50+ shades of grey matter

One of the commonest myths about the brain is that we use only 10% of it. The origin of this probably goes back to the unsung hero of neuroscience, William James, when he was jokingly commenting on the fact that the functioning neurons sum up to only 10% of the brain cells and the 90% are supportive cells.

The grey matter carries most of cells in the nervous system (the 10%+90% cells) as well as the extensive connections between these cells. Loss of these cells and their connections has been associated with disability of MS more than to white matter broadly speakig.

Grey matter is vulnerable to damage

Sometimes (personal opinion) I like to imagine grey matter as a busy odd looking scientist who needs silence and quite environment to do his work, but the immune reactions taking place around him keeps him distracted. Presence of a continous ongoing immune reaction within the nervous system is toxic to the grey matter, and the orchestrating complex function of the grey matter gradually collapse.

Grey matter pathology is well evident in MS, as well as other disease conditions that result in continous immune activation within the nervous system compartment, such as infections, and systemic autoimmune conditos,

Grey matter damage in MS

Grey matter structures such as the “thalamus” loses an observable amount of its volume in the early phase of the disease. Focal damage at that time is not stong enough to interpret such atrophic changes.

Grey matter loss in MS (deep grey matter in particular) has been recently linked to higher unemployment, even after adjustment for age, education and disease duration.

There cerebral cortex also suffer various form of damage. Brain coverings in MS host special collections of immune cells termed “lymphoid follicles” which maintains a level of continous damage and support to other immune cells. It is belived the chemicals secreted at these follicles, antibodies and cytotoxic cells all exert a direct damage to their nearest neighbour “the cerebral cortes. Subpial demyelination, cortical thinning and regional atrophy among many other forms of damage is observed frequently in progressive phase of the disease.

Spinal cord matters too

Recently, these very “lymphoid follicles” has been well observed in the coverings of the spinal cord in secondary progressive MS (SPMS). Comparing SPMS patients who showed lymphoid follicles to those who did not, CD20 B lymphocytes were 3 times more abundant within the meningies, perivascular spaces as well as grey and white mater. Other immune cells such as the antibody producing cells, T cells, and macrophages were present in abundance as well. Grey matter demyelination in the spinal cord was more pronounced than white matter, a number of studies show that grey matter demyelination causes significant neuronal and synaptic loss.

This is particularly interesting observation in MS because progressive loss of walking ability is one hallmark of the disease. The continous damage to grey matter of the spinal cord is different from that of the brain in one particular fact, the spinal cord has much less tissue and cells to withistand continous inflammation for long time. The whole spinal cord thickness is slightly larger than your little finger.

Spinal cord atrophy measued by MRI is strongly associated with disability progression independently from what is taking place upstairs in the brain. Grey matter atrophy of the spinal cord has been the most to correlate with disability using MRI in a number of other studies.

It is difficult to translate what we see in pathology studies directly to in-vivo MRI findings, as loss of cord volume does not necessarily reflect cell loss but both are linked and point towards the fact the spinal cord pathology is a main determinant to disease outcome and needs to be put as a priority in assessing disease trajectory on individual patient level.