Article / Clinical Case Report
Migrainous infarction: a rare and often overlooked diagnosis
Migrainous infarction: a rare and often overlooked diagnosis
Autopsy and Case Reports, vol. 7, no. 2, pp. 61-68, 2017
Hospital Universitário da Universidade de São Paulo
Received: 08 March 2017
Accepted: 01 June 2017
ABSTRACT: Migraine is a neurological entity and a well-known independent risk factor for cerebral infarction, which mostly afflicts the young female population. Researching focal neurological signs in this subset of the population with the diagnosis of a neurological ischemic event should always take into account the migraine as the etiology or as an associated factor. The etiology of central nervous system (CNS) ischemia is considerable. Migraine, although rare, also may be included in this vast etiological range, which is called migrainous infarction. In this setting, the diagnostic criteria required for this diagnosis is extensive. Herein, we present the case of a female adolescent who submitted to the emergency facility complaining of diplopia, dysarthria, and imbalance, which started concomitantly with a migrainous crisis with aura—a challenging clinical case that required extensive research to address all possible differential diagnoses.
Keywords: Migraine Disorders, Stroke, Internuclear Ophthalmoplegia.
CASE REPORT
A 16-year-old female patient was admitted to the emergency unit complaining of a pulsatile, frontal headache over the last 12 hours accompanied by nausea with photo- and phonophobia. The symptoms evolved with diplopia, difficulty in performing adduction of the right eye, and dysarthria; imbalance started subtly about 1 hour after the onset of pain. The patient reported that at the beginning of the symptoms she presented partial loss of vision on the lateral field of the right eye, scotomas, and blurry vision, which lasted about 30 minutes, with spontaneous resolution. She denied fever or any other neurological complaint, or the use of oral contraceptives. She took dipyrone before going to the emergency department. Her medical history included the diagnosis of migraine that started with the menarche at the age of 10 years, when she began presenting premenstrual migraine of variable intensity with visual aura, with predominant laterality also variable. The previous aura was characterized from scotomas, blurred vision, tunnel vision, and partial loss of vision, which was always reversible, with a maximum duration of 60 minutes. The patient did not remember having presented symptoms like diplopia or ataxia during previous events.
The physical examination revealed tachycardia, blood pressure of 150/80 mmHg, and a normal temperature. The neurologic examination revealed a wakeful, vigilant, and cooperative patient. Visual acuity was normal and without alterations on the field of vision; her pupils were isochoric and the direct response, the consensual response, and the accommodation of the pupils were normal. Paresis of the right eye when looking to the left was present (Figure 1), as well as diplopia, and a slow saccadic movement of the left eye in abduction, with horizontal nystagmus with the preservation of ocular convergence. Other cranial nerves presented normal function. Strength, sensitivity, and deep reflexes were preserved and symmetric. At the examination of station when the patient’s feet were close together, she swayed backward, which was slightly worsened when she closed her eyes. Her gait was ataxic and she had a fall tendency to the left. Diadochokinesis, appendicular movement speed, and the finger-to-nose test were normal, but the heel-shin test was dysmetric at the left side. Other systems showed no abnormalities.
Figure 1
Paresis of the right eye when looking to the left.
No improvement in the neurologic examination was noted after the patient was medicated with metoclopramide, ketoprofen, and dexamethasone; however, the pain and nausea did cease. The patient was hospitalized and submitted to a thorough etiological investigation.
The cerebral computed tomography (CT) and the angiotomography were normal. On the second day of hospitalization, a partial improvement of the symptoms was noted, but the diplopia remained steady. The cerebral magnetic resonance imaging (MRI) showed a focus of diffusional restriction in the paramedian right dorsal portion of the midbrain, which was consistent with the topography of the ipsilateral medial longitudinal fasciculus, without significant expansive effect, exhibiting hyperintense focus in T2 and fluid-attenuated inversion recovery (FLAIR), which did not show impregnation by the contrast medium (Figure 2). The cerebral (Figure 3) and cervical MRI angiography and the cerebrospinal fluid analysis with protein electrophoresis were normal. The electrocardiogram (ECG), echocardiogram, and Holter ECG were normal. Biochemical analysis and thyroid function tests were normal. Antinuclear antibodies (ANA) was positive 1/640 exhibiting a fine nuclear dot pattern. However, antibodies anti-SS-B/LA, anti-SS-A/Ro, anti-SM, anti-double strain DNA, anti-neutrophil cytoplasmic antibody, and lupus anticoagulant tests were negative. Complement fractions C3 and C4 were normal. Anti-HIV, HBsAg, and anti-hepatitis C virus were negative. Acute phase proteins, serum lactate, and muscle enzymes were normal. The serum dosage of protein C, homocysteine, and antithrombin III tests were normal. The search for factor V Leiden was negative.
Figure 2
Brain MRI - Axial T2-weighted (A) and FLAIR (B) showing hyperintensity focus in the right periaqueductal region of the midbrain (black arrow). Axial ADC map (C) and DWI (D) show ischemic insult characterized by the restriction of free water molecules in the same region of the midbrain (black arrow). ADC = apparent diffusion coefficient; DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery sequence; MRI = magnetic resonance imaging.
Figure 3
Cerebral magnetic resonance angiography (3D reconstructions). Oblique axial (A) and oblique coronal (B) images show normal intracranial arteries.
Thus, the clinical features, the imaging examinations, and the thorough investigation were consistent with the diagnosis of cerebral infarction without any risk factor other than migraine. The patient was prescribed salicylates and propranolol with gradual improvement. She was referred to an outpatient clinic for follow-up.
DISCUSSION
The interpretation of the physical examination, the laboratory testing, and the imaging, renders the conclusion of an internuclear ophthalmoparesis (INO) of ischemic origin.
INO is a syndrome derived from the medial longitudinal fasciculus (MLF) injury. The MLF is a set of myelinated fibers that extends along the entire brainstem and the spinal cord.1,2 These fibers present a varied origin and destiny in their paths and stand as an integration tool. In the pons and the midbrain, the MLF stays close to the midline, ventrally to the fourth ventricle and the cerebral aqueduct. The center of the conjugate gaze lies between the dorsal pons and the mesencephalic tegmentum where the MLF harbors the internuclear fibers of the sixth and third cranial nerves.3 Diplopia is an important symptom of INO, but in mild lesions it may present as a visual blur, which is unleashed when the conjugate gaze is directed towards the opposite side of the injured eye, or during the adduction of the affected eye.3
The most frequent causes of INO are cerebrovascular diseases in elderly patients, and demyelinating diseases, which mostly afflict the younger female patients.3-5
The other clinical features of our patient, which are consistent with INO and lead to anatomic localization are: (i) normal eye convergence (since the fibers responsible for the convergence are cranially located in the midbrain); (ii) nystagmus in adduction of the non-paretic eye;6 and (iii) sensitive and/or motor dysmetria on the left inferior limb.3
As shown in the MRI (Figure 2), the ischemia is located in the highly concentrated area of motor-related pathways, such as the rubrospinal tract, the medial lemniscus, and the pontocerebellar and tectospinal fibers of head adjustment to cocleo-vestibular stimuli. Therefore, motor and sensitive ataxia may be present if the area of ischemia is large enough.1
The cause of cerebral ischemia in children and young adults substantially differs from that of the adult/elderly population.7 Acute ischemic stroke accounts for approximately 50% of all strokes in children.8 The incidence among children is low and varies according to race (2.6/100,000 white children and 3.1/100,000 black children).9
There are many differential diagnoses that can cause focal neurologic symptoms in children and young adults, as shown in Table 1
MELAS = mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like symptoms.
The etiology also varies according to gender, age, and geographic localization.9 The main causes of ischemic stroke in this subset of the population are represented by congenital cardiac diseases and sickle cell anemia.17 However, up to 50% of pediatric patients do not present any etiological evidence.18 The main risk factors found in patients with stroke in the child population are presented in Table 2. The prevalence of risk factors differ in the literature.7,10
PHACES = malformations of the posterior fossa, facial hemangioma, arterial cerebrovascular anomalies, cardiovascular anomalies, abnormalities of the eye and sternum.
The management of stroke in children and young adults can be divided into initial and general supportive measures, diagnostic modalities, and appropriate treatment to the type of stroke identified, if possible.10
General supportive measures include maintaining normal oxygenation, treating dehydration, correcting anemia, controlling systemic hypertension with mild permissive high levels, normalizing serum glucose, and controlling fever.10
An imaging test must be done to exclude a hemorrhagic cause of stroke after the initial supportive measures. The non-contrast CT has great sensitivity to exclude any acute bleeding, and MRI can be useful for the early detection of an infarction. MR arteriography, CT angiography, or catheter angiography are used to study the vascular anatomy and to confirm vessel patency.10 Other investigations that may be useful are an ECG, a chest radiograph, and transthoracic or transesophageal echocardiography.10
There are no guidelines that establish the laboratory tests that should be assessed in the children and young adult population,10 but it makes sense for the tests to include those that can help the differential diagnosis (Table 1) and to find the possible risk factors (Table 2).
In our case, a thorough diagnostic work-up focused on the risk factors that were potentially associated with cerebral ischemic events, and migraine was the unique detected risk factor. The presence of the positive ANA in the absence of detectable autoantibodies and normal complement was interpreted as with feeble correlation with any autoimmunity disorder; therefore the positive ANA could be explained by the acute event.19
Migraine is a chronic neurovascular entity, which is present in 11% of the general population (men and women) of all ages. In the female population of all ages, migraine is present in 17%; however, this increases to 23.5% between the ages of 18 and 44 years old.20,21
Migraine is an independent risk factor for cardiovascular diseases. Patients with the diagnosis of migraine have a 1.5 times greater risk of developing acute myocardial infarction, angina, and stroke,22 which increases mortality by cardiovascular diseases by 1.37 times.23 The main risk is related to cerebral ischemia.24,25
The diagnostic work-up of a focal deficit in a young woman should always consider the migraine as a potential risk factor or the etiology of the ischemic event, since in this subset of the population the etiology of stroke is determined in only 40% of cases.26
A stroke in a person with migraine should be differentiated into: (i) the cerebral infarction of other cause in a person that has migraine (cerebral ischemia associated with migraine); (ii) the cerebral infarction of other cause presenting with symptoms resembling migraine with aura; and (iii) the migrainous infarction. They present diverse physiopathological mechanisms, and the therapeutic approach should be different.27
Cerebral ischemia associated with migraine represents every cerebral ischemic event in patients diagnosed with migraine. The patient who has a stroke during a migraine crisis with neurological focal signs that are different from the previous aura could be diagnosed with a cerebral infarction of other cause presenting with symptoms resembling migraine with aura.27
Migraine is a risk factor associated with cerebral ischemia mainly in women under the age of 45 years who use an oral contraceptive and smoke tobacco (independent risk factors). Migraine with aura presents the relative risk of 2.16 (confidence interval 95%, 1.53-3.03), although there are controversies in the literature.24,28,29 The presence of migraine in children with ischemic stroke in the study of Mackay et al.9 was 3%. The frequency of migraine attacks also affects the risk of ischemic stroke; that is, the greater the number of attacks, the greater the risk.
In addition to being the cause of a stroke, migraine enhances the risk of CNS ischemia by different mechanisms. There are many hypotheses to explain the association of migraine and stroke, which include (i) the adverse effect of migraine-specific medication;30 (ii) genetic associations that cause a predisposition to the hyperactivity of vessels; (iii) endothelial dysfunction that causes a predisposition to atheromatous plaque formation and its instability associated with procoagulant, proliferative, and proinflammatory states; and (iv) the prevalence of some conditions, such as arterial dissection; the presence of a patent foramen ovale; and clotting disorders, such as thrombophilia.31 Migraine also increases the risk of hemorrhagic stroke by still unknown causes.32
According to the third edition (2013) of the International Classification of Headache Disorders,27 migrainous infarction is defined as: “One or more migraine aura symptoms associated with an ischaemic brain lesion in the appropriate territory demonstrated by neuroimaging” (p. 651). Also, as diagnostic criteria, the aura must be typical of previous attacks, the focal deficit must remain longer than 60 minutes and it must be associated with the pain crisis, which fulfils the criteria of a migraine attack not explained by any other cause. The incidence of migrainous infarction is low, accounting for 0.2-0.5% of all cerebral ischemic causes.33,34 The physiopathology is still uncertain; however, the main hypothesis relates to an imbalance in the vessels’ control with severe vasoconstriction followed by downstream ischemia.30 The territory of the posterior circulation is mostly involved (70-82%). Young women are more affected, probably with a bias of selection, since the migraine with aura by itself is more frequent in this population.31 The imaging examinations more often reveal single or multiple small lesions limited to an unique vascular territory.35 The prognosis is generally favorable with complete recovery of the neurological deficits.36 Our patient could not meet the criteria for migrainous infarction, because the presented symptoms were not part of the crises previously presented.
The management of migraine in patients with ischemic stroke involves the avoidance of some drugs that can induce migraine in those patients, such as cilostazol37 and dipyridamole,38 and prescribing a treatment for preventing migraine.30 A beta-adrenergic blocker and a calcium channel blocker are well established for this propose.39,40 Statins, angiotensin receptor blockers, and angiotensin-converting-enzyme inhibitors have been reported as effective for migraine prophylaxis.41-43
The pharmacological prevention of stroke in migraineurs is not well established.30 It is important to eliminate modifiable risk factors, such as smoking and the use of oral contraceptives. Antihypertensives and statins must be used according to the indications. There are no recommendations for the use of antithrombotics to reduce the risk of stroke in this population.30
By definition and by exclusion, after extensive diagnostic investigation, we arrived at the diagnosis of cerebral infarction of other cause presenting with symptoms resembling migraine with aura, since the patient presented a typical episode of migraine with visual aura, and developed focal neurological signs that were different from those presented in previous auras, which made it impossible to fulfill all the criteria for migrainous infarction, excluding the main causes investigated for a cerebral infarction.
CONCLUSION
The case presented herein illustrates the case of a midbrain ischemic stroke in a young female, which was confirmed by the medical history, the neurological examination, the imaging examinations, and the extensive work-up, which ruled out a wide range of other possible etiologies. Although migrainous infarction is not common in medical practice, it is important to be reminded of its etiological role in young patients with headache and a lasting focal deficit.
Patients with migraine should be advised to prevent the modifiable risks factors, such as tobacco smoking, oral contraceptive use, obesity, a sedentary lifestyle, and treat—when indicated—the chronic migraine and other comorbidities, such as diabetes, hypertension, and dyslipidemia, to decrease the likelihood of ischemic episodes.
ACKNOWLEDGMENTS
The authors are thankful to Dr. Fernando Peixoto Ferraz de Campos for all the support and encouragement.
REFERENCES
1 Haines DE. Neuroanatomy: an atlas of structures, sections, and systems. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2011.
2 Campbell WW. DeJong’s the neurologic examination. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2013.
3 Ropper AH, Samuels MA, Klein JP, editors. Adams and Victor’s principles of neurology. 10th ed. New York: McGraw-Hill Education; 2014.
4 Keane JR. Internuclear ophthalmoplegia: unusual causes in 114 of 410 patients. Arch Neurol. 2005;62(5):714-7. 15883257 http://dx.doi.org/10.1001/archneur.62.5.714
5 Kim JS. Internuclear ophthalmoplegia as an isolated or predominant symptom of brainstem infarction. Neurology. 2004;62(9):1491-6. 15136670 http://dx.doi.org/10.1212/01.WNL.0000123093.37069.6D
6 Zee DS, Hain TC, Carl JR. Abduction nystagmus in internuclear ophthalmoplegia. Ann Neurol. 1987;21(4):383-8. 3579224 http://dx.doi.org/10.1002/ana.410210411
7 Williams LS, Garg BP, Cohen M, Fleck JD, Biller J. Subtypes of ischemic stroke in children and young adults. Neurology. 1997;49(6):1541-5. 9409343 http://dx.doi.org/10.1212/WNL.49.6.1541
8 Carvalho KS, Garg BP. Arterial strokes in children. Neurol Clin. 2002;20(4):1079-100, vii. 12616682 http://dx.doi.org/10.1016/S0733-8619(02)00012-9.
9 Mackay MT, Wiznitzer M, Benedict SL, Lee KJ, Deveber GA, Ganesan V. Arterial ischemic stroke risk factors: The international pediatric stroke study. Ann Neurol. 2011;69(1):130-40. 21280083 http://dx.doi.org/10.1002/ana.22224
10 Tsze DS, Valente JH. Pediatric stroke: a review. Emerg Med Int. 2011;2011:1-10. 22254140. http://dx.doi.org/10.1155/2011/734506
11 Kirkham FJ. Stroke in childhood. Arch Dis Child. 1999;81(1):85-9. 10373145 http://dx.doi.org/10.1136/adc.81.1.85
12 Eeg-Olofsson O, Ringheim Y. Stroke in children: clinical characteristics and prognosis. Acta Paediatr Scand. 1983;72(3):391-5. 6880725 http://dx.doi.org/10.1111/j.1651-2227.1983.tb09734.x.
13 Riela AR, Roach ES. Etiology of stroke in children. J Child Neurol. 1993;8(3):201-20. 8409261 http://dx.doi.org/10.1177/088307389300800302
14 Gold AP, Carter S. Acute hemiplegia of infancy and childhood. Pediatr Clin North Am. 1976;23(3):413-33. 958742 http://dx.doi.org/10.1016/S0031-3955(16)33313-2.
15 Sem S, Oppenheimer S. Bedside assessment of stroke and stroke mimics. Ann Indian Acad Neurol. 2008;11(5):S4-11.
16 Pavlakis SG, Kingsley PB, Bialer MG. Stroke in children: genetic and metabolic issues. J Child Neurol. 2000;15(5):308-15. 10830197 http://dx.doi.org/10.1177/088307380001500507
17 Roach ES, Riela AR. Pediatric cerebrovascular disorders. 2nd ed. New York: Futura; 1995.
18 Kirkham FJ. Stroke in childhood. Arch Dis Child. 1999;81(1):85-9. 10373145 http://dx.doi.org/10.1136/adc.81.1.85
19 Dellavance A, Gabriel A Jr, Cintra AFU, et al. II Brazilian Consensus on Antinuclear Antibodies in Hep-2 Cells Definitions for standardization of autoantibody testing against the nucleus (ANA Hep-2), nucleolus, cytoplasm and mitotic apparatus, as well as its clinical associations. Rev Bras Reumatol. 2003;43(3):129-40. http://dx.doi.org/10.1590/S0482-50042003000300002
20 Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343-9. 17261680 http://dx.doi.org/10.1212/01.wnl.0000252808.97649.21
21 Burch RC, Loder S, Loder E, Smitherman TA. The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies. Headache. 2015;55(1):21-34. 25600719 http://dx.doi.org/10.1111/head.12482
22 Rambarat CA, Elgendy IY, Johnson BD, et al. Migraine headache and long-term cardiovascular outcomes: an extended follow-up of the Women’s Ischemia Syndrome Evaluation. Am J Med. 2017;130(6):738-43. 28109970 http://dx.doi.org/10.1016/j.amjmed.2016.12.028
23 Kurth T, Winter AC, Eliassen AH, et al. Migraine and risk of cardiovascular disease in women: prospective cohort study. BMJ. 2016;353:i2610. 27247281 http://dx.doi.org/10.1136/bmj.i2610
24 Spector JT, Kahn SR, Jones MR, Jayakumar M, Dalal D, Nazarian S. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123(7):612-24. 20493462 http://dx.doi.org/10.1016/j.amjmed.2009.12.021
25 Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339(oct27 1):b3914. 19861375 http://dx.doi.org/10.1136/bmj.b3914
26 Abanoz Y, Gülen Abanoz Y, Gündüz A, et al. Migraine as a risk factor for young patients with ischemic stroke: a case-control study. Neurol Sci. 2017;38(4):611-7. 28083761 http://dx.doi.org/10.1007/s10072-017-2810-3
27 Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629-808. 23771276 http://dx.doi.org/10.1177/0333102413485658
28 Stang PE, Carson AP, Rose KM, et al. Headache, cerebrovascular symptoms, and stroke: the atherosclerosis risk in communities study. Neurology. 2005;64(9):1573-7. 15883318 http://dx.doi.org/10.1212/01.WNL.0000158326.31368.04
29 Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ. 2005;330(7482):63. 15596418 http://dx.doi.org/10.1136/bmj.38302.504063.8F
30 Lee MJ, Lee C, Chung C-S. The migraine-stroke connection. JoS. 2016;18(2):146-56. http://dx.doi.org/10.5853/jos.2015.01683. PMid:27283278
31 Spalice A, Del Balzo F, Papetti L, et al. Stroke and migraine is there a possible comorbidity? Ital J Pediatr. 2016;42(1):41. 27113086 http://dx.doi.org/10.1186/s13052-016-0253-8
32 Sacco S, Ornello R, Ripa P, Pistoia F, Carolei A. Migraine and hemorrhagic stroke: a meta-analysis. Stroke. 2013;44(11):3032-8. 24085027 http://dx.doi.org/10.1161/STROKEAHA.113.002465
33 Sochurkova D, Moreau T, Lemesle M, Menassa M, Giroud M, Dumas R. Migraine history and migraine-induced stroke in the Dijon stroke registry. Neuroepidemiology. 1999;18(2):85-91. 10023131 http://dx.doi.org/10.1159/000069411
34 Arboix A, Massons J, Garcia-Eroles L, Oliveres M, Balcells M, Targa C. Migrainous cerebral infarction in the Sagrat Cor Hospital of Barcelona stroke registry. Cephalalgia. 2003;23(5):389-94. 12780770 http://dx.doi.org/10.1046/j.1468-2982.2003.00534.x.
35 Wolf ME, Szabo K, Griebe M, et al. Clinical and MRI characteristics of acute migrainous infarction. Neurology. 2011;76(22):1911-7. 21624990 http://dx.doi.org/10.1212/WNL.0b013e31821d74d5
36 Laurell K, Artto V, Bendtsen L, et al. Migrainous infarction: a Nordic multicenter study. Eur J Neurol. 2011;18(10):1220-6. 21414105 http://dx.doi.org/10.1111/j.1468-1331.2011.03364.x.
37 Guo S, Olesen J, Ashina M. Phosphodiesterase 3 inhibitor cilostazol induces migraine-like attacks via cyclic AMP increase. Brain. 2014;137(Pt 11):2951-9. 25161294 http://dx.doi.org/10.1093/brain/awu244
38 Kruuse C, Lassen LH, Iversen HK, Oestergaard S, Olesen J. Dipyridamole may induce migraine in patients with migraine without aura. Cephalalgia. 2006;26(8):925-33. 16886928 http://dx.doi.org/10.1111/j.1468-2982.2006.01137.x.
39 Evers S, Afra J, Frese A, et al. EFNS guideline on the drug treatment of migraine: revised report of an EFNS task force. Eur J Neurol. 2009;16(9):968-81. 19708964 http://dx.doi.org/10.1111/j.1468-1331.2009.02748.x.
40 Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17):1337-45. 22529202 http://dx.doi.org/10.1212/WNL.0b013e3182535d20
41 Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003;289(1):65-9. 12503978 http://dx.doi.org/10.1001/jama.289.1.65
42 Schrader H, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with angiotensin converting enzyme inhibitor (lisinopril): randomised, placebo controlled, crossover study. BMJ. 2001;322(7277):19-22. 11141144 http://dx.doi.org/10.1136/bmj.322.7277.19
43 Liberopoulos EN, Mikhailidis DP. Could statins be useful in the treatment of patients with migraine? Headache. 2006;46(4):672-5. 16643563 http://dx.doi.org/10.1111/j.1526-4610.2006.00293.x.
Notes
Author notes
Correspondence Gabriel Afonso Dutra Kreling Hospital Universitário - Universidade de São Paulo (USP) Av. Professor Lineu Prestes, 2565 - Butantã - São Paulo/SP - Brazil CEP: 05508-000 Phone: +55 (43) 99956-2405 / +55 (11) 95236-0715 gabriel_dutra_@hotmail.com
Conflict of interest declaration