When does peri‑hematomal (perifocal) edema begin after an intracerebral hemorrhage?

When Does Perihematomal Edema Begin After Intracerebral Hemorrhage?

Perihematomal edema begins immediately after intracerebral hemorrhage onset, with early edema formation starting within the first few hours through clot retraction and hydrostatic pressure changes, followed by continued expansion that peaks around 7-14 days after the initial bleeding event. 1

Immediate Early Phase (First Hours)

Early perihematomal edema develops through clot retraction and hydrostatic pressure changes that force serum into the perihematomal space, forming vasogenic edema within the first hours after ICH. 1

• The coagulation cascade activates immediately as blood encounters brain tissue, initiating the edema formation process 2
• Edema is already measurable on imaging obtained within 3 hours of symptom onset, with median baseline edema volumes of approximately 7-9 mL documented in hyperacute ICH patients 3, 4
• This immediate edema formation occurs concurrently with the period of highest hematoma expansion risk (first 3 hours) 5

Rapid Expansion Phase (First 24-72 Hours)

Perihematomal edema volume increases most rapidly during the first 2 days after symptom onset, with approximately 75% volume expansion occurring within the first 24 hours. 3, 4

• Median absolute edema volume increases from approximately 7 cm³ at baseline to 11-14 cm³ at 24 hours 4
• Relative edema volume (edema volume/hematoma volume) increases from approximately 0.47-0.55 at baseline to 0.81 at 24 hours 4
• Thrombin formation, activation of the coagulation cascade, and early inflammatory responses contribute to vasogenic edema formation during this period 1

Continued Growth Phase (Days 3-14)

Edema continues to expand beyond 72 hours, with peak absolute edema volume occurring around 7-14 days after ICH onset. 3, 6

• Mean absolute edema volume reaches its peak of approximately 64-88 cm³ at days 7-11, representing a doubling from initial volumes 3, 6
• Erythrolysis, hemoglobin-mediated toxicity, and ongoing inflammation contribute to vasogenic edema formation during this extended period 1
• Neuronal death and energy failure contribute to cytotoxic edema formation during the later portion of this phase 1

Plateau and Resolution Phase (After 2 Weeks)

No significant changes in edema volume are typically observed after approximately 12-14 days post-ICH. 3, 6

• The timing of peak edema can be influenced by hematologic factors, with higher admission hematocrit associated with delayed peak edema 3
• Higher partial thromboplastin time is associated with greater peak relative edema 3

Clinical Implications and Pitfalls

The immediate onset and biphasic nature of edema formation creates distinct therapeutic windows for intervention. 1

• Early interventions (first 2-3 hours) should target hematoma expansion to limit both primary injury and subsequent edema formation 1
• Drugs targeting secondary brain injury have an approximate therapeutic window of 24-72 hours, as edema formation continues well beyond the hematoma expansion phase 1
• Edema volume growth in the first 48 hours correlates with neurological decline, particularly in basal ganglia hemorrhages and smaller hematomas (<30 mL) 7, 3
• The relationship between edema and long-term functional outcomes remains uncertain, though malignant edema can contribute to increased intracranial pressure, midline shift, and herniation 1

Common Pitfalls to Avoid:

• Do not assume edema is absent on hyperacute imaging—measurable edema is present from the moment of hemorrhage 4, 2
• Do not focus solely on hematoma volume—larger hematomas produce larger absolute edema but smaller relative edema, complicating clinical assessment 3, 4, 6
• Do not expect edema to stabilize within 24-72 hours—continued expansion occurs for up to 2 weeks, requiring prolonged monitoring 3, 6