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Neurology Oct 2021To determine the rate and predictors of early neurologic deterioration (END) in patients with lacunar strokes and its implications for management and outcome.
BACKGROUND AND OBJECTIVES
To determine the rate and predictors of early neurologic deterioration (END) in patients with lacunar strokes and its implications for management and outcome.
METHODS
We enrolled consecutive patients with MRI-defined lacunar stroke who presented within 12 hours after symptom onset from a prospective stroke database (2015-2019). END was defined as any persisting increase in NIH Stroke Scale (NIHSS) score of ≥2 points within 24 hours after admission and favorable outcome as modified Rankin Scale (mRS) score of 0 to 2 at 90 days. We assessed the association of END with clinical and imaging variables, acute treatment, and outcome using multivariable regression, calculating adjusted odds ratios (aORs).
RESULTS
Sixty-one of 365 (16.7%) patients with acute lacunar stroke (median age 71.8 years, 39.5% female, median NIHSS score on admission 3) had END. Lower NIHSS score on admission (per point, aOR 0.81, = 0.006), capsular warning syndrome (aOR 7.00, < 0.001), ventral pontine infarct (aOR 3.49, = 0.008), and hypoperfusion lesion on imaging (aOR 2.13, = 0.026) were associated with END. Acute dual antiplatelet therapy was associated with reduced risk of END (aOR 0.10, = 0.04). Patients with END had less favorable outcome at 90 days (aOR 0.13 < 0.001), but IV thrombolysis (IVT) was associated with favorable outcome at 90 days (aOR 3.95, = 0.002).
DISCUSSION
One in 6 patients with lacunar stroke has END, and patients at high risk of END can be identified with radiologic and clinical variables. Targeted therapeutic trials for this population seem justified.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that early neurologic deterioration in patients with acute lacunar stroke predicts poorer functional outcome at 90 days as determined by the mRS.
PubMed: 34400585
DOI: 10.1212/WNL.0000000000012661 -
Current Opinion in Neurobiology Feb 2022Small vessel disease (SVD) is a common instigator of dementia in the aging population. The hallmarks of SVD are enlargement of the perivascular spaces and white matter... (Review)
Review
Small vessel disease (SVD) is a common instigator of dementia in the aging population. The hallmarks of SVD are enlargement of the perivascular spaces and white matter hyperintensities. The latter represents local fluid accumulation in white matter that either subsides or develops into lacunar infarcts. We here propose that failure of brain fluid transport-via the glymphatic system-plays a key role in initiation and progression of SVD. Our major case for this concept is that perivascular spaces are utilized as waterways for influx of cerebrospinal fluid. Stagnation of glymphatic transport may drive loss of brain fluid homeostasis leading to transient white matter edema, perivascular dilation, and ultimately demyelination. This review will discuss how glymphatic rodent studies of hypertension and diabetes have provided new insight into the pathogenesis of SVD.
Topics: Aged; Brain; Cerebral Small Vessel Diseases; Humans; Magnetic Resonance Imaging; Stroke, Lacunar; White Matter
PubMed: 34407477
DOI: 10.1016/j.conb.2021.07.006 -
Cerebrovascular Diseases (Basel,... 2022Cerebral small-vessel diseases (cSVDs) encompass a number of causes involving, but not limited to, alterations in the intracranial microvasculature, leading to the... (Review)
Review
BACKGROUND
Cerebral small-vessel diseases (cSVDs) encompass a number of causes involving, but not limited to, alterations in the intracranial microvasculature, leading to the accumulation of brain tissue damage and the development of various degrees of cognitive impairment, behavioral alterations, gait instability, and localization signs, often associated with the occurrence of ischemic or hemorrhagic strokes.
SUMMARY
In 2021, although key questions remain unanswered, there is general agreement on the construct, its main pathophysiological bases, and the terms used to describe its main clinical and radiological features. However, this has not always been the case, and the 30th anniversary of Cerebrovascular Diseases is an opportunity to look back from 1991 to the present to understand how a number of features, sometimes considered independent, have been progressively brought together by successive scientific breakthroughs, gradually leading to the definition of the now widely accepted concept of cSVDs.
KEY MESSAGES
In the course of this journey, we will detail with particular attention the role of what we consider 2 crucial events: the advent of cerebral MRI and the building of large cohorts with monogenic forms of small-vessel disease of the brain.
Topics: Brain; Cerebral Small Vessel Diseases; Cognitive Dysfunction; Humans; Magnetic Resonance Imaging
PubMed: 35189622
DOI: 10.1159/000522213 -
International Journal of Stroke :... Jan 2023Small vessel disease (SVD) is associated with vascular cognitive impairment (VCI) but why VCI occurs in some, but not other patients, is uncertain. We determined the...
BACKGROUND
Small vessel disease (SVD) is associated with vascular cognitive impairment (VCI) but why VCI occurs in some, but not other patients, is uncertain. We determined the prevalence of, and risk factors for, VCI in a large cohort of patients with lacunar stroke.
METHODS
Participants with magnetic resonance imaging (MRI)-confirmed lacunar stroke were recruited in the multicenter DNA Lacunar 2 study and compared with healthy controls. A logistic regression model was used to determine which vascular risk factors and MRI parameters were independent predictors of VCI, assessed using the Brief Memory and Executive Test (BMET).
RESULTS
A total of 912 lacunar stroke patients and 425 controls were included, with mean () age of 64.6 (12.26) and 64.7 (12.29) years, respectively. VCI was detected in 38.8% lacunar patients and 13.4% controls. In a logistic regression model, diabetes mellitus (odds ratio (OR) = 1.98 (95% confidence interval (CI) = 1.40-2.80), < 0.001) and higher body mass index (BMI) (OR = 1.03 (95% CI = 1.00-1.05), = 0.029) were independently associated with increased risk of VCI, and years of full-time education with lower risk (OR = 0.92 (95% CI = 0.86-0.99), = 0.018). When entering both lacune count and white matter hyperintensity (WMH) in the same logistic regression model, only WMH grade was significantly associated with VCI (OR = 1.46 (95% CI = 1.24-1.72), < 0.001).
CONCLUSION
VCI is common in lacunar stroke patients, affecting almost 40%. This prevalence suggests that it should be routinely screened for in clinical practice. Risk factors for VCI in patients with lacunar stroke include diabetes mellitus, depressive symptoms, higher BMI, and WMH severity, while education is protective.
Topics: Humans; Stroke, Lacunar; Prevalence; Stroke; Risk Factors; Cognitive Dysfunction; Magnetic Resonance Imaging; Diabetes Mellitus
PubMed: 34983273
DOI: 10.1177/17474930211064965 -
Journal of Stroke and Cerebrovascular... Apr 2023Physical inactivity is a major risk factor for stroke. It is a challenge for patients to initiate and adhere to regular exercise post-stroke. Early initiation of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Physical inactivity is a major risk factor for stroke. It is a challenge for patients to initiate and adhere to regular exercise post-stroke. Early initiation of home-based high-intensity interval training (HIIT) may engage patients in physical activity, improve cardiorespiratory fitness, and reduce risk of recurrent stroke.
MATERIALS AND METHODS
Post-intervention follow-up of patients with lacunar stroke, randomized to three-months HIIT including weekly motivational calls, or usual care. At follow-up (six- and 12-months post-stroke), we investigated changes in cardiorespiratory fitness, physical activity, fatigue, depression, mental well-being, stress, cognition, cardiovascular function, and recurrent stroke.
RESULTS
We included 71 patients of whom 59 patients (mean age: 63.9 ± 8.8 years) completed six- and 12-month follow-up. No change was detected in cardiorespiratory fitness between groups from baseline to 12-months follow-up. At six months, vigorous-intensity activity (median hours/week [interquartile range]) was maintained in the intervention group (baseline, 0[0;2]; post-intervention, 2[0;3]; six-month, 2[0;4]) and increased in the usual care group (baseline, 0[0;1]; post-intervention, 1[0;2]; six-month, 1[0;3]), with no difference between groups. Vigorous-intensity activity declined to baseline levels at 12-months in both groups. Secondary outcomes improved from baseline to 12-months with no significant differences between groups. Similar rate of recurrent stroke (n=3) occurred in each group with a three-month delay in the intervention group.
CONCLUSIONS
Early initiated HIIT did not increase long-term cardiorespiratory fitness, but increased time spent doing vigorous-intensity activities post-stroke. Decline to baseline activity level at 12 months warrants identification of motivators to initiate and sustain physical activity post-stroke.
Topics: Humans; Middle Aged; Aged; Exercise Therapy; Stroke, Lacunar; Follow-Up Studies; Exercise; Cardiorespiratory Fitness; Stroke; Cerebral Infarction
PubMed: 36623990
DOI: 10.1016/j.jstrokecerebrovasdis.2022.106973 -
Frontiers in Neurology 2021Lacunar strokes are a common type of ischemic stroke. They are associated with long-term disability, but the factors affecting the dynamic of the infarcted lesion and...
Lacunar strokes are a common type of ischemic stroke. They are associated with long-term disability, but the factors affecting the dynamic of the infarcted lesion and the brain imaging features associated with them, reflective of small vessel disease (SVD) severity, are still largely unknown. We investigated whether the distribution, volume and 1-year evolution of white matter hyperintensities (WMH), one of these SVD features, relate to the extent and location of these infarcts, accounting for vascular risk factors. We used imaging and clinical data from all patients [ = 118, mean age 64.9 (SD 11.75) years old] who presented to a regional hospital with a lacunar stroke syndrome within the years 2010 and 2013 and consented to participate in a study of stroke mechanisms. All patients had a brain MRI scan at presentation, and 88 had another scan 12 months after. Acute lesions (i.e., recent small subcortical infarcts, RSSI) were identified in 79 patients and lacunes in 77. Number of lacunes was associated with baseline WMH volume (B = 0.370, SE = 0.0939, = 0.000174). RSSI volume was not associated with baseline WMH volume (B = 3.250, SE = 2.117, = 0.129), but predicted WMH volume change (B = 2.944, SE = 0.913, = 0.00184). RSSI location was associated with the spatial distribution of WMH and the pattern of 1-year WMH evolution. Patients with the RSSI in the centrum semiovale ( = 33) had significantly higher baseline volumes of WMH, recent and old infarcts, than patients with the RSSI located elsewhere [median 33.69, IQR (14.37 50.87) ml, 0.001 ≤ ≤ 0.044]. But patients with the RSSI in the internal/external capsule/lentiform nucleus experienced higher increase of WMH volume after a year [ = 21, median (IQR) from 18 (11.70 31.54) ml to 27.41 (15.84 40.45) ml]. Voxel-wise analyses of WMH distribution in patients grouped per RSSI location revealed group differences increased in the presence of vascular risk factors, especially hypertension and recent or current smoking habit. In our sample of patients presenting to the clinic with lacunar strokes, lacunar strokes extent influenced WMH volume fate; and RSSI location and WMH spatial distribution and dynamics were intertwined, with differential patterns emerging in the presence of vascular risk factors. These results, if confirmed in wider samples, open potential avenues in stroke rehabilitation to be explored further.
PubMed: 33746892
DOI: 10.3389/fneur.2021.640498 -
Stroke and Vascular Neurology Sep 2016Cerebral small vessel disease (CSVD) is a very common neurological disease in older people. It causes stroke and dementia, mood disturbance and gait problems. Since it... (Review)
Review
Cerebral small vessel disease (CSVD) is a very common neurological disease in older people. It causes stroke and dementia, mood disturbance and gait problems. Since it is difficult to visualise CSVD pathologies in vivo, the diagnosis of CSVD has relied on imaging findings including white matter hyperintensities, lacunar ischaemic stroke, lacunes, microbleeds, visible perivascular spaces and many haemorrhagic strokes. However, variations in the use of definition and terms of these features have probably caused confusion and difficulties in interpreting results of previous studies. A standardised use of terms should be encouraged in CSVD research. These CSVD features have long been regarded as different lesions, but emerging evidence has indicated that they might share some common intrinsic microvascular pathologies and therefore, owing to its diffuse nature, CSVD should be regarded as a 'whole-brain disease'. Single antiplatelet (for acute lacunar ischaemic stroke) and management of traditional risk factors still remain the most important therapeutic and preventive approach, due to limited understanding of pathophysiology in CSVD. Increasing evidence suggests that new studies should consider drugs that target endothelium and blood-brain barrier to prevent and treat CSVD. Epidemiology of CSVD might differ in Asian compared with Western populations (where most results and guidelines about CSVD and stroke originate), but more community-based data and clear stratification of stroke types are required to address this.
Topics: Brain; Cerebral Small Vessel Diseases; Disease Progression; Humans; Leukoencephalopathies; Prognosis; Risk Assessment; Risk Factors; Stroke, Lacunar; Terminology as Topic
PubMed: 28959468
DOI: 10.1136/svn-2016-000035 -
Stroke Dec 2022Cerebral small vessel disease (SVD) is common in older people and causes lacunar stroke and vascular cognitive impairment. Risk factors include old age, hypertension and...
BACKGROUND
Cerebral small vessel disease (SVD) is common in older people and causes lacunar stroke and vascular cognitive impairment. Risk factors include old age, hypertension and variants in the genes encoding collagen alpha-1(IV) and alpha-2(IV), here termed collagen-IV, which are core components of the basement membrane. We tested the hypothesis that increased vascular collagen-IV associates with clinical hypertension and with SVD in older persons and with chronic hypertension in young and aged primates and genetically hypertensive rats.
METHODS
We quantified vascular collagen-IV immunolabeling in small arteries in a cohort of older persons with minimal Alzheimer pathology (N=52; 21F/31M, age 82.8±6.95 years). We also studied archive tissue from young (age range 6.2-8.3 years) and older (17.0-22.7 years) primates () and compared chronically hypertensive animals (18 months aortic stenosis) with normotensives. We also compared genetically hypertensive and normotensive rats (aged 10-12 months).
RESULTS
Collagen-IV immunolabeling in cerebral small arteries of older persons was negatively associated with radiological SVD severity (ρ: -0.427, =0.005) but was not related to history of hypertension. General linear models confirmed the negative association of lower collagen-IV with radiological SVD (<0.017), including age as a covariate and either clinical hypertension (<0.030) or neuropathological SVD diagnosis (<0.022) as fixed factors. Reduced vascular collagen-IV was accompanied by accumulation of fibrillar collagens (types I and III) as indicated by immunogold electron microscopy. In young and aged primates, brain collagen-IV was elevated in older normotensive relative to young normotensive animals (=0.029) but was not associated with hypertension. Genetically hypertensive rats did not differ from normotensive rats in terms of arterial collagen-IV.
CONCLUSIONS
Our cross-species data provide novel insight into sporadic SVD pathogenesis, supporting insufficient (rather than excessive) arterial collagen-IV in SVD, accompanied by matrix remodeling with elevated fibrillar collagen deposition. They also indicate that hypertension, a major risk factor for SVD, does not act by causing accumulation of brain vascular collagen-IV.
Topics: Animals; Rats; Cerebral Small Vessel Diseases; Stroke, Lacunar; Hypertension; Brain; Blood Pressure; Collagen Type IV
PubMed: 36205142
DOI: 10.1161/STROKEAHA.122.037761 -
Journal of Neurology, Neurosurgery, and... May 2005
Topics: Brain; Brain Infarction; Brain Ischemia; Cerebral Arteries; Cerebrovascular Circulation; Corpus Striatum; Diagnosis, Differential; Endothelium, Vascular; Fibrin; Humans; Hypertension; Magnetic Resonance Imaging; Necrosis; Vasospasm, Intracranial
PubMed: 15834013
DOI: 10.1136/jnnp.2004.039982 -
Current Opinion in Neurology Feb 2020Diagnosis of stroke and understanding the mechanism of stroke is critical to implement optimal treatment. RNA expressed in peripheral blood cells is emerging as a... (Review)
Review
PURPOSE OF REVIEW
Diagnosis of stroke and understanding the mechanism of stroke is critical to implement optimal treatment. RNA expressed in peripheral blood cells is emerging as a precision biomarker to aid in stroke diagnosis and prediction of stroke cause. In this review, we summarize available data regarding the role of RNA to predict stroke, the rationale for these changes, and a discussion of novel mechanistic insight and clinical applications.
RECENT FINDINGS
Differences in RNA gene expression in blood have been identified in patients with stroke, including differences to distinguish ischemic from hemorrhagic stroke, and differences between cardioembolic, large vessel atherosclerotic, and small vessel lacunar stroke cause. Gene expression differences show promise as novel stroke biomarkers to predict stroke of unclear cause (cryptogenic stroke). The differences in RNA expression provide novel insight to stroke mechanism, including the role of immune response and thrombosis in human stroke. Important insight to regulation of gene expression in stroke and its causes are being acquired, including alternative splicing, noncoding RNA, and microRNA.
SUMMARY
Improved diagnosis of stroke and determination of stroke cause will improve stroke treatment and prevention. RNA biomarkers show promise to aid in the diagnosis of stroke and cause determination, as well as providing novel insight to mechanism of stroke in patients. While further study is required, an RNA profile may one day be part of the stroke armamentarium with utility to guide acute stroke therapy and prevention strategies and refine stroke phenotype.
Topics: Biomarkers; Gene Expression; Humans; MicroRNAs; Stroke
PubMed: 31809333
DOI: 10.1097/WCO.0000000000000786