The Efficacy of Percutaneous Patent Foramen Ovale Closure on Migraine: a Meta-Analysis of Randomized Controlled Trials and Observational Studies.

OBJECTIVES: Whether patent foramen ovale (PFO) closure is effective on migraine is controversial. This article was aimed at assessing the efficacy of PFO closure on migraine based on randomized controlled trials (RCTs) and observational studies. METHODS: We searched PubMed, Embase, and Cochrane databases up to October 2020 evaluating PFO closure versus control in patients with migraine, then conducted a meta-analysis of all RCTs and observational studies, respectively. The main outcomes were (1) respond rate: complete cessation of migraine; (2) reduction in the frequency of migraine attacks per month; and (3) reduction in migraine days per month. RESULTS: Seven studies (3 RCTs and 4 observational studies), containing 887 migraine patients, were identified. (1) The respond rate of PFO closure on migraine was significantly higher than control group both in RCT subgroup and observational studies subgroup (OR 3.86, 95% CI 1.35-11.04, P = 0.01 in RCTs; OR 8.28, 95% CI 2.31-29.67, P = 0.001 in observational studies). (2) Reduction in frequency of migraine attacks was higher in PFO closure group compared with control group in the RCT subgroup analysis (mean difference (MD) = 0.57, 95% CI 0.23-0.90, P = 0.0009). (3) Reduction in migraine days was also higher in PFO closure group compared with control group in the RCT subgroup analysis (MD = 1.33, 95% CI 0.35-2.31, P = 0.008). CONCLUSIONS: PFO closure might be suitable for migraine patients, especially for migraine with aura, by cessation of migraine headaches or reducing migraine attacks and migraine days.

Impact of right-to-left shunt and transcatheter closure on the clinical features of migraine.

Objectives: In this study, we aimed to explore the influence of right-to-left shunt (RLS) presence on the clinical features of migraine and to follow-up on the post-operative curative effect of transcatheter patent foramen ovale (PFO) closure on migraine features.Methods: A total of 103 migraine patients were divided into a mild volume RLS group, moderate volume RLS group, large volume RLS group and non-RLS group in accordance with contrast enhancement transcranial Doppler (c-TCD) findings. The Visual Analogue Scale (VAS) score, migraine frequency, migraine duration, migraine disability assessment (MIDAS) and headache impact test-6 (HIT-6) scores were compared amongst the different groups. A total of 39 patients with moderate or large RLS received transcatheter PFO closure and those patients were followed up by the same criteria.Results: The attack frequency, HIT-6 and MIDAS scores amongst the migraine patients with moderate or large RLS were significantly higher than those in patients from the mild RLS group and non-RLS group (p < .05). The transcatheter closure was successful in all patients (n = 39), and no post-operative complications were observed during the hospitalisation and follow-up period. The differences in VAS, HIT-6 and MIDAS scores as well as the headache duration were statistically significant amongst patients before and after PFO closure (p < .05).Conclusions: Moderate to large RLS significantly influenced the clinical features of migraine, and transcatheter PFO closure could significantly relieve headache symptoms in migraine patients with PFO.

Contrast-enhanced transthoracic echocardiography applied in evaluation of pulmonary right-to-left shunt: A preliminary study.

OBJECTIVE: To investigate the detection rate of patent foramen ovale-right to left shunt (PFO-RLS) and/or pulmonary-right to left shunt (P-RLS) via contrast-enhanced transthoracic echocardiography (c-TTE) in healthy participants, patients suffering from cryptogenic stroke and migraine with aura. METHODS: Initially, 20 healthy volunteers, 21 cases with cryptogenic stroke, and 18 cases with migraine aura were randomly selected, and all of them received c-TTE and transesophageal echocardiography (TEE) examinations. First of all, 0.9% sodium chloride solution was rapidly injected into upper extremiry vein, when these volunteers and patients were at rest or following a Valsalva maneuver with 40 mm Hg pressure exerted against a manometer. Secondly, c-TTE detection was carried out in order to distinguish PFO-RLS and P-RLS and make semi-quantitative classification of RLS from many different sources, according to the occurrence and duration time of microvesicles in left atrial after the developing of left atrium. In terms of c-TTE analyses, RLS could be diagnosed when micro bubbles were visualized in transition from the right atrium to the left atrium. Particularly, a small amounts of RLS was 1 level, indicating 1-10 microvesicles per frame could be seen in left atrium, moderate amounts of RLS was 2 level, indicating 11-30 microvesicles per frame could be seen in left atrium, and a large amounts of RLS was 3 level, indicating more than 30 microvesicles per frame, or the left atrium is filled with micro vesicles. RESULTS: A total of 20 healthy adult volunteers were identified into this research. RLS was detected in 7 cases, according to c-TTE method (7/20, 35%). In detail, 3 participants suffered from PFO-RLS and P-RSL (3/20, 15%) simultaneously, 5 cases suffered from PFO-RLS (5/20, 25%), and 5 cases suffered from P-RLS (5/20, 25%). Among 21 patients with cryptogenic stroke, RLS was detected in 14 cases, according to cTTE method (14/20, 67%), and then compared with healthy participants group, the difference between them was significant (χ2 = 4.11, P = 0.04). Specifically, 2 participants suffered from PFO-RLS and P-RSL (2/21, 9.5%), 11 cases suffered from PFO-RLS (11/21, 52.4%), and 5 cases suffered from P-RLS (5/21, 23.8%). Among 21 patients suffering from migraine with aura, RLS was detected in 13 cases, according to c-TTE method (13/18, 72%), and then compared with healthy participants group, the difference of detection rate between them was significant (χ2 = 5.2, P = 0.02). In detail, 3 participants suffered from PFO-RLS and P-RSL (3/18, 16.7%), 8 cases suffered from PFO-RLS (8/18, 44.4%), and 8 cases suffered from P-RLS (8/18, 44.4%). In addition, the grading of PFO-RLS in patients suffering from cryptogenic stroke and migraine with aura was mostly grade 2-grade 3. On the contrary, the grading of PFO-RLS in healthy adult volunteers was mostly grade 1-2. Besides, the semi-quantitative grading of P-RLS in each group was mostly grade 1 to grade 2, and difference between healthy volunteer group and cryptogenic stroke group was significant (Z = -2.77, P = 0.006). CONCLUSION: P-RLS with lower semiquantitative grade is common in healthy individuals, patients with cryptogenic stroke and migraine aura. And P-RLS can be considered as a significant influencing factor in the pathogenesis of migraine with aura.

Migraine with aura and persistent foramen ovale.

The association between migraine with aura and persistent foramen ovale (PFO), as well as other right-to-left shunts, is described. A hypothesis that might explain this association is discussed. Observational studies suggested that when a PFO is closed patients who have migraine with aura are usually improved. The Migraine Intervention with STARFlex Technology (MIST) Trial was a randomised double-blind trial in patients with severe intractable migraine with aura and a moderate-large PFO that compared implantation of STARFlex devices with the intention of closing their PFO versus a sham procedure. It was hoped that the trial would demonstrate whether PFO closure would cure migraine. A series of problems in design and execution of the trial are discussed.

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

Among patients with migrainous infarction, the long-term prognosis is unclear. This study aims to estimate the long-term risk of stroke recurrence and functional outcome in patients with migrainous infarction. In our study, 15 patients with migrainous infarction were followed for up to 7.5 years (12-240 months). For each patient, clinical and imaging data were reviewed. Disability after migrainous Infarction was assessed with modified Rankin Score. Mean age was 34.8 (±â€¯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 frequency 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 frequency, low recurrence rate, and good functional outcome for patients with migrainous infarction.

Greater Occipital Nerve Blockade: A Safe and Effective Option for the Acute Treatment of Hemiplegic Aura.

BACKGROUND: Prolonged auras such as those of hemiplegic migraine or migraine with brainstem aura may be extremely disabling. The availability of effective treatments is limited, but two case reports described cessation of the aura symptoms after a greater occipital nerve (GON) blockade. CASE: A 26-year-old woman with a history of hemiplegic migraine with prolonged auras came to our office with an episode of motor and sensory aura 1 hour after onset. Both muscle strength and sensory function started to improve immediately after a GON anesthetic blockade, and the patient was fully relieved in 50 minutes. CONCLUSION: GON blockade may be an effective option for the acute treatment of hemiplegic aura or other prolonged migraine auras.

Primary intracranial angiomatoid fibrous histiocytoma presenting with anaemia and migraine-like headaches and aura as early clinical features.

A 17-year-old female with migraine with aura complained of fatigue and was diagnosed with anemia. Three years later, changes in her headache pattern prompted hospital referral. Brain MRI showed a bi-lobed extra-axial intracerebral tumor encroaching both parieto-occipital regions. The resection specimen yielded a rare diagnosis of primary intracranial angiomatoid fibrous histiocytoma (AFH). Tumor removal resulted in cessation of her migraine and anemia. AFH may cause systemic symptoms--in this case fatigue and anemia--long before focal neurological symptoms are present. This is the first report of an intracranial AFH presenting as migraine with visual aura and anemia.

Arterial surgery for sporadic hemiplegic migraine: preliminary results.

My aim was to report for the first time (to my knowledge) the successful treatment of 3 patients with sporadic hemiplegic migraine by surgical cautery of terminal branches of the external carotid artery under conscious sedation. Since the operations (between 1 and 2 years) none of the patients have had further attacks of migraine or hemiplegia. This preliminary report suggests that for patients with sporadic hemiplegic migraine with a confirmed arterial component, surgical cautery of selected terminal branches of the external carotid artery may be effective treatment.

Unrecognized paraganglioma of the urinary bladder as a cause for basilar-type migraine.

Extra-adrenal paraganglioma with isolated localization in the urinary bladder is a rare neuroendocrine tumor. Although the typical symptoms like headache, nausea, weight loss, flushing, heart palpitation or paroxysmal hypertension during micturition are well established, we present an unusual case of bladder paraganglioma, 'misdiagnosed' with basilar-type migraine due to headache for the past 8 years. As urologists linked the presence of a tumor (by CT) and symptoms connected with micturition, no cystoscopy and no transurethral resection of the bladder was performed prior to detailed diagnostic workup. After diagnosis of an extra-adrenal paraganglioma, the patient was scheduled for open partial cystectomy. In consideration of the fact that bladder paraganglioma is an infrequent genitourinary cancer, this case report clearly points out the importance of an exact anamnesis and clinical examination to minimize the probability of misdiagnosis with possible fatal consequences in any case with clinical suspicion of bladder paraganglioma.

[Migraine and patent foramen ovale]. / Foramen ovale perméable et migraine.

Observational studies indicate an increased prevalence of patent foramen ovale (PFO) in migraineurs with aura and an increased prevalence of migraine and migraine with aura in patients with PFO but a recent stratified meta-analysis does not support pairwise association between PFO and migraine. There are conflicting data regarding causal relationship between these two conditions. According to recent studies, microembolization might provoke a decrease in cerebral oxygen saturation, thus triggering cortical spreading depression and, thereafter, migraine with aura attack. Release of vasoactive substances by activated platelets or atrial natriuretic factor are other pathophysiological explanations. Retrospective analyses of PFO closure suggest clinically significant improvements in migraine patterns. The MIST study is the only prospective study available with a good design but this study gave a negative response about cure of migraine with aura and revealed a high morbidity for such a benign condition. Although PFO closure sometimes appears to affect migraine patterns favorably, the very low grade of available evidence to support this association precludes definitive conclusions. To date, PFO closure in migraineurs with aura is not recommended in daily practice.

[Migraine and cadiac shunts - is there a link?]. / Migräne und kardiale Shunts - gibt es Zusammenhänge?

Recently an association between migraine and cardiac shunts (e.g. through a patent foramen ovale, PFO) has been described. There is evidence from mostly retrospective case series that PFO closure can significantly improve migraine. On the other hand an increase in attack frequency or de novo migraine after percutaneous closure of an atrial septal defect has been described. Animal experiments showed that microemboli in the cerebral circulation can trigger a cortical spreading depression, which is believed the pathophysiological substrate of migraine aura. A randomized controlled trial that investigated PFO closure for treatment resistant migraine with aura was negative. It is currently discussed whether certain subgroups, who have a high risk for paradoxical embolism, might improve after PFO closer.

[Patent foramen ovale and migraine: where is the connection]. / Foramen oval permeable y migraña: ¿dónde está la conexión?

Patent foramen ovale (PFO) is an anatomic remnant of the fetal circulation that is highly prevalent in the general population. Several observational studies show that migraine with aura and PFO have higher coincidences than expected by chance. Both conditions might be linked by certain pathophysiological mechanisms, such as right-to-left shunting of venous agents or paradoxical embolism. Alternatively, they might share a common genetic background. No relevant differences have been found between the clinical features of migraine with FOP and those of migraine without FOP. The results of several observational studies suggest that PFO closure may have a beneficial effect on migraine. However, the first randomized, double-blind, and sham-controlled trial has failed to support such conclusion. Until there is more evidence from ongoing trials, PFO closure should not be performed in clinical practice for the treatment of migraine.

Feasibility of patent foramen ovale closure with no-device left behind: first-in-man percutaneous suture closure.

OBJECTIVES: This study evaluated the feasibility of percutaneous patent foramen ovale (PFO) closure using a transcatheter suture (Superstitch), leaving no device behind. BACKGROUND: PFO has been implicated in cryptogenic strokes and migraine with auras. Percutaneous PFO closure, being less invasive than surgical closure, is increasingly performed. There are, however, early and long-term risks including device embolization, fracture, thrombosis, or infection, erosions into the free atrial wall and aorta, arrhythmias, and death. Furthermore, device implantation may complicate future percutaneous access to the left atrium. Partially reabsorbable devices and tissue welding to close PFO have recently been introduced. The first-in-man transcatheter suture closure of a PFO in an 18-year-old female with chronic migraine with aura and a well documented stroke is described. METHODS: The right femoral vein was cannulated under mild sedation and local anesthesia. Using intracardiac echocardiography imaging, bubble study demonstrated a right-to-left shunt through the PFO at rest. A Superstitch device was advanced across the PFO and sutures were delivered through the septum primum and secundum. The sutures were exteriorized and a knot was advanced to the right atrial septum and cut. RESULTS: Bubble study confirmed successful PFO suture closure. Transesophageal and transthoracic echocardiograms with bubble studies at 1 and 2 months, respectively showed complete closure with no right-to-left shunt even during Valsalva maneuver. At 6 months, the patient remained free of symptoms or migraine episodes. CONCLUSION: Percutaneous transcatheter suture closure of a PFO can be successfully achieved with no residual shunt and leaving no device behind. Technological refinements are required for wider scale use.

Migraine Intervention With STARFlex Technology (MIST) trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache.

BACKGROUND: Patent foramen ovale (PFO) is prevalent in patients with migraine with aura. Observational studies show that PFO closure resulted in migraine cessation or improvement in approximately 80% of such patients. We investigated the effects of PFO closure for migraine in a randomized, double-blind, sham-controlled trial. METHODS AND RESULTS: Patients who suffered from migraine with aura, experienced frequent migraine attacks, had previously failed > or = 2 classes of prophylactic treatments, and had moderate or large right-to-left shunts consistent with the presence of a PFO were randomized to transcatheter PFO closure with the STARFlex implant or to a sham procedure. Patients were followed up for 6 months. The primary efficacy end point was cessation of migraine headache 91 to 180 days after the procedure. In total, 163 of 432 patients (38%) had right-to-left shunts consistent with a moderate or large PFO. One hundred forty-seven patients were randomized. No significant difference was observed in the primary end point of migraine headache cessation between implant and sham groups (3 of 74 versus 3 of 73, respectively; P=0.51). Secondary end points also were not achieved. On exploratory analysis, excluding 2 outliers, the implant group demonstrated a greater reduction in total migraine headache days (P=0.027). As expected, the implant arm experienced more procedural serious adverse events. All events were transient. CONCLUSIONS: This trial confirmed the high prevalence of right-to-left shunts in patients with migraine with aura. Although no significant effect was found for primary or secondary end points, the exploratory analysis supports further investigation. The robust design of this study has served as the model for larger trials that are currently underway in the United States and Europe.