Lacunar Stroke

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Oscar R Benavente - One of the best experts on this subject based on the ideXlab platform.

  • the relationship between glucose control and cognitive function in people with diabetes after a Lacunar Stroke
    The Journal of Clinical Endocrinology and Metabolism, 2021
    Co-Authors: Leslie A Mcclure, Tali Cukiermanyaffe, Thomas Risoli, Jackie Bosch, Mike Sharma, Hertzel C Gerstein, Oscar R Benavente
    Abstract:

    CONTEXT Lacunar Strokes and diabetes are risk factors for cognitive dysfunction. Elucidating modifiable risk factors for cognitive dysfunction has great public health implications. One factor may be glycemic status, as measured by glycated hemoglobin (A1c). OBJECTIVE The aim of this study was to assess the relationship between A1c and cognitive function in Lacunar Stroke patients with diabetes. METHODS The effect of baseline and follow-up A1c on the baseline and the change in Cognitive Assessment Screening Instrument (CASI) score over time among participants with a median of 2 cognitive assessments (range, 1-5) was examined in 942 individuals with diabetes and a Lacunar Stroke who participated in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (ClinicalTrials.gov No. NCT00059306). RESULTS Every 1% higher baseline A1c was associated with a 0.06 lower standardized CASI z score (95% CI, -0.101 to -0.018). Higher baseline A1c values were associated with lower CASI z scores over time (P for interaction = .037). A 1% increase in A1c over time corresponded with a CASI score decrease of 0.021 (95% CI, -0.0043 to -0.038) during follow-up. All these remained statistically significant after adjustment for age, sex, education, race, depression, hypertension, hyperlipidemia, body mass index, cardiovascular disease, obstructive sleep apnea, diabetic retinopathy, nephropathy insulin use, and white-matter abnormalities. CONCLUSION This analysis of Lacunar Stroke patients with diabetes demonstrates a relationship between A1c and change in cognitive scores over time. Intervention studies are needed to delineate whether better glucose control could slow the rate of cognitive decline in this high-risk population.

  • inflammatory markers and outcomes after Lacunar Stroke levels of inflammatory markers in treatment of Stroke study
    Stroke, 2016
    Co-Authors: Amelia K Boehme, Leslie A Mcclure, Oscar R Benavente, Yu Zhang, Jorge M Luna, Oscar H Del Brutto, Mitchell S V Elkind
    Abstract:

    Background and Purpose— We hypothesized that concentrations of interleukin 6 (IL-6), serum amyloid A, tumor necrosis factor-α receptor 1, CD40 ligand, and monocyte chemoattractant protein 1 would predict recurrent ischemic Stroke and major vascular events after recent Lacunar Stroke. Methods— Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within the Secondary Prevention of Small Subcortical Strokes (SPS3) study, a Phase III trial in patients with recent Lacunar Stroke. Crude and Adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CI) for recurrence risks. Results— Among 1244 patients with Lacunar Stroke (mean age, 63.3±10.8 years), there were 115 major vascular events (Stroke, myocardial infarction, and vascular death). The risk of major vascular events increased with elevated concentrations of both tumor necrosis factor-α receptor 1 (adjusted HR per SD, 1.21; 95% CI, 1.05–1.41; P =0.01) and IL-6 (adjusted HR per SD, 1.10; 95% CI, 1.02–1.19; P =0.008). Compared with the bottom quartile (tumor necrosis factor-α receptor 1 3.63 ng/L) were at twice the risk of major vascular events after adjusting for demographics (partially adjusted HR, 1.98; 95% CI, 1.11–3.52), though the effect attenuated after adjusting for other risk factors and statin use (adjusted HR, 1.68; 95% CI, 0.93–3.04). Serum amyloid A, CD40 ligand, and monocyte chemoattractant protein 1 were not associated with prognosis. Conclusions— Among recent Lacunar Stroke patients, IL-6 and TNF receptor concentrations predict risk of recurrent vascular events, and they are associated with the effect of antiplatelet therapies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

  • effect of intensive versus usual blood pressure control on kidney function among individuals with prior Lacunar Stroke a post hoc analysis of the secondary prevention of small subcortical Strokes sps3 randomized trial
    Circulation, 2016
    Co-Authors: Carmen A Peralta, Leslie A Mcclure, Carole L White, Oscar R Benavente, Rebecca Scherzer, Michelle C Odden, Michael G Shlipak, Pablo E Pergola
    Abstract:

    Background —The effect of intensive blood pressure (BP) lowering on kidney function among persons with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established. Methods and Results —Among 2610 participants randomized to lower SBP target ( 30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with Stroke, major vascular events (MVE) and the composite Stroke, death, MVE or myocardial infarction, using multivariable Cox regression, separately and jointly including test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11; 949 (36%) were diabetic, mean eGFR was 80±19 ml/min/1.73m 2 . At 9 months, achieved SBP was 137±15 in higher vs. 127±14 mmHg in lower BP group, and differences were maintained throughout follow-up (mean 3.2 years). Compared with higher, lower BP target had -0.50 (95%CI - 0.79 to -0.21) ml/min/1.73m 2 /year faster eGFR decline. Differences were most pronounced during the first year (-2.1 ml/min/1.73m 2 (95%CI -0.97 to -3.2)), whereas rates of eGFR decline did not differ after year 1 (-0.095, -0.47 to 0.23). A total of 313 (24%) persons in the lower BP group had rapid kidney function decline, compared with 247 (19%) in higher (OR 1.4 (95%CI 1.1 to 1.6)). Differences in rapid decline by treatment arm were apparent in the first year (OR 1.4, 1.1-1.8), but were not significant after year 1 (OR 1.0, 0.73-1.4). Rapid decline was associated with higher risk for Stroke, MVE and composite after full adjustment among persons randomized to the higher BP target (Stroke HR 1.93 (1.15 to 3.21), but not the lower BP arm, Stroke HR 0.93 (0.50 to 1.75) (all p interaction <0.06). Conclusions —In persons with prior Lacunar Stroke and relatively preserved kidney function, intensive BP lowering was associated with greater likelihood of rapid kidney function decline. Differences were primarily observed during the first year of anti-hypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering. Clinical Trial Registration Information —ClinicalTrials.gov. Identifier: NCT00059306.

  • abstract wp160 inflammatory markers and outcomes after Lacunar Stroke the levels of inflammatory markers in treatment of Stroke study
    Stroke, 2016
    Co-Authors: Amelia K Boehme, Leslie A Mcclure, Oscar R Benavente, Jorge M Luna, Oscar H Del Brutto, Mitchell S V Elkind
    Abstract:

    Background: C-reactive protein predicts prognosis after Stroke, but relationships of other inflammatory biomarkers to prognosis is uncertain. We hypothesized that concentrations of interleukin 6 (IL6), serum amyloid A, tumor necrosis factor-α receptor 1 (TNFR1), CD40 ligand, and monocyte chemoattractant protein 1 predict recurrent major vascular events (MVE) after Lacunar Stroke. Methods: Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, ancillary biomarker study nested within the Secondary Prevention of Small Subcortical Strokes (SPS3) Phase 3 trial in patients with recent Lacunar Stroke. Patients were randomized to aspirin versus aspirin/clopidogrel. Blood samples were collected at enrollment, and markers measured centrally using ELISA. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (HR, 95% CI) for risk of MVE (Stroke, myocardial infarction, vascular death) after adjusting for demographics, comorbidities, and statin use. Results: Among 1244 Lacunar Stroke patients (mean age 63.3 ± 10.8 years), there were 115 MVE. Risk increased with concentrations of both TNFR1 (adj HR per standard deviation [SD] 1.21, 95% CI 1.05-1.41) and IL6 (adj HR per SD 1.10, 95% CI 1.02-1.19). Compared with the bottom quartile of TNFR1, those in the top quartile had twice the risk after adjusting for demographics (HR 1.98, 95% CI 1.11-3.52), though this attenuated after adjusting for other risk factors (adjusted HR 1.68, 95% CI 0.93-3.04). There was an interaction between antiplatelet assignment and TNFR1 (p=0.008; figure) and IL6 quartiles (p=0.035); as biomarker concentrations increased, dual antiplatelets became less effective than aspirin alone. Other markers were not associated with prognosis. Conclusions: Among recent Lacunar Stroke patients, IL6 and TNF receptor concentrations predict risk of recurrent vascular events and efficacy of antiplatelet therapies.

  • the effect of intensive vs usual blood pressure control on kidney function among persons with prior Lacunar Stroke a post hoc analysis of the sps3 randomized trial
    Circulation, 2016
    Co-Authors: Carmen A Peralta, Leslie A Mcclure, Carole L White, Oscar R Benavente, Rebecca Scherzer, Michelle C Odden, Michael G Shlipak, Pablo E Pergola
    Abstract:

    Background —The effect of intensive blood pressure (BP) lowering on kidney function among persons with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established. Methods and Results —Among 2610 participants randomized to lower SBP target ( 30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with Stroke, major vascular events (MVE) and the composite Stroke, death, MVE or myocardial infarction, using multivariable Cox regression, separately and jointly including test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11; 949 (36%) were diabetic, mean eGFR was 80±19 ml/min/1.73m 2 . At 9 months, achieved SBP was 137±15 in higher vs. 127±14 mmHg in lower BP group, and differences were maintained throughout follow-up (mean 3.2 years). Compared with higher, lower BP target had -0.50 (95%CI - 0.79 to -0.21) ml/min/1.73m 2 /year faster eGFR decline. Differences were most pronounced during the first year (-2.1 ml/min/1.73m 2 (95%CI -0.97 to -3.2)), whereas rates of eGFR decline did not differ after year 1 (-0.095, -0.47 to 0.23). A total of 313 (24%) persons in the lower BP group had rapid kidney function decline, compared with 247 (19%) in higher (OR 1.4 (95%CI 1.1 to 1.6)). Differences in rapid decline by treatment arm were apparent in the first year (OR 1.4, 1.1-1.8), but were not significant after year 1 (OR 1.0, 0.73-1.4). Rapid decline was associated with higher risk for Stroke, MVE and composite after full adjustment among persons randomized to the higher BP target (Stroke HR 1.93 (1.15 to 3.21), but not the lower BP arm, Stroke HR 0.93 (0.50 to 1.75) (all p interaction <0.06). Conclusions —In persons with prior Lacunar Stroke and relatively preserved kidney function, intensive BP lowering was associated with greater likelihood of rapid kidney function decline. Differences were primarily observed during the first year of anti-hypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering. Clinical Trial Registration Information —ClinicalTrials.gov. Identifier: NCT00059306.

Joanna M Wardlaw - One of the best experts on this subject based on the ideXlab platform.

  • improving clinical detection of acute Lacunar Stroke analysis from the ist 3
    Stroke, 2020
    Co-Authors: Francesco Arba, Joanna M Wardlaw, Peter Sandercock, Grant Mair, Stephen J Phillips
    Abstract:

    Background and Purpose- We aim to identify factors associated with imaging-confirmed Lacunar Strokes and improve their rapid clinical identification early after symptom onset using data from the IST-3 (Third International Stroke Trial). Methods- We selected patients likely to have Lacunar infarcts as those presenting with: Oxfordshire Community Stroke Project Lacunar syndrome; a random sample with National Institutes of Health Stroke Scale (NIHSS) score <7; and recent Lacunar infarct identified on imaging by IST-3 central blinded expert panel. An independent reviewer rated brain scans of this sample and classified visible infarcts according to type, size, and location. We investigated factors associated with presence of Lacunar infarct on a 24 to 48 hour follow-up scan using multivariable logistic regression and calculated sensitivity and specificity of Oxfordshire Community Stroke Project alone and in combination with NIHSS score <7. Results- We included 568 patients (330 Lacunar syndrome; 147 with NIHSS score <7; 91 with Lacunar infarct on baseline imaging, numbers exclude overlaps between groups), mean (±SD) age, 73.2 (±13.6) years, 316 (56%) males, and median NIHSS score 5 (IQR, 4-8). On 24 to 48 hour scan, 138 (24%) patients had Lacunar infarcts, 176 (31%) other infarct subtypes, 254 (45%) no visible infarct. Higher baseline systolic blood pressure (odds ratio, 1.01 [95% CI, 1.01-1.02]) and preexisting lacunes (odds ratio, 2.29 [95% CI, 1.47-3.57) were associated with recent Lacunar infarcts. Sensitivity and specificity of Lacunar syndrome was modest (58% and 45%, respectively), but adding NIHSS score <7 increased specificity (99%), positive and negative predictive values (97% and 87%, respectively). Conclusions- In patients presenting within 6 hours of Stroke onset, adding NIHSS score <7 to Oxfordshire Community Stroke Project Lacunar syndrome classification may increase specificity for identifying Lacunar Stroke early after Stroke onset. Our findings may help selection of patients for clinical trials of Lacunar Stroke and should be validated externally. Registration- URL: http://www.controlled-trials.com/; Unique identifier: ISRCTN25765518.

  • systematic review and meta analysis of interventions tested in animal models of Lacunar Stroke
    Stroke, 2014
    Co-Authors: Hugo Pedder, Hanna M Vesterinen, Malcolm R Macleod, Joanna M Wardlaw
    Abstract:

    Background and Purpose—A total of 25% of Strokes are Lacunar, and these are pathophysiologically different from large artery Strokes. Despite emerging evidence of a substantial impact on physical disability and dementia, little attention has been paid to the development of specific treatments. The optimal use of the animal models of Lacunar Stroke used to test candidate interventions is not known. Methods—We conducted a systematic review and meta-analysis of studies testing candidate interventions in animal models of Lacunar Stroke. We used random-effects meta-analysis to assess the impact of study characteristics and trim and fill to seek evidence of publication bias. Results—The efficacy of 43 distinct interventions was described in 57 publications. The median number of quality checklist items scored was 3 of 8 (interquartile range, 2–4). Many models reflected mechanisms of limited relevance to Lacunar Stroke. Meta-analysis of results from 27 studies showed that on average, infarct size and neurobehavio...

  • blood markers of coagulation fibrinolysis endothelial dysfunction and inflammation in Lacunar Stroke versus non Lacunar Stroke and non Stroke systematic review and meta analysis
    Cerebrovascular Diseases, 2014
    Co-Authors: Stewart Wiseman, Fergal Marlborough, Fergus N. Doubal, David J. Webb, Joanna M Wardlaw
    Abstract:

    Background: The cause of cerebral small vessel disease is not fully understood, yet it is important, accounting for about 25% of all Strokes. It also increases the risk of having another Stroke and contributes to about 40% of dementias. Various processes have been implicated, including microatheroma, endothelial dysfunction and inflammation. A previous review investigated endothelial dysfunction in Lacunar Stroke versus mostly non-Stroke controls while another looked at markers of inflammation and endothelial damage in ischaemic Stroke in general. We have focused on blood markers between clinically evident Lacunar Stroke and other subtypes of ischaemic Stroke, thereby controlling for Stroke in general. Summary: We systematically assessed the literature for studies comparing blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in Lacunar Stroke versus non-Stroke controls or other ischaemic Stroke subtypes. We assessed the quality of included papers and meta-analysed results. We split the analysis on time of blood draw in relation to the Stroke. We identified 1,468 full papers of which 42 were eligible for inclusion, including 4,816 ischaemic Strokes, of which 2,196 were Lacunar and 2,500 non-Stroke controls. Most studies subtyped Stroke using TOAST. The definition of Lacunar Stroke varied between studies. Markers of coagulation/fibrinolysis (tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), fibrinogen, D-dimer) were higher in Lacunar Stroke versus non-Stroke although fibrinogen was no different to non-Stroke in the acute phase. tPA and PAI were no different between Lacunar and non-Lacunar Stroke. Fibrinogen and D-dimer were significantly lower in Lacunar Stroke compared to other ischaemic Strokes, both acutely and chronically. Markers of endothelial dysfunction (homocysteine, von Willebrand Factor (vWF), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM), vascular cellular adhesion molecule-1 (VCAM)) were higher or had insufficient or conflicting data (P-selectin, VCAM) in Lacunar Stroke versus non-Stroke. Compared to other ischaemic Stroke subtypes, homocysteine did not differ in Lacunar Stroke while vWF was significantly lower in Lacunar Stroke acutely [atherothrombotic standardized mean difference, SMD, -0.34 (-0.61, -0.08); cardioembolic SMD -0.38 (-0.62, -0.14)], with insufficient data chronically. Markers of inflammation (C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)) were higher in Lacunar Stroke versus non-Stroke, although there were no studies measuring TNF-α chronically and the sole study measuring IL-6 chronically showed no difference between Lacunar Stroke and non-Stroke. Compared to other ischaemic Stroke subtypes, there was no difference (CRP) or insufficient or conflicting data (TNF-α) to Lacunar Stroke. IL-6 was significantly lower [atherothrombotic SMD -0.37 (-0.63, -0.10); cardioembolic SMD -0.52 (-0.82, -0.22)] in Lacunar Stroke acutely, with insufficient data chronically. Key Messages: Lacunar Stroke is an important Stroke subtype. More studies comparing Lacunar Stroke to non-Lacunar Stroke specifically, rather than to non-Stroke controls, are needed. Prospective studies with measurements taken well after the acute event are more likely to be helpful in determining pathogenesis. The available data in this review were limited and do not exclude the possibility that peripheral inflammatory processes including endothelial dysfunction are associated with Lacunar Stroke and cerebral small vessel disease.

  • cognitive impairment after Lacunar Stroke systematic review and meta analysis of incidence prevalence and comparison with other Stroke subtypes
    Journal of Neurology Neurosurgery and Psychiatry, 2013
    Co-Authors: Stephen Makin, Martin Dennis, Sarah Turpin, Joanna M Wardlaw
    Abstract:

    Background Cognitive impairment and dementia are common after Stroke. It is unclear if risk differs between ischaemic Stroke subtypes. Lacunar Strokes might be less likely to affect cognition than more severe, larger cortical Strokes, except that Lacunar Strokes are associated with cerebral small vessel disease (SVD), which is the commonest vascular cause of dementia. Methods We searched MEDLINE and PsychINFO for studies of mild cognitive impairment (MCI) or dementia after Lacunar or cortical ischaemic Stroke. We calculated the OR for cognitive impairment/dementia in Lacunar versus non-Lacunar Stroke, and their incidence and prevalence in Lacunar Stroke as a pooled proportion. Findings We identified 24 relevant studies of 7575 patients, including 2860 with Lacunar Stroke; 24% had MCI or dementia post Stroke. Similar proportions of patients with Lacunar and non-Lacunar Stroke (16 studies, n=6478) had MCI or dementia up to 4 years after Stroke (OR 0.72 (95% CI 0.43 to 1.20)). The prevalence of dementia after Lacunar Stroke (six studies, n=1421) was 20% (95% CI 9 to 33) and the incidence of MCI or dementia (four studies, n=275) was 37% (95% CI 23 to 53). Data were limited by short follow-up, subtype classification methods and confounding. Interpretation Cognitive impairment appears to be common after Lacunar Strokes despite their small size, suggesting that associated SVD may increase their impact. New prospective studies are required with accurate Stroke subtyping to assess long term outcomes while accounting for confounders.

  • cavitation of deep Lacunar infarcts in patients with first ever Lacunar Stroke a 2 year follow up study with mr
    Stroke, 2012
    Co-Authors: Caroline M. J. Loos, Joanna M Wardlaw, Julie Staals, Robert J Van Oostenbrugge
    Abstract:

    Background and Purpose—Studies in patients with Lacunar Stroke often assess the number of lacunes. However, data on how many symptomatic Lacunar infarcts cavitate into a lacune are limited. We assessed the evolution of symptomatic Lacunar infarcts over 2-year follow-up. Methods—In 82 patients with first-ever Lacunar Stroke with a Lacunar infarct in the deep brain regions (excluding the centrum semiovale), we performed a brain MR at presentation and 2 years later. We classified cavitation of Lacunar infarcts at baseline and on follow-up MR as absent, incomplete, or complete. We recorded time to imaging, infarct size, and vascular risk factors. Results—On baseline MR, 38 (46%) index infarcts showed complete or incomplete cavitation. Median time to imaging was 8 (0–73) days in noncavitated and 63 (1–184) days in cavitated lesions (P<0.05). On follow-up imaging, 94% of the Lacunar infarcts were completely or incompletely cavitated, most had reduced in diameter, and 5 (6%) had disappeared. Vascular risk factor...

Hugh S. Markus - One of the best experts on this subject based on the ideXlab platform.

  • causal impact of type 2 diabetes mellitus on cerebral small vessel disease a mendelian randomization analysis
    Stroke, 2018
    Co-Authors: Hugh S. Markus, Loes C A Ruttenjacobs, Junfeng Liu, Ming Liu, Matthew Traylor
    Abstract:

    Background and Purpose— The relationship between type 2 diabetes mellitus (T2D) and cerebral small vessel disease (CSVD) is unclear. We aimed to examine the causal effect of T2D, fasting glucose levels, and higher insulin resistance on CSVD using Mendelian randomization. Methods— Five CSVD phenotypes were studied; 2 were clinical outcomes associated with CSVD (Lacunar Stroke: n=2191/27 297 and intracerebral hemorrhage [ICH]: n=2254/8195 [deep and lobar ICH]), whereas 3 were radiological markers of CSVD (white matter hyperintensities: n=8429; fractional anisotropy [FA]: n=8357; and mean diffusivity: n=8357). We applied 2 complementary analyses to evaluate the association of T2D with CSVD. First, we used summarized data from genome-wide association study to calculate the effects of T2D-related variants on CSVD with inverse-variance weighted and weighted median approaches. Second, we performed a genetic risk score approach to test the effects of T2D-associated variants on white matter hyperintensities, FA, and mean diffusivity using individual-level data in UK Biobank. Results— T2D was associated with higher risk of Lacunar Stroke (odds ratio [OR], 1.15; 95% confidence interval [CI], 1.04–1.28; P =0.007) and lower mean FA (OR, 0.78; 95% CI, 0.66–0.92; P =0.004) but not white matter hyperintensities volume (OR, 1.01; 95% CI, 0.97–1.04; P =0.626), higher mean diffusivity (OR, 1.04; 95% CI, 0.89–1.23; P =0.612), ICH (OR, 1.07; 95% CI, 0.95–1.20; P =0.269), lobar ICH (OR, 1.07; 95% CI, 0.89–1.28; P =0.466), or deep ICH (OR, 1.16; 95% CI, 0.99–1.36; P =0.074). Weighted median and penalized median weighted analysis showed similar effect estimates of T2D on Lacunar Stroke and FA, but with wider CIs, meaning they were not significant. The genetic score on individual-level data was significantly associated with FA (OR, 0.63; 95% CI, 0.45–0.89; P =0.008) after adjusting for potential confounders. Conclusions— Our Mendelian randomization study provides evidence to suggest that T2D may be causally associated with CSVD, in particular with Lacunar Stroke and FA.

  • rare variants of the 3 5 dna exonuclease trex1 in early onset small vessel Stroke
    Wellcome Open Research, 2017
    Co-Authors: Sarah Mcglasson, Hugh S. Markus, Kristiina Rannikmae, Steven Bevan, Clare V Logan, Louise S Bicknell, Alexa Jury, Andrew P Jackson, Cathie Sudlow
    Abstract:

    Background: Monoallelic and biallelic mutations in the exonuclease TREX1 cause monogenic small vessel diseases (SVD). Given recent evidence for genetic and pathophysiological overlap between monogenic and polygenic forms of SVD, evaluation of TREX1 in small vessel Stroke is warranted. Methods: We sequenced the TREX1 gene in an exploratory cohort of patients with Lacunar Stroke (Edinburgh Stroke Study, n=290 Lacunar Stroke cases). We subsequently performed a fully blinded case-control study of early onset MRI-confirmed small vessel Stroke within the UK Young Lacunar Stroke Resource (990 cases, 939 controls). Results: No patients with canonical disease-causing mutations of TREX1 were identified in cases or controls. Analysis of an exploratory cohort identified a potential association between rare variants of TREX1 and patients with Lacunar Stroke. However, subsequent controlled and blinded evaluation of TREX1 in a larger and MRI-confirmed patient cohort, the UK Young Lacunar Stroke Resource, identified heterozygous rare variants in 2.1% of cases and 2.3% of controls. No association was observed with Stroke risk (odds ratio = 0.90; 95% confidence interval, 0.49-1.65 p=0.74). Similarly no association was seen with rare TREX1 variants with predicted deleterious effects on enzyme function (odds ratio = 1.05; 95% confidence interval, 0.43-2.61 p=0.91). Conclusions: No patients with early-onset Lacunar Stroke had genetic evidence of a TREX1-associated monogenic microangiopathy. These results show no evidence of association between rare variants of TREX1 and early onset Lacunar Stroke. This includes rare variants that significantly affect protein and enzyme function. Routine sequencing of the TREX1 gene in patients with early onset Lacunar Stroke is therefore unlikely to be of diagnostic utility, in the absence of syndromic features or family history.

  • oxidative phosphorylation and Lacunar Stroke genome wide enrichment analysis of common variants
    Neurology, 2016
    Co-Authors: Matthew Traylor, Christopher D Anderson, Robert Hurford, Steve Bevan, Hugh S. Markus
    Abstract:

    Objective: We investigated whether oxidative phosphorylation (OXPHOS) abnormalities were associated with Lacunar Stroke, hypothesizing that these would be more strongly associated in patients with multiple Lacunar infarcts and leukoaraiosis (LA). Methods: In 1,012 MRI-confirmed Lacunar Stroke cases and 964 age-matched controls recruited from general practice surgeries, we investigated associations between common genetic variants within the OXPHOS pathway and Lacunar Stroke using a permutation-based enrichment approach. Cases were phenotyped using MRI into those with multiple infarcts or LA (MLI/LA) and those with isolated Lacunar infarcts (ILI) based on the number of subcortical infarcts and degree of LA, using the Fazekas grading. Using gene-level association statistics, we tested for enrichment of genes in the OXPHOS pathway with all Lacunar Stroke and the 2 subtypes. Results: There was a specific association with strong evidence of enrichment in the top 1% of genes in the MLI/LA (subtype p = 0.0017) but not in the ILI subtype ( p = 1). Genes in the top percentile for the all Lacunar Stroke analysis were not significantly enriched ( p = 0.07). Conclusions: Our results implicate the OXPHOS pathway in the pathogenesis of Lacunar Stroke, and show the association is specific to patients with the MLI/LA subtype. They show that MRI-based subtyping of Lacunar Stroke can provide insights into disease pathophysiology, and imply that different radiologic subtypes of Lacunar Stroke subtypes have distinct underlying pathophysiologic processes.

  • genetic architecture of Lacunar Stroke
    Stroke, 2015
    Co-Authors: Matthew Traylor, Stephen Bevan, Jeanclaude Baron, Ahamad Hassan, Cathryn M Lewis, Hugh S. Markus
    Abstract:

    Background and Purpose—Lacunar Strokes comprise ≈20% of all Strokes. Despite this frequency, their pathogenesis is poorly understood. Previous genome-wide association studies in Lacunar Stroke have been disappointing, which may be because of phenotypic heterogeneity. Pathological and radiological studies suggest that there may be different pathologies underlying Lacunar Strokes. This has led to the suggestion of 2 subtypes: isolated Lacunar infarcts and multiple Lacunar infarcts and leukoaraiosis. Methods—We performed genome-wide analyses in a magnetic resonance imaging–verified cohort of 1012 younger onset Lacunar Stroke cases and 964 controls. Using these data, we first estimated the heritability of Lacunar Stroke and its 2 hypothesized subtypes, and secondly, we determined whether this is enriched for regulatory regions in the genome, as defined by data from Encyclopedia of DNA Elements (ENCODE) and other sources. Finally, we determine the evidence for a polygenic contribution from rare variation to la...

  • prevalence of cadasil and fabry disease in a cohort of mri defined younger onset Lacunar Stroke
    PLOS ONE, 2015
    Co-Authors: Laura L Kilarski, Hugh S. Markus, Ahamad Hassan, Steve Bevan, Loes C A Ruttenjacobs, Derralynn Hughes, R Baker, U Young Lacunar Stroke Dna K Study
    Abstract:

    Funding: The UK Young Lacunar Stroke DNA Study was funded by grants from the Wellcome Trust (WT072952, www.wellcome.ac.uk) and the Stroke Association (TSA 2010/01& TSA 2013/02, www.Stroke.org.uk). Fabry disease screening was supported by an unrestricted scientific grant from Shire Human Genetic Therapies (www.shire.com). The sponsors of the study had no role in the study design, data collection, data analysis, interpretation, writing of the manuscript, or the decision to submit the manuscript for publication. L R-J’s salary is funded by a Stroke Association/British Heart Foundation grant (TSA/BHF 2010/01). HM is supported by an National Institute for Health Research Senior Investigator award (www.nihr.ac.uk). HM and SB are supported by the Cambridge University Trust National Institute for Health Research Comprehensive Research Centre (www.cambridge-brc.org.uk).

Leslie A Mcclure - One of the best experts on this subject based on the ideXlab platform.

  • the relationship between glucose control and cognitive function in people with diabetes after a Lacunar Stroke
    The Journal of Clinical Endocrinology and Metabolism, 2021
    Co-Authors: Leslie A Mcclure, Tali Cukiermanyaffe, Thomas Risoli, Jackie Bosch, Mike Sharma, Hertzel C Gerstein, Oscar R Benavente
    Abstract:

    CONTEXT Lacunar Strokes and diabetes are risk factors for cognitive dysfunction. Elucidating modifiable risk factors for cognitive dysfunction has great public health implications. One factor may be glycemic status, as measured by glycated hemoglobin (A1c). OBJECTIVE The aim of this study was to assess the relationship between A1c and cognitive function in Lacunar Stroke patients with diabetes. METHODS The effect of baseline and follow-up A1c on the baseline and the change in Cognitive Assessment Screening Instrument (CASI) score over time among participants with a median of 2 cognitive assessments (range, 1-5) was examined in 942 individuals with diabetes and a Lacunar Stroke who participated in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (ClinicalTrials.gov No. NCT00059306). RESULTS Every 1% higher baseline A1c was associated with a 0.06 lower standardized CASI z score (95% CI, -0.101 to -0.018). Higher baseline A1c values were associated with lower CASI z scores over time (P for interaction = .037). A 1% increase in A1c over time corresponded with a CASI score decrease of 0.021 (95% CI, -0.0043 to -0.038) during follow-up. All these remained statistically significant after adjustment for age, sex, education, race, depression, hypertension, hyperlipidemia, body mass index, cardiovascular disease, obstructive sleep apnea, diabetic retinopathy, nephropathy insulin use, and white-matter abnormalities. CONCLUSION This analysis of Lacunar Stroke patients with diabetes demonstrates a relationship between A1c and change in cognitive scores over time. Intervention studies are needed to delineate whether better glucose control could slow the rate of cognitive decline in this high-risk population.

  • inflammatory markers and outcomes after Lacunar Stroke levels of inflammatory markers in treatment of Stroke study
    Stroke, 2016
    Co-Authors: Amelia K Boehme, Leslie A Mcclure, Oscar R Benavente, Yu Zhang, Jorge M Luna, Oscar H Del Brutto, Mitchell S V Elkind
    Abstract:

    Background and Purpose— We hypothesized that concentrations of interleukin 6 (IL-6), serum amyloid A, tumor necrosis factor-α receptor 1, CD40 ligand, and monocyte chemoattractant protein 1 would predict recurrent ischemic Stroke and major vascular events after recent Lacunar Stroke. Methods— Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within the Secondary Prevention of Small Subcortical Strokes (SPS3) study, a Phase III trial in patients with recent Lacunar Stroke. Crude and Adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CI) for recurrence risks. Results— Among 1244 patients with Lacunar Stroke (mean age, 63.3±10.8 years), there were 115 major vascular events (Stroke, myocardial infarction, and vascular death). The risk of major vascular events increased with elevated concentrations of both tumor necrosis factor-α receptor 1 (adjusted HR per SD, 1.21; 95% CI, 1.05–1.41; P =0.01) and IL-6 (adjusted HR per SD, 1.10; 95% CI, 1.02–1.19; P =0.008). Compared with the bottom quartile (tumor necrosis factor-α receptor 1 3.63 ng/L) were at twice the risk of major vascular events after adjusting for demographics (partially adjusted HR, 1.98; 95% CI, 1.11–3.52), though the effect attenuated after adjusting for other risk factors and statin use (adjusted HR, 1.68; 95% CI, 0.93–3.04). Serum amyloid A, CD40 ligand, and monocyte chemoattractant protein 1 were not associated with prognosis. Conclusions— Among recent Lacunar Stroke patients, IL-6 and TNF receptor concentrations predict risk of recurrent vascular events, and they are associated with the effect of antiplatelet therapies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

  • effect of intensive versus usual blood pressure control on kidney function among individuals with prior Lacunar Stroke a post hoc analysis of the secondary prevention of small subcortical Strokes sps3 randomized trial
    Circulation, 2016
    Co-Authors: Carmen A Peralta, Leslie A Mcclure, Carole L White, Oscar R Benavente, Rebecca Scherzer, Michelle C Odden, Michael G Shlipak, Pablo E Pergola
    Abstract:

    Background —The effect of intensive blood pressure (BP) lowering on kidney function among persons with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established. Methods and Results —Among 2610 participants randomized to lower SBP target ( 30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with Stroke, major vascular events (MVE) and the composite Stroke, death, MVE or myocardial infarction, using multivariable Cox regression, separately and jointly including test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11; 949 (36%) were diabetic, mean eGFR was 80±19 ml/min/1.73m 2 . At 9 months, achieved SBP was 137±15 in higher vs. 127±14 mmHg in lower BP group, and differences were maintained throughout follow-up (mean 3.2 years). Compared with higher, lower BP target had -0.50 (95%CI - 0.79 to -0.21) ml/min/1.73m 2 /year faster eGFR decline. Differences were most pronounced during the first year (-2.1 ml/min/1.73m 2 (95%CI -0.97 to -3.2)), whereas rates of eGFR decline did not differ after year 1 (-0.095, -0.47 to 0.23). A total of 313 (24%) persons in the lower BP group had rapid kidney function decline, compared with 247 (19%) in higher (OR 1.4 (95%CI 1.1 to 1.6)). Differences in rapid decline by treatment arm were apparent in the first year (OR 1.4, 1.1-1.8), but were not significant after year 1 (OR 1.0, 0.73-1.4). Rapid decline was associated with higher risk for Stroke, MVE and composite after full adjustment among persons randomized to the higher BP target (Stroke HR 1.93 (1.15 to 3.21), but not the lower BP arm, Stroke HR 0.93 (0.50 to 1.75) (all p interaction <0.06). Conclusions —In persons with prior Lacunar Stroke and relatively preserved kidney function, intensive BP lowering was associated with greater likelihood of rapid kidney function decline. Differences were primarily observed during the first year of anti-hypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering. Clinical Trial Registration Information —ClinicalTrials.gov. Identifier: NCT00059306.

  • abstract wp160 inflammatory markers and outcomes after Lacunar Stroke the levels of inflammatory markers in treatment of Stroke study
    Stroke, 2016
    Co-Authors: Amelia K Boehme, Leslie A Mcclure, Oscar R Benavente, Jorge M Luna, Oscar H Del Brutto, Mitchell S V Elkind
    Abstract:

    Background: C-reactive protein predicts prognosis after Stroke, but relationships of other inflammatory biomarkers to prognosis is uncertain. We hypothesized that concentrations of interleukin 6 (IL6), serum amyloid A, tumor necrosis factor-α receptor 1 (TNFR1), CD40 ligand, and monocyte chemoattractant protein 1 predict recurrent major vascular events (MVE) after Lacunar Stroke. Methods: Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, ancillary biomarker study nested within the Secondary Prevention of Small Subcortical Strokes (SPS3) Phase 3 trial in patients with recent Lacunar Stroke. Patients were randomized to aspirin versus aspirin/clopidogrel. Blood samples were collected at enrollment, and markers measured centrally using ELISA. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (HR, 95% CI) for risk of MVE (Stroke, myocardial infarction, vascular death) after adjusting for demographics, comorbidities, and statin use. Results: Among 1244 Lacunar Stroke patients (mean age 63.3 ± 10.8 years), there were 115 MVE. Risk increased with concentrations of both TNFR1 (adj HR per standard deviation [SD] 1.21, 95% CI 1.05-1.41) and IL6 (adj HR per SD 1.10, 95% CI 1.02-1.19). Compared with the bottom quartile of TNFR1, those in the top quartile had twice the risk after adjusting for demographics (HR 1.98, 95% CI 1.11-3.52), though this attenuated after adjusting for other risk factors (adjusted HR 1.68, 95% CI 0.93-3.04). There was an interaction between antiplatelet assignment and TNFR1 (p=0.008; figure) and IL6 quartiles (p=0.035); as biomarker concentrations increased, dual antiplatelets became less effective than aspirin alone. Other markers were not associated with prognosis. Conclusions: Among recent Lacunar Stroke patients, IL6 and TNF receptor concentrations predict risk of recurrent vascular events and efficacy of antiplatelet therapies.

  • the effect of intensive vs usual blood pressure control on kidney function among persons with prior Lacunar Stroke a post hoc analysis of the sps3 randomized trial
    Circulation, 2016
    Co-Authors: Carmen A Peralta, Leslie A Mcclure, Carole L White, Oscar R Benavente, Rebecca Scherzer, Michelle C Odden, Michael G Shlipak, Pablo E Pergola
    Abstract:

    Background —The effect of intensive blood pressure (BP) lowering on kidney function among persons with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established. Methods and Results —Among 2610 participants randomized to lower SBP target ( 30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with Stroke, major vascular events (MVE) and the composite Stroke, death, MVE or myocardial infarction, using multivariable Cox regression, separately and jointly including test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11; 949 (36%) were diabetic, mean eGFR was 80±19 ml/min/1.73m 2 . At 9 months, achieved SBP was 137±15 in higher vs. 127±14 mmHg in lower BP group, and differences were maintained throughout follow-up (mean 3.2 years). Compared with higher, lower BP target had -0.50 (95%CI - 0.79 to -0.21) ml/min/1.73m 2 /year faster eGFR decline. Differences were most pronounced during the first year (-2.1 ml/min/1.73m 2 (95%CI -0.97 to -3.2)), whereas rates of eGFR decline did not differ after year 1 (-0.095, -0.47 to 0.23). A total of 313 (24%) persons in the lower BP group had rapid kidney function decline, compared with 247 (19%) in higher (OR 1.4 (95%CI 1.1 to 1.6)). Differences in rapid decline by treatment arm were apparent in the first year (OR 1.4, 1.1-1.8), but were not significant after year 1 (OR 1.0, 0.73-1.4). Rapid decline was associated with higher risk for Stroke, MVE and composite after full adjustment among persons randomized to the higher BP target (Stroke HR 1.93 (1.15 to 3.21), but not the lower BP arm, Stroke HR 0.93 (0.50 to 1.75) (all p interaction <0.06). Conclusions —In persons with prior Lacunar Stroke and relatively preserved kidney function, intensive BP lowering was associated with greater likelihood of rapid kidney function decline. Differences were primarily observed during the first year of anti-hypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering. Clinical Trial Registration Information —ClinicalTrials.gov. Identifier: NCT00059306.

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  • preventing cognitive decline and dementia from cerebral small vessel disease the laci 1 trial protocol and statistical analysis plan of a phase iia dose escalation trial testing tolerability safety and effect on intermediary endpoints of isosorbide m
    International Journal of Stroke, 2018
    Co-Authors: Gordon W. Blair, Richard Dooley, Iona Hamilton, Katie Flaherty, Jason P. Appleton, Kirsten Shuler, Fergus N. Doubal, Carla Richardson, Michael Stringer, Julia Boyd
    Abstract:

    Rationale The pathophysiology of most Lacunar Stroke, a form of small vessel disease, is thought to differ from large artery atherothrombo- or cardio-embolic Stroke. Licensed drugs, isosorbide mononitrate and cilostazol, have promising mechanisms of action to support their testing to prevent Stroke recurrence, cognitive impairment, or radiological progression after Lacunar Stroke. Aim LACI-1 will assess the tolerability, safety, and efficacy, by dose, of isosorbide mononitrate and cilostazol, alone and in combination, in patients with ischemic Lacunar Stroke. Sample size A sample of 60 provides 80+% power (significance 0.05) to detect a difference of 35% (90% versus 55%) between those reaching target dose on one versus both drugs. Methods and design LACI-1 is a phase IIa partial factorial, dose-escalation, prospective, randomized, open label, blinded endpoint trial. Participants are randomized to isosorbide mononitrate and/or cilostazol for 11 weeks with dose escalation to target as tolerated in two centers (Edinburgh, Nottingham). At three visits, tolerability, safety, blood pressure, pulse wave velocity, and platelet function are assessed, plus magnetic resonance imaging to assess cerebrovascular reactivity in a subgroup. Study outcomes Primary: proportion of patients completing study achieving target maximum dose. Secondary Symptoms whilst taking medications; safety (hemorrhage, recurrent vascular events, falls); blood pressure, platelet function, arterial stiffness, and cerebrovascular reactivity. Discussion This study will inform the design of a larger phase III trial of isosorbide mononitrate and cilostazol in Lacunar Stroke, whilst providing data on the drugs’ effects on vascular and platelet function.

  • preventing cognitive decline and dementia from cerebral small vessel disease the laci 1 trial protocol and statistical analysis plan of a phase iia dose escalation trial testing tolerability safety and effect on intermediary endpoints of isosorbide m
    International Journal of Stroke, 2018
    Co-Authors: Gordon W. Blair, Richard Dooley, Iona Hamilton, Katie Flaherty, Jason P. Appleton, Kirsten Shuler, Fergus N. Doubal, Carla Richardson, Michael Stringer, Julia Boyd
    Abstract:

    Rationale The pathophysiology of most Lacunar Stroke, a form of small vessel disease, is thought to differ from large artery atherothrombo- or cardio-embolic Stroke. Licensed drugs, isosorbide mononitrate and cilostazol, have promising mechanisms of action to support their testing to prevent Stroke recurrence, cognitive impairment, or radiological progression after Lacunar Stroke. Aim LACI-1 will assess the tolerability, safety, and efficacy, by dose, of isosorbide mononitrate and cilostazol, alone and in combination, in patients with ischemic Lacunar Stroke. Sample size A sample of 60 provides 80+% power (significance 0.05) to detect a difference of 35% (90% versus 55%) between those reaching target dose on one versus both drugs. Methods and design LACI-1 is a phase IIa partial factorial, dose-escalation, prospective, randomized, open label, blinded endpoint trial. Participants are randomized to isosorbide mononitrate and/or cilostazol for 11 weeks with dose escalation to target as tolerated in two centers (Edinburgh, Nottingham). At three visits, tolerability, safety, blood pressure, pulse wave velocity, and platelet function are assessed, plus magnetic resonance imaging to assess cerebrovascular reactivity in a subgroup. Study outcomes Primary: proportion of patients completing study achieving target maximum dose. Secondary Symptoms whilst taking medications; safety (hemorrhage, recurrent vascular events, falls); blood pressure, platelet function, arterial stiffness, and cerebrovascular reactivity. Discussion This study will inform the design of a larger phase III trial of isosorbide mononitrate and cilostazol in Lacunar Stroke, whilst providing data on the drugs’ effects on vascular and platelet function.

  • blood markers of coagulation fibrinolysis endothelial dysfunction and inflammation in Lacunar Stroke versus non Lacunar Stroke and non Stroke systematic review and meta analysis
    Cerebrovascular Diseases, 2014
    Co-Authors: Stewart Wiseman, Fergal Marlborough, Fergus N. Doubal, David J. Webb, Joanna M Wardlaw
    Abstract:

    Background: The cause of cerebral small vessel disease is not fully understood, yet it is important, accounting for about 25% of all Strokes. It also increases the risk of having another Stroke and contributes to about 40% of dementias. Various processes have been implicated, including microatheroma, endothelial dysfunction and inflammation. A previous review investigated endothelial dysfunction in Lacunar Stroke versus mostly non-Stroke controls while another looked at markers of inflammation and endothelial damage in ischaemic Stroke in general. We have focused on blood markers between clinically evident Lacunar Stroke and other subtypes of ischaemic Stroke, thereby controlling for Stroke in general. Summary: We systematically assessed the literature for studies comparing blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in Lacunar Stroke versus non-Stroke controls or other ischaemic Stroke subtypes. We assessed the quality of included papers and meta-analysed results. We split the analysis on time of blood draw in relation to the Stroke. We identified 1,468 full papers of which 42 were eligible for inclusion, including 4,816 ischaemic Strokes, of which 2,196 were Lacunar and 2,500 non-Stroke controls. Most studies subtyped Stroke using TOAST. The definition of Lacunar Stroke varied between studies. Markers of coagulation/fibrinolysis (tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), fibrinogen, D-dimer) were higher in Lacunar Stroke versus non-Stroke although fibrinogen was no different to non-Stroke in the acute phase. tPA and PAI were no different between Lacunar and non-Lacunar Stroke. Fibrinogen and D-dimer were significantly lower in Lacunar Stroke compared to other ischaemic Strokes, both acutely and chronically. Markers of endothelial dysfunction (homocysteine, von Willebrand Factor (vWF), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM), vascular cellular adhesion molecule-1 (VCAM)) were higher or had insufficient or conflicting data (P-selectin, VCAM) in Lacunar Stroke versus non-Stroke. Compared to other ischaemic Stroke subtypes, homocysteine did not differ in Lacunar Stroke while vWF was significantly lower in Lacunar Stroke acutely [atherothrombotic standardized mean difference, SMD, -0.34 (-0.61, -0.08); cardioembolic SMD -0.38 (-0.62, -0.14)], with insufficient data chronically. Markers of inflammation (C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)) were higher in Lacunar Stroke versus non-Stroke, although there were no studies measuring TNF-α chronically and the sole study measuring IL-6 chronically showed no difference between Lacunar Stroke and non-Stroke. Compared to other ischaemic Stroke subtypes, there was no difference (CRP) or insufficient or conflicting data (TNF-α) to Lacunar Stroke. IL-6 was significantly lower [atherothrombotic SMD -0.37 (-0.63, -0.10); cardioembolic SMD -0.52 (-0.82, -0.22)] in Lacunar Stroke acutely, with insufficient data chronically. Key Messages: Lacunar Stroke is an important Stroke subtype. More studies comparing Lacunar Stroke to non-Lacunar Stroke specifically, rather than to non-Stroke controls, are needed. Prospective studies with measurements taken well after the acute event are more likely to be helpful in determining pathogenesis. The available data in this review were limited and do not exclude the possibility that peripheral inflammatory processes including endothelial dysfunction are associated with Lacunar Stroke and cerebral small vessel disease.

  • little association between intracranial arterial stenosis and Lacunar Stroke
    Cerebrovascular Diseases, 2011
    Co-Authors: Joanna M Wardlaw, Kirsten Shuler, Fergus N. Doubal, Francesca M Chappell, Elizabeth Eadie, Vera Cvoro
    Abstract:

    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 ai

  • fractal analysis of retinal vessels suggests that a distinct vasculopathy causes Lacunar Stroke
    Neurology, 2010
    Co-Authors: Fergus N. Doubal, Martin Dennis, Tom Macgillivray, Niall Patton, Baljean Dhillon, Joanna M Wardlaw
    Abstract:

    Objectives: Lacunar Strokes account for 25% of all ischemic Strokes and may represent the cerebral manifestation of a systemic small vessel vasculopathy of unknown etiology. Altered retinal vessel fractal dimensions may act as a surrogate marker for diseased cerebral vessels. We used a cross-sectional study to investigate fractal properties of retinal vessels in Lacunar Stroke. Methods: We recruited patients presenting with Lacunar Stroke and patients with minor cortical Stroke as controls. All patients were examined by a Stroke expert and had MRI at presentation. Digital retinal photographs were taken of both eyes. Monofractal and multifractal analyses were performed with custom-written semiautomated software. Results: We recruited 183 patients. Seventeen were excluded owing to poor photographic quality, leaving 166 patients (86 with Lacunar and 80 with cortical Stroke). The mean age was 67.3 years (SD 11.5 years). The patients with Lacunar Stroke were younger but the prevalence of diabetes, hypertension, and white matter hyperintensities did not differ between the groups. The mean Dbox (monofractal dimension) was 1.42 (SD 0.02), the mean D0 (multifractal dimension) 1.67 (SD 0.03). With multivariate analysis, decreased Dbox and D0 (both representing decreased branching complexity) were associated with increasing age and Lacunar Stroke subtype after correcting for hypertension, diabetes, Stroke severity, and white matter hyperintensity scores. Conclusions: Lacunar Stroke subtype and increasing age are associated with decreased fractal dimensions, suggesting a loss of branching complexity. Further studies should concentrate on longitudinal associations with other manifestations of cerebral small vessel disease. Neurology ® 2010;74:1102–1107

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