J Am Board Fam Pract: first published as 10.3122/jabfm.1.1.57 on 1 January 1988. Downloaded from Lacunar : Current Concepts Kent W. Davidson, M.D.

Abstract: Lacunar strokes result from occlusion of course of lacunar strokes. Recently, it has been penetrating in the deeper, subcortical parts of demonstrated that lacunar strokes may be embolic the cerebrum and stem. Approximately 19 or hemorrhagic in causation, are not invariably percent of all strokes are of the lacunar variety associated with , and may be larger with lacunar strokes representing the most common and associated with neurological manifestations that cerebrovascular complication of chronic hyperten- do not conform to the classic patterns. In most sion. Four major clinical syndromes are pure motor instances, however, recognition of the characteristic , pure sensory , ataxic hemipare- clinical presentation and confirmation of the diagno- sis, and the -clumsy hand syndrome. The sis with noninvasive studies spare many patients advent of computed tomography (CT) has allowed unnecessary risks associated with anticoagulation, the antemortem study of lacunar disease and has arteriography, or vascular surgery. (JABFP 1988; shed new light on the pathogenesis and clinical 1:57-62.)

It has been estimated that 19 percent of all strokes mid-1960~.~Due to the small size of the infarcts result from occlusion of penetrating arteries in the and the lack of appropriate imaging equipment deeper, subcortical parts of the cerebrum and available at the time, Fisher's work was done brain stem.' These cerebrovascular events are through meticulous brain dissection. Although termed lacunar strokes in reference to the small Fisher's contribution was considerable, several cavities or lacunae that are left behind after infarc- gaps in the understanding of lacunar disease re- tion of brain tissue with subsequent ~avitation.~ sulted from the inherent shortcomings of post- The size of the infarct is generally small, in the mortem histologic study. With the advent of range of 2 to 15 mm in diameter. The most com- computed tomography (CT), which facilitated mon sites for lacunar infarction include the puta- the antemortem study of lacunar strokes, a men, caudate, , , , new body of data has accumulated regarding the and convolutional white matter.%Lacunar disease pathogenesis and the clinical features of lacunar is a common neurological sequela of chronic hy- disease. This new information has augmented pertension and frequently produces characteristic rather than refuted Fisher's work and has pro- http://www.jabfm.org/ clinical syndromes. In many instances, through vided a clearer understanding of lacunar disease recognition of the characteristic clinical presenta- and its management. tion and confirmation of the lacunar stroke with noninvasive studies, patients may be spared the unnecessary risk associated with anticoagulation, Pathophysiology arteriography, or vascular surgery.j The pathological lesions responsible for lacunar on 26 September 2021 by guest. Protected copyright. Although the occurrence of lacunar infarctions strokes vary depending on the size of the vessel was noted as early as 1901,4 years passed until the involved and the size of the resulting infarct. In- pathological processes underlying the lesions and farcts in the range 3-7 mm in diameter involve the clinical features of lacunar strokes were inten- arteries 400 to 200 pm in diameter. The patho- sively investigated. The greatest contribution to logical process responsible for these tiny infarcts is modern understanding of lacunar strokes was called segmental arterial disorganization or lipo- made by Fisher and colleagues beginning in the hyalinosis and is thought to be the result of long- standing hyperten~ion.~,'These vascular lesions result from thickening of the arterial wall through From the Department of Family and Community Medicine, replacement of the normal muscular and elastic College of Medicine, University of Arkansas for Medical Sci- elements with connective tissue and giant macro- ences, Little Rock. Address reprint requests to Kent W. David- phages. Eventually, the arterial lumen is oc- son, M.D.,'Department of Family and Commu~~ityMedicine, College of Medicine, University of Arkansas for Medical Sci- cluded, and infarction occurs. Because of the ences, 4301 W. Markham-Slot X530. Little Rock, AR 72205. small size of the lacunae resulting from this proc-

Lacunar Strokes 57 J Am Board Fam Pract: first published as 10.3122/jabfm.1.1.57 on 1 January 1988. Downloaded from

ess, many of these infarcts are thought to remain ported the incidence of hypertension with lacunar asymptomatic.' infarction in only 57' percent to 65 percent of A second pathological process that involves Reports noting higher associations be- larger arteries in the 400 to 900 pm range also tween lacunar infarction and hypertension in- results from chronic hyperten~ion.',~Atheromata volve primarily patients with one of the classically that develop in the cerebral vessels of normoten- described syndromes with limited neurological in- sive individuals usually occur in the extracranial volvement and small deep infarcts.I6 Infarction in distribution of the carotid and basilar arteries. In these cases was due to lipohyalinosis or micro- individuals with chronic hypertension, the ather- in a penetrating . In series with a omata are more widespread and, additionally, in- lower association between hypertension and lacu- volve intracranial arteries and arterioles. lo When nar infarction, one usually finds larger lacunae these vessels become occluded due to atheroscle- with more complex neurological events and a rotic plaque, infarction results. Infarcts occurring higher frequency of emboli responsible for the in- via this process are generally larger and more farct or hypoperfusion due to extensive extra- symptomatic. cranial atherosclerosis. 14,' A third mechanism involves the obstruction of the penetrating artery due to atherosclerosis of the parent artery. Atherosclerotic plaques block- Clinical Features ing the penetrating arteries from the middle cere- As noted earlier, many lacunar strokes are asymp- bral and basilar arteries have been document- tomatic. This is because the vessels involved are of ed.".12 As would be expected, these infarcts are extremely small size, the area of infarcted tissue is generally larger because the entire region of the small, and the infarction occurs in a relatively si- brain supplied by the involved penetrating artery lent part of the brain. When lacunar strokes are is affected. symptomatic, however, they are often distinctive In Fisher's work, the possibility of embolic phe- in their clinical presentations. Fisher originally de- nomena from the heart or carotid systems causing scribed four clinical syndromes, referred to as la- lacunar strokes was postulated.' Additional data cunar syndromes, that he thought were specific to obtained through the study of patients with deep these infarcts. Subsequent to Fisher's original de- cerebral lesions utilizing CT scanning have con- scriptions, there have been several other neuro- firmed this ass~ciation.'~,~~It is thought the em- logical syndromes described that have been attrib- boli block the origin of the penetrating arteries uted to lacunar infarction, although these cases are few in number and in some instances not con-

after lodging in their parent arteries and produce http://www.jabfm.org/ larger and more symptomatic lesions. This is simi- fined to the deeper, noncortical parts of the brain. lar to the third mechanism previously described. There are a number of clinical features that are This mechanism is generally thought to be less common to all of the lacunar syndromes. Lacunar common than the other three in the pathophysiol- stroke syndromes characteristically evolve in a ogy of classic lacunar stroke syndromes. "leisurely" fashion, with as many as 30 percent In each instance, obliteration of the lumen developing over a period up to 36 hours.lh Lacu-

results in infarction of adjacent brain tissue. Mac- nar syndromes characteristically do not embody on 26 September 2021 by guest. Protected copyright. rophages eliminate the infarcted tissue, and certain neurological manifestations, including vis- the characteristic cavity or lacuna remains. In gen- ual field defects, aphasia, stupor, coma, loss of eral, the smaller lacunae, 3-7 pL, result from consciousness, or seizures." In only approxi- segmental arterial disorganization and lipohyalin- mately 30 percent of patients with one of the lacu- osis, whereas the larger lacunae, 1-2 cc, are the nar syndromes, the stroke will be preceded by a result of atheromatous or embolic occlusion of a transient ischemic attack. penetrating vessel. The larger lacunae are usually symptomatic, whereas smaller lacunae may be asymptomatic unless situated in a sensory or Pure Motor Hemiparesis motor tract. The most common lacunar syndrome involves At one time, lacunar strokes were thought to be pure motor hemiparesis of the face, arm, and leg virtually always associated with longstanding hy- on one side of the body." The stroke may involve pertension. Fisher reported a 97 percent incidence various combinations of these three body parts, of hypertension in &%e ~eries.~Others have re- and the extent of the paralysis is variable. Dys-

58 The Journal of the American Board of Family Practice-Vol. I No. 1 J Am Board Fam Pract: first published as 10.3122/jabfm.1.1.57 on 1 January 1988. Downloaded from arthria is frequently present with this syndrome. Table 1. Uncommon Lacunar Syndromes. Occasionally, mild sensory symptoms occur with- - - -. - -- - - out demonstrable impairment. This syndrome is Sensorimotor stroke Generalized chorea notable for its lack of certain neurological mani- Ataxic tetraparesis festations, including visual field defects, aphasia, Bilateral paramedian thalamic infarction apraxia, cortical sensory deficits, ataxia, and Focal dystonia cranial nerve abnormalities. Patients usually Pure motor hemiparesis with contralateral maintain full mental acuity. Increased deep ten- gaze paresis Isolated facial stroke don reflexes and an extensor plantar response Pure dysarthria are usually present on the hemiparetic side. The Hemichorea-hemiballism site of the lesion resulting in pure motor hemi- Unilateral asterixis paresis is in either the anterior or posterior limbs of the internal capsule, corona radiata, or in the base of the pons involving the corticospinal motor tract. than the arm, and gait disturbance is a prominent symptom. Neurological exam will reveal dys- metria of the arm and leg with predominately a Pure Sensory Stroke distal weakness on the same side with hyper- The second most frequent type of lacunar syn- reflexia and Babinski sign. Neurological signs char- drome results in unilateral sensory symptoms." acteristically absent include visual field defects, In this variant, termed pure sensory stroke, aphasia, intellectual impairment, dysarthria. dys- there is numbness involving the face, arm, and phagia, and sensory loss. leg on one side of the body. Axial structures in- cluding the scalp, neck, and trunk may also be involved, and the patient can have a sharp mid- Dysarthria-Clumsy Hand Syndrome line "plumb-bob" demarcation to the symp- A fourth common lacunar syndrome involves the toms. The sensory symptoms may be described combination of dysarthria and clumsiness of one as tingling, numbness, heat or cold sensation, hand.21 With this syndrome, there is dysarthria. a pressure sensation, or alteration in size or lower on one side, and clumsiness weight of the involved regions. In general, the with mild hand weakness on the same side. There patient's sensory complaints are out of propor- may be associated . The involved hand tion to the objective findings noted on examina- exhibits slight weakness with impairment in writ- http://www.jabfm.org/ tion. Because tactile sensation is usually dimin- ing and fine movements. There are usually hyper- ished rather than absent, Fisher suggested that a active reflexes of the involved upper extremity, more appropriate designation for the syndrome and Babinski's sign may be present on that side. would be "pure paresthetic stroke." This syn- Visual field and conical and cranial nerve deficits drome is unassociated with weakness, dysar- are not seen. The site of the lesion in this syn- thria, vertigo, diplopia, visual field defects, drome is in the pons or internal capsule. nystagmus, aphasia, or change in level of con- on 26 September 2021 by guest. Protected copyright. sciousness. The site of involvement with pure sensory strokes is in the sensory (postero- Other Lacunar Syndromes ventral) nucleus of the thalamus, and the most In addition to these four cominon syndromes, frequently responsible pathological process is there have been a number of other less common lipohyalinosis. lacunar syndromes described (see Table 1 ) .22-31 They are not associated with visual field defects, mental deficits, or other signs of conical involve- Ataxic Hemiparesis ment. They usually occur in the setting of chronic A third lacunar syndrome, also originally de- hypertension and are associated with a good prog- scribed by Fisher, is referred to as ataxic hemipar- nosis. The less common lacunar syndromes also e~is.~'The site of this lacunar infarct is in the pons typically evolve in a "leisurely" fashion rather and results in ipsilateral extremity ataxia and he- than producing their neurological picture sud- miparesis of varying degrees on the side opposite denly, as is characreristic of , intracere- the lesion. In most cases, the leg is involved more bra1 hemorrhage, or .

Lacunar Strokes 59 J Am Board Fam Pract: first published as 10.3122/jabfm.1.1.57 on 1 January 1988. Downloaded from

Diagnosis Recent data have suggested that emboli14 and Traditionally, the diagnosis of lacunar infarction carotid occlusive disease36may be more frequently has been made on clinical grounds through the associated with lacunar stroke than originally ap- recognition of the syndromes previously de- preciated. The usual source of emboli is the heart scribed. ' This remains true in most cases of a clas- with , mural thrombus, prosthetic sic lacunar syndrome. It should be noted, how- valves, and subacute bacterial endocarditis acting ever, that in some series, the classic lacunar as predisposing factors. However, embolic infarc- syndromes are manifested in only approximately tion more commonly is seen as 50 percent of case^,'^*^* with incomplete, com- of acute onset with cortical deficits. Clues to the plex, or atypical symptomatology present in the presence of carotid occlusive disease include evi- remainder of cases. Electroencephalography may dence of generalized atherosclerosis, bruits, and be of some help in that it is usually normal with diminished carotid upstroke. When extracranial subcortical infarcts. Examination of the cerebro- or cardiac emboli are sus- spinal fluid is generally not helpful in elucidating pected clinically, additional procedures such as a diagnosis. Because of the small size of the vessels echocardiography, carotid doppler, and ultra- generally involved, conventional angiography sound or arteriography may be necessary to estab- does not possess the resolution necessary to dem- lish the diagnosis. onstrate abnormalities responsible for lacunar strokes. The advent of computed tomography (CT) has Management allowed accurate localization of lacunar infarcts Patients with lacunar strokes most commonly ex- and has contributed greatly to the understanding hibit the triad of chronic hypertension, one of the of the pathogenesis and clinical course of lacunar four common lacunar syndromes, and a normal disease. Computed tomography of the brain will CT scan. It is generally agreed that patients with either demonstrate no abnormality or may dem- completed lacunar strokes should be treated ex- onstrate the characteristic lesions. Normal CT pectantly without specific therapy. Vigorous treat- scans can be compatible with lacunar infarcts that ment of mild to moderate hypertension, if present, were missed because of their small size, because of should be avoided. Gradual reduction of blood being located in a difficult region of the brain to pressure is preferred in order to avoid further de- visualize via CT or because of improper timing of terioration in the neurological status due to rela- the study. In a large prospective study, positive CT tive hypoperfusion and exacerbation of ischemia

scans were obtained in only 69 percent of the pa- in the tissue adjacent to the area of infarct.' http://www.jabfm.org/ tients who exhibited one of the classic lacunar In patients with one of the uncommon lacunar syndromes. 33 Fifty -five percent of these patients syndromes, no specific therapy is indicated if one had positive CT scans within 1 0 days of the stroke assumes the stroke is nonprogressive. However, or transient ischemic attack. By three months, an since other diseases involving the central nervous additional 13 percent of the study patients dem- system such as tumors or multiple sclerosis can onstrated CT changes consistent with lacunar in- mimic many of the uncommon lacunar syn-

farction. Presumably, a period of time must pass dromes, consultation with a neurologist is con- on 26 September 2021 by guest. Protected copyright. for cavitation to occur to produce the characteris- sidered prudent. tic lacuna. In the future, magnetic resonance The prognosis for survival and recovery in lacu- imaging (MRI) with its superior resolution and nar strokes is generally favorable. As would be capability for demonstrating the deeper noncorti- expected, prognosis and degree of recovery have cal pans of the cerebrum and brain stem may been found to be better with smaller lesions.14 prove to be better than CT in the evaluation of Following the acute phase, intensive physical lacunar strokes.34 therapy and rehabilitation should be encouraged, A useful property of CT is its ability to distinguish and control of hypertension, if present, should be between lacunar infarction and lacunar hemor- attained. rhage. Convention has held that it was unlikely for Thirty percent to 50 percent of patients will cerebral hemorrhage to cause lacunar syndromes. have a progression of neurological symptoms after Recently, however, investigators have described the the occurrence of a lacunar stroke, or they will occurrence of all four classic lacunar syndromes due have lacunar transient ischemic attack^.'^'^,",^^ to small .j5 Treatment in these cases is controversial. Many

The Journal of the American Board of Family PractirP-Vol. I No. I J Am Board Fam Pract: first published as 10.3122/jabfm.1.1.57 on 1 January 1988. Downloaded from authorities recommend treatment of evolving, with hypertension, represent a majority of lacunar cortical, thrombotic strokes in progression with strokes. Recent evidence demonstrates that some anticoagulation when the progression is due to lacunar strokes can be embolic14 or hemorrhag- increasing ischemia rather than edema, cardiopul- icj5 in etiology, are not invariably associated with monary complications, or hemorrhage. 3g,40 Fish- hyperten~ion,'~,~~may be la~-ger,'~,'~and can be er and others have discussed the benefits (based associated with neurological manifestations that on anecdotal or theoretical data) of anticoagu- do not conform to the classic lating patients with progressive lacunar strokes, In most cases of suspected lacunar stroke, a fa- specifically the hemiparetic variety, to decrease miliarity with the lacunar syndromes and per- neurological deteri~ration."~~,~~Conversely, formance of appropriate noninvasive studies will Fisher has advised against treatment of the pure confirm the diagnosis. Patients who have the triad sensory variety with anticoagulation since extrav- of chronic hypertension, one of the classical lacu- asation of erythrocytes is a characteristic feature. " nar syndromes, and a compatible CT scan can In a small prospective study involving anticoa- generally be spared angiography or the consider- gulation in progressive lacunar stroke of the hemi- ation of cerebrovascular surgery.43 Because of the paretic variety, no advantages to anticoagulation pathological heterogeneity of lacunar disease, were dem~nstrated.~~This study, which involved however, it is incumbent upon physicians to be only four patients, however, was too small to critical in the evaluation of patients whose clinical draw definite conclusions. In a second uncon- picture deviates from the classic presentation. trolled, nonrandomized study, 15 patients treated with either anticoagulation or were felt to The author would like to thank W. Steven Metzer, M.D., have had a more favorable outcome at one month Staff Neurologist, McClellan Memorial Veterans Administra- tion Hospital, Liule Rock, Arkansas, for his helpful suggestions than another group of 10 patients without either in the preparation of this article. treatment.42 There was no mention, however, of the type or severity of the lacunar strokes that their patients experienced, and the authors ad- References 1. Mohr JP, Caplan LR, Melski JW, et al. The Har- mitted that their results could have been skewed vard Cooperative Stroke Registry: a prospective by a selection bias. Thus, the efficacy of anticoagu- registry. (NY) 1978; 28:754-62. lation in the treatment of lacunar stroke in pro- 2. Adams RD, Victor M. Principles of neurology. gression has not been confirmed, although theo- New York: McGraw Hill, 1977:5 18-20. retical benefits with that form of therapy exist. If 3. Wanger SL. Lacunar strokes. Primary Care 1979; 6:757-69. anticoagulation is considered, it is imperative that 4. Marie P. Des foyers lacunaires de desintegration et http://www.jabfm.org/ intracerebral hemorrhage first be excluded by de differents autres etats cavitaires du cerveau. Rev means of computed tomography. Hopefully, pro- Med 1901; 21:281-98. spective studies will appear in the future to ad- 5. Fisher CM. Lacunes: small deep cerebral infarcts. dress this important aspect of the management of Neurology (NY) 1965; 15:774-84. 6. Idem. The arterial lesions underlying lacunes. Acta lacunar stroke. Neuropathol (Berl) 1968; 12: 1- 15. In regard to prevention of lacunar strokes, treat- 7. Idem. Cerebral miliary in hypertension. ment of hypertension and attention to other risk Am J Pathol 1972; 66:313-30. on 26 September 2021 by guest. Protected copyright. factors related to the development of cerebrovas- 8. Idem. Capsular infarcts: the underlying vascular cular disease are central points. Because of the lesions. Arch Neurol 1979; 36:65-73. 9. Fisher CM, Cole M. Homolateral ataxia and cmral established effectiveness of low-dose aspirin in paresis: a vascular syndrome. J Neurol Neurosurg treating transient cerebral ischemia in men, this Psychiatry 1965; 28:48-55. form of prophylaxis seems rea~onable.~~,~~ 10. Fisher CM, Gore I, Okabe N, White PD. Athero- sclerosis of the carotid and vertebral arteries: ex- tracranial and intracranial. J Neuropath Exp Neurol 1965; 24:455-76. Discussion 11. Fisher CM. Bilateral occlusion of basilar artery Much has been learned about lacunar strokes in branches. J Neurol Neurosurg Psychiatry 1977; recent years regarding their etiology, clinical pre- 40: 1 182-9. sentation, and clinical course. Fisher's contribu- 12. Araki G. Small infarctions of the basal ganglia with tion to the understanding of this disease process is special reference to ischemic attacks. In: Recent Advances in Gerontology 1978; 469: 161-2. Pro- enormous; it appears that his "small deep in- ceedings of the XI International Congress of Ger- farcts," which were almost invariably associated ontology, Tokyo, Aug 20-5, 1978. J Am Board Fam Pract: first published as 10.3122/jabfm.1.1.57 on 1 January 1988. Downloaded from

13. Santamaria J, Graus F, Rubio F, Arbizu T. Peres J. 31. Massey EW, Goodman JC, Steward C, Brannon Cerebral infarction of the basal ganglia due to em- WL. Unilateral asterixis: motor integrative dys- bolism from the heart. Stroke 1983; 14:911-4. function in focal vascular disease. Neurology (NY) 14. Pullicino P, Nelson RF, Kendall BE, Marshall J. 1979; 29: 1180-2. Small deep infarcts diagnosed on computed to- 32. Nelson RF, Pullicino P, Kendall BE, Marshall J. mography. Neurology (NY)1980; 30: 1090-6. Computed tomography in patients presenting 15. Weisberg LA. Lacunar infarcts: clinical and com- with lacunar syndromes. Stroke 1980; 11 :256- puted tomographic correlations. Arch Neurol 61. 1982; 39: 37-40. 33. Donnan GA, Tress BM, Bladin PF. A prospective 16. Mohr JP. Lacunes. Stroke 1982; 13:3-11. study of lacunar infarction using computed to- 17. Fisher CM. Lacunar strokes and infarcts: a review. mography. Neurology (NY) 1982; 32:49-56. Neurology (NY) 1982; 32:871-6. 34. Bydder GM, Steiner RE, Young IR, et al. Clinical 18. Fisher CM, Curry HB. Pure motor hemiplegia of NMR imaging of the brain: 140 cases. AJR 1982; vascular origin. Arch Neurol 1965; 13:30-44. 139:215-36. 19. Fisher CM. Pure sensory stroke involving face, 35. Mori E, Tabuchi M, Yamadori A. Lacunar syn- arm and leg. Neurology (NY) 1965; 15:76-80 drome due to intracerebral hemorrhage. Stroke 20. Idem. Ataxic hemiparesis.. A pathological study. 1985; 16:454-9. Arch Neurol 1978; 35: 126-8. 36. Aleksic SN, George AE. Pure motor hemiplegia 2 1. Idem. A lacunar stroke. The dysarthria-clumsy with occlusion of the extracranial carotid artery. hand syndrome. Neurology (NY) 1967; 17:614-7. J Neurol Sci 1973; 19:331-9. 22. Mohr JP, Kase CS, Meckler RJ, Fisher CM. Sen- 37. Rascol A, Clanet M, Manelfe C, Guiraud B, Bonafe sorimotor stroke due to thalamocapsular ische- A. Pure motor hemiplegia: CT study of 30 cases. mia. Arch Neurol 1977; 34:739-41. Stroke 1982; 13: 1 1-7. 23. Tabaton M, Mancardi G, Loeb C. Generalized cho- 38. Millikan CH, McDowell FH. Treatment of pro- rea due to bilateral small, deep cerebral infarcts. gressing stroke. Stroke 198 1; 12:397-409. Neurology (NY) 1985; 35:588-9. 39. Carter AB. Anticoagulant treatment of progressive 24. Van Gijn J, Venneulen M. Ataxic tetraparesis from stroke. Br Med J 1961; 2:70-3. lacunar infarction in the pons. J Neurol Neurosurg 40. Baker RN, Broward JA, Fang HC, et al. Anticoagu- Psychiatry 1983; 46:669-70. lant therapy in cerebral infarction. Neurology 25. Guberman A, Stuss D. The syndrome of bilater- (Minneapolis) 1962; 12:823-35. al paramedian thalamic infarction. Neurology 4 1. Dobkin BH. Heparin for lacunar stroke in progres- (Cleveland) 1983; 33:540-6. sion. Stroke 1983; 14:421-3. 26. Russo LS. Focal dystonia and lacunar infarction of 42. Lodder J, Gorsselink EL. Progressive stroke caused the basal ganglia: a case report. Arch Neurol 1983; by CT-verified small, deep infarcts: relation with 40:61-2. the size of the infarct and clinical outcome. Acta 27. Fisher CM. Cerebral ischemia-less familar types. Neurol Scand 1985; 7 1:328-30. Clin Neurosurg 1971; 18:267-336. 43. Miller VT. Lacunar stroke: a reassessment. Arch 28. Huang CY, Broe G. Isolated facial palsy: a new Neurol 1983; 40: 129-34. lacunar syndrome. J Neurol Neurosurg Psychiatry 44. Fields WS, Lemak NA, Frankowski RF, Hardy RJ. http://www.jabfm.org/ 1984; 47:84-6. Controlled trial of aspirin in cerebral ischemia. 29. Caplan LR. Lacunar infarction: a neglected con- Stroke 1977; 8:301-14. cept. Geriatrics 1976; 31:71-5. 45. A randomized trial of aspirin and sulfinpyra- 30. Kase CS, MauIsby GO, deJuan E, Mohr JP. Hemi- zone in threatened stroke. The Canadian Coop- chorea-hemiballism and lacunar infarction in the erative Study Group. N Engl J Med 1978; 299: basal ganglia. Neurology (NY) 1981; 31 :452-5. 53-9. on 26 September 2021 by guest. Protected copyright.

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