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Sometimes, doctors cannot find the cause of intracranial hypertension, a syndrome characterized by excess pressure inside the skull. Patients' symptoms are effectively relieved by a procedure that dilates a vein in the brain … yet no one truly understands why.
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At the Paris Brain Institute, Stéphanie Lenck, Jean-Léon Thomas and their colleagues have identified the mechanism behind this phenomenon. Their work, published in the journal Nature Neuroscience, sheds new light on the links between venous flow and the drainage of brain fluids, opening new therapeutic avenues.
Idiopathic intracranial hypertension (IIH) is a rare and poorly understood neurological disorder that affects 1–20 people per 100,000—most often women of childbearing age. It is characterized by increased pressure inside the skull in the absence of a tumor or any other identifiable cause.
Patients typically present with a narrowing of the venous sinuses—large veins located in the dura mater, the fibrous membrane that envelops the brain and spinal cord—as well as poor circulation of brain fluids.
Patients live with chronic headaches, often accompanied by visual disturbances, tinnitus, dizziness and severely disabling cognitive difficulties.
"When intracranial pressure is so high that it damages the optic nerve, patients receive emergency treatment to preserve their sight," explains Stéphanie Lenck (AP-HP), an interventional neuroradiologist at the Pitié-Salpêtrière Hospital and a researcher at the Paris Brain Institute.
"However, other symptoms—sleep disorders, attention difficulties and chronic fatigue—are often overlooked, even though they profoundly affect quality of life, sometimes for years. We still do not know why these symptoms vary so much from one patient to another and do not always match abnormalities seen on MRI."
Understanding the mechanisms of the disease is therefore essential for refining diagnosis and improving patient care in the short-, medium- and long-term.
A closer look at meningeal lymphatic vessels
One effective treatment for IIH involves dilating narrowed venous sinuses using a stent, a small mesh tube that restores blood flow and venous pressure in the brain.
In most cases, after a brief adjustment period, intracranial pressure drops and symptoms subside. Yet the mechanism behind this improvement has remained unclear: What is the relationship between veins and intracranial hypertension? Why is this intervention so effective?
To find out more, Lenck, Thomas and their colleagues followed 16 female patients with IIH and 20 healthy female volunteers, all of whom underwent thorough MRI examinations. In parallel, the researchers developed and studied a mouse model with altered cerebral venous flow.
Their findings are unequivocal: The circulation of brain fluids, including cerebrospinal fluid, is closely dependent on blood flow in the venous sinuses.
"The brain's drainage and immune surveillance rely on a network of specialized vessels: the meningeal lymphatics. They line the perisinus, an anatomical space between the outer layer of the dura mater, which is attached to the skull, and the inner layer, which runs alongside the venous sinuses. These delicate, highly environment-dependent vessels only function when blood flow in the large dural veins is normal," notes Jean-Léon Thomas (Yale University, Inserm).
When the venous sinuses are narrowed, venous pressure rises upstream and fluid circulation in the perisinus is impaired. Brain fluids accumulate, causing the brain and skull of patients to swell under pressure. In mice, the lymphatic vessels can regress until they disappear entirely.
Because meningeal lymphatic vessels also regulate brain inflammation and immune surveillance, this regression is likely to have multiple consequences for the brain. These findings therefore open new avenues of research.
"Our findings could shed light on the mechanisms of sleep, a period during which the glymphatic system is activated. This waste-clearance system of the central nervous system is closely connected to the meningeal lymphatic vessels," Thomas adds.
Science, health and prejudice
Idiopathic intracranial hypertension occurs mainly in obese or overweight women following rapid weight gain. It is still unknown why. This uncertainty contributes to the stigmatization of patients, who are sometimes unfairly blamed for being responsible for their own illness.
Such prejudice can lead to inadequate care, an underestimation of the severity of symptoms and a downplaying of patients' complaints, and patients may then withdraw and develop depressive symptoms.
"The disease remains largely underdiagnosed, probably because it is poorly understood. Too often, only the objective symptoms are considered, such as a cerebrospinal fluid leak or papilledema—that is, a swelling of the optic nerve. Yet IIH should be regarded as a neurological condition in its own right, one that has a major impact on brain function… and not as a mere collection of isolated symptoms. Patients describe their illness very well. Let us listen to them!" Lenck stresses.
"They are highly committed and have contributed enormously to our team's advances, notably through the AFHTIC patient association."
Clues to a female bias
There is probably a genetic predisposition to the disease, to which hormonal factors contribute. Moreover, in women, the meningeal lymphatic network is less developed than in men, making them more vulnerable to damage to these vessels. This may explain their overrepresentation in IIH—but also in other diseases, such as meningiomas.
But what link could there be between weight gain and the onset of intracranial hypertension?
"Lymphatic vessels play a key role in the transport of fats. In cases of excess weight, their function may be disrupted. There is a lead worth exploring here," the researcher concludes.
More information: El Kamouh, M-R. et al. Cerebral Venous Blood Flow Regulates Brain Fluid Clearance via Dural Lymphatics. Nature Neuroscience, July 2026. DOI: 10.1038/s41593-026-02358-1
Provided by Paris Brain Institute
This story was originally published on Medical Xpress.
