Stroke: causes and clinical features

Stroke is a clinically defined syndrome of acute, focal neurological deficit attributed to vascular injury (infarction, haemorrhage) of the central nervous system. Stroke is the second leading cause of death and disability worldwide. Stroke is not a single disease but can be caused by a wide range of risk factors, disease processes and mechanisms. Hypertension is the most important modifiable risk factor for stroke, although its contribution differs for different subtypes. Most (85%) strokes are ischaemic, predominantly caused by small vessel arteriolosclerosis, cardioembolism and large artery athero-thromboembolism. Ischaemic strokes in younger patients can result from a different spectrum of causes such as extracranial dissection. Approximately 15% of strokes worldwide are the result of intracerebral haemorrhage, which can be deep (basal ganglia, brainstem), cerebellar or lobar. Deep haemorrhages usually result from deep perforator (hypertensive) arteriopathy (arteriolosclerosis), while lobar haemorrhages are mainly caused by cerebral amyloid angiopathy or arteriolosclerosis. A minority (about 20%) of intracerebral haemorrhages are caused by macrovascular lesions (vascular malformations, aneurysms, cavernomas), venous sinus thrombosis or rarer causes; these are particularly important in young patients (<50 years). Knowledge of vascular and cerebral anatomy is important in localizing strokes and understanding their mechanisms. This guides rational acute management, investigation, and secondary prevention

Feasibility of clinical trial recruitment for cerebral amyloid angiopathy: A specialist single centre experience

INTRODUCTION Cerebral amyloid angiopathy (CAA) is a small vessel disease characterised by vascular amyloid-beta deposition and recurrent intracerebral haemorrhage, for which there are limited data on the practicalities of clinical trial recruitment. METHODS We describe our single centre recruitment experience for a small biomarker pilot study, which aimed to recruit 10 patients with CAA. RESULTS The BOCAA (Biomarkers and Outcomes in Cerebral Amyloid Angiopathy) study recruited 10 CAA patients over 18 months. All patients were recruited from a prospective CAA database (n = 186); the majority of patients (n = 146, 78.5%) were ineligible for the BOCAA study. The most common reasons for exclusion were co-existent cognitive impairment or dementia (n = 42), failure to meet the imaging (modified Boston) criteria (n = 41), and anticoagulant or dual antiplatelet use (n = 18). CONCLUSIONS Recruitment of CAA patients to a small pilot study is feasible from a single specialist centre; however, centralised multicentre research databases will allow for more effective and co-ordinated recruitment to larger studies. Any future trial will need to consider how best to define mild disease, factors that influence group heterogeneity, and the impact of comorbidities that could limit participation in multimodal testing - but be mindful that more stringent entry criteria will limit recruitment capabilities

Cognitive dysfunction and associated neuroimaging biomarkers in antiphospholipid syndrome: a systematic review

OBJECTIVES: Cognitive dysfunction is common in patients with antiphospholipid antibodies (aPL) (including primary antiphospholipid syndrome (APS) or APS associated with systemic lupus erythematosus (SLE)). Neuroimaging biomarkers may contribute to our understanding of mechanisms of cognitive dysfunction in these cohorts. This review aimed to investigate: (1) the prevalence of cognitive dysfunction in studies including neuroimaging biomarkers; and (2) associations between cognition and neuroimaging biomarkers in patients with APS/aPL. METHODS: We conducted a systematic search of electronic databases PubMed, Science Direct, Scopus and PsycINFO and included studies with descriptions of neuroimaging findings, cognitive dysfunction, or both, in patients with aPL positivity (lupus anticoagulant, IgG and IgM anticardiolipin and anti-β2 glycoprotein-I antibodies). RESULTS: Of 120 search results we included 20 eligible studies (6 APS, 4 SLE with APS/aPL and 10 neuropsychiatric SLE (NPSLE)). We identified a medium risk of bias in 6/11 (54%) of cohort studies and 44% of case-control studies, as well as marked heterogeneity in cognitive assessment batteries, APS and aPL definitions and neuroimaging modalities and protocols. The prevalence of cognitive dysfunction ranged between 11% and 60.5%. Structural MRI was the most common imaging modality, reporting cognitive dysfunction to be associated with white matter hyperintensities, ischaemic lesions and cortical atrophy (4 with cerebral atrophy, 2 with white matter hyperintensities, and 2 with cerebral infarcts). CONCLUSION: Our findings confirm that cognitive impairment is commonly found in patients with aPL (including APS, SLE and NPSLE). The risk of bias, and heterogeneity in cognitive and neuroimaging biomarkers reported does not allow for definitive