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- polyneuropathy (3) (entfernen)
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Polyneuropathy (PNP) is a term to describe diseases of the peripheral nervous system, 50% of which present with neuropathic pain. In some types of PNP, pain is restricted to the skin distally in the leg, suggesting a local regulatory process leading to pain. In this study, we proposed a pro-inflammatory pathway mediated by NF-κB that might be involved in the development of pain in patients with painful PNP. To test this hypothesis, we have collected nerve and skin samples from patients with different etiologies and levels of pain. We performed RT-qPCR to analyze the gene expression of the proposed inflammatory pathway components in sural nerve and in distal and proximal skin samples. In sural nerve, we showed a correlation of TLR4 and TNFα to neuropathic pain, and an upregulation of TNFα in patients with severe pain. Patients with an inflammatory PNP also presented a lower expression of TRPV1 and SIRT1. In distal skin, we found a reduced expression of TLR4 and miR-146-5p, in comparison to proximal skin. Our findings thus support our hypothesis of local inflammatory processes involved in pain in PNP, and further show disturbed anti-inflammatory pathways involving TRPV1 and SIRT1 in inflammatory PNP.
Neuropathies are a group of potentially treatable diseases with an often disabling and restricting course. Amyotrophic lateral sclerosis (ALS) is a lethal disease without causal treatment possibilities. The objective of this study was to examine the diagnostic utility of HRUS for the differentiation of subtypes of axonal and demyelinating neuropathies and to investigate its utility for the sonological differentiation of ALS.
The hypothetical statement that neuropathy causes enlargement of peripheral nerves compared to healthy controls proved to be right, but the adjunctive assumption that ALS does not cause enlargement of peripheral nerves proved to be wrong – in patients with ALS slight enlargement of peripheral nerves was visible as well. The statement that nerve enlargement can be detected by measurement of the cross-sectional area (CSA) and the longitudinal diameter (LD) with comparable results proved to be right, but the enlargement was slightly less present by measurement of the LD. The statement that axonal and demyelinating neuropathies show distinct patterns of nerve enlargement must be answered differentiated: The comparison between axonal and demyelinating neuropathies showed a stronger nerve enlargement in patients with demyelinating neuropathies than in patients with axonal neuropathies at proximal nerve segments of upper extremities. In the comparison of diagnose-defined subgroups of inflammatory demyelinating neuropathies a respective specific pattern of nerve enlargement was visible. However, remarkable in this context was the strong nerve enlargement found in patients with NSVN, which is classified as an axonal neuropathy. Stratification for specific findings in nerve biopsy did not lead to constructive differences in comparison between the different groups.
To sum up, HRUS showed to provide a useful contribution in the diagnostic process of neuropathies and ALS but needs to be integrated in a multimodal diagnostic approach.
FoxP3+Regulatory T Cells Determine Disease Severity in Rodent Models of Inflammatory Neuropathies
(2014)
Inflammatory neuropathies represent disabling human autoimmune disorders with considerable disease variability. Animal models provide insights into defined aspects of their disease pathogenesis. Forkhead box P3 (FoxP3)+ regulatory T lymphocytes (Treg) are anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. Dysfunction or a reduced frequency of Tregs have been associated with different human autoimmune disorders. We here analyzed the functional relevance of Tregs in determining disease manifestation and severity in murine models of autoimmune neuropathies. We took advantage of the DEREG mouse system allowing depletion of Treg with high specificity as well as anti-CD25 directed antibodies to deplete Tregs in mice in actively induced experimental autoimmune neuritis (EAN). Furthermore antibody-depletion was performed in an adoptive transfer model of chronic neuritis. Early Treg depletion increased clinical EAN severity both in active and adoptive transfer chronic neuritis. This was accompanied by increased proliferation of myelin specific T cells and histological signs of peripheral nerve inflammation. Late stage Treg depletion after initial disease manifestation however did not exacerbate inflammatory neuropathy symptoms further. We conclude that Tregs determine disease severity in experimental autoimmune neuropathies during the initial priming phase, but have no major disease modifying function after disease manifestation. Potential future therapeutic approaches targeting Tregs should thus be performed early in inflammatory neuropathies.