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Background: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes)., Methods: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present., Results: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant., Conclusion: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening., Competing Interests: Declaration of competing interest IR received travel grants and speaker's honoraria from Takeda, Sanofi, and Amicus; PN received speaker's honoraria from Takeda, Sanofi, and Amicus; MZ received fees as consultant and advisory board member from Takeda, Sanofi, and Amicus; SS received personal fees as speaker or advisor (Abbott, Allergan-Abbvie, AstraZeneca, Eli Lilly, Lundbeck, Novartis, NovoNordisk, Pfizer, Teva), research grants (Allergan, Novartis, Uriach), and fees for CME/education (Medscape, Neurodiem Ology Medical Education); UA received speaker's fees and honoraria from EISAI; AM received speaker's honoraria and travel grants from Takeda, Sanofi, and Amicus; DI received speaker's honoraria from Takeda. Other authors declared that they have no competing interests for FSIR study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Subclinical vascular brain lesions are highly prevalent in elderly patients with stroke. Little is known about predisposing factors and their impact on long-term outcome of patients with stroke at a young age., Methods: We quantified magnetic resonance-defined subclinical vascular brain lesions, including lacunes and white matter hyperintensities, perivascular spaces and cerebral microbleeds, and assessed total small-vessel disease (SVD) score in patients with first-ever acute ischemic stroke aged 18 to 45 years, and followed them up, as part of the multicentre Italian Project on Stroke in Young Adults. The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. We assessed the predictive accuracy of magnetic resonance features and whether the addition of these markers improves outcome prediction over a validated clinical tool, such as the Italian Project on Stroke in Young Adults score., Results: Among 591 patients (males, 53.8%; mean age, 37.5±6.4 years), 117 (19.8%) had subclinical vascular brain lesions. Family history of stroke was associated with lacunes (odds ratio, 2.24 [95% CI, 1.30-3.84]) and total SVD score (odds ratio, 2.06 [95% CI, 1.20-3.53] for score≥1), hypertension with white matter hyperintensities (odds ratio, 2.29 [95% CI, 1.22-4.32]). After a median follow-up of 36.0 months (25th-75th percentile, 38.0), lacunes and total SVD score were associated with primary end point (hazard ratio, 2.13 [95% CI, 1.17-3.90] for lacunes; hazard ratio, 2.17 [95% CI, 1.20-3.90] for total SVD score ≥1), and the secondary end point brain ischemia (hazard ratio, 2.55 [95% CI, 1.36-4.75] for lacunes; hazard ratio, 2.61 [95% CI, 1.42-4.80] for total SVD score ≥1). The predictive performances of the models, including magnetic resonance features were comparable to those of the random model. Adding individual magnetic resonance features to the Italian Project on Stroke in Young Adults score did not improve model prediction., Conclusions: Subclinical vascular brain lesions affect ≈2 in 10 young adults with ischemic stroke. Although lacunes and total SVD score are associated with thrombotic recurrence, they do not improve accuracy of outcome prediction over validated clinical predictors.

SCeAD affected predominantly a single artery (carotid, 870 patients [59.3%]; vertebral, 386 patients [26.3%]), whereas 212 patients (14.4%) had > 1 cervical artery involved. Dear Sirs, A recent hypothesis to explain the migraine-ischemic stroke (IS) association is that migraine might increase individual vulnerability to cerebral ischemia, making brain tissue more susceptible to ischemic injury [[1]]. Among migraine sufferers, we distinguished between "active migraine", which included participants with at least one self-reported migraine attack in the year preceding the baseline evaluation, and "prior (non-active) migraine", which included those who reported ever having had migraine but no attack in the year preceding the baseline evaluation. Actually, if the above is true, one would expect a higher prevalence of migraine and, possibly, migraine activity, among sCeAD patients who develop IS than among those who do not, as well as an association of migraine with sCeAD only or more prominent in the subgroup of patients with IS as disease manifestation compared to non-sCeAD subjects. [Extracted from the article]

Objective: Epidemiological data to characterize the individual risk profile of patients with spontaneous cervical artery dissection (sCeAD) are rather inconsistent. Methods and Results: In the setting of the Italian Project on Stroke in Young Adults Cervical Artery Dissection (IPSYS CeAD), we compared the characteristics of 1,468 patients with sCeAD (mean age = 47.3 ± 11.3 years, men = 56.7%) prospectively recruited at 39 Italian centers with those of 2 control groups, composed of (1) patients whose ischemic stroke was caused by mechanisms other than dissection (non‐CeAD IS) selected from the prospective IPSYS registry and Brescia Stroke Registry and (2) stroke‐free individuals selected from the staff members of participating hospitals, matched 1:1:1 by sex, age, and race. Compared to stroke‐free subjects, patients with sCeAD were more likely to be hypertensive (odds ratio [OR] = 1.65, 95% confidence interval [CI] = 1.37–1.98), to have personal history of migraine with aura (OR = 2.45, 95% CI = 1.74–3.34), without aura (OR = 2.67, 95% CI = 2.15–3.32), and family history of vascular disease in first‐degree relatives (OR = 1.69, 95% CI = 1.39–2.05), and less likely to be diabetic (OR = 0.65, 95% CI = 0.47–0.91), hypercholesterolemic (OR = 0.75, 95% CI = 0.62–0.91), and obese (OR = 0.41, 95% CI = 0.31–0.54). Migraine without aura was also associated with sCeAD (OR = 1.81, 95% CI = 1.47–2.22) in comparison with patients with non‐CeAD IS. In the subgroup of patients with migraine, patients with sCeAD had higher frequency of migraine attacks and were less likely to take anti‐migraine preventive medications, especially beta‐blockers, compared with the other groups. Interpretation: The risk of sCeAD is influenced by migraine, especially migraine without aura, more than by other factors, increases with increasing frequency of attacks, and seems to be reduced by migraine preventive medications, namely beta‐blockers. ANN NEUROL 2023;94:585–595 [ABSTRACT FROM AUTHOR]