syndromes (as a group) had a positive predictive value as high as 87 to 90 percent for detecting a radiological lacune [77,97], although some clinical syndromes were more predictive than others [98-102]. Preceding TIAs and nonsudden onset increased the positive predictive value for these lacunar syndromes in another report [103]. Clinical presentation does not always predict actual stroke type Patients with lacunar syndromes identified clinically are sometimes found to have an acute nonlacunar infarct by imaging. In one report of 478 patients with lacunar syndromes nonlacunar infarcts were https://www.uptodate.com/contents/lacunar-infarcts/print 12/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate the cause in 21 percent [104]. Another study evaluated 73 patients presenting with lacunar syndromes; all underwent DWI as well as extensive neurovascular and cardiac evaluations for potential embolic sources [105]. DWI radiologic patterns suggestive of nonlacunar infarction (mainly embolism) were seen in a total of 30 patients (41 percent); of these, 16 had one large or multiple acute lesions within a single vascular territory, and another 14 had multiple infarcts in different vascular territories [105]. Patients with more than one infarct on DWI were significantly more likely to have a clinically proven embolic source, although no embolic source was found in nine patients with a DWI pattern suggestive of a nonlacunar/embolic stroke mechanism. Conversely, brain imaging may identify acute lacunar infarcts that were not classified as lacunar syndromes on initial clinical evaluation [88]. In addition, the false negative rate with CT scan (ie, acute lacunar syndrome but no acute stroke on CT) ranges from 35 to 50 percent [87,106,107]. An inherent difficulty of both CT and conventional MRI, but not DWI, is the ability to differentiate between acute and chronic lesions. In one study, 16 percent of patients presenting with a lacunar syndrome had at least two lesions on conventional MRI that correlated with clinical symptoms [15]. Furthermore, in patients presenting with a lacunar syndrome, multiple chronic subcortical lesions are not rare, occurring in approximately 42 to 75 percent of cases [5,93]. For these reasons, knowledge of possible lesion locations based upon neurologic findings is necessary before implicating a particular lesion found on head CT or conventional MRI as responsible for the clinical symptoms ( table 2). Other studies Genetic screening for pathogenic variants in NOTCH3 is appropriate if there is suspicion for CADASIL, as suggested by a family history of stroke and dementia, absence of hypertension or known vascular risk factors, and clinical features including TIA and ischemic stroke predominately involving small vessels, cognitive deficits with early executive dysfunction, migraine with aura, neuropsychiatric disturbances, and brain MRI with white matter hyperintensities on T2 imaging in the anterior temporal lobes and external capsule. (See "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)".) ACUTE TREATMENT All patients with acute ischemic stroke should be evaluated to determine eligibility for reperfusion therapy with intravenous thrombolysis and/or mechanical thrombectomy. Screening https://www.uptodate.com/contents/lacunar-infarcts/print 13/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate patients with acute stroke for reperfusion therapies begins immediately upon presentation, even before the diagnosis is confirmed. (See 'Rapid evaluation' above.) Aspirin and other antithrombotic agents should not be given alone or in combination for the first 24 hours following treatment with intravenous thrombolysis. Otherwise, in the absence of contraindications, antiplatelet agents should be started as soon as possible after the diagnosis of transient ischemic attack (TIA) or ischemic stroke is confirmed, even before the evaluation for ischemic mechanism is complete. Reperfusion therapy Randomized controlled trials have shown that intravenous alteplase (recombinant tissue-type plasminogen activator or tPA) improves functional outcome from ischemic stroke and that benefits outweigh the risks for eligible patients who receive treatment within 4.5 hours of symptom onset (or within 4.5 hours of when the patient was last seen normal in cases when onset time is unknown). Intravenous thrombolysis may also be beneficial for select patients who wake-up with stroke more than 4.5 hours after they were last known well or those who have unknown time of symptom onset, if they have an acute ischemic brain lesion detected on diffusion MRI but no corresponding hyperintensity on fluid-attenuated inversion recovery (FLAIR) MRI. (See "Approach to reperfusion therapy for acute ischemic stroke", section on 'Alteplase'.) Most clinical trials investigating stroke treatment and prevention have failed to adequately study the lacunar infarct subpopulation. Nevertheless, subgroup analysis of trial data suggest that the benefit with thrombolysis is sustained in patients with lacunar stroke [108]. However, stroke subtype was classified mainly by clinical impression in the thrombolysis trials since vascular studies usually were not performed before treatment initiation. Thus, some patients with a large vessel or cardioembolic stroke mechanism (eg, those with proximal middle cerebral artery occlusion, good leptomeningeal collaterals, and recanalization after thrombolysis) may have been incorrectly classified as having a small vessel etiology. Nonetheless, until better data are available, we recommend that patients with lacunar syndromes be selected for thrombolysis according to current guidelines in the same way as patients with other subtypes of ischemic stroke ( table 3). (See "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use".) Thrombolytic therapy is associated with a 6 percent risk of symptomatic brain hemorrhage. This treatment option should be discussed with the patient and family in each individual case. Antiplatelet therapy Most patients with acute ischemic stroke should be treated with early antiplatelet therapy, and short-term dual antiplatelet therapy may be appropriate for https://www.uptodate.com/contents/lacunar-infarcts/print 14/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate select patients with high-risk TIA or minor ischemic stroke. This topic is discussed separately. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".) SECONDARY PREVENTION Most patients with ischemic stroke or transient ischemic attack (TIA) should be treated with intensive medical intervention and risk factor management, including blood pressure control, antiplatelet and statin therapy, and lifestyle modification. These interventions for secondary prevention apply both to patients who present with stroke or TIA and to patients who have no history of symptomatic stroke but have imaging evidence of lacunar infarction (ie, silent stroke). However, the risk/benefit of antiplatelet therapy has not been adequately studied for patients with silent lacunar infarcts. (See "Overview of secondary prevention of ischemic stroke".) After the acute phase of stroke (when permissive hypertension is often employed) antihypertensive therapy should be resumed in previously treated, neurologically stable patients with known hypertension for prevention of recurrent stroke and other vascular events. In addition, antihypertensive therapy should be started in previously untreated, neurologically stable patients with any type of stroke or TIA who have an established blood pressure that is above goal. (See "Antihypertensive therapy for secondary stroke prevention".) Beyond the acute phase of TIA and ischemic stroke (ie, >21 days), and in the absence of an indication for oral anticoagulation, long-term single-agent antiplatelet therapy for secondary stroke prevention should be continued with aspirin, clopidogrel, or aspirin- extended-release dipyridamole. Long-term dual antiplatelet therapy with aspirin and clopidogrel is not recommended. (See "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke".) Patients with ischemic stroke, all of whom are at high risk for recurrent cerebrovascular and cardiovascular events, should receive high-intensity statin therapy. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".) Recommended lifestyle modifications to reduce the risk of stroke include smoking cessation, limited alcohol consumption, weight control, regular aerobic physical activity, salt restriction, and a Mediterranean diet. (See "Overview of secondary prevention of ischemic stroke", section on 'Lifestyle modification'.) https://www.uptodate.com/contents/lacunar-infarcts/print 15/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate The efficacy of aspirin and other antiplatelet agents for preventing second strokes and mortality has been illustrated for patients with noncardioembolic ischemic stroke in general (see "Long- term antithrombotic therapy for the secondary prevention of ischemic stroke"). A 2015 meta- analysis identified two trials that evaluated antiplatelets versus placebo and reported outcomes in the subgroup of patients with lacunar stroke; in the pooled analysis, treatment with any single antiplatelet agent was associated with a significant reduction in ischemic stroke recurrence (relative risk 0.48, 95% CI 0.30-0.78) [109]. Despite early enthusiasm, results from the SPS3 trial suggest that the long-term use of combined antiplatelet therapy with aspirin plus clopidogrel is harmful for patients with lacunar stroke because it leads to an increased risk of hemorrhage and death but does not reduce the risk of recurrent stroke [110]. Therefore, it should not be employed for secondary prevention in this population in the absence of proven indications. The use of aspirin plus clopidogrel for prevention of different subtypes of ischemic stroke is discussed separately in detail. (See "Long- term antithrombotic therapy for the secondary prevention of ischemic stroke", section on 'Aspirin plus clopidogrel'.) PROGNOSIS Short-term outcomes Lacunar infarcts have a better short-term prognosis than infarcts due to other stroke mechanisms, at least up to one year after onset. As examples, 91 percent of patients with lacunar stroke from the placebo arm of a controlled clinical trial had a favorable outcome at three months, as defined by moderate to good recovery on the Glasgow Outcome Scale [111]. This contrasts with strokes due to large vessel atherosclerosis; only 55 percent of these patients had a favorable outcome at three months. In a later prospective study of 1425 ischemic stroke survivors, patients with lacunar stroke (n = 234) were more likely to have further neurologic improvement between three months and one year compared with patients with nonlacunar stroke [112]. Long-term outcomes The long-term prognosis after lacunar stroke may not differ greatly from nonlacunar stroke. This observation comes from a systematic review of 19 cohort studies involving 2402 patients with lacunar and 3462 patients with nonlacunar ischemic stroke [23]. The odds of death were significantly greater following nonlacunar than lacunar infarction at one month, 1 to 12 months, and one to five years (odds ratio [OR] 3.81, 2.32 and 1.77, respectively), although the difference gradually decreased. However, the odds of recurrent stroke were significantly greater for nonlacunar infarction only at one month (OR 2.11), and the difference in stroke recurrence between nonlacunar and lacunar groups was nonsignificant at 1 to 12 months and one to five years. https://www.uptodate.com/contents/lacunar-infarcts/print 16/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate Analogous findings were reported in a population-based study from Italy [47]. Patients with lacunar stroke (n = 491) had better five-year survival than patients with nonlacunar stroke (n = 2153), mainly due to lower mortality within the first year of follow-up for the lacunar stroke group. The lacunar group also had a lower average annual stroke recurrence rate within the first year. However, stroke recurrence and mortality rates were similar in the two groups from the second year through study completion at five years. Outcome predictors Among patients with recent lacunar stroke, factors associated with an increased risk of ischemic stroke recurrence include a prior lacunar stroke or transient ischemic attack (TIA), diabetes, being from a Black population, and male sex [113]. In addition, the risk of stroke recurrence is increased in the presence of cerebral microbleeds [114]. Patients with lacunar infarction and more severe initial motor deficits have worse functional outcome [108,115]. What is not known is whether patients with a lacunar infarct due to embolism or large vessel atherosclerosis obstructing the ostium of a penetrator branch have a different prognosis and response to therapy. As long as this question remains, investigation of the operating stroke mechanism remains important. (See 'Etiology' above.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".) SUMMARY AND RECOMMENDATIONS Description and location Lacunar infarcts are small (0.2 to 15 mm in diameter) noncortical infarcts caused by occlusion of a single penetrating branch of a large cerebral artery. These branches arise at acute angles from the large arteries of the circle of Willis, stem of the middle cerebral artery, and the basilar artery ( figure 1). Most lacunes occur in the basal ganglia (putamen, globus pallidus, caudate), thalamus, subcortical white matter (internal capsule and corona radiata), and pons. (See 'Introduction and definition' above and 'History' above and 'Vascular anatomy' above.) Etiology Several mechanisms for occlusion of small penetrator branches have been described (see 'Etiology' above): https://www.uptodate.com/contents/lacunar-infarcts/print 17/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate Hypertensive microangiopathy Branch atheromatous disease Embolism from cardiac or large artery sources Endothelial dysfunction and associated blood-brain barrier disruption Epidemiology Lacunes account for 15 to 26 percent of ischemic strokes. (See 'Epidemiology' above.) Risk factors The main risk factor and mechanism for lacunar stroke is related to a chronic vasculopathy associated with systemic hypertension. Other likely risk factors include diabetes mellitus and possibly smoking. (See 'Risk factors and associations' above.) Clinical features Lacunar syndromes More than 20 lacunar syndromes have been described. The five classic lacunar syndromes ( table 2), which may present as transient ischemic attacks (TIAs) in addition to stroke, are named according to their clinical features: - - - - Pure motor hemiparesis (see 'Pure motor hemiparesis' above) Pure sensory stroke (see 'Pure sensory stroke' above) Ataxic hemiparesis (see 'Ataxic hemiparesis' above) Sensorimotor stroke (see 'Sensorimotor stroke' above) Dysarthria-clumsy hand syndrome (see 'Dysarthria-clumsy hand syndrome' above) A large number of atypical lacunar syndromes are also recognized ( table 1). Absence of cortical signs As a general rule, lacunar syndromes lack findings such as aphasia, agnosia, neglect, apraxia, or hemianopsia (so-called "cortical" signs). Monoplegia, stupor, coma, loss of consciousness, and seizures also are typically absent. (See 'Clinical features' above.) Acute stroke evaluation All patients presenting with acute ischemic stroke, including those with suspected lacunar stroke, should be screened for treatment with intravenous thrombolysis and mechanical thrombectomy and be evaluated with a standard stroke evaluation that includes brain and neurovascular imaging, cardiac monitoring, and echocardiography. (See 'Rapid evaluation' above and 'Standard evaluation' above.) Diagnosis Lacunar infarction is suspected in patients who present with a recognized lacunar syndrome (eg, pure motor hemiparesis, pure sensory stroke, ataxic hemiparesis, sensorimotor stroke, dysarthria-clumsy hand syndrome) or other acute stroke symptoms without cortical involvement. The radiologic diagnosis of lacunar infarction relies upon https://www.uptodate.com/contents/lacunar-infarcts/print 18/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate finding a small noncortical infarct on CT or MRI whose location is consistent with the clinical lacunar syndrome defined by history and examination ( image 1). We obtain brain MRI with diffusion-weighted imaging (DWI) and conventional MRI when head CT is nondiagnostic for clinically diagnosed lacunar infarction. (See 'Clinical diagnosis' above and 'Imaging confirmation' above.) Acute treatment Intravenous thrombolysis improves outcomes for eligible patients with ischemic stroke. Aspirin and other antithrombotic agents should not be given alone or in combination for the first 24 hours following treatment with intravenous thrombolysis. Otherwise, in the absence of contraindications, antiplatelet agents should be started as soon as possible after the diagnosis of TIA or ischemic stroke is confirmed, even before the evaluation for ischemic mechanism is complete. (See 'Acute treatment' above.) Secondary prevention For secondary prevention, most patients with ischemic stroke or TIA should be treated with intensive medical intervention and risk factor management, including blood pressure control, antiplatelet and statin therapy, and lifestyle modification. (See 'Secondary prevention' above.) Prognosis Lacunar infarcts usually have a better short-term prognosis than infarcts due to other stroke mechanisms, at least up to one year after onset. However, the long-term prognosis after lacunar stroke may not differ greatly from nonlacunar stroke. (See 'Prognosis' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges J Philip Kistler, MD, who contributed to an earlier version of this topic review. 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Functional outcome in patients with lacunar infarction. Stroke 1996; 27:842. Topic 1136 Version 42.0 https://www.uptodate.com/contents/lacunar-infarcts/print 26/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate GRAPHICS [1-5] Vascular anatomy of lacunar strokes Anatomic location of lenticulostriate, thalamoperforating, and paramedian pontine branches. References: 1. Thieme Atlas of Anatomy: Head and Neuroanatomy, 3rd ed, Ross LM, Lamperti ED, Taub E (Eds), Thieme, Stuttgart 2010. 2. Qureshi AI, Tuhrim S, Broderick JP, et al. Spontaneous intracerebral hemorrhage. N Engl J Med 2001; 344:1450. 3. Kistler, JP, et al, Cerebrovascular diseases, Harrison's Principles of Internal Medicine, 13th ed, McGraw-Hill, New York 1994. Copyright 1994 McGraw-Hill Companies, Inc. 4. Nervous System, Part 1: Anatomy and Physiology (Ciba Collection of Medical Illustrations, Volume 1), Netter FH (Ed), Ciba-Geigy Corporation 1991. 5. Caplan's Stroke: A Clinical Approach, 4th ed, Caplan L, Saunders 2009. Graphic 73027 Version 2.0 https://www.uptodate.com/contents/lacunar-infarcts/print 27/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate Acute lacunar infarction on brain MRI Brain MRI of a 71-year-old woman with a two-day history of left-sided ataxic hemiparesis. Left panels: Diffusion-weighted MRI sequences show two acute lesions, one in the cerebellum (top panel) and one in the thalamocapsular region (bottom panel). T2-weighted (middle panels) and FLAIR (right panels) MRI sequences correctly identify the lesions (arrows), but neither could be called "acute" without diffusion imaging. A high-risk cardiac source (an akinetic left ventricular segment) was found on echocardiogram. MRI: magnetic resonance imaging; FLAIR: fluid-attenuated inversion recovery. Courtesy of Jamary Oliveira-Filho, MD. Graphic 54402 Version 4.0 https://www.uptodate.com/contents/lacunar-infarcts/print 28/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate Other lacunar stroke syndromes Modified pure motor hemiparesis with motor aphasia Pure motor hemiparesis sparing face Mesencephalo-thalamic syndrome Thalamic dementia Pure motor hemiparesis with horizontal gaze palsy Pure motor hemiparesis with crossed third-nerve palsy (Weber syndrome) Pure motor hemiparesis with crossed sixth-nerve palsy Pure motor hemiparesis with confusion Cerebellar ataxia with crossed third-nerve palsy (Claude syndrome) Hemiballismus Lower basilar branch syndrome dizziness, diplopia, gaze palsy, dysarthria, cerebellar ataxia, trigeminal numbness Lateral medullary syndrome Lateral pontomedullary syndrome Locked-in syndrome (bilateral pure motor hemiparesis) Pure dysarthria Acute dystonia of thalamic origin Lacunar state Adapted from: Fisher CM, Neurology 1982; 32:871. Graphic 57474 Version 4.0 https://www.uptodate.com/contents/lacunar-infarcts/print 29/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate Classic lacunar stroke syndromes Positive predictive value Lacunar syndrome Location Clinical findings Pure motor hemiparesis Internal capsule, corona radiata, basal Unilateral paralysis of face, arm and leg, no 52-85 percent pons, medial medulla sensory signs, dysarthria and dysphagia may be present Pure sensory syndrome Thalamus, pontine tegmentum, corona Unilateral numbness of face, arm and leg 95-100 percent radiata without motor deficit Ataxic hemiparesis Internal capsule- corona radiata, basal Unilateral weakness and limb ataxia 59-95 percent pons, thalamus Sensorimotor syndrome Thalamocapsular, maybe basal pons or Hemiparesis or hemiplegia of face, arm 51-87 percent lateral medulla and leg with ipsilateral sensory impairment Dysarthria-clumsy Basal pons, internal Unilateral facial About 96 percent hand syndrome capsule, corona radiata weakness, dysarthria and dysphagia, with mild hand weakness and clumsiness Graphic 67341 Version 4.0