Correlation of silent brain infarcts and leukoaraiosis in middle-aged ischemic stroke patients: a retrospective study.

Background: Cerebrovascular diseases of the brain are usually defined by transient ischemic attacks and strokes. However, they can also cause brain injuries without neurological events. Silent brain infarcts (SBI) and leukoaraiosis are symptoms of both vascular and neurological abnormalities. This study aims to investigate the association between SBI, leukoaraiosis, and middle-aged patients with ischemic stroke. Methods: A single-center retrospective study of 50 middle-aged, ischemic stroke patients were studied from November 2022 and May 2023. The patients were divided into two groups based on the presence or absence of leukoaraiosis. History taking, physical examination, brain CT scan, and MRI were all part of the diagnostic process. Metabolic syndrome (MetS) was also assessed through various factors. The statistical analysis included descriptive statistics, logistic regression analysis, and chi-square test. Results: Out of the cohort comprising 50 patients, characterized by a mean age of 52.26 years (SD 5.29), 32 were male, constituting 64% of the sample. Among these patients, 26 individuals exhibited leukoaraiosis, with 17 of them (65.4%) also presenting with SBI. Moreover, within this cohort, 22 patients were diagnosed with MetS, representing 84.6% of those affected. The Multivariate logistic regression analysis showed a strong and independent association between leukoaraiosis and SBI. Individuals with leukoaraiosis were nearly five times more likely to have SBI compared to those without leukoaraiosis. Conclusion: The study highlights leukoaraiosis as a significant risk factor for SBI, alongside MetS. Advanced imaging techniques have facilitated their detection, revealing a higher prevalence among stroke patients, particularly associated with age and hypertension. Further research is needed to fully understand their complex relationship and develop better management strategies for cerebrovascular diseases, ultimately improving patient outcomes.

Chronic kidney disease and its association with cerebral small vessel disease in the general older hypertensive population.

BACKGROUND: Cerebral small vessel disease can be identified using magnetic resonance imaging, and includes white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and brain atrophy. Cerebral small vessel disease and chronic kidney disease share many risk factors, including hypertension. This study aims to explore an association between chronic kidney disease and cerebral small vessel disease, and also to explore the role of hypertension in this relationship. METHODS: With a cross sectional study design, data from 390 older adults was retrieved from the general population study Good Aging in Skåne. Chronic kidney disease was defined as glomerular filtration rate < 60 ml/min/1,73m2. Associations between chronic kidney disease and magnetic resonance imaging markers of cerebral small vessel disease were explored using logistic regression models adjusted for age and sex. In a secondary analysis, the same calculations were performed with the study sample stratified based on hypertension status. RESULTS: In the whole group, adjusted for age and sex, chronic kidney disease was not associated with any markers of cerebral small vessel disease. After stratification by hypertension status and adjusted for age and sex, we observed that chronic kidney disease was associated with cerebral microbleeds (OR 1.93, CI 1.04-3.59, p-value 0.037), as well as with cortical atrophy (OR 2.45, CI 1.34-4.48, p-value 0.004) only in the hypertensive group. In the non-hypertensive group, no associations were observed. CONCLUSIONS: In this exploratory cross-sectional study, we observed that chronic kidney disease was associated with markers of cerebral small vessel disease only in the hypertensive subgroup of a general population of older adults. This might indicate that hypertension is an important link between chronic kidney disease and cerebral small vessel disease. Further studies investigating the relationship between CKD, CSVD, and hypertension are warranted.

Infarcts of a Cardioembolic Source Mimicking Lacunar Infarcts: Case Series With Clinical and Radiological Correlation.

Lacunar strokes are the hallmark of cerebral small vessel disease. There are several well-established mechanisms for the pathogenesis of lacunar stroke, but the cardioembolic mechanism is not well-established. Three cases of acute ischemic stroke following elective cardiac and cerebral catheterization are reported. These cases had typical lacunar-looking infarcts on neuroimaging despite strong evidence of an embolic source with temporal correlation. Awareness of such findings and pathogenesis may help investigational workup and management of these patients.

Arteriolosclerosis CSVD: a common cause of dementia and stroke and its association with cognitive function and total MRI burden.

Objective: Arteriolosclerosis cerebral small vessel disease (CSVD) is a common type of CSVD. This study aimed to explore the factors associated with cognitive function and total MRI burden related to the disease. Methods: The demographic characteristics, clinical manifestations, cognitive function score, Barthel Index (BI), blood test index, and follow-up results of arteriolosclerosis CSVD patients treated for the first time in our hospital from January 2014 to August 2022 were collected. White matter hyperintensity (WMH) Fazekas score, total MRI burden, and cerebral atrophy grade were evaluated according to brain MRI findings. Factors associated with CSVD cognitive function were analyzed by binary logistic regression. The correlative factors related to the total MRI burden of CSVD were analyzed by ordered multiple logistic regression. Results: A total of 146 patients were included in this study, of which 132 cases (90.4%) had hypertension. There were 108 patients (74.0%) with cognitive dysfunction, 97 patients (66.4%) with balance and gait disorders, and 83 patients (56.8%) with moderate-to-severe dependence in daily life (BI ≤ 60 points). Of 146 patients, 79 (54.1%) completed clinical and imaging follow-ups for a median of 3 years. The number of patients with cognitive impairment and BI ≤ 60 points after follow-up significantly increased compared with the first admission (P < 0.001). There were also significant differences in total MRI burden (P = 0.001), WMH Fazekas score, and cerebral atrophy grade (P < 0.001). Mean age (P = 0.012), median deep WMH Fazekas score (P = 0.028), and median deep (P < 0.001) and superficial (P =0.002) cerebral atrophy grade of patients with cognitive impairment at first admission were all higher than those with non-cognitive impairment. Multivariate analysis showed that deep cerebral atrophy was independently and significantly associated with cognitive impairment of CSVD (P = 0.024), and hypertension was significantly and independently associated with total MRI burden (P = 0.001). Conclusion: The disease course of arteriolosclerosis CSVD may be related to cognitive function and total MRI burden. Deep cerebral atrophy was an independent risk factor for cognitive dysfunction in arteriolosclerosis CSVD, and hypertension was an independent risk factor for total MRI burden.

Neutrophil-Lymphocyte Ratio as a Predictor of Cerebral Small Vessel Disease in a Geriatric Community: The I-Lan Longitudinal Aging Study.

Cerebral Small Vessel Disease (CSVD) frequently affects the elderly, with inflammation playing a crucial role in related health complications, including dementia, stroke, and SVD. Studies, including animal experiments, indicate a strong link between inflammation and SVD progression. The Neutrophil-Lymphocyte Ratio (NLR) serves as a possible biomarker for ongoing inflammatory risks. A total of 720 adults aged 50 years or older from the community-based I-Lan Longitudinal Aging Study were included in this study. General linear regression and ordinally logistic regression analyses were performed to evaluate the association between NLR and CSVD. We further examined the presence of lacune, microbleed, and white matter hyperintensity (WMH) on brain MRI, which were used to construct a combined CSVD score. The NLR was positively associated with WMH (adjusted r = 0.109, p = 0.003), microbleed (adjusted r = 0.102, p = 0.006), and lacune (adjusted r = 0.100, p = 0.008). After adjustments for smoking, drinking, and physical activity in the ordinal logistic regression analysis, age, gender, brachial Systolic Blood Pressure (SBP), fasting glucose, LDL-cholesterol, and Hs-CRP were compared among subjects with low tertile (T1), medium tertile (T2) and high tertile (T3) NLR. The results showed that T2 vs. T1 had an odds ratio of 1.23 (0.86-1.77); and T3 vs. T1 had an odds ratio of 1.87 (1.29-2.71) of CSVD scores in four groups (zero (reference group), one, two, and three or more). NLR could be used to assess the state of inflammation in cerebral vessels. A significant and positive correlation between NLR and CSVD was verified in this study. However, the practical clinical application of NLR in CSVD patients and prognosis prediction should be validated through more scientific attempts.

Regional Cerebral Small Vessel Disease (rCSVD) Score: A clinical MRI grading system validated in a stroke cohort.

BACKGROUND: Current methods for quantitative assessment of cerebral small vessel disease (CSVD) ignore critical aspects of the disease, namely lesion type and regionality. We developed and tested a new scoring system for CSVD, "regional Cerebral Small Vessel Disease" (rCSVD) based on regional assessment of magnetic resonance imaging (MRI) features. METHODS: 141 patients were retrospectively included with a derivation cohort of 46 consecutive brain MRI exams and a validation cohort of 95 patients with known cerebrovascular disease. We compared the predictive value of rCSVD against existing scoring methods. We determined the predictive value of rCSVD score for all-cause mortality and recurrent strokes. RESULTS: 46 (44 male) veteran patients (age: 66-93 years), were included for derivation of the rCSVD score. A non-overlapping validation cohort consisted of 95 patients (89 male; age: 34-91 years) with known cerebrovascular disease were enrolled. Based on ROC analysis with comparison of AUC (Area Under the Curve), "rCSVD" score performed better compared to "total SVD score" and Fazekas score for predicting all-cause mortality (0.75 vs 0.68 vs 0.69; p = 0.046). "rCSVD" and total SVD scores were predictive of recurrent strokes in our validation cohort (p-values 0.004 and 0.001). At a median of 5.1 years (range 2-17 years) follow-up, Kaplan-Meier survival analysis demonstrated an rCSVD score of 2 to be a significant predictor of all-cause-mortality. CONCLUSION: "rCSVD" score can be derived from routine brain MRI, has value in risk stratification of patients at risk of CSVD, and has potential in clinical trials once fully validated in a larger patient cohort.

[Small focal cerebral ischemic changes caused by hypertension and tandem atherostenosis of the cerebral arteries]. / Melkoochagovye ishemicheskie izmeneniya golovnogo mozga, obuslovlennye arterial'noi gipertoniei i tandemnym aterostenozom tserebral'nykh arterii.

Postmortem studies are of great importance in evaluating the effectiveness of clinical, diagnostic, therapeutic, and preventive measures aimed at combating a social disease, such as dyscirculatory encephalopathy, the leading causes of which are hypertension and atherosclerosis. The complexity of these studies is largely determined by a variety of brain changes with the frequent concurrence of hypertension and severe cerebral atherosclerosis and, at the same time, the similarity of some changes, for example, the localization and size of hypertensive and atherosclerotic lacunar infarcts. The paper describes a case of dyscirculatory encephalopathy with multiple small focal cerebral ischemic changes caused by both hypertension and athero-stenosis of several arteries in both the brain carotid systems and the vertebrobasilar system, namely tandem stenoses. It has been established that small infarcts in tandem stenosis can result from adaptive processes in the intracranial arteries. These infarcts have some features of localization, such as the areas of adjacent blood supply to the cerebral hemispheres and cerebellum, as well as the deep regions of the brainstem. It is shown that arterial pathological changes in the ischemic zones permit one to make a differential diagnosis of hypertensive lacunar infarcts and the same infarcts arising in tandem stenoses. In addition, among the typological signs of hypertensive lacunar infarcts, there are enlarged perivascular spaces in the peri-infarct region and ischemic destruction of myelin in the periventricular regions of the brain.

Study on imaging features of asymptomatic cerebral small vessel disease and related factors in the elderly population / 中华老年医学杂志

Objective:To investigate the incidence, neuroimaging features, and related factors for asymptomatic cerebral small vessel disease(CSVD)in the elderly population.Methods:A total of 201 elderly people with no neurological disease history who had undergone brain magnetic resonance imaging(MRI)examination from October 2019 to August 2020 were enrolled.We calculated the total CSVD score for each participant based on lacunar infarcts(LIs), white matter hyperintensities(WMH), enlarged perivascular spaces(EPVS), and cerebral microbleeds(CMBs)(0-4 points).CSVD neuroimaging features and the correlation between CSVD markers and clinical variables were analyzed.Results:In this study, 133 cases(66.2%)showed MRI features consistent with CSVD.Of whom, LIs were present in 44(21.9%), high-grade PVWMH in 88(43.8%), high-grade DWMH in 30(14.9%), basal ganglia EPVS in 61(30.3%), and CMBs in 92(45.8%).Total CSVD burden score( OR=1.876, 95% CI: 1.045-3.364, χ2=4.441, P=0.035), PVWMH( OR=2.821, 95% CI: 1.517-5.244, χ2=10.752, P=0.001), DWMH( OR=2.130, 95% CI: 1.108-4.092, χ2=5.145, P=0.023), and EPVS( OR=3.258, 95% CI: 1.675-6.334, χ2=12.129, P=0.000)were associated with hypertension.Total CSVD burden score, PVWMH, DWMH, EPVS, and CMB were correlated with increasing age( P<0.05).LIs was positively correlated with PVWMH( b=0.231, P=0.001), DWMH( b=0.247, P=0.000)and EPVS( b=0.215, P=0.001).There was a positive relationship between PVWMH and DWMH( b=0.546, P=0.000)as well as EPVS( b=0.388, P=0.000).DWMH was also positively correlated with EPVS( b=0.357, P=0.000)and CMB( b=0.177, P=0.009). Conclusions:The incidence of asymptomatic CSVD is high in the elderly population.The total CSVD score is a useful measure to evaluate asymptomatic cerebral small vessel disease in the elderly population.Neuroimaging features of asymptomatic CSVD are mainly correlated with age and hypertension.

Cortical degeneration detected by neurite orientation dispersion and density imaging in chronic lacunar infarcts.

BACKGROUND: Although lacunar infarcts are focal lesions, they may also have more widespread effects. A reduction in cortical thickness in the remote cortex after lacunar infarcts has been detected by structural imaging; however, its underlying microstructural changes are yet to be elucidated. This study aimed to investigate the effects of lacunar infarcts on the microstructural abnormalities associated with cortical thickness reduction in the remote cortex. METHODS: Thirty-seven patients with chronic lacunar infarcts were included. Brain structural magnetic resonance images (MRIs) and diffusion tensor images were acquired. We constructed the white matter tracts connecting with the lacunar infarcts and identified the connected cortical area based on a standard brain atlas warped into the subject space. Cortical thickness and microstructural neurite orientation dispersion and density imaging (NODDI) metrics of the ipsilesional and contralesional cortices were compared, and correlations between cortical thickness and NODDI metrics were also investigated. RESULTS: We found decreased cortical thickness and reduced neurite orientation dispersion index (ODI) in the ipsilesional cortex (2.47 vs. 2.50 mm, P=0.008; 0.451 vs. 0.456, P=0.035, respectively). In patients with precentral gyrus involvement (n=23), we found that ODI in the ipsilesional cortex was correlated with cortical thickness (r=0.437, P=0.037), and ODI in the contralesional cortex was also correlated with contralesional cortical thickness (r=0.440, P=0.036). CONCLUSIONS: NODDI metrics could reflect cortical microstructural changes following lacunar infarcts. The correlation between decreased ODI and reduced cortical thickness suggests that dendrites' loss might contribute to lacunar infarct-related cortical atrophy.

Cerebral small vessel disease: A review.

Cerebral small vessel disease (CSVD) is the most common, chronic and progressive vascular disease. The changes affect arterioles, capillaries and small veins supplying the white matter and deep structures of the brain. It is the most common incidental finding on brain scans, especially in people over 80 years of age. Magnetic resonance imaging (MRI) plays a key role in the diagnosis of CSVD. The nomenclature and radiological phenotypes of CSVD were published in 2013 based on the unified position of the so-called Centres of Excellence in Neurodegeneration. The disease is characterized by a diverse clinical and radiological picture. It is primarily responsible for stroke incidents, gait disturbances, depression, cognitive impairment, and dementia in the elderly. The CSVD contributes to about 20% of strokes, including 25% of ischemic strokes and 45% of dementias. Common causes of CSVD include arteriosclerosis, cerebral amyloid angiopathy (CAA), genetic small vessel angiopathy, inflammation and immune-mediated small vessel diseases, and venous collagenosis. There is no causal treatment and management is mainly based on combating known risk factors for cardiovascular disease (CVD).

Individual markers of cerebral small vessel disease and domain-specific quality of life deficits.

BACKGROUND: Cerebral small vessel disease (SVD) leads to reduced quality of life (QOL), but the mechanisms underlying this relationship remain unknown. This study investigated multivariate relationships between radiological markers of SVD and domain-specific QOL deficits, as well as potential mediators, in patients with SVD. METHODS: Clinical and neuroimaging measures were obtained from a pooled sample of 174 SVD patients from the St. George's Cognition and Neuroimaging in Stroke and PRESsure in established cERebral small VEssel disease studies. Lacunes, white matter hyperintensities, and microbleeds were defined as radiological markers of SVD and delineated using MRI. QOL was assessed using the Stroke-Specific Quality of Life Scale. Multivariate linear regression was used to determine whether SVD markers were associated with domain-specific QOL deficits. Significant associations were further investigated using mediation analysis to examine whether functional disability or cognition was potential mediators. RESULTS: Multivariate regression analyses revealed that lacunes were associated with total QOL score (ß = -8.22, p = .02), as well as reductions in mobility (ß = -1.41, p = .008) and language-related subdomains (ß = -0.69, p = .033). White matter hyperintensities and microbleeds showed univariate correlations with QOL, but these became nonsignificant during multivariate analyses. Mediation analyses revealed that functional disability, defined as reduced activities of daily living, and executive function, partially mediated the relationship between lacunes and total QOL, as well as mobility-related QOL, but not language-related QOL. CONCLUSIONS: Lacunar infarcts have the most detrimental effect on QOL in SVD patients, particularly in the mobility and language-related subdomains. These effects may be partially explained by a reduction in activities of daily living. These results may inform targeted interventions to improve QOL in patients with SVD.

A Review of Translational Magnetic Resonance Imaging in Human and Rodent Experimental Models of Small Vessel Disease.

Cerebral small vessel disease (SVD) is a major health burden, yet the pathophysiology remains poorly understood with no effective treatment. Since much of SVD develops silently and insidiously, non-invasive neuroimaging such as MRI is fundamental to detecting and understanding SVD in humans. Several relevant SVD rodent models are established for which MRI can monitor in vivo changes over time prior to histological examination. Here, we critically review the MRI methods pertaining to salient rodent models and evaluate synergies with human SVD MRI methods. We found few relevant publications, but argue there is considerable scope for greater use of MRI in rodent models, and opportunities for harmonisation of the rodent-human methods to increase the translational potential of models to understand SVD in humans. We summarise current MR techniques used in SVD research, provide recommendations and examples and highlight practicalities for use of MRI SVD imaging protocols in pre-selected, relevant rodent models.

Effects of hyperhomocysteinemia on ischemic cerebral small vessel disease and analysis of inflammatory mechanisms.

Purpose: Hyperhomocysteinemia is closely related to, but is not a confirmed risk factor of, cerebral small vessel disease (CSVD). This study aimed to determine whether hyperhomo-cysteinemia is correlated significantly with CSVD.Materials and methods: This cross-sectional study compared the homocysteine (Hcy) levels of patients with and without CSVD. High-sensitivity C-reactive protein (hs-CRP) levels were compared according to white matter lesion (WML) severity, which was classified using the Fazekas system. Risk factors for ischemic CSVD were analyzed through multivariate unconditional logistic regression analysis.Results: Hcy levels were significantly higher in patients with lacunar infarction (LI) than in controls (p=.0438), in patients with Fazekas 2-3 than in patients with Fazekas 0-1 WMLs (p=.0192), in patients with Fazekas 4-6 than in patients with Fazekas 2-3 WMLs (p=.0207), and in patients with LI than in patients without LI (p=.0043). hs-CRP levels were significantly higher in patients with LI than in patients without LI (p=.0068) and in patients with Fazekas 4-6 than in patients with Fazekas 0-1 WMLs (p=.0031). Three multivariate unconditional logistic regression analyses showed that hyperhomocysteinemia is a risk factor for LI (p=.006; odds ratio [OR], 27.668), severe WML (p=.028; OR, 1.984), and high hs-CRP level (p=.016; OR, 3.956).Conclusions: The assessment of Hcy levels is important for ischemic CSVD. Hyperhomocysteinemia is a risk factor for LI and severe WML. Further, hyperhomocysteinemia is associated with high hs-CRP levels, and this may involve an inflammatory mechanism; however, further studies are needed in this regard.

Lack of Association between Periodic Limb Movements during Sleep and Neuroimaging Signatures of Cerebral Small Vessel Disease in Stroke-Free Community-Dwelling Older Adults. The Atahualpa Project.

BACKGROUND: Evidence of the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease (cSVD) is limited and inconsistent. Here, we aimed to assess the independent association between PLMS and the different neuroimaging signatures of cSVD. METHODS: Atahualpa residents aged more than or equal to 60 years enrolled in the Atahualpa Project undergoing polysomnography and MRI with time intervals less than or equal to 6 months were included. MRI readings focused on white matter hyperintensities (WMH) of presumed vascular origin, deep cerebral microbleeds (CMB), silent lacunar infarcts (LI), and more than 10 enlarged basal ganglia-perivascular spaces (BG-PVS). Data from single-night polysomnograms were interpreted according to recommendations of the American Academy of Sleep Medicine. Associations between the PLMS index and neuroimaging signatures of cSVD (as dependent variables) were assessed by means of logistic regression models, adjusted for relevant confounders. RESULTS: A total of 146 individuals (mean age: 71.4 ± 7.5 years; 64% women) were included. A PLMS index more than or equal to 15 per hour were noted in 48 (33%) participants. Moderate-to-severe WMH were present in 33 individuals (23%), deep CMB in 9 (6%), silent LI in 16 (11%), and more than 10 BG-PVS in 44 (30%). In univariate analyses, silent LI (P = .035) and the presence of more than 10 enlarged BG-PVS (P = .034) were significantly higher among participants with a PLMS index more than or equal to 15 per hour. However, fully-adjusted multivariate models showed no significant association between PLMS index more than or equal to 15 per hour and any of the neuroimaging signatures of cSVD. CONCLUSIONS: This study shows no independent association between the PLMS index and neuroimaging signatures of cSVD in stroke-free community-dwelling older adults.

A Case of Leukoencephalopathy and Small Vessels Disease Caused by a Novel HTRA1 Homozygous Mutation.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a heritable, rare small vessel disease, which is caused by HTRA1 mutations and mostly reported Japanese and Chinese population. CARASIL is an orphan disease, which presents with progressive motor and cognitive impairment, alopecia, and spondylosis. The disease typically starts with lumbago at early twenties. Ischemic strokes start at mid-twenties. Patients have no cardiovascular or any other risk factors. Multiple lacunar infarcts and leukoencephalopathy cause progressive neurologic involvement. Leukoencephalopathy and small vessel disease without any risk factors is a significant finding for the differential diagnosis of HTRA1 gene pathology. This report presents clinical and genetic features of a rare case of typical CARASIL from Turkey who was followed with uncertain diagnoses for years.

7T TOF-MRA shows modulated orifices of lenticulostriate arteries associated with atherosclerotic plaques in patients with lacunar infarcts.

PURPOSE: To characterize the orifices of lenticulostriate arteries (LSAs) in vivo by using three-dimensional (3D) time-of-flight magnetic resonance angiography (TOF-MRA) and to investigate the spatial relationship between LSA orifices and atherosclerotic plaques in patients with lacunar infarcts (LI). METHOD: Seventeen healthy volunteers and fifteen patients with LI underwent 3D TOF-MRA and 3D vessel wall imaging (VWI) at 7 T. The orifices of LSAs and the locations of atherosclerotic plaques on MCA walls were categorized based on the involvement of the superior, inferior, ventral or dorsal sides of MCA wall. The distribution quadrants of LSA orifices on MCA walls were compared among different groups. RESULTS: Most orifices were located on the superior side of MCA firstly (46 of 95, 48.4%), followed by the dorsal side (22 of 95, 23.2%). In patients with LI, the visible numbers of ventral and inferior orifices on the ipsilateral side were significantly lower than healthy controls (p = 0.039 for ventral side, p = 0.002 for inferior side). Similarly, plaques occurred more frequently at the ventral (7 of 20, 35.0%) and the inferior (7 of 20, 35.0%) sides of MCA walls. CONCLUSIONS: TOF-MRA at 7 T is capable of imaging orifices of LSA on MCA. In patients with LI, the decreased number of LSA orifices on the ventral and inferior sides corresponded with the distribution of MCA plaques. The results may indicate the vulnerability of LSA orifices in intracranial atherosclerosis, which was supposed to be the cause of LI in basal ganglia.

Leukoaraiosis is an independent predictor of intracranial hemorrhage in patients with atrial fibrillation.

We evaluated the predictive value of several clinical, radiological and laboratory parameters on the risk of predict intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF). We conducted a case-control study on a consecutive hospital based series of patients with AF and ICH. A random sample of subjects with AF without ischemic or hemorrhagic stroke was selected from the same hospital in the same period to perform as the control group, with a ratio of two controls per case. All patients underwent the same evaluation protocol. Patients without neuroimaging exams were excluded. During the study period we identified 37 subjects with AF and ICH. 74 subjects without stroke events were randomly chosen among subjects with AF. Among cases 56.8% were female; mean age was 83.1 years. Patients with ICH were more often on anticoagulant therapy (75.7%), compared with controls (45.9%; p = 0.0002). On CT scans, cases had a greater severity of leukoaraiosis at the Blennow scale (p < 0.0001) and a higher frequency of lacunar infarcts (p = 0.006). No significant association was found between MRI parameters or the HAS-BLED score and the occurrence of ICH. CT scan is more useful than MRI and HAS-BLED score to predict ICH in patients with AF on antithrombotic therapy.

Cerebral perfusion and compensatory blood supply in patients with recent small subcortical infarcts.

Hypoperfusion is the typical perfusion pattern associated with recent small subcortical infarcts of the brain, but other perfusion patterns may be present in patients with these infarcts. Using CT perfusion, we studied 67 consecutive patients who had a small subcortical infarct at a follow-up MRI study to investigate the correlation between the perfusion pattern and the clinical and radiological course. On CT perfusion map analysis, 51 patients (76%) had focal hypoperfusion, 4 patients (6%) had hyperperfusion and the remaining 12 patients (18%) showed no abnormalities. On dynamic sequential imaging analysis obtained from the source perfusion images, 32 patients (48%) had a sustained hypoperfusion pattern, 11 patients (16%) had a reperfusion pattern, and 18 patients (27%) had a delayed compensation pattern. Systolic blood pressure was higher in patients with sustained hypoperfusion although the perfusion pattern was independent of the final volume of infarction. These results reinforce the notion that mechanisms other than hypoperfusion are at play in patients with small subcortical infarcts including the intervention of compensatory sources of blood flow. The ultimate clinical significance of these perfusion patterns remains to be determined in larger series of patients assessed longitudinally.

Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke.

Nitrones (e.g. α-phenyl-N-tert-butyl nitrone; PBN) are cerebroprotective in experimental stroke. Free radical trapping is their proposed mechanism. As PBN has low radical trapping potency, we tested Sgk1 induction as another possible mechanism. PBN was injected (100 mg/kg, i.p.) into adult male rats and mice. Sgk1 was quantified in cerebral tissue by microarray, quantitative RT-PCR and western analyses. Sgk1+/+ and Sgk1-/- mice were randomized to receive PBN or saline immediately following transient (60 min) occlusion of the middle cerebral artery. Neurological deficit was measured at 24 h and 48 h and infarct volume at 48 h post-occlusion. Following systemic PBN administration, rapid induction of Sgk1 was detected by microarray (at 4 h) and confirmed by RT-PCR and phosphorylation of the Sgk1-specific substrate NDRG1 (at 6 h). PBN-treated Sgk1+/+ mice had lower neurological deficit ( p < 0.01) and infarct volume ( p < 0.01) than saline-treated Sgk1+/+ mice. PBN-treated Sgk1-/- mice did not differ from saline-treated Sgk1-/- mice. Saline-treated Sgk1-/- and Sgk1+/+ mice did not differ. Brain Sgk3:Sgk1 mRNA ratio was 1.0:10.6 in Sgk1+/+ mice. Sgk3 was not augmented in Sgk1-/- mice. We conclude that acute systemic treatment with PBN induces Sgk1 in brain tissue. Sgk1 may play a part in PBN-dependent actions in acute brain ischemia.

Association Between the Serum Uric Acid Levels and Lacunar Infarcts in the Elderly.

Increasing evidence suggests that uric acid (UA) is a relevant risk factor for arteriolosclerosis and recent studies have demonstrated the positive relationship between UA concentrations and the severity of leukoaraiosis. However, the association between lacunar infarcts (LI) and UA levels has seldom been reported in the literature. The aim of our study was to assess whether serum UA levels may be related to the presence of LI. We recruited 242 patients (113 males and 129 females, aged 82.83 ± 6.49 years) from our Geriatric Department for whom CAT scans (CT) were available. Clinical and laboratory data was collected. Patients CT images were examined to identify the presence, the size, the number, and the location of LI. LI without neurological symptoms were considered silent LI. Serum UA levels were found to be positively associated with the presence (p = 0.0001), the number (p = 0.001), the size (p = 0.001), and the location of LI in the basal ganglia (p = 0.0038), the deep white matter (DWM) (p < 0.0001), and the pons (p = 0.0156). A significant association was also found between UA and silent LI (p = 0.0002). The prevalence of LI increased starting from UA levels of 5.7 mg/dl. Stepwise multiple regression analysis confirmed that UA was independently related with the presence, the number, the size, LI in the basal ganglia, the DWM, the pons, and with silent LI. Our study suggests a positive association between UA levels and LI, which is independent of traditional cardiovascular risk factors. This data suggests that UA plays an influential role on the physiopathology of LI and could represent a potential target to prevent cerebral microinfarcts.