Ischemic & Hemorrhagic Stroke

Ischemic strokes are characterized by impaired blood flow to the brain, leading to tissue ischemia and potentially infarction. The primary subtypes include thrombotic stroke and embolic stroke.

Thrombotic strokes are frequently a consequence of a atheromatous plaque rupture or thrombosis within cerebral vessels. Conversely, embolic strokes arise from proximal emboli, typically thrombi, that become lodged in cerebral vessels. Conditions fostering thrombus formation, like atrial fibrillation and hypercoagulable states, enhance the risk of embolic strokes.

Another subtype of cerebral ischemia, the hypoxic stroke, emanates from systemic hypoperfusion or hypoxemia, leading to global cerebral ischemia rather than a focal deficit. Events causing global hypoxic stroke encompass hypotension resulting from hemorrhage or hypovolemia, and shock from various origins like sepsis, post-myocardial infarction decreased cardiac output, or spinal cord injury.

Transient ischemic attacks (TIA) cause reversible focal ischemia, without resultant infarction or enduring cerebral damage. TIAs usually manifest as transient focal neurological deficits, such as sensorimotor loss or aphasia, typically resolving within 15 minutes and almost invariably within 30 minutes.

Diagnostic procedures for acute strokes commence with a non-contrast head CT to discern ischemic from hemorrhagic origins. In hemorrhagic strokes, blood appears as hyperdense (bright) regions on CT. Diffusion-weighted MRI is preferred for acute ischemic stroke, as it can show signs of ischemia as early as 30 minutes post injury. Notably, proximal vessel occlusion leads to a unique wedge-shaped ischemic pattern on imaging due to the outward branching of vessels as they travel towards the cortex.

From a pathological standpoint, the post-infarction trajectory is systematic. Within 12-24 hours post-infarction, affected neurons undergo morphological changes, evident as vacuolated, eosinophilic cytoplasm and nuclear fragmentation, or karyorrhexis, earning them the moniker red neurons. Approximately 24 hours post-infarction, the injured brain tissue attracts neutrophils, facilitating inflammation, degradation, and phagocytosis of cellular remnants, culminating in liquefactive necrosis. By 3 days, macrophages and microglial cells – the CNS's innate phagocytes – actively engulf the cellular debris and necrotic brain parenchyma. Post-infarction inflammation can escalate to cerebral edema, culminating in intracranial hypertension, especially after extensive infarctions. Around 1 week after injury, astrocytes proliferate, leading to reactive gliosis, which helps support the necrotic area structurally and stimulates angiogenesis. This reparative process eventually results in a fluid-filled cyst encased by a glial scar, contrasting the collagen-suffused lesions observed in coagulative necrosis.

Large vessel thrombotic strokes predominantly originate from the rupture or thrombosis of atherosclerotic plaques in the proximal circle of Willis (most commonly MCA). These strokes can also arise secondary to atherosclerosis at the vertebral arteries near their origin from the subclavian arteries or where they converge to form the basilar artery, as well as the carotid bifurcation and internal carotid artery, both contributors to the Circle of Willis. Large vessel thrombotic strokes can occur in various conditions such as vasospasms from migraines, vasculitides like giant cell arteritis and Takayasu arteritis, and from erythrocyte sickling in sickle cell disease, which particularly affects children.

In contrast, small vessel thrombotic strokes most commonly occur in the lenticulostriate arteries, which are small branches of the ACA/MCA that perfuse deep structures like the basal ganglia. This leads to the formation of small cystic lesions known as lacunar infarcts. Risk factors for lacunar infarcts include hypertension and poorly controlled diabetes mellitus, both of which propel atherosclerosis, fostering microatheroma formation in cerebral small vessels. Accumulation of these infarcts over time is a potential etiology for vascular dementia, the second most prevalent form of dementia following Alzheimer's disease.

Embolic strokes most commonly result from emboli that form in the left heart, such as in atrial fibrillation or mural thrombi following MI. Other sources include valvular vegetations, especially in infective endocarditis, or thrombi detaching from atherosclerotic lesions in the aorta, carotid arteries, or proximal cerebral vessels. Embolic strokes are also a consequence of a patent foramen ovale (PFO), which allows DVTs to sidestep the pulmonary vessels and move into the systemic circulation, resulting in paradoxical embolism. The MCA is the most susceptible to embolic strokes due to its size and direct connection with the internal carotid artery.

The thrombolytic agent tPA can be used to dissolve thrombi in both thrombotic and embolic strokes if administered early enough. Ideally, tPA should be given between 3-4.5hrs following following injury.

Hypoxic strokes often occur in patients with pre-existing occlusive atherosclerotic lesions like carotid stenosis or uncontrolled hypertension. The pyramidal cells of the hippocampus are particularly vulnerable to hypoxia, and are affected first in hypoxic ischemic injury. Watershed areas also vulnerable to hypoxic strokes—watershed infarcts appear as bilateral, wedge-shaped ischemic zones in the anterior and posterior cerebrum.

Hemorrhagic stroke (specifically spontaneous intracerebral hemorrhage) accounts for ~20% of all stroke types, and is characterized by bleeding within the brain parenchyma. Chronic hypertension is central to its pathogenesis and is the most significant risk factor. Chronic hypertension can induce detrimental vascular changes, leading to fibrinoid necrosis and hyaline arteriosclerosis of cerebral vessels, particularly the smaller ones—alterations that pave the way for intracranial hemorrhage. Charcot-Bouchard microaneurysms are associated with chronic hypertension and most commonly arise in the lenticulostriate arteries, where they can cause hemorrhagic intraparenchymal strokes.

Other conditions that can instigate intracerebral hemorrhage include cerebral amyloid angiopathy, which causes recurrent lobar and cerebellar hemorrhagic stroke in the elderly, cerebral vessel vasculitis, and certain brain tumors like astrocytomas