Clinical Neurology and Neurosurgery 165 (2018) 7–9

Contents lists available at ScienceDirect

Clinical Neurology and Neurosurgery

journal homepage: www.elsevier.com/locate/clineuro

Long-term follow-up of patients with migrainous infarction T

a,⁎ a a a a
Fabiola Serrano , Antonio Arauz , Rodrigo Uribe , Luis C Becerra , Katherine Mantilla ,
Fernando Zermeñob
a
Stroke Clinic, Instituto Nacional de Neurología and Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico
b
Headache Clinic, Instituto Nacional Neurología and Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico

A R T I C L E I N F O A B S T R A C T

Keywords: Among patients with migrainous infarction, the long-term prognosis is unclear. This study aims to estimate the
Migrainous infarction long-term risk of stroke recurrence and functional outcome in patients with migrainous infarction. In our study,
Migraine with aura 15 patients with migrainous infarction were followed for up to 7.5 years (12–240 months). For each patient,
Migraine clinical and imaging data were reviewed. Disability after migrainous Infarction was assessed with modified
Ischemic stroke
Rankin Score.
Stroke recurrence
Mean age was 34.8 ( ± 11.1) years. At the end of the follow-up 80% of the patients had favorable prognosis,
47% recovered completely and no patient died or had stroke recurrence. Our series also confirmed a low fre-
quency of the traditional risk factors and the reduction of migraine frequency after migrainous infarction.
This study has clinical implications and public health relevance, since our case series confirms a low fre-
quency, low recurrence rate, and good functional outcome for patients with migrainous infarction.

1. Introduction
Migraine is a common, chronic, and multifactorial disease that is
associated with a spectrum of vascular pathologies, including stroke
[1–3]. Migrainous infarction is a rare complication of an attack of mi-
graine with aura, associated with less than 1% of ischemic strokes [4,5].
Nevertheless, its incidence has increased in the younger population
[6,5]. There are plenty of studies and migrainous infarction series
published where the incidence [5,7], vascular risk factors, clinical
findings, and imaging results are well known [5,8]. Nevertheless, the
recurrence, functional evolution, and mortality of patients with mi-
grainous infarction at a long-term follow-up is unknown, which is the
main purpose of this study.
2. Patients and methods
This is a retrospective analysis of data collected prospectively in the
stroke clinic database of the National Institute of Neurology and
Neurosurgery in Mexico City from January 1990 to July 2016. The
database includes data on demographics, vascular risk factors, clinical
findings, laboratory and imaging results, as well as complication and
functional outcomes post-hospital discharge.
All stroke patients admitted to our hospital were included in our
database. All patients had a comprehensive stroke evaluation the first
week after stroke that includes MRI or CT to confirm the infarct, a 12-
lead EKG, 24 h telemetry, and at least one of the following procedures: a
conventional cerebral angiogram, a transcranial Doppler, or magnetic
resonance angiogram (MRA) of extracranial arteries along with carotid
ultrasound and 2D transthoracic echocardiogram (TTE). For patients
younger than 55 years, prothrombotic profiles including protein S,
protein C, and antithrombin III levels, antiphospholipid antibodies, and
anti-B2 glycoprotein were also collected. Prothrombotic screening was
performed three months after the stroke and repeated six months after.
For patients with a history of migraine, we also collected information
on the use and abuse of migraine abortive drugs, illicit drugs, and other
prescribed and non-prescribed medications or supplements before the
migrainous infarction and during follow-up. Follow-up was done in-
person at the stroke clinic, by telephone interviews or by medical chart
review; follow-up periods varied in length but were at least for one
year. Specific questions concerning clinical outcomes, therapy, com-
pliance, disability, and any recurrent infarction or vascular events were
evaluated. All patients were treated with prophylactic migraine drugs,
when it was necessary, plus aspirin for secondary stroke prevention
For this analysis, we identified patients who had a confirmed di-
agnosis of migrainous infarction, defined according to the HIS
Classification ICHD-3 Beta, as one or more migraines with aura symp-
toms associated with an ischemic brain lesion in the appropriate ter-
ritory demonstrated by neuroimaging and not better accounted for by

⁎
Corresponding author.
E-mail addresses: eunice.serrano13@gmail.com, eunice_13serrano@hotmail.com (F. Serrano).

https://doi.org/10.1016/j.clineuro.2017.12.008
Received 18 September 2017; Received in revised form 11 November 2017; Accepted 4 December 2017
Available online 09 December 2017
0303-8467/ © 2017 Elsevier B.V. All rights reserved.
F. Serrano et al. Clinical Neurology and Neurosurgery 165 (2018) 7–9

another diagnosis. For each patient, clinical, laboratory and imaging Table 1
data were reviewed by at least two neurologists (AA, FS). General characteristics of migrainous infarction cases.
The primary end-point of this analysis was recurrent ischemic stroke
Characteristics n = 15 (%)
(defined as a recurrent neurological deficit lasting more than 24 h in a
different territory or location compared with the baseline stroke, wor- Demographics
sening of an already known deficit corroborated by CT or MRI, exten- Female 8(53)
Age, years (median, IQR) 34, 8 (18–55)
sion of previous lesions or the presence of new ischemic events).
Follow-up, months (median, IQR) 7, 5 (12–240)
Disability at six months and at the end of the follow-up was assessed
using the modified Rankin Scale (mRS); a score of 0–2 on this scale was Risk factors
Oral contraceptives 4 (27)
considered a favorable functional outcome. Smoking habit 4 (27)
Hypertension 2 (13)
3. Statistical analysis Dyslipidemia 5 (33)

Clinical syndrome at end of follow-up

Data analysis on descriptive statistics was performed with the sta- Complete recovery 7 (47)
tistical package SPSS Version 21.0 software. We evaluated the pre- Right homonymous hemianopsia 3 (20)
Left homonymous hemianopsia 1 (7)
defined variables for each patient such as age and gender, as well as the
Left homonymous hemianopsia and hemiparesis 2 (13)
following variables, before and after the stroke: cardiovascular risk Right superior homonymous quadrantanopsia 2 (13)
factors, migraine characteristics, number of episodes, abortive treat-
Drugs for abortive episodes
ment, and prophylactic treatment. Ischemic territory, clinical symp- Ergotamine 3 (20)
toms, clinical sequelae, and modified Rankin scale (mRS) score were Triptan 1 (7)
evaluated at the end of the follow-up. Not treatment 11 (73)

Treatment after stroke

4. Results
The registry includes 5810 cases; among these, 4067 (70%) patients
has ischemic stroke, and 15 (0.36%) had stroke related to migraine. The
mean age of patients with migrainous infarction was 34.8 ± 11 years
(range 18–55 years) and 8 patients were men. Mean follow-up was 7.5
years (range 12–240 months). The most common vascular risk factors
were; oral contraceptive use (OC) in 4 patients (27%), smoking in 4
(27%), hypertension in 2 (13%), and dyslipidemia in 5 (33%). All pa-
tients presented with a visual aura episode before the onset of head-
ache; the aura later developed into a migrainous infarction.
The characteristic clinical and imaging data of the 15 patients with
migrainous infarction were reviewed by three neurologists, with com-
plete agreement (Table 1). All the infarcts were in the vertebrobasilar
arterial territory and the most frequent location was the occipital lobe
in 10 patients (67%). The mRS at discharge was 0–2 in 10 patients. At 6
months and final follow-up, 11 and 12 patients, respectively, had
mRS = 0–2. At the baseline neurological examination after migrainous
infarction; 67% of patients had mRS score that was considered favor-
able, and 73% of patients had a favorable score at the 6-month follow-
up, as did 80% of patients at the last evaluation. At the end of the
follow-up, 7 patients (47%) had complete recovery and did not have
deficits from the stroke, 4 (27%) had persistent homonymous hemi-
anopsia, 2 (13.4%) had homonymous hemianopsia and hemiparesis,
and 2 (13.4%) had a superior homonymous quadrantanopsia. None of
the patients had a stroke recurrence during follow-up. All patients were
prescribed 100 mg of aspirin daily as secondary prevention for stroke.
The migraine frequency as measured by mean-per-month changed
before (35 events) and after (2 events) the Migrainous infarction. After
the ischemic event, only one patient had residual visual aura during
migraine episodes.
5. Discussion
Even though migrainous infarction has been described as a cause of
ischemic stroke in young patients, there is paucity of data about the
functional outcome and recurrence risk in patients with migrainous
infarction. While other studies have shown a low recurrence rate and a
good functional outcome [5,9], in our patients we had a the longer
duration of follow-up. Our findings suggest that the risk of recurrence
stroke does not increase by time. We also confirmed a low frequency of
the traditional stroke risk factors in migrainous infarction patients. As
in other series, smoking and oral contraceptive use were the most fre-
quent risk factors observed [6]. Some authors have considered that
Beta-blockers 3 (15)
Antiepileptic 3 (15)
Serotonin-reuptake inhibitors 1 (7)
Non-steroidal anti-inflammatory (abortive) 2 (13)
Not treatment 6 (30)
Clinical outcome
Modified Rankin Score (0–2) discharge 10 (67)
Modified Rankin Score (0–2) at 90 days 11 (73)
Modified Rankin Score (0–2) at end of follow-up 12 (80)
migraine itself might be an independent risk factor for stroke [7,3,2].
As in other series, the clinical features of the patients with mi-
grainous infarction were suggestive of posterior circulation infarcts,
and imaging confirmed this location [10]. Some authors have suggested
an association between migrainous infarct and migraine treatment in-
cluding abortive-drugs, such as triptans or ergot alkaloids, which may
produce intracerebral vasospasm [11,6]. We did not find this associa-
tion
Effective migraine treatment with prophylactic drugs may decrease
the risk of stroke, reduce migraine attack frequency, and certainly re-
duce the need for abortive drugs and therapies [12]. In our series, most
patients with migraine had a decrease in the frequency of migraine after
the stroke: is the reduction in migraine frequency measured in mean-
per-month. Eight of our patients did not require migraine prophylaxis
after the stroke.
Early recurrence after migrainous infarction is uncommon. In our
study, we did not register any recurrence neither during the early nor
the long-term follow-up. Our results also confirm previous studies that
found good functional outcome [10].
Our study has significant strengths, such as the inclusion of a large
consecutive series of patients and the use of a standard protocol for
diagnosis, treatment and a long-term follow-up. However, certain lim-
itations need to be acknowledged: it is a retrospective analysis of col-
lected data with a long-study time period. In addition, while the reg-
istry is large, few patients had migrainous infarction. But the incidence
of stroke associated with migraine was similar to that observed in other
series [10].
6. Conclusion
Our study suggests that the frequency of migraine with aura de-
creases after migrainous infarction, while natural history of young pa-
tients with migrainous infarction is not modified over time.

8
F. Serrano et al.
Conflict of interests
The authors declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Contributions
All authors contributed equally to this work, discussed the results
and implications, and commented on the manuscript at all stages, and
finally approved the final version to be published.
Antonio Arauz: conceived and supervised the study and drafted the
manuscript.
Luis Becerra: drafted the manuscript and revised it critically.
Rodrigo Uribe: drafted the manuscript and revised it critically.
Katherine Mantilla: drafted the manuscript and revised it critically.
Fernando Zermeño: confirmed the diagnosis of migraine in all cases
and approved the manuscript to be published.
Fabiola Serrano: performed the statistic analysis and drafted the
manuscript.
Acknowledgements
Editorial support (limited to editing for style and referencing) was
provided by Jose Merino, MD.
Clinical Neurology and Neurosurgery 165 (2018) 7–9
References
[1] K. Eikermann-Haerter, J. Hyun Lee, I. Yuzawa, C.H. Liu, Z. Zhou, H. Kyoung Shin,
et al., Migraine mutations increase stroke vulnerability by facilitating ischemic
depolarizations, Circulation 125 (January (2)) (2012) 335–345.
[2] Z. Katsarava, C. Weimar, Migraine and stroke, J. Neurol. Sci. 299 (December (1–2))
(2010) 42–44.
[3] M.J. Lee, C. Lee, C. Chung, The Migraine–Stroke connection, J Stroke 18 (May (2))
(2016) 146–156.
[4] J. Mawet, T. Kurth, C. Ayata, Migraine and stroke: in search of shared mechanisms,
Cephalalgia 35 (2) (2015) 165–181.
[5] D. Sochurkova, T. Moreau, M. Lemesle, M. Menassa, M. Giroud, R. Dumas, Migraine
history and migraine-induced stroke in the dijon stroke registry,
Neuroepidemiology 18 (February (2)) (1999) 85–91.
[6] K. Laurell, E. Lundström, Migrainous infarction: aspects on risk factors and therapy,
Curr. Pain Headache Rep. 16 (June (3)) (2012) 255–260.
[7] M. Etminan, B. Takkouche, F.C. Isorna, A. Samii, Risk of ischaemic stroke in people
with migraine: systematic review and meta-analysis of observational studies, BMJ
330 (January(7482)) (2005) 63.
[8] A. Arboix, J. Massons, L. Garcia-Eroles, M. Oliveres, M. Balcells, C. Targa,
Migrainous cerebral infarction in the Sagrat Cor Hospital of Barcelona stroke reg-
istry, Cephalalgia 23 (June (5)) (2003) 389–394.
[9] J.B. Henrich, P.A.G. Sandercock, C.P. Warlow, L.N. Jones, Stroke and migraine in
the Oxfordshire Community Stroke Project, J. Neurol. 233 (October (5)) (1986)
257–262.
[10] K. Laurell, V. Artto, L. Bendtsen, K. Hagen, M. Kallela, E.L. Meyer, et al., Migrainous
infarction: a Nordic multicenter study, Eur. J. Neurol. 18 (October (10)) (2011)
1220–1226.
[11] A. Pezzini, E. Zotto, A. Giossi, I. Volonghi, M. Grassi, A. Padovani, The migraine-
ischemic stroke connection: potential pathogenic mechanisms, Curr. Mol. Med. 9
(March (9)) (2009) 215–226.
[12] E. Gretchen, M. Tietjen, Migraine and ischaemic heart disease and stroke: potential
mechanisms and treatment implications, Cephalalgia 27 (August (8)) (2007)
981–987.