Disrupted brain waste clearance system in ME/CFS

Researchers

Kiran Thapaliya, Sonya Marshall-Gradisnik, Maira Inderyas, Leighton Barnden

Institution

Griffith University, Gold Coast, Queensland, Australia

Publication

Frontiers in Neuroscience, 2026 June 19; 20:1875420

Key findings

MRI brain scans were performed in ME/CFS participants and healthy controls to assess the functioning of the glymphatic system, which is responsible for brain waste clearance.
Glymphatic dysfunction was demonstrated in the ME/CFS cohort.
Poorer glymphatic functioning was associated with greater severity of symptoms, including sleep dysfunction and cognitive impairment.
Impairment of the glymphatic system in ME/CFS may therefore contribute to accumulation of waste products in the brain, leading to inflammation and resulting in neurological symptoms.

About the study

Dr Kiran Thapaliya and colleagues at Griffith University in Australia conducted a preliminary study using neuroimaging to explore the glymphatic system in people with ME/CFS. The glymphatic system is responsible for clearing waste products from the brain, similar to the role of the lymphatic system in the rest of the body.

Waste clearance by the glymphatic system involves the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF), primarily through special channels known as aquaporins. This process is important as it washes away metabolic waste like amyloid-β (the driving force of Alzheimer’s disease) and distributes essential nutrients such as glucose, lipids and amino acids.

The researchers assessed lymphatic function using a method called DTI-ALPS (diffusion tensor imaging along the perivascular space), which is a non-invasive medical imaging technique using MRI (magnetic resonance imaging) to evaluate fluid dynamics in the brain. They highlight that, while DTI-ALPS has been used to assess glymphatic function in neurodegenerative diseases like Alzheimer’s disease and multiple sclerosis, it has not previously been used to study ME/CFS, despite the fact that the disease is associated with symptoms such as cognitive dysfunction and sleep difficulties.

The glymphatic system is thought to be more active during sleep rather than wakefulness. It is theorised that sleep disturbance impairs glymphatic function, resulting in the deposition of metabolic waste products in the brain, potentially causing inflammation leading to ME/CFS symptoms. This appears to be a vicious cycle where symptoms disrupt the glymphatic system leading to more and/or worsening symptoms.

Prof. Leighton Barnden, Dr Kiran Thapaliya & Prof. Sonya Marshall-Gradisnik

What did they do?

The aims of the study were to use the DTI-ALPS to assess glymphatic function in 31 individuals with ME/CFS compared with 27 healthy controls, and to explore the association between glymphatic function and ME/CFS. ME/CFS participants met either the Canadian Consensus Criteria or the International Consensus Criteria International Consensus Criteria for diagnosis.

Symptoms were assessed using a range of validated tools, while brain imaging data was acquired using a 3T Prisma MRI scanner, which provides exceptional image quality and is particularly useful for visualising fluid shifts and waste clearance in the brain’s glymphatic system. Various methods were then used to process the data and compare the participant groups.

What did they find?

The DTI-ALPS index (which estimates the efficiency of the glymphatic system) was significantly lower in people with ME/CFS than in healthy controls. This indicates impaired glymphatic clearance in people with ME/CFS; i.e. the brain cannot efficiently flush out waste products in these individuals.

Furthermore, the lower DTI-ALPS index was significantly associated with sleep disturbance and impaired concentration. In other words, greater severity of sleep disruption and cognitive impairment is associated with poorer functioning of the glymphatic system.

Based on these findings, the researchers suggest that glymphatic dysfunction could potentially contribute to the neurological symptoms experienced in ME/CFS.

Interestingly, the findings were only applicable to half the brain: “only the right hemisphere DTI-ALPS index was significantly lower in ME/CFS compared to healthy controls, with no differences observed in the left hemisphere”. The researchers say that “this kind of hemispheric asymmetry” has been previously reported in other diseases affecting the brain such as temporal lobe epilepsy and Parkinson’s disease.

Due to a lack of studies on glymphatic function in ME/CFS, a direct comparison of these results with other findings was not possible. While the underlying cause of right-hemisphere predominance remains unclear, the research group pointed to their prior work, which demonstrated asymmetric cortical thickness and volume in individuals with ME/CFS.

The researchers believe that multiple factors could be responsible for the reduced glymphatic function in ME/CFS, including sleep deprivation, reduced physical activity, elevated stress, omega-3 (essential fatty acid) and high blood pressure. It is suggested that other common ME/CFS symptoms may further suppress glymphatic function.

Study limitations and future directions

As this is a preliminary, cross-sectional study with a small sample size, the findings should be considered as exploratory. The researchers noted several factors that could influence the DTI-ALPS index – such as participant handedness, sleeping position and an uneven sex distribution – which were not controlled for in this study. Consequently, the authors suggest that future research must prioritise a larger sample size with balanced cohorts to validate their findings.

Conclusions

This preliminary study provides “first evidence” of glymphatic dysfunction in ME/CFS, associated with sleep dysfunction and impaired concentration.

The researchers suggest that impairment of the glymphatic system may contribute to accumulation of metabolic waste products in the brain causing inflammation, and ultimately leading to the neurological symptoms experienced in ME/CFS.

The researchers emphasise that the relatively small number of participants and the cross-sectional nature of the study mean that the results should be interpreted with caution, and long-term follow-up studies are needed to establish whether the abnormalities progress over time.

Media coverage

This article has received widespread media coverage, including:

Read more about what the Griffith group are doing in their ongoing ME Research UK-funded study in ME/CFS.