraine: sagepub.co.uk/journalsPermissions.nav

DOI: 10.1177/0333102417728250
journals.sagepub.com/home/cep
A systematic review

Raquel Gil-Gouveia1,2 and Isabel Pavão Martins2

Abstract
Introduction: Cognitive symptoms have been described during migraine attacks since the Roman era; while being
neglected throughout the centuries, they are relevant contributors to migraine-related disability.
Objective: To determine whether cognitive symptoms are included in clinical series describing migraine attack
phenomenology, and which symptoms occur in each attack phase.
Method: Systematic review of existing data on clinical descriptions of migraine attacks, focusing on cognitive
symptomatology. Data were organized and analyzed qualitatively, due to methodological differences between studies.
Results: Twenty-four articles were reviewed, with a total sample of 7007 patients, including 82.9% females with an
average age of 39.2 years. Twenty one (75%) studies analyzed one phase of the attack (eight prodromes, five auras, one
between aura and pain, three headaches and three postdromes), the remaining studied more than one phase. Cognitive
complaints were the most frequent symptom of the prodromic (30%) and headache (38%) phases, while fatigue (70%)
dominated the resolution phase. Not enough data is available to estimate the frequency of cognitive symptoms during the
aura.
Discussion: Cognitive symptoms are described in all phases of the migraine attack phenomenology in published clinical
series of migraine. Their characteristics appear to be different in each attack phase, although methodological limitations
prevent generalization of this finding.

Keywords
Migraine, cognition, headache, review
Date received: 14 August 2015; accepted: 18 July 2017

Introduction Headache Classification (4) has boosted the study of

Migraine is the third most frequent disease in the
world, affecting 14.7% of the population (1) and
impacting individuals during their most productive
working years, between the third and fourth decades
(24% of women, 7% of men) (2).
Migraine is a chronic disorder with episodic manifest-
ations during which most patients become disabled to
some degree (33% with severe, 47% moderate and 18%
mild disability). Only 1% of patients are fully functional
during attacks (2). The Burden of Migraine is estimated
using the proportion of time spent in the symptomatic
(ictal) state (5.3%) and the average disability (43.3%)
assigned to attacks. Migraine is ranked in the top 10
of the highest specific causes of disability globally (1,3).
Migraine attacks are complex phenomena that start
before pain onset. The elaboration of the International
migraine by providing a simple migraine definition
focused on its most expressive symptoms. The down-
side of this approach is that other ill-defined, less
expressive, or less consistent symptoms tend to have
been overlooked in the most recent years of migraine
research. Some of these symptoms can be as frequent or
as disturbing as pain, and may provide important clues
to the pathology of the brain processes underlying
1
Headache Center, Hospital da Luz, Lisboa, Portugal
2
Headache Outpatient Clinic, Department of Neurosciences and Mental
Health, Hospital de Santa Maria, Lisboa, Portugal
Corresponding author:
Raquel Gil-Gouveia, Hospital da Luz, Avenida Lusı́ada n 100, 1500-650
Lisboa, Portugal.
Email: raquelgilgouveia@gmail.com
2 Cephalalgia 0(0)
attacks, thereby helping to define relevant therapeutic
targets. One such example is the study of attack-related
allodynia (5,6); another may be migraine attack-related
cognitive dysfunction (7,8), with relevant impact on
attack disability.
We performed a systematic literature review to iden-
tify migraine clinical series that included non-migraine
defining symptoms occurring during migraine attacks
and, in particular, cognitive symptomatology. The spe-
cific research questions were: Are cognitive symptoms
included in clinical series describing the migraine attack
phenomenology? If so, in which phase of the attack
phase (prodromes, aura, pain, and postdromes) are
they noticed? Are different symptoms described in
different phases of the attack? Can published data be
used to estimate a frequency of occurrence?
Methods
Search strategy
Potentially eligible studies were identified by searches of
electronic databases: Medline (through PubMed) and
the Cochrane Library, from inception to November
2014, without limitations or restrictions. Our search
sequentially combined the free text term ‘‘migraine’’
with the terms ‘‘prodromes’’, ‘‘premonitory’’, ‘‘post-
drome’’, ‘‘resolution’’, ‘‘cognition’’, ‘‘cognitive’’,
‘‘neuropsychological’’, ‘‘executive’’, ‘‘memory’’, ‘‘lan-
guage’’, and ‘‘clinical characterization’’. Each of these
search combinations was analyzed separately; duplicate
references were identified during abstract review.
Study selection and data collection
Titles and abstract screening identified studies that
described cognitive symptoms in any attack phase,
including reviews, clinical series, and research studies.
Studies were excluded in title or abstract screening if
they reported (a) cognitive testing of migraine patients;
(b) cognitive symptoms associated with treatments used
in migraine; (c) cognitive symptoms of chronic migraine,
medication overuse headache or genetic migraine
disorders (CADASIL, Familial Hemiplegic Migraine);
(d) clinical characterization of migraine patients not
including cognitive symptoms; (e) psychological or psy-
chiatric symptoms; (f) cognitive behavioral therapy;
(g) letters or comments; (h) small series (fewer than
10 patients) or case reports; (i) papers in which clinical
characterization of attacks referred exclusively to ICHD
defining symptoms and (j) data published in the form
of abstracts. References to relevant papers and of
reviews were also screened using the same criteria;
selected papers were retrieved and evaluated using the
same process.
Data extraction and analysis
Tables were constructed to summarize the included
studies and their relevant results. Data was organized,
classified, and analyzed qualitatively. The different
symptoms listed in each series were grouped by charac-
teristics into four categories: Migraine-related
(including migraine defining symptoms and related
GI, sensorial or aching sensations), autonomic (related
to sleep, thirst, appetite, water balance or vascular
tone) emotional/behavioral (related to humor changes,
anxiety and associated behaviors) and cognitive/neuro-
psychological (related to changes of brain functions
such as perception, reasoning, memory, language or
learning and so on). Each attack phase (prodromes,
aura, headache, and postdromes) (9,10) was evaluated
independently. A study quality assessment was not
performed given the diversity of designs, objectives,
and outcome measurements. Only a narrative review
of study data was performed, without statistical
analysis. In this narrative review, we included a few
basic quantitative analyses for the purpose of data
organization. These include (a) average symptom
frequency (requiring at least three different studies
reporting frequency values for any given symptom);
(b) total number of different symptoms reported
within each group; (c) average number of symptoms
reported per study, within each group; and (d) average
symptom frequency within each group. Ethics commit-
tee authorization was not required as this study reviewed
previously published data.
Results
Study flow and details
The study flow is depicted in Figure 1. A total of 24
papers met the eligibility criteria for review, and their
characteristics are depicted in Table 1. The majority
(83%) of the studies had prospective data collection
that was mostly achieved by questionnaires (11 stu-
dies) and only one study was controlled (11) (see
Table 1).
Sample sizes varied from 20 (12) to 1675 patients
(13); the total number of patients included was 7007,
of which 5812 (82.9%) were females, with an average
age of 39.2 years. One study included only children
(14), one only females (13), five studies (530 patients)
only patients with aura (12,15–18); in total, more
than one third (3110, 37.1%) of patients studied
had aura. Nineteen (79%) studies recruited patients
exclusively in headache clinics, yet only 12 (50%) con-
tained information about headache impact (attack fre-
quency, duration, disease duration, or impact scales)
(13,14,18–27) and two were about current prophylactic
and/or acute medication for headache (9,20).
Gil-Gouveia and Martins 3

Records identified through Additional records identified

database searching through other sources
(n = 2802 ) (n = 4 )

Records after duplicates removed

(n = 54)

Titles screened Excluded after title review

(n = 2752) (n = 2585)

Excluded after abstract

review (n = 130)
• Clinical studies not including
Abstracts assessed for cognitive symptoms description
eligibility = 101
(n = 167 ) • Comments, Editorials= 6
• Reviews = 15
• Case reports = 4
• Abstracts = 4

Full-text articles excluded

(n = 17)
• Reviews, N = 6
• Description of precipitating
Full-text articles assessed
factors= 5
for eligibility
• Not including cognitive
(n = 37) symptoms, N =4
• Editorial, N =1
• Unable to obtain the
manuscript=1

Studies included in
qualitative synthesis
(n = 24)

Figure 1. Flow diagram.

Twenty one (75%) studies analyzed only one attack
phase (eight prodromes, five aura (12,15,17,18,28),
one analyzed between the end of the aura and the begin-
ning of pain, three headache and three postdromes
(Table 1)). Further data analysis will be presented per
attack phase.
Clinical description of the migraine attack
Prodromes. The prodrome includes symptoms attributed
to migraine that start before headache or the aura’s
onset (9), and can begin as early as three days before
the attack, most often in the 24 h preceding pain
(19,23–25,29). We chose to use the term prodrome to
distinguish this type of premonitory symptom from the
aura symptoms, which also warn about impending
headache (9). Self-reported impairment of cognitive
function has been described within the 25 to 36 hours
before pain onset, peaking in the last 12 preceding
hours (27). The estimated prevalence of prodromes
ranges from 7–88% (23,24,29) in adults and around
two thirds of children, with an average of 12 (19) and
two (14) different prodromal symptoms, respectively.
Cognitive complaints are frequent amongst prodromal
symptoms and are good attack predictors – difficulties
with speech predicted 92% of attacks, difficulties with
reading predicted 90%, increased emotionality 83% and
yawning 84% (29). One study controlled the occurrence
of prodromal symptoms with the occurrence of the
same symptoms in the interictal period, concluding
that impaired concentration, unhappiness, anxiety
and yawning were the most common and consistent
prodromal symptoms (25).
Ten (42%) of the 24 included studies analyzed
the prodromal phase of the migraine attack, while
eight studies included frequency data on non-migraine
 4
Table 1. Summary of included studies.

Migraine phase Method Population

Data Clinic Sample Age

Study Prodromes Aura Pain Postdromes Prospective Retrospective collection sample Population size MO:MA ,:< average

Lance 1966 (36) þ þ þ Structured clinical þ 500 176:324 375:125 NI

interview
Blau 1980 (9) þ þ Clinical interview þ 50 31:19 28:22 34
Blau 1982 (10) þ þ Clinical interview þ þy 50 34:16 35:15 42
Waelkens 1985 (20) þ þ þ þ Clinical interview þ 49 30:19 38:11 38
Amery 1986 (19) þ þ þ Self-fulfilled questionnaire þ 149 58:91 124:25 42
Bana 1986 (15) þ þ Clinical interview þ 325 0:325 248:77 36.8
Ardila 1988 (12) þ NI NI Clinical interview þ 20 0:20 14:6 35
Blau 1991 (38) þ þ Self-fulfilled questionnaire þ 40 29:11 31:9 39
Blau 1992 (16) þ* þ* þ* þ Clinical interview þy 25 0:25 17:8 42
Queiroz 1997 (17) þ þ Self-fulfilled questionnaire þ 100 0:100 90:10 39.8
Giffin 2003 (29) þ þ þ þ Electronic diary þ 82 61:21 78:4 42
Kelman 2004 (23) þ þ Clinical interview þ þ 893 NI 760:133 37.6
Questionnaire
Quintela 2006 (25) þ þ þ Clinical interview þ þ 100 85:15 82:18 39.3
Questionnaire
Kelman 2006 (22) þ þ Structured clinical þ 827 473:354 705:122 38.2
interview
Schoonman 2006 (24) þ þ Self-fulfilled questionnaire þ 374 179:195 300:74 NI
Kelman 2006 (21) þ þ Database review þ 1009 871:138 646:363 37.7
Vincent 2007 (28) þ þ Email Questionnaire þ 143 107:36 118:25 36.9
Cuvellier 2009 (14) þ þ Telephone interview þ 103 69:33 46:57 Child
Gil-Gouveia 2011 (26) þ þ Self-fulfilled questionnaire þR R
93 86:7 75:18 39.2
Schurks 2011 (13) þ þ Questionnaire þ þ 1675 674:1001 1675:0 NI
Ng-Mak 2011 (37) þ þ þ Concept elicitation þ 34 NI 20:14 40.7
focus group
Petrusic 2013 (18) þ þ Questionnaire þ 60 0:60 44:16 39.0
Houtveen 2013 (27) þ þ Electronic diary þ þ 87 54:32 74:13 44.5
Jurgens 2014 (11) þ þ þ þz Questionnaire þ 219 149:70 189:30 39.8
R
Note: *This study focused on the time lapse between the end of the aura and pain onset. y: Convenience sample of medical practitioners; z: controlled study; : sub-study of a clinical trial that recruited
female health professionals; MA: Migraine with aura; MO: Migraine without aura.
Cephalalgia 0(0)
Gil-Gouveia and Martins
defining symptoms (Table 2). Forty nine different
symptoms were described in the eight studies that
detailed the prodromal phase (Table 2), mostly
migraine-related (40%) or autonomic (30%). On aver-
age, 5.1 different symptoms were reported in each study
(8.4 migraine-related and 5.8 autonomic).
Of all the consistently reported symptoms, the most
frequent were fatigue/asthenia and tiredness (32–33%
patients), concentration problems (30%) and irritabil-
ity/mood changes (24–25%). Evaluating grouped
symptom frequency, cognitive symptoms were the
most frequent (30%), followed by mood/behavioral
(22%), migraine related (16%), and autonomic (13%).
The aura. The most frequent aura manifestation is
visual in 65 to 99% of patients. Other possible symp-
toms include sensory (31%), aphasic (18%) and motor
(6%), occurring in various combinations (15,30). Visual
phenomena are variable, yet photopsias, flickering lines
and zig-zag lines are present in 40–87% of auras
(17,30); typical fortification spectra are less frequent
(20%) (17). Examples of other visuo-perceptive changes
described during auras include macropsia, micropsia,
cromatopia, acromatopsia, palianopsia, pelopsia,
teleopsia, simultanagnosia or visual hallucinations in
1–13% of aura patients (12,17,18,28); less frequent
and more complex visuo-perceptive changes include
prosopoagnosia, visual agnosia (18,28) out-of-body
experiences or parasomatic (‘‘duplicated’’) body
phenomena (31). In a controlled study, only corona
phenomenon and visual splitting were specific for
migraine with aura, although many other visuo-percep-
tive symptoms seem to occur more frequently in aura
patients (11). Other symptoms, such as double vision,
inversion of 2D/3D vision and altered perception
of body weight and size were related to migraine,
but not aura. Micro and macropsia, teleopsia, pelopsia,
inverted vision, out-of-body experience, visual
hallucinations and altered perception of body position
were not more frequent in migraineurs than in healthy
controls (11).
Sensory symptoms are mostly unilateral (84%) and
present as tingling or paresthesias, sometimes followed
by numbness (30), while higher cortical sensory symp-
toms, such as hemiasomatognosia, are rare (0.5% of
aura patients) (12). Aphasic symptoms may occur in
up to 50% of auras (18,28), being most often expressive
(paraphasias 76%, non-fluent aphasia 72%), although
impaired comprehension (38%) (30) and/or alexia may
ensue. Rarely, other higher cortical functions are
involved, such as memory – anterograde or retrograde
amnesia may occur in up to 18%, other phenomena
being rarer (e.g. ‘‘dejá vu’’ and ‘‘jamais vu’’ phenom-
ena, depersonalization). One study evaluated symptoms
occurring outside and during migraine attacks and
5
some (such as prosopagnosia, proper name agnosia,
and transient amnesia) did not seem to be related to
the attacks (28).
Calculus may also be disturbed (dyscalculia or acal-
culia) in up to 13% (18) of auras, as well as other
‘‘mental or personality’’ changes, with a frequency of
around 3–7% (12,15,28). Hallucinations may occur as
migraine auras, either gustatory (0.5%), olfactory (up
to 1%) (12,32) or auditory (0.17%) (33).
Eight (33%) of the 24 included studies analyzed the
aura phase, including 39 different symptoms (Table 3),
mostly migraine-related (49%) or cognitive (28%).
On average, 2.6 different symptoms were reported in
each study (4.0 migraine-related and 3.8 cognitive).
Five studies provided symptom frequency data, two
of which contained details about sensorial migraine
related symptoms (blurred vision 36.7%, dizziness
20.4%, stiff neck 14.3%, nausea 8.2%, photophobia
8.2%, and phonophobia 4.1%), autonomic symptoms
(food craving 2.1 to 12.2%, yawning 1.4 to 12.2%,
sleepiness 10.2%, pallor 2%, and temperature changes
4.1%) or mood changes (irritability 4.2–10.2% and fati-
gue 2.8–6.1%) (20,28). The remaining symptoms were
mainly neuropsychological symptoms (other than
ICDH-III aura defining symptoms) but only three
symptoms were consistently described – speech and
language difficulties (32.8% patients), visuo-perceptive
changes (28.3%) and memory (19%).
The headache. The painful phase of migraine often
starts within the aura phase, with as many as 54% of
attacks already having a migraine defining pain within
15 minute of aura onset (34); the remaining patients
have a free interval between the end of the visual
aura and headache onset, during which some patients
feel completely well while others describe mood
changes (60%, including feeling fearful, euphoric, dys-
phoric or depressed), perception difficulties (40%,
including feeling distant, disoriented or below others),
cognitive changes (36%, including slowness of thinking,
difficulty in concentrating, difficulties in speaking, read-
ing and communicating) and somatic symptoms (72%,
including lack of energy, clumsiness, feeling ill or
light headache, nausea, facial edema) (16). It is unclear
whether these symptoms represent the onset of
prodromes after the aura, although some prodromes
persist through all attack phases (20,23,25,29).
Cognitive symptoms often accompany the headache
phase of migraine, such as being unable to think or con-
centrate (up to 71% of patients), unable to carry out
activities such as shopping (up to 83%), work or
taking care of children (60%). These symptoms are
recorded more often in high intensity attacks and con-
tribute to migraine associated disability (35). Cognitive
and non-cognitive prodromal symptoms persist thought
6 Cephalalgia 0(0)

Table 2. Frequency of non-migraine defining symptoms in the prodromic phase of Migraine Attacks, as described in the literature.

Blau Waelkens Amery Giffin Kelman Quintela Schoonman Cuvellier

Average 1980 (9) 1985 (20) 1986 (19) 2003 (29) 2004 (23) 2006 (25) 2006 (24) 2009 (14)

Emotional/behavior
Fatigue/asthenia 33 12 10–49 25.6 38 46.5 41.7
Tiredness 32 12 6 72.5 25.6 31
Adynamic/inactive – >50
Emotional/ 24 24 24.3 23.4
mood changes
Irritability 25 8 10 >50 38.5 42 28.1 24.3
Stress/anxiety 19 4 46 15.2 12.6
Claustrophobia – 4
Depression 16 4 10–49 39 17.6 1.9
Hyperactivity/ 8 10 5.2 9–13 15 2.9
excited/euphoric
Migraine-related
Nausea 18 8.2 23.5 24 28.6 5.8
Anorexia – 20
Vomiting – 6
Constipation 10 2 5.6 21
Diarrhea – 2 4
Flatulence/abdominal – 8.2 10–49 22
distension
Abdominal pain/ 13 6.1 22 11
GI disturbance
Phonophobia 23 6.1 >50 38.4 1.1 44 36.4 10.7
Photophobia 20 8.2 >50 48.8 1.3 37 7.8
Sensitive skin/ 4 4.1 >50 5.7 1.6
hyperesthesia
Smell distortion/ 0.7 3.9
osmophobia
Taste distortion – 2 0.4
Paresthesia – 6.1 0.9
Stiff neck 21 14.3 10–49 49.7 3 35 2.9
Muscle ache – 2 10–49 0.2
Body weakness/ – 8.2 10.49 0.5
clumsiness
Blurred vision 24 36.7 10–49 28 3.3 26
Dizziness 15 20.4 10–49 22.9 1.1
Ear symptoms/ – 0.5
tinnitus
Strained/swollen – 25 10–49 5.6
head
Cognitive
Concentration problems 30 >50 51.1 36 28.1 4.8
Difficulty with thoughts – 34.6
Difficult to read/write – >50 20.2
Difficulty with speech – 9 17
Hazy mind/intellectual – 4 >50 1.3
disturbance
(continued)
Gil-Gouveia and Martins 7

Table 2. Continued.

Blau Waelkens Amery Giffin Kelman Quintela Schoonman Cuvellier

Average 1980 (9) 1985 (20) 1986 (19) 2003 (29) 2004 (23) 2006 (25) 2006 (24) 2009 (14)

Autonomic
Pale face/ 21 2 >50 17.6 43.7
face changes
Dark rings – 10–49
around eyes
Yawning 20 14 12.2 10–49 27.8 0.5 40 35.8 10.7
Somnolence 13 2 2 35
Insomnia – 27
Sleep disturbances – 13.9 1.9
Thirst/water craving – 26 17
Hungry 12 6 12.2 10–49 18.2
Food craving 14 8 18.2 0.4 15 17.4 3.9
Frequent urination 10 2 16.2 12
Fluid retention – 2 12
Feeling cold/shivering 2 4.1 >50 1.1 1.9
Sweating – 2 10–49
Dry mouth/nose – 2 0.9
symptoms
Sighing/difficulty – 2 0.2
breathing
Note: Values represent percentages reported in each series. y: Average percentage was calculated for each symptom if the symptom was reported in at
least three different studies.

the headache phase (29) or may appear only during
headache (13,20,21,26,36,37).
Of the 28 included studies, one study analyzed the
time elapsed between the aura and the pain and nine
(32%) analyzed the headache phase of the attack,
detailing 41 different symptoms (Table 3), mostly
migraine-related (44%) or autonomic (22%). On aver-
age, 2.7 different symptoms were reported in each study
(4.6 migraine-related and 2.4 mood/behavior). The
most frequently occurring consistent symptoms were
impaired thinking (51.8% of patients), blurred vision
(36%), and stiff neck (34.7%). Other very frequent
symptoms included irritability (33.2%), fatigue/asthe-
nia and dizziness (32%). Evaluating symptom fre-
quency within each group, the most frequent
symptoms were cognitive (38%), followed by mood/
behavioral (32%) and migraine related (32%). Some
of the changes occurring during attacks are even
noticed by family or friends, and described as facial
changes (pallor, rings around eyes, altered facial expres-
sion, lusterless eyes, swollen frontal veins) as well as
irritability and mood swings (19).
Postdromes or resolution symptoms. The headache of the
migraine attack will at some point decrease progres-
sively, either imperceptibly or faster, until it disappears,
even without any intervention to shorten the attack
(10). Attacks can be shortened or interrupted with sev-
eral strategies, the most common being medication,
sleep or vomiting (10). However, 60–94% of patients
have persisting migraine symptoms after headache reso-
lution, lasting on average 25.2 hours (<12 h in 54% of
patients). On average, each migraineur reports up to
seven postdromal symptoms (10,22,25,38). The defin-
ition of postdromes varies in different studies, with
some authors even allowing the existence of mild head-
ache in this phase (22,37,38).
Six (25%) of the included studies analyzed 42 differ-
ent resolution symptoms (Table 4), the most frequent
being migraine-related (43%) or autonomic (24%),
with an average of 4.8 different symptoms being
reported in each study (8.7 migraine-related and 4.3
autonomic).
Among the consistently reported symptoms, the
most frequently occurring were fatigue/tiredness (70%
patients), mood disturbances (42%) and concentration
problems (40%). Evaluating frequency by symptom
group, the most frequent symptoms were of mood/
behavioral (38%), cognitive (30%), migraine related
(21%) and autonomic (13%). One study controlled
the occurrence of postdromal symptoms with the occur-
rence of the same symptoms in the interictal period,
concluding that tiredness, asthenia and somnolence
were the most common and consistent resolution
Table 3. Frequency of non-migraine defining symptoms occurring during the aura and headache phases of migraine attacks, as described in the literature. 8
Aura Headache

Ardila Queiroz Vincent Petrusic Blau Lance Waelkens Amery Kelman Giffin Ng-Mak Schurks
Waelkens 1988 1997 2007 2013 1992 1966 1985 1986 2006 2003 Gil-Gouveia 2011 2011
1985 (23) (15) (20) (31) (21) (19)* (44) (23) (22) (24) (32) 2011 (29) (51) (16)

Mood/behavior
Fatigue/asthenia 6.1 2.8 26.8 84.3 14.0 2.9
Eviction/isolation 10.7
Adynamia/lethargy 16.0 4.1 >50 26.9
Dysphoric/emotional 8.0 >50 29.9 63.0
Irritability/fear 10.2 4.2 24.0 8.2 >50 41.0 50.5
Depression 4.0 4.1 10–49
Hyperactivity/euphoria 12.0 4.1 2.7
Migraine-Related
Nausea 8.1 8.0 95.0 93.9 >50 54.5 67.6 89.1
Eructation 6.1 40.8
Abdominal distension 2.0 12.2 >50
Abdominal pain 6.1 2.0
Diarrhea 19.0 9.5
Constipation 6.6
Phonophobia 6.1 93.9 >50 68.8 64.7 86.1
Photophobia 8.2 100 >50 71.1 52.9 93.0
Sensitive skin/hyperesthesia 2.0 40.8 10–49 9.3
Smell distortion/osmophobia 4.1 53.1 13.6 8.8
Taste distortion 10.8
Paresthesia 6.1 22.4 10–49 39.7
Stiff neck 14.3 26.5 62.8 14.7
Muscle ache 2.0 10–49 12.3
Body weakness 8.2 6.1 2.9
Clumsy 16.0
Cranial autonomic 17.9
Feeling ill 12.0
Blurred vision 36.7 27.0 4.1 >50 34.7 17.6 50.9
Tinnitus 2.0 2.0
Dizziness 20.4 8.2 >50 36.3 31.1 23.5 61.0
Light/strained head 8.2 12.0
Swelling head 24.5 4.0
Tight head/pressure 6.1 >50 8.8
Throbbing blood vessels 12.2 10–49
Cephalalgia 0(0)

(continued)
Table 3. Continued.
Aura Headache

Ardila Queiroz Vincent Petrusic Blau Lance Waelkens Amery Kelman Giffin Ng-Mak Schurks
Waelkens 1988 1997 2007 2013 1992 1966 1985 1986 2006 2003 Gil-Gouveia 2011 2011
Gil-Gouveia and Martins

1985 (23) (15) (20) (31) (21) (19)* (44) (23) (22) (24) (32) 2011 (29) (51) (16)

Cognitive
Feels distant/ 7.7 28.0 >50 72.6 21.5
distracted/slow
Disorientation/confusion 8.3 12.0 6.8
Impaired thinking 16.0 >50 50.5 90.3 14.7
Color naming 13.3
Difficulty with speech/language 40 4.9 53.3 20.0 10.2 39.2 25.8 24.7
Dyscalculia 13.3
Visuo-perceptive 27.5 45.0 34.1 6.7
Cognitive-dysmnesic 17.5 7.7 31.7 12.9
Hallucinations 7.5 1.0
Sensorial perception 2.5 4.0
Automatisms 5.0
Apraxia 11.4 4.1
Difficulty problem 6.1 31.2
fixation/planning
Autonomic
Pale face 2.0 >50 32.2
Dark rings around eyes 2.0
Yawning 12.2 1.4 25.4
Thirst/water craving 32.2
Hungry/food craving 12.2 2.1 18.1 28.3
Fluid retention 55.9
Frequent urination 29.0 24.3
Lipothymia 2.0 12.2 2.0
Feels cold/shivers 4.1 2.0
Sweating 2.0
Dry mouth 2.0

Note: Values represent percentages reported in each series; migraine-defining symptoms are plotted in grey. *This study focused on the time lapse between the end of the aura and pain onset.
9
10 Cephalalgia 0(0)

Table 4. Frequency of non-migraine defining symptoms in the postdromic phase of migraine attacks, as described in the literature.

Blau 1982 Blau 1991 Giffin Quintela Kelman Ng-Mak

Averagey (10) (38) 2003 (29) 2006 (25) 2006 (22) 2011 (37)

Emotional/behavioral
Fatigue/tiredness 70 52.0 67.5 88.2 55.0 71.8 88.2
Emotional/mood changes – 23.5 6.8
Stress/anxiety – 15.0
Irritability 22 12.5 28.5 20.0 26.5
Depression/lower mood 42 56.0 42.5 26.0
Happy/euphoric 18 16.0 15.0 10.0 29.4
Introverted/isolation – 7.5 14.7
Hyperactivity – 2.4 9.0
Migraine-Related
Nausea/anorexia 21 14.8 10.0 38.2
Constipation/diarrhea 12 22.5 6.8 13.0 8.4
Abdominal pain – 6.0
Photophobia 16 12.5 36.0 26.0 2.1 5.9
Phonophobia 15 0.5 31.8 27.0 0.4 14.7
Osmophobia – 2.5 2.9
Taste distortion – 7.5
Sensitive skin/hypersensitivity – 5.2 10.0
Paresthesia – 1.8
Cranial autonomic – 2.5 0.5
Stiff/aching neck 26 35.0 41.9 3.2 23.5
Reduced physical energy 34 72.5 5.2 23.5
Muscular weakness 25 54.0 5.0 6.2 35.3
Clumsy/hungover 15 15.0 11.7 17.6
Blurred vision 13 17.5 17.4 16.0 2.0 11.8
Dizziness 20 19.3 5.7 35.3
Head tenderness – 57.5
Mild head pain 37 35.0 33.1 44.1
Cognitive
Concentration problems 40 65.0 55.5 28.0 11.7 38.2
Difficulty with thoughts – 33.4 8.8
Lower intellect/‘‘fog’’ – 56.0 14.7
Reduced attention span – 55.0
Difficulty reading/writing – 16.8
Difficulty with speech 19 42.5 8.5 6.0
Autonomic
Yawning 20 8.0 32.5 13.9 24.0
Thirst/drinking more 18 8.0 35.0 32.2 15.0 0.5
Frequent/lower urination 17 14.0 22.5 21.2 10.0
Fluid retention – 5.0
Feeling cold – 17.0
Less appetite – 32.0 23.5
Food craving 10 16.0 15.1 9.0 0.2
Pale face – 21.4 0.2
Somnolence – 29.0
Insomnia – 0.5 12.0
Note: Values represent percentages reported in each series. y: Average percentage was calculated for each symptom if the symptom was reported in at
least three different studies.
Gil-Gouveia and Martins
symptoms (25). The most common postdromal symp-
toms reported in a study using focus groups to detail
this phase of attacks were tiredness, nausea, head pain,
difficulty concentrating, and physical weakness (37).
These patients reported that postdromal symptoms
were clinically relevant, as they felt decreased physical
activity, difficulty at work, difficulty performing gen-
eral cognitive tasks and true impact on family and
social life (37).
A summary of each symptom frequency through the
headache phases is presented in Table 5.
Discussion
This review aimed to identify clinical information about
non-migraine defining symptomatology occurring
during migraine attacks, retrieved from clinical series
of migraine patients, with a special focus on cognitive
and neuropsychological symptoms. Addressing our first
research question, 24 studies including 7007 patients
were identified in which cognitive symptoms were
described, either spontaneously in clinical interviews
or actively sought by questionnaires, electronic diaries
or even specifically in a concept elicitation focus group.
The frequency of reporting cognitive symptoms in these
studies varied from 4% (9) to 90.3% (26) in different
studies and different phases of the attack. These obser-
vations support that cognitive symptoms are a part of
the subjective experience of the migraine attack, in
agreement with early historical descriptions of
migraine.
The oldest consistent description of the migraine
syndrome (39) was made by the Greek Aretaeus of
Cappadocia (30–90 A.D.) (40) and already included
details about attack related humor changes ‘‘. . .torpor,
heaviness of the head, anxiety, and ennui. . .’’. The
Treatise de Medicina, written by the Roman Aulus
Cornelius Celsus (25–50 A.D.) includes the first allusion
to attack-related cognitive symptoms: ‘‘In the head,
then, there is at times an acute and dangerous disease,
which the Greeks call cephalaia; the signs of which are
hot shivering, paralysis of sinews, blurred vision, alien-
ation of the mind, vomiting. . ..’’ (41). The English
Thomas Willis (1621–1675 A.D.) described migraine
prodromal symptoms including fatigue, bursts of
energy and hunger (42) and Edward living (43) (1832–
1919 A.D.) published the first medical book about
headache, where cognitive symptoms are included as
disturbance of ‘‘ideational consciousness’’ as described
in ‘‘Chapter III -Phenomena of the Paroxysm’’ (43). He
divided these phenomena into ‘‘intellectual’’ and ‘‘emo-
tional’’, describing the former as ‘‘. . .impairment of
memory and in confusion and incoordination of
ideas. . .’’, ‘‘. . . confusion of thought. . .’’, ‘‘. . .unable to
collect his thoughts. . .’’, ‘‘. . .feeling silly. . .’’, ‘‘. . .losing
11
their senses. . .’’; whereas ‘‘emotional’’ phenomena were
part of the attack premonition, including ‘‘. . .irritability
of temper. . .’’, ‘‘ill-humor’’ and a ‘‘vague and unaccount-
able sense of fear. . .’’, which could precede the attack by
one or two days, while ‘‘great mental depression’’ could
linger through the entire paroxysm (43).
Even by then, it was clear that the migraine attack
represented a complex phenomenon with different
phases. In this review, cognitive symptoms were
described in all phases of the attack, although the pat-
tern described in each phase differed. The prodromal
phase has the highest amount of available information
available, with 46% of the studies (involving 2106
patients) containing information about prodromes.
Forty-nine different prodromal symptoms were
described that were mostly migraine-related or auto-
nomic, supporting the view that the hypothalamus
may play a role in the development of migraine attacks
(44). Despite the high number of different autonomic
and migraine-related symptoms reported in this phase,
the pooled data revealed that those were not the most
frequent, but rather the cognitive symptoms were most
frequent (driven by the high frequency of ‘‘concentra-
tion problems’’ or attention complaints), and mood/
behavioral (‘‘fatigue, asthenia and mood changes’’).
The attentional networks depend on the thalamus, par-
ietal cortex and anterior cingulum (45), all structures
which have been found to be activated in the prodromal
phase of migraine attacks (44). Other relevant brain
activations in this phase include the cerebellar, tem-
poral, frontal and (again) the cingulum areas, which
may be implicated in the neural mechanism of mental
fatigue (46).
Studies about the aura were scarcer, with only five
(involving1416 patients) describing 39 different symp-
toms, mostly migraine related or cognitive. These
observations may be biased, as it is difficult to disen-
tangle certain complex neuropsychological phenomena
from vaguer cognitive symptoms – an example being
‘‘speech difficulties’’, which may reflect true aphasia
or mild word-finding hesitations. Additionally, since
pain does not always start only after the aura (34), so
some aura-related symptoms could actually belong to
the pain phase by itself. The most frequent symptoms
could not be determined, as very scarce frequency infor-
mation was available about other symptoms (described
in only two studies) yet most reflect probable cortical
involvement – speech and language problems, visuoper-
ceptive difficulties, apraxia or cognitive- dysmnesic
complaints. The aura phenomena are related to cortical
dysfunction, usually starting in the striate cortex and
propagating across different cortical areas, producing
different clinical manifestations according to the
involved areas (47). An fMRI study has concluded
that several extrastriate visual areas are involved in
12 Cephalalgia 0(0)

Table 5. Average frequency of non-migraine defining symptoms in each phase of migraine attacks.

Prodromes Aura Aura-headache Headache Postdromes

Emotional/behavioral
Fatigue/asthenia 33 4.4 32 70
Tiredness 32
Adynamic/inactive 50 16 27
Emotional/mood changes 24 8 47.6 15
Irritability 25 24 37.4 22
Stress/anxiety 19 15
Eviction/isolation – 10.7 11.1
Depression 16 4 4 16.8 42
Hyperactivity/excited/euphoric 8 10 12 3.4 11.8
Migraine-related
Nausea 18 8.1 8 75 21
Eructation 6.1 40.8
Taste distortion 1.2 10.8 7.5
Flatulence/abdominal distension 5.2 2 31.1
Abdominal pain/GI disturbance 13 6.1 2 6
Constipation/diarrhea 13 10.4 12
Cranial autonomic 17.9 1.5
Phonophobia 23 6.1 72.7 15
Photophobia 20 8.2 73.4 16
Sensitive skin/hyperesthesia 4 2 26.5 7.6
Smell distortion/osmophobia 2.3 4.1 25.2 2.7
Paresthesia 3.5 6.1 30.5 1.8
Stiff neck 21 14.3 34.7 26
Muscle ache/weakness 10.6 2.0 20.9 25
Body weakness/clumsiness 6.4 8.2 16 4.5 15
Blurred vision 24 31.8 31.5 13
Dizziness 15 20.4 35 20
Ear symptoms/tinnitus 1.2 2.0 2.0
Strained/swollen head 20 8.2 8
Tight head/pressure/mild pain 6.1 29.4 37
Throbbing blood vessels 12.2 29.5
Reduced physical energy/feeling ill 12 34
Cognitive
Concentration problems 30 7.7 28 48 40
Difficulty with thoughts 34.6 16 51.4 21.1
Visuo-perceptive – 28.3
Difficulty with speech 13 2.7 20 25 19
Hazy mind/intellectual 18.4 8.3 12 6.8 35.3
disturbance/‘‘fog’’
Cognitive-dysmnesic 19 12.9
Sensorial perception changes 2.5 4
Apraxia 11.4 4.1
Difficulty problem fixations/planning 4.5 55
Autonomic
Pale face/face changes 21 2 41.1 10.8
Dark rings around eyes 29.5 2
(continued)
Gil-Gouveia and Martins
Table 5. Continued.
Prodromes
Yawning 20
Somnolence 13
Insomnia 27
Sleep disturbances 7.9
Thirst/water craving 21.5
Hungry/food craving 13
Frequent urination 10
Fluid retention 7 55.9
Feeling cold/shivering 2 4.1
Sweating 15.6
Dry mouth/nose symptoms 1.5
Sighing/difficulty breathing 1.1
Note: Values represent percentages reported in each series.
visual manifestations, while somasthetic symptoms
probably relate to cortical changes in somatosensory
cortices (48).
Seven (25%) of studies including 3810 patients
described 41 different non-migraine defining symptoms
occurring in the headache phase of migraine attacks,
most migraine-related such as blurred vision, dizziness,
stiff neck, or osmophobia. However, the most frequent
occurring symptoms were cognitive, such as ‘‘impaired
thinking’’, ‘‘feeling distracted or slow’’, and ‘‘speech
difficulties’’, in line with previous studies suggesting
the existence of attack-related cognitive dysfunction
(7,8) in the domains of attention, processing speed,
working memory and language. Brain activations docu-
mented in the headache phase of migraine without aura
attacks include many structures relevant to these func-
tions, such as the cingulum, parietal cortex and thal-
amus (attention), additional subcortical structures such
as raphe nuclei (processing speed), pre-frontal cortex
(working memory) and fontal and temporal lobes (lan-
guage) (44,49,50).
There were six available studies detailing the post-
dromes, involving 1133 patients and describing 42
different symptoms, the majority migraine-related –
including persistent mild pain in 37% of patients.
Again, the most frequently reported symptoms were
mood or behavioral changes, specially fatigue and/or
tiredness, reported in all studies with frequencies vary-
ing from 52 to 88% (average 70%), depressive feelings
(42%) and reduced physical energy (34%), although
concentration problems were present in 40% of
patients. Persistent activation of the brain stem (51)
has been documented by PET in sumatriptan treated
attacks, which correlate to the decrease in the serotonin
synthesis burst observed during the attack (52).
13
Aura Aura-headache Headache Postdromes
6.8 25.4 20
29
6.2
32.2 18
2.1 23.2 10
26.6 17
5
2 17
2
2 2
2
Serotonin depletion in serotonergic projections to cor-
ticolimbic circuitry can influence the occurrence of
mood related symptoms. A different PET study has
shown persistent activation of all headache activated
areas after sumatriptan treatment – hypothalamus,
midbrain, dorso-medial pons, cerebellum, fronto-infer-
ior and cingulate cortex (53).
With the present data, it is possible to assume that
cognitive symptoms occur frequently in all phases
of the migraine attack, mostly affecting executive
function (concentration difficulties, impaired thinking,
and slow processing) and language, a pattern consist-
ent with evidence of attack-related neuropsychological
dysfunction (7,8). We cannot assume, with data from
this revision, that these symptoms are present in most
or all patients, nor if they occur consistently in
all attacks nor through all phases of the attack.
Having migraine predicts limitations in cognitively
demanding work (54), with specifically the migraine-
attack associated concentration problems contributing
to a perceived difficulty in handling the mental aspect
of work during attacks, such as making deci-
sions or performing out-of-the ordinary or complex
work tasks. Patients also report more errors in tasks
involving reading, writing, communication and
arithmetic, and the need to work in a slower pace.
Mood changes, such as irritability, additionally limit
patients’ working abilities and interfere with interper-
sonal issues at work (55). Patients spontaneously
discussing their experiences of migraine attacks on
Twitter report impact on productivity at work
(3.5%) and school (2.8%), but also in social life
(3.5%) and particularly in mood (43.9%) (56), which
are possibly a reflection of persisting mood changes in
the resolution phase.
14
There are a number of limitations to our study, the
most important being the heterogeneity of the included
studies, which precludes any attempt to determine the
quality of the studies and the performance of quantita-
tive analyses. None of the included studies shared the
same objectives, almost all were uncontrolled, and data
collection was different in each study – most studies
used clinical interviews and several different question-
naires, inducing an insurmountable bias on item selec-
tion and valorization. The quantitative analysis
performed in this review merely aims to be indicative
of the relative proportion of each symptom, and should
not be assumed at face value. The samples were mostly
clinic-based, yet little information was provided in each
study about attack frequency and disease impact.
Recruiting was heterogeneous, with some studies
including only aura patients, only children or only
females. Another methodological limitation includes
the definition of migraine attack phases, which was
not uniform across studies – as there is no consensus
about their definition, an overlap between phases is
likely. Additionally, the majority of studies did not
include information about the use of preventives or
acute attack treatments, which can produce concurrent
symptoms as side-effects. Adding to the potential
reporting bias in this review is the fact that not all the
patients experienced all attack phases. Furthermore,
the symptoms described for each attack phase were
Article highlights
. Migraine attack-related cognitive dysfunction is consistently described by patients in published clinical series
of migraine.
. Cognitive symptoms occur in all attack phases, being most relevant in the prodromal phase and during
headache.
Authors contributions
Raquel Gil-Gouveia and Isabel Pavão Martins have partici-
pated in study design, analysis and interpretation of data,
draft revision, and both have approved the final version sub-
mitted; Raquel Gil-Gouveia collected the data from the lit-
erature and drafted the manuscript.
Acknowledgment
The authors would like to thank Miguel Vaz Afonso MD,
PhD for editorial support.
Declaration of conflicting interests
The authors declared the following potential conflicts of inter-
est with respect to the research, authorship, and/or publica-
tion of this article: Dr. Gil-Gouveia reports non-financial
support from Allergan, and non-financial support from
Sanofi, outside the submitted work.
Cephalalgia 0(0)
reported by different patients, across different studies.
It can even be argued if patients noticing versus
not noticing prodromes and postdromes may be
different – in the Kelman series (23) patients seem to
be more sensitive to triggers, having longer duration of
every phase of the migraine attack and have higher
frequency of accompanying symptoms (nausea and
Cranial Autonomic Symptoms).
Conclusions
Due to the large number of patients implicated in this
review, it is possible to conclude that cognitive symptoms
are consistently included in the description of the
migraine attack phenomenology in published clinical
series of migraine patients. Existing data also seem to
support that cognitive symptoms are described for all
attack phases, while being the most frequent non-
migraine defining symptoms reported in the prodromal
phase and during headache. The cognitive symptoms
most frequently described by patients are ‘‘concentration
problems’’ in the prodromal phase and ‘‘impaired think-
ing’’ during headache. Concentration is also the most
relevant cognitive complaint during the resolution phase
of headache, but the most frequent non-migraine defining
symptom of this phase is fatigue. However, interpretation
of this data is limited due to important methodological
discrepancies and limitations of the evaluated studies.
Funding
The authors disclosed receipt of the following financial
support for the research, authorship, and/or publication of
this article: Dr. Gil-Gouveia reports grants from Sociedade
Portuguesa de Cefaleias – Tecnifar, outside the submitted
work.
References
1. Steiner TJ, Stovner LJ and Birbeck GL. Migraine: The
seventh disabler. J Headache Pain 2013; 14: 1.
2. Lipton RB, Bigal ME, Diamond M, et al. Migraine preva-
lence, disease burden, and the need for preventive therapy.
Neurology 2007; 68: 343–349.
3. Collaborators, Global Burden of Disease Study. Global,
regional, and national incidence, prevalence, and years
lived with disability for 301 acute and chronic diseases
Gil-Gouveia and Martins
and injuries in 188 countries, 1990–2013: A systematic
analysis for the Global Burden of Disease Study 2013.
Lancet 2015; 386: 743–800.
4. Classification and diagnostic criteria for headache dis-
orders, cranial neuralgias and facial pain. Headache Clas-
sification Committee of the International Headache
Society. Cephalalgia 1988; 8: S1–S96.
5. Schwedt TJ, Larson-Prior L, Coalson RS, et al. Allody-
nia and descending pain modulation in migraine: A rest-
ing state functional connectivity analysis. Pain Med 2014;
15: 154–165.
6. Aguggia M. Allodynia and migraine. Neurol Sci 2012; 33:
S9–S11.
7. Gil-Gouveia R, Oliveira AG and Martins IP. Assessment
of cognitive dysfunction during migraine attacks: A sys-
tematic review. J Neurol 2015; 262: 654–665.
8. Gil-Gouveia R, Oliveira AG and Martins IP. Cognitive
dysfunction during migraine attacks: A study on migraine
without aura. Cephalalgia 2015; 35: 662–674.
9. Blau JN. Migraine prodromes separated from the aura:
Complete migraine. Br Med J 1980; 281: 658–660.
10. Blau JN. Resolution of migraine attacks: Sleep and the
recovery phase. J Neurol Neurosurg Psych 1982; 45:
223–226.
11. Jürgens TP, Schulte LH and May A. Migraine trait
symptoms in migraine with and without aura.
Neurology 2014; 82: 1416–1424.
12. Ardila A and Sanchez E. Neuropsychologic symptoms in
the migraine syndrome. Cephalalgia 1988; 8: 67–70.
13. Schürks M, Buring JE and Kurth T. Migraine features,
associated symptoms and triggers: A principal compo-
nent analysis in the Women’s Health Study. Cephalalgia
2011; 31: 861–869.
14. Cuvellier JC, Mars A and Vallée L. The prevalence of
premonitory symptoms in paediatric migraine: A ques-
tionnaire study in 103 children and adolescents.
Cephalalgia 2009; 29: 1197–1201.
15. Bana DS and Graham JR. Observations on prodromes of
classic migraine in a headache clinic population.
Headache 1986; 26: 216–219.
16. Blau JN. Classical migraine: Symptoms between visual
aura and headache onset. Lancet 1992; 340: 355–356.
17. Queiroz LP, Rapoport AM, Weeks RE, et al. Character-
istics of migraine visual aura. Headache 1997; 37:
137–141.
18. Petrusic I, Zidverc-Trajkovic J, Podgorac A, et al. Under-
estimated phenomena: Higher cortical dysfunctions
during migraine aura. Cephalalgia 2013; 33: 861–867.
19. Amery WK, Waelkens J and Vandenbergh V. Migraine
warnings. Headache 1986; 26: 60–66.
20. Waelkens J. Warning symptoms in migraine: Character-
istics and therapeutic implications. Cephalalgia 1985; 5:
223–228.
21. Kelman L. Migraine changes with age: IMPACT on
migraine classification. Headache 2006; 46: 1161–1171.
22. Kelman L. The postdrome of the acute migraine attack.
Cephalalgia 2006; 26: 214–220.
23. Kelman L. The premonitory symptoms (prodrome): A
tertiary care study of 893 migraineurs. Headache 2004;
44: 865–872.
15
24. Schoonman GG, Evers DJ, Terwindt GM, et al. The
prevalence of premonitory symptoms in migraine: A
questionnaire study in 461 patients. Cephalalgia 2006;
26: 1209–1213.
25. Quintela E, Castillo J, Muñoz P, et al. Premonitory and
resolution symptoms in migraine: A prospective study in
100 unselected patients. Cephalalgia 2006; 26: 1051–1060.
26. Gil-Gouveia R, Oliveira AG and Martins IP. A subjective
cognitive impairment scale for migraine attacks. The
MIG-SCOG: Development and validation. Cephalalgia
2011; 31: 984–991.
27. Houtveen JH and Sorbi MJ. Prodromal functioning of
migraine patients relative to their interictal state – an
ecological momentary assessment study. PLoS One
2013; 8: e72827.
28. Vincent MB and Hadjikhani N. Migraine aura and
related phenomena: Beyond scotomata and scintillations.
Cephalalgia 2007; 27: 1368–1377.
29. Giffin NJ, Ruggiero L, Lipton RB, et al. Premonitory
symptoms in migraine: An electronic diary study.
Neurology 2003; 60: 935–940.
30. Russell MB and Olesen J. A nosographic analysis of the
migraine aura in a general population. Brain 1996; 119:
355–361.
31. Podoll K and Robinson D. Out-of-body experiences and
related phenomena in migraine art. Cephalalgia 1999; 19:
886–896.
32. Coleman ER, Grosberg BM and Robbins MS. Olfactory
hallucinations in primary headache disorders: case series
and literature review. Cephalalgia 2011; 31: 1477–1489.
33. Miller EE, Grosberg BM, Crystal SC, et al. Auditory
hallucinations associated with migraine: Case series and
literature review. Cephalalgia 2014; 35: 923–930.
34. Hansen JM, Lipton RB, Dodick DW, et al. Migraine
headache is present in the aura phase: A prospective
study. Neurology 2012; 79: 2044–2049.
35. Caro G, Caro JJ, O’Brien JA, et al. Migraine therapy:
Development and testing of a patient preference ques-
tionnaire. Headache 1998; 38: 602–607.
36. Lance JW and Anthony M. Some clinical aspects of
migraine. A prospective survey of 500 patients. Arch
Neurol 1966; 15: 356–361.
37. Ng-Mak DS, Fitzgerald KA, Norquist JM, et al. Key
concepts of migraine postdrome: A qualitative study to
develop a post-migraine questionnaire. Headache 2011;
51: 105–117.
38. Blau JN. Migraine postdromes: Symptoms after attacks.
Cephalalgia 1991; 11: 229–231.
39. Headache Classification Committee of the International
Headache Society. The International Classification of
Headache Disorders, 3rd edition (beta version).
Cephalalgia 2013; 33: 629–808.
40. Magiorkinis E, Diamantis A, Mitsikostas DD, et al.
Headaches in antiquity and during the early scientific
era. J Neurol 2009; 256: 1215–1220.
41. Spencer W. De Medicina. Celsus. Cambridge, MA:
Harvard University Press, 1971.
42. Diamond S and Franklin M (eds) Headache through the
ages. West Islip, NY: Professional Communications, Inc,
2005.
16
43. Liveing E. On megrim and sick-headache and some allied
disorders: A contribution to the pathology of nerve storms.
London: Churchill, 1873.
44. Maniyar FH, Sprenger T, Monteith T, et al. Brain acti-
vations in the premonitory phase of nitroglycerin-
triggered migraine attacks. Brain 2014; 137: 232–241.
45. Raz A and Buhle J. Typologies of attentional networks.
Nat Rev Neurosci 2006; 7: 367–379.
46. Cook DB, O’Connor PJ, Lange G, et al. Functional neu-
roimaging correlates of mental fatigue induced by cogni-
tion among chronic fatigue syndrome patients and
controls. Neuroimage 2007; 36: 108–122.
47. Hansen JM, Baca SM, Vanvalkenburgh P, et al. Distinc-
tive anatomical and physiological features of migraine
aura revealed by 18 years of recording. Brain 2013; 136:
3589–3595.
48. Hadjikhani N, Sanchez Del Rio M, Wu O, et al. Mechan-
isms of migraine aura revealed by functional MRI in
human visual cortex. Proc Nat Acad Sci USA 2001; 98:
4687–4692.
49. Afridi SK, Giffin NJ, Kaube H, et al. A positron emis-
sion tomographic study in spontaneous migraine. Arch
Neurol 2005; 62: 1270–1275.
Cephalalgia 0(0)
50. Demarquay G, Lothe A, Royet JP, et al. Brainstem
changes in 5-HT1A receptor availability during migraine
attack. Cephalalgia 2011; 31: 84–94.
51. Weiller C, May A, Limmroth V, et al. Brain stem activa-
tion in spontaneous human migraine attacks. Nat Med
1995; 1: 658–660.
52. Sakai Y, Dobson C, Diksic M, et al. Sumatriptan nor-
malizes the migraine attack-related increase in brain sero-
tonin synthesis. Neurology 2008; 70: 431–439.
53. Denuelle M, Fabre N, Payoux P, et al. Hypothalamic
activation in spontaneous migraine attacks. Headache
2007; 47: 1418–1426.
54. Munir F, Jones D, Leka S, et al. Work limitations and
employer adjustments for employees with chronic illness.
Int J Rehabil Res 2005; 28: 111–117.
55. Lerner DJ, Amick BC, Malspeis S, et al. The migraine
work and productivity loss questionnaire: Concepts and
design. Qual Life Res 1999; 8: 699–710.
56. Nascimento TD, DosSantos MF, Danciu T, et al. Real-
time sharing and expression of migraine headache suffer-
ing on Twitter: A cross-sectional infodemiology study.
J Med Internet Res 2014; 16: e96.