Sunday, 9 August 2015

Epilepsy can teach us about the tools to measure MS

Peixoto-Santos JE, Velasco TR, Galvis-Alonso OY, Araujo D, Kandratavicius L, Assirati JA, Carlotti CG, Scandiuzzi RC, Dos Santos AC, Leite JP. Temporal lobe epilepsy patients with severe hippocampal neuron loss but normal hippocampal volume: Extracellular matrix molecules are important for the maintenance of hippocampal volume. Epilepsia. 2015. doi: 10.1111/epi.13082. [Epub ahead of print]
OBJECTIVE: Hippocampal sclerosis is a common finding in patients with temporal lobe epilepsy (TLE), and magnetic resonance imaging (MRI) studies associate the reduction of hippocampal volume with the neuron loss seen on histologic evaluation. Astrogliosis and increased levels of chondroitin sulfate, a major component of brain extracellular matrix, are also seen in hippocampal sclerosis. Our aim was to evaluate the association between hippocampal volume and chondroitin sulfate, as well as neuronal and astroglial populations in the hippocampus of patients with TLE.
METHODS: Patients with drug-resistant TLE were subdivided, according to hippocampal volume measured by MRI, into two groups: hippocampal atrophy (HA) or normal volume (NV) cases. Hippocampi from TLE patients and age-matched controls were submitted to immunohistochemistry to evaluate neuronal population, astroglial population, and chondroitin sulfate expression with antibodies against neuron nuclei protein (NeuN), glial fibrillary acidic protein (GFAP), and chondroitin sulfate (CS-56) antigens, respectively.
RESULTS: Both TLE groups were clinically similar. NV cases had higher hippocampal volume, both ipsilateral and contralateral, when compared to HA. Compared to controls, NV and HA patients had reduced neuron density, and increased GFAP and CS-56 immunopositive area. There was no statistical difference between NV and HA groups in neuron density or immunopositive areas for GFAP and CS-56. Hippocampal volume correlated positively with neuron density in CA1, and with immunopositive areas for CS-56 in CA1, and negatively with immunopositive area for GFAP in CA1. Multiple linear regression analysis indicated that both neuron density and CS-56 immunopositive area in CA1 were statistically significant predictors of hippocampal volume.
SIGNIFICANCE: our findings indicate that neuron density and chondroitin sulfate immunopositive area in the CA1 subfield are crucial for the hippocampal volume, and that chondroitin sulfate is important for the maintenance of a normal hippocampal volume in some cases with severe neuron loss.

What's this got to do with MS,this is an epilepsy study. 

You can say nothing......but the tool to measure nerve loss in MS is the same as used here in epilepsy and this study shows that the tool is lacking in its ability to deliver meaningful information. 

If your brain or spinal cord is atrophying then you are loosing nerves and this is probably true. 

But what happens when you are not loosing brain volume? Are you OK? .........Well not necessarily. 

In this study they look at shrinking hippocampi (areas in the brain where short-term memory is formed). They compare brains where the hippocampi are shrinking by MRI and where they are not.

In both cases nerves were astrocytes (scar tissue) growth and the deposition of chondroitin sulfate a matrix (scaffolding) protein.

This correlated with the level of atrophy so MRI is not really measuring nerve loss but the ability to replace the nerve loss with scaffolding proteins. Therefore MRI is missing a lot if we are looking for nerve loss.

So when you see an MRI in Ms...be warned

No comments:

Post a Comment

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.