The Role of Meningeal Lymphatic Vessels in the Absorption of Chronic Subdural Hematoma and Its Injury Mechanism

Establishment of a Clinical Efficacy Prediction System Based on the Role of Meningeal Lymphatic Vessels in the Absorption of Chronic Subdural Hematoma and Its Injury Mechanism

Chronic subdural hematoma (CSDH) is a very common hemorrhagic disease of the nervous system, accounting for about 10% of hemorrhagic strokes. The incidence rate of elderly people over 65 years old is 58.1/100,000, and the incidence rate is increasing year by year, and it may reach 121/100,000 by 2030. At present, the specific pathogenesis of CSDH is still unclear. Although it has been clinically confirmed that a part of CSDH can be absorbed by itself, and some drugs such as atorvastatin can speed up the process, surgical treatments such as cranial craniotomy or cranial drilling hematoma removal are still the only options for patients with CSDH.

Lymphatic circulation spreads throughout most tissues of the human body, assists in removing metabolic wastes in the interstitium, maintains body fluid homeostasis, and plays a role in immune response and immune surveillance. For a long time, the central nervous system has been considered as an immune-privileged organ, that is, the central nervous system does not have the presence of the lymphatic system. Until 2015, Louveau et al. used immunofluorescence staining and other techniques to find functional lymphatic ducts adjacent to the dural venous sinuses in the mouse brain when looking for the channels for T cells to enter and leave the meninges, confirming the first intracranial meningeal lymphatic vessels. (mLVs), and found that mLVs express the classic markers of lymphatic endothelial cells (LECs), namely VEGFR3, prostate homeobox 1 (PROX 1), podoplanin, lymphatic endothelial markers transparent Ronidase receptor-1 (LYVE-1), etc. Relevant studies have confirmed that meningeal lymphatic vessels can drain interstitial fluid (ISF), macromolecular substances and immune cells out of the skull, providing a new drainage pathway for the excretion of metabolic waste from the central nervous system. Subsequent studies have confirmed that mLV is involved in the pathophysiological process of a series of neurological diseases such as Alzheimer's disease (AD), traumatic brain injury (TBI), and subarachnoid hemorrhage (SAH). This phenomenon suggests that mLVs play an important role in central nervous system diseases.

Study Overview

• Status: Recruiting
• Conditions: Hematoma, Subdural, Chronic
• Intervention / Treatment: Procedure: subdural hematoma burr hole drainage; Drug: drug conservative treatment

Detailed Description

Chronic subdural hematoma (CSDH) is a very common hemorrhagic disease of the nervous system, accounting for about 10% of hemorrhagic strokes. The incidence rate of elderly people over 65 years old is 58.1/100,000, and the incidence rate is increasing year by year, and it may reach 121/100,000 by 2030. At present, the specific pathogenesis of CSDH is still unclear. Although it has been clinically confirmed that a part of CSDH can be absorbed by itself, and some drugs such as atorvastatin can speed up the process, surgical treatments such as cranial craniotomy or cranial drilling hematoma removal are still the only options for patients with CSDH. However, these surgical methods have a high recurrence rate of hematoma and the incidence of surgery-related complications, which brings a huge burden to the patient's family and society. Despite the presence of a large number of inflammatory cytokines in the CSDH content, only a minority of patients exhibited systemic inflammatory responses such as fever and increased white blood cell count during hematoma resorption. On the contrary, more CSDH patients showed a certain degree of neurological deficit symptoms, such as hemiplegia of one limb and cognitive function decline. These clinical phenomena have stimulated thinking about how CSDH is drained. If the hematoma is absorbed through the vascular system, why is no corresponding inflammatory response or clinical symptoms observed in CSDH patients. In addition, the cerebrospinal fluid (CSF) of patients with CSDH was clear and the cell count was within the normal range, indicating that CSDH did not flow into the CSF. Therefore, further exploring the drainage pathway of CSDH, understanding the absorption process and recurrence mechanism of CSDH, and developing new effective treatment methods are important issues faced by neurosurgery clinicians.

Lymphatic circulation spreads throughout most tissues of the human body, assists in removing metabolic wastes in the interstitium, maintains body fluid homeostasis, and plays a role in immune response and immune surveillance. For a long time, the central nervous system has been considered as an immune-privileged organ, that is, the central nervous system does not have the presence of the lymphatic system. Until 2015, Louveau et al. used immunofluorescence staining and other techniques to find functional lymphatic ducts adjacent to the dural venous sinuses in the mouse brain when looking for the channels for T cells to enter and leave the meninges, confirming the first intracranial meningeal lymphatic vessels. (mLVs), and found that mLVs express the classic markers of lymphatic endothelial cells (LECs), namely VEGFR3, prostate homeobox 1 (PROX 1), podoplanin, lymphatic endothelial markers transparent Ronidase receptor-1 (LYVE-1), etc. Relevant studies have confirmed that meningeal lymphatic vessels can drain interstitial fluid (ISF), macromolecular substances and immune cells out of the skull, providing a new drainage pathway for the excretion of metabolic waste from the central nervous system. Subsequent studies have confirmed that mLV is involved in the pathophysiological process of a series of neurological diseases such as Alzheimer's disease (AD), traumatic brain injury (TBI), and subarachnoid hemorrhage (SAH). This phenomenon suggests that mLVs play an important role in central nervous system diseases.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: sheng Chen, M.D.; Email: saintchan@zju.edu.cn
• Study Contact Backup: Name: sheng chen, M.D; Phone Number: +8613645814323

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Second affiliated hosipital of zhejiang univerisity school of medicine
      • Contact: sheng chen, M.D; Email: saintchan@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis chronic subdural hematoma
• Hematoma thickness greater than 10mm on imaging

Exclusion Criteria:

• In patients with chronic subdural hematoma, only head CT examination was performed;
• There was previous brain injury (stroke, cerebral hemorrhage, etc., leaving relevant chronic changes on CT);
• Imaging data was lost and the onset of CSDH was accompanied by severe comorbidity disease patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Surgical; undergo surgery	Procedure: subdural hematoma burr hole drainage; For patients with larger hematoma, remove the hematoma by burr hole drainage
Other: non-surgical groups; no surgery	Drug: drug conservative treatment; The patient did not receive surgical treatment and chose conservative treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnetic resonance signal intensity of meningeal lymphatic vessels	The signal intensity of meningeal lymphatic vessels was measured by PACS system in hospital	The first day after admission
Magnetic resonance signal intensity of meningeal lymphatic vessels	The signal intensity of meningeal lymphatic vessels was measured by PACS system in hospital	3 days after surgery
Magnetic resonance signal intensity of meningeal lymphatic vessels	The signal intensity of meningeal lymphatic vessels was measured by PACS system in hospital	1 months after surgery
Magnetic resonance signal intensity of meningeal lymphatic vessels	The signal intensity of meningeal lymphatic vessels was measured by PACS system in hospital	6 months after surgery

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 20, 2023

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: June 16, 2022
• First Posted (Actual): June 22, 2022

Study Record Updates

• Last Update Posted (Actual): June 22, 2022
• Last Update Submitted That Met QC Criteria: June 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Hemorrhage; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Intracranial Hemorrhage, Traumatic; Hematoma; Hematoma, Subdural; Hematoma, Subdural, Chronic
• Other Study ID Numbers: 2022-0219

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No