ISSN 0017-8748
doi: 10.1111/j.1526-4610.2011.01963.x
Published by Wiley Periodicals, Inc.

Headache
© 2011 American Headache Society

Brief Communication
Hemiplegic Migraine Aura Begins With Cerebral
Hypoperfusion: Imaging in the Acute Phase
head_1963

1289..1296

Jakob M. Hansen, MD, PhD; Henrik W. Schytz, MD, PhD; Vibeke A. Larsen, MD, PhD;
Helle K. Iversen, MD, DrMSc; Messoud Ashina, MD, PhD, DrMSc

Imaging studies of spontaneous migraine aura have proved challenging because of the episodic and unpredictable nature
of migraine attacks. Two patients with signs of acute ischemic stroke were evaluated for thrombolysis and turned out to suffer
from familial hemiplegic migraine. It was possible to record the early phase of the hemiplegic aura with computed tomography
with perfusion sequences and magnetic resonance imaging. We found cerebral hypoperfusion in the relevant cortical areas
within the first hour after onset of aura symptoms. This report supports the concept that migraine aura across the migraine
spectrum is caused by similar mechanisms. In a setting with efficient cooperation between headache and stroke neurologists,
thrombolysis centers provide the set-up and opportunity to record aura symptoms at an early phase. Furthermore, in the time
of ready access to acute systemic thrombolysis treatment, these cases underscore the importance of an accurate headache
history, especially in younger patients.
Key words: familial hemiplegic migraine, migraine aura, cortical spreading depression, magnetic resonance imaging, computed
tomography
(Headache 2011;51:1289-1296)

INTRODUCTION
Imaging studies of spontaneous migraine aura
have proved challenging because of the episodic and

Address all correspondence to J.M. Hansen, Danish Headache
Center, Department of Neurology N01, Glostrup Hospital,
Faculty of Health Sciences, University of Copenhagen, Nordre
Ringvej 57, DK-2600 Glostrup, Copenhagen, Denmark, email:
jmh@dadlnet.dk.

unpredictable nature of migraine attacks. Two
patients with signs of acute ischemic stroke were
evaluated for thrombolysis and turned out to suffer
from familial hemiplegic migraine. It was possible
to record the early phase of the hemiplegic aura
with computed tomography (CT) with perfusion
sequences and magnetic resonance imaging (MRI).
We found cerebral hypoperfusion in the relevant cortical areas within the first hour after onset of aura
symptoms. This report supports the concept that
migraine aura across the migraine spectrum is caused
by similar mechanisms.
In a setting with efficient cooperation between
headache and stroke neurologists, thrombolysis
centers provide the set-up and opportunity to record
aura symptoms at an early phase. Furthermore, in the
time of ready access to acute systemic thrombolysis

Accepted for publication April 3, 2011.

Conflict of Interest: None

From Danish Headache Center, Department of Neurology,
Glostrup Hospital, Faculty of Health Sciences, University of
Copenhagen, Copenhagen, Denmark (J.M. Hansen, H.W.
Schytz, and M. Ashina); Glostrup Stroke Center, Department
of Neurology, Glostrup Hospital, Faculty of Health Sciences,
University of Copenhagen, Copenhagen, Denmark (H.K.
Iversen); Radiology and Functional Imaging Unit, Glostrup
Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (V.A. Larsen).
Patient confidentiality: All patients gave informed consent.

1289

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September 2011

NCCT

CBF

CBV

Fig 1.—Non-contrast computed tomography (NCCT) and CT perfusion of patient 1 performed 70 minutes after onset of symptoms.
NCCT shows no signs of infarcts. CT perfusion study performed with a 64 multi-detector CT scanner. Sixteen 5-mm slices were
performed using 50 mL Iomeron 400 mg I/mL with an injection rate of 5 mL/second. The images show a perfusion defect in the
right frontal lobe with decreased cerebral blood flow (CBF) and cerebral blood volume (CBV), indicating a vascular event in that
region.

treatment, these cases underscore the importance of
an accurate headache history, especially in younger
patients.

CASE 1
A 33-year-old man, non-smoker, noted acute
onset of anesthesia and paresthesia in the left part of
the face and neck. After a few minutes, the symptoms
spread to the left arm. Paramedics arrived 10 minutes
later and noted reduced motor response of the left
leg on ambulation. The patient was referred to the
Stroke Center and arrived 55 minutes after onset of
symptoms.
On admission, the patient was alert and
fully cooperative and reported aggravation of the
paresthesia in the left part of the face and arm, but
no headache. Physical examination revealed a discrete reduction in the motor response of the left
arm and leg (strength 4 of 5), no dysarthria or
aphasia (National Institutes of Health Stroke Scale
[NIHSS] 1-2). The patient was cardiorespiratory
stabile.
In 2004, the patient was diagnosed with hemiplegic migraine. He described his usual hemiplegic
attacks as acute right-sided migraine headache followed by a left-sided hemiparesis lasting up to 1 hour.
The previous diagnostic work-up, including cerebral
CT, MRI, lumbar puncture tab and ultrasound of the
heart, revealed no pathology. The last attack was 6
years before the current admission.

As the patient described a different quality to the
symptoms than his previous attacks of hemiplegic
migraine, he was taken to acute CT with perfusion
sequences (Fig. 1).
Computed tomography was performed 70
minutes after start of symptoms and showed a small
perfusion defect in the right frontal lobe with
increased cerebral blood volume (CBV), reduced
cerebral blood flow (CBF), and increased mean
transit time (MTT) (Fig. 1). Based on imaging, headache history and the gradual evaluation of symptoms,
no thrombolysis was given. Ninety minutes after
onset, the symptoms remitted gradually over 30
minutes. Approximately 3 hours after onset, the
patient reported a bilateral mild and pressing headache (Intensity 2 on visual analog scale). The patient
needed no analgesic treatment, and reported no
nausea, photo, or phonophobia.
Two days after ictus, the headache had resolved
spontaneously. The MRI with diffusion and angio
sequences 3 days after ictus showed no signs of stroke
or other pathology. Ultrasound of the carotid arteries
was normal.

CASE 2
A 25-year-old non-smoking man noted foggy
vision and dizziness quickly followed by acutely
beginning anesthesia and paresthesia in the right
hand spreading slowly proximally. After 10 minutes
the patient noted aphasia and difficulties controlling

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Fig 2.—Diffusion-weighted imaging and fluid-attenuated inversion recovery magnetic resonance imaging (MRI) performed 20
minutes after onset of symptoms in patient 2 is normal without signs of ischemia or infarct. MR perfusion measurement with
time-to-peak map showing delayed arrival of the contrast bolus in the left occipitoparietal region. The measurement was performed
on a 3T Philips scanner with the dynamic susceptibility contrast MRI.

the right arm. The patient was near the hospital and
was rushed there for an acute evaluation. Twenty
minutes after start of symptoms, the patient underwent 3 Tesla dynamic susceptibility contrast MRI
(Fig. 2).
Magnetic resonance imaging showed normal diffusion and no signs of infarction; diffusion-weighted
imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) were normal but MR perfusion showed
increased time to peak (TTP) in an area posteriorly in
the left hemisphere, indicating hypoperfusion in this
area (Fig. 2). The aura symptoms gradually resolved
within 20 minutes. Fifty minutes after start of symptoms, the patient reported left-sided headache,
described as pressing and aggravated after physical
strain, intensity 7 on visual analog scale.The headache
was associated with photophobia only. The headache
resolved spontaneously within 12 hours.
The patient had never previously experienced
similar episodes and only suffered from episodic
tension-type headache less than 2 days per month.
His mother, however, has had several similar episodes
and had been diagnosed with hemiplegic migraine.

DISCUSSION
We describe 2 cases of spontaneous hemiplegic
migraine aura, where imaging was carried out in the
acute phase 20-70 minutes after symptom onset. We
found signs of acute cerebral hypoperfusion similar to
what has been reported in migraine with typical aura.

Cortical spreading depression (CSD), described
by Leão,1 has been linked to migraine aura pathogenesis in both observational,2 animal,3 and human
studies.4-6 In patients with migraine with typical aura
(MA), the regional cerebral blood flow (rCBF) has
been measured during the aura by single-photon
emission computed tomography (SPECT), MRI,
and positron emission tomography (PET).7-9 During
the aura, spreading oligemia moves from posterior
to anterior brain areas,7-9 with a focal blood flow
decrease of 16-53% compared with the symmetrical
contralateral region.9-11 During the ensuing headache
phase, regional CBF gradually changes from abnormally low to abnormally high without apparent parallel changes in headache,6 but the hyperperfusion
often persists beyond the duration of the clinical
headache.12 Cerebral imaging in the acute phase of
the aura in MA show cerebral hypoperfusion.8,13,14
Most perfusion abnormalities have been reported in
the occipital cortex, corresponding with visual aura
symptoms, whereas aphasic aura is likely a symptom
of CSD in the parietal lobe.14,15 Subtle differences in
disease mechanisms may, however, exist across the
migraine spectrum.16
Hemiplegic migraine is a rare subtype of
migraine with transient hemiplegia during the aura
phase.17 Hemiplegic migraine is a very rare disease
with prevalence of 0.01%,18 and therefore imaging
studies in these patients are mostly single cases. Most
observations of spontaneous aura have been carried

MR perfusion; day 1

MR perfusion; 47 hours

MR perfusion; 1 week

MR perfusion; day 2

MR perfusion, DWI; 6
hours

SPECT; during the
attack, ND

SPECT; during the
attack, ND

MR perfusion, DWI;
day 2

MR perfusion, DWI;
during the attack, ND

MRI; within the time
limit for lytic therapy,
timing not disclosed
CT; on admission, ND

CT; within the time limit
for lytic therapy,
timing not disclosed

Hsu et al20

Masuzaki
et al21

Jacob et al22

Oberndorfer
et al23

Lindahl et al24

Friberg et al19

Cheng et al27

Yilmaz et al28

Altinok et al29

Chen et al30

Pettersen
et al31

Mjaset and
Russell26

Acute Imaging; Timing

Reference

Reduced perfusion

Normal

DWI normal

Hypoperfusion, small area of
restricted diffusion

Hypoperfusion
DWI normal

During aura: hypoperfusion
During headache:
hyperperfusion

Hypoperfusion, preceded by
focal hyperperfusion

Hyperperfusion
DWI normal

Hyperperfusion

Hyperperfusion

Hyperperfusion

Hyperperfusion

Perfusion

3 days

SPECT; day 22

DWI; day 9

ND

MR perfusion; 3 days

MR perfusion, DWI; 12 months

SPECT; 10 days

ND

MR perfusion; 4 days and 3
months

MR perfusion; days 9 and 24

3 months

MR perfusion; 1 month

CT perfusion; days 6 and 14

Follow-Up; Timing

Normal DWI

DWI: ischemia without
infarction
SPECT: reduced perfusion

ND

Normal

Near normal

Normal

ND

Hyperperfusion; day 4
Normal follow-up at 3 months

Hyperperfusion; day 9
Normal; day 24

Almost complete resolution

Normal

Hyperperfusion

Perfusion

Table.—Neuroimaging in Patients With Hemiplegic Migraine or Suspected Hemiplegic Migraine

DWI 3 days after onset was
normal

Readmitted on day 55: MRI
normal
SPECT: reduced perfusion

Evaluated for, but not given,
thrombolysis

—

Diagnosed with “headache with
neurological deficits and CSF
lymphocytosis (HaNDL)”

—

Triggered by angiography

—

SPECT showed increased (day
2) and normal (day 24) tracer
uptake

—

Initial imaging carried out
during headache phase

Two clonic seizures during
admission

Comment

1292
September 2011

DWI and MR perfusion:
normal
PET: reduced relative tracer
uptake
CT normal
DWI high signal

DWI; day 1
MR perfusion; day 2
PET; day 6

Contrast CT (1st visit);
ND
DWI (2nd visit); 3 weeks

CTC; 1 hour
DWI; 9 hours

MRI, DWI; 48 hours

MRA; 2 days

MRI and MRA; 2 days

Gutschalk
et al33

Butteriss
et al34

Toldo et al35

Kumar et al36

Gonzalez-Alegre
& Tippin37

Barbour
et al25

PET decrease cortical
metabolic activity
DWI normal
SPECT on day 6
hypoperfusion of the left
cerebral hemisphere
compared with the right
FLAIR; high signal
throughout the cortex of
the right cerebral
hemisphere
SPECT; hyperperfusion of the
right cerebral hemisphere

PET; 14 days

SPECT; 14 days

MRI-FLAIR; day 8

MRI, DWI; 5 days
SPECT; 6 days

MRA; 5 days
SPECT; 13 days

Diffuse cortical edema on
FLAIR that was reduced at
day 15; SPET on day 27;
showed a marked
hemispheric hypoperfusion
MRA showed increased flow
SPECT normal perfusion

Normal

Normal

Normal DWI
Diffuse cortical edema on
FLAIR

ND

MRI on days 4,11 and 15;
SPET on day 27; showed a
marked left hemispheric
hypoperfusion

MRI (1st visit); day 6
MRI (2nd visit); 6 months

DWI, MR perfusion; day 98

Day 10; MRI

ND

Left-sided hemiparesis. Patient
36 weeks pregnant

Left-sided hemiparesis. Patient
38 weeks pregnant

—

SHM
MRI and SPET at 6 months
was normal

Same patient examined on 2
episodes

—

SHM

Two cases evaluated for, but
not given, thrombolysis

CSF = cerebrospinal fluid; CTC = computed tomography colonography; DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; MRA = magnetic resonance angiography;
MRI = magnetic resonance imaging; ND = not described; PET = positron emission tomography; SHM = spontaneous hemiplegic migraine; SPECT = single-photon emission computed tomography;
SPET = single-photon emission tomography; — = inconclusive results.

Normal

MRA normal

DWI normal

CT normal
DWI normal

MRA, DWI were normal

MRA, DWI; not
disclosed

De Sanctis
et al32

Hypoperfusion
DWI normal

MR perfusion, DWI;
within the time limit
for lytic therapy,
timing not disclosed

Kraus et al13

Headache
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out over a large time span with respect to onset of
symptoms.
Cerebral blood flow studies during a hemiplegic
aura provoked by angiography showed a spreading
cortical hypoperfusion,19 similar to migraine with
aura,10 which suggest that CSD is the most likely
mechanism of hemiplegic aura.7,11 Most reports of
spontaneous hemiplegic migraine aura, however,
report cortical hyperperfusion,20-25 possibly because
imaging in these patients has been carried out late in
the aura phase, where blood flow is abnormally high
(see also the Table). Reduced perfusion long after
onset of symptoms26 and even hypoperfusion in the
right thalamus during the aura phase with SPECT27
have been reported. In a case of headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) with left-sided deficits, MRI was
performed 30 minutes after onset of symptoms and
showed focal hypoperfusion in the brain regions corresponding to the focal neurological deficits.28 A
recent paper reported cerebral hypoperfusion contralateral to the side of hemiplegic aura on perfusion
MRI performed during the aura phase (timing,
however, not disclosed).29 Concomitant susceptibilityweighted MRI showed prominent vessels in the left
cerebral hemisphere, likely caused by venous stasis
raising the possibility of stroke or vasculitis.
In these 2 cases of spontaneous hemiplegic
migraine attacks, the location of the perfusion defects
in the relevant cortical areas may explain the clinical
presentation with hemiplegia and aphasia (Figs. 1 and
2). Apart from the location, it seems that the cerebrovascular changes in hemiplegic migraine aura are
similar to the aura of typical migraine.
Both patients were evaluated for acute systemic
thrombolysis treatment. Migraine aura is a wellknown differential diagnosis to stroke and because of
the march of symptoms and taking into account the
patient’s family and headache history, thrombolysis
treatment was not indicated.

CONCLUSION
The 2 cases underscore the importance of an
accurate headache history, especially in younger
patients. In a streamlined set-up for admission and
evaluation of stroke patients for thrombolysis, some

September 2011
patients who actually suffer from migraine with aura
will be referred. Given an efficient cooperation
between headache and stroke neurologists, this
offers unique opportunities to study the early aura
phase.

STATEMENT OF AUTHORSHIP
Category 1
(a) Conception and Design
Jakob M. Hansen; Henrik W. Schytz; Vibeke A.
Larsen; Helle K. Iversen; Messoud Ashina
(b) Acquisition of Data
Jakob M. Hansen; Vibeke A. Larsen
(c) Analysis and Interpretation of Data
Jakob M. Hansen; Henrik W. Schytz; Vibeke A.
Larsen; Helle K. Iversen; Messoud Ashina
Category 2
(a) Drafting the Article
Jakob M. Hansen; Henrik W. Schytz; Messoud
Ashina
(b) Revising It for Intellectual Content
Jakob M. Hansen; Henrik W. Schytz; Vibeke A.
Larsen; Helle K. Iversen; Messoud Ashina
Category 3
(a) Final Approval of the Completed Article
Jakob M. Hansen; Henrik W. Schytz; Vibeke A.
Larsen; Helle K. Iversen; Messoud Ashina

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