Small Subcortical Infarcts Research Articles

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.

Abstract P374: Dolichoectacic Features of Basilar Artery Serve an Imaging Surrogate of Branch Artery Disease in Patients With Pontine Infarcts

Background: The arterial pathology underlying recent small subcortical infarctions (historically known as lacunar stroke) is heterogenous and includes lipohyalinosis, branch artery atherosclerosis or embolism. Although the use of high-resolution imaging studies directed to vessel wall might be helpful in teasing out these different pathologies, more readily available imaging surrogates such as size or spatial characteristics of the ischemic lesion are used for this purpose in clinical practice. Herein, we determined the distribution of dolichoectacic features of basilar artery in patients presenting with pontine penetrator artery stroke with different underlying occlusive pathologies. Methods: The dolichoectacic features of basilar artery were retrospectively evaluated according to Smoker’s criteria (diameter: >4.5 mm, laterality: more lateral to the lateral margin of clivus or dorsum sellae, and height of bifurcation: at least at the level of third ventricular floor) on CT angiography in ischemic stroke patients with a single penetrator artery occlusion in the pons. Patients with basilar artery pathologies such stenosis, dissection, or apparent dolichoectasia were excluded. Ischemic lesions extending to the surface of pontine base on DWI were judged to be secondary to branch artery occlusion, rather than lipohyalinosis. Results: Out of 122 patients, 68 (56%) had at least one feature suggestive of basilar artery dolichoectasia. Patients with lateral deviation of basilar artery were more likely to harbor infarcts extending to pontine surface (69% vs. 50%); no such relationship was identified for other imaging markers of dolichoectasia. After adjustment for age, gender and vascular risk factors, lateral deviation of the basilar artery remained significantly associated with an infarct pattern suggestive of branch artery occlusion (OR=2.8, 95%CI 1.1-7.3; p=0.031). There was also a tendency for ischemic lesions to be located on the ipsilateral side of the lateral deviation (63%; p=0.081). Conclusion: Our findings highlight that lateral displacement of basilar artery, an imaging feature of basilar dolichoectasia, can be used as an additional surrogate marker of branch artery pathology in patients with pontine penetrator artery infarction.

Magnetic resonance imaging manifestations of cerebral small vessel disease: automated quantification and clinical application.

The common cerebral small vessel disease (CSVD) neuroimaging features visible on conventional structural magnetic resonance imaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. The CSVD neuroimaging features have shared and distinct clinical consequences, and the automatic quantification methods for these features are increasingly used in research and clinical settings. This review article explores the recent progress in CSVD neuroimaging feature quantification and provides an overview of the clinical consequences of these CSVD features as well as the possibilities of using these features as endpoints in clinical trials. The added value of CSVD neuroimaging quantification is also discussed for researches focused on the mechanism of CSVD and the prognosis in subjects with CSVD.

Macula Structure and Microvascular Changes in Recent Small Subcortical Infarct Patients

Purpose: This study aimed to assess the macula structure and capillaries in the macula and optic nerve head in recent small subcortical infarct (RSSI) patients.Methods: This observational cross-sectional study included 40 RSSI patients and 46 healthy controls. Optical coherence tomography angiography was used to image the capillaries in the macula and optic nerve head. An inbuilt algorithm was used to measure the densities in the microvasculature of the macula [superficial retinal capillary plexus (SRCP) and deep retinal capillary plexus (DRCP)] and optic nerve head [radial peripapillary capillary (RPC)] and thickness around the optic nerve head, peripapillary retinal nerve fiber layer (pRNFL).Results: Densities in RPC (P < 0.001), SRCP (P = 0.001), and DRCP (P = 0.003) were reduced in RSSI patients when compared with healthy controls. The pRNFL thickness was thinner (P < 0.001) in RSSI patients than healthy controls. In the RSSI group, the SRCP density significantly correlated with the DRCP density (rho = 0.381, P = 0.042). The pRNFL thickness displayed a significant relationship with the RPC density (rho = 0.482, P = 0.003) in the RSSI group.Conclusions: RSSI patients showed interrupted capillary plexuses leading to its significant impairment and neurodegeneration. Our report provides insight into the macula capillary microcirculation changes in RSSI.

Comparison of plaque characteristics of small and large subcortical infarctions in the middle cerebral artery territory using high-resolution magnetic resonance vessel wall imaging

The characteristics of plaque that ultimately lead to different subcortical infarctions remain unclear. We explored the differences in plaque characteristics between patients with small subcortical infarction (SSI) and large subcortical infarction (LSI) of the middle cerebral artery (MCA) using high-resolution magnetic resonance vessel wall imaging (HR-MRVWI). The study group comprised 71 patients (mean age, 47.49±11.5 years; 55 male) with MCA territory ischemic stroke. Whole-brain HR-MRVWI was performed using a three-dimensional T1-weighted variable-flip-angle turbo spin echo (SPACE) sequence. Patients were divided into SSI and LSI groups based on routine MRI images. Plaque distribution was classified as the superior, inferior, ventral, or dorsal wall of the MCA. The number of quadrants with plaque formation, location of plaque, plaque burden (PB), arterial remodeling pattern (positive or negative), and degree of stenosis were analyzed and compared between groups. Of the 71 patients, 43 (60.6%) and 28 (39.4%) were identified as the SSI and LSI groups, respectively. The proportion of plaques involving only one quadrant was significantly higher in the SSI group, and these plaques were located in the superior or dorsal MCA vessel wall. There was no significant difference between groups in the proportion of plaques involving two or more quadrants, plaque distribution, or PB. Most plaques in both groups showed positive remodeling, and the percentage of remodeling pattern was similar. A significantly higher incidence of low-grade stenosis (<50%) was observed in the SSI group. Both SSI and LSI may be associated with major intracranial artery atherosclerosis, but patients with SSI showed relatively fewer quadrants with plaque formation and a lesser degree of stenosis.

Baseline white matter hyperintensities affect the course of cognitive function after small vessel disease-related stroke: a prospective observational study.

Background and purposeCognitive impairment is a common sequel of recent small subcortical infarction (RSSI) and might be negatively affected by preexisting cerebral small vessel disease (SVD). We investigated whether the course of cognitive function in patients with RSSI is influenced by the severity of white matter hyperintensities (WMH), an important imaging feature of SVD.MethodsPatients with magnetic resonance imaging (MRI)‐proven single RSSI were tested neuropsychologically concerning global cognition, processing speed, attention, and set‐shifting. Deep and periventricular WMH severity was assessed using the Fazekas scale, and total WMH lesion volume was calculated from T1‐weighted MRI images. We compared baseline function and course of cognition 15 months after the acute event in patients with absent, mild, and moderate‐to‐severe WMH.ResultsThe study cohort comprised 82 RSSI patients (mean age: 61 ± 10 years, 23% female). At baseline, 40% had cognitive impairment (1.5 standard deviations below standardized mean), and deficits persisted in one‐third of the sample after 15 months. After age correction, there were no significant differences in set‐shifting between WMH groups at baseline. However, although patients without WMH (deep: p < 0.001, periventricular: p = 0.067) or only mild WMH (deep: p = 0.098, periventricular: p = 0.001) improved in set‐shifting after 15 months, there was no improvement in patients with moderate‐to‐severe WMH (deep: p = 0.980, periventricular: p = 0.816). Baseline total WMH volume (p = 0.002) was the only significant predictor for attention 15 months poststroke.ConclusionsThis longitudinal study demonstrates that preexisting moderate‐to‐severe WMH negatively affect the restoration of cognitive function after RSSI, suggesting limited functional reserve in patients with preexisting SVD.

Susceptibility Vessel Sign in Deep Perforating Arteries in Patients with Recent Small Subcortical Infarcts

ObjectivesRecent small subcortical infarcts (RSSI) are considered an acute manifestation of cerebral small vessel disease. Paramagnetic signals in perforating arteries supplying RSSI may be detected on T2*-relaxation derived sequences on MRI and is defined as susceptibility vessel sign (SVS). We aimed to study the prevalence of SVS in patients with RSSI, and explore whether its identification is related to cerebral small vessel disease markers. Materials and MethodsWe selected patients with RSSI identified on MRI during admission from a single-center stroke registry. The main demographic and clinical features, including vascular risk factors, were collected. Radiological features of RSSI and cerebral small vessel disease [white matter hyperintensities in deep and periventricular regions, enlarged perivascular spaces, lacunae, microbleeds, and brain atrophy] were described using validated qualitative scores. The presence of SVS was assessed on T2*gradient-echo or other susceptibility-weighted imaging. We compared the clinical and radiological features of patients with or without SVS in uni- and multivariate models. ResultsOut of 210 patients with an RSSI on an MRI, 35 (17%) showed SVS. The proportion of SVS+ patients was similar in different susceptibility imaging modalities (p=.64). Risk factor profiles and clinical course were similar in SVS+ and SVS- patients. SVS+ patients had a higher grade of deep white matter hyperintensities and brain atrophy, more lacunae (p=.001, p=.034, p=.022, respectively), and a similar degree of the rest of radiological variables, compared to SVS- patients. In the multivariate analysis, the grade of deep white matter hyperintensities was the only independent factor associated with SVS [OR 3.1 (95% CI, 1.5-6.4)]. ConclusionsSVS in patients with RSSI is uncommon and related to a higher grade of deep white matter hyperintensities. Pathophysiological mechanisms underlying the deposition of hemosiderin in the path of occluded perforating arteries are uncertain and might include endothelial dysfunction or embolic mechanisms.

Elevated Serum Homocysteine Associated with Distal Type of Single Small Subcortical Infarction.

The aim of this investigation was to examine the association between the serum homocysteine (Hcy) level and the distal single small subcortical infarction (dSSSI). Consecutive patients were prospectively recruited in a registered hospital-based ischemic stroke database. Baseline characteristics and risk factors of single small subcortical infarction (SSSI), including the serum Hcy level, were assessed. The SSSI located in the lenticulostriate artery (LSA) territory was divided into proximal single small subcortical infarction (pSSSI) and dSSSI based on a standard template on axial diffusion-weighted imaging (DWI). The association between the serum Hcy level and dSSSI was analysed by multivariate logistic regression analysis. Out of 3,247 patients, a total of 572 patients were included in the final analysis. We found that dSSSI had a higher serum Hcy level than pSSSI. Elevated Hcy level was independently correlated with dSSSI. Compared with the lowest quartile, the upper quartiles of Hcy level were independently associated with dSSSI, the odds ratio for the second quartile was 1.748 (95%CI 1.019 to 3.000), 1.824 (95% CI 1.060 to 3.140) for the third quartile, and 2.010 (95% CI 1.155 to 3.497) for the fourth quartile. The restricted cubic spline showed that the higher level of Hcy, the greater risk of developing dSSSI. The dSSSI shows higher serum Hcy level than pSSSI. Elevated serum Hcy is more closely related to dSSSI. In the future, the effectiveness of Hcy-lowering therapy for dSSSI needs to be explored by further clinical studies.

Morphologic evolution of recent small sub-cortical infarcts and adjacent white matter in the basal ganglia in a Chinese cohort.

BackgroundData on the evolution of recent small sub-cortical infarcts are limited, especially in the Chinese. Previous studies have reported a large heterogeneity in cavitation and infarct location; therefore, the present study assessed the morphology of small sub-cortical infarcts in the basal ganglia in a Chinese cohort.MethodsPatients who had experienced a recent, single, small sub-cortical infarct in the basal ganglia and received at least one follow-up magnetic resonance imaging (MRI) scan were retrospectively identified from January 2014 to June 2018. Time to follow-up imaging, baseline infarct size, vascular risk factors, and other clinical data, as well as the morphologic changes of the index infarct and surrounding white matter were recorded. Demographic, clinical and MRI characteristics were respectively compared among three groups (white matter hyper-intensitie [WMH] vs. cavitation vs. absent) and between with and without new WMH formation groups. In addition, logistic regression analyses were performed in investigating the determinate independent predictors for new WMH formation.ResultsSeventy-eight subjects were included with a median follow-up time of 304 days (range: 124–552 days). We found a significant reduction in infarct size at follow-up: 46 of 78 (59.0%) infarctions showed some degree of cavitation, 19 of 78 (24.4%) index lesions resembled non-cavitated WMH, and 13 of 78 (16.7%) infarcts had disappeared at follow-up MRI. No factors were found to be associated with differential outcomes of the infarcts. In addition, 8 of 78 (10.3%) patients demonstrated new WMH formation surrounding the index infarct; white matter progression (odds ratio = 15.95, 95% confidence interval = 1.65–153.99; P = 0.017) was an independent risk factor of new WMH formation.ConclusionsMore than half of the small sub-cortical infarcts in the basal ganglia progressed to cavities, demonstrating that these infarcts can be reduced and go undetected. The presence of new WMH around the infarct may be indicative of the worsening progression of cerebral small vessel diseases. Additionally, white matter progression is an independent risk factor, which may be a potential therapeutic target.

Infarct site and prognosis in small subcortical infarction: Role of the corticospinal tract and lentiform

Objective: To determine the impact of infarct site combinations on prognosis of small subcortical infarction (SSI) by classifying the infarcted perforator area in relation to the anatomical structures that surround and/or involve the corticospinal tract.Methods: Consecutive patients with SSI ≤24 h from onset to initial magnetic resonance imaging (MRI) and ≤ 14 days from onset to second MRI were included. Infarct sites were defined as follows: caudate head, lentiform (L), corona radiata (CR), posterior limb and genu of the internal capsule (IC), thalamus, and brainstem with or without involvement of the corticospinal tract. An unfavorable outcome was defined as a modified Rankin Scale score of 2 to 6 at 3 months from onset. Infarct site combinations related to an unfavorable outcome were evaluated.Results: We screened 1558 consecutive patients with ischemic strokes, including 128 with SSI (99 [77%] male, median age 64 years). Of all, 29 (23%) had unfavorable outcomes. Factors associated with unfavorable outcomes were age (odds ratio (OR) 2.057, 95% confidence interval (CI) 1.230–3.493, p = 0.006), maximum infarct area (OR 1.094, 95% CI 1.030–1.163, p = 0.004), and infarct simultaneously involving the CR, IC, and L (OR 9.403, 95% CI 1.506–58.710, p = 0.016). Patients with simultaneous involvement of the CR, IC, and L were likely to have a higher subscore in the National Institutes of Health Stroke Scale item of arm motor impairment at discharge (OR 2.947, 95% CI 1.098–7.910, p = 0.032).Conclusions: Infarcts involving the CR, IC, and L predict unfavorable outcomes in SSI.

Factors Associated With the Occurrence and Evolution of Recent Small Subcortical Infarcts (RSSIs) in Different Locations.

Recent small subcortical infarcts (RSSIs) can occur in different brain regions. Distinct etiologies might be involved for RSSIs in different locations and could further affect RSSI cavitation and functional outcomes. In this study, we aim to analyze the baseline clinical and imaging characteristics associated with the occurrence and cavitation of RSSIs in different locations. We retrospectively include patients who presented with RSSIs from a database for cerebral small vessel disease. Detailed information, including demographic, clinical, laboratory, and radiological data, were collected. We identify baseline RSSIs on diffusion-weighted images and divide them into brainstem, subcortical white matter, and basal ganglia region groups. Cavitation is evaluated on follow-up T2 fluid-attenuated inversion recovery (FLAIR) images. Statistical analysis is performed to determine factors associated with the occurrence and cavitation of RSSIs in different locations. We find that patients with brainstem RSSIs have a higher proportion of diabetes (64.1%) compared to patients with subcortical white matter (27.3%, P < 0.001) and basal ganglia region RSSIs (35.2%, P = 0.006) and have higher levels of HbA1c (7.20%) compared to patients with subcortical white matter (6.10%, P = 0.001) and basal ganglia region RSSIs (6.20%, P = 0.003). In addition, patients with brainstem RSSIs have higher NIHSS scores than patients with subcortical white matter RSSIs (2 vs 0, P = 0.001). Patients with subcortical white matter RSSIs have higher a white matter hyperintensity (WMH) burden compared to patients with basal ganglia region RSSIs (21.64 cm3 vs 11.10 cm3, P = 0.004). Follow-up analysis demonstrates that basal ganglia region RSSIs are less likely to cavitate than subcortical white matter RSSIs (61.4% vs 83.6%, P = 0.010), and contacting with WMH is associated with the cavitation of subcortical white matter RSSIs (OR: 101.760, P = 0.003). Our study demonstrates that RSSIs in different locations are associated with different clinical and imaging characteristics. Furthermore, cavitation of RSSIs might be affected by local lesion features and the surrounding environment rather than general demographic and clinical factors.

Cavitation of symptomatic acute single small subcortical infarctions.

To investigate cavitation of symptomatic acute single small subcortical infarctions (SSSI). Acute SSSI were diagnosed with magnetic resonance (MR) diffusion-weighted imaging (DWI) combined with apparent diffusion coefficient (ADC) sequence on follow-up MR imaging. Cavitation of the acute SSSI was comprehensively viewed on FLAIR, T2-, and T1-weighted sequences. We enrolled 123 patients with acute SSSI. The follow-up median interval was 303 (125-390) days. The lesions of SSSI evolved into cavitation in 93 patients (75.6%), evolved into WMHs in nine patients (7.3%), and were no visible in 21 patients (17.1%). Cavitation was independently associated with larger infarct diameter on baseline DWI [odds ratio (OR), 1.250, 95% CI (1.078-1.451), P= 0.003], higher score of baseline old lacunar infarct [OR 3.44, 95% CI (1.49-7.91), P= 0.004], and lower rate of dyslipidemia [OR 0.30, 95% CI (0.10-0.76), P= 0.013]. Cavitation occurred more in the setting of small vessel diseased brain and less in the SSSI of possible atherosclerotic etiology. This suggested that the etiology of infarct was associated with cavitation after acute SSSI.

Protocol: The Lacunar Intervention Trial 2 (LACI-2). A trial of two repurposed licenced drugs to prevent progression of cerebral small vessel disease.

BackgroundSmall vessel disease causes a quarter of ischaemic strokes (lacunar subtype), up to 45% of dementia either as vascular or mixed types, cognitive impairment and physical frailty. However, there is no specific treatment to prevent progression of small vessel disease.AimWe designed the LACunar Intervention Trial-2 (LACI-2) to test feasibility of a large trial testing cilostazol and/or isosorbide mononitrate (ISMN) by demonstrating adequate participant recruitment and retention in follow-up, drug tolerability, safety and confirm outcome event rates required to power a phase 3 trial.Methods and designLACI-2 is an investigator-initiated, prospective randomised open label blinded endpoint (PROBE) trial aiming to recruit 400 patients with prior lacunar syndrome due to a small subcortical infarct. We randomise participants to cilostazol v no cilostazol and ISMN or no ISMN, minimising on key prognostic factors. All patients receive guideline-based best medical therapy. Patients commence trial drug at low dose, increment to full dose over 2–4 weeks, continuing on full dose for a year. We follow-up participants to one year for symptoms, tablet compliance, safety, recurrent vascular events, cognition and functional outcomes, Trails B and brain MRI. LACI-2 is registered ISRCTN 14911850, EudraCT 2016–002277-35.Trial outcome: Primary outcome is feasibility of recruitment and compliance; secondary outcomes include safety (cerebral or systemic bleeding, falls, death), efficacy (recurrent cerebral and cardiac vascular events, cognition on TICS, Trails B) and tolerability.SummaryLACI-2 will determine feasibility, tolerability and provide outcome rates to power a large phase 3 trial to prevent progression of cerebral small vessel disease.

Cerebral Small Vessel Disease.

This article reviews the clinical significance and neuroimaging characteristics of cerebral small vessel disease and the impact on neurologic disease and current and potential therapeutic approaches. Cerebral small vessel disease is increasingly prevalent and highly heterogeneous in neuroimaging and clinical presentation. Small subcortical infarcts, lacunes, cerebral microbleeds, cortical microinfarcts, and white matter hyperintensity of presumed vascular origin represent the major neuroimaging markers of small vessel disease. Increasing small vessel disease burden is associated with risk of incident stroke and dementia, as well as other neuropsychiatric symptoms. Current research strategies are targeting elucidation of the mechanisms of small vessel disease pathogenesis and pursuing clinical trials of therapeutic agents to reduce the clinical manifestations of cerebral small vessel disease. Cerebral small vessel disease is common in aging adults and represents a major risk factor for multiple acute and chronic neurologic diseases. Increased awareness of cerebral small vessel disease as a modifiable risk factor holds potential for reducing neurologic disease morbidity and mortality across diverse populations in the United States and worldwide.

Effects of Genetic Variants on Stroke Risk.

Effects of Genetic Variants on Stroke Risk.

Analysis of related factors affecting evolution of recent small subcortical infarcts with cerebral small vessel disease

Objective: To explore related factors affecting evolution of recent small subcortical infarct (RSSI) with small-artery occlusion. Methods: A total of 96 RSSI patients with RSSI were admitted from Shanghai Tongji Hospital between January 2015 and December 2018. The age of patients containing 60 men was 64.5 (58-73) years, and MRI follow-up time was 11.6 (6.3-11.8) months. Clinical information of patients, images data at baseline head MRI and evolution outcomes at follow-up MRI were collected. All patients were divided into cavitation group (lacunes) and no cavitation group (white matter hyperintensities (WMH) and disappearance) to analyze related factors. Results: Fifty-nine cases (61.5%) developed to cavities, 32 cases (33.3%) were focal WMH, and 5 cases (5.2%) disappeared.In the univariate analysis, RSSI maximum diameter on the DWI or T(2)WI sequence of cavitation group was significantly higher than non-cavitation group, but male proportion was lower (11.6 (9.9-16.6) vs 8.6 (6.9-13.0) mm, 11.8 (9.7-16.2) vs 8.8 (6.7-13.1) mm, 54.2% vs 75.7%, all P<0.05). In Logistic regression analysis,the maximum diameter on DWI sequence was an independent predictor of cavity formation (P=0.022,OR=1.138).When conducting quantitative analysis of infarct diameter and taking infarct maximum diameter ≤10 mm group as reference, the cavitation risk of maximum diameter>15 mm group was about 7.5 times higher (P=0.010, OR=7.464). The maximum diameter of 10-15 mm lost predictive value for cavity formation (P=0.129, OR=2.444). Conclusions: About 61.5% of RSSI develop to cavitation and 38.5% to WMH or disappear. The RSSI showing larger diameter on DWI has a greater possibility of cavitation.

Predictors of Lesion Cavitation After Recent Small Subcortical Stroke

Morphologic evolution of recent small subcortical infarcts (RSSI) ranges from lesion disappearance to lacune formation and the reasons for this variability are still poorly understood. We hypothesized that diffusion tensor imaging (DTI) and blood-brain-barrier (BBB) abnormalities early on can predict tissue damage 1 year after an RSSI. We studied prospectively recruited patients with a symptomatic MRI-defined RSSI who underwent baseline and two pre-specified MRI examinations at 1–3-month and 1-year post-stroke. We defined the extent of long-term tissue destruction, termed cavitation index, as the ratio of the 1-year T1-weighted cavity volume to the baseline RSSI volume on FLAIR. We calculated fractional anisotropy and mean diffusivity (MD) of the RSSI and normal-appearing white matter, and BBB leakage in different tissues on dynamic contrast-enhanced MRI. Amongst 60 patients, at 1-year post-stroke, 44 patients showed some degree of RSSI cavitation on FLAIR, increasing to 50 on T2- and 56 on T1-weighted high-resolution scans, with a median cavitation index of 7% (range, 1–36%). Demographic, clinical, and cerebral small vessel disease features were not associated with the cavitation index. While lower baseline MD of the RSSI (rs = − 0.371; p = 0.004) and more contrast leakage into CSF (rs = 0.347; p = 0.007) were associated with the cavitation index in univariable analysis, only BBB leakage in CSF remained independently associated with cavitation (beta = 0.315, p = 0.046). Increased BBB leakage into CSF may indicate worse endothelial dysfunction and increased risk of tissue destruction post RSSI. Although cavitation was common, it only affected a small proportion of the original RSSI.

Early renal dysfunction and fibroblast growth factor-23 in patients with small vessel disease-related stroke

Interactions between cerebral small vessel disease (CSVD) and renal dysfunction (RD) have been reported, but previous studies were mostly retrospective and limited to measurements of estimated glomerular filtration rate (eGFR). In this prospective, longitudinal study of patients with CSVD-related recent small subcortical infarcts (RSSI), we aimed at a comprehensive exploration of markers of early RD and their association with microvascular brain damage. We investigated 101 stroke patients (mean age: 60.2 ± 10.7 years) with an MRI-confirmed RSSI who underwent follow-up brain MRI 15 months post-stroke. Besides serum creatinine and eGFR, we assessed urinary Albumin-Creatinine Ratio and fibroblast growth factor-23 (FGF-23). RD was classified according to recent Kidney Disease: Improving Global Outcomes criteria. We identified 24 patients with RD, only six patients revealed an eGFR <60 mL/min/1.73 m². RSSI patients with RD more often had severe white matter hyperintensities (WMH, 58% vs. 36%, p = 0.04). CSVD progression was not dependent on RD. However, patients in the highest FGF-23 quartile more frequently had new microangiopathic lesions on follow-up MRI (50% vs. 21%, p = 0.03). Early RD was found in a quarter of RSSI patients and associated with WMH severity, but not CSVD progression. High FGF-23 indicates an increased risk for ongoing microvascular brain damage, warranting further studies.

Endothelial dysfunction on cerebral small vessel disease

Globally, Stroke represents the second leading cause of death and the third leading cause of disability and stroke incidence in low- and middle-income countries has more than doubled in the last decades [[2]Johnson W. Onuma O. Owolabi M. et al.Stroke: a global response is needed.Bull World Health Organ. 2016 Sep 1; 94 (634–634A)Google Scholar, [4]Rodríguez-Salinas L.C. Medina M.T. Stroke in developing countries.in: Bogousslvasky Stroke; Selected Topics. World Federation of Neurology (WFN) Seminars in Clinical Neurology, Demos, New York2006: 49-62Google Scholar] and is responsible for 85% of the deaths due to neurological disorders. Cerebral small vessel disease causes 25% of strokes [[1]Cannistraro R.J. Badi M. Eidelman B.H. et al.CNS small vessel disease: a clinical review.Neurology. 2019 Jun 11; 92: 1146-1156Google Scholar]. Cerebral Small vessel disease (CSVD), is a heterogeneous vascular entity, that includes lacunar cerebral infarctions which are small deep infarcts in the territory of small penetrating arteries (Deep perforator arteriopathy) or cerebral amyloid angiopathy among others, due to a local disease of these vessels which cause ischaemic stroke, intracebral haemorrhage, vascular cognitive impairment, abnormal movement disorders, focal neurologic syndromes, etc (Norrving et al. 2013; Sacco et al. 2013; Fisher 1982). CSVD is associated with blood-brain barrier disruption and endothelial dysfunction [[5]Schreiber S. Wilisch-Neumann A. Schreiber F. et al.The spectrum of age-related small vessel diseases: potential overlap and interactions of amyloid and non-amyloid vasculopathies.Neuropathol Appl Neurobiol. 2019 Aug; : 6Google Scholar]. Endothelial dysfunction represents a reduction on the nitric oxide-dependent-vascular dilatation and can be described as an imbalance between vasodilatation and vasoconstriction produced by the endothelium( [[3]Moncada S. Higgs E.A. The discovery of nitric oxide and its role in vascular biology.Br J Pharmacol. 2006; 147: S193-S201Google Scholar]). CSVD can be evaluated using Neuroimaging. Recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces and microbleeds are usually the most frequent findings [[6]Wardlaw J.M. Smith E.E. Biessels G.J. et al.Standards for reporting vascular changes on neuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration.Lancet Neurol. 2013; 12: 822-838Google Scholar]. Several risk factors are strongly associated with CSVD and endothelial dysfunction such as : High blood pressure, metabolic syndrome, hyper homocysteine, low plasma levels of vitamin B12, abnormal endothelium-dependent vasodilation among others. These factors associated with genetics factors and lifestyle changes in low- and middle-income countries can explain the increased stroke incidence mainly in CSVD patients from these countries.

Brain White Matter: A Substrate for Resilience and a Substance for Subcortical Small Vessel Disease.

Age-related brain white matter disease is a form of small vessel disease (SVD) that may be associated with lacunar and other small subcortical infarcts, cerebral microbleeds, and perivascular spaces. This common form of cerebrovascular disease may manifest clinically as cognitive impairment of varying degrees and difficulty with mobility. Whereas some persons show cognitive decline and mobility failure when there are brain white matter hyperintensities (WMH) and acute stroke, others recover, and not everyone with brain white matter disease is disabled. Thus, repair or compensation of brain white matter may be possible, and furthermore, certain vascular risks, such as raised blood pressure, are targets for prevention of white matter disease or are administered to reduce the burden of such disease. Vascular risk modification may be useful, but alone may not be sufficient to prevent white matter disease progression. In this chapter, we specifically focus on WMH of vascular origin and explore white matter development, plasticity, and enduring processes of myelination across the health span in the context of experimental and human data, and compare and contrast resilient brain white matter propensity to a diseased white matter state. We conclude with thoughts on novel ways one might study white matter resilience, and predict future healthy cognitive and functional outcomes.