Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis

Vogt, Johannes; Paul, Friedemann; Aktaş, Orhan; Müller-Wielsch, Kathrin; Dörr, Jan; Dörr, Susanne; Bharathi, B. Suman; Glumm, Robert; Schmitz, Christoph; Steinbusch, Harry; Raine, Cedric S.; Tsokos, Michael; Nitsch, Robert; Zipp, Frauke

doi:10.1002/ana.21719

Cited by 156 publications

(148 citation statements)

References 38 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…Our data corroborate MRI data showing neuroaxonal damage during the very earliest MS stages, 4,28 as well as histopathology data from brain 29 and eye, 13 and from experimental autoimmune encephalomyelitis. 30,31 In line with previous investigations, our study provides evidence that inflammatory attacks to the optic nerve to the extent of a clinical or subclinical ON may not be a pre-requisite for damage to the retinal GCIPL. 26 Our finding that neuronal retinal damage begins during very early disease stages raises urgent questions, the answers to which may challenge our understanding of the underlying pathology and mechanisms of MS. 32 Is the damage we found in the retina a consequence of the retrograde degeneration of retinal nerve fibres that occurs as a consequence of autoimmune brain inflammation in MS?…”

Section: Discussionsupporting

confidence: 90%

Retinal ganglion cell and inner plexiform layer thinning in clinically isolated syndrome

et al. 2013

Self Cite

View full text Add to dashboard Cite

Background: Axonal and neuronal damage are widely accepted as key events in the disease course of multiple sclerosis. However, it has been unclear to date at which stage in disease evolution neurodegeneration begins and whether neuronal damage can occur even in the absence of acute inflammatory attacks. Objective: To characterize inner retinal layer changes in patients with clinically isolated syndrome (CIS). Method: 45 patients with CIS and age-and sex-matched healthy controls were investigated using spectral domain optical coherence tomography. Patients' eyes were stratified into the following categories according to history of optic neuritis (ON): eyes with clinically-diagnosed ON (CIS-ON), eyes with suspected subclinical ON (CIS-SON) as indicated by a visual evoked potential latency of >115ms and eyes unaffected by ON (CIS-NON).Results: CIS-NON eyes showed significant reduction of ganglion cell-and inner plexiform layer and a topography similar to that of CIS-ON eyes. Seven eyes were characterized as CIS-SON and likewise showed significant retinal layer thinning. The most pronounced thinning was present in CIS-ON eyes. Conclusion: Our findings indicate that retinal pathology does occur already in CIS. Intraretinal layer segmentation may be an easily applicable, non-invasive method for early detection of retinal pathology in patients unaffected by ON.

show abstract

Section: Discussionsupporting

confidence: 90%

Retinal ganglion cell and inner plexiform layer thinning in clinically isolated syndrome

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Spinal cord pathology is an important determinant of permanent neurological disability with cardinal characteristics being inflammatory demyelination, synaptic, neuronal and axonal loss 6, 7, 8, 9, 10, 11. The precise nature of how these pathological alterations impact clinical phenotypes remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

Grussu

Schneider

Tur

et al. 2017

Ann Clin Transl Neurol

265

243

View full text Add to dashboard Cite

ObjectiveConventional magnetic resonance imaging (MRI) of the multiple sclerosis spinal cord is limited by low specificity regarding the underlying pathological processes, and new MRI metrics assessing microscopic damage are required. We aim to show for the first time that neurite orientation dispersion (i.e., variability in axon/dendrite orientations) is a new biomarker that uncovers previously undetected layers of complexity of multiple sclerosis spinal cord pathology. Also, we validate against histology a clinically viable MRI technique for dispersion measurement (neurite orientation dispersion and density imaging, NODDI), to demonstrate the strong potential of the new marker.MethodsWe related quantitative metrics from histology and MRI in four post mortem spinal cord specimens (two controls; two progressive multiple sclerosis cases). The samples were scanned at high field, obtaining maps of neurite density and orientation dispersion from NODDI and routine diffusion tensor imaging (DTI) indices. Histological procedures provided markers of astrocyte, microglia, myelin and neurofilament density, as well as neurite dispersion.ResultsWe report from both NODDI and histology a trend toward lower neurite dispersion in demyelinated lesions, indicative of reduced neurite architecture complexity. Also, we provide unequivocal evidence that NODDI‐derived dispersion matches its histological counterpart (P < 0.001), while DTI metrics are less specific and influenced by several biophysical substrates.InterpretationNeurite orientation dispersion detects a previously undescribed and potentially relevant layer of microstructural complexity of multiple sclerosis spinal cord pathology. Clinically feasible techniques such as NODDI may play a key role in clinical trial and practice settings, as they provide histologically meaningful dispersion indices.

show abstract

“…The data were confirmed by high-precision unbiased stereological quantification of spinal cord neurons in post-mortem MS tissue. In this material, T cells secreting TNF-related apoptosis inducing ligand TRAIL were found in close vicinity to apoptotic neurons (Vogt et al, 2009). …”

Section: Demyelination Axonal Damage and Gray Matter Pathology In C5mentioning

confidence: 86%

“…Motor neuron pathology as one aspect of gray matter disease has not been investigated extensively yet. Vogt and colleagues (Vogt et al, 2009) were able to demonstrate that in MS patients compound muscle action potential amplitudes and motor unit numbers were decreased compared to controls subjects, which was indicative of lower motor neuron loss. The data were confirmed by high-precision unbiased stereological quantification of spinal cord neurons in post-mortem MS tissue.…”

Section: Demyelination Axonal Damage and Gray Matter Pathology In C5mentioning

confidence: 96%

Studies on the CNS Histopathology of EAE and Its Correlation with Clinical and Immunological Parameters

Küerten¹,

Addicks²,

Lehmann³

2012

Experimental Autoimmune Encephalomyelitis - Models, Disease Biology and Experimental Therapy

View full text Add to dashboard Cite

Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis

Abstract: Our study indicates that damage to lower motor neurons and TRAIL-mediated inflammatory neurodegeneration in the spinal cord contribute to MS pathology.

Cited by 156 publications

References 38 publications

Retinal ganglion cell and inner plexiform layer thinning in clinically isolated syndrome

Retinal ganglion cell and inner plexiform layer thinning in clinically isolated syndrome

Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

Studies on the CNS Histopathology of EAE and Its Correlation with Clinical and Immunological Parameters

Contact Info

Product

Resources

About