Cryptogenic Ischemic Stroke Research Articles

Differential Lesion Patterns on T2-weighted Magnetic Resonance Imaging and Fluid-attenuated Inversion Recovery Sequences in Cryptogenic Stroke Patients with Patent Foramen Ovale

The present study aimed to determine lesion patterns and the stroke mechanisms in cryptogenic ischemic stroke patients with patent foramen ovale (PFO) on T2-weighted magnetic resonance imaging (T2WI) and fluid-attenuated inversion recovery (FLAIR) sequences combined. In this retrospective study, 38 patients with cryptogenic stroke and an isolated PFO compared with 51 cryptogenic stroke patients without PFO were evaluated and their characteristics of lesion patterns on T2WI and FLAIR sequences combined were investigated. The number, distribution of small ischemic lesions, and the frequency of multiple small ischemic lesions were analyzed between the 2 groups. Thirty-two of 38 patients had a total of 341 small ischemic lesions in cryptogenic stroke patients with PFO versus 24 of 51 patients with 156 small ischemic lesions in patients without PFO, and, 8.97±7.91 and 3.19±4.82 ischemic lesions per person, respectively. Multiple small ischemic lesions occurred more frequently in cryptogenic stroke patients with PFO (25 of 38 patients, 66%) than in patients without PFO (16 of 51 patients, 31%; P=.001). Subcortical frontal and parietal small lesions were more frequent in cryptogenic stroke patients with PFO (28 of 38 patients, 74%) than in patients without PFO (18 of 51 patients, 35%; P<.0001). Multiple small ischemic lesions and subcortical frontal and parietal small lesions were significantly associated with cryptogenic stroke patients with PFO, suggesting that paradoxical embolism may be the mechanism of PFO-associated cryptogenic stroke patients.

Paroxysmal atrial fibrillation occurs often in cryptogenic ischaemic stroke. Final results from the SURPRISE study

Atrial fibrillation (AF) increases the risk of stroke fourfold and is associated with a poor clinical outcome. Despite work-up in compliance with guidelines, up to one-third of patients have cryptogenic stroke (CS). The prevalence of asymptomatic paroxysmal atrial fibrillation (PAF) in CS remains unknown. The SURPRISE project aimed at determining this rate using long-term cardiac monitoring. Patients with CS after protocolled work-up including electrocardiography (ECG) and telemetry were included after informed consent. An implantable loop recorder (ILR) was implanted subcutaneously. PAF was defined by events of atrial arrhythmia >2min with a correlating one-lead ECG confirming the diagnosis. Eighty-five patients were monitored for a mean of 569days (SD ±310). PAF was documented in 18 patients (20.7%) during the study period and detected by ILR in 14 patients (16.1%). In three patients PAF was detected by other methods before or after monitoring and was undiscovered due to device sensitivity in one case. The first event of PAF was documented at a mean of 109days (SD ±48) after stroke onset. PAF was asymptomatic in all cases and occurred in episodes lasting predominantly between 1 and 4h. Four recurrent strokes were observed, three in patients with PAF; all three patients were on oral anticoagulation (OAC). One in five patients with CS had PAF, which occurred at low burden and long after stroke. Future studies should determine the role of implantable cardiac monitors after stroke and determine the potential therapeutic benefit of OAC treatment of patients with PAF.

Prime Time for Dissecting the Entity of Cryptogenic Stroke

See related article, p 1186. The term cryptogenic ischemic stroke (or stroke of undetermined pathogenesis) encompasses ischemic strokes without specific cause detected after adequate diagnostic workup. Cryptogenic stroke is, thus, a diagnosis done by exclusion. Strokes may remain cryptogenic if diagnostic evaluation is incomplete for one or another reason or in the presence of multiple competitive causes, such as atrial fibrillation (AF) and atherosclerotic stenosis in an ipsilateral relevant artery. Choosing the particular diagnostic investigation should always be balanced between the cost and potential yield, considering patient characteristics and the effect on treatment decisions. The only patients with stroke in whom thorough pathogenic workup may be unnecessary are those whose poor prognosis cannot be improved reasonably by pathogenic diagnosis. A substantial proportion of all strokes end up being cryptogenic. Among the 5017 patients in the German Stroke Data Bank, cryptogenic strokes accounted for 23%.1 Notably, the cryptogenic category is even larger among younger patients reflecting major challenges in defining their pathogenesis and interpreting causally relevant findings. A total of 40% of patients aged <50 years remained without elusive cause for their stroke in a recent large multicenter survey.2 Furthermore, another prospective study with MR-imaged patients aged <55 years showed higher rates of cryptogenic strokes with lower age.3 There is paucity of data to guide secondary prevention after cryptogenic stroke. Current guidelines either did not give statements specifically on cryptogenic stroke or recommended antiplatelet therapy.4,5 Anticoagulation (warfarin with target international normalized ratio, 1.4–2.8) has been compared against aspirin (325 mg/d) only in 1 …

Serum Albumin Levels Are Associated With Cardioembolic and Cryptogenic Ischemic Strokes

Low serum albumin concentrations have been associated with increased stroke risk, but the underlying mechanisms are less well studied. We aimed to investigate the association between serum albumin levels and ischemic stroke etiologies in a large, population-based, multiethnic, prospective, cohort study. Participants from the Northern Manhattan Study (NOMAS; n=2986; mean age, 69±10 years) free of stroke at baseline were followed for incident stroke (a median follow-up of 12 years). Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for baseline serum albumin levels and risk of ischemic stroke and ischemic stroke subtypes after adjusting for vascular risk factors. The mean baseline serum albumin level was 4.42±0.33 g/dL. There were 271 ischemic strokes during follow-up. Participants with serum albumin levels of 2.7 to 4.2 g/dL (the lowest tertile) had increased risk of all stroke (HR, 1.76; 95% CI, 1.32-2.35), ischemic stroke (HR, 1.67; 95% CI, 1.21-2.29), cardioembolic stroke (HR, 1.92; 95% CI, 1.10-3.34), and cryptogenic stroke (HR, 2.59; 95% CI, 1.21-5.53), compared with those with levels of 4.6 to 5.5 g/dL (the top tertile; reference). Low albumin levels (2.7-4.2 g/dL) were not associated with large vessel or lacunar stroke. Our study shows an association between low serum albumin levels and ischemic stroke, particularly cardioembolic and cryptogenic subtypes. These results suggest the potential shared pathophysiological relationship between low serum albumin levels, cardiac embolism, and cryptogenic infarction, which warrants further investigation.

Abstract 23: Neuroimaging and Echocardiographic Predictors of Paroxysmal Atrial Fibrillation on Outpatient Mobile Cardiac Outpatient Telemetry in Cryptogenic Ischemic Stroke and TIA Patients

Background: The objective of our study was to identify factors on MRI neuroimaging and echocardiography as part of routine workup of patients with cryptogenic ischemic stroke (IS) or transient ischemic attack (TIA) to identify those patients who are likely to have paroxysmal atrial fibrillation (PAF) as detected by subsequent outpatient mobile cardiac outpatient telemetry (MCOT). Methods: All cryptogenic IS or TIA patients seen at Emory University Hospital and The Emory Clinic from 2009-2013 and who underwent outpatient MCOT were included in this analysis.Using logistic regression, we analyzed the association between lesions seen on MRI FLAIR sequences with PAF and categorized them as the following: Cortical lesions (CL), defined as T2-hyperintense cortical-based infarcts; high subcortical (HS) T2-hyperintense lesions, defined as &lt;5mm beneath the cortex without any cortical involvement, or none. Left atrium (LA) functional and dimensional echocardiographic parameters were evaluated to determine their association with PAF. Results: Of 132 patients included in this analysis, 17 (13%) had evidence of newly diagnosed PAF on MCOT (mean duration of monitoring=25 days); median age was 72 (IQR: 64-79), 50% were women, diabetes was present in 23%, hypertension in 76%, dyslipidemia in 64%, and active tobacco use in 8%. CL seen on baseline MRI were found to be significant predictors of PAF (OR 5.2, 95 % CI: 1.3-19; p=0.01). HS lesions were not found to be a significant predictor of PAF. On baseline echocardiography, patients who had PAF (vs non-PAF) had significantly higher mean LA diameter (4.2 vs 3.7 cm, p=0.03), lower tissue Doppler velocity (a’) (5.5 vs 13.5 cm/s, p=0.03), a trend toward higher left atrium volume index (LAVI) (37.5 vs 29.2, p=0.07) and mean LAVI/late diastolic Doppler velocity (A) (0.67 vs. 0.37, P= 0.006). The Areas under the Curve (AUC) for the parameters were: LA diameter 71.4%, a’ 92.6%, LAVI 74.6%, LAVI/A 62.5%, LAVI/a’ 67.9%. Conclusion: Cortical-based infarcts seen on MRI FLAIR sequences and baseline echocardiographic variables may help to predict cryptogenic ischemic stroke or TIA patients who are likely to have PAF identified on outpatient MCOT.

Abstract 24: Predictors of Occult Atrial Fibrillation in Cryptogenic Stroke

Background and Purpose: Prolonged cardiac monitoring may identify paroxysmal atrial fibrillation (AF) in patients with cryptogenic stroke. We aimed to identify clinical, echocardiographic, and neuroimaging features which may increase the efficiency of detecting AF on cardiac monitoring. Methods: We studied a retrospective cohort of 227 subjects with cryptogenic ischemic stroke referred for 28 day mobile cardiac outpatient telemetry (MCOT). Patients with large artery disease or high risk sources of cardioembolism were excluded. We reviewed medical records, brain images, and echocardiograms, blinded to MCOT results. Acute and/or chronic infarctions were characterized by size, location, and as cortical, subcortical, or both; wedge-shaped; lacunar; borderzone; and/or multiple territories. Cardiac features included left atrial (LA) size, ejection fraction, aortic arch atheroma, and PFO. Variables were tested in univariate analyses and further incorporated in a multivariate logistic regression model to determine independent predictors of detecting AF. Results: The cohort age was 62.9±2.9 years, 42% were men, and 53% were white. Median CHADS was 3 and CHADS2Vasc was 5. Infarcts were &gt;1.5 cm in 62% of subjects, predominantly cortical in 47%, subcortical in 39%. Only 9% were single, deep, and &lt;1.5 cm. LA size was 3.6±0.7 cm and ejection fraction was 61±9%. MCOT detected AF in 30 (13%) patients. In multivariate analysis, AF was only associated with age&gt;60 (OR 3.6 [1.2-10.4], p=0.02) and prior (chronic) cortical or cerebellar infarction (OR 3.3 [1.3-8.6], p=0.013) (C-statistic 0.72). There was no association with any other clinical, echocardiographic, or radiographic parameter. AF was detected in 32% of patients with age &gt;60 and the presence of prior cortical or cerebellar infarction, compared to 4% with neither of these factors. Conclusion: Atrial fibrillation is detected on MCOT in a substantial minority of cryptogenic stroke patients. Age&gt;60 and the presence of prior cortical or cerebellar strokes are predictive of detecting AF in these patients. Other brain and cardiac characteristics were not found to be helpful. These data may aid in the selection of patients for prolonged arrhythmia monitoring.

Factor V Leiden does not have a role in cryptogenic ischemic stroke among Iranian young adults.

Background:Different risk factors have been suggested for ischemic stroke in young adults. In a group of these patients despite of extensive diagnostic work-up, the primary cause remains unknown. Coagulation tendency is accounted as a possible cause in these patients. Previous studies on factor V Leiden (FVL) as the main cause of inherited thrombophilia for clarifying the role of FVL in stroke have resulted in controversial findings. The current study investigates the role of this factor in ischemic stroke among Iranians.Materials and Methods:This case-control study was performed between September 2007 and December 2008 in Isfahan, Iran. The case group comprised of 22 patients of which 15 were males and 7 were females with age range of ≤50 years, diagnosed as ischemic stroke without classic risk factors and the control group consisted of 54 healthy young adults. After filling consent form, venous blood samples were obtained and sent to the laboratory for genetic examination.Results:No FVL mutation was found in the case group. There was one carrier of the mutation as heterozygous in the control group (relative frequency = 1.85%).Conclusions:Based on our study, FVL might not be considered as an independent risk factor for ischemic stroke in Iranian individuals who are not suffering from other risk factors of ischemic stroke.

Abstract 16646 : The Left Atrium Emptying Fraction Improves Diagnosis of Paroxysmal Atrial Fibrillation after Cryptogenic Ischemic Stroke: Results from The SURPRISE Study

Tor Biering- Sorensen, 2013 Finalist and Presenting Author

Multidisciplinary management of patent foramen ovale (PFO) and cryptogenic stroke/TIA

PurposePatent foramen ovale (PFO) has been implicated as a risk factor for cryptogenic ischemic stroke (CS). However, there is still a lack of widely accepted, undisputed indications for PFO closure. The present study describes the concept of the multidisciplinary PFO conference and a decision making process for closure versus no closure that was developed into a formalized clinical algorithm, and presents the results of implementing these, in terms of number and proportion of PFO closures as well as repeat referrals.DesignFive specialists in neurology, cardiology, internal medicine, thromboembolism, and echocardiography evaluated the clinical data of 311 patients at PFO conferences during 2006 to 2009. The main criteria for closure were patients with first-ever CS with PFO and atrial septal aneurysm, or patients with recurrent CS and PFO without atrial septal aneurysm.ResultsA total of 143 patients (46%) were accepted for closure and 167 patients were rejected. Patients accepted for closure were younger (mean 50 years versus 58 years) (P < 0.001). The acceptance rate for PFO closure was similar throughout these years, with an average of 45%. Three of 167 patients (1.8%) initially rejected for PFO closure were re-referred due to recurrent stroke, and the PFO closure was subsequently performed.ConclusionThe acceptance rate of less than 50% in the present study underscores the complex relationship between CS and PFO. Whatever the criteria used for PFO closure, any unit caring for these patients needs to have a rigorous process to avoid overtreatment as well as undertreatment and to ensure that personal preferences and economic incentives do not steer the selection process. Our algorithm provides a stable acceptance rate and a low rate of repeat referrals.

Detection of paroxysmal atrial fibrillation by an implantable subcutaneous holter in patients with non-lacunar cryptogenic ischemic stroke

Atrial Fibrillation (AF) is often paroxysmal and asymptomatic, and yet associated with a high risk of stroke. Finding AF after an ischemic cerebral event needs prescription of oral anticoagulants to reduce the risk of stroke recurrence. A 24-hour ECG monitoring has poor sensitivity for detection of paroxysmal AF (PAF) but the optimum duration of ECG monitoring is not known. Study: We hypothesized that asymptomatic PAF may be an under-recognized mechanism for cryptogenic ischemic stroke. So that, ECG monitoring by an implantable subcutaneous Holter and remote transmission may find episodes of PAF in patients with non-lacunar cryptogenic ischemic stroke. Inclusion criteria were sinus rhythm on 12-lead ECG on admission, no evidence of PAF in a 24 h ECG monitoring and freedom of structural heart disease. Embolism was further suspected by transcranial Duplex ultrasound and/or neuroimaging features. Results: One hundred and one patients have been followed up for a median 262 days (IQR: 119-471). Mean age was 67±13 years and 46% were male. Cardiovascular risk factors were: hypertension (56%), dislipidemia (32%), diabetes (18%) and smoking habit (37%). Median CHA2DS2-VASc Score was 2.5 (IQR: 1-4). Twenty-seven patients (27%) were previously on antiplatelet agent treatment. PAF (lasting more than 2 minutes) was present in 29 patients (28.7%). The first PAF episode was detected after 131 days (IQR: 50-240) of remote monitoring. PAF episodes were mainly at night in 9 patients, longer than 1 hour in 11 patients and the heart rate was below 100 bpm in 9 patients. The table shows the different profile of patients with PAF vs PAF free patients. View this table: Profile of patients with PAF vs PAF free patients Conclusions: In patients with ischemic cryptogenic stroke long ECG monitoring by an implantable subcutaneous Holter and remote transmission detects a significant rate of asymptomatic PAF. The actual pathological relevance of this finding is still unknown, so that wider controlled studies may be appropriate.

Differences of morphological and functional characteristics of patent foramen ovale between patients with and without cryptogenic brain ischemia

Purpose: To assess in a prospective study whether morphological and functional parameters of Patent Foramen Ovale (PFO) differ between patients with and without cryptogenic ischemic stroke or Transient Ischemic Attack (TIA). Methods: A total of 331 consecutive patients with cryptogenic brain ischemia underwent contrast multiplane transesophageal echocardiography (265 patients with ischemic stroke and 66 patients with TIA). The control group consisted of 312 consecutive patients without the history of stroke or TIA. We analysed 103 patients (64 male; mean age 52,9±12,3 years) with cryptogenic cerebrovascular event and PFO (Group I; 31,1% of all patiens with brain ischemia) and compared them to 56 control patients (19 male; mean age 50,0±12,7 years) with PFO (Group II; 18,0% of the control group). Following parameters were investigated: diameter of the PFO, length of the PFO, presence of the atrial septal aneurysm, presence of the Eustachian valve, shunt severity (graded with a 1-3 scale). Diameter and length of the channel were correlated with the shunt severity. Results: Patients with cryptogenic brain ischemia had significantly larger PFO diameter and higher prevalence of large PFO (≥ 4 mm) compared to the control group (2,5±1,6 mm vs 2,1±1,1 mm, p < 0,05; 17,5% vs 5,3%, p < 0,05). There was no significant difference between Group I and Group II in prevalence of the atrial septal aneurysm (14,6% vs 21,4%) and Eustachian valve (4,9% vs 7,1%), in the tunnel length (13,7±5,4 mm vs 12,8±5,8 mm) and in the degree of the shunt (1,8±0,7 vs 1,8±0,8). Both groups did not differ in the proportion of the shunt identified only after the Valsalva manoeuvre (41,7% vs 51,8%). There was a significant correlation between the PFO diameter and the degree of the shunt in patients with brain ischemia (r = 0,54, p < 0,0001). A weak but significant correlation was found between the tunnel length and the degree of the shunt in these patients (r = 0,21, p < 0,05). Morphological and functional parameters of PFO were not different between patients with ischemic stroke and TIA. Conclusions: The results may support the hypothesis that the decisive characteristic of the PFO distinguishing the patients with cryptogenic brain ischemia and asymptomatic patients is the diameter. Symptomatic patient have significantly larger PFO diameter and higher proportion of large PFO. The PFO diameter positively correlates with the degree of the shunt. Symptomatic and asymptomatic patients did not differ in the tunnel length, in the degree of the shunt and in the prevalence of atrial septal aneurysm or Eustachian valve.

Migraine with aura and silent brain infarcts lack of mediation of patent foramen ovale

Population-based studies have shown a heightened prevalence of clinically silent brain infarcts in subjects who have migraine with aura (MA). We sought to determine whether this association could be confirmed in young patients with cryptogenic ischemic stroke, and explored the role of patent foramen ovale (PFO) as a potential underlying mechanism. Patients were selected from a registry of young patients consecutively treated for ischemic stroke in a tertiary university hospital among those without definite cause of stroke. Patients with PFO were matched for age and gender with patients with normal atrial septum. Migraine and MA were evaluated after patient selection and matching. Silent brain infarcts were independently evaluated on MRI. We included 100 patients [60 men; mean age (SD), 44.8 years (8.3)], 50 patients with PFO. We found silent brain infarcts in 36 patients and MA in 13 patients. MA was more frequent in patients with silent brain infarcts than in patients without silent brain infarcts (25.0% vs. 6.3%; OR, 5; 95% CI, 1.4-17.6; P = 0.01). Traditional cardiovascular risk factors were not associated with silent brain infarcts. PFO was neither associated with MA (OR, 1.7; 95% CI, 0.5-5.3) nor silent brain infarcts (OR, 0.7; 95% CI, 0.3-1.5). The association of MA with silent brain infarcts was not altered after adjustment for PFO. Findings suggest that silent brain infarcts in young patients with cryptogenic stroke is associated with MA. We found no evidence for a mediating effect of PFO on this association.

Insertable Cardiac Event Recorder in Detection of Atrial Fibrillation After Cryptogenic Stroke

Atrial fibrillation (AF) is the most frequent risk factor in ischemic stroke but often remains undetected. We analyzed the value of insertable cardiac event recorder in detection of AF in a 1-year cohort of patients with cryptogenic ischemic stroke. All patients with cryptogenic stroke and eligibility for oral anticoagulation were offered the insertion of a cardiac event recorder. Regular follow-up for 1 year recorded the incidence of AF. Of the 393 patients with ischemic stroke, 65 (16.5%) had a cryptogenic stroke, and in 22 eligible patients, an event recorder was inserted. After 1 year, in 6 of 22 patients (27.3%), AF was detected. These preliminary data show that insertion of cardiac event recorder was eligible in approximately one third of patients with cryptogenic stroke and detected in approximately one quarter of these patients new AF.

Closure of Patent Foramen Ovale versus Medical Therapy after Cryptogenic Stroke

BackgroundWhether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age.MethodsIn this prospective, multicenter, randomized, event-driven trial, we randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated.ResultsWe enrolled 980 patients (mean age, 45.9 years) at 69 sites. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%). Treatment exposure between the two groups was unequal (1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group, P=0.009) owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat cohort, 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 95% confidence interval [CI], 0.22 to 1.11; P=0.08). The between-group difference in the rate of recurrent stroke was significant in the prespecified per-protocol cohort (6 events in the closure group vs. 14 events in the medical-therapy group; hazard ratio, 0.37; 95% CI, 0.14 to 0.96; P=0.03) and in the as-treated cohort (5 events vs. 16 events; hazard ratio, 0.27; 95% CI, 0.10 to 0.75; P=0.007). Serious adverse events occurred in 23.0% of the patients in the closure group and in 21.6% in the medical-therapy group (P=0.65). Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group (4.2%), but the rate of atrial fibrillation or device thrombus was not increased.ConclusionsIn the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270.)

Serial carotid MRI identifies rupture of a vulnerable plaque resulting in amaurosis fugax

A 66-year-old man with cryptogenic ischemic stroke and multiple acute ischemic lesions in the right middle cerebral artery territory was enrolled in the CAPIAS trial (Carotid Plaque Imaging in Acute Stroke; [NCT01284933][1]). Baseline carotid MRI demonstrated a right-sided nonstenotic American Heart Association type-VI plaque with a large lipid/necrotic core and intraplaque hemorrhage (figure 1). Eleven months later, the patient presented again after an episode of right eye amaurosis fugax. Repeat carotid MRI revealed a new ulceration on the right side with large parts of the former lipid/necrotic core missing (figure 2). We hypothesize that plaque rupture had caused embolization into the right retinal artery. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01284933&atom=%2Fneurology%2F80%2F12%2F1171.atom

Alto rendimiento del holter implantable en la detección de fibrilación auricular paroxística oculta en pacientes con ictus criptogénico y sospecha de mecanismo embólico

Implantable loop recorders (ILR) may allow detection of occult paroxysmal atrial fibrillation (PAF) in patients with cryptogenic ischemic stroke. However, optimal selection algorithm and ideal duration of monitoring remain unclear. AIM. To determine the incidence and time-profile of PAF in patients with cryptogenic ischemic stroke studied with Reveal XT ILR, who were selected based on a high suspicion of cerebral embolism. absence of stroke etiology after complete study including vascular imaging, transesophageal echocardiography and at least 24 hours of cardiac rhythm monitoring, and confirmation of acute embolic occlusion of intracranial artery by transcranial duplex or characteristics of acute ischemic lesion on neuroimaging suggesting embolic mechanism of ischemia. After implanting Reveal XT ILR, patients were trained to perform transmissions monthly or when symptoms occurred. We reviewed the information online each month and patients underwent clinical visits at 3rd and 6th month and then every six months. We included 101 patients with cryptogenic ischemic stroke and at least one month of follow-up after ILR implant. Mean age was 67 years, 54 women (53.5%). Mean follow-up after implantation was 281 ± 212 days. Occult PAF was detected in 34 patients (33.7%). Frequency of false positives: 22.8%. Median time from implant to arrhythmia detection was 102 days (range: 26-240 days). 24 (70%) patients with PAF had several arrhythmic episodes detected with ILR. The majority of events (75%) were detected during the first six months of monitoring. In our patients with probably embolic cryptogenic ischemic stroke, PAF was detected by Reveal XT ILR in 33.7%. One in four events occurred after the first six months of monitoring.

Analysis of the contribution of -5t/c polymorphism in the GP1BA gene to the development of ischemic stroke in young patients

The impact of -5T/C polymorphism in the GP1BA gene on the risk of ischemic stroke (IS) was studied in patients younger than 50 years of age. Ninety-two patients (73 men and 19 women; mean age 42.6+6.7years) with atherothrombotic, lacunar, and cryptogenic IS were examined on days 1—21 after its development. All the patients underwent brain magnetic resonance imaging or computed tomography, brachiocephalic artery duplex scanning, echocardiography, and laboratory studies (antiphospholipid antibodies, coagulogram and platelet aggregation, homocysteine, clinical and biochemical blood analyses, rheumatic tests, determination of -5T/C polymorphism in the GP1BA gene). An increased risk for IS was found in the young males versus the controls (healthy individuals; p = 0.03; OR 2.7; CI 1.14; 6.47). This association was not found in the women. Analysis of pathogenetic types ascertained that the lacunar IS men with CC and CT genotypes had a higher risk for stroke than the healthy individuals (p = 0.04, OR 3.5, CI 1.1; 10.9). In other subtypes of stroke, there was no association with this polymorphism. A group of patients with IS caused by thrombosis of the great arteries of the brain. In this group, the patients had CC and CT genotypes significantly more frequently than the controls (p = 0.003; OR 6.7; CI 2.0; 21.8), as well as C allele (p = 0.0008; OR 5.1; CI 1.97; 13.3). The -5T/C polymorphism in the GP1BA gene was associated with the development of IS in young males. The -5C allele and -5T/C and -5C/C genotypes are increased risk factors for lacunar and arterial thrombosis-induced IS in men.

Pilot Randomized Trial of Outpatient Cardiac Monitoring After Cryptogenic Stroke

Observational studies indicate that outpatient cardiac monitoring detects previously undiagnosed atrial fibrillation (AF) in 5% to 20% of patients with recent stroke. However, it remains unknown whether the yield of monitoring exceeds that of routine clinical follow-up. In a pilot trial, we randomly assigned 40 patients with cryptogenic ischemic stroke or high-risk transient ischemic attack to wear a Cardionet mobile cardiac outpatient telemetry monitor for 21 days or to receive routine follow-up alone. After thorough investigation, we excluded patients with documented AF or other apparent stroke pathogenesis. We contacted patients and their physicians at 3 months and at 1 year to ascertain any diagnoses of AF or recurrent stroke or transient ischemic attack. The baseline characteristics of our cohort broadly matched those of previous observational studies of monitoring after stroke. In the monitoring group, patients wore monitors for 64% of the assigned days, and 25% of patients were not compliant at all with monitoring. No patient in either study arm received a diagnosis of AF. Cardiac monitoring revealed AF in zero patients (0%; 95% confidence interval, 0%-17%), brief episodes of atrial tachycardia in 2 patients (10%; 95% confidence interval, 1%-32%), and nonsustained ventricular tachycardia in 2 patients (10%; 95% confidence interval, 1%-32%). In the first reported randomized trial of cardiac monitoring after cryptogenic stroke, the rate of AF detection was lower than expected, incidental arrhythmias were frequent, and compliance with monitoring was suboptimal. Our findings highlight the challenges of prospectively identifying stroke patients at risk for harboring paroxysmal AF and ensuring adequate compliance with cardiac monitoring. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00715533.

Prevalence of Fabry Disease in Young Patients with Cryptogenic Ischemic Stroke

A German study diagnosed 4% of young cryptogenic ischemic stroke patients with Fabry disease, an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A (α-GAL-A) gene resulting in an accumulation of glycosphingolipids. A lower prevalence was found in other geographic regions. To determine the prevalence of Fabry disease in a Canadian population of young cryptogenic ischemic stroke patients. Patients with cryptogenic ischemic stroke at age 16-55 were retrospectively identified in our institutional stroke database and underwent a focused clinical evaluation. We sequenced the α-GAL-A gene and measured the levels of blood globotriaosylsphingosine in subjects with mutations of undetermined pathogenicity. Fabry disease was diagnosed in patients with pathogenic mutations or increased levels of blood globotriaosylsphingosine. Ninety-three of 100 study subjects had normal α-GAL-A gene polymorphisms. Seven had mutations of undetermined pathogenicity, including one with increased globotriaosylsphingosine (prevalence, 1%; 95% confidence interval, <.01%-6%). No subjects had angiokeratomas or other clinical manifestations of Fabry disease. Investigation results suggestive of Fabry disease (idiopathic hypertrophic cardiomyopathy, proteinuria, vertebrobasilar dolichoectasia, and the pulvinar sign) were found only in subjects with normal α-GAL-A genes. Apart from the 100 study subjects, our database included another patient with a family history of Fabry disease and a pathogenic mutation identified before her ischemic stroke presentation as the first clinical manifestation of Fabry disease. Both Fabry patients experienced recurrent ischemic stroke. Fabry disease accounts for a small proportion of young Canadians with cryptogenic ischemic stroke. Identification of Fabry biomarkers remains a research priority to delineate stroke patients disserving routine screening.

Predictors of newly diagnosed atrial fibrillation in cryptogenic stroke: a cohort study

A significant proportion of cryptogenic ischaemic strokes are due to paroxysmal atrial fibrillation (AF). As paroxysmal AF appears to inexorably progress to persistent or permanent AF, this study with long-term follow-up was designed to establish the profile of patients who developed AF after hospital discharge. All patients with cryptogenic ischaemic stroke over a 1-year period were included (n=164). Patients were prospectively followed up at the outpatient clinic. Information on long-term outcome included the presence of newly diagnosed AF (NDAF). A specific NDAF assessment was performed at least 2years after the index stroke using a structured telephone interview. Baseline clinical, laboratory, and echocardiographic data of these patients were retrospectively recorded. Independent predictive factors were then used to produce a predictive grading score for NDAF, derived by logistic regression analysis. With a median follow-up of 854days, 22 cases of NDAF (13%) were observed. On multivariate analysis, factors associated with NDAF were age ≥72years (two points), history of coronary artery disease (one point) or stroke (one point), and left atrial area ≥16cm(2) (two points) (total score ranging from 0 to 6). Patients with a score ≤1 point did not have NDAF during follow-up. In cryptogenic ischaemic stroke, the NDAF score can be used to target patients at high risk of developing AF after hospital discharge, as a score of 0-1 was highly predictive of the absence of NDAF during follow-up. These results need to be confirmed in prospective studies.