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Diagnostics (Basel, Switzerland) Apr 2023The main theory underlying the use of perfusion imaging in acute ischemic stroke is the presence of a hypoperfused volume of the brain downstream of an occluded artery.... (Review)
Review
BACKGROUND
The main theory underlying the use of perfusion imaging in acute ischemic stroke is the presence of a hypoperfused volume of the brain downstream of an occluded artery. Indeed, the main purpose of perfusion imaging is to select patients for endovascular treatment. Computed Tomography Perfusion (CTP) is the more used technique because of its wide availability but lacunar infarcts are theoretically outside the purpose of CTP, and limited data are available about CTP performance in acute stroke patients with lacunar stroke.
METHODS
We performed a systematic review searching in PubMed and EMBASE for CTP and lacunar stroke with a final selection of 14 papers, which were examined for data extraction and, in particular, CTP technical issues and sensitivity, specificity, PPV, and NPV values.
RESULTS
A global cohort of 583 patients with lacunar stroke was identified, with a mean age ranging from 59.8 to 72 years and a female percentage ranging from 32 to 53.1%.CTP was performed with different technologies (16 to 320 rows), different post-processing software, and different maps. Sensitivity ranges from 0 to 62.5%, and specificity from 20 to 100%.
CONCLUSIONS
CTP does not allow to reasonable exclude lacunar infarct if no perfusion deficit is found, but the pathophysiology of lacunar infarct is more complex than previously thought.
PubMed: 37174955
DOI: 10.3390/diagnostics13091564 -
Cureus Dec 2020Stroke is a leading cause of death, disability, and dementia worldwide. Strokes can be divided into ischemic strokes and hemorrhagic strokes. At the moment, tissue... (Review)
Review
Stroke is a leading cause of death, disability, and dementia worldwide. Strokes can be divided into ischemic strokes and hemorrhagic strokes. At the moment, tissue plasminogen activator (tPA) is the only FDA-approved drug for ischemic stroke. Minocycline (MC) and Magnesium (Mg) are promising therapies for ischemic stroke, especially in the pre-hospital setting. These drugs are readily available, inexpensive, and generally safe. We decided to investigate these drugs' neuroprotective effects in treating ischemic stroke in the acute and chronic setting. We conducted a systematic review of the published literature on MC and Mg's functional outcome in ischemic stroke. This paper's methodology included only clinical trials published in the last 15 years, using PubMed as a database. The systematic review demonstrated that MC infusion in the pre-hospital and hospital setting improved functional outcomes and disability scores. Furthermore, MC also decreased matrix metalloproteinase 9 (MMP-9) levels. MC might have a more significant effect on men than women because different molecular pathways of cerebral ischemia seem to be involved between both genders. The systematic review showed that patients with ischemic stroke did not benefit from magnesium sulfate infusion in the pre-hospital and hospital setting. Nevertheless, patients with lacunar strokes and patients who supplemented their meals with potassium-magnesium salt in the diet had better functional outcomes. Future studies would need a more significant sample of participants and a better selection to increase the study's power and avoid selection bias, respectively. Further publications could benefit from subcategorizing strokes and investigating the gender role in stroke treatment. These directives could give a more robust conclusion regarding the neuroprotective effects of these drugs.
PubMed: 33520535
DOI: 10.7759/cureus.12339 -
Journal of Neurology, Neurosurgery, and... Aug 2013Cognitive impairment and dementia are common after stroke. It is unclear if risk differs between ischaemic stroke subtypes. Lacunar strokes might be less likely to... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Cognitive impairment and dementia are common after stroke. It is unclear if risk differs between ischaemic stroke subtypes. Lacunar strokes might be less likely to affect cognition than more severe, larger cortical strokes, except that lacunar strokes are associated with cerebral small vessel disease (SVD), which is the commonest vascular cause of dementia.
METHODS
We searched MEDLINE and PsychINFO for studies of mild cognitive impairment (MCI) or dementia after lacunar or cortical ischaemic stroke. We calculated the OR for cognitive impairment/dementia in lacunar versus non-lacunar stroke, and their incidence and prevalence in lacunar stroke as a pooled proportion.
FINDINGS
We identified 24 relevant studies of 7575 patients, including 2860 with lacunar stroke; 24% had MCI or dementia post stroke. Similar proportions of patients with lacunar and non-lacunar stroke (16 studies, n=6478) had MCI or dementia up to 4 years after stroke (OR 0.72 (95% CI 0.43 to 1.20)). The prevalence of dementia after lacunar stroke (six studies, n=1421) was 20% (95% CI 9 to 33) and the incidence of MCI or dementia (four studies, n=275) was 37% (95% CI 23 to 53). Data were limited by short follow-up, subtype classification methods and confounding.
INTERPRETATION
Cognitive impairment appears to be common after lacunar strokes despite their small size, suggesting that associated SVD may increase their impact. New prospective studies are required with accurate stroke subtyping to assess long term outcomes while accounting for confounders.
Topics: Cerebral Small Vessel Diseases; Cognition Disorders; Cognitive Dysfunction; Data Interpretation, Statistical; Dementia; Humans; Incidence; Intelligence; Intelligence Tests; Neuropsychological Tests; Odds Ratio; Prevalence; Stroke; Stroke, Lacunar; Tomography, X-Ray Computed
PubMed: 23457225
DOI: 10.1136/jnnp-2012-303645 -
Cerebrovascular Diseases (Basel,... 2014The cause of cerebral small vessel disease is not fully understood, yet it is important, accounting for about 25% of all strokes. It also increases the risk of having... (Meta-Analysis)
Meta-Analysis Review
Blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-lacunar stroke and non-stroke: systematic review and meta-analysis.
BACKGROUND
The cause of cerebral small vessel disease is not fully understood, yet it is important, accounting for about 25% of all strokes. It also increases the risk of having another stroke and contributes to about 40% of dementias. Various processes have been implicated, including microatheroma, endothelial dysfunction and inflammation. A previous review investigated endothelial dysfunction in lacunar stroke versus mostly non-stroke controls while another looked at markers of inflammation and endothelial damage in ischaemic stroke in general. We have focused on blood markers between clinically evident lacunar stroke and other subtypes of ischaemic stroke, thereby controlling for stroke in general.
SUMMARY
We systematically assessed the literature for studies comparing blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-stroke controls or other ischaemic stroke subtypes. We assessed the quality of included papers and meta-analysed results. We split the analysis on time of blood draw in relation to the stroke. We identified 1,468 full papers of which 42 were eligible for inclusion, including 4,816 ischaemic strokes, of which 2,196 were lacunar and 2,500 non-stroke controls. Most studies subtyped stroke using TOAST. The definition of lacunar stroke varied between studies. Markers of coagulation/fibrinolysis (tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), fibrinogen, D-dimer) were higher in lacunar stroke versus non-stroke although fibrinogen was no different to non-stroke in the acute phase. tPA and PAI were no different between lacunar and non-lacunar stroke. Fibrinogen and D-dimer were significantly lower in lacunar stroke compared to other ischaemic strokes, both acutely and chronically. Markers of endothelial dysfunction (homocysteine, von Willebrand Factor (vWF), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM), vascular cellular adhesion molecule-1 (VCAM)) were higher or had insufficient or conflicting data (P-selectin, VCAM) in lacunar stroke versus non-stroke. Compared to other ischaemic stroke subtypes, homocysteine did not differ in lacunar stroke while vWF was significantly lower in lacunar stroke acutely [atherothrombotic standardized mean difference, SMD, -0.34 (-0.61, -0.08); cardioembolic SMD -0.38 (-0.62, -0.14)], with insufficient data chronically. Markers of inflammation (C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)) were higher in lacunar stroke versus non-stroke, although there were no studies measuring TNF-α chronically and the sole study measuring IL-6 chronically showed no difference between lacunar stroke and non-stroke. Compared to other ischaemic stroke subtypes, there was no difference (CRP) or insufficient or conflicting data (TNF-α) to lacunar stroke. IL-6 was significantly lower [atherothrombotic SMD -0.37 (-0.63, -0.10); cardioembolic SMD -0.52 (-0.82, -0.22)] in lacunar stroke acutely, with insufficient data chronically.
KEY MESSAGES
Lacunar stroke is an important stroke subtype. More studies comparing lacunar stroke to non-lacunar stroke specifically, rather than to non-stroke controls, are needed. Prospective studies with measurements taken well after the acute event are more likely to be helpful in determining pathogenesis. The available data in this review were limited and do not exclude the possibility that peripheral inflammatory processes including endothelial dysfunction are associated with lacunar stroke and cerebral small vessel disease.
Topics: Biomarkers; Blood Coagulation; Blood Proteins; Brain Ischemia; Cell Adhesion Molecules; Cytokines; Endothelium, Vascular; Fibrinolysis; Homocysteine; Humans; Inflammation; Stroke; Stroke, Lacunar
PubMed: 24401164
DOI: 10.1159/000356789 -
Cerebrovascular Diseases (Basel,... 2009Endothelial dysfunction is thought to play an important role in the pathogenesis and progression of cerebral small-vessel disease in lacunar stroke patients. (Review)
Review
BACKGROUND
Endothelial dysfunction is thought to play an important role in the pathogenesis and progression of cerebral small-vessel disease in lacunar stroke patients.
METHODS
We systematically searched the literature (MEDLINE, EMBASE) for evidence of endothelial activation and dysfunction in lacunar stroke. The selected papers were assessed by a predefined checklist to estimate methodological and informative quality. The papers were categorized into subheadings concerning the different physiologic functions of the endothelium and a subheading concerning toxins for the endothelium.
RESULTS
29 articles were eligible for further analysis. We found 16 publications on regulation of vascular tone by the endothelium, which showed an impaired function at several time points after the stroke by means of different clinical methods (e.g. flow-mediated vasodilatation and CO2 reactivity). Nine references showed elevated levels of markers of hemostatic function of the vascular endothelium (e.g. von Willebrand factor, thrombomodulin) in acute and subsequent phases. In 4 papers, adhesion molecules (e.g. E- and P-selectin) were elevated only during the acute phase. Homocysteine, a toxin for the endothelium, was elevated in patients in 3 papers.
CONCLUSIONS
The current literature suggests that endothelial dysfunction might be involved in the pathogenesis of lacunar stroke, especially in those patients with concomitant silent lacunar infarcts and ischemic white matter lesions. Future research on endothelial function in lacunar stroke should concentrate on long-term clinical as well as radiological follow-up in well-defined cases and combine multiple methods to evaluate endothelial function.
Topics: Brain Infarction; Endothelium, Vascular; Hemostasis; Homocysteine; Humans; Stroke; Vasodilation
PubMed: 19372654
DOI: 10.1159/000212672 -
Cerebrovascular Diseases (Basel,... 2015The small vessel disease (SVD) that appears in the brain may be part of a multisystem disorder affecting other vascular beds such as the kidney and retina. Because renal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The small vessel disease (SVD) that appears in the brain may be part of a multisystem disorder affecting other vascular beds such as the kidney and retina. Because renal failure is associated with both stroke and white matter hyperintensities we hypothesised that small vessel (lacunar) stroke would be more strongly associated with renal failure than cortical stroke. Therefore, we performed a systematic review and meta-analysis to establish first if lacunar stroke was associated with the renal function, and second, if cerebral small vessel disease seen on the MRI of patients without stroke was more common in patients with renal failure.
METHODS
We searched Medline and EMBASE for studies in adults with cerebral SVD (lacunar stroke or white matter hyper intensities (WMH) on Magnetic Resonance Imaging (MRI)), in which renal function was assessed (estimated glomerular filtration rate (eGFR) or proteinuria). We extracted data on SVD diagnosis, renal function, demographics and comorbidities. We performed two meta-analyses: first, we calculated the odds of renal impairment in lacunar (small vessel) ischaemic stroke compared to other ischaemic stroke subtypes (non-small vessel disease); and second, we calculated the odds of renal impairment in non-stroke individuals with WMH on MRI compared to individuals without WMH. We then performed a sensitivity analysis by excluding studies with certain characteristics and repeating the meta-analysis calculation.
RESULTS
After screening 11,001 potentially suitable titles, we included 37 papers reporting 32 studies of 20,379 subjects: 15 of stroke patients and 17 of SVD features in non-stroke patients. To diagnose lacunar stroke, 13/15 of the studies used risk factor-based classification (none used diffusion-weighted MRI). 394/1,119 (35%) of patients with lacunar stroke had renal impairment compared with 1,443/4,217 (34%) of patients with non-lacunar stroke, OR 0.88, (95% CI 0.6-1.30). In individuals without stroke the presence of SVD was associated with an increased risk of renal impairment (whether proteinuria or reduced eGFR) OR 2.33 (95% CI 1.80-3.01), when compared to those without SVD. After adjustment for age and hypertension, 15/21 studies still reported a significant association between renal impairment and SVD.
CONCLUSION
We found no specific association between renal impairment and lacunar stroke, but we did find that in individuals who had not had a stroke, having more SVD features on imaging was associated with a worse renal function, which remained significant after controlling for hypertension. However, this finding does not exclude a powerful co-associate effect of age or vascular risk factor exposure. Future research should subtype lacunar stroke sensitively and control for major risk factors.
Topics: Cerebral Small Vessel Diseases; Glomerular Filtration Rate; Humans; Magnetic Resonance Imaging; Renal Insufficiency, Chronic; Stroke, Lacunar; White Matter
PubMed: 25547195
DOI: 10.1159/000369777 -
Neurology Jan 2013To quantitatively characterize domain-specific cognition in individuals with symptomatic lacunar stroke in a systematic review. (Review)
Review
OBJECTIVE
To quantitatively characterize domain-specific cognition in individuals with symptomatic lacunar stroke in a systematic review.
METHODS
Systematic searches of MEDLINE and EMBASE were conducted. Inclusion criteria were all articles published prior to December 2011 evaluating domain-specific cognitive status in individuals with a symptomatic lacunar infarct. Data extraction identified cognitive domains with reported impairment and effect size calculations and heterogeneity analyses were completed to assess the magnitude of this impairment for all studies with control group data.
RESULTS
Results of the search yielded 12 cross-sectional and 5 longitudinal studies that met inclusion criteria. Effect size calculations revealed small to medium effect sizes (ES) estimations for impairment after stroke in the domains of executive function (ES -0.44, 95% confidence interval [CI] -0.83, -0.50), memory (ES -0.55, 95% CI -0.96, -0.13), language (ES -0.63, 95% CI -0.92, -0.33), attention (ES -0.37, 95% CI -0.67, -0.07), and visuospatial abilities (ES -0.61, 95% CI -1.03, 0.19), and large effect sizes for global cognition (ES -0.90, 95% CI -1.48, -0.31) and information processing speed (ES -0.93, 95% CI -1.63, -0.23). Heterogeneity analyses revealed that a subset of these domains were heterogeneous and identified moderating factors accounting for this heterogeneity.
CONCLUSIONS
Results of this systematic review are consistent with previous characterizations of cognitive impairment associated with lacunar strokes. However, impaired cognition in this stroke subtype appears less selective than previously thought, involving all major cognitive domains.
Topics: Aged; Cognition Disorders; Cross-Sectional Studies; Data Interpretation, Statistical; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Stroke, Lacunar; Tomography, X-Ray Computed
PubMed: 23319476
DOI: 10.1212/WNL.0b013e31827deb85 -
Neurology Jul 2013We aimed to systematically assess the evidence for differences in the incidence of stroke and distribution of its subtypes in Chinese compared with white populations. (Review)
Review
OBJECTIVE
We aimed to systematically assess the evidence for differences in the incidence of stroke and distribution of its subtypes in Chinese compared with white populations.
METHODS
We comprehensively sought studies conducted since 1990 in Chinese populations of 1) first-ever stroke incidence (community-based studies only), and 2) pathologic types/subtypes of stroke (hospital- or community-based studies of first-ever or recurrent strokes). We identified community-based studies in white populations from a recent systematic review. For each study, we calculated age-standardized stroke incidence and the proportions of each pathologic type and ischemic subtype, using random-effects meta-analysis to pool proportions of stroke types/subtypes in Chinese and in white populations.
RESULTS
Age-standardized annual first-ever stroke incidence in community-based studies was higher among Chinese than white populations (for ages 45-74 years, range 205-584 vs 170-335 per 100,000, respectively). Intracerebral hemorrhage accounted for a larger, more variable proportion of strokes in China than Taiwan (range 27%-51% vs 17%-28%), in Chinese community-based than hospital-based studies (27%-51% vs 17%-30%), and in community-based Chinese than white studies (pooled proportion 33% vs 12%). Although the overall proportion of lacunar ischemic stroke appeared higher in Chinese than white populations, variable study methodologies precluded reliable comparisons.
CONCLUSIONS
There is good evidence for a slightly higher overall stroke incidence and higher proportion of intracerebral hemorrhage in Chinese vs white populations, but no clear evidence for different distributions of ischemic stroke subtypes. Studies using comparable, population-based case ascertainment and similar classification methods are needed to address this.
Topics: Adult; Aged; Aged, 80 and over; Asian People; Brain Ischemia; Cerebral Hemorrhage; China; Female; Humans; Incidence; Male; Middle Aged; Registries; Risk Factors; Stroke; White People
PubMed: 23858408
DOI: 10.1212/WNL.0b013e31829bfde3 -
Brain Pathology (Zurich, Switzerland) Sep 2012Twenty-five percent of ischemic strokes are lacunar in type, but the cause remains unclear. Pathological descriptions of lacunar lesions are available but have not been... (Review)
Review
Twenty-five percent of ischemic strokes are lacunar in type, but the cause remains unclear. Pathological descriptions of lacunar lesions are available but have not been systematically assessed. We therefore systematically summarized studies describing lacunar lesions by extracting data on the number of patients and lesions, clinical details, pathological methods, brain regions and/or vessels examined, and both parenchymal and vascular findings. Among 39 papers describing >4000 lesions (>50% from one study), 15 papers examined patients with a clinical lacunar syndrome. Terminology varied, many studies only reported macroscopic pathology and many lesions were cavitated (ie, old). Aside from symptomatic lesions occurring more often in the internal capsule or caudate nucleus, we found no other differences between symptomatic and asymptomatic patients. Perivascular edema and thickening, inflammation and disintegration of the arteriolar wall were common, whereas vessel occlusion was rare. The causal mechanisms of lacunar stroke remain poorly defined because of methodological inconsistencies and challenges. Standardised pathological definitions based on well-characterized post-mortem derived material supported by detailed clinical and imaging data are needed.
Topics: Brain Ischemia; Databases, Factual; Humans; Stroke, Lacunar; Terminology as Topic
PubMed: 22329603
DOI: 10.1111/j.1750-3639.2012.00575.x -
European Stroke Journal Dec 2023The pathogenesis of cerebral small vessel disease (cSVD) remains elusive despite evidence of an association between white matter hyperintensities (WMH) and endothelial... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The pathogenesis of cerebral small vessel disease (cSVD) remains elusive despite evidence of an association between white matter hyperintensities (WMH) and endothelial cerebrovascular dysfunction. Neurovascular coupling (NVC) may be a practical alternative measure of endothelial function. We performed a systematic review of reported associations between NVC and cSVD.
METHODS
EMBASE and PubMed were searched for studies reporting an association between any STRIVE-defined marker of cSVD and a measure of NVC during functional magnetic resonance imaging, transcranial Doppler, positron emission tomography, near-infrared spectroscopy or single-photon emission computed tomography, from inception to November 3rd, 2022. Where quantitative data was available from studies using consistent tests and analyses, results were combined by inverse-variance weighted random effects meta-analysis.
FINDINGS
Of 29 studies (19 case-controls; 10 cohorts), 26 reported decreased NVC with increasing severity of cSVD, of which 18 were individually significant. In 28 studies reporting associations with increasing WMH, 25 reported reduced NVC. Other markers of cSVD were associated with reduced NVC in: eight of nine studies with cerebral microbleeds (six showing a significant effect); three of five studies with lacunar stroke; no studies reported an association with enlarged perivascular spaces. Specific SVD diseases were particularly associated with reduced NVC, including six out of seven studies in cerebral amyloid angiopathy and all four studies in CADASIL. In limited meta-analyses, %BOLD occipital change to a visual stimulus was consistently reduced with more severe WMH (seven studies, SMD -1.51, < 0.01) and increasing microbleeds (seven studies, SMD -1.31, < 0.01).
DISCUSSION AND CONCLUSION
In multiple, small studies, neurovascular coupling was reduced in patients with increasing severity of all markers of cSVD in sporadic disease, CAA and CADASIL. Cerebrovascular endothelial dysfunction, manifest as impaired NVC, may be a common marker of physiological dysfunction due to small vessel injury that can be easily measured in large studies and clinical practice.
Topics: Humans; CADASIL; Neurovascular Coupling; Tomography, X-Ray Computed; Cerebral Small Vessel Diseases; Cerebral Hemorrhage
PubMed: 37697725
DOI: 10.1177/23969873231196981