Polyneuropathy in POEMS syndrome

Role of angiogenic factors in the pathogenesis

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

In order to clarify the role of angiogenic factors in polyneuropathy of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome, we measured the serum concentrations of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) in 11 patients and correlated these with VEGF and EPO peripheral nerve expression and the degree of endoneurial vessel involvement. We found that POEMS syndrome was associated with high levels of serum VEGF and, conversely, low levels of serum EPO. Similarly, in POEMS nerves VEGF was highly expressed in blood vessels and some non-myelin-forming Schwann cells. In contrast, the expression of VEGF receptor 2 was down-regulated compared with that in normal nerves. Both EPO and EPO receptor were localized to the nerve vasculature and were expressed to similar extents in normal and POEMS nerves. The inverse correlation between VEGF and EPO serum levels was maintained during the clinical course; however, both levels returned to normal when there was a response to therapy. High serum VEGF, low serum EPO and high peripheral nerve VEGF were all associated with more severe endoneurial vessel involvement and nerve damage. Light microscopy showed an increased thickness of the basal lamina and a narrowing of the lumina of endoneurial vessels in POEMS samples, while proliferation of endothelial cells and opening of tight junctions were observed by electron microscopy. The present data support the role of angiogenic factors as diagnostic and prognostic markers of POEMS syndrome. They also suggest that VEGF and EPO are involved in the pathogenesis of polyneuropathy. In conclusion, establishing the role of angiogenic factors in polyneuropathy may lead to a better understanding of the effects of VEGF and EPO on microangiopathy and Schwann cell function.

Original languageEnglish
Pages (from-to)1911-1920
Number of pages10
JournalBrain
Volume128
Issue number8
DOIs
Publication statusPublished - Aug 2005

Fingerprint

POEMS Syndrome
Paraproteinemias
Polyneuropathies
Angiogenesis Inducing Agents
Vascular Endothelial Growth Factor A
Erythropoietin
Skin
Serum
Schwann Cells
Lead Poisoning, Nervous System, Adult
Peripheral Nerves
Erythropoietin Receptors
Vascular Endothelial Growth Factor Receptor-2
Tight Junctions
Basement Membrane
Blood Vessels
Microscopy
Electron Microscopy
Endothelial Cells

Keywords

  • Endoneurial vessels
  • EPO
  • Nerve
  • POEMS
  • VEGF

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Polyneuropathy in POEMS syndrome : Role of angiogenic factors in the pathogenesis. / Scarlato, Marina; Previtali, Stefano Carlo; Carpo, Marinella; Pareyson, Davide; Briani, Chiara; Del Bo, Roberto; Nobile-Orazio, Eduardo; Quattrini, Angelo; Comi, Giacomo Pietro.

In: Brain, Vol. 128, No. 8, 08.2005, p. 1911-1920.

Research output: Contribution to journalArticle

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abstract = "In order to clarify the role of angiogenic factors in polyneuropathy of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome, we measured the serum concentrations of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) in 11 patients and correlated these with VEGF and EPO peripheral nerve expression and the degree of endoneurial vessel involvement. We found that POEMS syndrome was associated with high levels of serum VEGF and, conversely, low levels of serum EPO. Similarly, in POEMS nerves VEGF was highly expressed in blood vessels and some non-myelin-forming Schwann cells. In contrast, the expression of VEGF receptor 2 was down-regulated compared with that in normal nerves. Both EPO and EPO receptor were localized to the nerve vasculature and were expressed to similar extents in normal and POEMS nerves. The inverse correlation between VEGF and EPO serum levels was maintained during the clinical course; however, both levels returned to normal when there was a response to therapy. High serum VEGF, low serum EPO and high peripheral nerve VEGF were all associated with more severe endoneurial vessel involvement and nerve damage. Light microscopy showed an increased thickness of the basal lamina and a narrowing of the lumina of endoneurial vessels in POEMS samples, while proliferation of endothelial cells and opening of tight junctions were observed by electron microscopy. The present data support the role of angiogenic factors as diagnostic and prognostic markers of POEMS syndrome. They also suggest that VEGF and EPO are involved in the pathogenesis of polyneuropathy. In conclusion, establishing the role of angiogenic factors in polyneuropathy may lead to a better understanding of the effects of VEGF and EPO on microangiopathy and Schwann cell function.",
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