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Multiple System Atrophy (MSA) is a rare and aggressive neurodegenerative disorder characterized by a combination of motor impairments, autonomic dysfunction, and cerebellar ataxia, with no currently available disease-modifying therapies. Emerging evidence suggests that impaired glymphatic clearance of pathological α-synuclein aggregates may contribute to disease progression. This clinical study investigates the potential of bilateral cervical lymphatic-venous anastomosis (LVA) - a microsurgical procedure connecting deep cervical lymphatics to veins - to enhance glymphatic drainage and slow disease progression in MSA patients.
This single-center prospective clinical study will enroll patients with clinically confirmed MSA to undergo bilateral cervical lymphatic-venous anastomosis (LVA). Through comprehensive pre- and postoperative evaluations including clinical scale assessments, blood biomarker testing, and neuroimaging examinations, the study aims to evaluate the short-term and long-term effects of bilateral LVA on patients' motor function, autonomic symptoms, and quality of life, as well as its potential to delay disease progression.
The study will further investigate whether the potential clinical improvements from LVA are mediated through enhanced intracranial lymphatic drainage function and subsequent clearance of pathological α-Syn protein in the brain. Safety assessments will include monitoring and recording both short-term and long-term postoperative complications. This research may provide a novel non-pharmacological intervention approach for MSA treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Immediate LVA group | Experimental | Participants will undergo bilateral cervical lymphatic-venous anastomosis (LVA) surgery within 2 weeks after baseline assessments (including clinical scales, biomarker testing, and neuroimaging). |
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| Delayed LVA Group | Active Comparator | Identical LVA procedure performed at 6 months (±2 weeks) post-baseline |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Immediate LVA | Procedure | Bilateral cervical lymphatic-venous anastomosis (LVA) performed within 2 weeks after baseline assessments. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of Bilateral LVA on MSA Symptoms at 3 Months (UMSARS-II Score Change) | Description: Change in Unified Multiple System Atrophy Rating Scale Part II (UMSARS-II) scores from baseline to 3 months post-LVA surgery. Scale Range: 0-56 (higher scores = worse motor function). Metric: Mean difference in total score. | Baseline to 3 months post-operation. |
| Safety of Bilateral LVA (Surgical Adverse Events) | Incidence of surgery-related adverse events (e.g., infection, bleeding, anastomosis failure) within 3 months post-operation. Metric: Percentage of participants with ≥1 adverse event (AE). | Intraoperative to 3 months post-operation. |
| Measure | Description | Time Frame |
|---|---|---|
| Long-term Efficacy of LVA on MSA Symptoms | Change in UMSARS-II scores from baseline to 6, 9, and 12 months post-LVA. Scale Range: 0-56 (higher = worse). Metric: Mean difference at each timepoint. | Baseline to 6, 9, and 12 months post-operation. |
| Effect of LVA on Plasma Biomarkers |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Shengdi Chen, MD, PhD | Contact | +86 13818018166 | chensd@rjh.com.cn | |
| Chao Gao, MD, PhD | Contact | +86 18217590273 | anshangaochao@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ruijin Hospital, Shanghai Jiao Tong University School of Medicine | Shanghai | Shanghai Municipality | 200025 | China |
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| ID | Term |
|---|---|
| D019578 | Multiple System Atrophy |
| ID | Term |
|---|---|
| D054969 | Primary Dysautonomias |
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D001480 | Basal Ganglia Diseases |
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| Delayed LVA | Procedure | Identical LVA procedure performed at 6 months (±2 weeks) post-baseline |
|
Change in plasma biomarkers from baseline to 3 months post-LVA. Metric: Concentration (pg/mL) via ELISA. |
| Baseline to 3 months post-operation. |
| Assessment of Glymphatic Function via MRI ALPS Index | Assessment of Glymphatic Function via MRI ALPS Index Glymphatic activity will be quantitatively evaluated using Diffusion Tensor Imaging along the Perivascular Space (DTI-ALPS) sequence on 3T MRI. The ALPS index will be calculated from diffusivity ratios (Dx/Dz) in the perivascular spaces of deep white matter (centrum semiovale level), reflecting interstitial fluid clearance efficiency. Higher ALPS indices indicate enhanced glymphatic function. | Preoperatively (baseline)，3 months post-LVA，12 months post-LVA |
| Cognitive Improvement Post-LVA | Change in Montreal Cognitive Assessment (MoCA) scores from baseline to 3/6/9/12 months. Scale Range: 0-30 (higher = better cognition). | Baseline to 3, 6, 9, and 12 months post-operation. |
| Quality of Life Improvement | Change in Parkinson's Disease Questionnaire-39 (PDQ-39) scores from baseline to 3/6/9/12 months. Scale Range: 0-100 (lower = better QoL). | Baseline to 3, 6, 9, and 12 months post-operation. |
| Disease-Modifying Effect of LVA (Delayed vs. Immediate Surgery) | Differences in Unified Multiple System Atrophy Rating Scale Part II (UMSARS-II) Changes from Baseline to 3 Months，6 Months，9Months，and 12 Months | Baseline， 3 Months，6 Months，9Months，and 12 Months |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |