Evidence of axonal damage in human acute demyelinating diseases

Ghosh, Nandita; DeLuca, Gabriele C.; Esiri, Margaret M.

doi:10.1016/j.jns.2004.03.032

Cited by 37 publications

(22 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Comparable white matter infiltrates of IL-21 + cells in MS were also observed in SSPE and HSE, suggesting a similar role of IL-21 in these neuro-inflammatory CNS diseases (Figure 3). In intriguing contrast, IL-21 + inflammatory cells were unexpectedly rare in ADEM, an acute monophasic neuro-inflammatory demyelinating disease 31 . This difference suggests that IL-21 is involved in the maintenance of chronic more than acute inflammation in the brain 32 and also in psoriatic skin 33 .…”

Section: Discussionmentioning

confidence: 96%

IL-21 and IL-21 Receptor Expression in Lymphocytes and Neurons in Multiple Sclerosis Brain

Tzartos¹,

Craner²,

Friese

et al. 2011

The American Journal of Pathology

120

View full text Add to dashboard Cite

IL-17–producing CD4+ T cells (Th-17) contribute to the pathogenesis of experimental autoimmune encephalomyelitis and are associated with active disease in multiple sclerosis (MS). In addition to IL-17, Th-17 cells can also express IL-21, IL-22, and IL-6 under Th-17–polarizing conditions (IL-6 and transforming growth factor-β). In this study we investigated IL-21 and IL-21 receptor (IL-21R) expression in MS lesions by in situ hybridization and immunohistochemistry. We detected strongly IL-21+ infiltrating cells predominantly in acute but also in chronic active white matter MS lesions in which IL-21 expression was restricted to CD4+ cells. In contrast, IL-21R was much more broadly distributed on CD4+, CD19+, and CD8+ lymphocytes but not major histocompatibility complex class-II+ macrophages/microglia. Interestingly, in cortical areas we detected both IL-21 and IL-21R expression by neurons. These findings suggest role(s) for IL-21 in both the acute and chronic stages of MS via direct effects on T and B lymphocytes and, demonstrated for the first time, also on neurons.

show abstract

Section: Discussionmentioning

confidence: 96%

IL-21 and IL-21 Receptor Expression in Lymphocytes and Neurons in Multiple Sclerosis Brain

Tzartos¹,

Craner²,

Friese

et al. 2011

The American Journal of Pathology

120

View full text Add to dashboard Cite

show abstract

“…Although DEM is typically described as white matter demyelination with relative preservation of axons, axonal damage has been identified in the brain of some patients [119,120].…”

Section: Immunopathogenesismentioning

confidence: 99%

Disseminated encephalomyelitis in children

Tenembaum

2008

Clinical Neurology and Neurosurgery

View full text Add to dashboard Cite

The advent of MRI has contributed to increase the interest and awareness in childhood white matter disorders. A major priority is to distinguish transient and self-limited demyelinating syndromes like disseminated encephalomyelitis (DEM), from life-long diseases like multiple sclerosis (MS). However, the term DEM has been inconsistently applied across studies due to the lack of clear clinical and neuroimaging diagnostic criteria. The present review summarizes the available literature on DEM in children, outlines the main clinical and neuroimaging features at presentation, pathogenesis and outcome, and its differentiation from other conditions with acute impact in the CNS. The recently proposed clinical definitions for monophasic disseminated encephalomyelitis and its relapsing variants are discussed, and controversies surrounding the diagnosis of MS in children are addressed.

show abstract

“…While demyelination may be considered the hallmark of MS pathology, axonal damage is hypothesized to be the histologic substrate for disability (Trapp et al, 1998). Axonal loss can occur early in active disease (Ferguson et al, 1997; Ghosh et al, 2004) and is commonly observed later in the disease subtypes of primary progressive MS (PPMS) and secondary progressive MS (SPMS) (Tallantyre et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

Radial diffusivity predicts demyelination in ex vivo multiple sclerosis spinal cords

et al. 2011

View full text Add to dashboard Cite

Objective Correlation of diffusion tensor imaging (DTI) with histochemical staining for demyelination and axonal damage in multiple sclerosis (MS) ex vivo human cervical spinal cords. Background In MS, demyelination, axonal degeneration, and inflammation contribute to disease pathogenesis to variable degrees. Based upon in vivo animal studies with acute injury and histopathologic correlation, we hypothesized that DTI can differentiate between axonal and myelin pathologies within humans. Methods DTI was performed at 4.7 Tesla on 9 MS and 5 normal control fixed cervical spinal cord blocks following autopsy. Sections were then stained for Luxol fast blue (LFB), Bielschowsky silver, and hematoxylin and eosin (H&E). Regions of interest (ROIs) were graded semi-quantitatively as normal myelination, mild (<50%) demyelination, or moderate-severe (>50%) demyelination. Corresponding axonal counts were manually determined on Bielschowsky silver. ROIs were mapped to co-registered DTI parameter slices. DTI parameters evaluated included standard quantitative assessments of apparent diffusion coefficient (ADC), relative anisotropy (RA), axial diffusivity and radial diffusivity. Statistical correlations were made between histochemical gradings and DTI parameters using linear mixed models. Results: Within ROIs in MS subjects, increased radial diffusivity distinguished worsening severities of demyelination. Relative anisotropy was decreased in the setting of moderate-severe demyelination compared to normal areas and areas of mild demyelination. Radial diffusivity, ADC, and RA became increasingly altered within quartiles of worsening axonal counts. Axial diffusivity did not correlate with axonal density (p=0.091). Conclusions Increased radial diffusivity can serve as a surrogate for demyelination. However, radial diffusivity was also altered with axon injury, suggesting that this measure is not pathologically specific within chronic human MS tissue. We propose that radial diffusivity can serve as a marker of overall tissue integrity within chronic MS lesions. This study provides pathologic foundation for on-going in vivo DTI studies in MS.

show abstract

Evidence of axonal damage in human acute demyelinating diseases

Cited by 37 publications

References 17 publications

IL-21 and IL-21 Receptor Expression in Lymphocytes and Neurons in Multiple Sclerosis Brain

IL-21 and IL-21 Receptor Expression in Lymphocytes and Neurons in Multiple Sclerosis Brain

Disseminated encephalomyelitis in children

Radial diffusivity predicts demyelination in ex vivo multiple sclerosis spinal cords

Contact Info

Product

Resources

About