Wallerian and trans-synaptic degeneration contribute to optic radiation damage in multiple sclerosis: a diffusion tensor MRI study

Rocca, Maria A.; Mesaroš, Šarlota; Preziosa, Paolo; Pagani, Elisabetta; Stošić-Opinćal, Tatjana; Dujmovic-Basuroski, Irena; Drulović, Jelena; Filippi, Massimo

doi:10.1177/1352458513485146

Cited by 59 publications

(56 citation statements)

References 35 publications

(55 reference statements)

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“…This supports the scenario put forth by Brown et al where T cells first infiltrate sensory nerves near the meningeal barrier causing trans-synatpic and Wallerian degeneration of cortical neurons leading to microglial activation and secondary inflammation in associated cortex. This is supported by studies in MS patients where optic neuritis and retinal injury were associated with increased levels of MRI abnormality in the optic radiation and visual cortex (Pfueller et al, 2011, Reich et al, 2009, Rocca et al, 2013). …”

Section: Discussionmentioning

confidence: 57%

Mapping the accumulation of co-infiltrating CNS dendritic cells and encephalitogenic T cells during EAE

Clarkson

Walker

Harris

et al. 2014

Journal of Neuroimmunology

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Evidence from experimental autoimmune encephalomyelitis (EAE) suggests that CNS-infiltrating dendritic cells (DCs) are crucial for restimulation of coinfiltrating T cells. Here we systematically quantified and visualized the distribution and interaction of CNS DCs and T cells during EAE. We report marked periventricular accumulation of DCs and myelin-specific T cells during EAE disease onset prior to accumulation in the spinal cord, indicating that the choroid plexus-CSF axis is a CNS entry portal. Moreover, despite emphasis on spinal cord inflammation in EAE and in correspondence with MS pathology, inflammatory lesions containing interacting DCs and T cells are present in specific brain regions.

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Section: Discussionmentioning

confidence: 57%

Mapping the accumulation of co-infiltrating CNS dendritic cells and encephalitogenic T cells during EAE

Clarkson

Walker

Harris

et al. 2014

Journal of Neuroimmunology

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“…Furthermore, patients with relapsing–remitting MS (RRMS) (Pagani et al, 2005) and clinically isolated syndrome (CIS) (Lin et al, 2007) were shown to have abnormal diffusion indices in the corticospinal tract that correlated with lesion load, which was interpreted as being associated with ongoing pathologic processes such as Wallerian degeneration and diffuse inflammation (Ciccarelli et al, 2008). Previous in vivo studies using DTI and tractography in MS patients have demonstrated changes in DTI measures along fibers affected by MS lesions; however, these changes were not associated with the effects of an isolated lesion (Bammer et al, 2000; Rocca et al, 2013; Walsh et al, 2011). In a combined post-mortem histology and MRI study, Kolasinski et al were able to demonstrate diffuse WM damage as a result of a focal MS lesion reflected by DTI measures.…”

Section: Introductionmentioning

confidence: 82%

The impact of isolated lesions on white-matter fiber tracts in multiple sclerosis patients

Droby

Fleischer

Carnini

et al. 2015

NeuroImage: Clinical

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Infratentorial lesions have been assigned an equivalent weighting to supratentorial plaques in the new McDonald criteria for diagnosing multiple sclerosis. Moreover, their presence has been shown to have prognostic value for disability. However, their spatial distribution and impact on network damage is not well understood. As a preliminary step in this study, we mapped the overall infratentorial lesion pattern in relapsing–remitting multiple sclerosis patients (N = 317) using MRI, finding the pons (lesion density, 14.25/cm3) and peduncles (13.38/cm3) to be predilection sites for infratentorial lesions. Based on these results, 118 fiber bundles from 15 healthy controls and a subgroup of 23 patients showing lesions unilaterally at the predilection sites were compared using diffusion tensor imaging to analyze the impact of an isolated infratentorial lesion on the affected fiber tracts. Fractional anisotropy, mean diffusion as well as axial and radial diffusivity were investigated at the lesion site and along the entire fiber tract. Infratentorial lesions were found to have an impact on the fractional anisotropy and radial diffusivity not only at the lesion site itself but also along the entire affected fiber tract. As previously found in animal experiments, inflammatory attack in the posterior fossa in multiple sclerosis impacts the whole affected fiber tract. Here, this damaging effect, reflected by changes in diffusivity measures, was detected in vivo in multiple sclerosis patients in early stages of the disease, thus demonstrating the influence of a focal immune attack on more distant networks, and emphasizing the pathophysiological role of Wallerian degeneration in multiple sclerosis.

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“…Another study found higher MD values to be correlated with higher T2 lesion volume [118]. These results were consistently interpreted as a consequence of anterograde and retrograde axonal degeneration due to inflammatory lesional impact within the OR [115,118]. One study reported regional RD elevation in the OR parts that were affected by OR-specific white matter lesions corroborating the role of RD as a potential marker for demyelination [91].…”

Section: Optic Radiation Dtimentioning

confidence: 90%

“…Moreover, positive correlations between mean P100 VEP and RD were demonstrated [85], suggesting putative underlying anterograde trans-synaptic degeneration in the visual pathway to occur and to be quantifiable by OR DTI measurements. Whereas one study showed OR FA to be altered in ON patients compared to non-ON patients [115], another study found no changes in all OR DTI indices between the ON and non-ON group, at all [87]. Although OR DTI provides evidence on possible OR damage consecutively following after ON, the concrete processes and mechanisms of trans-synaptic degeneration within the visual system in vivo have still not been fully elucidated.…”

Section: Optic Radiation Dti In Ms-onmentioning

confidence: 97%

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Diffusion tensor imaging for multilevel assessment of the visual pathway: possibilities for personalized outcome prediction in autoimmune disorders of the central nervous system

et al. 2017

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The afferent visual pathway represents the most frequently affected white matter pathway in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Diffusion tensor imaging (DTI) can reveal microstructural or non-overt brain tissue damage and quantify pathological processes. DTI facilitates the reconstruction of major white matter fiber tracts allowing for the assessment of structure-function and damage-dysfunction relationships. In this review, we outline DTI studies investigating the afferent visual pathway in idiopathic optic neuritis (ON), NMOSD, and MS. Since MS damage patterns are believed to depend on multiple factors, i.e., ON (anterior visual pathway damage), inflammatory lesions (posterior visual pathway damage), and global diffuse inflammatory and neurodegenerative processes, comprehensive knowledge on different contributing factors using DTI in vivo may advance our understanding of MS disease pathology. Combination of DTI measures and visual outcome parameters yields the potential to improve routine clinical diagnostic procedures and may further the accuracy of individual prognosis with regard to visual function and personalized disease outcome. However, due to the inherent limitations of DTI acquisition and post-processing techniques and the so far heterogeneous and equivocal data of previous studies, evaluation of the true potential of DTI as a possible biomarker for afferent visual pathway dysfunction is still substantially limited. Further research efforts with larger longitudinal studies and standardized DTI acquisition and post-processing validation criteria are needed to overcome current DTI limitations. DTI evaluation at different levels of the visual pathway has the potential to provide markers for individual damage evaluation in the future. As an imaging biomarker, DTI may support individual outcome prediction during personalized treatment algorithms in MS and other neuroinflammatory diseases, hereby leveraging the concept of predictive, preventive, and personalized medicine in the field of clinical neuroimmunology.

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Wallerian and trans-synaptic degeneration contribute to optic radiation damage in multiple sclerosis: a diffusion tensor MRI study

Abstract: Both trans-synaptic degeneration secondary to optic nerve damage and Wallerian degeneration due to local T2 lesions contribute to OR damage in MS.

Cited by 59 publications

References 35 publications

Mapping the accumulation of co-infiltrating CNS dendritic cells and encephalitogenic T cells during EAE

Mapping the accumulation of co-infiltrating CNS dendritic cells and encephalitogenic T cells during EAE

The impact of isolated lesions on white-matter fiber tracts in multiple sclerosis patients

Diffusion tensor imaging for multilevel assessment of the visual pathway: possibilities for personalized outcome prediction in autoimmune disorders of the central nervous system

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