An unusual case of stroke in a young patient

The patent foramen ovale (PFO) has been increasingly implicated in the aetiology of stroke, particularly in young patients with no other identifiable cause (cryptogenic stroke). A case of Parinaud's syndrome secondary to thromboembolism from a PFO is reported here.     

Migrainous cerebral infarction in the Sagrat Cor Hospital of Barcelona stroke registry

Nine of 2000 consecutive stroke patients included in the Sagrat Cor Hospital of Barcelona Stroke Registry over a 10-year period fulfilled the strictly defined International Headache Society criteria for migrainous stroke and in whom other causes of stroke were ruled out. They accounted for 13% of all first-ever ischaemic stroke of unusual cause. Migrainous stroke was more common in women (67%) and in patients aged 45 years or younger (78%) compared to the remaining ischaemic strokes of unusual cause. No patient died during hospital stay and 67% were symptom-free at discharge. In the multivariate analysis, nausea or vomiting (odds ratio (OR) 8.40, 95% confidence interval (CI) 1.49-47.21) and age (OR 0.95, 95% CI 0.91-0.99) were predictors of migrainous stroke. Migrainous stroke is a rare entity. Vascular risk factors are uncommon and the prognosis is generally good. Patients with migrainous stroke present some different clinical features from other ischaemic strokes of unusual aetiology.     

偏头痛和隐源性脑卒中患者经食管超声心动图右心声学造影特征分析

目的：分析偏头痛和隐源性脑卒中患者经食管超声心动图右心声学造影(c-TEE)特征,探讨 c-TEE在不同疾病右向左分流类型评估中的作用。方法：选取2018年1月至2018年10月我院收治的疑诊右向左分流相关的偏头痛患者146例,隐源性脑卒中患者167例作为研究对象进行回顾性分析。所有入选患者均完成TEE、c-TEE检查,分析患者一般情况,并比较两组间TEE及c-TEE右向左分流阳性结果及c-TEE左房内微气泡来源、分流程度等特征。结果：偏头痛组女性居多,且年龄小于隐源性脑卒中患者(P均＜0.05)。TEE观察到隐源性脑卒中组PFO 患者82例,偏头痛组32例,均未发现肺静脉异常;c-TEE检查中偏头痛组肺相关右向左分流(P-RLS)66例,PFO相关右向左分流(PFO-RLS)80例;隐源性脑卒中组P-RLS 71例,PFO-RLS 96例,c-TEE在偏头痛组的PFO检出率明显高于TEE(P＜0.05),隐源性脑卒中组无明显统计学差异(P>0.05)。两组间c-TEE检查不同类型右向左分流比例无统计学差异(P>0.05),但偏头痛组1级RLS(65/127,51%)显著高于隐源性卒中组(38/153,25%,P＜0.05),其中偏头痛患者的P-RLS和PFO-RLS均显著高于隐源性脑卒中患者( P均＜0.05);隐源性卒中组3级RLS比例 (51/153,33%)显著高于偏头痛组 (22/127,18%)(P＜0.05),其中隐源性脑卒中组PFO-RLS显著高于偏头痛组(P＜0.05)。结论： c-TEE可明确偏头痛和隐源性脑卒中患者右向左分流来源并进行半定量分析,为病因学诊断提供可靠的影像学依据。     

经食管超声心动图联合PLR、NLR对卵圆孔未闭合并隐源性卒中患者的诊断价值

  目的  探讨经食道心脏超声(TEE)联合血小板/淋巴细胞比值(PLR)、中性粒细胞/淋巴细胞比值(NLR)在卵圆孔未闭(PFO)患者合并隐源性卒中的评估应用。  方法  选取本院2019年8月~2021年8月收治的卵圆孔未闭患者132例,其中合并隐源性卒中23例。所有患者均接受TEE检测,测量PFO直径,并行血常规检测,根据血小板、淋巴细胞、中性粒细胞计数计算PLR、NLR比值,比较PFO合并隐源性卒中和未合并隐源性卒中PLR、NLR比值的差异性,采用Spearman法分析PFO直径、PLR、NLR与PFO合并隐源性卒中的相关性,采用ROC曲线分析PFO直径和PLR、NLR检测在卵圆孔未闭合并隐源性卒中的评估价值。  结果  TEE检测发现PFO未合并隐元性卒中患者PFO直径低于合并隐源性卒中(P < 0.05),造影可见房水平不同级别的右向左分流;PFO患者合并隐源性卒中PLR、NLR比值高于未合并隐源性卒中患者(P < 0.05);Spearman分析显示:PFO直径及PLR、NLR比值与PFO合并隐源性卒中风险呈正相关关系(r=0.385、0.429、0.378,P < 0.05);ROC曲线显示:PFO直径联合PLR、NLR评估PFO合并隐源性卒中风险曲线下面积高于PLR、NLR单项指标曲线下面积(P < 0.05)。  结论  TEE可以较好地分辨PFO直径,结合PLR、NLR检测有助于评估PFO合并隐源性卒中的发生风险。      

Clinical impact of patent foramen ovale diagnosis with transcranial Doppler.

The role of patent foramen ovale (PFO) in cryptogenic stroke is still debated, but from recent follow-up studies it seems that the amount of right-to-left shunt (RLS) and the association with atrial septal aneurysm (ASA) are major determinants of stroke recurrence. PFO and RLS through the atrial chambers have been recently studied in a number of conditions not or marginally related to cerebrovascular disease. Historically the first studies addressed the presence of RLS in scuba divers as a possible abnormality related to decompression sickness (DS) of unknown aetiology. Despite initial debate there is now robust evidence to claim that patency of foramen ovale increases the risk of developing DS by two and half to four times. Patients with PFO-related DS tend to have early occurrence of symptoms after surfacing and a clinical presentation that indicates brain or upper cervical spinal cord involvement. Recent reports suggest that divers with hemodynamically significant RLS may have an increased risk of developing clinically asymptomatic multiple brain lesions. PFO has been found in patients suffering from migraine with aura with approximately the same frequency as that encountered in cryptogenic stroke patients. This finding has prompted speculations on the possible role of RLS in increasing the stroke risk in migraineurs and in the pathophysiology of the aura. Recent reports showing that migraine with aura is dramatically improved after transcatheter closure of PFO suggest that migraine with aura may indeed be triggered by humoral factors that reach the brain by escaping the pulmonary filter. A RLS is involved in a rare condition known as platypnea-orthodeoxia and perhaps underlies an increased risk of cerebral complications after major orthopedic surgery. Valsalva-like activities often precede the occurrence of attacks of transient global amnesia (TGA) and abnormalities consistent with hypoperfusion of deep limbic structures have been reported during a typical TGA episode. This had raised the hypothesis that TGA may be triggered by paradoxical embolism of platelets aggregates in the posterior circulation, but the search for an increased frequency of PFO in TGA patients has yielded conflicting results. Conditions that determine an increase in pulmonary pressure may facilitate the opening of the virtual interatrial valve and thus promoting shunting of blood to the left heart chambers which in turn might contribute to further desaturation of arterial blood. It is therefore not surprising that RLS has been found in 70% of patients with chronic obstructive pulmonary disease and increased pulmonary pressure and in the same proportion of patients with obstructive sleep apnoea, a condition that ultimately may result in pulmonary hypertension. In conclusion, from the evidence gathered so far the picture is emerging of an important role of PFO in a number of non-stroke conditions, either as causative factor or as associated condition predisposing to complications. The availability of simple diagnostic techniques such as transcranial Doppler (TCD) to assess RLS will undoubtedly contribute a great deal of knowledge on the relevance in medicine of this hitherto neglected condition.     

Similar frequency of TT virus infection in patients with liver enzyme elevations and healthy subjects

TT virus (TTV) is a novel DNA virus that has been identified in patients with post-transfusional hepatitis of unknown aetiology. However, its pathogenic role in liver injury remains unclear. To determine its frequency and clinical impact in cryptogenic liver diseases, we investigated the TTV prevalence in patients with liver enzyme elevations of unknown aetiology and in healthy subjects. Fifty-four patients (33 male, 21 female) who have been followed up for elevated ALT/AST levels of unknown aetiology and 118 healthy subjects (99 male and 19 female) were included in the study. TTV DNA was investigated by the polymerase chain reaction. Other possible causes of transaminase elevation were excluded in detailed biochemical and serological tests. A liver biopsy was performed in 45 patients. TTV DNA was detected in 46 patients with liver enzyme elevations (85.1%) and in 94 healthy subjects (79.6%). There was no statistical difference between the groups (p = 0.51). Histological examination of the liver revealed no specific change in TTV DNA positive patients that could be attributed to this virus infection. These results showed that TTV is a common virus in patients with liver enzyme elevation of unknown aetiology and even among healthy subjects in our geographical area. TTV infection is therefore widespread in the general population and does not seem to be associated with liver damage.     

Population-based study of the relationship between patent foramen ovale and cerebrovascular ischemic events

OBJECTIVE: To determine whether patent foramen ovale (PFO) is a risk factor for a cryptogenic cerebrovascular ischemic event (CIE). METHODS: This case-control study of 1072 residents of Olmsted County, Minnesota, who underwent contrast transesophageal echocardiography between 1993 and 1997 included 519 controls without CIE randomly selected from the population, 262 controls without CIE referred for transesophageal echocardiography because of cardiac disease, 158 cases with incident CIE of obvious cause (noncryptogenic), and 133 cases with incident CIE of uncertain cause (cryptogenic). RESULTS: Large PFOs were detected in 108 randomly selected controls (20.8%), 22 referred controls (8.4%), 17 noncryptogenic CIE cases (10.8%), and 22 cryptogenic CIE cases (16.5%). After adjustment for age, sex, hypertension, smoking, atrial fibrillation, ischemic heart disease, and number of contrast injections, the presence of a large PFO was not significantly associated with group status (P=.07). Using the odds of the presence of large PFO in the randomly selected controls as the reference, the odds ratio (95% confidence interval) of the presence of large PFO was 0.47 (0.26-0.87) for referred controls, 0.69 (0.37-1.29) for noncryptogenic CIE cases, and 1.10 (0.63-1.90) for cryptogenic CIE cases. CONCLUSIONS: Patent foramen ovale is not a risk factor for cryptogenic ischemic stroke or transient ischemic attack in the general population. The PFO's importance in the genesis of cryptogenic CIE may have been overestimated in previous studies because of selective referral of cases and underascertainment of PFO among comparison groups of patients referred for echocardiography for clinical indications other than cryptogenic CIE.     

Polymorphism of 5,10-methylenetetrahydropholate reductase, prothrombin, and coagulation factor V genes in young patients with ischemic stroke

The study included 142 patients (87 women, 55 men) (mean age 36.2 +/- 8.3 yr) after ischemic stroke caused by dissection of cerebral arteries (D) (n = 37), anti-phospholipid syndrome (APS) (n = 55) or cardiogenic embolism (CE) (n = 11). Stroke of unknown origin (cryptogenic) was diagnosed in 39 patients. Mutations of 5,10-methylenetetrahydropholate reductase (MTGPR), prothrombin, and coagulation factor V genes were documented by PCR in 38, 0, 3% of D cases, 55.9, 9, 13% of APS cases, 73, 9, 0 CE cases, 57, 5, 0% of cases with cryptogenic stroke compared with 43, 0, 0% in controls. Mutations in MTGPR gene in CE cases, prothrombin gene in APS and CE cases, coagulation factor V gene in APS cases occurred more frequently than in control (p < 0.05). They, were more frequent in APS/CE than in D (p < 0.05). Mutation rate in cryptogenic stroke was not significantly different from that in control (p < 0.05). It is concluded that the above mutations are not involved in pathogenesis of cryptogenic stroke, whereas those of prothrombin and coagulation factor V genes may enhance the thrombogenic potential in APS and CE patients. The role of MTGPR gene mutation in pathogenesis of cardiogenic stroke needs clarification.     

Sustained risk of recurrent thromboembolic events in patients with patent foramen ovale and paradoxical embolism: long-term follow-up over more than 15 years

Background  

Patients with patent foramen ovale (PFO) and cryptogenic stroke are at risk of recurrence. Therapeutic regimens range from no treatment to anticoagulation treatment to surgical or interventional closure. However, long-term follow-up is only available for up to 4 years.     

Patent foramen ovale transcatheter closure device thrombosis

The role of patent foramen ovale (PFO) in patients with cryptogenic stroke (stroke of unknown cause) remains controversial, although an association seems likely in younger patients with atrial septal aneurysms and PFO. The mechanism of cryptogenic stroke in these patients is presumed to be paradoxical embolism via right-to-left shunt across the PFO. The available options for treatment include medical therapy with antiplatelet or anticoagulant therapy or closure of the PFO surgically or with use of transcatheter PFO closure devices. We describe 2 cases of bilateral device thrombosis associated with use of a transcatheter PFO closure device (CardioSEAL). To our knowledge, only 1 other case of thrombosis associated with use of this device has been reported.     

Population-based study of the relationship between atherosclerotic aortic debris and cerebrovascular ischemic events

OBJECTIVE: To assess the validity of the suggestion that protruding atheromatous material in the thoracic aorta is an important cause of cerebrovascular ischemic events (CIEs) (ie, transient ischemic attack or ischemic stroke). METHODS: This case-control study of Olmsted County, Minnesota, residents who underwent transesophageal echocardiography (TEE) from 1993 to 1997 included controls without CIE randomly selected from the population, controls without CIE referred for TEE because of cardiac disease, cases with incident CIE of obvious cause (noncryptogenic), and cases with incident CIE of uncertain cause (cryptogenic). RESULTS: Of the 1135 subjects, 520 were randomly selected controls without CIE, 329 were controls without CIE referred for TEE, 159 were noncryptogenic CIE cases, and 127 were cryptogenic CIE cases. Complex atherosclerotic aortic debris in ascending and transverse segments of the arch was detected in 8 randomly selected controls (1.5%), 13 referred controls (4.0%), and 15 noncryptogenic (9.4%) and 4 cryptogenic (3.1%) CIE cases. After adjusting for age, sex, hypertension, smoking, atrial fibrillation, valvular heart disease, congestive heart failure, and atherosclerosis other than in the thoracic aorta, complex atherosclerotic aortic debris was not significantly associated with group status. With randomly selected controls as the referent group, odds ratios (95% confidence intervals) were 1.72 (0.61-4.87) for referred controls, 3.16 (1.18-8.51) for noncryptogenic CIE cases, and 1.39 (0.39-4.88) for cryptogenic CIE cases. CONCLUSIONS: Complex atherosclerotic aortic debris is not a risk factor for cryptogenic ischemic stroke or transient ischemic attack but is a marker for generalized atherosclerosis and well-established atherosclerotic and cardioembolic mechanisms of cerebral ischemia. Embolization from the aorta is not a common mechanism of ischemic stroke or transient ischemic attack.     

The potential role of the left atrial septal pouch in cryptogenic stroke

The left atrial septal pouch (LASP) is an anatomic variant of the atrial septum that forms a blind-ending pouch, communicating exclusively with the left atrium (LA). Case reports have demonstrated thrombus within LASP and in the setting of cryptogenic stroke. Initial epidemiologic results are mixed, one study showing and others not showing an association between LASP and cryptogenic stroke. Additional investigation should take place to determine the clinical significance of LASP and what interventions are required to prevent ischemic stroke in at-risk individuals.     

Recurrent juvenile ischemic stroke caused by bow hunter’s stroke revealed by carotid duplex ultrasonography

Bow hunter’s stroke (BHS) is a rare cause of vertebrobasilar insufficiency due to rotational vertebral artery (VA) occlusion associated with head turning. We report a juvenile patient presenting with recurrent ischemic stroke caused by BHS, which was revealed by carotid duplex ultrasonography. Carotid duplex ultrasonography performed in the neutral position showed normal findings. However, disappearance of end-diastolic blood flow of contralateral VAs was observed with head rotation. Digital subtraction angiography confirmed occlusion at C1/2 levels in the VA contralateral to the head rotation, bilaterally. Importantly, our patient did not recognize the association of head rotation and previous episodes of stroke. We suggest that BHS should be considered in patients with cryptogenic stroke occurring in the vertebrobasilar artery territory.     

右心声学造影与经颅多普勒发泡试验诊断隐源性卒中患者卵圆孔未闭的对比研究

目的：探讨右心声学造影(c-TTE)及经颅多普勒发泡试验(c-TCD)对隐源性卒中患者并卵圆孔未闭(PFO)的诊断价值。方法：选取2020年1月～2022年12月在我院诊治的隐源性卒中患者102例,均行c-TCD及c-TTE检查,以经食管超声心动图(TEE)作为诊断金标准,比较c-TTE、c-TCD检查对隐源性卒中患者PFO的诊断价值。结果：TEE检查证实102例隐匿性卒中患者有44例PFO,c-TCD检查结果显示,真阳性36例,假阳性10例,假阴性8例,真阴性48例；c-TTE检查结果显示,真阳性42例,假阳性3例,假阴性2例,真阴性55例。受试者工作特征(ROC)曲线分析显示,c-TCD检查、c-TTE诊断隐匿性卒中患者PFO的AUC分别为0.823,0.951,c-TCD检查诊断隐源性卒中患者PFO的敏感度、特异度、准确率分别为81.82%、82.76%、82.35%,明显低于c-TTE检查的95.45%、94.83%、95.10%(P<0.05)。c-TCD检查对右向左分流半定量分级低于c-TTE(P<0.05),c-TCD检查对右向左分流的检出率为30.39%,明显低于c-TTE的58.82%(P<0.05)。结论：与c-TCD检查相比较,c-TTE对隐源性卒中患者PFO具有更高的诊断价值,且对隐源性卒中PFO患者的右向左分流半定量分级程度更高、检出率更高。     

Statins after recent stroke reduces recurrence and improves survival in an aging Mediterranean population without known coronary heart disease

What is known and Objective: The effect of a statin‐based medical intervention on prevention of fatal and non‐fatal stroke recurrence and the incidence of all‐causes mortality have been explored previously in aging populations within the scope of clinical trials research. However, such evidence needs to be explored under conditions of routine clinical practice. The objective of this study was to determine whether statin therapy in patients with a first stroke episode reduces the incidence of 6‐year recurrent fatal or non‐fatal stroke and all‐cause mortality in an aging Mediterranean population without known coronary heart disease followed in routine medical practice. Methods: A retrospective study was carried out using records on death, hospitalizations owing to stroke and history of statin therapy included in the Badalona Serveis Assistencials (BSA) database. The cohort studied consisted of consecutive patients covered by the BSA health provider plan with a first‐ever acute stroke episode during January 2003 until December 2008, for whom there was available information covering the 6‐year follow‐up period. Recurrence rate (RR) and incidence rate (IR) of fatal/non‐fatal stroke and all‐causes mortality were computed. Association with statin therapy was assessed by means of calculation of relative risk (RR) and hazard ratio (HR) using multivariate logistic regression and Cox proportional hazards models controlling for confounding covariates. Results and Discussion: The cohort comprised a series of 601 consecutive patients [57% men, 75·9 (12·4) years old (88% >60 years)]. Of these, 32% received statins, which were associated with lower fatal/non‐fatal recurrent stroke RR; 7% vs. 18% [adjusted RR = 0·32 (CI: 0·16–0·61), P = 0·001] and lower IR; 16·78 vs. 45·22 events/year‐1000 subjects [adjusted HR = 0·35 (0·19–0·64), P = 0·001]. Similarly, observed all‐causes mortality was lower in the cohort receiving statins; 11% vs. 16% [adjusted RR = 0·29 (CI: 0·08–1·12), P = 0·072], and also mortality rate; 26·09 vs. 36·25 deaths/year‐1000 subjects [adjusted HR = 0·23 (0·08–0·67), P = 0·007]. What is new and Conclusions:  Statin therapy in patients with first‐ever acute stroke lowers the risk of 6‐year stroke recurrence and improves survival in an aging Mediterranean cohort. These results add additional evidence in routine clinical practice to the observed effects of statins in clinical trials.     

不明原因栓塞性卒中的诊治进展

不明原因栓塞性卒中（embolic stroke of undetermined source,ESUS）是一种特殊类型的隐源性卒中,阵发性心房颤动和卵圆孔未闭是其最主要的潜在病因。ESUS概念自2014年被提出后相关研究报道越来越多,尤其在ESUS二级预防方面取得不少进展。本文就ESUS的流行病学、临床特征、诊断标准、二级预防治疗策略和预后方面进行了综述。     

Prevention of recurrent ischemic stroke.

Treatment after an ischemic stroke or transient ischemic attack (TIA) should target the presumed cause of the initial episode to facilitate focused prophylaxis. In the majority of ischemic strokes, degenerative large- and small-vessel disease is the cause. In these patients, attention to modifiable risk factors is an important priority. However, uncertainty and controversy remain regarding therapy, although issues are gradually being settled. There are now strong scientific data to support the use of carotid endarterectomy in patients with 70% to 99% stenosis and an ipsilateral TIA or nondisabling stroke. Aspirin is accepted as standard preventive therapy and should be used in all patients with a TIA or stroke, including those who undergo endarterectomy. Although the dose most commonly used in clinical trials is 1,300 mg/day, a daily dose of 325 mg is probably equally effective with less gastrotoxicity. Given present evidence, use of dipyridamole (Persantine) is not warranted. The role of ticlopidine hydrochloride (Ticlid) in stroke prophylaxis is not well defined. Its superiority over aspirin demonstrated in one study may make it the drug of first choice despite its expense and side effects. The efficacy of warfarin sodium (Coumadin, Panwarfin, Sofarin) or heparin in ischemic stroke caused by degenerative cerebrovascular disease is not supported by scientific data, but no prospective controlled studies have demonstrated that these agents are ineffective. Therefore, it seems prudent to reserve anticoagulant therapy for situations in which an ongoing thrombotic process is likely (eg, progressing stroke). Heparin therapy in the immediate post-TIA period is not warranted on the basis of current scientific evidence.     

Diabetes mellitus and stroke

The aim of this article was to describe (i) the epidemiology and outcomes of stroke relating to diabetes; (ii) the pathophysiology of diabetes as a risk factor for stroke; (iii) the management of acute stroke in patients with diabetes; (iv) the evidence of primary and secondary prevention of stroke in patients with diabetes; and (v) the risk of new-onset diabetes using older antihypertensive agents. The combination of diabetes and stroke disease is a major cause of morbidity and mortality worldwide. Evidence from large clinical trials performed in patients with diabetes supports the need for aggressive and early intervention to target patients' cardiovascular (CV) risks in order to prevent the onset, recurrence and progression of acute stroke. Identification of at-risk patients with diabetes and metabolic syndrome has also allowed the delivery of early and effective intervention to reduce stroke risks, while active treatment during the acute phase of stroke will reduce long-term neurological and functional deficits. While the ongoing debate on the risk benefits of different antihypertensive, lipid-lowering and antiplatelet agents should not detract clinicians from pursuing aggressive CV risk reduction, the application of evidence-based medicine specifically in patients with diabetes will facilitate the use of appropriate agents to improve clinical outcomes. The overall management of patients with diabetes and acute stroke or at risk of secondary stroke should also include multifactorial intervention that not only targets patient's CV risk but also includes behavioural, lifestyle and, where appropriate, surgical intervention.     

Closing the gap on patent foramen ovale and cryptogenic stroke

Introduction: The treatment options for prevention of recurrent of cryptogenic stroke in patients with patent foramen ovale (PFO) have been intensely debated in the recent decades. The suggested options were percutaneous closure of PFO versus medical therapy. However, up to these date there is a controversy regarding the indication of percutaneous closure. Multiple meta-analysis and recent randomized control trials showed the benefit of PFO closure when compared with medical therapy alone.

Areas covered: The article reviews the prevalence, physiology, diagnosis and treatment options of PFO after cryptogenic stroke. Furthermore, it will discuss the results of randomized control trials that compared the PFO closure to medical therapy.

Expert opinion: The association between PFO and unexplained cryptogenic stroke has been well established in the multiple studies. The diagnosis and management of PFO might be challenging in some cases. Although multiple studies showed that PFO closure is associated with lower rates of recurrent stroke in patients presenting with cryptogenic stroke, the indication and patient selection for this intervention are not well established yet in the guidelines.