Multiple Sclerosis: Functional Changes After Inflammation May Partly Explain Clinico-Radiological Paradox Interview with:
Netta Levin MD PhD
fMRI lab
Neurology Department
Hadassah Hebrew University Medical Center
Jerusalem What is the background for this study?

Response: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, manifesting with episodes of local inflammatory processes, called relapses. The most useful surrogate laboratory test for MS is magnetic resonance imaging (MRI), in which dissemination of demyelinating lesions in space and time are the hallmark of the disease. However, there is a discrepancy between the lesion load – the number, size, and location of the lesions – and the clinical state of the patients, reflected in their disability. This discrepancy is known as the “clinico-radiological paradox” and suggests that something other than the well-known mechanisms of demyelination, remyelination, and axonal loss may tip the scale of recovery from an acute episode. Global effects of the local damage and compensatory mechanisms were suggested as an explanation to this paradox.

In this study, we compared the visual system of patients with clinically isolated syndrome optic neuritis (ON) to patients with clinically isolated episodes in other functional systems, exploring changes, both anatomical and functional, caused to the system following the demyelinating episode. Optic neuritis was deemed a good in vivo model for studying the pathophysiology of tissue damage and repair in MS due to its characteristic clinical manifestation and to the visual pathways’ amenability to investigation using various techniques. To assess anatomical wiring ,i.e the white matter fibers themselves , we used diffusion tensor imaging (DTI). To assess functional networking as reflected by signal synchronization between distinct brain regions, we used resting state fMRI. What are the main findings?

Response: We found that in our cohort the local, Wallerian-like damage sustained by the optic tract did not progress beyond the synapse in the lateral geniculate nucleus (LGN), thus rejecting the possibility of trans-synaptic degeneration reflecting a more global effect. However, even when no other damage is found in the anatomical visual wiring, a change in functional connectivity was found within the visual network, suggesting that these changes reflect the brain’s modification abilities, acting together with its recovery abilities to overcome insult. What should readers take away from your report?

Response: Functional visual network changes occur in the post-ON brain even in the absence of anatomical changes beyond the local lesion damage extension. This may explain to some extent the clinico-radiological paradox.We suggest that these changes emphasize the need to evaluate the brain as a whole and highlight the importance of using complementing modalities in studies of this type. What recommendations do you have for future research as a result of this study?

Response: We believe that future research should focus on whether the global changes caused to the system, as well as the effects observed in both networking and wiring of the visual system may predict the success of a given new treatment or the overall prognosis of the individual patient. It is important to know if such considerations need to be taken into the equation when a clinician decides on a course of treatment. 

Disclosures: This is a collaborative work performed in the Hadassah-Hebrew University Medical Center, Jerusalem, Israel, and the NeuroCure Clinical Research Center in Charité Universitätsmedizin Berlin, Berlin, Germany. Thank you for your contribution to the community.

Citation: Backner Y, Kuchling J, Massarwa S, Oberwahrenbrock T, Finke C, Bellmann-Strobl J, Ruprecht K, Brandt AU, Zimmermann H, Raz N, Paul F, Levin N. Anatomical Wiring and Functional Networking Changes in the Visual System Following Optic Neuritis. JAMA Neurol. Published online January 02, 2018. doi:10.1001/jamaneurol.2017.3880

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions. 

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Last Updated on January 4, 2018 by Marie Benz MD FAAD