Impaired Glymphatic and Meningeal Lymphatic Functions in Patients with Chronic Migraine
Chia-Hung Wu MD, PhD
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Search for more papers by this authorFeng-Chi Chang MD
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Search for more papers by this authorYen-Feng Wang MD, PhD
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
Search for more papers by this authorJiing-Feng Lirng MD
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Search for more papers by this authorHsiu-Mei Wu MD
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Search for more papers by this authorLi-Ling Hope Pan PhD
Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
Search for more papers by this authorCorresponding Author
Shuu-Jiun Wang MD
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
S.-P.C. and S.-J.W. contributed equally.
Address correspondence to Dr Chen, Institute of Clinical Medicine, National Yang Ming Chiao Tung University, 112304, Taipei, Taiwan. E-mail: [email protected]
Dr S.-J. Wang, Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, 11217, Taipei, Taiwan. E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Shih-Pin Chen MD, PhD
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
S.-P.C. and S.-J.W. contributed equally.
Address correspondence to Dr Chen, Institute of Clinical Medicine, National Yang Ming Chiao Tung University, 112304, Taipei, Taiwan. E-mail: [email protected]
Dr S.-J. Wang, Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, 11217, Taipei, Taiwan. E-mail: [email protected]
Search for more papers by this authorChia-Hung Wu MD, PhD
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Search for more papers by this authorFeng-Chi Chang MD
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Search for more papers by this authorYen-Feng Wang MD, PhD
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
Search for more papers by this authorJiing-Feng Lirng MD
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Search for more papers by this authorHsiu-Mei Wu MD
Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Search for more papers by this authorLi-Ling Hope Pan PhD
Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
Search for more papers by this authorCorresponding Author
Shuu-Jiun Wang MD
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
S.-P.C. and S.-J.W. contributed equally.
Address correspondence to Dr Chen, Institute of Clinical Medicine, National Yang Ming Chiao Tung University, 112304, Taipei, Taiwan. E-mail: [email protected]
Dr S.-J. Wang, Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, 11217, Taipei, Taiwan. E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Shih-Pin Chen MD, PhD
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
S.-P.C. and S.-J.W. contributed equally.
Address correspondence to Dr Chen, Institute of Clinical Medicine, National Yang Ming Chiao Tung University, 112304, Taipei, Taiwan. E-mail: [email protected]
Dr S.-J. Wang, Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, 11217, Taipei, Taiwan. E-mail: [email protected]
Search for more papers by this authorAbstract
Objective
This study was undertaken to investigate migraine glymphatic and meningeal lymphatic vessel (mLV) functions.
Methods
Migraine patients and healthy controls (HCs) were prospectively recruited between 2020 and 2023. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index for glymphatics and dynamic contrast-enhanced magnetic resonance imaging parameters (time to peak [TTP]/enhancement integral [EI]/mean time to enhance [MTE]) for para-superior sagittal (paraSSS)-mLV or paratransverse sinus (paraTS)-mLV in episodic migraine (EM), chronic migraine (CM), and CM with and without medication-overuse headache (MOH) were analyzed. DTI-ALPS correlations with clinical parameters (migraine severity [numeric rating scale]/disability [Migraine Disability Assessment (MIDAS)]/bodily pain [Widespread Pain Index]/sleep quality [Pittsburgh Sleep Quality Index (PSQI)]) were examined.
Results
In total, 175 subjects (112 migraine + 63 HCs) were investigated. DTI-ALPS values were lower in CM (median [interquartile range] = 0.64 [0.12]) than in EM (0.71 [0.13], p = 0.005) and HCs (0.71 [0.09], p = 0.004). CM with MOH (0.63 [0.07]) had lower DTI-ALPS values than CM without MOH (0.73 [0.12], p < 0.001). Furthermore, CM had longer TTP (paraSSS-mLV: 55.8 [12.9] vs 40.0 [7.6], p < 0.001; paraTS-mLV: 51.2 [8.1] vs 44.0 [3.3], p = 0.002), EI (paraSSS-mLV: 45.5 [42.0] vs 16.1 [9.2], p < 0.001), and MTE (paraSSS-mLV: 253.7 [6.7] vs 248.4 [13.8], p < 0.001; paraTS-mLV: 252.0 [6.2] vs 249.7 [1.2], p < 0.001) than EM patients. The MIDAS (p = 0.002) and PSQI (p = 0.002) were negatively correlated with DTI-ALPS index after Bonferroni corrections (p < q = 0.01).
Interpretation
CM patients, particularly those with MOH, have glymphatic and meningeal lymphatic dysfunctions, which are highly clinically relevant and may implicate pathogenesis for migraine chronification. ANN NEUROL 2024;95:583–595
Potential Conflicts of Interest
Nothing to report.
Open Research
Data Availability
Anonymized data will be available upon reasonable request from qualified investigators.
Supporting Information
| Filename | Description |
|---|---|
| ana26842-sup-0001-Supinfo.docxWord 2007 document , 1.1 MB | TABLE S1. Migraine Disability Assessment (MIDAS) Questionnaire. TABLE S2. Widespread Pain Index (WPI) Questionnaire. TABLE S3. Pittsburgh Sleep Quality Index (PSQI) Questionnaire. TABLE S4. Diagnostic Criteria of Episodic Migraine, Chronic Migraine, and Medication-Overuse Headache. TABLE S5. Use of Analgesics in Migraine Subjects within 3 Months before the MRI. TABLE S6. Comparisons of Sex and Age between Individual Subgroups (p Values). TABLE S7. Correlations of DTI-ALPS Index with Headache Frequency (FQ) in Migraine Subgroups. TABLE S8. Age-Adjusted Simple and Multiple Linear Regression of Clinical Parameters to DTI-ALPS Index in Migraine Subjects with Headache Frequency ≥ 5 Days/Month. TABLE S9. Headache Attacks during the MRI. FIGURE S1. Diagram of the study protocols. FIGURE S2. Other major results of Bundle 2. FIGURE S3. Major results in Bundle 3. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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