A comparison of location of acute symptomatic vs. 'silent' small vessel lesions

Background: Acute lacunar ischaemic stroke, white matter hyperintensities, and lacunes are all features of cerebral small vessel disease. It is unclear why some small vessel disease lesions present with acute stroke symptoms, whereas others typically do not. Aim: To test if lesion location could be one reason why some small vessel disease lesions present with acute stroke, whereas others accumulate covertly. Methods: We identified prospectively patients who presented with acute lacunar stroke symptoms with a recent small subcortical infarct confirmed on magnetic resonance diffusion imaging. We compared the distribution of the acute infarcts with that of white matter hyperintensity and lacunes using computational image mapping methods. Results: In 188 patients, mean age 67 ± standard deviation 12 years, the lesions that presented with acute lacunar ischaemic stroke were located in or near the main motor and sensory tracts in (descending order): posterior limb of the internal capsule (probability density 0·2/mm3), centrum semiovale (probability density = 0·15/mm3), medial lentiform nucleus/lateral thalamus (probability density = 0·09/mm3), and pons (probability density = 0·02/mm3). Most lacunes were in the lentiform nucleus (probability density = 0·01–0·04/mm3) or external capsule (probability density = 0·05/mm3). Most white matter hyperintensities were in centrum semiovale (except for the area affected by the acute symptomatic infarcts), external capsules, basal ganglia, and brainstem, with little overlap with the acute symptomatic infarcts (analysis of variance, P < 0·01). Conclusions: Lesions that present with acute lacunar ischaemic stroke symptoms may be more likely noticed by the patient through affecting the main motor and sensory tracts, whereas white matter hyperintensity and asymptomatic lacunes mainly affect other areas. Brain location could at least partly explain the symptomatic vs. covert development of small vessel disease

A Large Web-Based Observer Reliability Study of Early Ischaemic Signs on Computed Tomography. The Acute Cerebral CT Evaluation of Stroke Study (ACCESS)

BACKGROUND: Early signs of ischaemic stroke on computerised tomography (CT) scanning are subtle but CT is the most widely available diagnostic test for stroke. Scoring methods that code for the extent of brain ischaemia may improve stroke diagnosis and quantification of the impact of ischaemia. METHODOLOGY AND PRINCIPAL FINDINGS: We showed CT scans from patients with acute ischaemic stroke (n = 32, with different patient characteristics and ischaemia signs) to doctors in stroke-related specialties world-wide over the web. CT scans were shown twice, randomly and blindly. Observers entered their scan readings, including early ischaemic signs by three scoring methods, into the web database. We compared observers' scorings to a reference standard neuroradiologist using area under receiver operator characteristic curve (AUC) analysis, Cronbach's alpha and logistic regression to determine the effect of scales, patient, scan and observer variables on detection of early ischaemic changes. Amongst 258 readers representing 33 nationalities and six specialties, the AUCs comparing readers with the reference standard detection of ischaemic signs were similar for all scales and both occasions. Being a neuroradiologist, slower scan reading, more pronounced ischaemic signs and later time to CT all improved detection of early ischaemic signs and agreement on the rating scales. Scan quality, stroke severity and number of years of training did not affect agreement. CONCLUSIONS: Large-scale observer reliability studies are possible using web-based tools and inform routine practice. Slower scan reading and use of CT infarct rating scales improve detection of acute ischaemic signs and should be encouraged to improve stroke diagnosis

Variation in risk factors for recent small subcortical infarcts with infarct size, shape and location

BACKGROUND AND PURPOSE: Lacunar infarction is due to a perforating arteriolar abnormality. Possible causes include embolism, atheromatosis or intrinsic disease. We examined whether the size, shape or location of the lacunar infarct varied with embolic sources, systemic atheroma or vascular risk factors. METHODS: We examined data from three prospective studies of patients with clinical and diffusion-weighted imaging (DWI) positive symptomatic lacunar infarction who underwent full clinical assessment and investigation for stroke risk factors. Lacunar infarct size (maximum diameter; shape, oval/tubular; location, basal ganglia/centrum semiovale/brainstem) were coded blind to clinical details. RESULTS: Amongst 195 patients, 48 infarcts were tubular, 50 were 15-20mm diameter, 97 were in the basal ganglia and 74 in the centrum semiovale. There was no association between infarct size or shape and any risk factors. Centrum semiovale infarcts were less likely to have a potential relevant embolic source (4% v 11%, OR 0.16 95% confidence interval (CI) 0.03-0.83) and caused a lower National Institute of Health Stroke Scale (NIHSS) (2 v 3, OR 0.78 95% CI 0.62-0.98) than basal ganglia infarcts. There were no other differences by infarct location. CONCLUSIONS: Lacunar infarcts in the basal ganglia caused marginally more severe strokes and were three times as likely to have a potential embolic source than those in the centrum semiovale but the overall rate of carotid or known cardiac embolic sources (11%) was low. We found no evidence that other risk factors differed with location, size or shape suggesting that most lacunar infarcts share a common intrinsic arteriolar pathology

Vascular contributions to cognitive impairment and dementia: Research consortia that focus on etiology and treatable targets to lessen the burden of dementia worldwide

The research into vascular contributions to cognitive impairment and dementia (VCID) aims to understand the importance of cerebrovascular biology in cognitive decline. Prevention and treatment of VCID is poised to have major impact on dementia-related disease burden and is thus a critical emerging objective in dementia research. This article presents VCID consortia focused on multidisciplinary approaches to identify key pathologic targets and develop diagnostic tools with the goal of bridging the divide between basic research and clinical trials. Members of these multi-institute, multidisciplinary consortia provide a prospective on the history and emerging science of VCID and how VCID consortia can address some of the more complex questions in VCID and drive the field forward. These consortia, and others like them, are uniquely suited to tackle some of the most difficult obstacles in translating research to the clinic

Management of incidental findings during imaging research in "healthy" volunteers: current UK practice

OBJECTIVES: Incidental findings (IF) are becoming increasingly common due to the proliferation of imaging research. IFs can be life-changing for “healthy” volunteers. This study examined variation in IF management in UK research studies of healthy volunteers, including comparison with ethical and legal guidelines, thus providing baseline data and informing future practice. METHODS: Questionnaire of participant background [medical/non-medical; radiologist/non-radiologist; years as principal investigator (PI)], type of research (involving children or not), institutional policy, volunteer information, radiologist involvement in reporting scans and IF disclosure mechanisms. Investigator's current and perceived “ideal” practice was examined. Participants were PIs performing imaging research of healthy volunteers approved by UK ethics committees (2006–2009). RESULTS: 63/146 (43%) surveys completed. 54/61 (88.5%) had site-specific guidelines. Information commonly provided to volunteers should IF be found: personal data (51/62; 82%), contingency plans (54/62; 87%) and disclosure to general practitioner (GP)/treating physician (47/62; 76%). PIs used different strategies for image review. Commonest: radiologist reports research scans only when researcher suspicious of IF [15/57 (26%) compared with 5/28 (16%) in ideal practice]. Commonest ideal reporting strategy: routine reporting by specialist radiologists [9/28 (29%) compared with 8/57 (14%) in current practice]. 49/56 (87.5%) have a standardised disclosure contingency plan, usually involving GP. PIs most commonly disclosed IFs to volunteers when judged relevant (27/58; 47%), most commonly face to face (22/54; 41%), by volunteer's GP (26/60; 43%). Background of PI influenced consent, reporting and disclosure practice. CONCLUSION: There is wide variation in handling IFs in UK imaging research. Much of the current practice contravenes the vague existing legal and ethical guidelines, and is unlikely to be in the best interests of volunteers or researchers