Small Subcortical Infarcts Research Articles

Prediction of Symptoms on Admission with Early Neurological Deterioration in Single Small Subcortical Infarct.

Early neurological deterioration (END) often occurs during hospitalization in single small subcortical infarct (SSSI). While, symptoms on admission were rarely reported about its performance on predicting the risk of END. The objective of this study is to explore the relationship between symptoms on admission and END in SSSI. Patients with SSSI in the lenticulostriate artery (LSA) territory presenting within 72 hours of stroke onset were screened prospectively. Clinical characteristics, including symptoms on admission, laboratory tests and imaging findings, were collected. Based on the body regions involved including spherical face (SF), upper limb (UL) or lower limb (LL), symptoms on admission were classified into single spherical face (sSF) and any involvement of limbs (AL). END was defined as ≥2 points increase in total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 point increase in motor score within 72 hours after admission. Multivariate logistic regression was used to analyze factors associated with END. Out of 5,832 ischemic stroke patients in the database, 394 patients were finally enrolled in analysis. 65 patients (16.5%) developed END. Multivariable logistic regression revealed that symptoms with LL (OR 2.337, 95% CI 1.041-5.246), UL (OR 2.936, 95% CI 1.349-6.390) were both associated with END, while the involvement of SF (OR 0.447, 95% CI 0.249-0.804) showed the opposite result. Further analysis found that symptoms with AL (OR 3.958, 95% CI 1.355-11.565) showed a higher risk of END compared to sSF after adjustment. Our results discovered that symptoms with AL carried a higher risk of END than those involving sSF in SSSI.

Evaluation of clinical relevance and underlying pathology for hemodynamic compromise in acute small subcortical infarction using MRI-based neuroimaging markers

BackgroundHemodynamic compromise has been observed in patients with acute small subcortical infarction (SSI), and it may play a critical role in the development of early neurological deterioration (END). This study aimed to evaluate the clinical relevance and underlying pathology of hemodynamic compromise in SSI using MRI-based neuroimaging markers. MethodsWe retrospectively analyzed data and imaging of previous prospective studies. Patients with acute SSI in penetrating artery territories were recruited, all of whom underwent perfusion MRI within 24 h of stroke onset. We examined the relationships among perfusion defects and neuroimaging markers of small vessel disease, including white matter hyperintensities, cerebral microbleeds, enlarged perivascular spaces (EPVSs) and lacunes. ResultsOne hundred and seven patients were recruited, of whom 21 (19.6%) had END and 55 (51.4%) had visible perfusion defects. Patients with perfusion defects were associated with a higher rate of END (34.5% vs. 3.8%; p < 0.001), higher initial National Institutes of Health Stroke Scale scores (5.4 vs. 3.4, p < 0.001), higher rate of branch atheromatous disease (61.8% vs. 34.6%, p = 0.005) and higher rate of poor outcome at 3 months (40.0% vs. 5.4%; p = 0.005). In multiple logistic regression, perfusion defects were significantly associated with basal ganglia EPVS scores (adjusted odds ratio [aOR]: 3.93; 95% confidence interval [CI]: 1.76–8.77; p = 0.001) and branch atheromatous disease (aOR: 2.64; 95% CI: 1.06–6.60; p = 0.037). ConclusionHemodynamic compromise in acute SSI was highly related to the development of END, basal ganglia EPVS and branch atheromatous disease, suggesting the correlation with underlying pathologies of hypertensive arteriopathy and atherosclerosis.

Increased level of FAM19A5 is associated with cerebral small vessel disease and leads to a better outcome.

ObjectiveFAM19A5 plays an essential role in the development and acute or chronic inflammation of the central nervous system. The present study aimed to explore the association between FAM19A5 and cerebral small vessel disease (cSVD).MethodsA total of 344 recent small subcortical infarct (RSSI) patients and 265 healthy controls were included in this study. The difference in the FAM19A5 level between the two groups was compared and the correlation between FAM19A5 and cerebral infarction volume was analyzed. Also, the association between FAM19A5 and the total magnetic resonance imaging (MRI) burden with its imaging characteristics was explored. Moreover, the correspondence of FAM19A5 with the outcome was assessed via Δ National Institutes of Health Stroke Scale score (NIHSS) and the percentage of NIHSS improvement.ResultsFAM19A5 was highly expressed in the RSSI group (P = 0.023), showing a positive correlation with cerebral infarction volume (P < 0.01). It was positively correlated with total MRI cSVD burden (P < 0.001) and reflected the severity of white matter hyperintensity (WMH) (P < 0.01) and enlarged perivascular space (EPVS) (P < 0.01), but did not show any association with cerebral microbleed (CMB) and lacune. Moreover, FAM19A5 suggested a larger Δ NIHSS (P = 0.021) and NIHSS improvement percentage (P = 0.007).ConclusionSerum FAM19A5 was increased in RSSI and positively correlated with the infarct volume. It also reflects the total MRI burden of cSVD, of which the imaging characteristics are positively correlated with WMH and EPVS. In addition, higher FAM19A5 levels reflect better outcomes in RSSI patients.

Hemorrhagic Focus Within the Recent Small Subcortical Infarcts on Long-Term Follow-Up Magnetic Resonance Imaging.

Hemorrhagic Focus Within the Recent Small Subcortical Infarcts on Long-Term Follow-Up Magnetic Resonance Imaging.

The influence of cerebrovascular disease in dementia with Lewy bodies and Parkinson's disease dementia.

Lewy body dementia (LBD), including dementia with Lewy bodies (DLB) and Parkinson's disease dementia, is a common form of neurodegenerative dementia. The frequency and influence of comorbid cerebrovascular disease is not understood but has potentially important clinical management implications. A systematic literature search was conducted (MEDLINE and Embase) for studies including participants with DLB and/or Parkinson's disease dementia assessing cerebrovascular lesions (imaging and pathological studies). They included white matter changes, cerebral amyloid angiopathy, cerebral microbleeds (CMB), macroscopic infarcts, microinfarcts and intracerebral haemorrhage. Of 4411 articles, 63 studies were included. Cerebrovascular lesions commonly studied included white matter changes (41 studies) and CMB (18 studies). There was an increased severity of white matter changes on magnetic resonance imaging (visualized as white matter hyperintensities), but not neuropathology, in LBD compared to Parkinson's disease without dementia and age-matched controls. CMB prevalence in DLB was highly variable but broadly similar to Alzheimer's disease (0%-48%), with a lobar predominance. No relationship was found between large cortical or small subcortical infarcts or intracerebral haemorrhage and the presence of LBD. The underlying mechanisms of white matter hyperintensities in LBD require further exploration, as their increased severity in LBD was not supported by neuropathological examination of white matter. CMB in LBD had a similar prevalence to Alzheimer's disease. There is a need for larger studies assessing the influence of cerebrovascular lesions on clinical symptoms, disease progression and outcomes.

Incidental DWI Lesions in Patients with Recent Small Subcortical Infarctions

ObjectivesIncidental acute ischemic lesions distinct from the primary neurological insult are identified on diffusion-weighted imaging (DWI) in a number of conditions where cerebral microvascular pathology plays a central role. Another major manifestation of cerebral small vessel disease (CSVD) is ischemic stroke named as recent small subcortical infarction (RSSI). In this study, we sought to identify the prevalence and predictors of incidental DWI lesions in patients with RSSI. Materials and MethodsWe retrospectively analyzed a consecutive series of acute ischemic stroke patients with DWI evidence of acute lesions solely localized to perforator artery territories. Images were evaluated for the presence of additional acute or subacute subcortical DWI lesions, apart from the symptomatic lesion. Clinical features including vascular risk factor burden, together with imaging markers of chronic CSVD, were compared among patients with and without incidental acute or subacute lesions. ResultsAmong 396 patients with no alternate stroke etiology additional incidental subcortical DWI bright lesions were identified in 74 (19%) cases. These lesions were primarily localized in the corona radiata, or centrum semiovale. Patients with incidental DWI lesions were more likely to have a history of hypertension, a higher white matter hyperintensities burden in the periventricular and subcortical region, higher perivascular spaces burden in the basal ganglia, multiple cerebral microbleeds, and multiple chronic lacunes. Presence of multiple chronic lacunes (OR 5.98, 95% CI 3.18-11.24) and ≥2 vascular risk factors (OR 2.03, 95% CI 1.05-3.91) stood out as features significantly associated with incidental DWI lesions in multivariate analysis. ConclusionsOur study shows that acute or subacute ischemic lesions can be incidentally detected in approximately one-fifth of patients with RSSI. This observation suggests that the course of CSVD might be more active, temporally and spatially, in a distinct subgroup of RSSI patients, specifically those with a higher chronic lacune and vascular risk factor burden.

Total magnetic resonance imaging of cerebral small vessel disease burden predicts dysphagia in patients with a single recent small subcortical infarct

BackgroundThis study was performed to identify the association between the total magnetic resonance imaging burden of small vessel disease and the occurrence of post-stroke dysphagia in patients with a single recent small subcortical infarct (RSSI).MethodsWe retrospectively identified all patients with a magnetic resonance imaging-confirmed single RSSI. The water-swallowing test and volume-viscosity swallow test were performed within the first 24 h following admission to assess swallowing. Demographic and clinical data were extracted from our stroke database. Based on brain magnetic resonance imaging, we independently rated the presence of cerebral microbleeds, lacunes, white matter hyperintensities and enlarged perivascular spaces. The presence of each small vessel disease feature was summed to determine the total small vessel disease burden, ranging from 0 to 4.ResultsIn total, 308 patients with a single RSSI were enrolled. Overall, 54 (17.5%) were diagnosed with post-stroke dysphagia. The risk factors related to post-stroke dysphagia included the following: older age, higher National Institute of Health Stroke Scale scores, higher C-reactive protein level and higher fibrinogen level. Based on multiple logistic regression, National Institute of Health Stroke Scale scores and total small vessel disease burden were independent risk factors of post-stroke dysphagia in patients with a single RSSI, after adjusting for age, gender, history of hypertension, C-reactive protein level and fibrinogen level.ConclusionsDysphagia in patients with a single RSSI was associated with a more severe total small vessel disease burden as reflected by MRI. Total MRI of cerebral small vessel disease burden may predict dysphagia in these patients. Furthermore, more severe total small vessel disease burden was associated with systemic inflammation.

Association of total cerebral small vessel disease burden with the cavitation of recent small subcortical infarcts.

Recent small subcortical infarcts (RSSIs) could evolve into cavitation (lacunes) or non-cavitation (white matter hyperintensities or disappearance) during the chronic period, but the factors involved remain unclear. To explore the association between total cerebral small vessel disease (CSVD) burden and lesion cavitation. We retrospectively selected 202 inpatients with an isolated RSSI who underwent baseline and follow-up magnetic resonance imaging (median interval = 16.6 months; interquartile range [IQR]=8.2-30.1). Inpatients were divided into cavitation and non-cavitation groups depending on whether a fluid-filled cavity formed. Data including demographic, clinical, and radiological features were collected and analyzed. To determine total CSVD burden, four imaging markers, including lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces, were rated and summed as a final practical score between 0 and 4. Overall, 137 (67.8%) patients progressed to cavitation and 65 (32.2%) to non-cavitation. Binary multivariable regression analysis showed that the baseline total CSVD burden (P = 0.005) and infarct diameter (P = 0.002) were independent risk factors for cavitation. A severe total burden (scores of 3-4) at baseline was independently related to cavitation (P = 0.001). Moreover, the total CSVD burden score varied from 2 (IQR=1-3) at baseline to 3 (IQR=2-4) at follow-up. The extent of the increase in total burden was correlated with cavitation (r = 0.201; P = 0.004). Total CSVD burden, both the baseline value and extent of increase, was positively associated with cavitation. RSSIs with severe total CSVD burden at baseline have a greater potential to become cavitated.

The synergistic effects of ischemic stroke and amyloid pathology on cerebrovascular function.

Stroke survivors are at four times higher risk of developing cognitive decline1 and aging patients who carry silent infarcts are at double the risk of dementia2 . Importantly, cerebrovascular reactivity (CVR) and neurovascular coupling (NVC) are attenuated in stroke patients3 . As cerebrovascular dysregulation is one of the earliest changes that precede the descent into dementia in Alzheimer's disease (AD)4 , exploring cerebrovascular effects of stroke may hold the key to understanding AD etiology. We optimized a model of mild ischemic stroke by performing a 30-minute middle cerebral artery occlusion (MCAo) which yielded a small subcortical infarct. 30-minute MCAos were performed in 6-month old Tg2576 mice, a model of amyloid pathology, and strain/age-matched wild types (WT). Cerebrovascular function was then tested at chronic time points. CVR to a hypercapnic challenge was quantified using arterial spin labeling magnetic resonance imaging (MRI) 4 and 8 months after MCAo. NVC was examined using laser Doppler flowmetry, 8 months after MCAo, by measuring cerebral blood flow (CBF) changes in response to hind paw stimulation. 4 months after a mild ischemia, MRI showed that CVR was attenuated in both hemispheres compared to naïve mice. This attenuation was significant in Tg2576 ischemic mice. At the 8 month time point, naïve mice also showed an age-related decline in this response, although this decrease did not reach significance, while ischemia-exposed Tg2576 and WT showed essentially no CVR. NVC was impaired 8 months after ischemia, with this impairment being most severe in the ipsilateral hemisphere of Tg2576 mice. These findings indicate that whilst ischemic stroke alone may impair CBF, it can synergize with amyloid pathology to bring about earlier and more severe changes to cerebrovascular function. Future histological analyses are expected to reveal cellular changes at the neurovascular unit that may underlie these changes and their correlation to amyloid pathology. This study sheds light on the cascade of events after stroke that may trigger AD and could guide therapeutics aimed at preserving cerebrovascular function.

Tamoxifen offers long-term neuroprotection after hippocampal silent infarct in male rats

Silent infarcts (SI) are a cerebral small vessel disease characterized by small subcortical infarcts. These occur in the absence of typical ischemia symptoms but are linked to cognitive decline and dementia. While there are no approved treatments for SI, recent results from our laboratory suggest that tamoxifen, a selective estrogen receptor modulator, is a viable candidate. In the present study, we induced SI in the dorsal hippocampal CA1 region of rats and assessed the effects of systemic administration of tamoxifen (5 mg/kg, twice) 21 days after injury on cognitive and pathophysiological measures, including cell loss, apoptosis, gliosis and estrogen receptors (ERs). We found that tamoxifen protected against the SI-induced cognitive dysfunction on the hippocampal-dependent, place recognition task, cell and ER loss, and increased apoptosis and gliosis in the CA1. Exploratory data analyses using a scatterplot matrix and principal component analysis indicated that SI-tamoxifen rats were indistinguishable from sham controls while they differed from SI rats, who were characterized by enhanced cell loss, apoptosis and gliosis, lower ERs, and recognition memory deficit. Supervised machine learning using support vector machine (SVM) determined predictors of progression from the early ischemic state to the dementia-like state. It showed that caspase-3 and ERα in the CA1 and exploration proportion were reliable and accurate predictors of this progression. Importantly, tamoxifen ameliorated SI-induced effects on all three of these variables, providing further evidence for its viability as a candidate treatment for SI and prevention of associated dementia.

Atrial Fibrillation Related and Unrelated Stroke Recurrence Among Ischemic Stroke Patients With Atrial Fibrillation.

Background: Ischemic stroke with atrial fibrillation (AF) may recur despite appropriate treatment. It may be AF-related or AF-unrelated. We compared the factors associated with AF-related and AF-unrelated recurrences among ischemic stroke patients with AF.Methods: Patients with ischemic stroke and AF were enrolled from 11 centers in Korea. Ischemic stroke recurrence was classified as AF-related if the lesion pattern was compatible with cardioembolism without significant stenosis or as AF-unrelated if the lesion was more likely due to small vessel disease or arterial stenosis. Factors associated with stroke recurrence (AF-related and AF-unrelated) were investigated.Results: Among the 2,239 patients, 115 (5.1%) experienced recurrence (75 AF-related and 40 AF-unrelated). Factors independently associated with any stroke recurrence included AF diagnosed before stroke, small subcortical infarctions, and small scattered lesions in a single vascular territory. Type of AF was associated with the type of stroke recurrence, with persistent AF being associated with AF-related stroke [hazard ratio (HR) = 2.94, 95% confidence interval (CI) 1.69–5.26; p < 0.001]. By contrast, paroxysmal AF (HR = 3.76, 95% CI 1.56–9.04; p = 0.003), AF diagnosed before stroke (HR = 2.38, 95% CI 1.19–4.55; p = 0.014), small scattered lesions in a single vascular territory (reference: corticosubcortical lesion, HR = 3.19, 95% CI 1.18–8.63; p = 0.022), and the use of antiplatelet agents (HR = 2.11, 95% CI 1.11–4.03; p = 0.024) were independently associated with AF-unrelated stroke.Conclusion: Persistent AF was more associated with AF-related stroke recurrence, whereas paroxysmal AF was more associated with AF-unrelated stroke recurrence. A scattered lesion in a single vascular territory may predict AF-unrelated stroke recurrence.

Perfusion Defects and Collateral Flow Patterns in Acute Small Subcortical Infarction: a 4D Dynamic MRI Study

The hemodynamic changes of acute small subcortical infarction (SSI) are not well understood. We evaluate the hemodynamic changes and collaterals in acute SSI using perfusion magnetic resonance imaging (MRI). A total of 103 patients with acute SSI in penetrating artery territories were recruited and underwent MRI within 24 h of stroke onset. Using 4D dynamic perfusion MRI, they were divided into three patterns: 25 (24%) with normal perfusion, 31 (30%) with compensated perfusion, and 47 (46%) with hypoperfusion. The development of anterograde or retrograde collaterals was also evaluated. Patients with hypoperfusion pattern had the highest rate of early neurological deterioration (32%, p = 0.007), the largest initial and final infarction volumes (p < 0.001 and p = 0.029), the lowest relative cerebral blood flow (0.63, p < 0.001), and the lowest rate of anterograde and retrograde collaterals (19%, p < 0.001; 66%, p = 0.002). The anterograde collaterals were associated with higher relative cerebral blood volume (0.91 vs. 0.77; p = 0.024) and a higher rate of deep cerebral microbleeds (48 vs. 21%; p = 0.028), whereas retrograde collaterals were associated with higher systolic and diastolic blood pressure (p = 0.031 and 0.020), smaller initial infarction volume (0.81 vs. 1.34 ml, p = 0.031), and a higher rate of lobar cerebral microbleeds (30 vs. 0%; p = 0.013). Both anterograde and retrograde collaterals may play a critical role in maintaining cerebral perfusion and can have an impact on patient clinical outcomes. Further studies are warranted to verify these findings and to investigate effective treatments.

Small Vessel Disease, a Marker of Brain Health: What the Radiologist Needs to Know.

Small vessel disease, a disorder of cerebral microvessels, is an expanding epidemic and a common cause of stroke and dementia. Despite being almost ubiquitous in brain imaging, the clinicoradiologic association of small vessel disease is weak, and the underlying pathogenesis is poorly understood. The STandards for ReportIng Vascular changes on nEuroimaging (STRIVE) criteria have standardized the nomenclature. These include white matter hyperintensities of presumed vascular origin, recent small subcortical infarcts, lacunes of presumed vascular origin, prominent perivascular spaces, cerebral microbleeds, superficial siderosis, cortical microinfarcts, and brain atrophy. Recently, the rigid categories among cognitive impairment, vascular dementia, stroke, and small vessel disease have become outdated, with a greater emphasis on brain health. Conventional and advanced small vessel disease imaging markers allow a comprehensive assessment of global brain heath. In this review, we discuss the pathophysiology of small vessel disease neuroimaging nomenclature by means of the STRIVE criteria, clinical implications, the role of advanced imaging, and future directions.

Hemispheric cerebral blood flow predicts outcome in acute small subcortical infarcts

The association between baseline perfusion measures and clinical outcomes in patients with acute small subcortical infarcts (SSIs) has not been studied in detail. Post-processed acute perfusion CT and follow-up diffusion-weighted imaging of 71 patients with SSIs were accurately co-registered. Relative perfusion values were calculated from the perfusion values of the infarct lesion divided by those of the mirrored contralateral area. The association between perfusion measures with clinical outcomes and the interaction with intravenous thrombolysis were studied. Additionally, the perfusion measures for patients having perfusion CT before and after thrombolysis were compared. Higher contralateral hemispheric cerebral blood flow (CBF) was the only independent predictor of an excellent clinical outcome (modified Rankin Scale of 0-1) at 3 months (OR = 1.3, 95% CI 1.1–1.4, P = 0.001) amongst all the perfusion parameters, and had a significant interaction with thrombolysis (P = 0.04). Patients who had perfusion CT after thrombolysis demonstrated a better perfusion profile (relative CBF ≥1) than those who had perfusion CT before thrombolysis (After:45.5%, Before:21.1%, P = 0.03). This study implies that for patients with SSIs, hemispheric CBF is a predictor of clinical outcome and has an influence on the effect of intravenous thrombolysis.

Vascular dementia neurovisual markers according routine and diffusion-tensor MRI (publications’ review)

The article presents review of the most significant neurovisual biomarkers-predictors of the cognitive disfunction caused by brain vascular pathology. Also given quantitative and qualitative characteristics of this pathology including localization that can be detected using routine and diffusion-tensor MRI. Following biomarkers were noted when using standard MRI protocols: atrophy of gray matter and white matter tracts and basal nuclei; white matter hyperintensities (foci of gliosis and periventricular leukoaraiosis), micro-bleeding (large vessels, white and gray matter deposits of hemosiderin), enlarged perivascular spaces (cystic enlargement of the penetrating arteries, arterioles, veins and venules), recent small subcortical infarcts andpost-ischemic damages in cortex, basal nuclei and white matter tracts. The article outlines diffusion tensor MRI latest developments for cognitive deficits’ risk assessment, such as threshold coefficients (indexes) of the fraction anisotropy, received in neocortex tracts (frontal and temporal lobes; fronto-thalamic pathway).

Intracranial Atherosclerotic Burden and Cerebral Parenchymal Changes at 7T MRI in Patients With Transient Ischemic Attack or Ischemic Stroke.

The relevance of intracranial vessel wall lesions detected with MRI is not fully established. In this study (trial identification number: NTR2119; www.trialregister.nl), 7T MRI was used to investigate if a higher vessel wall lesion burden is associated with more cerebral parenchymal changes in patients with ischemic stroke or transient ischemic attack (TIA). MR images of 82 patients were assessed for the number of vessel wall lesions of the large intracranial arteries and for cerebral parenchymal changes, including the presence and number of cortical, small subcortical, and deep gray matter infarcts; lacunes of presumed vascular origin; cortical microinfarcts; and periventricular and deep white matter hyperintensities (WMHs). Regression analyses showed that a higher vessel wall lesion burden was associated with the presence of small subcortical infarcts, lacunes of presumed vascular origin, and deep gray matter infarcts (relative risk 1.18; 95% CI, 1.03–1.35) and presence of moderate-to-severe periventricular WMHs (1.21; 95% CI, 1.03–1.42), which are all manifestations of small vessel disease (SVD). The burden of enhancing vessel wall lesions was associated with the number of cortical microinfarcts only (1.48; 95% CI, 1.04–2.11). These results suggest an interrelationship between large vessel wall lesion burden and cerebral parenchymal manifestations often linked to SVD or, alternatively, that vascular changes occur in both large and small intracranial arteries simultaneously.

Higher Cerebral Small Vessel Disease Burden in Patients with White Matter Recent Small Subcortical Infarcts

Recent small subcortical infarcts (RSSI) are considered an acute manifestation of cerebral small vessel disease (CSVD). We assessed whether the topography of RSSI was related to CSVD markers on magnetic resonance imaging (MRI). We screened the local registries of two independent stroke centers in Catalonia and selected patients with a symptomatic RSSI on MRI performed during admission. RSSI location was classified into brainstem, supratentorial subcortical structures (SSS), and centrum semiovale (CSO) regions. Clinical variables, including vascular risk factors, were collected. Radiological markers of CSVD on MRI were evaluated individually and by means of the global CSVD burden score. The associations between each RSSI location and CSVD markers were studied in uni- and multivariate logistic regression analysis. Among 475 patients with RSSI, 152 (32%) had an infarct in the brainstem, 227 (48%) in SSS, and 96 (20%) in CSO region. The median CSVD burden score was 2 (IQR, 1-3). After adjusting for confounding factors, a RSSI in CSO was associated with higher periventricular and deep white matter hyperintensity scores [OR 1.64 (95% CI, 1.16-2.33), and OR 1.44 (95% CI, 1.07-1.93), respectively]. Higher CSVD burden score was positively associated with CSO [OR 1.48 (95% CI, 1.22-1.81)] and inversely associated with SSS [0.85 (95% CI, 0.72-0.99)] location after adjusting for relevant confounders. CSO RSSI were related to a higher burden of CSVD, particularly to white matter hyperintensities, compared to other RSSI locations. The pathophysiological significance of such findings should be investigated in the future with advanced neuroimaging techniques.

Clopidogrel Plus Aspirin in Patients With Different Types of Single Small Subcortical Infarction.

Background: We aim to investigate the effects and safety of clopidogrel plus aspirin in patients with different types of single small subcortical infarction (SSSI) in the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial.Methods: SSSI was defined as single DWI lesion of ≤2.0 cm. Patients with SSSI were divided into SSSI + PAD (parent artery disease) and SSSI – PAD, according to the stenosis of the parent artery. The efficacy outcome was stroke recurrence during 90-day follow-up. Cox proportional hazards models or logistic regression models were used to assess the interaction of the treatment effects of clopidogrel plus aspirin vs. aspirin alone among patients with and without PAD.Results: Among 338 patients with SSSI included in the subanalysis, 105 were with PAD and 233 without. The efficacy of clopidogrel plus aspirin compared with aspirin alone on any stroke was consistent between patients with [adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI), 0.25–2.75] and without PAD (adjusted HR 1.03; 95% CI, 0.40–2.68, interaction P = 0.83). In patients with SSSI + PAD, the rate of stroke recurrence in those treated with dual antiplatelet therapy and mono antiplatelet therapy was not significantly different (10.9 vs. 13.6%, P = 0.77). The number of bleeding events was similar between the clopidogrel-aspirin group and aspirin group regardless of SSSI + PAD or SSSI – PAD.Conclusions: There was no significant difference in the efficacy of clopidogrel plus aspirin compared with aspirin alone between patients with SSSI + PAD and SSSI – PAD in the CHANCE trial. Studies in other populations and with adequate power are needed to further verify such findings.

Lacunar Stroke Lesion Extent and Location and White Matter Hyperintensities Evolution 1 Year Post-lacunar Stroke.

Lacunar strokes are a common type of ischemic stroke. They are associated with long-term disability, but the factors affecting the dynamic of the infarcted lesion and the brain imaging features associated with them, reflective of small vessel disease (SVD) severity, are still largely unknown. We investigated whether the distribution, volume and 1-year evolution of white matter hyperintensities (WMH), one of these SVD features, relate to the extent and location of these infarcts, accounting for vascular risk factors. We used imaging and clinical data from all patients [n = 118, mean age 64.9 (SD 11.75) years old] who presented to a regional hospital with a lacunar stroke syndrome within the years 2010 and 2013 and consented to participate in a study of stroke mechanisms. All patients had a brain MRI scan at presentation, and 88 had another scan 12 months after. Acute lesions (i.e., recent small subcortical infarcts, RSSI) were identified in 79 patients and lacunes in 77. Number of lacunes was associated with baseline WMH volume (B = 0.370, SE = 0.0939, P = 0.000174). RSSI volume was not associated with baseline WMH volume (B = 3.250, SE = 2.117, P = 0.129), but predicted WMH volume change (B = 2.944, SE = 0.913, P = 0.00184). RSSI location was associated with the spatial distribution of WMH and the pattern of 1-year WMH evolution. Patients with the RSSI in the centrum semiovale (n = 33) had significantly higher baseline volumes of WMH, recent and old infarcts, than patients with the RSSI located elsewhere [median 33.69, IQR (14.37 50.87) ml, 0.001 ≤ P ≤ 0.044]. But patients with the RSSI in the internal/external capsule/lentiform nucleus experienced higher increase of WMH volume after a year [n = 21, median (IQR) from 18 (11.70 31.54) ml to 27.41 (15.84 40.45) ml]. Voxel-wise analyses of WMH distribution in patients grouped per RSSI location revealed group differences increased in the presence of vascular risk factors, especially hypertension and recent or current smoking habit. In our sample of patients presenting to the clinic with lacunar strokes, lacunar strokes extent influenced WMH volume fate; and RSSI location and WMH spatial distribution and dynamics were intertwined, with differential patterns emerging in the presence of vascular risk factors. These results, if confirmed in wider samples, open potential avenues in stroke rehabilitation to be explored further.

Post-stroke Cognition at 1 and 3 Years Is Influenced by the Location of White Matter Hyperintensities in Patients With Lacunar Stroke.

Lacunar strokes are a common type of ischemic stroke. They are known to have long-term cognitive deficits, but the influencing factors are still largely unknown. We investigated if the location of the index lacunar stroke or regional WMH and their change at 1 year could predict the cognitive performance at 1 and 3 years post-stroke in lacunar stroke patients. We used lacunar lesion location and WMH-segmented data from 118 patients, mean age 64.9 who had a brain MRI scan soon after presenting with symptoms, of which 88 had a repeated scan 12 months later. Premorbid intelligence (National Adult Reading Test) and current intelligence [Addenbrooke's Cognitive Exam-Revised (ACE-R)] were measured at 1, 12, and 36 months after the stroke. ANCOVA analyses adjusting for baseline cognition/premorbid intelligence, vascular risk factors, age, sex and total baseline WMH volume found that the recent small subcortical infarcts (RSSI) in the internal/external capsule/lentiform nucleus and centrum semiovale did not predict cognitive scores at 12 and 36 months. However, RSSI location moderated voxel-based associations of WMH change from baseline to 1 year with cognitive scores at 1 and 3 years. WMH increase in the external capsule, intersection between the anterior limb of the internal and external capsules, and optical radiation, was associated with worsening of ACE-R scores 1 and 3 years post-stroke after accounting for the location of the index infarct, age and baseline cognition.