Stroke Cerebrovasc Dis 2017; 26:1254. 92. Kwon HS, Cho AH, Lee MH, et al. Evolution of acute lacunar lesions in terms of size and shape: a PICASSO sub-study. J Neurol 2019; 266:766. 93. Arboix A, Mart -Vilalta JL, Pujol J, Sanz M. Lacunar cerebral infarct and nuclear magnetic resonance. A review of sixty cases. Eur Neurol 1990; 30:47. 94. Brown JJ, Hesselink JR, Rothrock JF. MR and CT of lacunar infarcts. AJR Am J Roentgenol 1988; 151:367. 95. Singer MB, Chong J, Lu D, et al. Diffusion-weighted MRI in acute subcortical infarction. Stroke 1998; 29:133. 96. 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. 97. Boiten J, Lodder J. Lacunar infarcts. Pathogenesis and validity of the clinical syndromes. Stroke 1991; 22:1374. 98. Gorman MJ, Dafer R, Levine SR. Ataxic hemiparesis: critical appraisal of a lacunar syndrome. Stroke 1998; 29:2549. 99. Melo TP, Bogousslavsky J, van Melle G, Regli F. Pure motor stroke: a reappraisal. Neurology 1992; 42:789. 100. 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. 101. Moulin T, Bogousslavsky J, Chopard JL, et al. Vascular ataxic hemiparesis: a re-evaluation. J Neurol Neurosurg Psychiatry 1995; 58:422. 102. Kim JS. Pure sensory stroke. Clinical-radiological correlates of 21 cases. Stroke 1992; 23:983. 103. Herv D, Gautier-Bertrand M, Labreuche J, et al. Predictive values of lacunar transient ischemic attacks. Stroke 2004; 35:1430. 104. Giacomozzi S, Caso V, Agnelli G, et al. Lacunar stroke syndromes as predictors of lacunar and non-lacunar infarcts on neuroimaging: a hospital-based study. Intern Emerg Med 2020; 15:429. https://www.uptodate.com/contents/lacunar-infarcts/print 25/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate 105. Wessels T, R ttger C, Jauss M, et al. Identification of embolic stroke patterns by diffusion- weighted MRI in clinically defined lacunar stroke syndromes. Stroke 2005; 36:757. 106. Mead GE, Lewis SC, Wardlaw JM, et al. How well does the Oxfordshire community stroke project classification predict the site and size of the infarct on brain imaging? J Neurol Neurosurg Psychiatry 2000; 68:558. 107. Stapf C, Hofmeister C, Hartmann A, et al. Predictive value of clinical lacunar syndromes for lacunar infarcts on magnetic resonance brain imaging. Acta Neurol Scand 2000; 101:13. 108. Generalized efficacy of t-PA for acute stroke. Subgroup analysis of the NINDS t-PA Stroke Trial. Stroke 1997; 28:2119. 109. 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. 110. SPS3 Investigators, Benavente OR, Hart RG, et al. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. 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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 https://www.uptodate.com/contents/lacunar-infarcts/print 30/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate Time course of lacunar infarction Penetrating artery occlusions usually cause symptoms that develop over a short period of time, hours or at most a few days, compared to large artery-related brain ischemia which can evolve over a longer period. A stuttering course may ensue, as with large artery thrombosis. This patient had a pure motor hemiparesis. Graphic 52246 Version 1.0 https://www.uptodate.com/contents/lacunar-infarcts/print 31/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate Eligibility criteria for the treatment of acute ischemic stroke with intravenous thrombolysis (recombinant tissue plasminogen activator or tPA) Inclusion criteria Clinical diagnosis of ischemic stroke causing measurable neurologic deficit Onset of symptoms <4.5 hours before beginning treatment; if the exact time of stroke onset is not known, it is defined as the last time the patient was known to be normal or at neurologic baseline Age 18 years Exclusion criteria Patient history Ischemic stroke or severe head trauma in the previous three months Previous intracranial hemorrhage Intra-axial intracranial neoplasm Gastrointestinal malignancy Gastrointestinal hemorrhage in the previous 21 days Intracranial or intraspinal surgery within the prior three months Clinical Symptoms suggestive of subarachnoid hemorrhage Persistent blood pressure elevation (systolic 185 mmHg or diastolic 110 mmHg) Active internal bleeding Presentation consistent with infective endocarditis Stroke known or suspected to be associated with aortic arch dissection Acute bleeding diathesis, including but not limited to conditions defined under 'Hematologic' Hematologic 3 Platelet count <100,000/mm * Current anticoagulant use with an INR >1.7 or PT >15 seconds or aPTT >40 seconds* Therapeutic doses of low molecular weight heparin received within 24 hours (eg, to treat VTE and ACS); this exclusion does not apply to prophylactic doses (eg, to prevent VTE) Current use (ie, last dose within 48 hours in a patient with normal renal function) of a direct thrombin inhibitor or direct factor Xa inhibitor with evidence of anticoagulant effect by laboratory tests such as aPTT, INR, ECT, TT, or appropriate factor Xa activity assays Head CT Evidence of hemorrhage https://www.uptodate.com/contents/lacunar-infarcts/print 32/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate Extensive regions of obvious hypodensity consistent with irreversible injury Warnings Only minor and isolated neurologic signs or rapidly improving symptoms Serum glucose <50 mg/dL (<2.8 mmol/L) Serious trauma in the previous 14 days Major surgery in the previous 14 days History of gastrointestinal bleeding (remote) or genitourinary bleeding Seizure at the onset of stroke with postictal neurologic impairments Pregnancy** Arterial puncture at a noncompressible site in the previous seven days Large ( 10 mm), untreated, unruptured intracranial aneurysm Untreated intracranial vascular malformation Additional warnings for treatment from 3 to 4.5 hours from symptom onset Age >80 years Oral anticoagulant use regardless of INR Severe stroke (NIHSS score >25) Combination of both previous ischemic stroke and diabetes mellitus ACS: acute coronary syndrome; aPTT: activated partial thromboplastin time; ECT: ecarin clotting time; INR: international normalized ratio; PT: prothrombin time; NIHSS: National Institutes of Health Stroke Scale; tPA: intravenous alteplase; TT: thrombin time; VTE: venous thromboembolism. Although it is desirable to know the results of these tests, thrombolytic therapy should not be delayed while results are pending unless (1) there is clinical suspicion of a bleeding abnormality or thrombocytopenia, (2) the patient is currently on or has recently received anticoagulants (eg, heparin, warfarin, a direct thrombin inhibitor, or a direct factor Xa inhibitor), or (3) use of anticoagulants is not known. Otherwise, treatment with intravenous tPA can be started before availability of coagulation test results but should be discontinued if the INR, PT, or aPTT exceed the limits stated in the table, or 3 if platelet count is <100,000 mm . With careful consideration and weighting of risk-to-benefit, patients may receive intravenous alteplase despite one or more warnings. Patients who have a persistent neurologic deficit that is potentially disabling, despite improvement of any degree, should be treated with tPA in the absence of other contraindications. Any of the following should be considered disabling deficits: Complete hemianopia: 2 on NIHSS question 3, or Severe aphasia: 2 on NIHSS question 9, or Visual or sensory extinction: 1 on NIHSS question 11, or Any weakness limiting sustained effort against gravity: 2 on NIHSS question 5 or 6, or Any deficits that lead to a total NIHSS >5, or https://www.uptodate.com/contents/lacunar-infarcts/print 33/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate Any remaining deficit considered potentially disabling in the view of the patient and the treating practitioner using clinical judgment Patients may be treated with intravenous alteplase if glucose level is subsequently normalized. The potential risks of bleeding with alteplase from injuries related to the trauma should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. The increased risk of surgical site bleeding with alteplase should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. There is a low increased risk of new bleeding with alteplase in the setting of past gastrointestinal or genitourinary bleeding. However, alteplase administration within 21 days of gastrointestinal bleeding is not recommended. Alteplase is reasonable in patients with a seizure at stroke onset if evidence suggests that residual impairments are secondary to acute ischemic stroke and not to a postictal phenomenon. * Alteplase can be given in pregnancy when the anticipated benefits of treating moderate or severe stroke outweigh the anticipated increased risks of uterine bleeding. The safety and efficacy of administering alteplase is uncertain for these relative exclusions. Although these were exclusions in the trial showing benefit in the 3 to 4.5 hour window, intravenous alteplase appears to be safe and may be beneficial for patients with these criteria, including patients taking oral anticoagulants with an INR <1.7. Adapted from: 1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359:1317. 2. Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. A science advisory from the American Heart Association/American Stroke Association. Stroke 2009; 40:2945. 3. Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force:, Levine SR, Khatri P, et al. Review, historical context, and clari cations of the NINDS rt-PA stroke trials exclusion criteria: Part 1: rapidly improving stroke symptoms. Stroke 2013; 44:2500. 4. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scienti c rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2016; 47:581. 5. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2019; 50:e344. Graphic 71462 Version 26.0 https://www.uptodate.com/contents/lacunar-infarcts/print 34/35 7/6/23, 12:00 PM Lacunar infarcts - UpToDate Contributor Disclosures Jamary Oliveira-Filho, MD, MS, PhD No relevant financial relationship(s) with ineligible companies to disclose. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/lacunar-infarcts/print 35/35