Nerve loss due to lack of repair

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Tonietto M, Poirion E, Lazzarotto A, Ricigliano V, Papeix C, Bottlaender M, Bodini B, Stankoff B. Periventricular remyelination failure in multiple sclerosis: a substrate for neurodegeneration. Brain. 2022 Sep 13:awac334.

In multiple sclerosis, spontaneous remyelination is generally incomplete and heterogenous across patients. A high heterogeneity in remyelination may also exist across lesions within the same individual, suggesting the presence of local factors interfering with myelin regeneration.

In this study we explored in-vivo the regional distribution of myelin repair and investigated its relationship with neurodegeneration.

We first took advantage of the myelin binding property of the…..tracer [11C]PiB to conduct a repeated imaging study in an original cohort of 19 participants with a relapsing-remitting form of multiple sclerosis, followed-up over a period of 1-4 months.

We then replicated our results on an independent cohort of 40 people with multiple sclerosis followed-up over one year with magnetization transfer imaging, an MRI metrics sensitive to myelin content……Maps of myelin content changes were generated ………. We demonstrated a selective failure of remyelination in periventricular white (edge around the ventricules which are fluid filled areas in the brain) matter lesions of people with multiple sclerosis in both cohorts. In both the original and the replication cohort, we estimated that the probability of demyelinated to remyelinate over the follow-up increased significantly as a function of the distance from ventricular cerebro-spinal fluid. Enlarged choroid plexus (a area of blood vessels where spinal fluid is generated), a recently discovered biomarker linked to neuroinflammation, was found to be associated with the periventricular failure of remyelination in the two cohorts (r=-0.79, p = 0.0018; r=-0.40, p = 0.045 respectively), suggesting a role of the brain-cerebrospinal fluid barrier in affecting myelin repair in surrounding tissues.

In both cohorts, the failure of remyelination in periventricular white matter lesions was associated with lower thalamic volume (r = 0.86, p < 0.0001; r = 0.33; p = 0.069 respectively) an imaging marker of neurodegeneration.

Interestingly, we also showed an association between the periventricular failure of remyelination and regional cortical atrophy that was mediated by the number of cortex-derived tracts passing through periventricular white matter lesions, especially in patients at the relapsing-remitting stage. Our findings demonstrate that lesion proximity to ventricles is associated with a failure of myelin repair and support the hypothesis that a selective periventricular remyelination failure in combination with the large number of tracts connecting periventricular lesions with cortical areas is a key mechanism contributing to cortical damage in multiple sclerosis.

So it suggests the failure to repair is associated with nerve loss

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