Measuring progression with atrophy

Valsasina P, Rocca MA, Horsfield MA, Copetti M, Filippi M.A longitudinal MRI study of cervical cord atrophy in multiple sclerosis. J Neurol. 2015. [Epub ahead of print]

There is an urgent need of fast and accurate methods for the longitudinal quantification of cervical cord atrophy in multiple sclerosis (MS). Aim of this study was to compare a new semi-automatic method [SA method] with an existing cord segmentation standard method [S method] to measure cervical cord atrophy progression in MS patients. Normalized cervical cord cross-sectional area (CSA) was compared between 35 MS patients and 9 healthy controls (HC) at baseline and after 2.3 years of follow-up. Correlations with clinical/conventional MRI variables and a power calculation study were also performed. At follow-up, the S method detected a 1 % CSA increase in HC and a 3.5 % decrease in MS patients (p = 0.01), while the SA method detected a 0.1 % decrease in HC and 3 % decrease in MS patients (p = 0.02). The SA method was more sensitive to associations with disability/conventional MRI variables and also provided lower numbers of subjects per arm compared to the S method in a putative clinical trial scenario. Cord SA CSA measurements were more sensitive to longitudinal changes in MS patients than S method measurements. 

This method compares two methods to measure shrinkage of the spinal cord. Because shrinkage is associated with nerve loss and the accumulation of disability. However, what you have to remember when you see atrophy mentioned in papers it that it may be the tip of an iceberg and much is being missed. This is based on what we can see in animals. Whilst there may be atrophy  but because we can do histology we can say that there is massive nerve loss that being missed because the tissue damage is being replaced by scar.
So in the above case the spinal cord area was assessed after one attack occurring around day 15-20, on day 30 and also at day105
and at day 105 in animals that had had four attacks. In terms of atrophy you can see there is only about 10% volume loss. However if you count nerves in these spinal cords there are massive differences. So if you count nerve numbers in the dorsal columns (top bit in the dashedtriangle) you can see after one attack there there is a 10% loss of nerves and there is progression so that by Day 105 actually 30% of the nerves will be loss. If you compare what happens after 4 attacks about 75% of the nerves have been loss compared to the 10% atophy that would be seen by MRI. This amount of nerve loss is high in selected regons, but even overall the is about 40% total nerve loss in the spinalcord of these mice.

Hampton DW, Serio A, Pryce G, Al-Izki S, Franklin RJ, Giovannoni G, Baker D, Chandran S.

Neurodegeneration progresses despite complete elimination of clinical relapses in a mouse model of multiple sclerosis. Acta Neuropathol Commun. 2013;1(1):84.