Expansion-floating Craniotomy for the Treatment of Malignant Cerebral Edema Caused by Acute Ischemic Stroke

NCT ID: NCT07195786

Last Updated: 2025-09-29

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 356 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-10-01
• Study Completion Date: 2027-05-30

Brief Summary

This clinical study investigates Expansion-floating Craniotomy (EC), a novel surgical technique for treating life-threatening malignant cerebral edema following large hemispheric infarction (commonly known as massive stroke). Malignant edema causes rapid increases in intracranial pressure, compressing vital brain structures and risking fatal brain herniation, requiring urgent intervention.

The current international standard treatment is traditional decompressive craniectomy (DC). DC involves removing a section of the skull to allow brain swelling, effectively reducing pressure and mortality risk. It is strongly recommended (Class I, Level A evidence) in major guidelines. However, DC typically requires a second major surgery (cranioplasty) approximately 3 months later to replace the removed bone flap, involving additional costs and risks like progressive intracranial hemorrhage or subdural hygroma.

EC is a newer approach designed to potentially eliminate the need for a second surgery. During EC, surgeons use medical titanium plates to temporarily elevate the bone flap, creating immediate space for brain swelling while keeping the bone flap attached. Once brain swelling subsides (usually within weeks), a minor procedure flattens the titanium plates, allowing the patient's own bone to naturally reposition without requiring cranioplasty. EC may be performed based on surgeon assessment of brain swelling, guideline considerations, or experience. If EC is deemed unsuitable during surgery, DC will be performed instead.

While early research suggests EC achieves decompression similar to DC while preserving the bone flap, its safety and effectiveness compared to the established DC procedure are not yet fully proven. DC is a well-understood, mature technique with known risks and benefits, including the certainty of needing cranioplasty. Conservative management is reserved for patients unfit for surgery but may not prevent neurological deterioration.This study aims to conduct a preliminary assessment of the outcomes of EC versus DC.

Detailed Description

Extensive cerebral infarction leads to progressive brain edema within 24-48 hours of ischemic injury. This edema can cause secondary damage over subsequent days through elevated intracranial pressure (ICP) and brain herniation. When edema is severe enough to cause decompensated ICP elevation, it is termed malignant edema, which can compromise potentially salvageable peri-infarct penumbral tissue.

Decompressive craniectomy (DC) is widely used to alleviate elevated ICP and prevent herniation. Cochrane reviews incorporating data from three major randomized trials (DECIMAL, DESTINY, HAMLET) demonstrate that DC improves survival and favorable outcomes compared to medical management alone. However, morbidity associated with DC and subsequent cranioplasty is significant, reaching up to 40%. Complications include delayed postoperative seizures (reported in 37-61.1% of cases), hydrocephalus (40%), neurological deficits like the syndrome of the trephined (26%), and chronic headaches often resolving only after cranioplasty (17%). Specific complication rates reported by Ban et al. include contralateral hematoma (5.6%), contusion expansion (12.4%), postoperative seizures (3.4%), external brain herniation (14.6%), CSF leakage (2.2%), infection (4.5%), subdural hygroma (32.6%), post-traumatic hydrocephalus (11.2%), and syndrome of the trephined (9.0%).

To address the limitations of DC, techniques like decompressive cranioplasty (DCP), also known as hinge craniotomy (HC), have been proposed. Unlike DC, HC preserves the bone flap, suspending it above the skull using specific fixation devices to avoid the long-term sequelae of bone removal. HC aims to reduce elevated ICP, prevent worsening edema and herniation, reduce the complexity of subsequent cranioplasty, and offer potential cost benefits. First described in 2007 for refractory post-traumatic ICP, HC has been used off-label for other indications. Potential advantages over DC include controlling moderate edema while avoiding a second major cranioplasty surgery, a crucial factor in resource-limited settings, and potentially lower complication rates.

However, HC may have limitations, primarily concerning the adequacy of the achieved expansion volume and potential subsequent need for conversion to DC. Early HC techniques reportedly provided only 40-60ml of expansion, potentially insufficient for malignant edema, though recent modifications claim volumes of 100-120ml. While some studies suggest comparable ICP control between HC and DC, rigorous data on HC's safety and efficacy, particularly its ability to sufficiently mitigate midline shift, brain swelling, and prevent herniation in large hemispheric infarctions, remain limited and require validation through systematic clinical studies.

Our team recently reported a novel technique termed Expansion-floating Craniotomy (EC). EC utilizes three peptide plates to elevate the bone flap to a predetermined position, ensuring adequate decompression while preserving the potential for outward displacement. As cerebral swelling subsides, subsequent loosening of the plates allows the bone flap to spontaneously reposition. EC was successfully implemented in four emergency cases, achieving the desired decompression volume while preserving the bone flap. This technique aims to provide optimal decompression without bone removal, potentially reducing complications associated with prior techniques. Potential advantages include superior cosmetic outcomes, maintenance of appropriate ICP, cost reduction, and simplified bone flap repositioning.

Study Design: This is a multicenter, non-inferiority cohort study. Patients with acute, large anterior circulation ischemic stroke will be allocated to one of three groups based on family consent:

Expansion-floating Craniotomy (EC) Group Decompressive Craniectomy (DC) Group Conservative Management Group

Objectives:

To evaluate the non-inferiority of EC compared to DC in treating patients with acute large anterior circulation infarction.

To further explore the clinical acceptability of the EC technique.

To assess differences in the postoperative complication profile, including:

Delayed intracranial hemorrhage (confirmed by CT >72 hours post-op) Incisional infection / CSF leakage rate Incidence of paradoxical brain herniation

Conditions

Ischemic Stroke, Acute; Malignant Cerebral Edema

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Treatment group

Expansion-floating Craniotomy (EC) is performed, preserving the bone flap, while suspending it above the skull using specific fixation devices.

Expansion-floating Craniotomy

Intervention Type: PROCEDURE

Following craniotomy with bone flap removal, cerebral edema is assessed. The bone flap is then elevated using 2-3 titanium connectors. The elevation height must be sufficient to at least prevent contact between the bone flap and the underlying brain tissue. If cerebral swelling proves less severe than anticipated or begins to subside, the connectors can be loosened minimally invasively after a maximum scalp expansion period of 7-10 days. The elevated bone flap gradually repositions itself. Mild compression is applied using an elastic bandage for fixation, thereby restoring cranial integrity.

Standard treatment control group

Decompressive Craniectomy (DC) is performed, removing a section of skull bone to reduce intracranial pressure (ICP).

decompressive craniectomy

Intervention Type: PROCEDURE

The patient is placed supine with the head rotated contralaterally. A large retroauricular question-mark incision is made in the scalp. Alternatively, a Kempe incision or preauricular incision may be used according to surgeon preference. Meticulous preservation of the superficial temporal artery (STA) is essential during the procedure to prevent ischemic complications in the flap. After elevating the myocutaneous flap to expose the operative field, a fronto-temporo-parietal craniectomy is performed. For unilateral decompressive craniectomy, the bone window should measure at least 15 × 12 cm, extending inferiorly to the floor of the temporal fossa to ensure adequate decompression.

Conservative treatment group

Conservative pharmacological therapy was administered instead, as surgical intervention indicated per guidelines was refused by the patient or family.

drug conservative therapeutic

Intervention Type: DRUG

Pharmacotherapy for malignant cerebral edema has been implemented according to current guidelines.

Interventions

Expansion-floating Craniotomy

Following craniotomy with bone flap removal, cerebral edema is assessed. The bone flap is then elevated using 2-3 titanium connectors. The elevation height must be sufficient to at least prevent contact between the bone flap and the underlying brain tissue. If cerebral swelling proves less severe than anticipated or begins to subside, the connectors can be loosened minimally invasively after a maximum scalp expansion period of 7-10 days. The elevated bone flap gradually repositions itself. Mild compression is applied using an elastic bandage for fixation, thereby restoring cranial integrity.

Intervention Type: PROCEDURE

decompressive craniectomy

The patient is placed supine with the head rotated contralaterally. A large retroauricular question-mark incision is made in the scalp. Alternatively, a Kempe incision or preauricular incision may be used according to surgeon preference. Meticulous preservation of the superficial temporal artery (STA) is essential during the procedure to prevent ischemic complications in the flap. After elevating the myocutaneous flap to expose the operative field, a fronto-temporo-parietal craniectomy is performed. For unilateral decompressive craniectomy, the bone window should measure at least 15 × 12 cm, extending inferiorly to the floor of the temporal fossa to ensure adequate decompression.

Intervention Type: PROCEDURE

drug conservative therapeutic

Pharmacotherapy for malignant cerebral edema has been implemented according to current guidelines.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age requirement: Adults aged >18 but <80 years
• Acute cerebral infarction diagnosis: Patients with internal carotid artery or middle cerebral artery occlusion within 48 hours, meeting all three criteria:

NIHSS score ≥16 with item 1a (level of consciousness) ≥1 CT demonstrating >50% MCA territory infarction or hypoperfused area >2/3, OR DWI hyperintensity volume >82 ml within 6 hours of onset, OR DWI infarct volume >145 ml within 14 hours

• Imaging evidence: Midline shift ≥5 mm to the contralateral side on CT, OR significant ipsilateral ventricular compression with effacement of cerebral sulci/cisterns.

Exclusion Criteria

• Pre-stroke mRS score ≥1
• Significant contralateral cerebral infarction
• Symptomatic intracranial hemorrhage
• Any known coagulopathy
• Life expectancy <3 years
• Any severe comorbidities potentially interfering with treatment evaluation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Meng Zhang, Chief Physician, Professor

Role: CONTACT

zhangmeng861@qq.com

86+13708332600

Other Identifiers

2025-230

Identifier Type: -

Identifier Source: org_study_id