Cryptogenic stroke in children: possible role of patent foramen ovale

Stroke is a rare disorder in childhood. The majority of these cases is of an ischemic nature. In spite of the long list of known causes, many strokes remain undetermined, so-called cryptogenic strokes. Increasing evidence indicates that, in the young adults, many cases of cryptogenic stroke are presumably due to paradoxical embolism. In childhood, this is usually not considered, unless in the context of a complex cyanotic heart disease. We present two cases, a 6-year-old boy and an 11-year-old girl who had an episode of cerebral ischemia documented by MRI, and in whom the only anomaly found was a patent foramen ovale (PFO) with intermittent left to right shunt at rest, but with a large right to left shunt during the Valsalva maneuvre. We assumed that, in our cases, in the absence of identifiable causes, the cerebral ischemia was most likely due to paradoxical embolism through the PFO. Of course, as in the adult, the paradoxical embolism could not be proved, but in our opinion it remains the most concrete possibility. Therefore, in presence of a cryptogenic stroke, a PFO should be investigated also in children.     

Cryptogenic stroke and patent foramen ovale: clinical clues to paradoxical embolism

BACKGROUND: Patent foramen ovale (PFO) is an independent risk factor for cerebral infarction. Since ~25% of the population have a PFO, the simple association of PFO with stroke is not enough to establish the diagnosis of paradoxical embolism. We evaluated possible clinical clues to the diagnosis of paradoxical embolism. METHODS: Among patients with cryptogenic ischemic stroke (CS) who were investigated for a right-to-left shunt (RLS), we compared clinical, coagulation and biochemical parameters in patients with PFO versus without PFO. RESULTS: Among 1689 new patients referred for TIA/non-disabling stroke between 2001 and 2007, 175 with cryptogenic stroke (CS) were investigated for RLS by transcranial Doppler (TCD) bubble studies; 89 (5.5%) with positive TCD had a PFO confirmed by TEE. In multivariate logistic regression, a history of DVT or pulmonary embolism (OR, 4.39; 95% CI, 1.23-15.69; p=0.023), prolonged travel (OR, 8.77; 95% CI, 1.775-43.3; p=0.008) , migraine (OR, 2.30: 95% CI, 1.07-4.92; p=0.031), a Valsalva maneuver preceding the onset of focal neurological symptoms (OR, 3.33; 95% CI, 1.15-9.64; p=0.026) and waking up with stroke/TIA (OR, 4.53, 95% CI, 1.26-16.2; p=0.018) were independently associated with PFO-associated cerebrovascular events. Patients with PFO had higher plasma total homocysteine levels than patients without PFO (8.9+/-3 versus 7.9+/-2.6 micromol/L respectively; p=0.021). CONCLUSIONS: A history of DVT or pulmonary embolism, migraine, recent prolonged travel, sleep apnea, waking up with TIA or stroke or a Valsalva maneuver preceding the event are clinical clues to the diagnosis of paradoxical embolism among patients with CS.     

Ischaemic stroke in patients with patent foramen ovale

Patent foramen ovale (PFO) is one of the most common defects of the atrial septum. PFO can be linked to several brain disorders including stroke. PFO is more prevalent in young patients with cryptogenic stroke than in the general stroke population. Data from the literature do not indicate the role of PFO and/or atrial septal aneurysm in pathogenesis of first-ever and recurrent stroke. Antithrombotics seem to decrease the risk of stroke recurrence, but oral anticoagulants also increase the risk of haemorrhagic complications. Results of studies on percutaneous or surgical closure of PFO are insufficient to make clinical therapeutic decisions. Both the role of PFO in recurrent stroke as well as the most efficacious therapeutic approach in preventing recurrent strokes remain to be elucidated in further studies.     

与卵圆孔未闭相关的不明原因脑卒中的研究进展

卵圆孔未闭(PFO)是一种先天性心脏病,在普通人群中发病率达25%,在青年不明原因脑卒中(CS)患者中高达46%。PFO与多种疾病相关,其中最重要的是脑卒中,与PFO相关的脑卒中大多归属于CS,目前认为PFO造成的反常栓塞是其最常见的致病机制。与PFO相关的CS的特点、诊断与治疗已经越来越受到重视。本文现围绕近年来相关的研究进展进行综述,以期为PFO相关的CS的诊治提供临床依据。     

Outcome of patients with cryptogenic stroke and patent foramen ovale

OBJECTIVES: The aim was to estimate the recurrence rate and to define subgroups at increased risk for recurrent cerebral ischaemia in patients with patent foramen ovale (PFO) and so called cryptogenic stroke due to paradoxical embolism. METHODS: Patent foramen ovale was diagnosed in 318 patients with otherwise unexplained ischaemic stroke or transient ischaemic attack (TIA). One hundred and fifty nine were treated medically (oral anticoagulation 79, platelet inhibitors 80) and represent the study population. The remaining 159 patients underwent endovascular or surgical closure of the PFO and are not part of this study. RESULTS: Mean age was 50.7 (SD 13.5) years. The event leading to the diagnosis of PFO was a TIA in 38 patients (23.9%), an ischaemic stroke in 119 (74.8%), and an amaurosis fugax in two patients (1.3%). Forty four patients (27.7%) had experienced multiple cerebrovascular ischaemic events before the diagnosis of the PFO. During mean follow up of 29 (SD 23) months 21 patients (13.4%) had a recurrent cerebrovascular event (seven strokes and 14 TIAs). The average annual rate of recurrent strokes was 1.8% and that of recurrent strokes or TIAs was 5.5%. When patients with PFO with multiple cerebrovascular events before the diagnosis of the PFO were analyzed separately, the average annual rates of recurrent cerebral ischaemia were 3.6% for recurrent strokes and 9.9% for recurrent strokes or TIAs. These rates were significantly higher than in patients with first ever stroke or TIA (p=0.02). CONCLUSIONS: The study confirms a risk of stroke recurrence that is similar to the rates of previously published series of patients with PFO and cryptogenic strokes. Patients with more than one previous event were at increased risk of recurrent cerebral ischaemia.     

Management of patients with stroke and a patent foramen ovale

Observational studies have established a strong association between the presence of patent foramen ovale (PFO) and increased risk of ischemic stroke. The mechanism involved is presumed to be a paradoxical embolism from a venous thrombus that travels via the PFO to the systemic circulation. The best treatment modality to prevent recurrent stroke in patients with PFO remains undefined. There are four major choices: 1) medical therapy with anticoagulants, 2) medical therapy with antiplatelet agents, 3) surgical closure, and 4) percutaneous device closure. The Patent Foramen Ovale in Cryptogenic Stroke Study has demonstrated that antiplatelet and anticoagulant therapies are of equal benefit in preventing recurrent neurologic events in stroke patients with a PFO. Medical therapy should remain as the initial choice of secondary prophylactic therapy. PFO closure, either surgical or percutaneous, may further reduce event rates; however, this remains to be demonstrated because no randomized trial to date has compared PFO closure with medical therapy.     

Factor V Leiden mutation and patent foramen ovale in ischemic stroke

We report a 47-years-old male with ischemic stroke, whose arteriographic and echocardiographic investigations did not reveal any steno-occlusive arterial disease or embolic source from the left cardiac chambers. A transesophageal echocardiogram showed a patent foramen ovale (PFO), whilst laboratory screening for coagulation abnormalities showed heterozygosity for factor V Leiden mutation. The significance of the association of PFO with factor V Leiden mutation is discussed as a possible cause of ischemic stroke through paradoxical embolism from a venous source. The high prevalence of these two conditions in the general population is emphasized and the indication for anticoagulant therapy is discussed. Received: 7 December 2001 / Accepted in revised form: 16 July 2002     

Recurrent stroke/TIA in cryptogenic stroke patients with patent foramen ovale

BACKGROUND: Patent foramen ovale (PFO) is present in 40% of patients with cryptogenic stroke and may be associated with paradoxical emboli to the brain. Therapeutic options include antiplatelet agents, anticoagulation, percutaneous device and surgical closure. We assessed the hypothesis that there are differences in rates of recurrent TIA or stroke between patients in the four treatment groups. METHODS: Patients presenting from January 1997 with cryptogenic stroke or TIA and PFO were followed prospectively until June 2003. Treatment choice was made on an individual case basis. The primary outcome was recurrent stroke. The secondary outcome was a composite of stroke, TIA, and vascular death. RESULTS: Baseline. Our cohort consisted of 121 patients; 64 (53%) were men. Median age was 43 years. Sixty-nine percent presented with stroke and 31% with TIA. One or more vascular risk factor was present in 40%. Atrial septal aneurysm (ASA) was present in 24%. Treatment consisted of antiplatelet agents (34%), anticoagulation (17%), device (39%) and surgical closure (11%). Follow-up. Recurrent events occurred in 16 patients (9 antiplatelet, 3 anticoagulation, 4 device closure); 7 were strokes, 9 were TIA. Comparing individual treatments there was a trend toward more strokes in the antiplatelet arm (p = 0.072); a significant difference was seen for the composite endpoint (p = 0.012). Comparing closure versus combined medical therapy groups, a significant difference was seen for primary (p = 0.014) and secondary (p = 0.008) outcomes, favoring closure. Age and pre-study event predicted outcome. CONCLUSION: Patent foramen ovale closure was associated with fewer recurrent events. Complications of surgical and device closure were self-limited.     

伴有卵圆孔未闭的隐源性脑梗死的临床特点

目的探讨伴有卵圆孔未闭(PFO)的隐源性脑梗死的临床特点。方法回顾性分析8例伴有PFO的隐源性脑梗死患者的临床资料。结果 8例患者年龄15~55岁,平均39.75岁,均急性起病。主要临床表现为肢体无力5例,言语障碍2例,行走不稳、双下肢无力、癫痫发作、偏身针刺觉减退各1例。超声心动图检查示患者均有PFO。头颅MRI表现为额叶、顶叶、颞叶、枕叶、岛叶皮质、脑室体旁、内囊后肢、基底节、小脑半球T1低信号,T2高信号;单侧受累4例,双侧受累4例;6例为多发病灶,2例为单一病灶;累及前循环系统4例,后循环系统1例,前后循环均累及3例。8例患者治疗后未再复发。结论伴有PFO的隐源性脑梗死患者发病年龄相对偏小。头颅MRI多发病灶多见,可累及双侧,前后循环系统均可受累。伴有PFO的隐源性脑梗死预后较好。     

Coagulation abnormalities in adults with cryptogenic stroke and patent foramen ovale

A patent foramen ovale (PFO) is found by transesophageal echocardiography in one half of patients with cryptogenic stroke (CS). Coagulation abnormalities may promote paradoxical emboli in these patients. Seventeen patients were identified with PFO and CS. Thirty-one percent of patients had hematologic risk factors for venous thrombosis. These included abnormal activated protein C resistance and increased anticardiolipin antibodies. Patients with coagulation abnormalities and a PFO were three times as likely to be treated with warfarin compared to aspirin (P<0.05). Prothrombotic states are common in patients with PFO and CS and identifying these conditions may impact the choice of antithrombotic therapy.     

合并卵圆孔未闭的脑梗死患者临床及磁共振影像特点分析

目的通过分析合并卵圆孔未闭（PFO）的脑梗死患者的临床特点及MRI弥散加权相（diffusion--weightedimaging,MRI—DWI）的病灶形式,探讨其可能发病机制。方法回顾性分析102例合并不同大小心脏PFO的脑梗死患者的临床资料、经食道超声及MRI资料。结果102例合并PFO的急性脑梗死患者按PFO大小分为两组：小PFO组（〈1．9mm）患者49例（48．03％）,而大PFO组（≥2．0mm）患者53例（51．96％）。小PFO组伴发房间隔膨胀瘤3例,大PFO组合并房间隔膨胀瘤7例,差异有统计学意义（P〈0．05）。大PFO组有51例患者（96．23％）心脏超声显示异常的右向左分流,比例高于小PFO组（25例,51．02％,P〈0．001）。所有患者中静脉异常栓子的来源检出率为20．59％。MRI—DwI示梗死主要分布于前循环,以皮质下穿支动脉梗死为主,两组患者的梗死病灶分布无差异。结论不同大小PFO患者的MRI—DWI上脑梗死病灶特点无差异。卵圆孔未闲患者的梗死病灶以皮质下穿支动脉梗死,可能不同于大动脉粥样硬化性脑梗死发病机制。     

Transcatheter closure of patent foramen ovale in patients after cryptogenic stroke

Paradoxical embolism through a patent foramen (PFO) is a possible mechanism of ischaemic stroke in patients with cryptogenic stroke. Occlusion of PFO in such patients is considered by some authors as most effective in stroke prevention. We present our initial experience with transcatheter closure of PFO with the new self-expanding device--the Amplatzer PFO occluder in three young patients (age < 50 years). Each of them experienced at least one ischaemic stroke episode, without a left heart or carotid source and each had an interatrial communication with right-to-left shunting during Valsalva manoeuvre on echocardiography. The PFO's were closed completely without complications, under transoesophageal echo guidance in general anaesthesia. Complete closure was confirmed at one-month follow-up echocardiogram in each patient. No repeat cerebral accidents occurred at that time. The procedures were relatively easy and the clear presentation of the implant on TEE and fluoroscopy, made implantation fully controlled. The unique feature of the device is, that until release it can easily be retrieved, repositioned or removed. Transcatheter closure of PFO with the Amplatzer PFO occluder may become the new therapeutic option for patients with cryptogenic stroke and presumed paradoxical embolism.     

Pregnancy, patent foramen ovale and stroke: a case of pseudoperipheral facial palsy

Abstract The pathogenetic role of patent foramen ovale (PFO) in embolic stroke and its prognostic and therapeutic implications have not yet been clearly defined. Nonetheless, recent availability of non-invasive diagnostic techniques, such as the transcranial Doppler (TCD), has increased the frequency with which this anomaly is diagnosed. Here we present the case of a young woman affected by post-partum peripheral facial palsy: further exams disclosed not only its truncal-ischaemic origin, but also, significantly, the presence of PFO, as well as of anticardiolipin antibodies (acL). Given the increased embolic risk in labouring women, this study highlights the importance of searching for PFO in case of a stroke during pregnancy.     

Patent foramen ovale and stroke

Journal of Neurology - A patent foramen ovale (PFO) is a highly prevalent finding in cryptogenic ischaemic stroke, particularly in young adults. A common challenge in clinical practice is to...