Share：
Share this content in WeChat
X
[Chinese] [PDF] 68 1
• Clinical Article •
Investigating bidirectional differences in glymphatic system function between vestibular migraine and migraine without aura using DTI-ALPS
HOU Xiaoying  ZHONG Liqun  LI Xiaozhen  HUANG Lixian  XIE Cunxiang  DOU Jinjuan  ZHAO Tianzuo  WANG Weitao  CHEN Zhengguang 

DOI:10.12015/issn.1674-8034.2026.05.006.


[Abstract] Objective To investigate glymphatic function differences between migraine without aura (MO) and vestibular migraine (VM) using the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index and explore their clinical implications.Materials and Methods This prospective study enrolled 40 MO patients, 40 VM patients, and 20 healthy controls (HC). The DTI-ALPS index was calculated using an automated atlas-based method. Independent predictors of the ALPS index were identified, and potential mechanistic associations with clinical symptoms were explored.Results The ALPS index showed a significant gradient difference among the three groups (MO > HC > VM, P < 0.05). Disease subtype (B = -0.055, P = 0.002), headache duration (B = -0.003, P = 0.001), and headache attack frequency (B = -0.053, P = 0.001) were independent predictors of the ALPS index. In VM patients, the ALPS index was significantly negatively correlated with headache duration (r = -0.714, P < 0.001) and Dizziness Handicap Inventory (DHI) scores (r = -0.564, P = 0.002). Mediation analysis further revealed that the ALPS index significantly mediated the effect of headache duration on vertigo severity (mediation proportion: 79.53%).Conclusions We propose a "bidirectional dynamic evolution" hypothesis for migraine glymphatic function. Constrained by vestibular pathway vulnerability and high disease burden, VM patients are more susceptible to clearance failure. These findings provide a novel perspective on the mechanisms of migraine heterogeneity.
[Keywords] migraine；vestibular migraine；migraine without aura；diffusion tensor imaging analysis along the perivascular space；magnetic resonance imaging；glymphatic system

HOU Xiaoying1   ZHONG Liqun1   LI Xiaozhen2   HUANG Lixian1   XIE Cunxiang3   DOU Jinjuan1   ZHAO Tianzuo2   WANG Weitao4   CHEN Zhengguang2*  

1 Department of Encephalopathy, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China

2 Department of Radiology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China

3 Department of Rheumatology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China

4 Department of Encephalopathy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China

Corresponding author: CHEN Z G, E-mail: guangchen999@sina.com

Conflicts of interest   None.

Received  2026-01-28
Accepted  2026-04-16
DOI: 10.12015/issn.1674-8034.2026.05.006
DOI:10.12015/issn.1674-8034.2026.05.006.

[1]
DONG L, DONG W, JIN Y, et al. The global burden of migraine: a 30-year trend review and future projections by age, sex, country, and region[J]. Pain Ther, 2025, 14(1): 297-315. DOI: 10.1007/s40122-024-00690-7.
[2]
ÖZÇELIK P, KOÇOĞLU K, ÖZTÜRK V, et al. Characteristic differences between vestibular migraine and migraine only patients[J]. J Neurol, 2022, 269(1): 336-341. DOI: 10.1007/s00415-021-10636-0.
[3]
TU Y H, HUANG T C, TZENG Y S, et al. Prevalence, clinical correlates, and functional implications of vestibular symptoms in patients with migraine[J/OL]. Neurology, 2025, 105(9): e214248 [2026-01-22]. https://www.neurology.org/doi/10.1212/WNL.0000000000214248. DOI: 10.1212/WNL.0000000000214248.
[4]
VITTORINI M G, SAHIN A, TROJAN A, et al. The glymphatic system in migraine and other headaches[J/OL]. J Headache Pain, 2024, 25(1): 34 [2026-01-22]. https://pubmed.ncbi.nlm.nih.gov/38462633/. DOI: 10.1186/s10194-024-01741-2.
[5]
RASMUSSEN M K, MESTRE H, NEDERGAARD M. The glymphatic pathway in neurological disorders[J]. Lancet Neurol, 2018, 17(11): 1016-1024. DOI: 10.1016/S1474-4422(18)30318-1.
[6]
KIM M, SONG Y S, HAN K, et al. Impaired glymphatic flow on diffusion tensor MRI as a marker of neurodegeneration in Alzheimer's disease: correlation with gray matter volume loss and cognitive decline independent of cerebral amyloid deposition[J]. J Alzheimers Dis, 2024, 99(1): 279-290. DOI: 10.3233/JAD-231131.
[7]
HONG H, HONG L, LUO X, et al. The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer's disease continuum participants[J/OL]. Alzheimers Res Ther, 2024, 16(1): 43 [2026-01-22]. https://alzres.biomedcentral.com/articles/10.1186/s13195-024-01407-w. DOI: 10.1186/s13195-024-01407-w.
[8]
HABLITZ L M, PLÁ V, GIANNETTO M, et al. Circadian control of brain glymphatic and lymphatic fluid flow[J/OL]. Nat Commun, 2020, 11(1): 4411 [2026-01-22]. https://doi.org/10.1038/s41467-020-18115-2. DOI: 10.1038/s41467-020-18115-2.
[9]
LIU X, BARISANO G, SHAO X, et al. Cross-vendor test-retest validation of diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) for evaluating glymphatic system function[J]. Aging Dis, 2024, 15(4): 1885-1898. DOI: 10.14336/AD.2023.0321-2.
[10]
RAN L, FANG Y, CHENG C, et al. Genome-wide and phenome-wide studies provided insights into brain glymphatic system function and its clinical associations[J/OL]. Sci Adv, 2025, 11(3): eadr4606 [2026-01-22]. https://pubmed.ncbi.nlm.nih.gov/39823331/. DOI: 10.1126/sciadv.adr4606.
[11]
SIOW T Y, TOH C H, HSU J L, et al. Association of sleep, neuropsychological performance, and gray matter volume with glymphatic function in community-dwelling older adults[J/OL]. Neurology, 2022, 98(8): e829-e838 [2026-01-22]. https://pubmed.ncbi.nlm.nih.gov/34906982/. DOI: 10.1212/WNL.0000000000013215.
[12]
WU C H, CHANG F C, WANG Y F, et al. Impaired glymphatic and meningeal lymphatic functions in patients with chronic migraine[J]. Ann Neurol , 2024, 95(3): 583-595. DOI: 10.1002/ana.26842.
[13]
CAI X, SUN W, CAI M, et al. Impaired glymphatic function contributes to high-frequency attacks in patients with episodic migraine[J/OL]. J Headache Pain, 2025, 26(1): 132 [2026-01-22]. https://pubmed.ncbi.nlm.nih.gov/40461958/. DOI: 10.1186/s10194-025-02070-8.
[14]
ZHANG X, WANG W, BAI X, et al. Increased glymphatic system activity in migraine chronification by diffusion tensor imaging analysis along the perivascular space[J/OL]. J Headache Pain, 2023, 24(1): 147 [2026-01-22]. https://pubmed.ncbi.nlm.nih.gov/37926843/. DOI: 10.1186/s10194-023-01673-3.
[15]
Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition[J]. Cephalalgia, 2018, 38(1): 1-211. DOI: 10.1177/0333102417738202.
[16]
MELO-CARRILLO A, STRASSMAN A, BURSTEIN R. Elucidating the nociceptive role of CGRP in migraine headache[J/OL]. Brain, 2026: awag008 [2026-01-22]. https://pubmed.ncbi.nlm.nih.gov/41503630/. DOI: 10.1093/brain/awag008.
[17]
ASHINA M, HANSEN J M, DO T P, et al. Migraine and the trigeminovascular system-40 years and counting[J]. Lancet Neurol, 2019, 18(8): 795-804. DOI: 10.1016/S1474-4422(19)30185-1.
[18]
RUSSO A F, HAY D L. CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond[J]. Physiol Rev , 2023, 103(2): 1565-1644. DOI: 10.1152/physrev.00059.2021.
[19]
HUANG W, ZHANG Y, ZHOU Y, et al. Glymphatic dysfunction in migraine mice model[J]. Neuroscience, 2023, 528: 64-74. DOI: 10.1016/j.neuroscience.2023.07.027.
[20]
SCHAIN A J, MELO-CARRILLO A, STRASSMAN A M, et al. Cortical spreading depression closes paravascular space and impairs glymphatic flow: implications for migraine headache[J]. J Neurosci, 2017, 37(11): 2904-2915. DOI: 10.1523/JNEUROSCI.3390-16.2017.
[21]
XU W J, BARISANO G, PHUNG D, et al. Structural MRI in migraine: a review of migraine vascular and structural changes in brain parenchyma[J/OL]. J Cent Nerv Syst Dis, 2023, 15: 11795735231167868 [2026-01-22]. https://pubmed.ncbi.nlm.nih.gov/37077432/. DOI: 10.1177/11795735231167868.
[22]
LIU X, WU G, TANG N, et al. Glymphatic drainage blocking aggravates brain edema, neuroinflammation via modulating TNF-α, IL-10, and AQP4 after intracerebral hemorrhage in rats[J/OL]. Front Cell Neurosci, 2021, 15: 784154 [2026-01-22]. https://pubmed.ncbi.nlm.nih.gov/34975411/. DOI: 10.3389/fncel.2021.784154.
[23]
BOJARSKAITE L, NAFARI S, RAVNANGER A K, et al. Role of aquaporin-4 polarization in extracellular solute clearance[J]. Fluids Barriers CNS, 2024, 21(1): 28-38. DOI: 10.1186/s12987-024-00527-7.
[24]
MADER S, BRIMBERG L. Aquaporin-4 water channel in the brain and its implication for health and disease[J]. Cells, 2019, 8(2): 90-106. DOI: 10.3390/cells8020090.
[25]
NEGM M, HOUSSEINI A M, ABDELFATAH M, et al. Relation between migraine pattern and white matter hyperintensities in brain magnetic resonance imaging[J]. Egypt J Neurol Psychiatr Neurosurg, 2018, 54(1): 24-32. DOI: 10.1186/s41983-018-0027-x.
[26]
CHONG P L H, GARIC D, SHEN M D, et al. Sleep, cerebrospinal fluid, and the glymphatic system: a systematic review[J/OL]. Sleep Med Rev, 2022, 61: 101572 [2026-01-22]. https://pubmed.ncbi.nlm.nih.gov/34902819/. DOI: 10.1016/j.smrv.2021.101572.
[27]
HAUGLUND N L, NEDERGAARD M. Is glymphatic clearance the secret to restorative sleep?[J/OL]. Brain, 2025: awaf453 [2026-01-22]. https://pubmed.ncbi.nlm.nih.gov/41325105/. DOI: 10.1093/brain/awaf453.
[28]
ZHANG Z N, CHENG S H, WANG H X, et al. Association of MRI indexes of brain glymphatic function with sleep status in insomnia patients disorders and the effects of repetitive transcranial magnetic stimulation treatment on them[J]. Chin J Magn Reson Imaging, 2025, 16(5): 88-95. DOI: 10.12015/issn.1674-8034.2025.05.014.
[29]
VGONTZAS A, PAVLOVIĆ J M. Sleep disorders and migraine: review of literature and potential pathophysiology mechanisms[J]. Headache, 2018, 58(7): 1030-1039. DOI: 10.1111/head.13358.
[30]
LOHELA T J, LILIUS T O, NEDERGAARD M. The glymphatic system: implications for drugs for central nervous system diseases[J]. Nat Rev Drug Discov, 2022, 21(10): 763-779. DOI: 10.1038/s41573-022-00500-9.
[31]
TAOKA T, ITO R, NAKAMICHI R, et al. diffusion tensor imaging analysis along the perivascular space (DTI-ALPS): revisiting the meaning and significance of the method[J]. Magn Reson Med Sci, 2024, 23(3): 268-290. DOI: 10.2463/mrms.rev.2023-0175.
[32]
LEE D A, LEE H J, PARK K M. Normal glymphatic system function in patients with migraine: a pilot study[J]. Headache, 2022, 62(6): 718-725. DOI: 10.1111/head.14320.
[33]
WANG W T, LI X Z, ZHONG L Q, et al. Analysis of thalamic glutamate-glutamine complex metabolism and related factors in patients with vestibular migraine[J]. Chin J Magn Reson Imaging, 2024, 15(10): 93-97, 114. DOI: 10.12015/issn.1674-8034.2024.10.016.
[34]
ZHANG Y, ZHANG Y, WANG Y, et al. Inhibition of glutamatergic trigeminal nucleus caudalis- vestibular nucleus projection neurons attenuates vestibular dysfunction in the chronic-NTG model of migraine[J/OL]. J Headache Pain, 2023, 24(1): 77 [2026-01-30]. https://pubmed.ncbi.nlm.nih.gov/37386456/. DOI: 10.1186/s10194-023-01607-z.
[35]
CHO L Y, BELL T K, CRADDOCK L, et al. Region-specific changes in brain glutamate and gamma-aminobutyric acid across the migraine attack in children and adolescents[J]. Pain, 2024, 165(12): 2749-2761. DOI: 10.1097/j.pain.0000000000003289.
[36]
MONTARDY Q, WEI M, LIU X, et al. Selective optogenetic stimulation of glutamatergic, but not GABAergic, vestibular nuclei neurons induces immediate and reversible postural imbalance in mice[J/OL]. Prog Neurobiol, 2021, 204: 102085 [2026-01-22]. https://linkinghub.elsevier.com/retrieve/pii/S030100822100099X. DOI: 10.1016/j.pneurobio.2021.102085.
[37]
YU H L, AN Y, JIANG H Y, et al. Changes of amino acid concentrations in the rat medial vestibular nucleus following unilateral labyrinthectomy[J]. Acta Physiologica Sinica, 2007, 59(1): 71-78. DOI: 10.13294/j.aps.2007.01.012.
[38]
CASTILLO-BUSTAMANTE M, HERRÓN-ARANGO A F, BEDOYA M J, et al. The impact of neuroglia on vestibular disorders: insights and implications[J/OL]. Neuroglia, 2025, 6(1): 10 [2026-01-22]. https://www.mdpi.com/2571-6980/6/1/10. DOI: 10.3390/neuroglia6010010.
[39]
PENG S, LIU J, LIANG C, et al. Aquaporin-4 in glymphatic system, and its implication for central nervous system disorders[J/OL]. Neurobiol Dis, 2023, 179: 106035 [2026-01-22]. https://pubmed.ncbi.nlm.nih.gov/36796590/. DOI: 10.1016/j.nbd.2023.106035.
[40]
SZLUFIK S, KOPEĆ K, SZLESZKOWSKI S, et al. Glymphatic system pathology and neuroinflammation as two risk factors of neurodegeneration[J]. Cells, 2024, 13(3): 286-302. DOI: 10.3390/cells13030286.
[41]
ORNELLO R, SALFI F, VITTORINI M G, et al. The potential role of sleep quality in the relationship between glymphatic function and migraine frequency: insights from a cross-sectional study[J]. Headache, 2025, 66(3): 576-583. DOI: 10.1111/head.15019.
[42]
LIU X, MAILLARD P, BARISANO G, et al. MRI free water mediates the association between diffusion tensor imaging analysis along the perivascular space and executive function in four independent middle to aged cohorts[J/OL]. Alzheimers Dement, 2025, 21(2): e14453 [2026-01-22]. https://pubmed.ncbi.nlm.nih.gov/39740225/. DOI: 10.1002/alz.14453.
[43]
AYRAL V, PASTOR-BERNIER A, DANEAULT V, et al. Association of DTI-ALPS glymphatic index with differential phenoconversion in isolated REM sleep behavior disorder[J/OL]. Neurology, 2025, 105(7): e214042 [2026-01-22]. https://pmc.ncbi.nlm.nih.gov/articles/PMC12456434/. DOI: 10.1212/WNL.0000000000214042.

PREV Hemodynamic study of white matter hyperintensities using multi-delay arterial spin labeling
NEXT Application value of an interpretable 3D directional attention network based on prior knowledge of directional atrophy in Alzheimer<sup><sup>,</sup></sup>s disease diagnosis
  


LINK


Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn