A research team from the Department of Neurosurgery at West China Hospital, Sichuan University, led by Professor Liu Hao and Professor Xu Jianguo, has published a comprehensive study titled "Mapping the evolving evidence in chronic subdural hematoma: a 20-year landscape analysis of clinical trials" in SCIENCE CHINA Life Sciences . The study offers the first systematic panoramic analysis of 156 registered cSDH clinical trials from 2005 to 2025, identifying research hotspots, persistent evidence gaps, and future priorities to inform both clinical practice and trial design.
I. Exponential Growth Since 2018, Yet Geographic Imbalance Persists
Over the past two decades, 74% (116/156) of all trials were initiated between 2018 and 2025, peaking at 23 in 2020—reflecting sharply rising global interest in cSDH. Geographically, trial activity remains heavily concentrated in Europe, China, and the United States, while most Asia-Pacific regions and Africa show marked underrepresentation. The study attributes this disparity to limited research funding and weak healthcare infrastructure, which not only constrain local high-quality investigations but also widen the global accessibility gap for advanced therapies like MMAE.
II. Recurrence Remains the Unresolved Core Challenge; Anticoagulation Management Lacks Standardization
Recurrence rate was the most frequently adopted primary endpoint, used in 48.7% of trials—confirming that postoperative recurrence remains the most prominent and unresolved clinical hurdle in cSDH care. In parallel, the study identifies a critical void in perioperative anticoagulation management: despite its frequent clinical occurrence, there is no universally accepted guidance on the optimal timing for resuming anticoagulants or appropriate maintenance dosing regimens, highlighting an urgent need for high-quality evidence.
III. Three Major Therapeutic Tracks: Pharmacotherapy, Surgery, and MMAE
Pharmacotherapy: Multiple trials have shown that dexamethasone, due to its significant adverse effects and limited efficacy, is no longer recommended as routine adjunctive therapy. Instead, tranexamic acid has become a leading research candidate, with seven ongoing trials assessing its value in conservative or postoperative settings. On perioperative anticoagulation, the SECA trial found that continuous aspirin use does not increase recurrence risk, while two other trials are actively comparing early versus delayed resumption strategies for oral anticoagulants to establish standardized protocols.
Surgical interventions: Ongoing studies continue to refine surgical techniques, drainage methods, and anesthetic protocols, reflecting steady iterative progress in operative management.
MMAE: Middle meningeal artery embolization has rapidly emerged as a promising intervention to reduce cSDH recurrence, with 39 trials registered since 2017. Four landmark RCTs were published simultaneously in NEJM and JAMA : EMBOLISE (P=0.008) and STEM (P=0.001) demonstrated significant reductions in recurrence and treatment failure, while MAGIC-MT and EMPROTECT yielded neutral results—a divergence largely explained by differences in population stratification and outcome definitions. Despite its promise, two major barriers remain: high procedural costs with insufficient cost-effectiveness data, and the absence of globally standardized implementation guidelines. Currently, only expert consensus supports MMAE for patients at high recurrence risk, those with high surgical risk, or those unfit for surgery. The authors emphasize the need for refined patient stratification to better define optimal indications, treatment timing, and embolic material selection.
Looking Forward
The study concludes that future cSDH research should prioritize cost-effective trial designs, pragmatic anticoagulation strategies, and rigorous validation of MMAE efficacy across diverse populations. Ultimately, these efforts aim to move cSDH treatment decisions toward both standardization and individualization, bridging critical evidence gaps and improving outcomes for the rapidly growing elderly population affected by this condition.
Science China Life Sciences
Literature review