BRAIN and NERVE－神経研究の進歩60巻6号

2008年06月発行

特集 Crow-深瀬症候群（POEMS症候群）

Crow-深瀬症候群の末梢神経病理

著者： 神田隆¹

所属機関： ¹山口大学大学院医学系研究科神経内科

ページ範囲：P.603 - P.610

文献概要

はじめに

　末梢神経系はCrow-Fukase症候群（CFS）の病変の主座の1つであり，病理学的所見についても，本症候群が一疾患単位として認知された頃から精力的に解析が進められてきた。1970～1980年代にかけては本邦からの報告が他を圧しているが，近年は欧米からも重要な知見が多数集積されてきている。本稿ではCFSの病理所見について今まで報告されてきた生検所見，剖検所見を概括し，近年明らかになった本症でのVEGF高値と病理所見（特に血管病変）との関連について述べることとする。

参考文献

1) Adams D, Said G: Ultrastructural characterization of the M protein in nerve biopsy of patients with POEMS syndrome. J Neurol Neurosurg Psychiatry 64: 809-812, 1998

2) 佐藤雄二, 大西晃生, 立石　潤, 岩下　宏, 椎　裕章: ポリニューロパチー, 皮膚色素沈着, 剛毛, 浮腫などを伴う骨硬化性骨髄腫2剖検例の末梢神経病変. 臨床神経20: 742-749, 1980

3) Viard J, Lesavre P, Boitard C, Noel LH, Roth A, et al: POEMS syndrome presenting as systemic sclerosis. Clinical and pathologic study of a case with microangiopathic glomerular lesions. Am J Med 84: 524-528, 1988

4) Gherardi R, Baudrimont M, Kujas M, Malapert D, Lange F, et al: Pathological findings in three non-japanese patients with the POEMS syndrome. Virchows Archiv A Pathol Anat 413: 357-365, 1988

5) Donaghy M, Hall P, Gawler J, Gregson NA, Leibowitz S, et al: Peripheral neuropathy associated with Castleman's disease. J Neurol Sci 89: 253-267, 1989

6) Mandler R, Kerrigan D, Smart J, Kuis W, Villiger P, et al: Castleman's disease in POEMS syndrome with elevated interleukin-6. Cancer 69: 2697-2703, 1992

7) Pareyson D, Marazzi R, Confalonieri P, Mancardi G, Schenone A, et al: The POEMS syndrome: report of six cases. Ital J Neurol Sci 15: 353-358, 1994

8) Watanabe O, Maruyama I, Arimura K, Kitajima I, Arimura H, et al: Overproduction of vascular endothelial growth factor / vascular permeability factor is causative in Crow-Fukase (POEMS) syndrome. Muscle Nerve 21: 1390-1397, 1998

9) Dispenzieri A, Kyle R, Lacy M, Rajkumar SV, Therneau TM, et al: POEMS syndrome: definitions and long-term outcome. Blood 101: 2496-2506, 2003

10) 大西晃生, 佐藤雄二, 立石　潤, 岩下　宏, 黒岩義五郎: ポリニューロパチー, 皮膚色素沈着・剛毛・浮腫を伴う骨硬化性骨髄腫例の末梢神経病変. 神経内科7: 540-542, 1977

11) Berkovic S, Scarlett J, Symington G, Dennett X, Woodruff R: Proximal motor neuropathy, dermato-endocrine syndrome, and IgGκ paraproteinemia. Arch Neurol 43: 845-848, 1986

12) Semble EL, Challa VR, Holt DA, Pisko EJ: Light and electron microscopic findings in POEMS, or Japanese multisystem syndrome. Arthritis Rheum 29: 286-291, 1986

13) Reulecke M, Dumas M, Meier C: Specific antibody activity against neuroendocrine tissue in a case of POEMS syndrome with IgG gammopathy. Neurology 38: 614-616, 1988

14) Teixeira F, Aranda F, Cabanas A, Estanol B: POEMS syndrome: ultrastructural observations on the sural nerve. Ultrastruct Pathol 14: 31-40, 1990

15) Romas E, Storey E, Ayers M, Byrne E: Polyneuropathy, organomegaly, endocrinopathy, M protein and skin change (POEMS) syndrome with IgGκ paraproteinemia. Pathology 24: 217-220, 1992

16) Simmons Z, Ward J, Albers J, Feldman E: The natural history of a "benign" rib lesion in a patient with a demyelinating polyneuropathy and an unusual variant of POEMS syndrome. Muscle Nerve 17: 1055-1059, 1994

17) Saida K, Kawakami H, Ohta M, Iwamura K: Coagulation and vascular abnormalities in Crow-Fukase syndrome. Muscle Nerve 20: 486-492, 1997

18) Nakanishi T, Sobue I, Toyokura Y, Nishitani H, Kuroiwa Y, et al: The Crow-Fukase syndrome: a study of 102 cases in Japan. Neurology 34: 712-720, 1984

19) Shelley W, Shelley E: The skin changes in the Crow-Fukase (POEMS) syndrome. Arch Dermatol 123: 85-87, 1987

20) Iwashita H, Ohnishi A, Asada M, Kanazawa Y, Kuroiwa Y: Polyneuropathy, skin hyperpigmentation, edema, and hypertrichosis in localized osteosclerotic myeloma. Neurology 27: 675-681, 1977

21) Kanda T, Tsukagoshi H, Oda M, Miyamoto K, Tanabe H: Morphological changes in unmyelinated nerve fibers in the sural nerve with age. Brain 114: 585-599, 1991

22) Vital C, Vital A, Ferrer X, Viallard JF, Pellegrin JL, et al: Crow-Fukase (POEMS) syndrome: a study of peripheral nerve biopsy in five new cases. J Peripher Nerv Syst 8: 136-144, 2003

23) 西谷　裕, 野口貞子, 小西哲郎, 永井朝子, 今井輝國, 他: 色素沈着を伴う形質細胞性ポリニューロパチー―とくにその病理像と成因について―. 神経内科7: 548-550, 1977

24) Sobue G, Doyu M, Watanabe M, Hayashi F, Mitsuma T: Extensive demyelinating changes in the peripheral nerves of Crow-Fukase syndrome: a pathological study of one autopsied case. Acta Neuropathol 84: 171-177, 1992

25) Watanabe O, Arimura K, Kitajima I, Osame M, Maruyama I: Greatly raised vascular endothelial growth factor (VEGF) in POEMS syndrome. Lancet 347: 702, 1996

26) Scarlato M, Previtali S, Carpo M, Pareyson D, Briani C, et al: Polyneuropathy in POEMS syndrome: role of angiogenic factors in the pathogenesis. Brain 128: 1911-1920, 2005

27) Kanda T, Yamawaki M, Iwasaki T, Mizusawa H: Glycosphingolipid antibodies and blood-nerve barrier in autoimmune demyelinative neuropathy. Neurology 54: 1459-1464, 2000

28) Santoro L, Manganelli F, Bruno R, Nolano M, Provitera V, et al: Sural nerve and epidermal vascular abnormalities in a case of POEMS syndrome. Eur J Neurol 13: 93-102, 2006

29) Ohnishi A, Hirano A: Uncompacted myelin lamellae in dysglobulinemic neuropathy. J Neurol Sci 51: 131-140, 1981

30) Ohnishi A: Geographical patterns of neuropathy: Japan. In: Asbury A, Gilliart R, (eds.) Peripheral Nerve Disorders. A Practical Approach. London, Butterworth, 1984, pp303-319

31) Bergouignan F, Massonnat R, Vital C, Barat M, Henry P, et al: Uncompacted lamellae in three patients with POEMS syndrome. Eur Neurol 27: 173-181, 1987

32) Umehara F, Izumo S, Zyounosono M, Osame M: An autopsied case of the Crow-Fukase syndrome: a neuropathological study with emphasis on spinal roots. Acta Neuropathol 80: 563-567, 1990

33) Vital C, Gherardi R, Vital A, Kopp N, Pellissier JF, et al: Uncompacted myelin lamellae in polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes syndrome: ultrastructural study of peripheral nerve biopsy from 22 patients. Acta Neuropathol 87: 302-307, 1994

34) Vital C, Bouillot S, Vital A: Significance of uncompacted myelin lamellae in POEMS syndrome ［letter］. Muscle Nerve 27: 253-254, 2003

35) Gabreels-Festen A, Hoogendijk J, Meijerink P, Gabreels FJ, Bolhuis PA, et al: Two divergent types of nerve pathology in patients with different P0 mutations in Charcot-Marie-Tooth disease. Neurology 47: 761-765, 1996

36) Ohnishi A, Yamamoto T, Yamamori S, Sudo K, Fukushima Y, et al: Myelinated fibers in Charcot-Marie-Tooth disease type 1B with Arg98His mutation of P0 protein. J Neurol Sci 171: 97-109, 1990

37) Lagueny A, Latour P, Vital A, Le Masson G, Rouanet M, et al: Mild recurrent neuropathy in CMT1B with a novel nonsense mutation in the extracellular domain of the MPZ gene. J Neurol Neurosurg Psychiatry 70: 232-235, 2001

38) Yoshikawa H, Dyck P: Uncompacted inner myelin lamellae in inherited tendency to pressure palsy. J Neuropathol Exp Neurol 50: 649-657, 1991

39) Minamitani S, Ohfuji S, Nishiguchi S, Shiomi S, Ogami M, et al: An autopsy case of POEMS syndrome with a high level of IL-6 and VEGF in the serum and ascitic fluid. Intern Med 41: 233-236, 2002

40) Lewerenz J, Gocht A, Hoeger PH, von der Driesch P, Eckert B, et al: Multiple vascular abnormalities and a paradoxical combination of vitamin B12 deficiency and thrombocytosis in a case with POEMS syndrome. J Neurol 250: 1488-1491, 2003

41) 斎藤光典, 平山惠造, 楢林博太郎, 朝長正徳, 桑原紀之: 皮膚色素沈着・剛毛・疣状腫瘤・浮腫・うっ血乳頭・全身リンパ節腫脹・肝腫大・耐糖能低下・陰萎・単クローン性IgG増加・孤立性骨髄腫を伴う多発性神経根炎の1剖検例. 神経内科7: 543-547, 1977

42) Fukatsu A, Tamai H, Nishikawa K, Matsukawa W, Yoshida F, et al: The kidney disease of Crow-Fukase (POEMS) syndrome: a clinico-pathological study of four cases. Clin Nephrol 36: 76-82, 1991

43) Shibata M, Yamada T, Tanahashi N, Koto A, Kuramochi S, et al: POEMS syndrome with necrotizing vasculitis: a novel feature of vascular abnormalities. Neurology 54: 772, 2000

44) Sharabi Y, Raanani P, Shenkar A, Thaler M, Grossman E: Plasma cell dyscrasia with polyneuropathy--POEMS syndrome presenting with vasculitic skin lesions and responding to combination chemotherapy. Leuk Lymphoma 40: 209-213, 2000

45) Sakai K, Komai K, Yanase D, Yamada M: Plasma VEGF as a marker for the diagnosis and treatment of vasculitic neuropathy. J Neurol Neurosurg Psychiatry 76: 296, 2005

46) Goebels N, Walther E, Schaller M, Pongratz D, Mueller-Felber W: Inflammatory myopathy in POEMS syndrome. Neurology 55: 1413-1414, 2000

47) Rosenstein J, Krum J: New roles for VEGF in nervous tissue--beyond blood vessels. Exp Neurol 187: 246-253, 2004

48) Kanda T, Iwasaki T, Yamawaki M, Tai T: Anti-GM1 antibody facilitates leakage in an in vitro blood-nerve barrier model. Neurology 55: 585-587, 2000

49) Hashiguchi T, Arimura K, Matsumuro K, Otsuka R, Watanabe O, et al: Highly concentrated vascular endothelial growth factor in platelets in Crow-Fukase syndrome. Muscle Nerve 21: 1390-1397, 2000