How early can you detect neurodegeneration in MS?

Henry et al. Regional grey matter atrophy in clinically isolated syndromes at presentation. J Neurol Neurosurg Psychiatry. 2008 Nov;79(11):1236-44.

BACKGROUND: The presence and degree of neuronal degeneration already existing in MSers at their initial presentation with a clinically isolated syndrome suggestive of multiple sclerosis (CIS) is unclear, and whole brain or whole normalised grey matter analyses have not demonstrated significant atrophy in CIS cohorts at clinical presentation. Voxel-based analyses allow detection of regional atrophy throughout the brain and, therefore, may be sensitive to regional atrophy in CIS patients, and these changes may correspond with clinical disability.

METHODS: This study used a modified voxel-based morphometry (VBM) method to correct for lesion effects to analyse regional atrophy and perform voxel-wise correlations between volume and clinical metrics in 41 untreated CISers at presentation compared with 49 healthy controls.

" Voxel-based morphometry (VBM) is a technique that has been developed by MRIers to look at anatomical or structural features of the brain. A voxel is the 3D-analgoue to a pixel, which is a 2D enity."

RESULTS: The results confirmed that there was no significant difference in whole normalised grey matter volume between CIS and controls, whereas VBM showed significant areas of bilateral thalamic, hypothalamic, putamen and caudate atrophy. 

"The thalamus, hypothalamus, putamen and caudate are deep gray matter or cluster of neurones deep within the brain. These structures are often referred to as the deep gray matter."

Voxel-wise correlations with clinical measures showed that cerebellar volumes correlated with clinical cerebellar function, nine-hole peg test scores and the Multiple Sclerosis Functional Composite (MSFC) score, and that the MSFC score was also correlated with putamen volume. Lastly, T1 lesion volumes were found to correlate with thalamic and hippocampal atrophy, suggesting a link between white matter lesions and grey matter degeneration at the earliest stages of multiple sclerosis.

CONCLUSIONS: Atrophy is present in CISers at presentations, particularly in the thalamus, and other deep grey matter structures. Furthermore, the correlations with clinical metrics suggest the importance of this atrophy to clinical status and the correlation with T1 lesion load suggests a possible role of Wallerian degeneration.

"This is one of many studies to show that subtle brain atrophy exists at the very earliest clinical stage of MS, i.e. at presentation with the first attack. Many, including myself, would therefore argue that neurodegeneration is present from the clinical onset of MS. What drives this neurodegeneration is up for debate; is it inflammation that has occurred in the past or is the neurodegeneration driving the inflammation. We are currently trying to sort this out with several treatment trials; each trial is an experiment that adds knowledge. What this study, however  is telling us that we need to take the progressive component of MS very seriously and start looking at ways to prevent or slow down the gray matter loss as early as possible. Apart from MS prevention this is one of the biggest research challenges in MS at present. On a more positive note several emerging DMTs have positive effects on the progressive brain atrophy  that occurs in MSers; therefore I am confident that we will be able to impact on the neurodegenerative processes of MS that appear to occur independently of inflammation."

CoI: multiple 

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