Why Lacunar Syndromes Are Different and Important

Why Lacunar Syndromes Are Different and Important: 

The lacunar hypothesis has been one of the hallmarks of the modern understanding of the clinical categorization of the pathogenesis of stroke. Stated simply, the hypothesis implies that classical lacunar syndromes are caused by small deep brain infarcts, due to occlusion of a single penetrating artery. The underlying pathology has been documented to be either in situ microatheroma or lipohyalinosis, rather than embolism.

The controversy arises because many clinicians remain less than convinced that embolism is not a frequent cause of lacunar infarcts and hence would not warrant a different investigative strategy from other ischemic stroke syndromes. As we see it, the established facts are as follows:

1. There is no animal model of lacunar infarction due to in situ small-vessel disease, in contrast to the embolic model quoted by Futrell.

2. The proportion of embolic sources in patients with lacunar syndromes is substantially lower than for other hemispheric ischemic strokes, as stated by Norrving.

3. MRI studies have demonstrated that variable proportions of patients presenting with classical lacunar syndromes have sometimes shown multiple concurrent infarcts or more widespread perfusion abnormalities suggesting embolism.

4. Other evidence for a possible embolic source in some cases includes a benefit to the subset of patients with lacunar syndromes and ipsilateral high-grade carotid stenosis in the NASCET trial. Further, aortic arch atheroma has been shown to be a risk factor for lacunar stroke.

While recognizing that there is some heterogeneity of mechanism within the lacunar syndromes, we believe that the concept is clinically useful, and that the evidence favors the view that the majority are due to in situ, small-vessel disease. Hence, their recognition enables clinicians to be less aggressive in the search for an embolic source, although we would suggest that exclusion of large-vessel disease and cardiac screening is appropriate. Further, there are compelling clinical and epidemiological reasons to separate lacunar from nonlacunar ischemic strokes. For example, their outcome is substantially more favorable and their location in deep white matter may have implications for therapy. Intriguingly, in the recently reported IMAGES trial, a planned subanalysis showed an unexpected benefit for lacunar syndromes. We encourage further trials of therapy within this group such as the current SPS3 trial of combined antiplatelet and blood pressure lowering therapy. It may well be that the therapeutic response in lacunar infarcts may be somewhat different than in predominantly gray matter infarcts, given the well-known differences in ischemic neurochemical cascades.

Given the importance of small-vessel disease, particularly in Asian countries, and its relationship to both clinical stroke and cognitive decline, we strongly believe that this disease entity deserves specific recognition to focus future research initiatives. While embolism is the likely cause of a minority of lacunar infarcts, we do not see it as the key, but perhaps a small component of a combination lock.

Images Trial

Lancet. 2004 Feb 7;363(9407):439-45.

Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial.

Muir KW, Lees KR, Ford I, Davis S; Intravenous Magnesium Efficacy in Stroke (IMAGES) Study Investigators.

BACKGROUND: Magnesium is neuroprotective in animal models of stroke, and findings of small clinical pilot trials suggest potential benefit in people. We aimed to test whether intravenous magnesium sulphate, given within 12 h of stroke onset, reduces death or disability at 90 days.

METHODS: 2589 patients were randomised within 12h of acute stroke to receive 16 mmol MgSO4 intravenously over 15 min and then 65 mmol over 24 h, or matching placebo. Primary outcome was a global endpoint statistic expressed as the common odds ratio for death or disability at day 90. Secondary outcomes were mortality and death or disability, variously defined as Barthel score less than 95, Barthel score less than 60, and modified Rankin scale more than 1. Predefined subgroup analyses were for the primary endpoint in patients in whom treatment commenced within 6 h versus after 6 h, ischaemic versus non-ischaemic strokes, and cortical stroke syndromes versus non-cortical strokes. Intention-to-treat and efficacy analyses were done.

FINDINGS: The efficacy dataset included 2386 patients. Primary outcome was not improved by magnesium (odds ratio 0.95, 95% CI 0.80-1.13, p=0.59). Mortality was slightly higher in the magnesium-treated group than in the placebo group (hazard ratio 1.18, 95% CI 0.97-1.42, p=0.098). Secondary outcomes did not show any treatment effect. Planned subgroup analyses showed benefit of magnesium in non-cortical strokes (p=0.011) whereas greater benefit had been expected in the cortical group.

INTERPRETATION: Magnesium given within 12 h of acute stroke does not reduce the chances of death or disability significantly, although it may be of benefit in lacunar strokes.

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