Tag: glymphatic system

Glymphatic System Dysregulation as a Key Contributor to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Defined by the World Health Organization as a neurological disorder, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling illness, affecting millions of people worldwide. First reported in the early nineteenth century, ME/CFS is uniquely characterized by a wide array of symptoms, including fatigue, brain fog, post-exertional malaise (PEM), sleep dysfunction, and orthostatic intolerance (OI). Despite decades of extensive research, there are no effective medical treatments or simple diagnostics for ME/CFS, with an estimated 90% of patients remaining undiagnosed.

The recently discovered glymphatic system, a lymphatic analog of the brain, is believed to be responsible for the removal of toxic metabolic wastes accumulated in the course of daily activities, primarily during sleep. A link between glymphatic dysfunction and some neurological disorders such as Alzheimer’s disease has already been established, raising the possibility of its involvement in ME/CFS. Accordingly, we believe the ME/CFS medical/scientific community will be interested in seriously considering GD an important contributor to its pathophysiology. If so, therapeutics that modulate glymphatic function may also benefit patients with ME/CFS.

Source: Nemat-Gorgani M, Jensen MA, Davis RW. Glymphatic System Dysregulation as a Key Contributor to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int J Mol Sci. 2025 Nov 27;26(23):11524. doi: 10.3390/ijms262311524. PMID: 41373677. https://www.mdpi.com/1422-0067/26/23/11524 (Full text)

Retinal nerve fiber layer thinning in chronic fatigue syndrome as a possible ocular biomarker of underlying glymphatic system dysfunction

In a recent article published in Medical Hypotheses, my colleague and I speculated that glymphatic dysfunction, causing toxic build up within the central nervous system, may be responsible for at least some cases of chronic fatigue syndrome (CFS) [1]. We further postulated that cerebrospinal fluid diversion such as lumboperitoneal shunting may be beneficial to this subgroup of patients by restoring glymphatic transport and waste removal from the brain. In this context, it would be helpful to have a predictive biomarker that can identify CFS patients who are good candidates for this specific treatment. For reasons discussed below, I believe that retinal nerve fiber layer (RNFL) thinning may be a sign of underlying glymphatic system dysfunction in neurodegenerative diseases that result from protein toxicity.

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