As one might surmise, small penetrating branches of the cerebral arteries may become occluded, and the resulting infarcts may be so small or so situated as to cause no symptoms whatsoever. As the softened tissue is removed by macrophages, a small cavity, or lacune, remains. Early in the twentieth century, Pierre Marie referred to the condition as état lacunaire (the lesions were first described by Durant-Fardel in 1843). He distinguished these lesions from a fine loosening of tissue around thickened small vessels that enter the anterior and posterior perforated spaces, a change to which he gave the name état criblé (cribriform change). Pathologists have not always agreed on these distinctions, but we have adhered to the view of Fisher that lacunes are usually caused by occlusion of small arteries, 50 to 200 μm in diameter, and the cribriform state, to mere thickening of vessels and fraying of the surrounding tissue—that is, dilated perivascular spaces (Virchow-Robin spaces) that do not have a corresponding neurologic disease.
In almost all clinical and pathologic material, there has been a strong relationship between the lacunar state and chronic hypertension, but also diabetes and hyperlipidemia. Sacco and colleagues (1991), in a population-based study in Rochester, Minnesota, found that 81 percent of patients with lacunar infarctions were also hypertensive. There appear to be three mechanisms for lacunar infarction but variants of atherothrombosis are foremost. The first, and traditionally most characteristically tied to lacunes, is a local type of fibrohyalinoid arteriolar sclerosis that involves the orifice or proximal part of a small penetrating blood vessel (lipohyalinosis as described below). The second is atherosclerosis of a large trunk vessel that occludes the origin of these same small vessels. This is prone to involve several adjacent vessels and cause, at times, larger lacunes or the atherosclerosis extends from a trunk vessel into a smaller one. Third is the entry of small embolic material into one of the vessels. The relative frequency of these three pathologies is not known, but the first seems to be most common and occurs without pathologic change in the trunk vessel of the circle of Willis whereas the embolic type is least frequent. When Fisher (1975) examined a series of such lesions in serial sections, from a basal parent artery up to and through the lacune, he was able to confirm a lipohyalin degeneration of the vessel wall and occlusion in the initial course of small vessels in most cases. In some, lipohyalinotic changes had resulted in false aneurysm formation, resembling the Charcot-Bouchard aneurysms, another hypertension-related change that underlies brain hemorrhage (see further on). In a series of 1,042 consecutive adults whose brains were examined postmortem, Fisher (1965b) observed one or more lacunes in 11 percent but that certainly reflected the lack of adequate treatment of hypertension and hyperlipidemia of that time. He found 4 to 6 and sometimes up to 10 to 15 lacunes in any given brain specimen. In recent years, better treatment of hypertension has greatly reduced this number and the overall frequency of lacunar infarction, at least as judged by MRI.
Lacunes are situated, in descending order of frequency, in the putamen and caudate nuclei, thalamus, basis pontis, internal capsule, and deep in the central hemispheral white matter. The cavities range from 3 to 15 mm in diameter, and whether they cause symptoms depends entirely on their location.