Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Lacunar infarcts

Jamary Oliveira Filho, MD, MS, PhD
Section Editor
Scott E Kasner, MD
Deputy Editor
John F Dashe, MD, PhD


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 [1]. These branches arise at acute angles from the large arteries of the circle of Willis, stem of the middle cerebral artery (MCA), or the basilar artery. Although this definition implies that pathological confirmation is necessary, diagnosis in vivo may be made in the setting of appropriate clinical syndromes and radiological tests.


Dechambre first used the term "lacune" in 1838 to describe softenings in subcortical regions of the brain found on autopsy [2]. At the time, there was dispute regarding whether these lacunes were caused by encephalitis, a late phase of a small hemorrhage, or ischemic necrosis. Marie in 1901 first described a clinical syndrome associated with multiple lacunes, characterized by sudden hemiplegia with good recovery, a characteristic gait with small steps ("marche a petits pas de Dejerine"), pseudobulbar palsy, and dementia [3].

In the 1960s, careful clinicopathological correlations by Fisher generated the so-called "lacunar hypothesis," which suggested that lacunes are due to a chronic vasculopathy related to systemic hypertension, cause a variety of defined clinical syndromes, and imply a generally good prognosis [4].

The introduction of CT and MRI has generated data that both supports and opposes the lacunar theory [5,6]. Some authors have suggested abandoning the concept altogether [7,8]. Detractors of the lacunar hypothesis note the lack of animal data or an animal model of lacunar infarction and the demonstration of embolic sources from the heart, aorta, or large arteries in a substantial percentage of lacunar strokes [9,10]. Proponents concede that some small number of lacunes may result from emboli, but they point out that the proportion of embolic sources found in association with lacunar syndromes is far lower than for other ischemic stroke types and that there are clear clinical and epidemiologic reasons to separate lacunes from other ischemic stroke subtypes [10,11].

One of the major difficulties in interpreting these data stems from the inability of imaging techniques to show that an infarct was due to occlusion of a single penetrating artery. Furthermore, various studies have used different sets of criteria to define "lacunar infarcts" and the many lacunar syndromes [12,13]. However, continuing publications on the subject have demonstrated that the term "lacune" is clinically useful and has gained wide acceptance in the literature.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Aug 28, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Fisher CM. Lacunar strokes and infarcts: a review. Neurology 1982; 32:871.
  2. Dechambre A. Mémoire sur la curabilité du ramollissement cérébral. Gaz Med Paris 1838; 6:305.
  3. Marie P. Des foyers lacunaires de désintégration et de différents autres états cavitaires du cerveau. Rev Méd (Paris) 1901; 21:281.
  5. Bamford JM, Warlow CP. Evolution and testing of the lacunar hypothesis. Stroke 1988; 19:1074.
  6. Bogousslavsky J. The plurality of subcortical infarction. Stroke 1992; 23:629.
  7. Millikan C, Futrell N. The fallacy of the lacune hypothesis. Stroke 1990; 21:1251.
  8. Landau WM. Clinical neuromythology VI. Au clair de lacune: holy, wholly, holey logic. Neurology 1989; 39:725.
  9. Futrell N. Lacunar infarction: embolism is the key. Stroke 2004; 35:1778.
  10. Davis SM, Donnan GA. Why lacunar syndromes are different and important. Stroke 2004; 35:1780.
  11. Norrving B. Lacunar infarction: embolism is the key: against. Stroke 2004; 35:1779.
  12. Baumgartner RW, Sidler C, Mosso M, Georgiadis D. Ischemic lacunar stroke in patients with and without potential mechanism other than small-artery disease. Stroke 2003; 34:653.
  13. Caplan LR. Small deep brain infarcts. Stroke 2003; 34:653.
  14. Hommel M, Besson G, Le Bas JF, et al. Prospective study of lacunar infarction using magnetic resonance imaging. Stroke 1990; 21:546.
  15. Arboix A, Martí-Vilalta JL, García JH. Clinical study of 227 patients with lacunar infarcts. Stroke 1990; 21:842.
  16. Fisher CM. Capsular infarcts: the underlying vascular lesions. Arch Neurol 1979; 36:65.
  17. Feekes JA, Hsu SW, Chaloupka JC, Cassell MD. Tertiary microvascular territories define lacunar infarcts in the basal ganglia. Ann Neurol 2005; 58:18.
  18. Caplan LR. Intracranial branch atheromatous disease: a neglected, understudied, and underused concept. Neurology 1989; 39:1246.
  19. Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 2013; 12:483.
  20. Lee DK, Kim JS, Kwon SU, et al. Lesion patterns and stroke mechanism in atherosclerotic middle cerebral artery disease: early diffusion-weighted imaging study. Stroke 2005; 36:2583.
  21. Macdonald RL, Kowalczuk A, Johns L. Emboli enter penetrating arteries of monkey brain in relation to their size. Stroke 1995; 26:1247.
  22. Hart RG, Foster JW, Luther MF, Kanter MC. Stroke in infective endocarditis. Stroke 1990; 21:695.
  23. Cacciatore A, Russo LS Jr. Lacunar infarction as an embolic complication of cardiac and arch angiography. Stroke 1991; 22:1603.
  24. Wardlaw JM, Sandercock PA, Dennis MS, Starr J. Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia? Stroke 2003; 34:806.
  25. Wardlaw JM. What causes lacunar stroke? J Neurol Neurosurg Psychiatry 2005; 76:617.
  26. Wardlaw JM, Doubal F, Armitage P, et al. Lacunar stroke is associated with diffuse blood-brain barrier dysfunction. Ann Neurol 2009; 65:194.
  27. Ihara M, Yamamoto Y. Emerging Evidence for Pathogenesis of Sporadic Cerebral Small Vessel Disease. Stroke 2016; 47:554.
  28. Tomimoto H, Akiguchi I, Suenaga T, et al. Alterations of the blood-brain barrier and glial cells in white-matter lesions in cerebrovascular and Alzheimer's disease patients. Stroke 1996; 27:2069.
  29. Lammie GA, Brannan F, Wardlaw JM. Incomplete lacunar infarction (Type Ib lacunes). Acta Neuropathol 1998; 96:163.
  30. Giwa MO, Williams J, Elderfield K, et al. Neuropathologic evidence of endothelial changes in cerebral small vessel disease. Neurology 2012; 78:167.
  31. Lammie GA, Brannan F, Slattery J, Warlow C. Nonhypertensive cerebral small-vessel disease. An autopsy study. Stroke 1997; 28:2222.
  32. Jackson C, Sudlow C. Comparing risks of death and recurrent vascular events between lacunar and non-lacunar infarction. Brain 2005; 128:2507.
  33. Chamorro A, Sacco RL, Mohr JP, et al. Clinical-computed tomographic correlations of lacunar infarction in the Stroke Data Bank. Stroke 1991; 22:175.
  34. Horowitz DR, Tuhrim S, Weinberger JM, Rudolph SH. Mechanisms in lacunar infarction. Stroke 1992; 23:325.
  35. Tegeler CH, Shi F, Morgan T. Carotid stenosis in lacunar stroke. Stroke 1991; 22:1124.
  36. Sacco SE, Whisnant JP, Broderick JP, et al. Epidemiological characteristics of lacunar infarcts in a population. Stroke 1991; 22:1236.
  37. Inzitari D, Eliasziw M, Sharpe BL, et al. Risk factors and outcome of patients with carotid artery stenosis presenting with lacunar stroke. North American Symptomatic Carotid Endarterectomy Trial Group. Neurology 2000; 54:660.
  38. Tejada J, Díez-Tejedor E, Hernández-Echebarría L, Balboa O. Does a relationship exist between carotid stenosis and lacunar infarction? Stroke 2003; 34:1404.
  39. Ay H, Oliveira-Filho J, Buonanno FS, et al. Diffusion-weighted imaging identifies a subset of lacunar infarction associated with embolic source. Stroke 1999; 30:2644.
  40. Wessels T, Röttger C, Jauss M, et al. Identification of embolic stroke patterns by diffusion-weighted MRI in clinically defined lacunar stroke syndromes. Stroke 2005; 36:757.
  41. Sacco S, Marini C, Totaro R, et al. A population-based study of the incidence and prognosis of lacunar stroke. Neurology 2006; 66:1335.
  42. Petty GW, Brown RD Jr, Whisnant JP, et al. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke 1999; 30:2513.
  43. Woo D, Gebel J, Miller R, et al. Incidence rates of first-ever ischemic stroke subtypes among blacks: a population-based study. Stroke 1999; 30:2517.
  44. Kubo M, Kiyohara Y, Ninomiya T, et al. Decreasing incidence of lacunar vs other types of cerebral infarction in a Japanese population. Neurology 2006; 66:1539.
  45. Bezerra DC, Sharrett AR, Matsushita K, et al. Risk factors for lacune subtypes in the Atherosclerosis Risk in Communities (ARIC) Study. Neurology 2012; 78:102.
  46. Bots ML, Launer LJ, Lindemans J, et al. Homocysteine and short-term risk of myocardial infarction and stroke in the elderly: the Rotterdam Study. Arch Intern Med 1999; 159:38.
  47. Eikelboom JW, Hankey GJ, Anand SS, et al. Association between high homocyst(e)ine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke 2000; 31:1069.
  48. Iso H, Moriyama Y, Sato S, et al. Serum total homocysteine concentrations and risk of stroke and its subtypes in Japanese. Circulation 2004; 109:2766.
  49. Khan U, Porteous L, Hassan A, Markus HS. Risk factor profile of cerebral small vessel disease and its subtypes. J Neurol Neurosurg Psychiatry 2007; 78:702.
  50. Jackson CA, Hutchison A, Dennis MS, et al. Differing risk factor profiles of ischemic stroke subtypes: evidence for a distinct lacunar arteriopathy? Stroke 2010; 41:624.
  51. Knopman DS, Penman AD, Catellier DJ, et al. Vascular risk factors and longitudinal changes on brain MRI: the ARIC study. Neurology 2011; 76:1879.
  52. Lodder J, Bamford JM, Sandercock PA, et al. Are hypertension or cardiac embolism likely causes of lacunar infarction? Stroke 1990; 21:375.
  53. van Dijk EJ, Prins ND, Vermeer SE, et al. Plasma amyloid beta, apolipoprotein E, lacunar infarcts, and white matter lesions. Ann Neurol 2004; 55:570.
  54. de Leeuw FE, Richard F, de Groot JC, et al. Interaction between hypertension, apoE, and cerebral white matter lesions. Stroke 2004; 35:1057.
  55. Jannes J, Hamilton-Bruce MA, Pilotto L, et al. Tissue plasminogen activator -7351C/T enhancer polymorphism is a risk factor for lacunar stroke. Stroke 2004; 35:1090.
  56. Hassan A, Lansbury A, Catto AJ, et al. Angiotensin converting enzyme insertion/deletion genotype is associated with leukoaraiosis in lacunar syndromes. J Neurol Neurosurg Psychiatry 2002; 72:343.
  57. Richards A, van den Maagdenberg AM, Jen JC, et al. C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat Genet 2007; 39:1068.
  58. Grand MG, Kaine J, Fulling K, et al. Cerebroretinal vasculopathy. A new hereditary syndrome. Ophthalmology 1988; 95:649.
  59. Jen J, Cohen AH, Yue Q, et al. Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). Neurology 1997; 49:1322.
  60. Vodopivec I, Oakley DH, Perugino CA, et al. A 44-year-old man with eye, kidney, and brain dysfunction. Ann Neurol 2016; 79:507.
  61. Kolar GR, Kothari PH, Khanlou N, et al. Neuropathology and genetics of cerebroretinal vasculopathies. Brain Pathol 2014; 24:510.
  62. Stam AH, Kothari PH, Shaikh A, et al. Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. Brain 2016.
  63. Hara K, Shiga A, Fukutake T, et al. Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. N Engl J Med 2009; 360:1729.
  64. Nozaki H, Nishizawa M, Onodera O. Features of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke 2014; 45:3447.
  65. Bugiani M, Kevelam SH, Bakels HS, et al. Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL). Neurology 2016; 87:1777.
  66. Verdura E, Hervé D, Scharrer E, et al. Heterozygous HTRA1 mutations are associated with autosomal dominant cerebral small vessel disease. Brain 2015; 138:2347.
  67. Vahedi K, Massin P, Guichard JP, et al. Hereditary infantile hemiparesis, retinal arteriolar tortuosity, and leukoencephalopathy. Neurology 2003; 60:57.
  68. Gould DB, Phalan FC, van Mil SE, et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med 2006; 354:1489.
  69. Sibon I, Coupry I, Menegon P, et al. COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke. Ann Neurol 2007; 62:177.
  70. Vahedi K, Boukobza M, Massin P, et al. Clinical and brain MRI follow-up study of a family with COL4A1 mutation. Neurology 2007; 69:1564.
  71. Steinke W, Ley SC. Lacunar stroke is the major cause of progressive motor deficits. Stroke 2002; 33:1510.
  72. Gan R, Sacco RL, Kargman DE, et al. Testing the validity of the lacunar hypothesis: the Northern Manhattan Stroke Study experience. Neurology 1997; 48:1204.
  73. Boiten J, Lodder J. Lacunar infarcts. Pathogenesis and validity of the clinical syndromes. Stroke 1991; 22:1374.
  74. Gorman MJ, Dafer R, Levine SR. Ataxic hemiparesis: critical appraisal of a lacunar syndrome. Stroke 1998; 29:2549.
  75. Melo TP, Bogousslavsky J, van Melle G, Regli F. Pure motor stroke: a reappraisal. Neurology 1992; 42:789.
  76. Toni D, Del Duca R, Fiorelli M, et al. Pure motor hemiparesis and sensorimotor stroke. Accuracy of very early clinical diagnosis of lacunar strokes. Stroke 1994; 25:92.
  77. Moulin T, Bogousslavsky J, Chopard JL, et al. Vascular ataxic hemiparesis: a re-evaluation. J Neurol Neurosurg Psychiatry 1995; 58:422.
  78. Kim JS. Pure sensory stroke. Clinical-radiological correlates of 21 cases. Stroke 1992; 23:983.
  79. Hervé D, Gautier-Bertrand M, Labreuche J, et al. Predictive values of lacunar transient ischemic attacks. Stroke 2004; 35:1430.
  80. Toni D, Iweins F, von Kummer R, et al. Identification of lacunar infarcts before thrombolysis in the ECASS I study. Neurology 2000; 54:684.
  82. Bamford J, Sandercock P, Jones L, Warlow C. The natural history of lacunar infarction: the Oxfordshire Community Stroke Project. Stroke 1987; 18:545.
  83. Schonewille WJ, Tuhrim S, Singer MB, Atlas SW. Diffusion-weighted MRI in acute lacunar syndromes. A clinical-radiological correlation study. Stroke 1999; 30:2066.
  84. Donnan GA, O'Malley HM, Quang L, et al. The capsular warning syndrome: pathogenesis and clinical features. Neurology 1993; 43:957.
  87. Mohr JP, Kase CS, Meckler RJ, Fisher CM. Sensorimotor stroke due to thalamocapsular ischemia. Arch Neurol 1977; 34:739.
  88. Fisher CM. A lacunar stroke. The dysarthria-clumsy hand syndrome. Neurology 1967; 17:614.
  89. Bogousslavsky J, Regli F, Assal G. The syndrome of unilateral tuberothalamic artery territory infarction. Stroke 1986; 17:434.
  90. Bogousslavsky J, Regli F, Uske A. Thalamic infarcts: clinical syndromes, etiology, and prognosis. Neurology 1988; 38:837.
  91. Perani D, Vallar G, Cappa S, et al. Aphasia and neglect after subcortical stroke. A clinical/cerebral perfusion correlation study. Brain 1987; 110 ( Pt 5):1211.
  92. Pappata S, Mazoyer B, Tran Dinh S, et al. Effects of capsular or thalamic stroke on metabolism in the cortex and cerebellum: a positron tomography study. Stroke 1990; 21:519.
  93. Kwan LT, Reed BR, Eberling JL, et al. Effects of subcortical cerebral infarction on cortical glucose metabolism and cognitive function. Arch Neurol 1999; 56:809.
  94. Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003; 348:1215.
  95. Mungas D, Harvey D, Reed BR, et al. Longitudinal volumetric MRI change and rate of cognitive decline. Neurology 2005; 65:565.
  96. van Dijk EJ, Prins ND, Vrooman HA, et al. Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan study. Stroke 2008; 39:2712.
  97. Jokinen H, Gouw AA, Madureira S, et al. Incident lacunes influence cognitive decline: the LADIS study. Neurology 2011; 76:1872.
  98. Arboix A, Martí-Vilalta JL, Pujol J, Sanz M. Lacunar cerebral infarct and nuclear magnetic resonance. A review of sixty cases. Eur Neurol 1990; 30:47.
  99. Brown JJ, Hesselink JR, Rothrock JF. MR and CT of lacunar infarcts. AJR Am J Roentgenol 1988; 151:367.
  100. Singer MB, Chong J, Lu D, et al. Diffusion-weighted MRI in acute subcortical infarction. Stroke 1998; 29:133.
  101. Oliveira-Filho J, Ay H, Schaefer PW, et al. Diffusion-weighted magnetic resonance imaging identifies the "clinically relevant" small-penetrator infarcts. Arch Neurol 2000; 57:1009.
  102. Koch S, McClendon MS, Bhatia R. Imaging evolution of acute lacunar infarction: leukoariosis or lacune? Neurology 2011; 77:1091.
  103. Khan A, Kasner SE, Lynn MJ, et al. Risk factors and outcome of patients with symptomatic intracranial stenosis presenting with lacunar stroke. Stroke 2012; 43:1230.
  104. Generalized efficacy of t-PA for acute stroke. Subgroup analysis of the NINDS t-PA Stroke Trial. Stroke 1997; 28:2119.
  105. Kwok CS, Shoamanesh A, Copley HC, et al. Efficacy of antiplatelet therapy in secondary prevention following lacunar stroke: pooled analysis of randomized trials. Stroke 2015; 46:1014.
  106. SPS3 Investigators, Benavente OR, Hart RG, et al. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med 2012; 367:817.
  107. Mohr JP, Thompson JL, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001; 345:1444.
  108. Low molecular weight heparinoid, ORG 10172 (danaparoid), and outcome after acute ischemic stroke: a randomized controlled trial. The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. JAMA 1998; 279:1265.
  109. Hart RG, Pearce LA, Bakheet MF, et al. Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial. J Stroke Cerebrovasc Dis 2014; 23:618.
  110. Shoamanesh A, Pearce LA, Bazan C, et al. Microbleeds in the Secondary Prevention of Small Subcortical Strokes Trial: Stroke, mortality, and treatment interactions. Ann Neurol 2017; 82:196.
  111. Samuelsson M, Söderfeldt B, Olsson GB. Functional outcome in patients with lacunar infarction. Stroke 1996; 27:842.