Brain Advance Access published online on June 23, 2005
Brain, doi:10.1093/brain/awh519
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1 Department of Neurological Sciences, Centro Dino Ferrari, University of Milan, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy; Department of Neurology, San Raffaele Scientific Institute, Milan, Italy
* To whom correspondence should be addressed. 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.
Received September 21, 2004
Revised March 3, 2005
Accepted March 18, 2005
Article
Polyneuropathy in POEMS syndrome: role of angiogenic factors in the pathogenesis
2 Department of Neurology, San Raffaele Scientific Institute, Milan, Italy
3 Department of Neurological Sciences, Centro Dino Ferrari, University of Milan, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy
4 ‘C. Besta’ National Neurological Institute, Milan, Italy
5 Department of Neurosciences, University of Padova, Padova, Italy
Marina Scarlato, E-mail: mamasca{at}hotmail.com
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