Perihematomal Edema After Intracerebral Hemorrhage: An Update on Pathogenesis, Risk Factors, and Therapeutic Advances

Abstract

Intracerebral hemorrhage (ICH) has one of the worst prognoses among patients with stroke. Surgical measures have been adopted to relieve the mass effect of the hematoma, and developing targeted therapy against secondary brain injury (SBI) after ICH is equally essential. Numerous preclinical and clinical studies have demonstrated that perihematomal edema (PHE) is a quantifiable marker of SBI after ICH and is associated with a poor prognosis. Thus, PHE has been considered a promising therapeutic target for ICH. However, the findings derived from existing studies on PHE are disparate and unclear. Therefore, it is necessary to classify, compare, and summarize the existing studies on PHE. In this review, we describe the growth characteristics and relevant underlying mechanism of PHE, analyze the contributions of different risk factors to PHE, present the potential impact of PHE on patient outcomes, and discuss the currently available therapeutic strategies.

Keywords: intracerebral hemorrhage; neuroinflammation; pathophysiology; perihematomal edema; therapies.

Figure 1

A 47-year-old male who manifested weakness of the right limb and gradually developed mild disturbance of consciousness without clear inducement. There exists a past medical history with hypertension, which the admission blood pressure is 166/106 mmHg and the Glasgow Coma Scale score was 12. The head NCCT revealed left basal ganglia hemorrhage. The patient received the standardized medical management, and the discharge Glasgow Outcome Scale score is 3. (A–C) The image features of PHE (in red) and ICH against the onset time.

Figure 2

Timeline of PHE volumes after intracerebral hemorrhage based on real-world clinical research of the natural history of PHE. Triphasic patterns of growth of PHE (fast-growing phase: 1–3 days; slow-growing phase and peak period: 1–3 weeks; resorption phase: >3 weeks) were observed.

Figure 3

Mechanism of PHE formation. Po indicated the difference in oncotic pressure between the capillaries and interstitial tissue. Ph indicated the difference in hydraulic pressure between the capillaries and interstitial tissue. NKCC1, Na–K–Cl cotransporter 1; SUR1–TRPM4, sulfonylurea receptor 1–transient receptor potential cation channel subfamily M member 4; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α; IL-1β, interleukin 1β; MMPs, matrix metalloproteinases; BBB, blood–brain barrier; AQPs, aquaporins.