Embolism is the Key: Against
No stroke syndrome is specific to cause, but several are suggestive. According to a recent classification, lacunar infarcts are small subcortical infarcts that result from occlusion of a single perforating artery.1 When symptomatic, lacunar infarcts present with lacunar syndromes, 5 of which are well documented: pure motor stroke, pure sensory stroke, sensorimotor stroke, ataxic hemiparesis, and dysarthria (ie, clumsy hand).
I am aware of no clinical stroke syndrome that is absolutely specific with respect to pathophysiology. The lacunar syndromes are no exception. In 5% to 10% a small hemorrhage is the underlying cause. A lacunar syndrome may also result from restricted striatocapsular infarct, anterior choroidal artery territory infarct, cortical infarct, and infarcts simultaneously affecting penetrator and cortical artery territories. However, several studies using diffusion-weighted MRI (dw-MRI) show that a small subcortical ischemic area corresponding to the territory of a penetrating artery is the most common finding, being present in 84% to 94% of patients with a lacunar syndrome. Simultaneous involvement of penetrator territory and cortical artery territories was demonstrated in 16% in a recent series.2 Such lesion patterns are obviously important to recognize, but they constitute a minority.
Mechanisms of Occlusion in Patients With a Lacunar Syndrome Caused by a Single Ischemic Lesion Confined to Penetrating Artery Territory
Although subject to some limitations, the original neuropathological studies should not be forgotten because they proved that occlusion due to in situ disease of the penetrating artery was by far the most common finding in this setting.3–4 Findings suggesting previous embolism were seen in few cases only.
Several clinical studies have analyzed the association between verified small deep infarcts presenting with a lacunar syndrome and presence of cardioembolic or large artery disease. The methodologically and most carefully conducted studies show that small-vessel occlusion is the most likely mechanism in ≈three fourths of cases.5 Are associated findings of large artery atherosclerosis or a cardioembolic source coincidental, or are they causative? Probably they are a mix of both. In a recent study,6 there was a 7% absolute excess of ipsilateral, compared with contralateral, carotid stenosis >75%, and another study showed that atrial fibrillation is not always coincidental.7 However, on best estimate, atherosclerosis, cardioembolism, cryptogenetic, and unusual causes add up only to about a quarter of cases.
The early recurrence rate in lacunar infarcts is low compared to infarcts due to cardioembolism and large artery disease. A recent dw-MRI study showed that clinical recurrence substantially underestimates the true incidence of early recurrent ischemic lesions.8 New ischemic areas consistent with active embolism or fragmentation of an embolus was seen in ≈half of patients with large-artery atherosclerosis or cardioembolism, but in none of the patients classified as small-vessel occlusion. A transcranial Doppler study has also shown that asymptomatic circulating emboli in the middle cerebral artery are rare in the lacunar infarct subtype.9
Animal stroke models are instrumental to study the molecular basis and salvage of ischemic brain tissue, but they are not suitable to explore the risk factors and underlying causes of human stroke. White matter constitutes half of the brain volume in humans compared to 14% in rodents, and vascular topographies differ. The finding that a small embolus can lodge in a penetrating artery, or in any artery, in an experimental stroke model cannot be extrapolated to assess the quantitative importance of embolic mechanisms in lacunar infarcts in humans.
Most Lacunar Infarcts Do Not Present With Stroke
Unrecognized (“silent”) lacunar infarcts are at least 5 times more common than symptomatic infarcts: both types are part of a broader spectrum of cerebral small-vessel disease which also includes vascular white matter disease. Small-vessel disease is an important determinant for the development of vascular cognitive impairment and dementia. There is at present no evidence to suggest that embolism plays any important role in these disorders.
“Lacunar Infarct” Remains a Clinically Useful Term
In my view, the best available data show that in situ penetrating artery disease is the most common cause of lacunar infarcts. Embolism from cardiac and large artery sources is undoubtedly clinically relevant, but account for a quarter or less of symptomatic lacunar infarcts. In clinical practice, patients with presumed lacunar infarcts should, of course, be investigated with respect to embolic sources along the same principles as patients with ischemic stroke in general, and findings might well change therapy. Nevertheless, such findings are only present in a minority of patients. To state that embolism is the key in lacunar infarction would be to ignore the key findings in several reports that belong to the classics in stroke research.
Section Editors: Geoffrey A. Donnan, MD, FRACP, and Stephen M. Davis, MD, FRACEP
- Received April 16, 2004.
- Accepted April 16, 2004.
Donnan GA, Norrving B, Bamford JM, Bogousslavsky J. Classification of subcortical infarcts. In: Donnan G, Norrving B, Bamford J, Bogousslavsky J, eds. Subcortical Stroke. 2nd ed. Oxford, UK: Oxford Medical Publications; 2002: 27–34.
Ay H, Oliviera-Filho J, Buonanno FS, Ezzeddine M, Schaefer PW, Rordorf G, Schwamm LH, Gonzalez RG, Koroshetz WJ. Diffusion-weighted imaging identifies a subset of lacunar infarction associated with embolic source. Stroke. 1999; 30: 2644–2650.
Fisher CM. Lacunar strokes and infarcts: a review. Neurology. 1982; 32: 871–876.
Gan R, Sacco RL, Kargman DE, Roberts JK, Boden-Albala B, Gu Q. Testing the validity of the lacunar hypothesis: the Northern Manhattan Stroke Study Experience. Neurology. 1997; 48: 1204–1211.
Tejada J, Diez-Tejedor E, Hernandez-Echebarria L, Balboa O. Does a relationship exist between carotid stenosis and lacunar infarction? Stroke. 2003; 34: 1404–1411.
Jung DK, Devuyst G, Maeder P, Bogousslavsky J. Atrial fibrillation with small subcortical infarcts. J Neurol Neurosurg Psychiatry. 2001; 70: 344–349.
Kaposzta Z, Young E, Bath PMW, Markus HS. The clinical application of asymptomatic embolic signal detection in acute stroke: a prospective study. Stroke. 1999; 30: 1814–1818.