MR Lymphatic Imaging in Idiopathic Intracranial Hypertention

NCT05762367 | Completed

• 2 other identifiers: C22-132022-A01422-41
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

In the brain and its borders, blood vessels coexist with lymphatic vessels exclusively in the dura mater, the outermost layer of meninges. Dural lymphatics are present in various vertebrate species, including humans, and a cluster of experimental studies in the mouse strongly suggest their relevance in the pathophysiology of chronic and acute neurological disorders in humans. Demonstrating this assumption is however still at stake and the lymphatic regulatory mechanisms involved remain poorly characterized. Our main objective is to assess dural lymphatics contribution to the pathophysiology of a rare neurological disorder: idiopathic intracranial hypertension (IIH). In IIH patients, intracranial hypertension causes severe headache and visual loss and is associated with a stenosis of dural sinuses and abnormal retention of fluids in the central nervous system. Angioplasty treatment by stent placement into venous sinuses is frequently followed by recurrent stenosis suggesting that, in addition to the blood vessels, the duro-lymphatic environment contributes to disease progression. Several studies have found hot spots of lymphatic uptake at confluence points between cerebral veins and dural sinuses. Based on this premise, the investigators predict a causal link between lymphatic and venous behavior around dural sinuses and the remodeling of dural lymphatics in neurovascular conditions such as IIH. Our approach will combine radiological observations from human patients with experimental analyses in mouse models. The investigators have recently developed a technique of high resolution vessel wall imaging to explore and compare the lymphatic networks between individuals. This advanced MR-imaging technique has been validated through a translational study comparing the lymphatic networks in mice and humans (Jacob et al. 2022, JExpMed). Using this tool, the investigators aim to monitor dural lymphatic and sinus wall abnormalities in patients with IIH. In this view, cohorts of IIH patients and controls without neurological disorders (n = 20/cohort) will be scanned by MRI to perform high resolution vessel wall imaging of the dural lymphatics, sinus and cerebral veins.

Conditions

Idiopathic Intracranial Hypertension

Keywords

Dural venous stenoses; MRI; Vessel Wall Imaging; Headache; Papilledema

Outcome Measures

Primary Outcomes (1)

• Morphometric study of the dural lymphatic network in patients with IIH vs controls

  Measurement of the dural lymphatic network volume (mm3) in patients with IIH vs controls

  Immediate

Secondary Outcomes (3)

• Characterization of lateral sinus stenoses using high resolution vessel wall imaging in patients with IIH

  Immediate

• Morphometric study of the cervical lymphatic network in patients with IIH vs controls

  Immediate

• Comparison of the volumes of the different compartments of the skull in patients with IIH vs controls

  Immediate

Study Arms (2)

Patients with IIH

EXPERIMENTAL

Female patients with IIH between 20 and 40 years old

Diagnostic Test: 3T MRI with Gadobutrol injection

Healthy volunteers

ACTIVE COMPARATOR

Female healthy volunteers between 20 and 40 years old

Diagnostic Test: 3T MRI with Gadobutrol injection

Interventions

3T MRI with Gadobutrol injection DIAGNOSTIC_TEST

MRI will be performed in all participants before and after Gadobutrol injection

Healthy volunteers; Patients with IIH

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For all participants:
• Age \> 18 years and ≤ 40 years female gender Absence of previous neurosurgical or endovascular neurological history Participant able to express her consent Medical insurance
• For participants with IIH No required criterion of severity or evolution of IIH Definite diagnosis of IIH according to Dandy's modified criteria. All of the following criteria must be met and verified by medical reports or certificates from a neurologist, especially the value of the CSF opening pressure measured during the lumbar puncture must be clearly noted on the reports
• History of papilledema
• Normal neurological examination, except for paralysis of the VIth cranial nerve
• Neuroimaging: normal cerebral parenchyma without hydrocephalus, intracranial expansive process, or structural anomaly, and absence of meningeal contrast enhancement in MRI without and with contrast product. A venous angio-MRI is necessary in atypical patients; if MRI is unavailable or contraindicated, a brain scan without and with contrast product can be done in combination with a venous angioscan with contrast injection
• Normal CSF composition
• High CSF opening pressure (≥ 25 cm of water) obtained from a lumbar puncture performed in lateral decubitus
• For healthy volunteers No previous history of neurological or neurosurgical disorder

You may not qualify if:

• For participants with IIH Participants with a probable but not definite diagnosis of IIH according to the Dandy modified criteria
• For healthy volunteers Chronic headaches (\>15 days per month) Uncorrected and/or unlabeled visual symptoms (visual blurriness, diplopia, visual eclipses, papilledema, optic atrophy)

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

Service de Neuroradiologie, Groupe Hospitalier Pitié Salpêtrière, Paris, France

Paris, Île-de-France Region, 75000, France

Location

Related Publications (10)

• Ahn JH, Cho H, Kim JH, Kim SH, Ham JS, Park I, Suh SH, Hong SP, Song JH, Hong YK, Jeong Y, Park SH, Koh GY. Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid. Nature. 2019 Aug;572(7767):62-66. doi: 10.1038/s41586-019-1419-5. Epub 2019 Jul 24.

  PMID: 31341278 BACKGROUND

• Lenck S, Radovanovic I, Nicholson P, Hodaie M, Krings T, Mendes-Pereira V. Idiopathic intracranial hypertension: The veno glymphatic connections. Neurology. 2018 Sep 11;91(11):515-522. doi: 10.1212/WNL.0000000000006166.

  PMID: 30201744 BACKGROUND

• Ma Q, Ineichen BV, Detmar M, Proulx ST. Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice. Nat Commun. 2017 Nov 10;8(1):1434. doi: 10.1038/s41467-017-01484-6.

  PMID: 29127332 BACKGROUND

• Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, Herod SG, Knopp J, Setliff JC, Lupi AL, Da Mesquita S, Frost EL, Gaultier A, Harris TH, Cao R, Hu S, Lukens JR, Smirnov I, Overall CC, Oliver G, Kipnis J. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018 Oct;21(10):1380-1391. doi: 10.1038/s41593-018-0227-9. Epub 2018 Sep 17.

  PMID: 30224810 BACKGROUND

• Lenck S, Nicholson P. Cerebral Venous Wall Diseases: The Other Side of the Picture. AJNR Am J Neuroradiol. 2021 Jan;42(2):297-298. doi: 10.3174/ajnr.A6914. Epub 2021 Jan 7. No abstract available.

  PMID: 33414232 BACKGROUND

• Lenck S, Vallee F, Labeyrie MA, Touitou V, Saint-Maurice JP, Guillonnet A, Tantot A, Crassard I, Bernat AL, Houdart E. Stenting of the Lateral Sinus in Idiopathic Intracranial Hypertension According to the Type of Stenosis. Neurosurgery. 2017 Mar 1;80(3):393-400. doi: 10.1227/NEU.0000000000001261.

  PMID: 27218234 BACKGROUND

• Kedra A, Lahlouh M, Shotar E, Chenoune Y, Boistard L, Boussac A, Shor N, Savatovsky J, Hage R, Touitou V, Nicholson P, Clarencon F, Piotin M, Blanc R, Lenck S. Global collapse of the dural sinuses after venous stenting in idiopathic intracranial hypertension. J Neurol Neurosurg Psychiatry. 2021 Dec;92(12):1363-1364. doi: 10.1136/jnnp-2020-325717. Epub 2021 Jun 24. No abstract available.

  PMID: 34168084 BACKGROUND

• Absinta M, Ha SK, Nair G, Sati P, Luciano NJ, Palisoc M, Louveau A, Zaghloul KA, Pittaluga S, Kipnis J, Reich DS. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. Elife. 2017 Oct 3;6:e29738. doi: 10.7554/eLife.29738.

  PMID: 28971799 BACKGROUND

• Xie Y, Yang Q, Xie G, Pang J, Fan Z, Li D. Improved black-blood imaging using DANTE-SPACE for simultaneous carotid and intracranial vessel wall evaluation. Magn Reson Med. 2016 Jun;75(6):2286-94. doi: 10.1002/mrm.25785. Epub 2015 Jul 8.

  PMID: 26152900 BACKGROUND

• Jacob L, de Brito Neto J, Lenck S, Corcy C, Benbelkacem F, Geraldo LH, Xu Y, Thomas JM, El Kamouh MR, Spajer M, Potier MC, Haik S, Kalamarides M, Stankoff B, Lehericy S, Eichmann A, Thomas JL. Conserved meningeal lymphatic drainage circuits in mice and humans. J Exp Med. 2022 Aug 1;219(8):e20220035. doi: 10.1084/jem.20220035. Epub 2022 Jul 1.

  PMID: 35776089 BACKGROUND

MeSH Terms

Conditions

Pseudotumor Cerebri; Headache; Papilledema

Condition Hierarchy (Ancestors)

Intracranial Hypertension; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: MRI will be pseudo-anonymised and blindly analyzed
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 20 patients with IIH and 20 volunteers paired on age (20-40 yo) and gender will be prospectively enrolled in the study

Study Record Dates

• First Submitted: February 28, 2023
• First Posted: March 9, 2023
• Study Start: March 10, 2023
• Primary Completion: April 11, 2025
• Study Completion: May 11, 2025
• Last Updated: October 6, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)