Familial aggregation of stroke amongst young patients in Lund Stroke Register.

BACKGROUND AND PURPOSE: The known monogenic forms of stroke are rare. The aim of this study was to analyze pedigrees of young stroke patients regarding possible monogenic cerebrovascular disease and to evaluate the possibility of genetic stroke in these families. This may contribute to a better understanding of disease mechanism in stroke. METHODS: Lund Stroke Register includes consecutive patients with first-ever stroke from a defined geographical area in southern Sweden. Early-onset (≤55 years) stroke patients were systematically screened with regard to family history (FHx), and families with stroke aggregation were compiled. Participants provided information in a questionnaire on occurrence of stroke or transient ischaemic attack (TIA) in their families. Information on cardiovascular risk factors (VRFs) and clinical stroke subtype was collected. FHx for stroke was considered positive when the patient reported either ≥1 first-degree relative with stroke/TIA, or no first-degree relative but ≥3 second- or third-degree relatives with stroke/TIA in a distribution compatible with monogenic inheritance. RESULTS: Of 4103 stroke patients registered, 426 (10%) had first-ever stroke at ≤55 years and 338 (79%) of these answered the questionnaire. Of them, 159 (47%) reported a positive FHx. Twenty-eight (18%) of the probands with positive FHx had no known VRFs. Thirty-two families with ≥4 members with stroke were identified. In all these larger families the affected individuals with stroke were present in more than one generation. CONCLUSION: Aggregation of stroke in families of early-onset stroke patients is not uncommon. Genetic factors with impact on stroke risk, including monogenic causes, need to be evaluated in future stroke studies.

Predominance of caudate nucleus lesions in acute ischaemic stroke patients with impairment in language and speech.

BACKGROUND AND PURPOSE: Whereas traditional views of language processing in the brain have assumed that the language function is concentrated to a limited number of cortical areas (Broca's and Wernicke's areas), current knowledge points at a much more complex system of language and speech processing involving many brain areas, both cortical and subcortical. The purpose of the current study was to make an unbiased assessment of which cerebral areas are affected in first-ever acute ischaemic stroke patients identified as having language and speech impairments according to the National Institutes of Health Stroke Scale (NIHSS). METHODS: Data from 34 patients with language and speech impairment, with a score of 1-3 on item 9 of the NIHSS, following ischaemic stroke were collected from the Lund Stroke Register. Magnetic resonance images acquired up to 20 days after stroke onset were used to create an overlap lesion image using MRIcron software. RESULTS: The classical language areas, Wernicke's and Broca's areas, were affected in less than one-fourth of the patients. The most frequently affected region was a subcortical region--the left caudate nucleus and the adjacent corona radiata. CONCLUSIONS: These findings contribute to the growing body of evidence that the basal ganglia have a crucial role in the control over language and speech processing.

The Causative Classification of Stroke system: an international reliability and optimization study.

BACKGROUND: Valid and reliable ischemic stroke subtype determination is crucial for well-powered multicenter studies. The Causative Classification of Stroke System (CCS, available at http://ccs.mgh.harvard.edu) is a computerized, evidence-based algorithm that provides both causative and phenotypic stroke subtypes in a rule-based manner. We determined whether CCS demonstrates high interrater reliability in order to be useful for international multicenter studies. METHODS: Twenty members of the International Stroke Genetics Consortium from 13 centers in 8 countries, who were not involved in the design and development of the CCS, independently assessed the same 50 consecutive patients with acute ischemic stroke through reviews of abstracted case summaries. Agreement among ratings was measured by kappa statistic. RESULTS: The κ value for causative classification was 0.80 (95% confidence interval [CI] 0.78-0.81) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.70 (95% CI 0.69-0.71) for the 16-subtype CCS. Correction of a software-related factor that generated ambiguity improved agreement: κ = 0.81 (95% CI 0.79-0.82) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.79 (95% CI 0.78-0.80) for the 16-subtype CCS. The κ value for phenotypic classification was 0.79 (95% CI 0.77-0.82) for supra-aortic large artery atherosclerosis, 0.95 (95% CI 0.93-0.98) for cardioembolism, 0.88 (95% CI 0.85-0.91) for small artery occlusion, and 0.79 (0.76-0.82) for other uncommon causes. CONCLUSIONS: CCS allows classification of stroke subtypes by multiple investigators with high reliability, supporting its potential for improving stroke classification in multicenter studies and ensuring accurate means of communication among different researchers, institutions, and eras.