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20
M. E. Jurno and L. B. de Oliveira
2.6 Diagnostic Algorithm
The diagnostic approach to status migrainosus begins with a careful evaluation of
the clinical history, with particular attention to the duration and course of the headache. According to the International Classication of Headache Disorders (ICHD-3),
status migrainosus is dened as a migraine attack lasting longer than 72h, with
either continuous pain or only brief periods of remission. In most cases, patients
have a pre-existing diagnosis of migraine, and the episode typically evolves from a
standard migraine attack that fails to resolve with usual treatment.
The symptom prole is essential in guiding the diagnosis. Common features
include severe, often unilateral, pulsatile headache, accompanied by nausea, vomiting, photophobia, and phonophobia. Patients often report worsening of symptoms
with routine physical activity and signicant impairment in daily functioning.
Disruption of sleep and emotional distress are also frequently observed. The presence of these typical features, in the absence of alarming neurological signs, supports the diagnosis of a primary migraine complication rather than a secondary
headache disorder.
An important step in the diagnostic process is assessing the response to standard
acute migraine treatments, such as triptans, NSAIDs, or rest in a dark room. In status migrainosus, these measures typically fail to provide relief. This lack of therapeutic response is a hallmark of the condition and indicates the need for more
aggressive management.
A neurological examination should always be performed to exclude secondary
causes of prolonged headache. In status migrainosus, the examination is usually
normal, without focal decits, meningeal signs, or altered mental status. However,
if any of these ndings are present, clinicians must consider other serious etiologies
such as subarachnoid hemorrhage, central nervous system infections, or spaceoccupying lesions, and order appropriate investigations.
Neuroimaging, particularly magnetic resonance imaging (MRI), may be indicated in patients with atypical features, a rst-time prolonged headache episode, or
poor response to treatment. This helps to rule out secondary causes and may occasionally reveal reversible changes associated with prolonged migraine attacks, such
as cortical spreading depression or mild vasogenic edema. In cases of persistent
vomiting, laboratory investigations including electrolytes, renal function, and
inammatory markers may also be useful to assess for dehydration and systemic
effects.
Finally, the application of ICHD-3 diagnostic criteria (code 1.4.1) helps conrm
the diagnosis. These include: a prior diagnosis of migraine, an attack lasting more
than 72 h, continuous or nearly continuous headache, and signicant functional
impairment that is unresponsive to acute treatment. Recognizing this condition
early is critical, as delayed diagnosis can lead to hospitalization, medication overuse, and progression to chronic migraine.
2 Migrainous Status
21
2.7 Management
The management of migrainous status is not yet standardized, and different
approaches are used in outpatient and hospital settings. In the early stages of this
condition, many specialists recommend treating the crisis within 72h, using medications such as corticosteroids, NSAIDs, neuroleptics, and triptans [4].
In refractory cases, where patients no longer respond to traditional therapies,
treatment in a hospital setting with intravenous medication administration is recommended. Commonly used options include intravenous uids, magnesium sulfate,
anticonvulsants, and serotonergic agents such as sumatriptan [6].
In emergencies, the primary focus is to alleviate pain and associated symptoms
such as nausea and vomiting. Some studies suggest that a combination of different
classes of medications, including antiemetics, NSAIDs, and corticosteroids, may be
effective in reducing symptoms [6
quality clinical trials exploring the efcacy of the various available therapies.
For patients with chronic status migrainosus, prolonged use of migraine medications without an effective prophylactic approach may exacerbate the condition,
leading to medication overuse headache. In these cases, a gradual discontinuation of
medications, combined with an appropriate preventive therapy, may prove to be an
effective strategy [6, 7].
Although status migrainosus is a temporary condition, its recurrence is associated with a poorer prognosis for patients with migraine. One study indicated that
approximately 15% of patients experiencing an episode of status migrainosus have
a recurrence within 1year [3]. Furthermore, these patients are at increased risk of
developing chronic migraine, particularly if triggering factors, such as sleep disorders and inappropriate medication use, are not managed [5].
Status migrainosus is also linked to high hospitalization and treatment costs,
reecting its severity and the complexity of its management. Studies estimate that
the average price of hospitalization for the treatment of status migrainosus can
range from US$3800 to US$7000 per episode, depending on the severity and treatments utilized [5].
]. Nonetheless, there is a notable lack of high-
2.8 Conclusion
Status migrainosus is a debilitating condition, the pathophysiology of which is not
yet fully understood. While several therapeutic options are available, there remains
a need for high-quality randomized clinical trials to determine the best management
strategies. Early treatment and personalized use of prophylactics appear to be key in
preventing the evolution to this complication, thereby reducing both morbidity and
the economic impact of the condition.
22
M. E. Jurno and L. B. de Oliveira
References
1. Olesen J.Headache classication committee of the international headache society (IHS) the
international classication of headache disorders. Cephalalgia. 2018;38(1):1–211.
2. Karlsson WK, Ostinelli EG, Zhuang ZA, Kokoti L, Christensen RH, Al-Khazali HM,
Deligianni CI, Tomlinson A, Ashina H, Ruiz de la Torre E, Diener HC, Cipriani A, Ashina
M.Comparative effects of drug interventions for the acute management of migraine episodes
in adults: systematic review and network meta-analysis. BMJ. 2024;386:e080107. https://doi.
org/10.1136/bmj- 2024- 080107.
3. Vander Pluym JH, Mangipudi K, Mbonde AA, Gritsch D, Caronna E, Halker Singh RB,
Buttereld RJ, Smith JH. Incidence of status migrainosus in Olmsted County, Minnesota,
United States: characterization and predictors of recurrence. Neurology. 2023;100(3):e255–63.
https://doi.org/10.1212/WNL.0000000000201382.
4. Kamourieh S, Rozen T, Anderson JM.Status migrainosus. Handb Clin Neurol. 2024;199:413–39.
5. Orr SL.Status migrainosus: one of the most poorly understood but important complications of
migraine. Neurology. 2023;100(3):107–8. https://doi.org/10.1212/WNL.0000000000201477.
6. Vécsei L, Szok D, Nyári A, Tajti J.Treating status migrainosus in the emergency setting: what
is the best strategy? Expert Opin Pharmacother. 2018;19(14):1523–31. https://doi.org/10.108
0/14656566.2018.1516205.
7. Robblee J, Orlova YY, Ahn AH, Ali AS, Birlea M, Charleston L 4th, Singh NN, Souza
MNP.Real-world approaches to outpatient treatment of status migrainosus: a survey study.
Headache. 2024;64(8):1040–8. https://doi.org/10.1111/head.14769.
Chapter 3
Migrainous Infarction
AlessandroBorrelli , FabianaUrsitti , andMassimilianoValeriani
3.1 Introduction
Migrainous infarction is an ischemic stroke that originates during a typical migraine
with aura attack. It initially presents with the usual features of previous episodes but
lasts longer (more than 60min), is often accompanied by new symptoms, and may
be associated with greater headache severity. It must be distinguished from ischemic strokes of other causes that mimic migraine symptoms, as well as from ischemic strokes occurring in patients with a concurrent diagnosis of migraine with aura
[1]. Thus, migrainous infarction represents a distinct clinical entity among the possible ischemic stroke manifestations in patients with migraine with aura. Based on
the few available studies, the prevalence of ischemic strokes is estimated to be
between 0.05% and 0.8%.
A. Borrelli · F. Ursitti
Developmental Neurology Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
M. Valeriani (
Developmental Neurology Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
Systems Medicine Department, Tor Vergata University of Rome, Rome, Italy
Translational Pain Neuroscience and Precision Medicine, CNAP, Department of Health
Science and Technology, School of Medicine, Aalborg University, Aalborg, Denmark
e-mail: valeriani@opbg.net; massimiliano.valeriani@opbg.net
Switzerland AG 2026
D. Uludüz et al. (eds.), Rare Causes of Headache Disorders, Headache,
https://doi.org/10.1007/978-3-032-10242-3_3
*)
23© The Author(s), under exclusive license to Springer Nature
24
A. Borrelli et al.
3.2 Pathophysiology
The relationship between migraine and stroke is complex. Migraine with aura is
recognized as an independent risk factor for ischemic stroke, while data regarding
migraine without aura are less indicative [2, 3]. Cortical spreading depolarization
(CSD) is an essential electrophysiological phenomenon underlying aura. Its relationship with ischemia is ambivalent: CSD increases metabolic demands while
reducing cerebral blood ow, potentially damaging metabolically compromised
brain tissue and leading to ischemia [4], but it can also be induced by ischemia itself
[5], thus worsening brain tissue damage and neurologic outcomes [4]. The complex
mechanisms underlying the association between migraine and ischemic stroke are
largely unidentied; however, endothelial dysfunction, hormones (especially estrogens), and genetic factors may play essential roles in this relationship, which is
beyond the scope of this chapter [3, 4].
Most reported cases in the literature do not indicate a precise underlying pathophysiological mechanism. While cases of migraine-related strokes with associated
vasospasm were described [6–9], adherence to the diagnostic criteria for a migrainous infarction could be found only in one patient [9]. Lebedeva etal. described signs
of multiple microemboli in the middle cerebral artery of a patient experiencing
migrainous infarction, though no clear embolic source was identied [10].
3.3 Case Presentation
Our exemplary patient is a 32-year-old non-smoking woman in good health. She
does not take any medications, except for an oral contraceptive pill containing drospirenone and ethinyl estradiol. The patient has been suffering from occasional
headache attacks since her adolescence. Her attacks are sometimes preceded by
visual symptoms such as fortication spectra or scintillating scotomas. Her headaches are typically unilateral, pulsatile, and associated with photophobia, occurring
approximately once per week. She usually takes naproxen, with good
effectiveness.
One evening, she experienced a right-sided scintillating scotoma, accompanied
by the occurrence, after 40min, of a bilateral parietal headache, associated with
nausea and photophobia. She was not particularly concerned by these symptoms, as
they resembled her usual migraine with aura episodes. Still, she noticed that the
visual symptoms progressively evolved into a negative scotoma, which persisted
throughout the headache. She went to bed expecting that these symptoms would
disappear during sleep. Upon waking the following morning, her right visual eld
defect had worsened, along with increased headache intensity, prompting her to
present to the emergency department. Clinical examination revealed a right homonymous hemianopia. Her blood pressure was normal. As her headache persisted,
she was administered intravenous ketorolac. After neurological consultation, the
3 Migrainous Infarction
patient underwent a contrast-enhanced brain CT (computed tomography) scan,
which revealed a hypodensity in the left occipital lobe. A migraine-related ischemic
stroke was suspected and secondary prevention with aspirin 100mg was started.
Later that day, brain MRI (magnetic resonance imaging) with angiography conrmed an infarction in the left occipital cortex and excluded major vascular disease.
Laboratory testing showed normal glucose, cholesterol, and triglyceride levels. A
complete hypercoagulation panel of laboratory tests was negative, including Protein
C, Protein S, prothrombin time (PT), activated partial thromboplastin time (aPTT),
antithrombin III, Factors II and VII, D-dimer, antiphospholipid, anticardiolipin, and
anti-β2-glycoprotein antibodies, lupus anticoagulant, MTHFR gene mutations, and
Factor V Leiden. Transesophageal echocardiography and Holter electrocardiography yielded unremarkable ndings. Oral contraception was discontinued. On follow- up, the patient gradually regained normal vision.
25
3.4 Case Discussion
This case illustrates the typical features of migrainous infarction. The patient had a
history of migraine with aura and use of oral contraception, with no additional
stroke risk factors identied. Her symptoms initially presented with the typical
characteristics of her migrainous attacks, but persisted throughout the headache
phase. She sought medical attention after several hours, reporting the development
of an atypical symptom (homonymous hemianopia) and aura persistence beyond
1h. Neuroimaging conrmed an infarction in the occipital cortex, a location consistent with the clinical presentation. Secondary prevention with aspirin was initiated.
3.5 Clinical Characteristics
Episodes begin with the typical symptoms of previous aura attacks, with additional
symptoms potentially arising due to the extension of brain involvement to other
areas. Although the denition of migrainous infarction requires one or more aura
symptoms to persist for more than 1h, many patients may seek medical attention
after hours or days. Additionally, patients may report increased headache severity or
experience unusually intense nausea, phonophobia, or photophobia [11] or resistance to the usual medications [6].
The infarction most commonly occurs in the territory supplied by the posterior
cerebral artery. Scotomas, positive visual symptoms, and sensory decits are common early manifestations, often progressing to homonymous hemianopia in many
patients. The majority of cases involve the posterior cerebral vascular territory, as
this was the case in 84% of patients in the most extensive case series [12], particu-
larly the vertebrobasilar system. Localization in the anterior and middle cerebrovascular systems is less common, causing different clinical manifestations [6, 10–15].
26
A. Borrelli et al.
Interestingly, a reduction in both the frequency and severity of headaches has
been reported in the months following migrainous infarction [16, 17]. This phenom-
enon may not be specic to migrainous infarction, as a reduction in headache frequency has also been observed in migraine patients with ischemic stroke, regardless
of etiology [18].
We reviewed the frequency of various traditional risk factors in cases of migrainous infarction (as outlined in the inclusion criteria). Most patients were female
(60%), and 31% of them used oral contraceptives. The age of patients reported in
the literature ranges from 18 to 93years, with a weighted median of 39years and an
interquartile range (IQR) of 22.5 (inclusive of extremes). Hyperlipidemia was present in 23%, a smoking habit in 24%, and hypertension in 12%. A patent foramen
ovale (PFO) was not consistently investigated across all articles; however, when
considering only patients who underwent an echocardiogram, it was present in
24%. Notably, two case series reported a high prevalence of PFO. Wolf et al.
reported that 64.7% of patients with migraine-related stroke had a PFO [19]. In
comparison, Laurell etal. reported a prevalence of 40% among the 30 patients with
migrainous infarction who underwent echocardiography [12]. PFO persistence into
adulthood is more common among patients with migraine with aura than in the
general population (Table3.1).
Traditional cardiovascular risk factors, such as diabetes, hypertension, and dyslipidemia, appear to play a less signicant role when compared with other types of
ischemic strokes. Case-series reports a low prevalence of these factors, while oral
contraceptives and smoking are both common. A retrospective study of 33
Scandinavian patients with migrainous infarction found a statistically signicant
lower frequency of current smoking, hypertension, hyperlipidemia, and diabetes
compared to a cohort of 1008 young Finnish patients with stroke of any cause [12].
Similarly, in a vast cohort of 17,633 young patients aged 18–50years with ischemic
stroke due to any cause, there were higher frequencies of hypertension (36.6%),
diabetes (13.8%), dyslipidemia (31.7%), and smoking (49.2%) [33].
Female sex and young age (<45years) are established risk factors for ischemic
stroke in migraine patients [34, 35], with the risk further increasing in combination
with oral contraceptive use and smoking [34].
The use of vasoactive medications, such as triptans and ergotamines, has been
proposed as a potential risk factor for migrainous infarction, and caution has been
advised regarding their use in patients with migraine with aura [4]. Despite their
widespread use, limited data exist concerning cardiovascular risk in the use of both
classes of drugs. A meta-analysis by Roberto etal., which synthesized data from
four studies, was unable to draw denitive conclusions due to variations in study
design and potential biases [36
]. More recently, an extensive retrospective casecrossover study identied an increased risk of myocardial and cerebral infarction
following triptan initiation [37]. However, this risk was exceptionally low in patients
without other cardiovascular risk factors (1) new case per 30,000 patients). Still,
other sources reported that a higher rate of major cardiovascular events was observed
with the use of triptans in patients with previous cardiovascular risk factors [38].
3 Migrainous Infarction
patients)
27
(continued)
patients who underwent
EC
3 2 Unclear number of
1 1 71
Total Male Female Age HT Smoking Diabetes OC Dyslipidemia PFO
Kandemir Yılmaz and Kirikli
Table 3.1 Risk factors reported in cases of migrainous infarction in the literature
2 1 1 54 and 53 2 1 1 EC NR
[20]
Lebedeva etal. [10] 1 1 18
Lebedeva etal. (2015) as
2 4 4 5
18–55
Khardenavis etal. [14] 1 1 27
Campagna etal. [24] 1 1 47 1 1 1 1
Serrano etal. [17] 15 7 8 34.8 median; range
Terrin etal. [22] 1 1 56
Vinciguerra etal. [9] 1 1 44
Bylund etal. [21] 1 1 49 1 1
reported in Lebedeva etal. [10]
Mancini etal. [15] 1 1 32 1
Morais etal. [23] 1 1 37 1
Renard etal. [25] 1 1 47 EC NR
4 7 1 6 10 12 (EC only in 30
Laurell etal. [12] 33 13 20 39 median; range
Wolf etal. [19] 11 NR NR NR 5 4 5 3 8
Lai and Hong [26] 1 1 60 1 1
19–76
Decima etal. [7] 1 1 41 1 1
range 23–40
Male: 36
Liang and Scott [28] 1 1 57
Tzoulis etal. [11] 1 1 93
Arai etal. [27] 1 1 64 1
Frigerio etal. [13] 6 1 5 Female: 29 median;
28
A. Borrelli et al.
b
23% 24%
a
1 2 1
16 24 3 22 23 21
Total Male Female Age HT Smoking Diabetes OC Dyslipidemia PFO
Tang etal. [29] 1 1 29
Table 3.1 (continued)
39–65
24–60
Linetsky etal. [16] 6 1 5 56 median; range
Arboix etal. [30] 9 3 6 32 median; range
Sacquegna etal. [31] 1 1 31 1
median; IQR 22.5
Prevalence / 37% 60% / 16% 24% 3% 31%
Total 100 34 55 39 weighted
Moen etal. [32] 1 1 37 1
Note: This list includes all articles stating adherence to ICHD-3 criteria and available in English language. We excluded works that clearly reported in the text
Percentage of patients who underwent an echocardiogram
Percentage of total female patients, with the exclusion of cases by Wolf etal. [19] who do not report the share of female patients
features not meeting ICHD-3 criteria (e.g., patients who did not experience migraine with aura attacks previously)
EC echocardiogram, HT hypertension, ICHD-3 International Classication of Headache Disorders-III, IQR interquartile range (including extremes), NR not
a
b
reported, OC oral contraception, PFO patent foramen ovale
3 Migrainous Infarction
29
Other conditions are associated with both migraine and stroke and could explain
some cases of migrainous infarction: atrial brillation, hereditary small vessel diseases, dissection of cervical artery, antiphospholipid syndrome [4].
Further research is needed to elucidate the role and prevalence of risk factors in
migrainous infarction, as well as the underlying pathophysiological mechanisms.
International Classication of Headache Disorders III (ICHD-3)
Criteria for Migrainous Infarction [1]
A.A migraine attack fullling criteria B and C
B.Occurring in a patient with 1.2 Migraine with aura and typical of previous
attacks except that one or more aura symptoms persist for >60min
1
C.Neuroimaging demonstrates ischemic infarction in a relevant area
D.Not better accounted for by another ICHD-3 diagnosis
Note: 1. There may be additional symptoms attributable to the infarction
3.6 Diagnostic Algorithm
A diagnosis of migrainous infarction primarily demands the clinical distinction
from transient ischemic attacks (TIAs) and uncomplicated attacks of migraine with
aura. After this distinction has been made, neuroimaging can conrm the presence
of ischemia and rule out vascular diseases. It is also recommended to rule out hypercoagulation disorders, cardioembolism, and rare genetic causes of stroke, like
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts
and Leukoencephalopathy) and MELAS (Mitochondrial Encephalopathy, Lactic
Acidosis, Stroke).
A distinction from a typical attack of migraine with aura is difcult. Migraine is
implicated in both false positives (“stroke mimics”) and false negatives (“stroke
chameleons”), with misdiagnoses being relatively common [3]. Clinical suspicion
of migrainous infarction should be guided by the long duration of aura symptoms,
especially if they persist after headache relief, and presence of unusual accompanying manifestations. Sometimes the attack is more severe than usual, leading patients
to seek medical attention. Hemiplegic migraine and migraine with unilateral motor
symptoms are two conditions that can be mistaken for migrainous infarction and
must be thoughtfully excluded.
TIA symptoms typically manifest suddenly and tend to appear simultaneously
from the onset, whereas aura symptoms usually develop more gradually and evolve
[39]. Patients with migrainous infarction initially present with their typical aura
symptoms, followed by the progressive emergence of additional symptoms depending on the extent of brain involvement. TIA symptoms are typically negative in
nature, whereas aura must include at least one positive manifestation [1].