Background and Purpose-Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. Methods-Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396) *Drs Rolfs, Fazekas and Grittner contributed equally to this work. Authors contributions: Dr Rolfs has conceptualized, initiated, and designed and organized the study, has been involved in the recruitment of the patients, and wrote significant parts of the manuscript. Dr Fazekas was involved in the study planning and has done together with Drs Enzinger and Schmidt the analysis of all MRI scans; this group was mainly involved in the statistical analysis of the MRI data. Drs Martus, Grittner, Holzhausen have taken responsibility for all statistical analysis and for the data structure of the total data bank. Drs Dichgans, Böttcher, Tatlisumak, Tanislav, Jungehulsing, Putaala, Huber, Bodechtel, Lichy, Hennerici, Kaps, Meyer, Kessler have been most active in the recruitment of the patients, drafting the manuscript and significantly influencing the scientific discussion. Dr Heuschmann was involved in drafting the manuscript and influencing the scientific discussion. Dr Norrving chaired the steering and publication committees of sifap, has written parts of the manuscript, and has significantly influenced the scientific discussions. Drs Lackner and Paschke, H. Mascher, Dr Riess have been involved in the laboratory analyses. Dr Kolodny has mostly contributed to the discussion of the Fabry cases. Dr Giese assisted in writing and editing the manuscript. All authors have reviewed, critically revised and approved the final version of the manuscript.The sponsors of the study had no role in the study design, data collection, data analysis, interpretation, writing of the manuscript, or the decision to submit the manuscript for publication. The academic authors had unrestricted access to the derived dataset, and assume full responsibility for the completeness, integrity, and interpretation of the data, as well as writing the study report and the decision to submit for publication.†Listed in Appendix I in the online-only Data Supplement. Jeffrey L. Saver, MD, was guest editor for this article.

Since sleep apnea (SA) and stroke have many shared risk factors an independent contribution of SA to the overall risk of stroke is not easily proven and has been questioned recently. To contribute to this controversy, we analysed the frequency of SA in groups of patients with first and recurring ischemic stroke. We prospectively studied 102 patients admitted to our stroke unit. The prevalence of vascular risk factors and a history of previous stroke were recorded. All patients received cardio-respiratory polygraphy during the first 72 hours after admission. CT and MRI scans were evaluated for the location of the acute stroke and the presence of older vascular lesions. Thirty-four women and 68 men with a mean age of 64.5 +/- 13.7 years were included in the study. Cerebral lesions attributable to a previous stroke were identified in 25 patients, of whom 19 reported to have suffered a stroke before. Patients with stroke recurrence had a higher mean apnea-hypopnea index (AHI) (26.6/h vs. 15.1/h, p<0.05) and more often presented with a sleep apnea syndrome (SA) defined by an AHI >or=10/h (80 vs. 52%, p < 0.05) than patients with first ever stroke. Logistic regression analysis including the variables "age", "gender", "cumulative risk factors", "AHI >or=10/h", and "diabetes" identified diabetes (Odd's ratio [OR]=4.5) and AHI >or=10/h (OR=3.5) as independent risk-factors for stroke recurrence. According to our results SA is an independent risk factor for stroke recurrence. We therefore advocate routine sleep-apnea screening in all patients having suffered an ischemic stroke.

Cerebral ischaemia in young adults is a well-recognised disease, and approximately half of the cases remain aetiologically unclear despite extensive investigations. Thrombophilias are known to cause a subset of ischaemic strokes in this population. The factor V Leiden (FVL) mutation, causing resistance to activated protein C, has recently been recognised as the most important genetic thrombophilia in the Western population. Carriers of this gene mutation have a sevenfold increased risk of phlebothrombosis. We undertook this study to evaluate whether the FVL mutation constitutes a risk factor for juvenile cerebral ischaemias. A total of 225 patients aged < or = 45 years at onset of cerebral ischaemia and 200 age-matched healthy controls were investigated. The overall frequency of heterozygosity for the FVL mutation did not differ significantly between patients (8.4%) and controls [6.0%; odds ratio (OR) 1.4, 95% confidence interval (CI) 0.7-3.1]. In the subgroup of patients with cryptogenic cerebral ischaemia (n = 94), however, a significantly higher frequency of this gene defect (15.9%) was found compared with the controls (OR 3.0, CI 1.3-6.6). Further trends towards higher frequencies of the FVL mutation were found in patients with patent foramen ovale (OR 1.9), individual (OR 2.1) or family history of previous thrombembolisms (OR 2.0), and in those aged 25 years at onset of disease (OR 1.9, all not significant). In conclusion, the FVL mutation is not a risk factor for cerebral ischaemia of the young. However, our results suggest that this gene mutation plays an aetiological role in the subgroup of patients suffering from 'cryptogenic' ischaemic events.

Echocontrast agents (ECA) are known to improve transcranial color-coded duplex (TCCD) imaging, but its diagnostic benefit in the routine clinical setting has not clearly been defined. The authors investigated the diagnostic benefit of ECA application in 54 patients with insufficient transtemporal bone window, consecutively referred to their ultrasound laboratory. According to the precontrast imaging quality, patients were assigned to three categories: A, no intracranial structures or vessel segments visible on B-mode imaging and TCCD (n = 5); and intracranial structures visible on B-mode imaging and vessel segments less than 5 mm in length (B, n = 21), or larger than 5 mm in length (C, n = 28) visible on TCCD. The effect of the echocontrast enhancement was assessed with respect to signal enhancement, imaging quality, and diagnostic confidence. In 49 out of 54 patients (91%), a significant improvement of the imaging quality was noted, enabling 43 (80%) neurovascular diagnoses of sufficient diagnostic confidence. The diagnostic ECA effect was strongly dependent on the precontrast imaging quality: upon echoenhancement, a satisfactory image quality was obtained in none of the patients of category A, as opposed to 16 (76%) and 27 (96%) patients of categories B and C, respectively. In summary, in 80% of our consecutive patient series with insufficient transtemporal bone window, application of ECA allowed for a conclusive TCCD study. Properties of the transtemporal precontrast scans are strongly predictive of the diagnostic benefit and should be taken into the decisive consideration.

Atrial fibrillation (AF) is a well-recognized independent risk factor of ischemic stroke. The aim of this study was to investigate the amount of microembolic signals (MES) in 15 patients with 'lone' AF representing the subgroup of AF patients with the lowest lifelong risk of stroke. All patients had been put on effective anticoagulation due to a scheduled electric cardioversion. Additional cardiac and arterial sources of embolism were excluded by echocardiography and extracranial color-coded duplex sonography of the carotid arteries. Unilateral one-hour transcranial Doppler monitorings revealed complete absence of MES in this series. This observation fits the concept that the amount of microembolisation is related to the risk of manifest thromboembolism. Further studies on this patient group treated with less intensive antihemostatic therapy should be undertaken to define more clearly the disease-specific microembolic activity.