Hemorrhagic stroke as a rare complication of a migraine without aura

Being one of the most spread neurological disorders, and one of the leading neurological disabling disease, migraine has been the matter of interest for researches for the last several decades. Migraine is known to have a female predominance with the twofold risk of a stroke among active migraine sufferers [1‐3]. The pathophysiology of the migraine is still disputable. Although, it is considered to involve the trigeminalvascular system, which comprises trigeminal nerve and its axonal projections to the intracranial vasculature [4]. The key factor for understanding the pathophysiological mechanism of a migraine and for the development of pathogenetic therapies was finding of signaling molecules, which take part in a migraine attack facilitation [5]. Nevertheless, there is no confident data upon the incidence rate of migraine associated with HS, there are still some studies resultant for revealing mechanisms possibly responsible for a HS as a complication of a migraine. Following this, new research is needed to look for more data upon shared mechanisms for migraine and HS, as well as risk factors and preventive treatment for migraine associated HS.

A 57-year-old White woman admitted to the hospital accompanied by her daughter complaining of the severe headache and behavioral changes during the last 4 days. The patient reports of suffering from severe MwtA for more than 20 years. She was diagnosed with an episodic migraine without aura according to the International Headache Society criteria, on the second year of the disease. The patient underwent a head MRI, but by the time of the present admission, she did not have the results. Usually, her migraine attacks are severe with vomiting, phonophobia and lasting period of maximum 72 h, MIDAS grade IV (47 score). She takes zolmitriptan 5 mg together with 2 ml of metoclopramide intramuscular injection to treat a migraine attack, which used to bring a relief. Four days before the admission she complained of having another migraine attack, followed by two time vomiting and phonophobia. The migraine attack onset was quite usual for her, without any preceding provocative factors or head trauma. The headache was described as a unilateral, left-sided, pulsating character, worsening with the physical activity and in the presence of loud sound and bright light, evaluated as 8 scores by VAS. She unsuccessfully tried to treat this attack using her regular medications. The relatives of the patient decided to refer her to the doctor 2 days after the headache onset, when they mentioned the signs of sensory aphasia and personality changes in terms of unusually prolonged headache attack. Upon the evaluation, the patient was hardly reachable for a verbal contact because of the severity of the headache, she was notable to have signs of sensory aphasia and phonophobia, the deep tendon reflexes were symmetrically exaggerated, there were no signs of paresis or other focal neurological deficit. The fundoscopy was not performed. General blood analysis was unremarkable HGB 135 g/l, RBC 4.28 × 10¹²/l, PLT 192 10³/μl, total leukocyte count of 6.7 × 10⁹/l, except for elevated ESR 38 mm/h. The patient underwent also biochemical analysis of the blood which did not reveal any abnormal values (glucose 7 mmol/l, total cholesterol level 225 mg/dl, AST 23 U/L, ALT 21 U/l, creatinine 0.62 mg/dl, total bilirubin 22 mcmol/l). She has no history of family cerebrovascular diseases, no history of any other comorbid diseases. The patient’s daughter denied any consumption of the psychotropic substances by her mother, taking any regular medication, as well as any other medication during the migraine attack, except for zolmitriptan and metoclopramide. A brain MRI scan, performed on Philips Achieva 3.0T, India, was significant for revealing intraparenchymal hemorrhage in the left temporal lobe, with perifocal edema and two subdural hematomas in frontal and temporal regions on the left (Fig. 1).

Computed tomography angiography (CTA), performed on Siemens, Somatom Sensation 16, did not reveal any aneurysmatic dilatations vascular malformations (Fig. 2).

The patient was suspicious for having either primary or secondary neoplastic lesion of the left temporal lobe with consequent hemorrhage in it. She was referred to the neurosurgeon, where she was prescribed to take dexamethasone 4 mg once per day and regular hemorrhagic stroke treatment until getting the control contrast enhancing MRI scan and spectroscopy. She was discharged without any clinical symptoms in 10 days. Control brain MRI scan (Philips Achieva 3.0T), which was performed in 2 weeks (Fig. 3) revealed decrease in size of the intraparenchymal hemorrhage, complete involution of the subdural hematomas. MR spectroscopy did not prove the diagnosis of a neoplasm.

Based on patient’s medical history, the results of clinical, laboratory and neuroimaging studies, the diagnosis of a complicated migraine was made. The patient was prescribed candesartan 4 mg/day with the weekly increase of dosage for 4 mg up to 16 mg/day, with both blood pressure control and migraine prophylaxis aim. On the follow-up visit in 3 weeks, the patient was without any signs of neurological deficit presence, the blood pressure controlled at the level of 110/70 mm/Hg. None of the adverse effects were present. The consent for participation and publication of the study was received from the patient. The study was approved by the local ethics committee.

Migraine is a neurological disorder which is characterized by the recurrent episodes of headache [6] moderate-to-severe, with unilateral predominance, photo- or phonophobia, nausea or vomiting, and exaggeration from physical activities. When there is any somatosensory symptom present before the migraine attack, this is called a migraine with aura (MwA) [7]. There is also a complicated and simple migraine. A migraine attack followed by a stroke received the name of complicated migraine. A number of researches on the connection of migraine and cerebrovascular disease and migraine and stroke, did not reveal consistent results [1, 3, 8‐10]. However, the next two cohort studies [11, 12] showed an association between MwA and HS, and one of them showed an association between MwtA and HS [11]. In the cohort prospective study of Kurth and colleagues, they found that women with active MwtA had no increased risk for a hemorrhagic stroke [12]. A big nationwide, population-based cohort study of a Danish group of investigators revealed an increased risk among the patients with migraine for any cerebrovascular pathology, including HS. And in contrast to the results of the previous study, it was stated that the women suffering from the MwtA have also higher risk for a HS [13]. Another study performed in Denmark among the migraineurs, showed a higher risk for cerebrovascular events among the migraineurs being treated with the triptans [14]. In one of the latter studies on the mechanisms and risk factors for association of a migraine and stroke by Hassan and colleagues they mentioned several shared mechanisms for strokes in migraineurs. The first one is based on the combination of decrease of progenitor endothelial cells quantity circulation together with vessel wall changes [15]. The second one is a hypertension, hyperlipidemia and platelet dysfunction [16]. The third one is based on the NSAIDs overuse during migraine attacks, which leads to antithrombotic effect [17].

However, our patient does not have any comorbid states, she does not take NSAIDs during her migraine attacks and moreover, she has a MwtA. Unfortunately, the patient did not undergo a head CT or fundoscopy, as well as genetic analysis for CADASIL or any other genetic cerebrovascular disease. However, the performed MRI and spectroscopy were helpful in excluding the differential diagnosis of neoplasm or secondary lesion. One of the most well known risk factors for HS is hypertension [18‐20]. And although, our patient was not suffering from hypertension, migraine attacks are known to be followed by an increased blood pressure [21], which by itself or in the combination with other risk factors, such as a triptan intake, could lead to a HS in this case. Since the patient does not have vascular malformation, and the intraparenchymal hemorrhage size greatly decreased on the control brain MRI, as well as the absence of neurological symptoms, no surgical treatment is needed. The patient is supposed to continue taking migraine prophylactic treatment to control the blood pressure and migraine attacks. She expects no further complications of this event, as well as recurrent HS.

Our case is important for indicating the possibility of connection between MwtA and HS, which could play an important role in prevention of such a complication of the migraine as a HS. However, the relatively low number of migraine-related HS and attributable risk should caution against definitive conclusions and requires further confirmation of these observations. It also underlines the importance of knowing of the possibility of occurrence of HS in patients suffering from MWtA.