Presence Of Right-to-left Shunt Research Articles

High Eosinophil Rates in Patients With Right-to-Left Shunts: An Expected Role, or an Unexpected Risk?

Background and objectiveEosinophils are associated with thromboembolic events. Since eosinophils are eliminated in the pulmonary vasculature, right-to-left shunt (RLS) through patent foramen ovale may increase eosinophils in the peripheral blood. In this report, we evaluated the eosinophils of patients with regard to the presence of RLS and its quantity.Patients and methodsIn this retrospective observational study, we analyzed the complete blood cell count (CBC) of patients with RLS (n=47) and without RLS (n=31) diagnosed by contrast echocardiography (CE). RLS was identified as mild (5-10 bubbles) and moderate shunt (10-25 bubbles).ResultsAge and CBC were not significantly different between the groups, with the exception of eosinophils. Patients with RLS had higher eosinophils percentage compared to patients without RLS (3.1 ±1.5 vs. 1.7 ±0.7, p=0.001). Additionally, eosinophils percentage was significantly higher in the mild RLS group (2.4 ±0.9 vs. 1.7 ±0.7, p=0.016) and the moderate RLS group (4.3 ±1.6 vs. 1.7 ±0.7, p=0.001) compared to normal subjects. Also, it was significantly higher in the moderate RLS group compared to the mild group (4.3 ±1.6 vs. 2.4 ±0.9, p=0.001).ConclusionsEosinophils percentage was higher in patients with mild and moderate RLS compared to normal individuals. Moreover, the eosinophil rate was higher in patients with moderate RLS than in patients with mild RLS.

Clinical features of right-to-left shunt in the different subgroups of migraine.

ObjectiveSeveral investigations have documented an association between migraine and right‐to‐left shunt (RLS). However, whether there are specific clinical features that can distinguish between migraine patients with and without RLS is unclear. This study aims to explore whether there are specific clinical features that can distinguish between migraine patients with and without RLS, and to investigate the relationship between the degree of shunt and clinical parameters of headache.MethodsIn this study, we enrolled consecutive migraineurs who underwent a structured, standardized questionnaire for family and personal history and for detailed migraine features. RLS was diagnosed based on a contrast enhancement transcranial Doppler (c‐TCD) examination.ResultsOverall, 113 migraine with aura (MA) and 192 migraine without aura (MO) patients were included. Patients with MA and RLS (MARLS+) had a higher frequency for sensory aura symptoms than those with MA without RLS (MARLS−) (27.4% vs. 10.0%, p = .03). Patients with MO and RLS (MORLS+) presented with significantly younger initial age of migraine onset and experienced more severe pain intensity than those with MO without RLS (MORLS−) (mean ± SD, 25.6 ± 8.9 vs. 29.8 ± 12.7 years, p = .008 and 5.9 ± 1.4 vs. 5.3 ± 1.3, p = .006, respectively). There was no relationship between the degree of shunt and the clinical parameters of headache.ConclusionsOur results indicate that MO patients presented with a younger initial age of migraine onset and that sensory aura symptoms in MA patients may predict the presence of RLS. However, we did not find support for relationship between the degree of shunt and clinical parameters of headache.

Right-to-Left Shunt and the Clinical Features of Migraine with Aura: Earlier but Not More

Background: The causal relationship between patent foramen ovale (PFO) and migraine with aura (MA) is controversial. We aimed at exploring whether attack clinical features relate to the presence of right-to-left shunt (RLS) in MA patients. Methods: We retrospectively examined a cohort of consecutive patients diagnosed with MA in our headache center and undergoing transcranial doppler (TCD) for RLS detection. We collected from our clinical electronic dossiers, clinical features of MA attacks (type, frequency, duration of aura phenomenon, trigger factors, onset age), family history for MA, thrombophilia genotypes, and the response to preventive treatments. RLS was stratified for severity according to the results of the TCD examination. Results: We found 111 patients. Binary logistic regression analysis showed that among features of MA attacks, only onset age was associated with the presence of RLS (p < 0.0001). Patients with RLS presented the first MA attack at a younger age (p < 0.0001). The greater RLS severity, the younger was onset age (p < 0.00001) and the presence of atrial septal aneurysms (ASA) was associated with a further decrease in onset age (ρ = –539, p < 0.00001). Family history for MA was associated with the presence of RLS (chi-square p = 0.022). Response to preventive treatments was not influenced by the type of treatment (antiplatelet compared with no antiplatelet drugs), comorbidity with migraine without aura, RLS presence, or by their double interactions (Logistic regression, consistently p > 0.05). Conclusion: Our findings support the hypothesis that although PFO does not influence MA attack frequency, it is not merely a bystander in MA physiopathology, as RLS, its severity, and the presence of ASA possibly make a difference in the disease history.

Right-to-left shunt and idiopathic sudden sensorineural hearing loss.

SUMMARYIn the present retrospective cohort study, we investigated the association between idiopathic sudden sensorineural hearing loss (ISSNHL) and right-to-left shunt (RLS). For this study, we recruited 40 patients with ISSNHL treated in our department between January 2015 and January 2016. Inclusion criteria were: ≥ 18 years old, unilateral sensorineural hearing loss diagnosed within 2 weeks after onset, unknown cause, no previous surgery in the respective ear and no fluctuation in hearing loss. All patients underwent a pure-tone audiogram and a trans-cranial Doppler ultrasonography (TCD) with contrast saline (c-TCD) and received hyperbaric oxygen (HBO) and concomitant steroid therapy. C-TCD examination detected the RLS in 20 patients (50%). ISSNHL patients with RLS were younger than those without RLS (p = 0.007). Vertigo was present mainly in the RLS group, while hypercholesterolaemia, arterial hypertension and hyperglycaemia were mainly seen in the “no RLS” group. The proportion of complete recovery was highest in the “No RLS” Group (40%), although it was not statistically significant. In conclusion, RLS is frequent in ISSNHL, particularly in young patients without comorbidities and with associated dizziness, who should routinely undergo TCD to exclude the presence of RLS. Unfortunately, TCD can only detect the RLS, and not the location of the shunt. This would be possible through transesophageal echocardiography (TEE) or intracardiac echocardiography (ICE), which are much more invasive than TCD, and require further study.

Modified Right Heart Contrast Echocardiography Versus Traditional Method in Diagnosis of Right-to-Left Shunt: A Comparative Study.

SummaryBackgroundThe purpose of this study was to evaluate the reliability, effectiveness, and safety of modified right heart contrast transthoracic echocardiography (cTTE) in comparison with the traditional method.Material/MethodsWe performed a modified right heart cTTE using saline mixed with a small sample of patient’s own blood. Samples were agitated with varying intensity. This study protocol involved microscopic analysis and patient evaluation. 1. Microscopic analysis: After two contrast samples had been agitated 10 or 20 times, they underwent a comparison of bubble size, bubble number, and red blood cell morphology. 2. Patient analysis: 40 patients with suspected RLS (right- to-left shunt) were enrolled. All patients underwent right heart contrast echocardiography. Oxygen saturation, transit time and duration, presence of RLS, change in indirect bilirubin and urobilinogen concentrations were compared afterward.ResultsModified method generated more bubbles (P<0.05), but the differences in bubble size were not significant (P>0.05). Twenty-four patients were diagnosed with RLS (60%) using the modified method compared to 16 patients (40%) with the traditional method. The transit time of ASb20 group was the shortest (P<0.05). However, the duration time in this group was much longer (P<0.05). Also, in semi-quantitative analysis mean rank of RLS was higher after injecting the modified contrast agent agitated 20 times (P<0.05).ConclusionsModified right heart contrast echocardiography is a reliable, effective and safe method of detecting cardiovascular RLS.

Juxtacortical Spots on Fluid-Attenuated Inversion Recovery Images in Cryptogenic Transient Ischemic Attack

Background and PurposeJuxtacortical spots are detected frequently on fluid-attenuated inversion recovery (FLAIR) images, but have not been extensively researched in patients with transient ischemic attack (TIA). We hypothesized that juxtacortical spots on FLAIR images are partly associated with right-to-left shunt (RLS) in TIA without clear etiology. The possibility of an association between the presence of RLS and juxtacortical spots on FLAIR images in patients with TIA without clear etiology was investigated, and the imaging findings of patients with and without RLS were compared.MethodsThis was a retrospective study of TIA patients who visited our tertiary stroke center consecutively within 72 hours of TIA onset. Cryptogenic TIA was defined as no clear etiology despite a routine diagnostic workup. The presence of RLS was examined by transcranial Doppler with an agitated saline test or transesophageal echocardiography. Juxtacortical spots were defined as small and round hyperintensities in the juxtacortex on FLAIR images, excluding white-matter hyperintensities.ResultsOf the 132 patients with cryptogenic TIA examined for this study, 70 (53.0%) had RLS. Juxtacortical spots on FLAIR images were detected more frequently in patients with RLS than in those without. The independent factors for the presence of juxtacortical spots were RLS [odds ratio (OR)=3.802, 95% confidence interval (95% CI)=1.74-8.2; p=0.001] and age (OR=1.058, 95% CI=1.01-1.10; p=0.004) by multivariate analysis. The number of juxtacortical spots was significantly higher among patients with a moderate-to-large RLS than in those with a small or no RLS.ConclusionsThe findings of the present study demonstrate a significant association between the presence of RLS and the occurrence of juxtacortical spots on FLAIR images in patients with cryptogenic TIA.

Transcranial Doppler with Bubble Study as a Method to Detect Extracardiac Right‐to‐Left Shunts in Patients with Ischemic Stroke

Paradoxical embolism through extracardiac right-to-left shunts (ECRLS) may represent an under-detected stroke mechanism. Stroke patients without evidence of cardiac right-to-left shunt (RLS) on echocardiogram may benefit from transcranial Doppler with bubble study (TCD-b) to aid in recognition of stroke etiology. This study assesses the usefulness of TCD-b in the stroke evaluation. Retrospective cohort study of consecutive patients undergoing TCD-b performed in our neurovascular laboratory from February 2005 to August 2009. Echocardiography results were reviewed in patients with positive TCD-b. Detailed medical record review was performed on patients with positive TCD-b and negative echocardiogram findings for RLS. Of 502 patients undergoing TCD-b, 48.4% (n = 243) had a positive study suggesting the presence of RLS. Of these, 59.2% (n = 144) had an echocardiogram demonstrating a cardiac RLS, 26% (n = 63) had echocardiograms without evidence of cardiac RLS, and 14.8% (n = 36) had no echocardiogram. Data on the evaluation to determine source of potential shunting in patients with discrepant findings was available in 11(17.5%). Of these, 63.6% (7/11) had potential mechanisms for positive TCD-b: one pulmonary arteriovenous malformation (AVM), one arteriovenous fistula thrombus, one parietal AVM, and four had malignancy. TCD-bubble studies may prove useful in uncovering treatable causes of stroke.

Right‐to‐left shunts as a cause of juxtacortical spots in patients with migraine

Juxtacortical spots on fluid-attenuated inversion recovery (FLAIR) images can be frequently detected in patients with migraine. However, the origins of the cerebral lesions (including juxtacortical spots on FLAIR images) found in the previous studies are not known. We sought to investigate the association between juxtacortical spots on FLAIR images and right-to-left shunt (RLS) in migraine patients. Juxtacortical spots on FLAIR images were arbitrarily defined as small areas of hyperintensities in the juxtacortex and cortico-subcortical junction. The presence of RLS was examined by a transcranial Dopper (TCD) with the agitated saline test. The degree of RLS was categorized into four grades according to the number of microemboli: no shunt, <10 microbubbles (MB), >10 MB single spots pattern, and >10 MB shower/curtain pattern. We compared the results for migraine patients (n = 49) with those for healthy controls (n = 49). Juxtacortical spots on FLAIR images occurred in 38/98 subjects; of them, 27/49 (55.1%) had migraines and 11/49 (22.2%) were healthy controls (P = 0.002). The independent factors associated with juxtacortical spots on FLAIR images were female, migraine patients, and RLS by multivariate analysis. In migraine patients, RLS was independently associated with juxtacortical spots on FLAIR images. Our results suggest that juxtacortical spots on FLAIR images were frequently found in migraine patients and might be associated with the presence of RLS in those patients. Further studies are needed to assess whether juxtacortical spots have clinical implications in patients with migraine.

Right-to-left shunts may be not uncommon cause of TIA in Japan

Background and purposeAlthough 30% to 60% of transient ischemic attacks (TIAs) have embolic sources, the etiology of the remaining TIAs is unknown. Right-to-left shunt (RLS) is one of the most important etiologies of cryptogenic stroke. The aim of this study was to determine whether RLS is related to transient ischemic attack (TIA) of unknown etiology. MethodsWe performed transesophageal echocardiography (TEE) and/or transcranial Doppler (TCD) studies for consecutive TIA patients in order to detect RLS from April 2004 to December 2006. TIA patients were divided into three groups, as follows: 1) Cardioembolic TIA, with a patent cardioembolic source, 2) thrombotic TIA, with an atherothrombotic and/or lacunar mechanism, and 3) undetermined TIA, without identified cause of TIA. We compared the characteristics and presence of RLS among these three groups. ResultsWe enrolled 124 TIA patients (age: 67±13 years old, 80 men). There were 13 patients with Cardioembolic TIA, 25 with Thrombotic TIA, and 86 with Undetermined TIA. TEE and/or TCD were able to detect RLS in 61 of the 124 (49%) patients. RLS was frequent in patients with Undetermined TIA compared with those in the other TIA groups (60% in the Undetermined TIA group, 28% in the Thrombotic TIA group, and 15% in the Cardioembolic TIA group; p<0.001). Smoking and previous history of TIA were frequent in the Thrombotic TIA group (p=0.030 and p=0.016, respectively). ConclusionRLS may play an important role in the etiology of TIA of undetermined cause.

Ischaemic stroke with malignancy may often be caused by paradoxical embolism

Background: Although ischaemic stroke with malignancy occasionally occurs, the mechanisms of stroke in such cases have not been investigated in detail. Objective: To examine the mechanisms of ischaemic stroke with...

Prevalence of right–to–left shunt in patients with cluster headache

Recent investigations documented that the prevalence of right–to–left shunt (RLS) in patients with migraine with aura (MA) is significantly higher than in healthy controls and similar to prevalence of RLS in young patients with cryptogenic stroke (CS). Nevertheless, little data are available in the literature about RLS prevalence in the other forms of primary headache. The aim of this study was to investigate the occurrence of RLS in patients with cluster headache (CH). We enrolled 30 consecutive patients with CH diagnosis according to the IHS criteria and 40 controls. RLS was assessed with bilateral transcranial Doppler contrast (TCDc) monitoring of middle cerebral arteries. Eleven patients (37%) resulted positive to TCDc monitoring for evaluation of RLS. These data show that the presence of RLS in this group is more prevalent than in the general population and similar to that found in MA and in CS.

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.