Lacunar infarction and small vessel disease: pathology and pathophysiology

Abstract

Two major vascular pathologies underlie brain damage in patients with disease of small size penetrating brain arteries and arterioles; 1) thickening of the arterial media and 2) obstruction of the origins of penetrating arteries by parent artery intimal plaques. The media of these small vessels may be thickened by fibrinoid deposition and hypertrophy of smooth muscle and other connective tissue elements that accompanies degenerative changes in patients with hypertension and or diabetes or can contain foreign deposits as in amyloid angiopathy and genetically mediated conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These pathological changes lead to 2 different pathophysiologies: 1) brain ischemia in regions supplied by the affected arteries. The resultant lesions are deep small infarcts, most often involving the basal ganglia, pons, thalami and cerebral white matter. And 2) leakage of fluid causing edema and later gliosis in white matter tracts. The changes in the media and adventitia effect metalloproteinases and other substances within the matrix of the vessels and lead to abnormal blood/brain barriers in these small vessels. and chronic gliosis and atrophy of cerebral white matter.

Keywords: CADASIL; Cerebral amyloid angiopathy; Cerebral small vessel diseases; Pathophysiology.

Figure 1

Small penetrating artery showing lipohyalinosis and fibrinoid necrosis (white arrow); lumen is considerably compromised (upper black arrow). The thickened media contains lipohyalinotic material (Lower black arrow) (Supplied by Dr. C. Miller Fisher.).

Figure 2

Periodic acid Schiff (PAS) stain showing bright pink staining material within small cerebral arteries in a patient with CADASIL.

Figure 3

Drawing showing the arterial pathology in atheromatous branch disease: (A) plaque in parent artery obstructing a branch, (B) junctional plaque extending into the branch, (C) microatheroma formed at the orifice of a branch.

Figure 4

A necropsy specimen showing a cavity due to an old lacunar infarct that is located in and the medial basal ganglia (mostly the globus pallidus) and extends through the internal capsule in a patient with a pure motor hemiplegia during life.

Figure 5

Luxol fast blue (LFB) stained specimen of a cerebral hemisphere showing extensive loss of myelin staining.In a normal brain the entire white matter should stain uniformly blue.

Figure 6

Diagram showing the relationship of a lacune in the pons to the causative penetrating artery vascular lesion. The artery beyond the region of arterial disorganization is thrombosed and thrombus has also formed in a retrograde manner extending toward the parent basilar artery (Reproduced with permission from C Miller Fisher.).