Stroke Of Undetermined Origin Research Articles

Comparison of right-to-left shunt characteristics in cryptogenic embolic ischemic stroke and non-cardioembolic ischemic stroke

Patent foramen ovale (PFO) has been considered a potential mechanism of embolic stroke of undetermined origin. The aim of the present study was to identify the features of the right-to-left shunt (RLS) in patients with undetermined embolic ischemic stroke and compare them with those of patients with non-cardioembolic ischemic stroke. A retrospective study was conducted with 168 patients with stroke and RLS separated into the following two groups: the undetermined embolic stroke group (UES group) and non-cardioembolic stroke group (NCES group). All patients were assessed by transcranial Doppler to evaluate the presence and quantification of microembolic signals (MES) at rest and under Valsalva maneuver. Of all patients evaluated in the current study, 96 were included in the UES group and 72 in the NCES group. In the UES group, 65 patients had RLS with ≥10 MES (67.7%), which was higher than that observed in the NCES group (51.4%, p=0.038). According to the moment of the cardiac cycle, 75 patients (78.1%) in the UES group had a positive test at rest compared to 42 (58.3%) in the NCES group (p=0.007). The current study demonstrated that almost 70% of patients with undetermined embolic stroke and PFO presented a large RLS and more than 75% had RLS at rest. These findings suggest that the size of the shunt should be taken into account when evaluating whether PFO could be a possible mechanism underlying cryptogenic stroke.

No Association Between Thrombus Perviousness and Cardioembolic Stroke Etiology in Basilar Artery Occlusion Stroke.

Background: Thrombus perviousness (TP) quantified by thrombus attenuation increase (TAI) assessed on acute non-contrast computed tomography (NCCT) and CT angiography (CTA) may be associated with stroke etiology in anterior circulation ischemic stroke. We investigated whether TP is associated with stroke etiology and recanalization after mechanical thrombectomy in patients with acute basilar artery occlusion (BAO).Methods: Eighty patients with complete BAO and in-house acute imaging from a prospectively maintained database were included. Two raters independently segmented the complete thrombus on co-registered NCCT and CTA to determine TAI in Hounsfield units (HUCTA–HUNCCT); averaged values of the raters were used for analysis. Recanalization to modified treatment in cerebral ischemia (mTICI) score 2b/3 was considered successful, and 90-day modified Rankin Scale score 0–2 was considered favorable.Results: TAI did not differ between patients with different stroke etiologies; median TAI in patients with cardioembolic stroke (n = 36) was −0.47 (interquartile range −4.08 to 7.72), 1.94 (−8.14 to 10.75) in patients with large artery atherosclerosis (LAA; n = 25), and −0.99 (−6.49 to 5.40) in patients with stroke of undetermined origin (n = 17; p = 0.955). Binary logistic regression analyses did not identify TAI as an independent indicator of cardioembolic stroke (adjusted odds ratio [OR] vs. LAA stroke: 1.0 [95% CI: 0.95–1.0], p = 0.751). There was no association with successful recanalization (adjusted OR 1.4 [0.70–2.7], p = 0.345) or favorable outcome (adjusted OR 1.1 [95% CI: 0.94–1.2], p = 0.304).Conclusion: In contrast to proximal middle cerebral artery occlusions, TP in BAO patients is not associated with cardioembolic stroke etiology. Larger confirmatory studies to establish the potential role of TP for clinical applications should focus on patients with anterior circulation stroke.

Are Early Seizures Predictive of Epilepsy after a Stroke? Results of a Population-Based Study

Background: In addition to determining the cumulative incidence and risk factors for early seizures (ES), late seizures (LS) and post stroke epilepsy (PSE), we aimed at checking if ES represented a risk factor for epilepsy and if early treatment after ES prevented the occurrence of subsequent seizures. Methods: This study was part of a 2-year prospective community-based registry of all cerebrovascular events in the district of Udine (153,312 inhabitants), North-Eastern Italy, between April 1, 2007 and March 31, 2009. People with transient ischemic attacks (TIAs) were excluded from this study. Results: In all, 782 cases of stroke (79.28% ischemic, 14.83% hemorrhagic, 3.20% subarachnoid hemorrhage and 2.69% undetermined) were identified. The incidence of ES, LS and PSE was 5.10, 3.14 and 2.22%, respectively. Intracerebral hemorrhage, subarachnoid hemorrhage, stroke of undetermined origin and hyponatremia, represented risk factors for ES (p < 0.05). Among ischemic strokes, ES risk factors were hyponatremia (p = 0.024) and hemorrhagic transformation (p = 0.046). LS risk factors were younger age (p = 0.004) and cortical location of stroke (p = 0.004). Within ischemic strokes, LS risk factors were younger age (p = 0.020) and cortical location (p < 0.0001). Within intracerebral hemorrhages, the only risk factor for LS was the presence of a previous ES (p = 0.017). PSE risk factors were the same as for LS. Conclusions: All acute conditions related to the occurrence of stroke are implicated in the pathogenesis of ES, which becomes a risk factor for LS only in the setting of intracerebral hemorrhages. Therefore, early antiepileptic treatment is needed only in this situation.

Ischaemic stroke of undetermined cause

The definition of cryptogenic stroke or stroke of undetermined origin is affected by the current knowledge of the cause and pathogenesis of stroke and by the availability, comprehensiveness, quality, and timeliness of the ancillary investigations undertaken to discover the cause of the stroke. In The Lancet Neurology, Linxin Li and colleagues report findings from a populationbased study of the burden, outcome, risk factors, and long-term prognosis of cryptogenic stroke in patients with a first transient ischaemic attack (TIA) or ischaemic stroke. They found that of 2555 first ischaemic events, 812 (32%) were cryptogenic. The study shows that the prognosis of cryptogenic stroke and the risk of recurrence are similar to those of large artery disease and small vessel disease. For example, death or dependency at 6 months was similar after cryptogenic stroke compared with large artery and small vessel subtypes combined (23% vs 27%; p=0·26), as was the 10-year risk of recurrence (32% vs 27%; p=0·91). Secondary stroke prevention must be similarly aggressive and appropriate in stroke with and without identified cause. The findings from this Article question the role of paroxysmal atrial fibrillation as the major cause of cryptogenic stroke, which contrasts with the present enthusiasm for the use of technology to detect paroxysmal atrial fibrillation and for the possibility to prevent recurrent cryptogenic stroke with anticoagulants.

An unusual case of paradoxical embolism in a young patient affected by stroke

The majority of ischemic strokes are due to atherothrombosis, cardioembolism, systemic hypoperfusion (general decrease in blood supply, e.g., in shock), or small vessel occlusive disease. However, many ischemic strokes occur without a well-defined etiology and are labeled as cryptogenic, and they constitute 30–40 % of all ischemic strokes. By the TOAST classification, which is the most commonly used in clinical practice, cryptogenic stroke (or stroke of undetermined origin in TOAST terminology) is defined as brain infarction that is not attributable to a source of definite cardioembolism, large artery atherosclerosis, or small artery disease despite extensive vascular, cardiac, and serologic evaluation. This means that in a large part of our patients we are unable to identify stroke etiology. In our report we described an unusual cause of stroke discovered by non-routinary investigations.

A bioclinical pattern for the early diagnosis of cardioembolic stroke.

Background and Scope. Early etiologic diagnosis of ischemic stroke subtype guides acute management and treatment. We aim to evaluate if plasma biomarkers can predict stroke subtypes in the early phase from stroke onset. Methods. Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP), D-dimer, C-reactive protein, serum albumin, and globulin levels have been investigated in 114 consecutive patients presenting at the emergency room within 6 hours of the ischemic stroke onset. Plasma levels of biomarkers have been correlated with stroke aetiology (based on TOAST criteria) by multivariable logistic regression analysis, adjusted for several covariates. Results. Of the 114 patients, 34 (30%) had cardioembolic stroke, 27 (23%) atherothrombotic stroke, 19 (17%) lacunar stroke, and 34 (30%) stroke of undetermined origin. Patients with cardioembolic stroke had significantly higher levels of NT-proBNP and lower globulin/albumin (G/A) ratio compared with the other subgroups. At multiple logistic regression NT-proBNP > 200 pg/mL, G/A ratio > 0.70, and NIHSS score were independent predictors of cardioembolic stroke with high accuracy of the model, either including (AUC, 0.91) or excluding (AUC, 0.84) atrial fibrillation. Conclusions. A prediction model that includes NT-proBNP, G/A ratio, and NIHSS score can be useful for the early etiologic diagnosis of ischemic stroke.

Extended Electrocardiographic Poincare Analysis (EPA) for Better Identification of Patients with Paroxysmal Atrial Fibrillation

Background: Atrial fibrillation (AF) – be it permanent or paroxysmal – is the most frequent and most effectively treatable cause of stroke. However, when paroxysmal, even electrocardiography for 24 hours (24h-ECG) misses AF in more than 50% of cases. We assessed whether extended Poincare analysis of ECG R-R intervals (EPA) can help to identify electrocardiographic remodeling suggestive of paroxysmal AF (PAF). Methods: Twenty-nine patients with previously diagnosed PAF were re-assessed by 24h-ECG using conventional analysis and EPA based on a previously trained algorithm considering among other ratios of R-R interval duration, number of premature atrial complexes, approximate entropy, and standard deviation of Poincare plots-axes. 24h-ECG from 21 healthy subjects without a history of AF served as negative, and 9 patients with permanent AF as positive controls. Results: PAF during 24h-ECG was detected in 4 out of 29 (14%) patients with a history of PAF by conventional analysis. EPA classified ECGs of these and 22 additional patients with a history of PAF, i.e. a total 90%, as suggestive of PAF. All patients with permanent AF were identified by both tools. EPA additionally classified the ECG in 4 out of 21 control subjects as suggestive of PAF. Conclusions: Extended Poincare analysis in patients with a history of PAF is more sensitive to electrocardiographic abnormalities than is conventional 24h- ECG analysis. These findings warrant prospective studies of EPA in patients with a high likelihood of PAF, i.e. with stroke of undetermined origin.

High Serum Levels of Pro-Brain Natriuretic Peptide (pro BNP) Identify Cardioembolic Origin in Undetermined Stroke

Background: Stroke subtype diagnosis leads to specific therapies to reduce recurrences. Because nearly one third of patients remain with unknown etiology after a complete screening workup, we aim to investigate whether molecular markers of myocardial damage were associated with cardioembolic stroke and if they were useful to reclassify strokes of undetermined etiology.Methods: We included 262 patients with first ischemic stroke within the first 12 hours. Stroke subtype was evaluated by TOAST criteria. Stroke of undetermined origin were reclassified into likely atherothrombotic or likely cardioembolic according to a predefined non-validated algorithm. Blood samples were obtained on admission to determine serum levels of molecular markers (pro-BNP, pro-ANP and CK-MB) of myocardial damage.Results: Patients with cardioembolic infarct showed higher levels of pro-BNP, pro-ANP and CK-MB. Pro-BNP &gt; 360 pg/mL was independently associated with cardioembolic stroke (OR: 28.51, CI95%: 5.90–136.75,p&lt; 0.0001). Stroke etiology was undetermined in 82 patients (31%); 34 were reclassified as likely cardioembolic, 22 as likely atherothrombotic, and 26 remained as undetermined. Pro-BNP &gt; 360 pg/mL was the only factor independently associated with likely cardioembolic stroke.Conclusions: Pro-BNP levels higher than 360 pg/mL are associated with cardioembolic stroke and may be useful to reclassify undetermined strokes as of cardioembolic origin.

High serum levels of pro-brain natriuretic peptide (pro BNP) identify cardioembolic origin in undetermined stroke.

Background: Stroke subtype diagnosis leads to specific therapies to reduce recurrences. Because nearly one third of patients remain with unknown etiology after a complete screening workup, we aim to investigate whether molecular markers of myocardial damage were associated with cardioembolic stroke and if they were useful to reclassify strokes of undetermined etiology. Methods: We included 262 patients with first ischemic stroke within the first 12 hours. Stroke subtype was evaluated by TOAST criteria. Stroke of undetermined origin were reclassified into likely atherothrombotic or likely cardioembolic according to a predefined non-validated algorithm. Blood samples were obtained on admission to determine serum levels of molecular markers (pro-BNP, pro-ANP and CK-MB) of myocardial damage. Results: Patients with cardioembolic infarct showed higher levels of pro-BNP, pro-ANP and CK-MB. Pro-BNP > 360 pg/mL was independently associated with cardioembolic stroke (OR: 28.51, CI95%: 5.90–136.75, p < 0.0001). Stroke etiology was undetermined in 82 patients (31%); 34 were reclassified as likely cardioembolic, 22 as likely atherothrombotic, and 26 remained as undetermined. Pro-BNP > 360 pg/mL was the only factor independently associated with likely cardioembolic stroke. Conclusions: Pro-BNP levels higher than 360 pg/mL are associated with cardioembolic stroke and may be useful to reclassify undetermined strokes as of cardioembolic origin.

Recurrent asystolia in right middle cerebral artery infarct with predominant insular involvement

A 42-year-old woman who smoked had a right middle cerebral artery (MCA) stroke of undetermined origin (initial NIHSS 19). CT and perfusion-CT after 7 h (fig 1B) showed no mass...

Screening for MELAS mutations in young patients with stroke of undetermined origin

It has been suggested that mitochondrial disease may be responsible for a substantial proportion of strokes of indetermined origin. We have preliminarily screened for MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) mutations in young patients with cryptogenic strokes. The mitochondrial mutations A3243G and T3271C were investigated in 38 subjects aged less than 46 years. Group 1: 15 patients with cryptogenic strokes; Group 2: 3 patients with diagnosis of MELAS syndrome, including stroke-like episodes; Group 3: 20 healthy subjects. The A3243G mutation was absent in all subjects in Groups 1 and 3 but was present in all subjects in Group 2. Our results do not support screening for these mutations to diagnose oligosymptomatic forms of MELAS in cryptogenic strokes in the absence of other features of the syndrome. We suggest that clinical findings should guide mitochondrial genetic testing.

Patent Foramen Ovale and Stroke: Prognosis and Treatment in Young Adults

A patent foramen ovale (PFO) is found with increased frequency in patients with stroke of undetermined origin but the significance and therapeutic implications of this observation remain unclear. Several lines of evidence suggest a role for the PFO in stroke pathophysiology for some cryptogenic stroke patients, such as those whose PFO is accompanied by a prothrombotic state, atrial septal aneurysm, or lower extremity/pelvic DVT. Diagnostic evaluation of the patient with cryptogenic stroke and PFO is directed at identifying these subgroups. Appropriate therapy for primary and secondary stroke prevention in a subject with a PFO remains unclear given current uncertainties as to the pathophysiological significance of PFO. Additional studies are needed, such as those focused on lower extremity veins or the cardiac interatrial septum, to guide therapy in specific stroke subpopulations.

Trends in Stroke Incidence and 10-Year Survival in Söderhamn, Sweden, 1975-2001

Stroke mortality rates have declined in many countries. Stroke incidence rates have also declined, but not to the same extent and not always in parallel with stroke mortality. The aim of the present study was to investigate trends in stroke incidence and long-term survival in a Swedish population. A population-based survey of the incidence of first-ever stroke was performed prospectively in the periods 1975 to 1977, 1983 to 1986, and 1987 to 1990. Case fatality ratios and survival rates were followed to 2001. Crude incidence rates increased between 1975 to 1977 and 1983 to 1986, but age- and sex-adjusted incidence rates were stable during the whole period of 1975 to 1990. The incidence of intracerebral hemorrhage decreased by approximately two thirds, whereas the incidence of mild brain infarction almost doubled. The case fatality ratio at 28 days did not change, but the 10-year survival ratio increased from 13% to 35%. Mean survival time increased significantly among patients with intracerebral hemorrhage and brain infarction but not among patients with subarachnoidal hemorrhage or stroke of undetermined origin. Stroke incidence and short-term case fatality did not change between 1975 and 1990 in the Söderhamn population. Long-term survival after stroke, on the other hand, has continued to improve to 2001. The implication of these changes is that the burden of stroke is likely to increase unless strokes are becoming less severe.

Aetiologic diagnosis of ischaemic stroke in the emergency department: relevance for triage and clinical management.

Effective strategies for the aetiologic diagnosis in patients with ischaemic stroke can be implemented based on simple clinical criteria and instrumental tests which can be performed in a modern emergency room (ER) within 24 hours from admission. This may bear prognostic and therapeutic relevance for patients with acute stroke. Therefore, in this study we set out to establish the feasibility and accuracy of the aetiologic diagnosis of ischaemic stroke in an ER. A total of 136 consecutive patients (mean age 72+/-10 years, 60 females) with first ever ischaemic stroke admitted during 1996-1997 were evaluated with assessment of clinical features, CT scan, ECG, ultrasonography of the extracranial arteries, transthoracic echocardiography, and, in selected patients, transoesophageal echocardiography. Patients were classified into two major categories defined as stroke of determined origin and stroke of undetermined origin (a stroke with two or more possible causes or with a negative evaluation), according to the TOAST criteria. Ninety-six patients were considered affected by stroke of determined origin (70.5%), (22.7% with large artery atherosclerosis, 19.1% with cardioembolic stroke, 26.4% with lacunar stroke and 1.4% with other aetiology). The remaining 40 patients (29.4%) had stroke of undetermined origin: of these, 13 patients (9.5%) had a totally negative evaluation, 15 patients (12.5%) showed cardioembolism among the two or more possible causes of stroke and seven patients (5.1%) had atherothrombotic or lacunar aetiology. Additional work-up with transoesophageal echocardiography succeeded in demonstrating aortic embolism in five patients (3.6%; i.e. four patients with aortic plaques more than 4 mm in thickness and one patient with ulcerated plaques). In conclusion, the subtype classification system for ischaemic stroke allowed the aetiological diagnosis in 70.5% of patients while in the ER. Stroke of undetermined origin represented one-third of patients in a consecutive population with acute onset neurologic deficit of ischaemic origin. In approximately half of the patients with negative standard evaluation, cardiogenic or aortic arch embolic sources could be identified by transoesophageal echocardiography. Thus, the latter is indicated in patients with stroke of undetermined origin with negative first-line evaluation in order to identify embolic sources in the aortic arch.

Patent foramen ovale as a risk factor for cryptogenic stroke.

To determine and compare the prevalence of patent foramen ovale in patients with stroke of undetermined origin (cryptogenic) and in patients with stroke of determined origin to assess the possible role of patent foramen ovale as a risk factor for cryptogenic stroke. Cross-sectional study with nested case-control analysis. A total of 146 patients (73 men, 73 women) with acute ischemic stroke referred to the echocardiography laboratory for evaluation. Neurovascular Unit and Echocardiography Laboratory, Columbia-Presbyterian Medical Center, New York, New York. Patients were considered to have strokes of determined origin or cryptogenic strokes according to National Institute of Neurological Disorders and Stroke (NINDS) Stroke Data Bank criteria. The presence of patent foramen ovale was assessed by contrast echocardiography, performed blinded for type of stroke. The association between patent foramen ovale and type of stroke was tested after correcting for patients' demographic variables and stroke risk factors. The overall prevalence of patent foramen ovale was 26 of 146 patients (18%; 95% Cl, 11.4% to 24.6%). Patients with cryptogenic stroke (31%) had a significantly higher prevalence of patent foramen ovale than did patients with an identifiable cause of stroke (69%) in both the younger (less than 55 years; 48% compared with 4%; P less than 0.001) and the older (greater than or equal to 55 years; 38% compared with 8%; P less than 0.001) age groups. Multiple logistic regression analysis was used to identify the presence of a patent foramen ovale as strongly associated with the diagnosis of cryptogenic stroke (odds ratio, 7.2; Cl, 2.4 to 21.7), irrespective of patient age and other stroke risk factors. Patients with cryptogenic stroke have a higher prevalence of patent foramen ovale than patients with stroke of determined cause in all age groups, even after correcting for the presence of recognized stroke risk factors. This identifies patent foramen ovale as a risk factor for cryptogenic stroke. Regardless of patient age, contrast echocardiography should be considered when the cause of stroke is unknown.