Roughly 25% of all ischemic strokes are due to small vessel occlusion. The most common mechanism of small vessel occlusion is lipohyalinosis. This is when the walls of small penetrating vessels undergo progressive concentric thickening and narrowing. Pathologically, this is characterized by hypertension-related hypertrophy and fibrinoid degeneration of the vessel wall, resulting in progressive luminal narrowing and ultimately obliteration of the lumen. And what is the biggest risk factor? Hypertension (#1). Diabetes and smoking are also important risk factors. The second pathologically proven mechanism of small vessel occlusion is actually from atherosclerosis. How? These small vessels originate from much larger vessels. We call these small vessels the perforators of the larger vessels. For instance, perforators of the basilar artery are small vessels originating from the basilar artery that supply regions of the pons. Perforators of the middle cerebral artery supply structures including the basal ganglia and internal capsule. Perforators arising from the posterior communicating artery and posterior cerebral artery supply regions of the thalamus. Thus, an intrinsic defect in the perforator itself can result in lipohyalinosis and progressive vessel narrowing, eventually culminating in a lacunar stroke. But what if the problem is not primarily within the perforator? If you have atherosclerosis in the parent vessel, that plaque can grow and encroach upon the ostium of the perforator, eventually occluding the small vessel and causing a stroke in the territory supplied by that particular perforator. Make sense? This is called branch atheromatous disease (BAD). So how do we tell the difference between the two? This distinction matters because the underlying stroke etiologies are different and may have different therapeutic implications. If this is true intrinsic small vessel disease from lipohyalinosis, CHANCE and POINT support short-term dual antiplatelet therapy in appropriate patients with minor ischemic stroke. In practice, DAPT is generally continued for 21 days, with much of the benefit occurring when therapy is initiated early, particularly within the first 24 hours. If this is due to atherosclerotic disease of the parent vessel, dubbed branch atheromatous disease (BAD), things become more interesting. When BAD occurs in the setting of significant symptomatic intracranial atherosclerotic disease (ICAD), then it should be treated as ICAD. DAPT is generally extended to 90 days, rather than 21 days, and AGGRESSIVE lipid-lowering therapy becomes particularly important. But there is an important caveat. BAD can occur from atherosclerotic plaque without significant luminal stenosis. In these substenotic cases, there is a strong biological argument that DAPT should perhaps be extended to 90 days, treating the underlying atherosclerotic mechanism similarly to stroke from symptomatic ICAD. Why might aggressive lipid lowering be particularly important when atherosclerosis is the mechanism? Because we are no longer simply dealing with an occluded tiny vessel. We are dealing with an active atherosclerotic plaque in the parent artery. Lipid lowering helps stabilize plaque and reduces future atherosclerotic cardiovascular risk. The earlier aggressive lipid-lowering therapy is implemented, the greater the potential benefit. There is also growing interest in targeting the inflammatory component of atherosclerosis. Therapies such as low-dose colchicine have reduced major adverse cardiovascular events in patients with established atherosclerotic cardiovascular disease. This leads me to neuroimaging. Not only can neuroimaging help distinguish between these two mechanisms of lacunar infarction, advanced neuroimaging can further evaluate the vessel wall and characteristics of the plaque, increasing our certainty that the underlying mechanism is indeed branch atheromatous disease. How do we distinguish between these two mechanisms of lacunar infarction with neuroimaging? First, you have to distinguish a true lacunar stroke from an embolic stroke. Location is key. Lacunar infarctions occur in territories supplied by penetrating arteries, including the basal ganglia, internal capsule, thalamus and pons. Size can also give you a clue. Previous literature suggests that infarctions from lipohyalinosis are typically around 3 to 7 mm in size. Once the lesion becomes larger than 7 mm, you should at least consider another mechanism, including branch atheromatous disease. A practical rule of thumb is that if you're scrolling through thin axial DWI slices and you see the lesion on more than 3 cuts, it is probably larger than 7 mm and BAD should at least enter your differential. A common misconception I had during my residency days was that if the mechanism were atherosclerosis, you should see major plaque or significant stenosis on CTA or MRA. This is not necessarily true. The plaque may be subtle and may involve the ostium of the perforator without causing significant narrowing of the parent vessel lumen. And this is where vessel wall imaging, sometimes called black-blood MRI, becomes useful. Why is it called black-blood MRI? Conventional CTA and MRA primarily show you the lumen. Black-blood MRI suppresses the signal from flowing blood and surrounding CSF, allowing you to better interrogate the vessel wall itself and even appreciate features of an active diseased vessel wall. So what are we looking for? In intracranial atherosclerosis, the plaque typically produces eccentric, non-uniform thickening of the vessel wall. On T2-weighted vessel wall imaging, the plaque is typically T2 hyperintense. See image C in Pic 1. And in the setting of a recent stroke, the plaque can enhance on post-contrast T1 imaging. This enhancement can reflect an active atherosclerotic plaque with inflammatory changes and increased vessel-wall permeability. See image D in Pic 1. Now look carefully at where that abnormal vessel wall sits. White arrows in images C and D. If you see eccentric plaque involving the side of the parent vessel where the responsible perforator originates, particularly with enhancement after contrast, and that perforator supplies the territory of your infarction, then you have another clue that this may be branch atheromatous disease rather than plain old lipohyalinosis. Same small deep infarction. Potentially very different underlying vascular pathology. How often do you get vessel wall imaging? And what other vascular diseases can vessel wall imaging help diagnose? Drop your thoughts below 👇👇 #Neurology #Stroke #FOAMed #Neuroradiology Image courtesy of Yaghi et al., Lacunar Stroke: Mechanisms and Therapeutic Implications, JNNP, 2021. Post inspired by this excellent review and other readings on the topic.