Recent findings outlined the existence of an astrocytic-dependent waste cleaning system in the central nervous system called ‘glymphatic system’, that has been demonstrated to be impaired in neurodegenerative disorders such as Alzheimer’s disease. However, the lack of non-invasive techniques for the in vivo assessment of glymphatic function has hampered its assessment so far. Taoka et al. (1), considering that glymphatic function relies on the cerebrospinal-interstitial fluid diffusion in the space between vessel walls and astrocytic end-feet, namely the perivascular space, proposed an indirect measure of glymphatic function based on diffusion-weighted imaging: the diffusion along the perivascular space index (DTI-ALPS index). Using this measure, Carotenuto et al. (2) sought to explore glymphatic function in multiple sclerosis (MS) and its association with disability and brain pathology. Authors reported a significantly lower DTI-ALPS index in MS patients vs healthy controls. Progressive MS patients showed the lowest DTI-ALPS index, being significantly lower compared to both healthy controls and relapsing-remitting MS. In addition, lower DTI-ALPS index was associated with more severe clinical disability and structural damage (focal white matter and cortical lesions, normal-appearing white matter microstructural abnormalities and grey matter volume loss). Finally, DTI-ALPS index was found to decline in the first four years from disease onset without further reduction thereafter. This study suggested that glymphatic impairment may contribute to MS pathology and may fuel disability accrual. However, further studies applying more direct glymphatic function measures (i.e., contrast-based imaging) should confirm this finding and longitudinal studies should better characterise the dynamic of glymphatic damage in MS.
Key Points:
- Brain tissue is cleaned through a recently discovered glymphatic system which is impaired in neurodegenerative disorders such as Alzheimer’s disease.
- DTI-ALPS index is a diffusion-imaging based indirect measure of glymphatic function
- Multiple sclerosis patients show a lower DTI-ALPS index compared with healthy controls with progressive patients showing the lowest values.
- Lower DTI-ALPS index correlated with more severe clinical disability and tissue damage.
- Glymphatic system impairment may contribute to multiple sclerosis pathology and may underpin disability accrual
References:
Taoka T, Masutani Y, Kawai H, et al. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases. Jpn J Radiol. Apr 2017;35(4):172-178. doi:10.1007/s11604-017-0617-z. https://pubmed.ncbi.nlm.nih.gov/28197821/
Carotenuto A, Cacciaguerra L, Pagani E, et al. Glymphatic system impairment in multiple sclerosis: relation with brain damage and disability. Brain. 2021 Dec 17. doi: 10.1093/brain/awab454 (Online ahead of print). https://pubmed.ncbi.nlm.nih.gov/34919648/