What is stroke involution?

Stroke Involution

Stroke involution refers to the natural reduction in infarct size that occurs after the initial expansion phase of acute ischemic stroke, typically beginning several days after stroke onset and continuing through the chronic phase. This process represents the brain's endogenous response to injury, involving tissue resorption, glial scar formation, and structural remodeling that results in a smaller final lesion volume compared to the maximum lesion size observed during the acute period.

Temporal Evolution of Stroke Lesions

Acute Expansion Phase

• Stroke lesions typically reach their maximum size at a mean of 70.4 hours after symptom onset, with diffusion-weighted imaging (DWI) lesion volumes increasing between initial imaging and follow-up scans in the majority of patients. 1
• The acute phase is characterized by progressive ischemic injury developing over hours to days, driven by both primary vascular occlusion and secondary pathophysiological processes including excitotoxicity, peri-infarct depolarizations, inflammation, and apoptosis. 1, 2
• Approximately 25% of patients experience neurological worsening during the first 24 to 48 hours after stroke, reflecting ongoing tissue injury and lesion expansion. 3

Involution Phase

• Final lesion volume is smaller than maximum lesion volume in the majority of patients (12 of 14 patients in serial MRI studies), demonstrating that stroke involution is a common phenomenon. 1
• The apparent diffusion coefficient (ADC) ratio, which falls during acute injury (mean 0.73 at initial imaging), does not rise above normal until 42 days after stroke onset, marking the transition from acute cytotoxic edema to chronic tissue remodeling. 1
• Involution involves structural and functional remodeling of brain vasculature, including changes in vascular integrity, cerebral blood flow regulation, and tissue architecture that continue well beyond the acute phase. 4

Mechanisms Underlying Involution

Cellular and Molecular Processes

• Stroke recovery and involution occur through changes in synaptic signaling in existing neuronal networks, formation of new neuronal networks via axonal sprouting and dendritic branch growth, and alterations in glial cells through glial progenitor responses. 3
• The process involves tissue resorption of necrotic material, glial scar formation at the infarct border, and reorganization of surviving peri-infarct tissue. 4
• Vascular remodeling includes angiogenesis, changes in blood-brain barrier integrity, and restoration of cerebral blood flow regulation in surviving tissue. 4

Imaging Correlates

• Fluid-attenuated inversion recovery (FLAIR) imaging demonstrates permanent tissue injury, with hyperintense lesions becoming visible once ischemia causes cellular death, distinguishing irreversible damage from potentially reversible DWI abnormalities. 3
• Serial imaging reveals that some small DWI hyperintensities may completely reverse early, consistent with absence of permanent cerebral injury, though this is mainly limited to small embolic lesions. 3
• The initial DWI lesion volume correlates strongly with the largest T2 lesion volume (r=0.97), but the final chronic lesion is typically smaller due to involution. 1

Clinical Significance

Prognostic Implications

• Initial DWI lesion volume and maximum T2 lesion volume correlate positively with follow-up neurological deficit scores (r=0.67 and r=0.77 respectively), indicating that larger acute lesions predict worse outcomes despite subsequent involution. 1
• The degree of involution does not necessarily correlate with functional recovery, as neurological outcomes depend more on the location and initial severity of injury than on the absolute reduction in lesion size. 1

Distinction from Stroke Evolution

• Stroke involution must be distinguished from "stroke-in-progression" or "stroke-in-evolution," which refers to worsening neurological deficits during the acute phase due to ongoing ischemic injury, not the later reduction in lesion size. 5
• Stroke evolution involves various pathophysiological mechanisms including thromboembolism, hypoperfusion, and secondary injury cascades that expand the initial lesion, whereas involution represents the resolution phase. 5, 2

Monitoring and Assessment

Imaging Timeline

• Peak swelling and maximum lesion size occur several days after stroke onset, necessitating serial imaging to distinguish acute expansion from subsequent involution. 3
• Chronic phase imaging (>42 days) is required to assess final infarct volume and the full extent of involution. 1
• The dynamic nature of stroke lesions over hours to days emphasizes that single time-point imaging provides incomplete information about ultimate tissue fate. 1