Nerve pathologic features differentiate POEMS syndrome from CIDP
Tóm tắt
The objective of this study is to determine if the nerve pathology in patients with POEMS syndrome is different from CIDP. We hypothesized that nerve biopsies from patients with POEMS syndrome would have more small vessels and axonal degeneration but less inflammation than CIDP. We performed a retrospective analysis of nerve biopsies performed on “classic” CIDP and POEMS cases. Nerve biopsies were blinded and reviewed by two of the authors (EAP, PJBD). Teased fibers, paraffin-embedded sections, semithin sections and immunostains were analyzed. Small endoneurial and epineurial vessels were counted on paraffin sections with smooth muscle actin (SMACTIN) preparation to judge for neovascularization. A total of 61 cases (35-POEMS, 26-CIDP) were included. The POEMS-group had significantly higher axonal degeneration and fewer normal myelinated fibers on teased fiber preparations. The CIDP-group had significantly more endoneurial mononuclear inflammation on paraffin sections and immunostains. Large onion-bulbs were present only in CIDP cases. A significantly higher number of epineurial vessels was present in POEMS biopsies, with a total count of 120 epineurial vessels predicted as best cutoff to differentiate both conditions (77 % specific and 54 % sensitive). In conclusion, nerve biopsy can be helpful in distinguishing POEMS syndrome from CIDP. POEMS syndrome demonstrates more axonal degeneration and epineurial neovascularization whereas CIDP has greater endoneurial inflammation and onion-bulb formation. These findings support the idea that there are differing underlying mechanisms for these disorders, POEMS being related to paraneoplastic vasculopathy associated with angiogenic factors and CIDP related to inflammatory demyelination.
Tài liệu tham khảo
Kulkarni GB, et al. Clinicopathological profile of polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome. J Clin Neurosci. 2011;18(3):356–60.
Dyck PJ, et al. Chronic inflammatory polyradiculoneuropathy. Mayo Clin Proc. 1975;50(11):621–37.
Daube JR, So ER. Application of clinical neurophysiology: assessing symptom complexes. In: Clinical Neurophysiology. 2nd ed. New York: Oxford University Press; 2002.
Laughlin RS, et al. Incidence and prevalence of CIDP and the association of diabetes mellitus. Neurology. 2009;73(1):39–45.
Dispenzieri A, et al. POEMS syndrome: definitions and long-term outcome. Blood. 2003;101(7):2496–506.
Dyck PJ, Giannini C, Lais A. Pathologic alterations of nerves. In: Dyck PJ, Thomas PK, Low PA, Griffin JW, Poduslo JF, editors. Peripheral neuropathy. Philadelphia: W.B. Saunders; 1993.
Nasu S, et al. Different neurological and physiological profiles in POEMS syndrome and chronic inflammatory demyelinating polyneuropathy. J Neurol Neurosurg Psychiatry. 2012;83(5):476–9.
Thakral S, et al. Prominent dysautonomia in a patient with POEMS syndrome. Clin Auton Res. 2016;26(3):223–8.
Hashimoto R, et al. Uncompacted myelin lamellae and nodal ion channel dysruption in POEMS syndrome. J Neuropathol Exp Neurol. 2015;74(12):1127–36.
Watanabe O, et al. Greatly raised vascular endothelial growth factor (VEGF) in POEMS syndrome. Lancet. 1996;347(9002):702.
Watanabe O, et al. Overproduction of vascular endothelial growth factor/vascular permeability factor is causative in Crow-Fukase (POEMS) syndrome. Muscle Nerve. 1998;21(11):1390–7.
Gherardi RK, et al. Overproduction of proinflammatory cytokines imbalanced by their antagonists in POEMS syndrome. Blood. 1996;87(4):1458–65.
Kanai K, et al. Markedly upregulated serum interleukin-12 as a novel biomarker in POEMS syndrome. Neurology. 2012;79(6):575–82.
Yamada Y, et al. Multiple angiogenetic factors are upregulated in POEMS syndrome. Ann Hematol. 2013;92(2):245–8.
Scarlato M, et al. Polyneuropathy in POEMS syndrome: role of angiogenic factors in the pathogenesis. Brain. 2005;128(Pt 8):1911–20.
Santoro L, et al. Sural nerve and epidermal vascular abnormalities in a case of POEMS syndrome. Eur J Neurol. 2006;13(1):99–102.
Donaghy M, et al. Peripheral neuropathy associated with Castleman’s disease. J Neurol Sci. 1989;89(2–3):253–67.
Saida K, et al. Coagulation and vascular abnormalities in Crow-Fukase syndrome. Muscle Nerve. 1997;20(4):486–92.
Mauermann ML, et al. Uniform demyelination and more severe axonal loss distinguish POEMS syndrome from CIDP. J Neurol Neurosurg Psychiatry. 2012;83(5):480–6.
Sung JY, et al. Patterns of nerve conduction abnormalities in POEMS syndrome. Muscle Nerve. 2002;26(2):189–93.
Mathis S, et al. POEMS syndrome with prominent acute axonal lesions. J Neurol Sci. 2012;313(1–2):185–8.
Dyck PJ, Engelstad J, Dispenzieri A. Vascular endothelial growth factor and POEMS. Neurology. 2006;66(1):10–2.
Vital C, et al. Crow-Fukase (POEMS) syndrome: a study of peripheral nerve biopsy in five new cases. J Peripher Nerv Syst. 2003;8(3):136–44.