MR LYMPHATIC IMAGING IN IDIOPATHIC INTRACRANIAL HYPERTENSION

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, we 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.

Inclusion Criteria: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 insuranceFor 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 reportsHistory of papilledemaNormal neurological examination, except for paralysis of the VIth cranial nerveNeuroimaging: 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 injectionNormal CSF compositionHigh CSF opening pressure (≥ 25 cm of water) obtained from a lumbar puncture performed in lateral decubitusFor healthy volunteers No previous history of neurological or neurosurgical disorderExclusion Criteria:For all participants Pregnant or breastfeeding woman Contraindication to cerebral MRI: metallic implant, pacemaker, artificial heart valve, cerebral vascular malformation, aneurysm clips, metallic fragments, artificial implants, peripheral or neural pacemaker, insulin pump, intravenous catheter, epilepsy , metallic contraceptive device, claustrophobia, refusal to be informed in case of abnormal MRI (with a significant medical abnormality) Hypersensitivity to the active substance of the contrast agent or to any of the excipients (Sodium calcobutrol, Trometamol, 1N hydrochloric acid (pH adjustment), Water for injections) lumbar puncture in the month preceding the brain MRI Neurological tumoral, degenerative, vascular, inflammatory or progressive pathology Renal or hepatic impairment MRI with gadolinium injection performed in the 7 days preceding the inclusion visit Person subject to a measure of legal protection (safeguard of justice, curatorship, guardianship), deprived of liberty by judicial or administrative decisionFor participants with IIH Participants with a probable but not definite diagnosis of IIH according to the Dandy modified criteriaFor healthy volunteers Chronic headaches (>15 days per month) Uncorrected and/or unlabeled visual symptoms (visual blurriness, diplopia, visual eclipses, papilledema, optic atrophy)