Pseudotumor Cerebri and Glymphatic Dysfunction

Abstract

In contrast to virtually all organ systems of the body, the central nervous system was until recently believed to be devoid of a lymphatic system. The demonstration of a complex system of paravascular channels formed by the endfeet of astroglial cells ultimately draining into the venous sinuses has radically changed this idea. The system is subsidized by the recirculation of cerebrospinal fluid (CSF) through the brain parenchyma along paravascular spaces (PVSs) and by exchanges with the interstitial fluid (IF). Aquaporin-4 channels are the chief transporters of water through these compartments. This article hypothesizes that glymphatic dysfunction is a major pathogenetic mechanism underpinning idiopathic intracranial hypertension (IIH). The rationale for the hypothesis springs from MRI studies, which have shown many signs related to IIH without evidence of overproduction of CSF. We propose that diffuse retention of IF is a direct consequence of an imbalance of glymphatic flow. This imbalance, in turn, may result from an augmented flow from the arterial PVS into the IF, by impaired outflow of the IF into the paravenous spaces, or both. Our hypothesis is supported by the facts that (i) visual loss, one of the main complications of IIH, is secondary to the impaired drainage of the optic nerve, a nerve richly surrounded by water channels and with a long extracranial course in its meningeal sheath; (ii) there is a high association between IIH and obesity, a condition related to paravascular inflammation and lymphatic disturbance, and (iii) glymphatic dysfunction has been related to the deposition of β-amyloid in Alzheimer’s disease. We conclude that the concept of glymphatic dysfunction provides a new perspective for understanding the pathophysiology of IIH; it may likewise entice the development of novel therapeutic approaches aiming at enhancing the flow between the CSF, the glymphatic system, and the dural sinuses.

Signs of Intracranial Hypertension, Hypermobility, and Craniocervical Obstructions in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Other mechanisms that may cause neuroinflammation in the CNS are also possible. For instance, the “glymphatic system,” a functional metabolic waste clearance system that engages the CNS, can contribute to IH, and obstructions or flow disturbances can compromise the glymphatic system ( 27 ). Komaroff recently expressed this view of ME/CFS pathophysiology ( 3 ).…”

Pattern and severity of transverse sinus stenosis in patients with pulsatile tinnitus associated with sigmoid sinus wall anomalies

“…Furthermore, although transverse sinus diameter alone is not an adequate proxy for posterior fossa venous outflow, quantitative methods for measuring overall and segmental posterior fossa venous outflow are still not available. Numerous alternative pathways exist, including the occipital sinuses; occipital emissary veins; suboccipital venous plexus; a petrosquamous sinus; condylar veins and others that could play a role; as well as meningeal lymphatics and glymphatics, which are not visible at all with conventional imaging . A dynamic, flow‐based method that accounted for all possible alternative pathways would allow for systematic comparison between different cohorts of subjects.…”

“…Numerous alternative pathways exist, including the occipital sinuses; occipital emissary veins; suboccipital venous plexus; a petrosquamous sinus; condylar veins and others that could play a role; as well as meningeal lymphatics and glymphatics, which are not visible at all with conventional imaging. [18][19][20] A dynamic, flow-based method that accounted for all possible alternative pathways would allow for systematic comparison between different cohorts of subjects.…”

Blood–Brain Barrier, Lymphatic Clearance, and Recovery: Ariadne’s Thread in Labyrinths of Hypotheses

“…Bezerra et al [100] proposed that the glymphatic dysfunction is identified as a major pathogenetic mechanism underpinning idiopathic intracranial hypertension.…”