Effect of Cervical Lymphaticovenous and Lymph Node-to-Vein Anastomosis in Patients With Intracranial Lymphatic Circulation Disorder

Effect of Cervical Lymphaticovenous Anastomosis and Cervical Lymph Node to Vein Anastomosis for the Patient With Intracranial Lymphatic Circulation Disorder

This study is a single-center, prospective clinical trial designed to evaluate the therapeutic effects of lymphaticovenular anastomosis (LVA) and lymph node-venous anastomosis (LNVA) in patients with intracranial lymphatic circulation disorders. Following voluntary written informed consent, screening assessments will be performed in accordance with the clinical trial protocol. Eligibility will be determined based on the predefined inclusion and exclusion criteria, and eligible subjects will be enrolled in the study. Enrolled participants will undergo cognitive function assessments at baseline (pre-surgery) and at 1, 3, 6, 9, 12, 18, and 24 months postoperatively for follow-up. Cognitive evaluations will not be additionally performed for research purposes but will be conducted in accordance with the existing clinical care schedule and standard treatment guidelines.

There are several theories regarding the causes of mild cognitive impairment (MCI) and dementia, and one of the commonly proposed mechanisms involves the accumulation of amyloid, a metabolic waste product, within the brain parenchyma. This accumulation is thought to result from impaired clearance of waste from the brain. Accordingly, impaired function of the brain's waste drainage system may contribute to the development of cognitive symptoms.

Because waste clearance from the brain occurs through lymphatic pathways, dysfunction of lymphatic circulation has been identified as an important contributing factor to MCI and dementia. However, due to the minute diameter of lymphatic vessels-typically less than 1 mm-direct therapeutic interventions targeting lymphatic function have long remained unexplored.

Recent advances in supermicrosurgical techniques have enabled procedures on lymphatic vessels as small as 0.2-0.3 mm, leading to the development of novel treatments for lymphatic circulation disorders. For example, patients with upper or lower extremity lymphedema, a representative condition of lymphatic dysfunction, have shown significant improvement following lymphaticovenular anastomosis (LVA) or lymph node-venous anastomosis (LNVA).

Lymphedema results from obstruction or damage to lymphatic pathways, causing the accumulation of lymphatic fluid in tissues. LVA and LNVA are microsurgical procedures that create new bypass routes by connecting lymphatic vessels or lymph nodes directly to adjacent veins, thereby allowing lymphatic fluid to drain into the venous system and re-enter systemic circulation. These procedures have been performed for more than two decades, with excellent therapeutic outcomes reported over the past five years. At Asan Medical Center, more than 100 such procedures are successfully performed annually.

Furthermore, based on the same principle applied in limb lymphedema, recent case-level studies have suggested that performing LVA or LNVA in lymphatic pathways or lymph nodes responsible for cerebral waste clearance may improve degenerative neurological conditions, including Alzheimer's disease. Based on this accumulated knowledge and surgical expertise, cervical lymphaticovenular anastomosis and cervical lymph node-venous anastomosis will be performed to connect lymphatic vessels and lymph nodes involved in cerebral lymphatic drainage to adjacent veins.

It is hypothesized that this procedure may help slow disease progression, preserve quality of life, and potentially improve cognitive function in patients with mild cognitive impairment or dementia.

Inclusion Criteria:

• Patients aged 19 years or older who are diagnosed with intracranial lymphatic circulation disorder based on neurological evaluation.
• Global Deterioration Scale (GDS) score between 3 and 5 at screening.
• Diagnosis of Alzheimer's disease confirmed by amyloid PET-CT or CSF amyloid testing, showing amyloid accumulation associated with lymphatic circulation disorder.
• Able to provide written informed consent to participate in the study voluntarily.

Exclusion Criteria:

• Unable to undergo follow-up evaluation for at least 12 months after surgery.
• Diagnosed with vascular dementia.
• Presence of structural brain disease other than intracranial lymphatic circulation disorder.
• Known hypersensitivity to indocyanine green (ICG).
• Uncontrolled systemic medical conditions such as severe cardiopulmonary, renal, hepatic, or endocrine disorders.
• History of previous neck surgery.
• Refusal to participate or failure to provide informed consent.
• Determined by the principal investigator to be unsuitable for participation due to any other clinical reason.