Transcranial Doppler and risk of recurrence in patients with stroke and patent foramen ovale

The importance of patent foramen ovale (PFO) in stroke of unknown cause remains disputed, as PFO may be present in up to 20% of normal people and in a high proportion of patients with non-vascular disorders. Recent evidence suggests that the amount of right-to-left shunt (RLS) may be the crucial factor for stroke occurrence and relapse. The aim of the study was to assess predictors of recurrence in PFO-related stroke patients with particular emphasis on amount of shunting. Patients less than 61 years old who had been admitted for a PFO-related stroke within the previous 5 years, were re-evaluated on a follow-up visit. The clinical syndrome, residual disability, vascular risk factors and number of relapses as the index event were assessed. RLS sizing was semi-quantitatively performed with saline-enhanced transcranial Doppler (TCD), by assuming a cut-off of more or less 10 bubbles recorded in the cerebral vessels as a criterion to discriminate large versus small shunt, respectively. Thereafter patients were prospectively followed-up for a median time of 23 months. Total follow-up was 61 months. Fifty-nine patients (M/F = 23/36, mean age 43 +/- 13) were studied. Overall there were 23 relapses in 13 patients. The amount of shunting was the only significant independent variable associated with relapse: at the end of the follow-up period the recurrence rate was 0.66 and 8.2% per patient per year in patients with small and large shunt, respectively. This difference was statistically significant (chi2 = 10.39, P = 0.0012; OR 17.05, 95% CI 2.10-755.22). In patients with PFO-related stroke, the amount of RLS as assessed with TCD is the only independent predictor of relapse. PFO sizing is mandatory in patients with PFO.     

Effect of body positioning during transcranial Doppler detection of right-to-left shunts

We adopted an expanded transcranial Doppler (TCD) protocol to evaluate if additional injections of agitated saline in different positions would improve shunt detection or grading. We report the safety and feasibility of this expanded contrast TCD protocol. Patients with ischemic stroke were evaluated. The standard protocol for RLS detection was followed and expanded after the initial injection in the supine position to the right lateral decubitus, upright sitting, and sitting with right lateral leaning. Changes in blood pressure, heart rate, and any subjective complaints were noted. Changes in body position and additional agitated saline injections were tolerated. Right-to-left shunt (RLS) was detected in 35% of patients ( n  = 55). If the initial supine testing was negative, all subsequent positions/injections were also negative for RLS. However, if the supine injection was positive for RLS, the change in body positions increased the microbubble ( μ B) count in eight of 19 (42%) RLS-positive patients. The mean μ B count in RLS-positive patients was 20 (95% CI: 9–32). The use of three additional body positions increased the μ B count to 73 (95% CI: 13–132). The highest μ B yield was achieved in the upright sitting position. Our findings support the safety and feasibility of the expanded TCD protocol. If the initial supine Valsalva-aided contrast TCD test is negative, there may be no need to study the patient in additional positions. However, if μ B are detected in the supine position, additional testing for RLS in alternative positions may be found to be worthwhile.     

Paradoxical Brain Embolism as a Cause of Central Retinal Artery Occlusion: A Case Report

A 79-year-old right-handed woman was admitted to hospital following sudden onset of severe visual loss in the left eye. Left central retinal artery occlusion (CRAO) was diagnosed. Diffusion-weighted imaging showed an asymptomatic hyperintensity in left middle cerebral artery territory. Transcranial Doppler and transesophageal echocardiography revealed patent foramen ovale. No other embolic sources were identified in the carotid artery, aortic arch, or heart. We report herein a case of CRAO caused by paradoxical brain embolism.     

Stroke due to paradoxical embolism

We present a case of stroke in a young girl, preceded by a deep vein thrombosis and pulmonary embolism, both clinically asymptomatic, and accompanied by upper limb acute ischemia. Diagnosis of paradoxical embolism through a patent foramen ovale was made on clinical grounds and with contrast echocardiography. We discuss the main points leading to diagnosis, stressing the importance of contrast echocardiography. We also suggest that paradoxical embolism could be a more frequent cause of stroke than usually suspected.

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Sommario Presentiamo il caso di un ictus in una ragazza, preceduto da trombosi venosa profonda ed embolia polmonare, entrambi clinicamente asintomatici, ed accompagnato da ischemia acuta di un braccio. Abbiamo diagnosticato un'embolia paradossa attraverso un forame ovale pervio, sulla scorta dei dati clinici e dell'ecocardiogramma con mezzo di contrasto. Discutiamo poi le basi diagnostiche dell'embolia paradossa, sottolineando l'importanza dell'ecocardiografia con contrasto. Suggeriamo inoltre che l'embolia paradossa possa essere causa di ictus più frequentemente di quanto solitamente si sospetti.

     

Paradoxical Emboli from Calf and Pelvic Veins in Cryptogenic Stroke

PURPOSE: The increased prevalence of patent foramen ovale in patients with cryptogenic strokes suggests the occurrence of paradoxical embolism. The identification of deep venous thromboses (DVTs) in this population would strengthen this hypothesis. The purpose of this study was to image the subdiaphragmatic venous system in a cohort of patients with cryptogenic strokes. MATERIALS AND METHODS: In 37 patients with cryptogenic brain ischemia and interatrial communication, duplex studies of calf, popliteal, and femoral veins, and magnetic resonance imaging venograms of the pelvis veins were performed. RESULTS: In 10 patients, DVTs were diagnosed that were considered to be the cause of cryptogenic brain ischemia on probable (n = 6) or possible (n = 4) bases. In these patients, the median time from stroke to DVT was 3.25 days. In 5 of these 10 patients, DVTs did not involve popliteal and femoral veins, areas thought most important to pulmonary embolism, but instead were isolated to calf or pelvic veins. Although none of these 10 patients had abnormal blood hypercoagulation tests, 8 of the 10 did have clinical conditions suggesting predisposition to developing DVTs, such as concomitant neoplasms or pulmonary embolism. CONCLUSIONS: Increased evidence for paradoxical embolism may emerge when diagnostic strategies use multiple imaging methods and evaluate a broad extent of the subdiaphragmatic veins.     

Power M-Mode Transcranial Doppler for Diagnosis of Patent Foramen Ovale and Assessing Transcatheter Closure

BACKGROUND AND PURPOSE: Transcatheter closure of patent foramen ovale (PFO) can benefit from a less invasive diagnostic method than transesophageal echocardiography (TEE). Thirty-three gate power m-mode transcranial Doppler (pmTCD) was evaluated for its accuracy in diagnosis of PFO and utility in evaluating residual intracardiac right-to-left shunt (RLS) following transcatheter closure. METHODS: The sensitivity of pmTCD and single-gate TCD (sgTCD) to detect contrast bubble emboli through RLS was compared during transcatheter PFO closure. During 100 preclosure diagnostic evaluations and in 81 postclosure assessments, embolic tracks on pmTCD were counted following intravenous contrast injections and were graded using a 6-level logarithmic scale. The accuracy of TEE and pmTCD was separately compared to PFO anatomical findings during transcatheter closures. RESULTS: There were significantly more microemboli detectable on pmTCD (322 +/- 166; 95% confidence interval [CI], 388-257) than on sgTCD (186 +/- 109; 95% CI, 229-143; P < .001). McNemar change tests suggest that the diagnostic capabilities of pmTCD and TEE for detecting PFO are comparable and correspond to the anatomical findings determined during cardiac catheterization (P = .69 and .45, respectively). During 6-month postclosure evaluation (mean = 185 days), 66% of the patients demonstrated successful closure without significant RLS (ie, grades 0, I, or II), and 34% were found to have incomplete closure with significant RLS (ie, grades III, IV, or V). CONCLUSIONS: pmTCD provides greater sensitivity to contrast bubble emboli than does sgTCD. Among candidates for transcatheter closure, pmTCD provides an improved noninvasive method for diagnosing PFO and evaluating transcatheter closure.     

不明原因晕厥与心脏卵圆孔未闭高度相关

目的探讨不明原因晕厥与卵圆孔未闭的相关性。方法选取61例不明原因晕厥的门诊及住院患者,进行右心声学造影检查,筛查是否合并卵圆孔未闭,并对检查结果进行统计学分析,确定不明原因晕厥与卵圆孔未闭之间是否存在某种关联。结果 61例不明原因晕厥患者中46例(男21例,女25例)为心脏卵圆孔未闭患者(75.41%)。46例患者中,30例静息状态下及Valsalva动作后均发生右向左分流,16例仅在Valsalva动作后出现分流;少量分流7例,中量分流5例,大量分流34例;13例在运动中起病,22例在腹压变化时起病,11例在静息状态下起病。26例患者行经导管卵圆孔未闭封堵术治疗,术后随访1~6个月,仅有2例患者再发晕厥一次,余患者均未再发晕厥。结论心脏卵圆孔未闭为不明原因晕厥常见的诱因,不明原因晕厥与心脏卵圆孔未闭高度相关,不明原因晕厥患者应常规筛查心脏右向左分流。     

Almost Perfect Concordance Between Simultaneous Transcranial Doppler and Transesophageal Echocardiography in the Quantification of Right-to-Left Shunts

BACKGROUND AND PURPOSE: Transesophageal echocardiography (TEE) and transcranial Doppler (TCD) are the methods of choice to study patent foramen ovale (PFO), but there are discrepancies between the 2 concerning PFO detection. No study has analyzed right-to-left shunt (RLS) quantification concordance. The 2 methods are carried out in different hemodynamic states, and the Valsalva maneuver (VM) required in each also differs. The authors compared PFO detection and concordance of RLS quantification classifications performing the 2 studies simultaneously. METHODS: The authors prospectively included consecutive stroke patients undergoing TEE and applied the TCD protocol of the Consensus Conference. Echocardiographic PFO was diagnosed when at least 3 microbubbles (MBs) were detected in the left atrium within 3 heartbeats after opacification of the right atrium. RLS quantification was (1) TCD: minimum (1-10 MBs), moderate (11-25 MBs), and massive (>25 MBs) and (2) TEE: small (3-10 MBs), moderate (11-30 MBs), and large (>30 MBs). Statistics: contingency tables (chi(2) and K test). Results. The authors studied 110 patients whose mean age was 56.7 +/- 12.1 years, and 60.9% were men. PFO was detected at the first VM in 30% of patients with TCD and in 31.8% with TEE. At the second VM, both methods detected the same patients (32.7%). RLS was minimum (14), moderate (5), and massive (17) in TCD and small (13), moderate (3), and large (20) in TEE. There was an almost perfect concordance in RLS quantification (K = 0.928, P = .001), with only 4 discrepancies. CONCLUSIONS: Simultaneous study with TCD and TEE showed an almost perfect concordance in PFO detection and RLS quantification.     

Paradoxical Brain Embolism From Thrombus Associated With Vena Caval Filter in a Patient With Cancer

A 71-year-old man experienced sudden onset of hemiparesis and aphasia. He had a 4-month history of gallbladder cholangiocarcinoma, complicated with a postoperative deep-vein thrombosis (DVT) that necessitated a vena caval filter placement. Diffusion-weighted magnetic resonance imaging of the brain showed multiple hyperintense foci. Magnetic resonance spectroscopy was compatible with cerebral infarction. Abdominal computed tomography showed a thrombus in the inferior vena cava extending through the filters. A transcranial Doppler bubble study revealed the presence of a right-to-left shunt. Paradoxical cerebral embolism must be considered in patients with DVT who have new onset neurologic deficits even in the presence of a caval filter.     

Transesophageal echocardiography in patients less than 60 years of age without obvious cardiac source of embolism

Abstract

Minor potential cardioembolic sources of stroke such as atrial septal aneurysms (ASA) or patent foramen ovale (PFO) are important risk factors for cryptogenic stroke. We aim to determine the prevalence of these abnormalities through an exhaustive etiological workup including transesophageal echocardiography and cervical arteries assessment in stroke patients younger than 60 years of age who had no evidence of a significant source of embolism. We classified 118 stroke patients into four groups according to transesophageal echocardiography (TEE) and cervical arteries assessment findings. Group A, consisted of 30 (25.4%) patients who had an arteriopathy likely related to stroke without any cardiac abnormality; Group B, 49 (41%) patients who had only a potential cardiac source; Group C, 9 (7.6%) patients who had an obvious arterial source of stroke and incidental cardiac abnormalities, and Group D, 30 (25.4%) patients who had neither cardiac nor arterial source. Data were analysed with X2 test for the comparison of risk factors between groups. Variance analysis was used to compare age between groups. Significance was assessed as p <0.05. ASA represented 56.8% of the cardiac abnormalities and was diagnosed in 35.4% of the 79 patients who had an unexplained stroke (B and D). A PFO was found in 34.1% of the patients who had a cryptogenic stroke (B and D). According to Fisher's exact test, ASA was significantly associated to PFO (p"0.001). According to this selection one fourth of the patients might have a truly cryptogenic stroke as the etiological workup failed to demonstrate any source of stroke. Comparison between groups showed that the patients in whom an arterial source was detected also had a potential cardioembolic source in 23% of the cases (G), versus 62% in patients who had no arterial source (B and D) (p = 0.0007). Our study confirmed the strong association between ASA, PFO and stroke. Although there was a lower incidence of minor potential cardioembolic sources in patients who had a cervical artery disease, we suggest a systematic TEE screening in all patients with stroke without major cardiac source, in order to ensure a better prevention. [Neurol Res 1995; 17: 368-372]     

Silent brain embolism during transcatheter closure of patent foramen ovale: a transcranial Doppler study

Abstract The aim of this report is to quantify the amount of spontaneous microembolism detected in brain vessels by transcranial Doppler (TCD) during transcatheter closure of right-to-left shunt (RLS). We examined 29 patients who had had a stroke or a transient ischaemic attack (17 females and 12 males; mean age 45±15 years). They all underwent TCD monitoring during the procedure and microembolic signals (MES) were recorded. Detection of MES was distributed as follows: during femoral catheterisation in 8 patients (25%), during atrial catheterisation in 5 patients (17%), during transeptal crossing in 14 patients (48%), during left disc opening in 28 patients (96%) and during right disc opening in 7 patients (24%). The highest rates of MES were observed during left disc opening and less during transeptal crossing with an average count of 31 (range 3–135) and 3 (range 1–18) respectively. Brain embolism occurs throughout the procedure after femoral catheterisation for PFO closure. Our results indicate that the majority of MES reached the brain during the opening of the left disc in the left atrium: 28/29 patients exhibited MES with an average of 31 (3–135), thus supporting the notion that gas embolism accounted for the findings.     

反常性栓塞风险量表在合并卵圆孔未闭的隐源性卒中或短暂性脑缺血发作患者中的应用

目的 描述卵圆孔未闭（patent foramen ovale,PFO）造成反常性栓塞（paradoxical embolism,PE）的临
床表现、影像学特点。验证反常性栓塞风险量表（Risk of Paradoxical Embolism,RoPE）评分。
方法 本研究为单中心观察性研究,连续性入选2013年1月～2014年6月首都医科大学附属北京天
坛医院神经科收治的隐源性卒中或短暂性脑缺血发作（transient ischemic attack,TIA）患者79例,其
中经经颅多普勒超声发泡试验（contrast-enhanced transcranial Doppler,cTCD）和经食管超声心动图
（transesophageal echocardiography,TEE）确诊合并PFO的患者44例,其中37例为PFO所致PE,7例仅合并
PFO无栓塞症状。由另一名神经科医师盲法评价颅脑磁共振成像,确定其影像学的特点,收集两组
患者的人口学信息,临床资料,相关辅助检查（如cTCD、TEE、颈部血管超声及双下肢静脉超声结果）,
计算并比较两组RoPE评分情况。PFO所致PE患者根据PFO大小分为3组,依据右向左分流量（rightto-
left shunt,RLS）大小分为3组。比较不同PFO大小和不同RLS患者之间的临床和影像学特点,并评
估不同PFO大小和不同RLS之间的关联性及RoPE评分与PFO的大小和RLS的严重程度之间的关系。
结果 两组的RoPE评分分别为5（4.5,7.0）和6（4.0,8.0）,差异无显著性（P＞0.05）。合并颈内
动脉重度狭窄或闭塞,高度提示非PFO相关缺血性卒中（P＜0.01）。小PFO组（＜2 mm）和中/大PFO组
（≥2 mm）相比较,两组的RoPE评分分别为（5.5±1.9 vs 6.3±2.0,P＞0.05）,后者更容易累及后循
环。不同RLS患者之间相比较,3组的RoPE评分分别为（5.4±1.7,6.5±2.7,5.8±2.0,P＞0.05）。PFO
大小和RLS之间无显著性相关（r =0.031,P＞0.05）。
结论 PFO和脑梗死的关系可以分为：无相关性（即PFO合并存在）或有相关性（即PE）,PE的影像学
特点和PFO大小有一定的相关性。RoPE可能有助于进一步区分PFO的大小和RLS的严重程度。