Stroke & Vascular Disorders
Ischemic stroke
Oct. 29, 2024
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Lacunar infarction …
- Updated 09.29.2022
- Released 09.01.1995
- Expires For CME 09.29.2025
Lacunar infarction
Introduction
Overview
In this article, the authors summarize the epidemiology, pathophysiology, clinical manifestations, and management of lacunar infarction. The authors report developments, including clinical MRI correlations and distinct imaging patterns associated with gender, age, vascular risk factors, genetic makeup, race, and ethnicity.
Key points
• A lacune is typically between 3 and 15 mm in size and is observed on imaging as a round or ovoid and fluid-filled cavity consistent with a previous acute subcortical brain infarct or, less commonly, previous hemorrhage. | |
• A lacunar infarct is a common manifestation of cerebral small vessel disease and is usually the end result of the occlusion of a perforating artery. | |
• The clinical stroke subtype associated with lacunar infarction often presents as a classic lacunar syndrome. | |
• Lacunar infarction can be caused by multiple pathological mechanisms, including lipohyalinosis, atherosclerosis, and, rarely, embolic disease. | |
• Lacunes contribute to cerebral small vessel disease burden overall, which can lead to cognitive impairment and functional disability that is often independent of the occurrence of a clinical stroke event. | |
• Acute management of lacunar infarction includes intravenous thrombolytic therapy, and secondary prevention includes risk factor management and antithrombotic therapy. |
Historical note and terminology
In 1838, Deschambre coined the term “lacune” to describe small cavities caused by the resorption of small deep brain infarcts. Durand-Fardel noted that some small cerebral cavities contained a small blood vessel and were not infarcts but enlarged perivascular spaces. He introduced the term état criblé to describe multiple enlarged perivascular spaces. Subsequent authors often called any small hole in the brain a “lacune” and failed to distinguish between lacunar infarcts and enlarged perivascular spaces. In 1901, Pierre Marie made a distinction between lacunar infarcts, état cribilé, and état porose (cerebral porosis), holes in the brain caused by postmortem gas formation. He established the morphological characteristics and the common association of lacunes with isolated hemiplegia (58). He called multiple lacunar infarcts état lacunaire, a term that is now also referred to as the “lacunar state." Marie did not fully understand the pathogenesis of lacunar infarcts and thought that some were due to an inflammatory process, “vaginalite destructive." In 1960, Charles Miller Fisher stressed the major role of arterial hypertension and intracranial atherosclerosis in the pathogenesis of lacunes and redefined lacunes as “small, deep cerebral infarcts” due to occlusion of a single perforating vessel (22; 23). He coined the term “lipohyalinosis” for the segmental arterial pathology that affects small penetrating arteries and causes lacunar infarcts. He also showed that atherosclerosis of the origins of penetrating arteries, “microatheroma,” is a frequent cause of lacunar infarcts.
Clinical manifestations
Presentation and course
Clinically, a lacunar infarct presents abruptly within 3 hours stepwise in one third of stroke patients; gradually over 2 to 3 (up to 6) days in one third; and is preceded by a transient ischemic attack within 24 hours in one third (24). Transient ischemic attacks preceding a lacunar infarct tend to be stereotypic and to occur in the days immediately prior to the stroke. Many lacunar infarcts are clinically silent (or covert), and more than 80% of silent or covert brain infarctions are lacunar infarcts (83).
Because of their small size, lacunar infarcts tend to cause restricted neurologic signs, which have been categorized into “lacunar” syndromes. There are five “classical” lacunar syndromes (See Table 1) and at least 70 other (miscellaneous) clinical lacunar syndromes (See Table 2) (58; 01). A small proportion of lacunar infarctions can present with an atypical lacunar syndrome, most frequently with isolated dysarthria or dysarthria facial paresis (05). Lacunar syndromes can be produced by nonlacunar infarctions (eg, from large artery disease or cardioembolism) or occasionally by nonvascular lesions (eg, secondary to a tumor or multiple sclerosis). In a patient presenting with a lacunar syndrome, one cannot assume the presence of a lacunar infarct, and it is important to establish the underlying pathogenesis by investigation.
Pure motor stroke is the most frequent lacunar syndrome. The hemiparesis may be complete with face, arm, and leg equally involved, or there may be a partial brachiocrural motor deficit, isolated central facial palsy, or isolated monoplegia. Twenty-eight percent of cases with pure motor stroke have an associated dysarthria. Eighty-five percent of pure motor strokes are caused by a lacunar infarct and by other stroke subtypes in 15% of cases. The second most frequent lacunar syndrome is sensorimotor stroke. This can be classified into four types according to the nature and the extent of the sensory loss: (1) all sensory modalities affected, (2) only nociceptive deficits present, (3) only proprioceptive deficits present, and (4) only one limb involved. Each of these types can be qualified into two groups: (A) submaximal motor or sensory deficit and (B) total paralysis or total sensory loss in at least one limb. Pure sensory stroke may involve nociceptive deficits, proprioceptive deficits, or both. The deficit may involve face, arm, and leg (83%) (cheiro-oral-pedal syndrome, 88% of which are caused by a lacunar infarct); face and arm (7%) (cheiro-oral syndrome, 35% caused by lacunar infarct); or arm and leg (8%). Partial pure sensory deficits include an isolated oral sensory loss and restricted acral sensory loss. Fractional anisotropy maps can make a more accurate diagnosis of lacunar infarction subtype. Sensorimotor syndromes are mostly caused by thalamic lacunes (50%), whereas pure motor hemiparesis is caused by lacunar infarctions in the internal capsule and corona radiata (91%) or basal ganglia (83%) (34). The clinical features and pathogenesis of pure midbrain infarctions was described showing isolated anterior internuclear ophthalmoplegia with paramedian area involvement (95). Of 4257 stroke registry patients between January 2000 and December 2015, 25 patients demonstrated pure midbrain infarctions. In those with lacunar stroke involving the paramedian area, 6 of 8 patients had diabetes mellitus, and five of these diabetic patients presented with internuclear ophthalmoplegia, demonstrating that internuclear ophthalmoplegia should be considered as a manifestation of lacunar stroke, especially in the setting of diabetes.
Due to associated cerebral small vessel disease, lacunar infarcts are no less likely to affect cognition than large cortical infarcts. A meta-analysis involving more than 7000 patients with different stroke subtypes comparing the prevalence of dementia and minimal cognitive impairment reported similar rates after lacunar (638/2222 [29%]) and nonlacunar infarcts (1001/4256 [24%]) (46). Cognitive impairment associated with lacunar infarcts is less selective than previously thought, affecting all major cognitive domains: executive function, memory, language, attention, visuospatial abilities, and global cognition (21). Lacunar infarcts may cause dementia in different ways. At one end of the spectrum is the classical lacunar state with multiple small deep infarcts and traditional clinical findings: (1) pseudobulbar syndrome (dysarthria, dysphagia, and emotional lability); (2) small stepped gait (marche á petit pas); (3) parkinsonian-like rigidity; (4) hyperreflexia; (5) Babinski sign; (6) dementia, gait imbalance, and urinary incontinence; (7) variable motor and sensory focal signs.
At the other end of the spectrum is a single strategically located lacunar infarct, causing persistent cognitive deficits. Lacunar infarcts in several locations can impair cognition: paramedian thalamic, anterior thalamic, and genu of the internal capsule. Lacunar infarcts in the internal capsule, corona radiata, putamen, or caudate nuclei can also cause subtle cognitive impairments or emotional disturbances. Secondary neurodegeneration, a focal cortical thinning in remote areas connected by fiber tracts to the lacunar infarction, has been demonstrated in a series of 32 patients that underwent multimodal brain MRI imaging (20). Dementia in patients with lacunar infarction often represents a combination of lacunes with diffuse cerebral small vessel disease. These patients tend to have frontal signs on clinical examination. Cerebral blood flow and cerebral vessel reactivity may be significantly decreased in patients with multiple lacunar infarctions and leukoaraiosis, causing cognitive impairment not related to the extent of tissue loss or anatomical location of lesions. With this mechanism in mind, the LACI-1 trial, a phase IIa dose-escalation trial, tested the tolerability, safety, and efficacy of isosorbide mononitrate and cilostazol in the secondary prevention of lacunar infarcts and cognitive decline related to small vessel disease (10). The drugs have been shown to have promising mechanisms of action to support their testing in the prevention of stroke recurrence, cognitive impairment, or radiological progression after lacunar stroke, and this trial demonstrated their tolerability and safety with dose escalation. A larger follow-up trial is underway (87). The DISCOVERY (Determinants of Incident Stroke Cognitive Outcomes and Vascular Effects on RecoverY) study is currently ongoing to investigate the clinical factors, blood-based biomarkers, and neuroimaging markers that may predict the occurrence of cognitive impairment and dementia after stroke, including after lacunar infarction (64).
Table 1. Classical Lacunar Syndromes
Pure motor stroke (absent sensory and visual symptoms, absent aphasia) | |
Clinical deficit | |
• Contralateral hemiparesis | |
Most frequent localization | |
• Internal capsule (posterior limb) | |
Sensorimotor stroke | |
Clinical deficit | |
• Contralateral hemiparesis | |
Most frequent localization | |
• Thalamocapsular | |
Pure sensory stroke (absent motor weakness, visual symptoms, or neuropsychological balance) | |
Clinical deficit | |
• Contralateral numbness with sensory loss (all modalities or dissociated), cheiro-oral-pedal, cheiro-oral, or oral | |
Most frequent localization | |
• Lateral thalamus | |
Ataxic hemiparesis (homolateral ataxia and crural paresis ± hypesthesia) | |
Clinical deficit | |
• Pyramidal (weakness) | |
Most frequent localization | |
• Pons | |
Dysarthria-clumsy hand syndrome | |
Clinical deficit | |
• Dysarthria and clumsiness of one hand ± central facial paralysis | |
Most frequent localization | |
• Upper basis pontis | |
Table 2. Miscellaneous Lacunar Syndromes
Lacunar syndromes with oculomotor palsies | |
Clinical deficits | |
• Pure hemiplegia + oculomotor nerve palsy | |
Most frequent localization | |
• Midbrain | |
Lacunar syndromes with isolated eye movements | |
Clinical deficit | |
• Isolated ocular nerve palsy | |
Most frequent localization | |
• Midbrain | |
Lacunar syndromes with movement disorders | |
Clinical deficit | |
• Chorea | |
Most frequent localization | |
• Deep striatum | |
Lacunar syndromes with neuropsychological disturbances | |
Clinical deficit | |
• Acute perseverative behavior | |
Most frequent localization | |
• Thalamus (anterior nuclei) | |
Prognosis and complications
Lacunes have some of the lowest mortality and recurrence rates as well as the best recovery and functional outcome of all strokes. However, the concept that lacunar strokes represent benign lesions is contradicted by studies of mortality, recurrent stroke, and functional outcomes. In a review of 24 studies involving 2863 patients, case fatality at 30 days was 2.5%, at 1 year was 2.8%, and at 5 years was up to 27.4% (51). The rate of loss of living independently was 42% at 3 years. A population-based study involving 442 patients showed that the recurrence rate of lacunes increases from 1.4% in the first month to 7% at 1 year and 25% after 5 years, whereas in atherothrombotic stroke the recurrence rate is 18.5% in the first month and goes as high as 40% after 5 years (56). Although in the first year the recurrence rate for lacunar infarctions is lower than in nonlacunar strokes, from the second year it becomes similar to the recurrence of other stroke subtypes (65). Similarly, differences between survival after lacunar versus non-lacunar stroke were attenuated after the first year in a hospital-based cohort study of 812 patients (57). In a contemporary clinical trial of secondary prevention after lacunar stroke (Secondary Prevention of Small Subcortical Stroke trial [SPS3]), overall mortality is much lower than previous population-based estimates, 1.78% per year, which is likely due to the younger age of trial participants, a population meeting trial inclusion criteria, and aggressive risk factor management (71). More than 80% of patients with lacunar infarction have minimal or no disability after stroke. A good premorbid functional status and lacunar stroke subtype are predictors for a good outcome (56; 31), whereas the severity of motor deficit is highly predictive of a poor outcome (68). Some authors consider that leukoaraiosis and nondipping nocturnal hypertension are independent predictors for subsequent dementia, whereas diabetes, multiple lacunes, and high 24 hour-systolic hypertension are independent predictors for recurrent strokes (92). Symptomatic lacunes accompanied by multiple silent lacunes, hypertension, and arteriolosclerosis confer a much poorer prognosis than solitary symptomatic lesions associated with microatheroma (18). A trial involving 1331 participants with prior lacunar stroke determined that those at higher baseline systolic blood pressure and systolic blood pressure variability were at a higher risk for adverse outcomes. Those with mildly elevated baseline systolic blood pressure and minimal visit-to-visit blood pressure variability were shown to have less risk of adverse outcomes (43). Overall, though lacunar infarction is thought to have a good prognosis compared to other stroke types, the risk factors that cause lacunar stroke are also associated with atherosclerotic disease in other organs. At 10 years after a lacunar infarction, less than a third of patients are free of recurrent stroke, cognitive impairment, or functional disability (52).
Biological basis
Etiology and pathogenesis
Lacunar infarction is caused by occlusion of individual small vessels that are, on average, 400 micrometers in size. Because these small vessels have no collateral circulation, the resulting infarct affects the entire territory of the occluded vessel (86).
There are a variety of etiologies for lacunar infarction, each with their own pathophysiology. There is overlap, however, in the risk factors that contribute to these different mechanisms. The primary mechanisms for lacunar infarction include lipohyalinosis, atherosclerotic disease, arterial stiffness/arteriosclerosis, and, rarely, embolism.
Lipohyalinosis
Pathophysiology. Lipohyalinosis was one of the first identified mechanisms of lacunar infarction (22). It is characterized by a focal, destructive angiopathy involving vessels smaller than 200 microns. The arterial wall is disorganized and replaced by connective tissue and fatty macrophages; this results in occlusion of the arterial lumen (23).
Risk factors. There are several risk factors for lipohyalinosis.
Hypertension. In Fisher’s original work, the majority of patients (111/114) examined at autopsy had a clinical history of hypertension, thereby identifying this risk factor as a primary etiology of lacunar infarcts (22). Besides the absolute level of blood pressure, important risk factors include persistent nighttime hypertension, high pulse pressure, and abnormal circadian variation, such as a higher magnitude of nocturnal systolic and diastolic blood pressure dip (14).
Diabetes mellitus. Diabetes mellitus is present in 2% to 37% of patients with lacunes, and lacunar infarctions are more common in diabetics than in nondiabetics (35.1% vs. 23.9%) (06). Excessive glycation and oxidation, endothelial dysfunction, increased platelet aggregation, and impaired fibrinolysis appear to underlie the pathogenesis of diabetes-related stroke. Insulin resistance was found to be an independent risk factor for cerebral small vessel disease (94). This can be estimated by the Homeostatic Model for Insulin Resistance (HOMA-IR) score, which has population-dependent cutoff values (26). In a post hoc analysis of the SPS3 trial, diabetes was found to independently double the risk of recurrent lacunar stroke, and diabetics tended to have higher rates of intracranial atherosclerosis (54).
Chronic kidney disease. Chronic kidney disease with poor glomerular filtration rate may associate glomerular and cerebral small vessel disease due to similarities of the two vascular beds (33). By causing endothelial dysfunction, chronic renal disease can independently increase the risk of lacunar infarcts, even in individuals without hypertension or diabetes (84). Kidney dysfunction was found to be an independent risk factor for the presence and number of silent lacunar infarctions in generally healthy adults (37).
Hyperlipidemia. Lipid and lipoprotein abnormalities have been implicated in the pathogenesis of cerebrovascular disease. Increased apolipoprotein B and apolipoprotein A are considered risk factors for lacunes. A Chinese study showed that an increased plasma level of lipoprotein(a) causes a 2.05-fold increased risk for lacunar infarction (77). Serum saturated fatty acids may increase the risk for lacunes, whereas serum linoleic acid appears to be protective. In Japanese individuals, a linear and independent association between plasma levels of homocysteine and lacunes was observed. Homocysteine may be a stronger predictor for diffuse white matter disease than an isolated lacune, acting via endothelial dysfunction (32).
A Japan Public Health Center–based prospective study looking into the association of high-density lipoprotein cholesterol concentration with different types of stroke identified 1712 stroke events over a median 15-year follow-up (66). A low high-density lipoprotein cholesterol concentration slightly raised the risk for total strokes in men but not in women. An inverse relationship between high-density lipoprotein cholesterol concentration and the incidence of lacunar infarction was also demonstrated. Conclusions of the study brought forth likely associations of high-density lipoprotein cholesterol concentration with lacunar infarction as being related to different functional properties of high-density lipoprotein rather than to its protective function against lipid-rich atherosclerosis.
Other established risk factors. Other established risk factors for lipohyalinosis and lacunar infarction include age, excess body weight, ischemic heart disease, transient ischemic attacks, and cigarette smoking.
Arterial stiffness/arteriosclerosis
Pathophysiology. Another proposed mechanism for lacunar infarction is a loss of cerebrovascular reactivity in the setting of increased arterial rigidity. In lacunar stroke patients with neuropathology at autopsy, cases have shown thickening of the media and deposition of fibrinoid material in the vessel wall (12). These pathologic changes lead to alterations within the endothelium of the vessel to the point that cerebral autoregulation is impaired, and these small vessels are no longer able to appropriately dilate to maintain perfusion (62). Augmentation index measured by applanation tonometry at the radial artery has been found to be significantly increased in patients with lacunar infarcts when compared with patients with other stroke subtypes, suggesting that aortic arterial stiffness is increased in patients with lacunar stroke and may be related to the pathogenesis (11). Impaired cerebrovascular reactivity may reflect diffusely increased arteriosclerosis and rigidity of the vascular wall (48). Thus, cerebral blood flow is not maintained when a drop in systolic blood pressure occurs, which can contribute to the development of white matter disease (53).
Risk factors. Risk factors for arterial stiffness are similar to those for lipohyalinosis. Hypertension is an especially important risk factor for arterial stiffness and arteriosclerosis.
Atherosclerotic disease
Pathophysiology. Another known mechanism for lacunar infarction is intracranial branch occlusive (or atheromatous) disease. Instead of disease of the small penetrating arteries, this refers to atherosclerotic disease of the parent artery, which can obstruct the ostium of the small perforators, thus, leading to lacunar infarction (12). The degree of intracranial stenosis caused by atheromatous disease does not need to be severe in order to obstruct flow to small penetrating branches, particularly in the posterior circulation (91). Atheromatous disease of larger arteries can often be visualized with CT angiogram or MR angiogram and is an important part of the stroke work-up (12). Branch atheromatous disease has a poorer prognosis than lacunar infarcts and clinically presents more frequently as a progressive stroke (worsening of the NIHSS score with > 2 points within 48 hours of onset), even if the parent artery has less than 50% stenosis (93). The most common risk factors are poorly controlled diabetes and dyslipidemia (49).
Risk factors. Diabetics tend to have more intracranial atherosclerotic disease (54). Hyperlipidemia and smoking are also major contributors to intracranial atherosclerosis that can lead to lacunar infarction, in addition to the risk factors listed in the previous sections.
Embolic disease
Pathophysiology. Though less common, embolic sources should be considered in the differential for the etiology of lacunar stroke. This is particularly true when subcortical infarcts are larger than the typical 15 mm that defines a lacune. One study suggests that up to 25% of patients with lacunar disease have evidence of large artery occlusion and perfusion deficit. Many of these patients present clinically with lacunar syndromes and subcortical infarcts, though they may have had an embolic stroke mechanism (78). The location of the infarct can help to determine the mechanism: infarcts in the centrum semiovale, which is supplied by pial branches of the middle cerebral artery (called also medullary arteries), may be more susceptible to embolic pathology.
Risk factors. Cardioembolism, most commonly from atrial fibrillation, is a mechanism that should be considered. Atrial fibrillation is more frequent in patients older than 85 years of age with lacunar infarcts than in patients younger than 85 (28.2% vs. 8.7%). It is possible that in this age group, cardioembolic pathogenesis of lacunes is more important than originally thought. Large artery atheroembolism is another consideration, both from intracranial or extracranial sources, including carotid or vertebral disease as well as aortic arch atheroma. A higher prevalence of thoracic aorta atherosclerosis has been found in patients with lacunar infarction (67). Isolated carotid stenosis has also been more frequently associated with multiple, ipsilateral lacunar infarctions, particularly when the stenosis is greater than or equal to 75% (50).
Genetics
The pathogenesis of lacunar infarction, and of cerebrovascular disease in general, results from a combination of genetics and environmental and lifestyle risk factors. Family history of stroke is a moderate risk factor for stroke in cohort studies. In the Framingham Heart Study, parental history of stroke is associated with a category of stroke called atherosclerotic brain infarction, which includes the subtypes of lacunar infarction and large-artery atherosclerosis (70). Although lacunar stroke is typically the result of a complex pattern of inheritance, some rare, monogenic Mendelian disorders are associated with lacunar infarction, particularly disorders of the small arteries of the brain (Table 3). Lacunar infarction may be an expression of hereditary forms of cerebral small vessel disease, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) or small vessel disease associated with mutations of the COL4A1 and COL4A2 genes. CADASIL is caused by a genetic mutation of the NOTCH3 gene, with inheritance linked to chromosome 19p13.1, and is the most common monogenic form of cerebral small vessel disease (1 per 20,000) (47). Additionally, NOTCH3 variants in the general population appear to be more common than expected, with 1 per 450 participants in the UK Biobank (N=200,632) carrying cysteine-altering variants of NOTCH3 (16). The COL4A2 gene was found to be associated with lacunar ischemic stroke in a meta-analysis among 21,500 cases and 40,600 controls (61). Other monogenic disorders causing stroke also develop small artery disease that may manifest as lacunar infarction, including sickle cell disease, Fabry disease, hyperhomocysteinemia, neurofibromatosis 1, and pseudoxanthoma elasticum. Research has only identified a small proportion of the genes associated with non-Mendelian inheritance that contributes to the risk of lacunar infarction. Genome-wide association studies (GWAS) have unraveled the genetic underpinnings of stroke (ischemic or hemorrhagic); however, only 56 loci have been associated with any stroke or specific subtypes of stroke to date (19). This contrasts with the estimate that up to 24% of brain imaging–defined small vessel stroke may be heritable (81). Genetic variants associated with vascular risk factors (eg, hypertension) may contribute to the genetic underpinnings of lacunar infarction, whereas other genes or proteins, such as APOE, may help to determine the resilience of the brain to vascular injury. Individual loci that have been identified to alter the risk of lacunar infarction have only small effects on risk.
Table 3. Mendelian Disorders Associated with Lacunar Infarction
Mendelian disorder | Gene, gene function |
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) | NOTCH3, functions as a transmembrane receptor protein with a key role in the function/survival of vascular smooth muscle cells of blood vessels; autosomal dominant inheritance |
CARASIL (Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) | HTRA1, makes an enzyme, serine protease, that interacts with transforming growth factor-beta family proteins; autosomal recessive inheritance |
HERNS (Hereditary Endotheliopathy with Retinopathy, Nephropathy, and Stroke) | TREX1, encodes the 3-prime DNA repair exonuclease 1 enzyme; autosomal dominant inheritance |
Type IV collagen mutations | COL4A1/2, provides instructions for making alpha1 and alpha2 collagen chains, which play a role in basement membrane structure and cell function; autosomal dominant inheritance |
Epidemiology
In the white population, lacunar infarction has an age- and sex-adjusted incidence comparable with the incidence of large vessel atherosclerotic stroke (ie, 25 out of 100,000 and 27 out of 100,000 persons respectively), with no significant sex-related differences (55). In patients older than 85 years the incidence is higher in women (56.4%) than in men (37.3%) (04). Lacunar infarctions are the most common type of stroke in the Japanese population, with an incidence almost double in men (3.8 out of 1000 persons-years) than in women (2.0 out of 1000 persons-years) (79). In Western countries, lacunes account for 15% to 20% of all strokes, whereas in Japan they represent 30% to 40% of all strokes (92). The Northern Manhattan Stroke Study reported that lacunar infarcts were the second most prevalent ischemic stroke subtype in their population (second to cardioembolic stroke), affecting non-Hispanic Black and Hispanic individuals more than non-Hispanic White individuals. This ethnic disparity was true in most stroke subtypes and thought to be due to an increased burden of vascular risk factors in the Black and Hispanic population (25). The African-American population of the metropolitan area of Cincinnati, Ohio, has a higher lacunar stroke incidence of 52 out of 100,000, compared to the White population with 29 out of 100,000 (90). The TOAST (Trial of Org 10172 in Acute Stroke Treatment) trial also reported a higher incidence of lacunar infarction in the African-American population, with poorer prognosis (31). A study of a multiethnic stroke population reported the highest prevalence of lacunar infarcts in Caribbean Blacks (44%), primarily associated with hypertension (41). Smoking and dyslipidemia were more frequent in African-American and Caribbean-Hispanic participants, resulting in a similar prevalence of lacunar infarcts (25% and 22%, respectively), whereas only 7% of non-Hispanic whites were found to have lacunar infarcts. In a large multiethnic cohort of patients with recent lacunar infarcts, MRI analysis demonstrated distinct imaging patterns associated with sex, vascular risk factors, race, and ethnicity. Multiple lacunar infarcts were associated with increased age (1.2 per 20 years, 95% CI 1.1, 1.5) and prior stroke (3.8 per 20 years; 95% CI 2.9, 5.0). Moderate-to-severe white matter hyperintensities were associated with increased age (4.3 per 20 years, 95% CI 3.4, 5.4), hypertension (1.8 per 20 mmHg, 95% CI 1.4, 2.3), and prior stroke (3.3 per 20 mmHg, 95% CI 2.3, 4.5). Black and Hispanic individuals had more infarcts in the brainstem/cerebellum (P < 0.001) than non-Hispanic white individuals, and women often had more thalamic lacunes than men (P < 0.001) (09).
Prevention
Although the management of hypertension is the single most important preventive strategy for lacunar infarctions, optimal primary prevention involves the management of all modifiable risk factors for atherosclerosis and ischemic stroke:
(1) Hypertension control. The SPRINT trial randomized patients with hypertension to intensive (goal systolic < 120) or to standard (goal systolic < 140) treatment (73). Primary outcome was a composite of myocardial infarction, stroke, heart failure, other acute coronary syndrome, or death from other cardiovascular disease. Intensive management was found to lower rates of cardiovascular events. Professional guidelines have endorsed a treatment target of less than 130/80 for the primary prevention of cardiovascular disease (07). Guidelines suggest the use of an angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, or thiazide diuretic to reach this goal (40).
(2) Smoking cessation. Cigarette smoking is associated with lacunar infarction more frequently than with other types of stroke (65). In a meta-analysis of smoking cessation trials, a multimodal approach including behavioral therapy and pharmacologic interventions was found to be most beneficial to patients (75). It is crucial to engage patients in methods for smoking cessation, both as part of primary prevention and secondary prevention after an infarct.
(3) Glycemic control is recommended to reduce microvascular complications and prevent the development of cerebral small vessel disease. The American Diabetes Association recommends a target HbA1c of less than 7% in most adult patients. Stroke prevention guidelines suggest a multidimensional approach to glycemic control, including diet and lifestyle counseling as well as medications. Specifically, in patients with cardiovascular risk factors, including prior stroke, the use of GLP-1 receptor agonists is recommended. In patients with renal dysfunction or heart failure, the use of sodium glucose cotransporter 2 (SGLT2) inhibitors is recommended (40).
(4) Patients with elevated cholesterol and elevated risk for heart disease should receive treatment with statins, in addition to lifestyle modification (07).
(5) Other modifiable risk factors: obesity, physical inactivity, alcohol abuse, hyperhomocysteinemia, and substance use disorders (28). Visceral adipose tissue has been associated with cerebral small vessel disease and lacunar infarcts. Visceral obesity is a potential therapeutic target for the prevention of cerebral small vessel disease (38). Other modifiable risk factors include vitamin deficiency. In 2015, the China Stroke Primary Prevention Trial (CSPPT) involved over 20,000 participants followed for 5 years and showed a significant reduction of stroke with folic acid administration in a setting where folate fortification was not previously implemented (72). In the setting of folate fortification, the main causes of elevated total homocysteine are renal failure and metabolic B12 deficiency.
Differential diagnosis
Lacunar syndromes may be caused by a variety of pathologies, such as neurocysticercosis, tumors, demyelinating lesions, and small hemorrhages. Large cerebral infarcts are differentiated from lacunar infarcts using the neurologic exam and neuroimaging. A pure motor monoparesis or a hemiparesis associated with “cortical” signs such as aphasia suggest a nonlacunar infarct. Restricted acral sensory syndromes or pseudothalamic sensory strokes can result from minor parietal strokes. A report details the case of a patient with ataxic hemiparesis resulting from acute infarction associated with localized lesions of the postcentral gyrus (39). A lacunar infarct must be differentiated from a deep cerebral watershed infarct. Deep watershed “low flow” infarcts tend to present with a combination of a lacunar syndrome and a “cortical” sign. Confluent low-flow white matter infarcts are larger than lacunar infarcts and have a worse prognosis (22). Symptomatic small centrum semiovale infarcts may be caused by large-vessel occlusive disease or cardioembolism and should be distinguished from lacunes and leukoaraiosis. The presence of retinal microangiopathy on retinography, white matter disease on MRI, and increased carotid pulsatility index on ultrasound is a marker of lacunar infarcts not secondary to macrovascular lesion (63). Diffusion-weighted MRI is more sensitive than other MRI sequences or CT in detecting them. Multiple diffusion-weighted imaging hyperintense lesions raise the possibility of an embolic mechanism rather than microvascular disease (08). A diffusion-weighted/perfusion-weighted imaging mismatch reliably distinguishes between a single perforating vessel occlusion and a large artery embolism for solitary small subcortical infarctions (27). Multiple acute ischemic lesions in different vascular territories might not always be of proximal cardiovascular embolic origin. Simultaneous small subcortical ischemic lesions may reflect remote ischemia due to small vessel disease reflecting simultaneous hemorheological dysfunction (89).
Diagnostic workup
CT or MRI of the brain, including ultrasound, CT angiography, or MR angiography imaging of the extracranial and intracranial large arteries, is necessary to rule out non-lacunar pathology. The diagnostic workup should be performed emergently in acute stroke, particularly if there is any sign of clinical progression or fluctuation. CT is less sensitive than MRI for smaller lacunes in the brainstem and thalamus. In acute settings, MRI-DWI sequence overestimates the final infarct size. One third of lacunar infarcts will not result in a cavity (42). The carotid arteries should be evaluated following a lacunar stroke with Doppler ultrasonography, CT angiogram, or MR angiogram. Cervical carotid arteries with moderate or greater stenosis ipsilateral to the side of infarct should be considered for carotid endarterectomy or stenting. Transcranial Doppler ultrasonography is an alternative, noninvasive method of detecting intracranial vascular stenoses. Clinical findings should be used to indicate the need for other tests. A review of 214 patients indicated that although transesophageal echocardiography has a well-established value in the investigation of the stroke mechanism, evidence suggests that the combination of a small subcortical infarction with a typical lacunar syndrome has a 100% negative predictive value for a cardioembolic source (60).
Management
Acute management
Acute lacunar infarcts seen within 4.5 hours of onset and presenting with disabling symptoms should be considered for intravenous thrombolysis (ie, tissue-type plasminogen activator [alteplase] or tenecteplase). Intravenous thrombolysis is the only treatment for lacunar infarction proven to improve clinical outcome. Lacunar strokes showed the most favorable outcome following intravenous thrombolysis (80), with the lowest rate of post-thrombolysis hemorrhagic transformation. Imaging identifies the lacunar infarct prior to thrombolysis better than the identification of a clinical lacunar syndrome (44). Between 24% and 37% of lacunar strokes progress and have a fluctuating course of motor deficit for the first 24 hours and up to 72 hours or 1 week. Multiple mechanisms have been considered responsible for progression: the inflammatory response, glutamate excitotoxicity, stepwise occlusion of the small penetrators (76), and severe hypoperfusion of the ischemic area with distal embolization (13). The only treatment proven to be effective in progressing lacunar stroke is augmentation of cerebral blood flow. Blood pressure should not be lowered, and volume expanders or pressor medication can be used, if necessary. Hyperglycemia has a detrimental effect on nonlacunar stroke outcome, but a moderate hyperglycemia (8-12 mmol/L) seems to be beneficial in lacunar infarct. A higher blood pressure during the first 24 hours after the occurrence of an acute lacunar infarct carries a better neurologic outcome (69). Although hyperglycemia is associated with worsened outcome in acute ischemic stroke, the impact may not be similar in lacunar versus non-lacunar infarct. Hyperglycemia has a detrimental effect on non-lacunar stroke outcome, but a moderate hyperglycemia (8-12 mmol/L) seems to be beneficial in lacunar infarct. This beneficial effect diminishes with severe hyperglycemia with more than 12 mmol/L (82).
Antiplatelets and neuroprotectants have limited utility as long as perfusion failure persists (13). Anticoagulation may not stop stroke progression, and, in addition, it may increase the already existing risk for cerebral hemorrhage. The T2-weighted gradient-echo MRI is sensitive in detecting hemosiderin resulting from cerebral microbleeds. One study showed an increased incidence of silent microbleeds in patients with Binswanger disease (77%) and multiple lacunar infarctions (51%), indicating an advanced bleeding-prone cerebral microangiopathy (30). This finding has important implications in clinical management. Rehabilitation, prevention, and treatment of medical complications are important measures.
Secondary prevention
A large part of secondary prevention in lacunar infarction is related to risk factor optimization. The section on Prevention includes more detail on overall risk factor management. An optimal blood pressure goal has been studied in various trials. In 2014, the SPS3 trial randomized patients with lacunar infarction to target blood pressure goals of less than 130 and 130 to 150 (74). There was a reduction in stroke recurrence in patients with a lower target blood pressure goal; however, the result was not statistically significant. The American Heart Association guideline as of 2017 defined stage 1 hypertension as less than 130/80, which should be the threshold for treatment in most stroke patients (88).
The Insulin Resistance Intervention after Stroke (IRIS) trial showed that pioglitazone could reduce the incidence of stroke recurrence among persons with insulin resistance, but the intervention was associated with a high frequency of weight gain, bone fractures, and edema (36). Thus, pioglitazone is not regularly used in clinical practice for secondary prevention.
A lipid panel should be checked as a part of the stroke work up. Patients with a target LDL cholesterol of less than 70 mg/dL were found to have a lower risk of subsequent cardiovascular events when compared to patients with a goal of less than 110 mg/dL (03). Independent of lipid-lowering properties, statins may have other vascular effects: improved endothelial function, plaque stabilization, and antithrombotic and neuroprotective properties. Antithrombotic therapy is another important aspect of secondary stroke prevention. Determining appropriate antithrombotic therapy for lacunar infarcts depends on the etiology. For lacunar infarcts thought to be due to lipohyalinosis, antithrombotic therapy typically includes a single antiplatelet agent.
Aspirin (160 or 325 mg) reduces the risk of early recurrent ischemic stroke (absolute risk reduction = 0.7%) (17). Aspirin in a dose as low as 30 mg daily, dipyridamole, and the combination of extended-release dipyridamole with aspirin are available measures for the secondary prevention of lacunar infarcts (02). Clopidogrel and ticlopidine are alternatives for patients who are intolerant to aspirin. In patients with minor stroke (NIHSS < 5) or classified as a high-risk transient ischemic attack (ABCD2 ≥4), there is a benefit of short-term dual antiplatelet therapy (DAPT) with aspirin and clopidogrel (or ticagrelor as an alternative) for 21 days followed by single antiplatelet therapy (85; 35). DAPT could also be considered for lacunar infarcts due to large artery atherosclerosis of a parent artery, occluding penetrator arteries. In this case, patients could be treated with DAPT for 90 days per the SAMMPRIS (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Arterial Stenosis) trial, which compared DAPT to intracranial stenting in patients with intracranial atherosclerosis greater than 70% to 99% (15). It is important to note, however, that this trial did not compare DAPT to single antiplatelet therapy for stroke prevention in intracranial atherosclerotic disease, and more data are needed to answer this question.
Finally, for the smaller percentage of lacunar infarcts that are due to atrial fibrillation, patients should receive anticoagulation for secondary stroke prevention. Novel oral anticoagulants (NOACs) or warfarin can be used; however, data support the use of NOACs, especially apixaban, for stroke prevention with lower bleeding risk (29).
Special considerations
Pregnancy
Cerebrovascular disorders other than eclampsia include uncommon and unpredictable complications of pregnancy and puerperium associated with serious maternal morbidity and mortality. Venous infarctions, large arterial strokes (secondary to cardiac emboli, coagulopathies, and vascular dissection), and intracranial hemorrhages account for most cerebrovascular complications, but lacunar infarctions can occur. Experts recommend that pregnant women with acute ischemic stroke not be systematically denied the potential benefits of intravenous recombinant tissue plasminogen activator (45).
Media
References
- 01
- Adams HP, Hachinski V, Norris WJ. Lacunar syndromes. In: Gilman S, Herdman WJ, editors. Ischemic cerebrovascular disease. New York: Oxford University Press, 2001:82.
- 02
- Albers GW, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 1998;114:683S-98S. PMID 9822071
- 03
- Amarenco P, Kim JS, Labreuche J, et al. A comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med 2020;382(1):9. PMID 31738483
- 04
- Arboix A, Garcia-Eroles L, Massons J, Oliveres M, Targa C. Lacunar infarcts in patients aged 85 years and older. Acta Neurologica Scandinavica 2000;101:25-9. PMID 10660148
- 05
- Arboix A, Lopez-Grau M, Casasnovas C, Garcia-Eroles L, Massons J, Balcells M. Clinical study of 39 patients with atypical lacunar syndrome. J Neurol Neurosurg Psychiatry 2006;77(3):381-4. PMID 16484649
- 06
- Arboix A, Rivas A, Garcia-Eroles L, de Marcos L, Massons J, Oliveres M. Cerebral infarction in diabetes: Clinical pattern, stroke subtypes, and predictors of in-hospital mortality. BMC Neurol 2005;5(1):9. PMID 15833108
- 07
- Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;140(11):e596-646. PMID 30879355
- 08
- Ay H, Oliveira-Filho J, Buonanno FS, et al. Diffusion-weighted imaging identifies a subset of lacunar infarctions associated with embolic source. Stroke 1999;30:2644-50. PMID 10582991
- 09
- Benavente OR, Pearce LA, Bazan C, et al. Clinical-MRI correlations in a multiethnic cohort with recent lacunar stroke: the SPS3 trial. Int J Stroke 2014;9(8):1057-64. PMID 24862645
- 10
- Blair GW, Appleton JP, Law ZK, et al. Preventing cognitive decline and dementia from cerebral small vessel disease: The LACI-1 Trial. Protocol and statistical analysis plan of a phase IIa dose escalation trial testing tolerability, safety and effect on intermediary endpoints of isosorbide mononitrate and cilostazol, separately and in combination. Int J Stroke 2018;13(5):530-8. PMID 28906205
- 11
- Byun DS, Han SW, Park JH, Kim JY, Baik JS, Park JH. Relationship between augmentation index and acute ischemic stroke subtype. J Clin Neurosci 2014;21(7):1220-4. PMID 24855972
- 12
- Caplan LR. Lacunar infarction and small vessel disease: pathology and pathophysiology. J Stroke 2015;17(1):2-6. PMID 25692102
- 13
- Caplan LR. Worsening in ischemic stroke patients: it is time for a new strategy. Stroke 2002;33:1443-5. PMID 12052964
- 14
- Castilla-Guerra L, Espino-Montoro A, Fernandez-Moreno MC, Lopez-Chozas JM. Abnormal blood pressure circadian rhythm in acute ischemic stroke: are lacunar strokes really different. Int J Stroke 2009;4(4):257-61. PMID 19689751
- 15
- Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 2011;365(11):993-1003. PMID 21899409
- 16
- Cho BPH, Nannoni S, Harshfield EL, et al. NOTCH3 variants are more common than expected in the general population and associated with stroke and vascular dementia: an analysis of 200 000 participants. J Neurol Neurosurg Psychiatry 2021;92(7):694-701. PMID 33712516
- 17
- Coull BM, Williams LS, Goldstein LB, et al. Anticoagulants and antiplatelet agents in acute ischemic stroke. Stroke 2002;33:1934-42. PMID 12105379
- 18
- de Jong G, Kessels F, Lodder J. Two types of lacunar infarcts: further arguments from a study on prognosis. Stroke 2002;33:2072-6. PMID 12154265
- 19
- Debette S, Markus HS. Stroke genetics: discovery, insight into mechanisms, and clinical perspectives. Circ Res 2022;130(8):1095-111. PMID 35420914
- 20
- Duering M, Righart R, Wollenweber FA, Zietemann V, Gesierich B, Dichgans M. Acute infarcts cause focal thinning in remote cortex via degeneration of connecting fiber tracts. Neurology 2015;84:1685-92. PMID 25809303
- 21
- Edwards JD, Jacova C, Sepehry AA, Pratt B, Benavente OR. A quantitative systematic review of domain-specific cognitive impairment in lacunar stroke. Neurology 2013;80(3):315-22. PMID 23319476
- 22
- Fisher CM. Lacunes: small, deep cerebral infarcts. Neurology 1965;15:774-84. PMID 14315302
- 23
- Fisher CM. The arterial lesions underlying lacunes. Acta Neuropathol 1969;12:1-15. PMID 5708546
- 24
- Fisher CM. Lacunar infarcts: a review. Cerebrovasc Dis 1991;1:311-20.
- 25
- Gardener H, Sacco RL, Rundek T, Battistella V, Cheung YK, Elkind MSV. Race and ethnic disparities in stroke incidence in the Northern Manhattan Study. Stroke 2020:51(4):1064-9. PMID 32078475
- 26
- Gayoso-Diz P, Otero-González A, Rodriguez-Alvarez MX, et al. Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: effect of gender and age: EPIRCE cross-sectional study. BMC Endocr Disord 2013;13:47. PMID 24131857
- 27
- Gerraty RP, Parsons MW, Barber PA, et al. Examining the lacunar hypothesis with diffusion and perfusion Magnetic Resonance Imaging. Stroke 2002;33:2019-24. PMID 12154256
- 28
- Goldstein LB, Adams R, Becker K, et al. Primary prevention of ischemic stroke. Circulation 2001;103:163-82. PMID 11136703
- 29
- Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365(11):981-92. PMID 21870978
- 30
- Hanyn H, Tanaka Y, Shimizu S, et al. Cerebral microbleeds in Binswanger’s disease: a gradient-echo T2- weighted magnetic resonance imaging study. Neurosci Lett 2003;340:213-6. PMID 12672544
- 31
- Hassaballa H, Gorelick PB, West CP, Hansen MD, Adams HP Jr. Ischemic stroke outcome: racial differences in the trial of danaparoid in acute stroke (TOAST). Neurology 2001;57:691-7. PMID 11524481
- 32
- Hassan A, Hunt BJ, O’Sullivan M, et al. Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction. Brain 2004;127(Pt 1):212-9. PMID 14607791
- 33
- Ikram MA, Vernooij MW, Hofman A, Niessen WJ, van der Lugt A, Breteler MM. Kidney function is related to cerebral small vessel disease. Stroke 2008;39(1):55-61. PMID 18048865
- 34
- Jeong HK, Lee SK, Kim DI, Heo JH. The usefulness of fractional anisotropy maps in localization of lacunar infarctions in striatum, internal capsule and thalamus. Neuroradiology 2005;47(4):267-70. PMID 15806429
- 35
- Johnston SC, Amarenco P, Denison H, et al. Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA. N Engl J Med 2020;383(3):207-17. PMID 32668111
- 36
- Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 2016;374(14):1321-31. PMID 26886418
- 37
- Kim KW, Seo H, Kwak MS, Kim D. Visceral obesity is associated with white matter hyperintensity and lacunar infarct. Int J Obes (Lond) 2017a;41(5):683-8. PMID 28104915
- 38
- Kim SH, Shin DW, Yun JM, et al. Kidney dysfunction and silent brain infarction in generally healthy adults. J Neurol Sci 2017b;379:89-93. PMID 28716287
- 39
- Kinjo Y, Suda S, Sakamoto Y, Okubo S, Kimura K. Ataxic hemiparesis associated with cortical infarct localized in the postcentral gyrus. Intern Med 2017;56(18):2503-5. PMID 28824079
- 40
- Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke 2021;52(7):e364-467. PMID 34024117
- 41
- Koch S, Gupta R, McClendon MS, Romano JG. Racial-ethnic differences in lacunar infarction in a multiethnic stroke population. J Stroke Cerebrovasc Dis 2013;22(2):107-12. PMID 21821432
- 42
- Koch S, McClendon MS, Bhatia R. Imaging evaluation of acute lacunar infarctions: leukoariosis or lacune. Neurology 2011;77(11):1091-5. PMID 24589036
- 43
- Ku E, Scherzer R, Odden MC, et al. Patterns of blood pressure response during intensive BP lowering and clinical events: results from the secondary prevention of small subcortical strokes trial. Blood Press 2018;27(2):73-81. PMID 28952798
- 44
- Lee SJ, Saver JL, Liebeskind DS, et al. Safety of intravenous fibrinolysis in imaging-confirmed single penetrator artery infarcts. Stroke 2010;41(11):2587-91. PMID 20947857
- 45
- Majersik JJ. Inherited and uncommon causes of stroke. Continuum (Minneap Minn) 2017;23(1, Cerebrovascular Disease):211-37. PMID 28157751
- 46
- Makin SD, Turpin S, Dennis MS, Wardlaw JM. Cognitive impairment after lacunar stroke: a systematic review and meta-analysis of incidence, prevalence and comparison with other stroke subtypes. J Neurol Neurosurg Psychiatry 2013;84(8):893-900. PMID 23457225
- 47
- Malik R. Genetics of small vessel disease. In: Sharma P, Meschia J, editors. Stroke genetics. Springer, Cham, 2017.
- 48
- Molina C, Sabin JA, Montaner J, et al. Impaired cerebrovascular reactivity as a risk marker for first-ever lacunar infarction: a case-control study. Stroke 1999;30:2296-301. PMID 10548661
- 49
- Nakase T, Yoshioka S, Sasaki M, Suzuki A. Clinical evaluation of lacunar infarction and branch atheromatous disease. J Stroke Cerebrovasc Dis 2013;22(4):406-12. PMID 22133744
- 50
- Nam KW, Kwon HM, Lim JS, Han MK, Nam H, Lee YS. The presence and severity of cerebral small vessel disease increases the frequency of stroke in a cohort of patients with large artery occlusive disease. PLoS One 2017;12(10):e0184944. PMID 28991905
- 51
- Norrving B. Long-term prognosis after lacunar infarction. Lancet Neurol 2003;2(4):238-45. PMID 12849212
- 52
- Norrving B. Chapter 27: Lacunar syndromes, lacunar infarcts and cerebral small vessel disease. In: Grotta JC, Albers G, Broderick J, et al. Stroke: pathophysiology, diagnosis, and management. 7th edition. Elsevier, 2022:404-20.
- 53
- O’Sullivan M, Lythgoe DJ, Pereira AC, et al. Patterns of cerebral blood flow reduction in patients with ischemic leukoaraiosis. Neurology 2002;59:321-6. PMID 12177363
- 54
- Palacio S, McClure LA, Benavente OR, et al. Lacunar strokes in patients with diabetes mellitus: risk factors, infarct location, and prognosis: the secondary prevention of small subcortical strokes study. Stroke 2014;45(9):2689-94. PMID 25034716
- 55
- Petty GW, Brown RD, Whisnant JP, et al. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke 1999;30(12):2513-6. PMID 10582970
- 56
- Petty GW, Brown RD, Whisnant JP, et al. Ischemic stroke subtypes: a population-based study of functional outcome, survival, and recurrence. Stroke 2000;31:1062-8. PMID 10797166
- 57
- Portegijs S, Ong AY, Halbesma N, Hutchison A, Sudlow CL, Jackson CA. Long-term mortality and recurrent vascular events in lacunar versus non-lacunar ischaemic stroke: a cohort study. Eur Stroke J 2022;7(1):57-65. PMID 35287300
- 58
- Pullicino PM, Caplan LR, Hommel M. Lacunar syndromes. In: Pullicino PM, Caplan LR, Hommel M, editors. Cerebral small artery disease. New York: Raven Press, 1993:141-60.
- 59
- Pullicino PM, Lincoff N, Truax BT. Abnormal vergence with upper brainstem infarcts. Pseudoabducens palsy. Neurology 2000;55:352-8. PMID 10932266
- 60
- Rabinstein AA, Chirinos JA, Fernandez FR, Zambrano JP. Is TEE useful in patients with small subcortical strokes. Eur J Neurol 2006;13(5):522-7. PMID 16722979
- 61
- Rannikmae K, Sivakumaran V, Millar H, et al. COL4A2 is associated with lacunar ischemic stroke and deep ICH: Meta-analyses among 21,500 cases and 40,600 controls. Neurology 2017;89(17):1829-39. PMID 28954878
- 62
- Regenhardt RW, Das AS, Lo EH, Caplan LR. Advances in understanding the pathophysiology of lacunar stroke: a review. JAMA Neurol 2018;75(10):1273-81. PMID 30167649
- 63
- Rodriguez I, Lema I, Blanco M, Rodriguez-Yanez M, Leira R, Castillo J. Vascular retinal, neuroimaging and ultrasonographic markers of lacunar infarcts. Int J Stroke 2010;5(5):360-6. PMID 20854618
- 64
- Rost NS, Meschia JF, Gottesman R, et al. Cognitive impairment and dementia after stroke: design and rationale for the DISCOVERY study. Stroke 2021;52(8):e499-516. PMID 34039035
- 65
- Sacco S, Marini C, Totaro R, Russo T, Cerone D, Carolei A. A population-based study of the incidence and prognosis of lacunar stroke. Neurology 2006;66(9):1335-8. PMID 16682663
- 66
- Saito I, Yamagishi K, Kokubo Y, et al. Association of high-density lipoprotein cholesterol concentration with different types of stroke and coronary heart disease: The Japan Public Health Center-based prospective (JPHC) study. Atherosclerosis 2017;265:147-54. PMID 28888808
- 67
- Saleem MA, Aronow WS, McClung JA, Belkin RN. Association of transesophageal echocardiographic findings with the site of arterial occlusion in patients with thromboembolic stroke. Heart disease 2003;5(5):320-2. PMID 14503929
- 68
- Samuelsson M, Soderfeldt B, Olsson GB. Functional outcome in patients with lacunar infarction. Stroke 1996;27:842-6. PMID 8623103
- 69
- Semplicini A, Maresca A, Boscolo G, et al. Hypertension in acute ischemic stroke: a compensatory mechanism or an additional damaging factor. Arch Intern Med 2003;163(2):211-6. PMID 12546612
- 70
- Seshadri S, Beiser A, Pikula A, et al. Parental occurrence of stroke and risk of stroke in their children: the Framingham study. Circulation 2010;121(11):1304-12. PMID 20212282
- 71
- Sharma M, Pearce LA, Benavente OR, et al. Predictors of mortality in patients with lacunar stroke in the secondary prevention of small subcortical strokes trial. Stroke 2014;45(10):2989-94. PMID 25158772
- 72
- Spence JD. Homocysteine lowering for stroke prevention: unravelling the complexity of evidence. Int J Stroke 2016;11(7):744-7. PMID 27462097
- 73
- SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373(22):2103-16. PMID 26551272
- 74
- SPS3 Study Group. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. Lancet 2013;382(9891):507-15. PMID 23726159
- 75
- Stead LF, Koilpillai P, Fanshawe TR, Lancaster T. Combined pharmacotherapy and behavioural interventions for smoking cessation. Cochrane Database Syst Rev 2016;3:CD008286. PMID 27009521
- 76
- Steinke W, Ley SC. Lacunar stroke is the major cause of progressive motor deficits. Stroke 2002;33:1510-6. PMID 12052983
- 77
- Sun L, Li Z, Zhang H, et al. Pentanucleotide TTTA repeat polymorphism of apolipoprotein(a) gene and plasma level lipoprotein(a) are associated with ischemic and hemorrhagic stroke in Chinese: a multicenter case-control study in China. Stroke 2003;34(7):1617-22. PMID 12791946
- 78
- Tan MYQ, Singhal S, Ma H, et al. Examining subcortical infarcts in the era of acute multimodality CT imaging. Front Neurol 2016;7:220. PMID 27994572
- 79
- Taniazaki Y, Kiyohara Y, Kato I, et al. Incidence and risk factors for subtypes of cerebral infarction in a general population: The Hisayama Study. Stroke 2000;31:2616-22. PMID 11062284
- 80
- The NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-7. PMID 7477192
- 81
- Traylor M, Bevan S, Baron JC, Hassan A, Lewis CM, Markus HS. Genetic architecture of lacunar stroke. Stroke 2015;46(9):2407-12. PMID 26243229
- 82
- Uyttenboogaart M, Koch MW, Stewart RE, Vroomen PC, Luijckx GJ, de Keyser J. Moderate hyperglycemia is associated with favourable outcome in acute lacunar stroke. Brain 2007;130:1626-30. PMID 17525141
- 83
- Vermeer SE, Koudstaal PJ, Oudkerk M, Hofman A, Breteler MM. Prevalence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. Stroke 2002;33:21-5. PMID 11779883
- 84
- Wada M, Nagasawa H, Iseki C, et al. Cerebral small vessel disease and chronic kidney disease (CKD): results of a cross-sectional study in community-based Japanese elderly. J Neurol Sci 2008;272(1-2):36-42. PMID 18541269
- 85
- Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013;369(1):11-9. PMID 23803136
- 86
- Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013;12(8):822-38. PMID 23867200
- 87
- Wardlaw J, Bath PMW, Doubal F, et al. Protocol: The Lacunar Intervention Trial 2 (LACI-2). A trial of two repurposed licenced drugs to prevent progression of cerebral small vessel disease. Eur Stroke J 2020;5(3):297-308. PMID 33072884
- 88
- Whelton PK, Carey RM. The 2017 clinical practice guideline for high blood pressure. JAMA 2017;318(21):2073-4. PMID 29159375
- 89
- Wolf ME, Sauer T, Kern R, Szabo K, Hennerici MG. Multiple subcortical acute ischemic lesions reflect small vessel disease rather than cardiogenic embolism. J Neurol 2012;259(9):1951-7. PMID 22349872
- 90
- Woo D, Gebel J, Miller R, et al. Incidence rates of first-ever ischemic stroke subtypes among blacks: a population-based study. Stroke 1999;30(12):2517-22. PMID 10582971
- 91
- Yaghi S, Raz E, Yang D, et al. Lacunar stroke: mechanisms and therapeutic implications. J Neurol Neurosurg Psychiatry 2021. [Epub ahead of print] PMID 34039632
- 92
- Yamamoto Y, Akiguchi I, Oiwa K, et al. Twenty-four-hour blood pressure and MRI as predictive factors for different outcomes in patients with lacunar infarct. Stroke 2002;33:297-305 PMID 11779928
- 93
- Yang D, Gutierrez J, Cutting S, et al. Mild luminal stenosis of parent artery and neurologic deterioration after acute lacunar stroke. Stroke: Vascular and Interventional Neurology 2022;2:e000132.
- 94
- Yang X, Zhang S, Dong Z, et al. Insulin resistance is a risk factor for overall cerebral small vessel disease burden in old nondiabetic healthy adult population. Front Aging Neurosci 2019;11:127.
- 95
- Zhang Y, Wang L, He M. Isolated INO as a presentation of midbrain paramedian area lacunar infarction in patients with diabetes. J Clin Neurosci 2017;45:261-4. PMID 28869134
Contributors
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Authors
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Hugo J Aparicio MD MPH
Dr. Aparicio of Boston University School of Medicine has no relevant financial relationships to disclose.
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Rakhee Lalla MD
Dr. Lalla of Boston Medical Center has no relevant financial relationships to disclose.
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Jose Gutierrez MD MPH
Dr. Gutierrez of Columbia University has no relevant financial relationships to disclose.
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Editor
-
Steven R Levine MD
Dr. Levine of the SUNY Health Science Center at Brooklyn has no relevant financial relationships to disclose.
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Former Authors
- Mary-Ann Fares MD
- Christina A Wilson MD PhD
- Anna Khanna MD
- Vladimir Hachinski MD, John Maher MB (original authors), Patrick Pullicino MD, and Catalina Ionita MD
Patient Profile
- Age range of presentation
-
- 19 to 65+ years
- Sex preponderance
-
- male>female, >2:1
- Heredity
-
- heredity may be a factor
- autosomal dominant in CADASIL
- Population groups selectively affected
-
- Hispanics
- Japanese
- People of African descent
- Occupation groups selectively affected
-
- none selectively affected
ICD & OMIM codes
- ICD
-
- Cerebral artery occlusion, unspecified: 434.9
- Cerebral infarction due to unspecified occlusion or stenosis of cerebral arteries: I63.5
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