Little Association between Intracranial Arterial Stenosis and Lacunar Stroke

Atheromatous middle cerebral artery (MCA) stenosis could cause lacunar stroke by occluding lenticulostriate artery origins, but atheroma is common, and previous studies lacked suitable controls. We aimed to determine if intracranial atheroma was more common in lacunar than in cortical ischaemic stroke. We recruited patients with lacunar stroke and controls with mild cortical stroke, confirmed the stroke subtype with magnetic resonance imaging and used transcranial Doppler ultrasound imaging to record flow velocity and focal stenoses in the basal intracranial arteries 1 month after stroke. We compared ipsi- and contralateral MCA mean flow velocities between stroke subtypes and tested for associations using linear mixed models. Amongst 67 lacunar and 67 mild cortical strokes, mean age 64 and 67 years, respectively, we found no difference in MCA mean flow velocity between cortical and lacunar patients. Increasing age and white matter lesion scores were independently associated with lower MCA flow velocities (0.2 cms−1 fall in velocity per year increase in age, p = 0.045; 3.75 cms−1 fall in flow velocity per point increase in white matter lesion score, p = 0.004). We found no intracranial arterial stenoses. MCA atheromatous stenosis is unlikely to be a common cause of lacunar stroke in white populations. Falling velocities with increasing white matter lesion scores may reflect progressive brain tissue loss leaving less tissue to supply

A systematic review of dynamic cerebral and peripheral endothelial function in lacunar stroke versus controls

Background: The aetiology of cerebral small vessel disease is unknown. An association with endothelial dysfunction has been suggested. We systematically assessed all relevant studies of dynamic endothelial function in patients with lacunar stroke, as a marker of small vessel disease. Methods: We searched for studies of cerebral or peripheral vascular reactivity in patients with lacunar or cortical (i.e. large artery atheromatous) ischaemic stroke or non-stroke controls. We calculated standardised mean difference (SMD) in vascular reactivity, +/- 95% confidence intervals (CI) between small vessel disease and control groups. Results: Sixteen publications (974 patients) were included. In lacunar stroke: cerebrovascular reactivity (n=534) was reduced compared with age-matched normal (SMD -0.94, 95%CI -1.17, -0.70), but not age+risk factor-matched controls (SMD 0.08, 95%CI -0.36, 0.53) or cortical strokes (SMD -0.29, 95%CI -0.69, 0.11); forearm flow mediated dilatation (n=401) was reduced compared with age-matched normal controls (SMD -1.04, 95%CI -1.33, -0.75) and age+risk factor-matched controls (SMD -0.94, 95%CI -1.26, -0.61), but not cortical strokes (SMD -0.23, 95%CI -0.55, 0.08). Conclusions: Endothelial dysfunction is present in patients with lacunar stroke but may simply reflect exposure to vascular risk factors and having a stroke, as a similar degree of dysfunction is found in cortical (large artery atheromatous) stroke. Current data do not confirm that endothelial dysfunction is specific to small vessel stroke. Future studies should include controls with non-lacunar stroke

“Can It Read My Mind?” – What Do the Public and Experts Think of the Current (Mis)Uses of Neuroimaging?

Emerging applications of neuroimaging outside medicine and science have received intense public exposure through the media. Media misrepresentations can create a gulf between public and scientific understanding of the capabilities of neuroimaging and raise false expectations. To determine the extent of this effect and determine public opinions on acceptable uses and the need for regulation, we designed an electronic survey to obtain anonymous opinions from as wide a range of members of the public and neuroimaging experts as possible. The surveys ran from 1st June to 30 September 2010, asked 10 and 21 questions, respectively, about uses of neuroimaging outside traditional medical diagnosis, data storage, science communication and potential methods of regulation. We analysed the responses using descriptive statistics; 660 individuals responded to the public and 303 individuals responded to the expert survey. We found evidence of public skepticism about the use of neuroimaging for applications such as lie detection or to determine consumer preferences and considerable disquiet about use by employers or government and about how their data would be stored and used. While also somewhat skeptical about new applications of neuroimaging, experts grossly underestimated how often neuroimaging had been used as evidence in court. Although both the public and the experts rated highly the importance of a better informed public in limiting the inappropriate uses to which neuroimaging might be put, opinions differed on the need for, and mechanism of, actual regulation. Neuroscientists recognized the risks of inaccurate reporting of neuroimaging capabilities in the media but showed little motivation to engage with the public. The present study also emphasizes the need for better frameworks for scientific engagement with media and public education

Blood-Brain Barrier Permeability and Long-Term Clinical and Imaging Outcomes in Cerebral Small Vessel Disease

BACKGROUND AND PURPOSE: Increased blood-brain barrier (BBB) permeability occurs in cerebral small vessel disease (SVD). It is not known if BBB changes predate progression of SVD. METHODS: We followed up patients with non-disabling lacunar or cortical stroke and BBB permeability MR imaging following their original stroke. About three years later, we assessed functional outcome (Oxford Handicap Score, OHS, poor outcome defined as 3-6), recurrent neurological events and white matter hyperintensity (WMH) progression on MRI. RESULTS: Amongst 70 patients, mean age 68 (SD±11) years, median time to clinical follow up was 39 months (IQR 30-45), median OHS was 2 (IQR 1-3); poor functional outcome was associated with higher baseline WMH score (p<0.001) and increased basal ganglia BBB permeability (p=0.046). Amongst 48 patients with follow-up MRI, WMH progression at follow-up was associated with baseline WMH (ANCOVA p<0.0001) and age (ANCOVA p=0.032). CONCLUSIONS: Further long term studies to evaluate the role of BBB dysfunction in progression of SVD are required in studies that are large enough to account for key prognostic influences such as baseline WMH and age

Functional, cognitive and physical outcomes 3 years after minor lacunar or cortical ischaemic stroke

Chest, Heart Stroke Scotland, Ref No: Res14/A157; NHS Research Scotland; The Wellcome Trust (WT088134/Z/09/A); the Row Fogo Charitable Trust; the European Union Horizon 2020, PHC-03-15, project No 666881, ’SVDs@ target’; the Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease, Ref No: 16 CVD 05; the Medical Research Council through the UK Dementia Research Institute; the Scottish Funding Council through the Scottish Imaging Network, APeer reviewedPublisher PD

Stability of estimated premorbid cognitive ability over time after minor stroke and its relationship with post-stroke cognitive ability

Considering premorbid or &#8220;peak&#8221; adult intelligence (IQ) is important when examining post-stroke cognition. The stability of estimated premorbid IQ and its relationship to current cognitive ability in stroke is unknown. We investigated changes in estimated premorbid IQ and current cognitive ability up to three years post-stroke. Minor stroke patients (NIHSS &lt; 8) were assessed at one to three months, one and three years&#8217; post-stroke. The National Adult Reading Test (NART) and Addenbrooke&#8217;s Cognitive Examination-Revised (ACE-R) were used to estimate premorbid IQ (NART IQ) and current cognitive ability respectively at each time-point. Baseline demographics, vascular and stroke characteristics were included. Of the 264 patients recruited (mean age 66), 158 (60%), 151 (57%), and 153 (58%) completed cognitive testing at each time-point respectively. NART IQ initially increased (mean difference (MD) = 1.32, 95% CI = 0.54 to 2.13, p &lt; 0.001) before decreasing (MD = &#8722;4.269, 95% CI = &#8722;5.12 to &#8722;3.41, p &lt; 0.001). ACE-R scores initially remained stable (MD = 0.29, 95% CI = &#8722;0.49 to 1.07, p &gt; 0.05) before decreasing (MD = &#8722;1.05, 95% CI = &#8722;2.08 to &#8722;0.01, p &lt; 0.05). Adjusting for baseline variables did not change the relationship between NART IQ and ACE-R with time. Increases in NART IQ were associated with more education. For ACE-R, older age was associated with declines, and higher NART IQ and more education was associated with increases. Across 3 years, we observed fluctuations in estimated premorbid IQ and minor changes in current cognitive ability. Future research should aim to identify variables associated with these changes. However, studies of post-stroke cognition should account for premorbid IQ

Integrity of normal-appearing white matter: influence of age, visible lesion burden and hypertension in patients with small vessel disease

White matter hyperintensities accumulate with age and occur in patients with stroke, but their pathogenesis is poorly understood. We measured multiple magnetic resonance imaging biomarkers of tissue integrity in normal-appearing white matter and white matter hyperintensities in patients with mild stroke, to improve understanding of white matter hyperintensities origins. We classified white matter into white matter hyperintensities and normal-appearing white matter and measured fractional anisotropy, mean diffusivity, water content (T1-relaxation time) and blood–brain barrier leakage (signal enhancement slope from dynamic contrast-enhanced magnetic resonance imaging). We studied the effects of age, white matter hyperintensities burden (Fazekas score) and vascular risk factors on each biomarker, in normal-appearing white matter and white matter hyperintensities, and performed receiver-operator characteristic curve analysis. Amongst 204 patients (34.3–90.9 years), all biomarkers differed between normal-appearing white matter and white matter hyperintensities (P < 0.001). In normal-appearing white matter and white matter hyperintensities, mean diffusivity and T1 increased with age (P < 0.001), all biomarkers varied with white matter hyperintensities burden (P < 0.001; P = 0.02 signal enhancement slope), but only signal enhancement slope increased with hypertension (P = 0.028). Fractional anisotropy showed complex age-white matter hyperintensities-tissue interactions; enhancement slope showed white matter hyperintensities-tissue interactions. Mean diffusivity distinguished white matter hyperintensities from normal-appearing white matter best at all ages. Blood–brain barrier leakage increases with hypertension and white matter hyperintensities burden at all ages in normal-appearing white matter and white matter hyperintensities, whereas water mobility and content increase as tissue damage accrues, suggesting that blood–brain barrier leakage mediates small vessel disease-related brain damage

Diffusion-weighted imaging and diagnosis of transient ischaemic attack

Peer reviewedPublisher PD

White matter hyperintensity reduction and outcomes after minor stroke

Objective: To assess factors associated with white matter hyperintensity (WMH) change in a large cohort after observing obvious WMH shrinkage 1 year after minor stroke in several participants in a longitudinal study. Methods: We recruited participants with minor ischemic stroke and performed clinical assessments and brain MRI. At 1 year, we assessed recurrent cerebrovascular events and dependency and repeated the MRI. We assessed change in WMH volume from baseline to 1 year (normalized to percent intracranial volume [ICV]) and associations with baseline variables, clinical outcomes, and imaging parameters using multivariable analysis of covariance, model of changes, and multinomial logistic regression. Results: Among 190 participants (mean age 65.3 years, range 34.3–96.9 years, 112 [59%] male), WMH decreased in 71 participants by 1 year. At baseline, participants whose WMH decreased had similar WMH volumes but higher blood pressure (p = 0.0064) compared with participants whose WMH increased. At 1 year, participants with WMH decrease (expressed as percent ICV) had larger reductions in blood pressure (β = 0.0053, 95% confidence interval [CI] 0.00099–0.0097 fewer WMH per 1–mm Hg decrease, p = 0.017) and in mean diffusivity in normal-appearing white matter (β = 0.075, 95% CI 0.0025–0.15 fewer WMH per 1-unit mean diffusivity decrease, p = 0.043) than participants with WMH increase; those with WMH increase experienced more recurrent cerebrovascular events (32%, vs 16% with WMH decrease, β = 0.27, 95% CI 0.047–0.50 more WMH per event, p = 0.018). Conclusions: Some WMH may regress after minor stroke, with potentially better clinical and brain tissue outcomes. The role of risk factor control requires verification. Interstitial fluid alterations may account for some WMH reversibility, offering potential intervention targets

Small vessel disease and dietary salt intake: cross sectional study and systematic review

Background: Higher dietary salt intake increases the risk of stroke and may increase white matter hyperintensity (WMH) volume. We hypothesized that a long-term higher salt intake may be associated with other features of small vessel disease (SVD). Methods: We recruited consecutive patients with mild stroke presenting to the Lothian regional stroke service. We performed brain magnetic resonance imaging, obtained a basic dietary salt history, and measured the urinary sodium/creatinine ratio. We also carried out a systematic review to put the study in the context of other studies in the field. Results: We recruited 250 patients, 112 with lacunar stroke and 138 with cortical stroke, with a median age of 67.5 years. After adjustment for risk factors, including age and hypertension, patients who had not reduced their salt intake in the long term were more likely to have lacunar stroke (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.10-3.29), lacune(s) (OR, 2.06; 95% CI, 1.09-3.99), microbleed(s) (OR, 3.4; 95% CI, 1.54, 8.21), severe WMHs (OR, 2.45; 95% CI 1.34-4.57), and worse SVD scores (OR, 2.17; 95% CI, 1.22-3.9). There was limited association between SVD and current salt intake or urinary sodium/creatinine ratio. Our systematic review found no previously published studies of dietary salt and SVD. Conclusion: The association between dietary salt and background SVD is a promising indication of a potential neglected contributory factor for SVD. These results should be replicated in larger, long-term studies using the recognized gold-standard measures of dietary sodium