Neuroradiology (2012) 54:255–260
DOI 10.1007/s00234-011-0946-z

FUNCTIONAL NEURORADIOLOGY

Perfusion-weighted MR imaging in persistent
hemiplegic migraine
Isabelle Mourand & Nicolas Menjot de Champfleur &
Clarisse Carra-Dallière & Emmanuelle Le Bars &
Agathe Roubertie & Alain Bonafé & Eric Thouvenot

Received: 12 May 2011 / Accepted: 26 July 2011 / Published online: 11 August 2011
# Springer-Verlag 2011

Abstract
Introduction Hemiplegic migraine is a rare type of migraine
that has an aura characterized by the presence of motor
weakness, which may occasionally last up to several days,
and then resolve without sequela. Pathogenesis of migraine
remains unclear and, recently, perfusion-weighted imaging
(PWI) has provided a non-invasive method to study
hemodynamic changes during acute attacks.
Methods Two female patients were admitted in our hospital
suffering from prolonged hemiparesis. In both cases, they
underwent MRI examination using a 1.5 T magnet
including axial diffusion-weighted and perfusion sequences.
From each perfusion MRI acquisition two regions of interest
were delineated on each hemisphere and, the index of flow,
cerebral blood volume, mean transit time, and time to peak
were recorded and asymmetry indices from each perfusion
parameter were calculated.
Results Perfusion alterations were detected during the
attacks. In one case, we observed, after 3 h of left
hemiparesia, hypoperfusion of the right hemisphere. In the
other case, who presented a familial hemiplegic migraine
attack, on the third day of a persistent aura consisting of
right hemiplegia and aphasia, PWI revealed hyperperfusion
of the left hemisphere. Asymmetry indices for temporal
I. Mourand (*) : N. Menjot de Champfleur : C. Carra-Dallière :
E. Le Bars : A. Bonafé : E. Thouvenot
Service de Neuroradiologie, Hôpital Gui de Chauliac,
80 avenue Augustin Fliche,
34295 Montpellier Cedex 5, France
e-mail: i-mourand@chu-montpellier.fr
A. Roubertie
Service de Neuropédiatrie, Hôpital Gui de Chauliac,
80 avenue Augustin Fliche,
34295 Montpellier Cedex 5, France

parameters (mean transit time and time to peak) were the
most sensitive. These findings resolved spontaneously after
the attacks without any permanent sequel or signs of
cerebral ischemia on follow-up MRI.
Conclusions PWI should be indicated for patients with
migraine attacks accompanied by auras to assess the
sequential changes in cerebral perfusion and to better
understand its pathogenesis.
Keywords Hemiplegic migraine . Familial hemiplegic
migraine . MRI . Persistent aura
Abbreviations
PWI
perfusion-weighted imaging
HM
Hemiplegic migraine
FHM
familial hemiplegic migraine
SHM
sporadic hemiplegic migraine
DWI
diffusion-weighted imaging
CBV
cerebral blood volume
FLAIR fluid-attenuated inversion recovery
ICBF
Index of Cerebral Blood Flow
MTT
mean transit time
TTP
time to peak
TOF
3D time-of-flight
MRA
MR angiography

Introduction
Hemiplegic migraine (HM) is a rare variety of migraine
defined by migraine attacks, which include the presence of
motor weakness during the aura. HM has two main forms
according to the familial history. Patients with at least one
first- or second-degree relative, who presents with aura

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characterized by motor weakness, fulfil the criteria for
familial hemiplegic migraine (FHM), whereas patients
without a familial history have a sporadic hemiplegic
migraine (SHM). Molecular biology is increasingly being
used to diagnose FHM, by screening for the three known
genes involved in FHM (CACNA1A, ATP1A2, and SCNA1)
[1]. FHM and SHM are equally frequent, and the prevalence
of HM is ~1/10,000 people. Attacks usually start in
childhood or adolescence. Although prognosis is usually
good, severe attacks may occur with prolonged hemiplegia,
confusion, coma, fever, and seizures [1]. Earlier reports
have shown that attacks can last up to several hours or
days, but without any permanent neurological deficit or
infarct [2, 3].
The pathogenesis of migraine remains unclear, and
conflicting theories between vascular or neuronal dysfunction have been suggested. In this context, imaging
techniques have proved helpful in understanding the
pathogenesis of migraine. Many reports have demonstrated
changes in cerebral blood flow (CBF) in classic migraine
attacks [2, 4–8]. However, there are still few reports on
multimodal neuroimaging in HM [4, 9–16]. Collecting this
information could provide important information about HM
and help us understand its pathology.
The objective of this report is to describe two patients
with HM, where perfusion-weighted imaging (PWI) was
used at different time courses. This revealed opposite
changes in cerebral perfusion during the migraine attacks.
We also documented the course of neurological deficit in
one patient who presented with a FHM attack, and whose
aura persisted for >9 days, but did not cause any permanent
sequela or ischemic lesion or infarct on follow-up MRI.

Patients and methods
The patients underwent MRI examination using a 1.5 T
magnet (Intera, Philips, Best, the Netherlands). The MRI
protocol included T1-weighted images, T2-weighted
images, axial fluid-attenuated inversion recovery (FLAIR)
sequence, and axial isotropic diffusion-weighted EPI
sequence (27 slices, slice thickness 5 mm, gap 0 mm) with
b=0 and b=1,000 s/mm2, as well as a 3D time-of-flight
(TOF) sequence, to determine intracranial abnormalities of
the cerebral arteries. The ADC map was calculated in line
on the acquisition station. A susceptibility-based MR
perfusion sequence was performed as a 3D-segmented
EPI technique (T2*-weighted PRESTO). Twenty-seven
slices, covering the entire brain (acquisition matrix size
64×64), were acquired with a time resolution of 1.2 s, with
Phase array coil. The total scan time was 1 min and 17 s. A
bolus of gadolinium (0.2 mmol/kg body weight) was

Neuroradiology (2012) 54:255–260

administered at an injection rate of 6 ml/s, and was then
flushed with 20 ml of saline.
All perfusion data were processed at a workstation (View
Forum, version 3.2, Philips Medical System) with commercially available software. The curve of the timedependent concentration of the contrast bolus was analyzed.
These curves were computed from the changes in signal
intensity and were fitted to a γ-variate function to correct
for recirculation. Perfusion-parameter maps were computed
on a voxel, by voxel analysis. The negative integral under
the curve corresponded to the relative CBV. The index map
that corresponded to relative index of CBF was calculated
as the ratio of the negative integral under the curve and the
mean transit time (MTT). The time-to-peak was calculated
pixel by pixel and corresponded to the signal drop was the
largest. From each perfusion MRI acquisition, from all
slices, two regions of interest were delineated on each
hemisphere and, the index of flow (ICBF), CBV, MTT, and
TTP were recorded. The mean of all brain analyses for each
parameter were obtained and asymmetry indices (AIs;
pathological hemisphere compared to controlateral hemisphere) from each perfusion parameter were calculated
100× (pathological hemisphere − controlateral hemisphere)/
[(pathological hemisphere + controlateral hemisphere)/2].
Case 1
The first patient was a 12-year-old right-handed girl with a
personal and family history of migraine without auras. She
experienced sudden severe headache, nausea, and blurred
vision with flashing red dots, followed by left-sided
hemiparesis, dysarthria, and paresthesia of the left hand.
She was admitted to our hospital 2 h after onset of
symptoms with a persistent headache and vomiting. The
neurological examination revealed left-sided hemiparesis.
Routine blood tests, electroencephalography, visual-evoked
potentials, brain angiography, computed tomography, and
extracranial and transcranial Doppler were normal. Brain
MRI examination with T1- and T2-weighted images,
FLAIR, diffusion-weighted images (DWI), and MR angiography (MRA) showed no abnormalities (Fig. 1a–c). PWI
performed 3 h after the onset of symptoms revealed
hypoperfusion of the right cerebral (pathological) hemisphere compared to the left hemisphere (Fig. 1d). The AIs
were very high for ICBF but were also moderate for CBV at
that time (Table 1). All parameters of perfusion (ICBF, CBV,
MTT, and TTP) were significantly modified (Wilcoxon test),
as illustrated on Fig. 1d.
The condition of the patient gradually improved in a
few hours and she completely recovered in less than
24 h. Since then, she has had no recurrent attack of
HM. A search for mutations of the CACNA1A and

Neuroradiology (2012) 54:255–260

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Fig. 1 Multimodal MRI of case 1 after 3 h of left hemiplegia. DWI (a), FLAIR (b), and MRA (c) show no abnormality. Maps from PWI
parameters (d) show an asymmetry of CBV, ICBF, and TTP

ATP1A2 genes was negative. On the basis of these clinical
findings, a diagnosis of SHM was considered the most
likely, even if the diagnostic criteria for this disease were not
fully satisfied.
Case 2
A 36-year-old woman was referred to our hospital for
subacute development of right-sided hemiplegia, aphasia,
and fever that had been developing for 60 h. She was

known to have suffered from FHM since the age of 9, but
the auras she had usually lasted less than 2 h and always
consisted of right-sided hemiplegia and aphasia. Only two
attacks had occurred during the past year since FHM had
been diagnosed. Her mother, her grandmother, and her 13year-old daughter also suffered from migraine with intermittent neurological deficits. The patient’s FHM was linked
to a mutation of the CACNA1A gene, as was her daughter’s.
At presentation, she reported global blurring of vision
for a few minutes. Recognizing the first sign of a migraine

Table 1 Analysis of MRI perfusion parameters during hemiplegic migraine
Case 1

Case 2

MRI delay

3h

72 h

Parameters

AI

p

AI

p

AI

p

Difference

CBV
ICBF
TTP
MTT

−12.8%
−40.2%
+14.1%
+26.9%

0.0028
0.00032
0.00032
0.00032

+49.8%
+47.3%
−5.2%
+3.4%

0.00047
0.00048
0.00048
0.23

+11.6%
+13.9%
−2.3%
−2.0%

0.00082
0.0082
0.00070
0.33

−82.7%
−81.1%
−58.4%
NA

120 h

Evolution of MRI parameters
p
0.00047
0.00071
0.00072
0.15

Asymmetry indices for the parameters of the PWI show a strong decrease in ICBF of the pathological hemisphere at 3 h after the onset of an aura
in case 1. In contrast, the ICBF increases in case 2, and corresponds to hyperperfusion of the pathological hemisphere after 72 h, though this
becomes less intense after 120 h. The difference (pathological hemisphere–controlateral hemisphere) strongly decreases from 72 to 120 h for CBV,
ICBF, and TTP, and is then correlated with clinical improvement of the patient

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Neuroradiology (2012) 54:255–260

attack, she took a naratriptan tablet (2.5 mg). In the
following hour, she developed sudden-onset right-sided
weakness with continuous headache and vomiting. Her
mother gave her dihydroergotamine (nasal spray, 0.5 mg).
On admission, a neurological examination demonstrated
right hemiparesis and global aphasia. Routine blood tests,
including an ionogram, complete blood count, and coagulation tests, were normal. An ECG was also normal.
An MRI was performed 72 h after the onset of symptoms.
Routine T1- and T2-weighted images, FLAIR, and DWI did
not show any pathological findings, in particular any cerebral
tissue injury (Fig. 2a, b). MRA, performed with a 3D TOF
sequence, did not show arterial occlusion (Fig. 2c). PWI
revealed hyperperfusion of the left cerebral hemisphere
(pathological) compared to the controlateral hemisphere

a

b

(Fig. 2d), demonstrating significant findings of ICBF, CBV,
and TTP, but not MTT (Table 1). At the time, the AIs were
very high for ICBF and CBV. ICBF and CBV maps showed
asymmetry for these perfusion parameters.
A new PWI, performed 120 h after the onset of symptoms,
while mild aphasia was still present, also showed asymmetry
of perfusion, though this was then less marked (Table 1,
Fig. 2e). Quantitative data for all PWI studies indicated a
continuous decrease in the AIs of CBV, ICBF, TTP, and an
increase in the AI of TTP in the first MRI (after 72 h)
compared to the second MRI (after 120 h). Nevertheless, the
differences between the two hemispheres remained significant (Wilcoxon test). At 9 days after the onset of the
migraine attack, the patient was discharged. Neurological
examination revealed only mild aphasia, with complete

c

d

CBV

ICBF

TTP

MTT

CBV

ICBF

TTP

MTT

e

Fig. 2 Multimodal MRI of case 2 after 72 and 120 h of right
hemiplegia and aphasia. DWI (a), FLAIR (b) show no abnormality.
MRA (c) shows dilatation of the left ACM branches. Maps of PWI

parameters at 72 h (d) show important asymmetry of CBV, ICBF, and
TTP, which tend to normalize after 120 h (e)

Neuroradiology (2012) 54:255–260

remission of hemiparesis. A migraine-preventive treatment,
consisting of lamotrigine 100 mg/day, was introduced
progressively. No HM attack has been reported since then.

Discussion
In migraine with aura, the symptoms related to the cerebral
cortex or to brain-stem dysfunction usually develop gradually
over 5 min and then usually last for less than 60 min.
Occasionally, the duration of the neurological deficit is
prolonged over several hours or days. In the 2004 revision
of the International Classification of Headache Disorders, a
rare but well-documented complication of migraine was
inserted, which was characterized by aura symptoms that
persisted for more than 1 week without radiological evidence
of tissue injury [10]. Effectively, HM may mimic an acute
ischemic stroke, making clinical distinction challenging,
especially considering the urgency of stroke treatment
(thrombolysis) [11]. Clinically, HM attacks can be distinguished from stroke by the gradual development and
progression of aura symptoms, the reporting of a migraine,
and the patient’s personal and family history regarding HM, if
the information is available.
In case 1, the PWI examination was conducted 3 h after the
onset of symptoms, and showed cortical hypoperfusion while
the neurological symptoms were still present. The reduction of
ICBF and the increase in TTP occurred concomitantly with
the aura symptoms. These parameters’ values seem to be
above the ischemic threshold as a cerebral infarction did not
develop, as assessed by DWI. These results are in concordance with Andersen’s findings, who reported, by means of
SPECT, initial hypoperfusion that persisted for up to 3 h in the
appropriate hemisphere of a neurological deficit [17]. The
results from case 1 are also in concordance with Kapinos and
Linn’ findings, who reported, by means of PWI in the
hyperacute phase (2 h and 30 min), initial hypoperfusion
above the ischemic threshold [11, 13].
In case 2, we report on a young woman suffering from
FHM, who experienced a severe and long-lasting migraine
attack. In contrast to case 1, PWI, performed several days
after the onset of aura, showed persistent hyperperfusion of
the pathological hemisphere. Moreover, we did not observe
any abnormality of DWI, which is consistent with the
literature for patients with migraine with aura [13]. These
cases demonstrate the usefulness of multimodal MRI in
patients with acute hemiparesis to distinguish between HM
and ischemic lesion. To comfort us in the diagnostic of HM,
hemodynamic changes observed, in both cases, during the
acute phase, were not respecting any single arterial territory,
DWI was negative and we did not see vascular occlusion
on TOF.

259

Alterations in cerebral perfusion have been well documented in patients with migraine attacks. Hemodynamic
changes have been observed in migraine patients with and
without aura [10, 15, 18]. During a typical aura, transient
hypoperfusion is usually observed [9, 15]. Linn et al.
reported that clinical function can be restored before
resolution of hypoperfusion in PWI [13]. In patients with
a prolonged or persistent aura, some authors have described
hyperperfusion [4, 12, 16] as well as hypoperfusion [14], as
assessed by PWI and/or by SPECT. Findings in the
literature may seem ambivalent because the temporal
acquisition for perfusion imaging greatly influences the
results, between initial hypoperfusion and subsequent
hyperperfusion/hyperpermeability.
There are only a few reports on neuroimaging for HM
[2, 4–8]. In case 2, PWI showed hyperperfusion at 72 h
after the onset of hemiparesis and aphasia. At that time, the
AIs were very high for ICBF and CBV (Table 1). In the
second MRI, asymmetry of perfusion was still present, but
was less marked. However, mild aphasia persisted, and the
differences between the two hemispheres remained significant (Wilcoxon test). In this patient, PWI findings were
concordant with the literature. Indeed, previous studies have
reported normal DWI in patients with MHF, whereas PWI
and SPECT revealed hyperperfusion in the affected hemisphere, in particular, in cases where there was a long-lasting
migraine attack [6–8]. Nevertheless, it remains unclear why
neurological deficits are still present under conditions of
subsequent hyperperfusion. Hemispheric hyperperfusion in
patients with FHM and long-lasting aura, as in case 2, could
argue against an ischemia mechanism. The concomittant
neurological deficit and elevated CBV and CBF, rather
support the hypothesis that etiopathogenesis in migraine is
caused by primary neuronal dysfunction. Although the
spread of cortical depression [19] may well explain a typical
migraine aura, as well as the initiation of a prolonged aura in
FHM, it can hardly account for neuronal dysfunctions that
can occur for days or weeks [2].
The two cases presented here nicely link to imaging data
from the literature on migraine patients [6–9, 11–16].
Previous reports reveal a brief wave of initial hyperperfusion,
followed by hypoperfusion of the affected hemisphere,
which causes neurological symptoms and, later, a temporary
and variable state of hyperperfusion [8, 17]. We observed, in
both cases, that AI of ICBF was the parameter that showed
the greatest variability (>40%) associated with either
hypoperfusion or hyperperfusion. In contrast, the AIs of the
temporal parameters, MTT and TTP, were most significant in
the early scan of the patient with hypoperfusion (case 1).
Thus, AIs for perfusion mapping temporal parameters could
be the most sensitive markers for early hypoperfusion,
whereas AI of CBV could be more representative of

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hyperperfusion during a prolonged aura. These imaging
findings may depend on the type of the migraine, on the
delay between the onset of attack, and when a MRI is
conducted.

Conclusion
Many different findings from imaging have been described
in patients with migraine, but observations of brain
perfusion, as assessed by PWI during HM attacks, are rare.
The changes depend, at least in part, on when the imaging
is done and the course of the migraine attack. Thus, we
suggest that DWI and PWI imaging are useful during HM
attacks, not only to diagnose HM and exclude cerebral
infarction, but to also play a role in our future understanding of
the pathogenesis of HM. Further serial studies are required to
confirm data and to better define the changes observed here.

Conflict of interest We declare that we have no conflict of interest.

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