POEMS综合征的临床与周围神经病理分析

目的：探讨POEMS综合征的临床和周围神经病理特点。方法：回顾性分析5例POEMS综合征的临床特征和4例周围神经活检结果。结果：5例患者临床上均有感觉运动性周围神经损害和肢端凹陷性水肿，腹水3例，胸腔积液2例，心包积液2例。肝脏肿大2例，脾脏肿大3例，淋巴结肿大2例。皮肤变黑5例，多毛症3例。4例腓肠神经活检中，3例神经束膜增厚，束间小血管增多，周围散在有单核细胞。4例均可见脱髓鞘改变和有髓纤维减少，3例可见到少数纤维轴索变性。单神经纤维剥离检查4例，均可见阶段性脱髓鞘改变和薄髓纤维。结论：POEMS综合征是一组以多发性神经病、脏器肿大、内分泌病变、M蛋白、皮肤损害等多系统损害的临床症候群。周围神经病理改变主要为薄髓纤维和脱髓鞘改变，晚期可见轴索变性。     

复合肌肉动作电位波幅和肌力的相关性在危重病瘫痪诊断中的价值

  目的  探讨复合肌肉动作电位(compound muscle action potential, CMAP)波幅和肌力的相关性在协助重症患者肢体瘫痪定位中的价值。  方法  采用床旁肌电图测定, 对30例伴有肢体无力的重症患者进行运动神经传导测定, 同时收集测定神经所支配肌肉的肌力, 与CMAP波幅进行比较。  结果  5例患者神经传导测定CMAP波幅和速度均正常, 其中3例为明显无力, 符合中枢神经系统病变的诊断。6例肢体明显无力的患者, 发现有运动神经传导阻滞和传导速度减慢, CMAP波幅下降, 符合脱髓鞘性周围神经病的诊断。19例表现为CMAP波幅下降, 其中8例波幅明显下降(3例未引出波形), 无潜伏期延长或传导速度减慢, 临床查体可见8例明显无力, 10例轻度无力, 1例肌力正常, 支持神经肌肉病变的诊断。  结论  将CMAP波幅和肌力结合进行分析有助于重症患者肢体瘫痪的定位, 尤其在明显无力的肢体测定时价值更大。     

腓肠神经形态学观察及半定量分析在多发性周围神经病中的作用

目的 :评价腓肠神经的形态学观察及半定量分析在多发性周围神经病诊断中的作用。方法 :回顾性分析 3例急性炎性脱髓鞘性周围神经病、12例慢性炎性脱髓鞘性周围神经病和 3例遗传性感觉运动神经病患者的病理资料 ,并通过PharmaciaBiotech图象分析仪在患者腓肠神经的半薄切片上随机选取 30条有髓纤维 ,计算平均纤维直径、平均轴索直径、g比率、髓鞘面积与轴索面积的比值。结果 :各组患者腓肠神经的纤维平均直径和轴索平均直径均大于正常对照 ,但仅遗传性感觉运动神经病组有显著差异 (P <0 .0 1) ,而 g比率、髓鞘与轴索面积之比在各组间未显示明显差异 (P >0 .0 5 )。患者组腓肠神经的形态学改变为非特异性 ,炎性细胞浸润较少见。结论 :腓肠神经半定量分析对于诊断急性及慢性炎性脱髓鞘性周围神经病有一定价值。     

小鼠耳蜗神经及其与内毛细胞突触后谷氨酸受体发育的特点

  目的  了解小鼠耳蜗神经发育特点及耳蜗内毛细胞与蜗神经突触后谷氨酸受体发育的时间特点。  方法  采用免疫组化方法, 通过共聚焦显微镜观察和记录不同发育阶段小鼠前庭耳蜗神经/耳蜗神经纤维及内毛细胞与蜗神经纤维突触后谷氨酸受体(glutamate receptor, GluR)2和3的发育与分布。  结果  胚胎9.5 d(E9.5)在听囊听上皮、前庭耳蜗神经核团及面神经核团中即可观察到NeuroD高信号表达; L1在面神经核团亦开始有明显表达。至E12.5, L1和Tuj1在前庭耳蜗神经核团和面神经核团均有强信号表达, 表达位置基本重合; 在听上皮组织可观察到明确的Tuj1信号, 显示听上皮与前庭耳蜗神经核团间神经纤维联系已建立。E12.5, 还可发现前庭耳蜗神经核团和神经管核团间神经纤维, 显示前庭耳蜗神经中枢方向的神经纤维已经发育。E13.5, 耳蜗内可见L1和Tuj1在螺旋神经核团及神经纤维结构中高信号表达, 提示内耳分化为耳蜗和前庭两个部分后传入神经进一步发育。E16.5, 自螺旋神经节至毛细胞的神经纤维清晰可见, L1和Tuj1高信号表达; 同时可以看到耳蜗内毛细胞周围有大量神经纤维分布; 但内毛细胞周围未见明显谷氨酸受体(GluR2/R3)表达。E18.5可以看到耳蜗内毛细胞周围大量神经纤维分布, 神经纤维末梢有高信号GluR2/R3表达。出生后1 d, 内毛细胞底部周围突触后GluR2/R3信号更为明显, 并为L1标记的神经纤维所包裹, GluR2/R3与L1信号共标记, 主要位于靠近内毛细胞底部的神经纤维末梢。  结论  小鼠耳蜗神经元与感觉上皮和中枢神经系统在胚胎发育较早期即建立了纤维联系, 神经纤维支配的建立早于内毛细胞成熟; 而内毛细胞与蜗神经纤维的突触联系在胚胎发育晚期及出生后才逐渐发育和完善。     

吉兰-巴雷综合征的脑脊液细胞学特点及诊断意义

  目的  探讨吉兰-巴雷综合征(Guillain-Barré syndrome, GBS)的脑脊液(cerebrospinal fluid, CSF)细胞学特点及其诊断意义。  方法  回顾性分析北京协和医院2010年1月至2012年12月收治的GBS患者的临床、神经电生理和CSF检查资料。入组病例均符合《中国吉兰-巴雷综合征诊治指南》(2010年)诊断标准。CSF细胞学检查采用CSF细胞沉淀器(自然沉淀法)制片, MGG法染色。采用χ²检验比较CSF常规计数和CSF细胞学的阳性率。  结果  共28例GBS患者纳入研究, 其中男19例, 女9例, 平均年龄39岁(8~69岁)。均急性起病, 肢体无力22例, 感觉减退13例, 感觉过敏3例, 球麻痹7例, 需要呼吸机辅助通气3例, 尿潴留5例, 体位性低血压1例, 眼肌麻痹5例, 面瘫10例, 共济失调4例。临床分型:急性炎性脱髓鞘性多发神经根神经病20例, 急性运动轴索性神经病1例, 急性运动感觉轴索性神经病1例, 急性感觉神经病1例, Miller Fisher综合征4例, 抗GQ1b抗体阳性的眼肌麻痹1例。CSF蛋白0.39~4.23 g/L, 蛋白升高26例, 其中11例蛋白>1.0 g/L; CSF白细胞计数:(0~5)×10⁶/L 26例, (6~10)×10⁶/L 2例。CSF寡克隆区带阳性者14例, 髓鞘碱性蛋白升高者18例。抗GM1抗体阳性3例, 抗GQ1b抗体阳性2例。CSF细胞学检查异常12例, 其中9例为淋巴细胞为主的炎症, 3例为单核细胞与淋巴细胞为主的炎症, 1例见2%的中性粒细胞, 6例可见激活的淋巴细胞, 2例可见激活的单核吞噬细胞, 3例可见浆细胞。病例中CSF细胞数超过5/μl者2例(7.1%), CSF细胞学提示炎性改变者12例(42.9%), CSF细胞学阳性率高于常规细胞计数(P < 0.01)。  结论  GBS的CSF细胞学检查可见淋巴细胞性炎症等炎性改变, 与GBS的多发性神经根炎的病理机制相一致。与CSF常规细胞计数相比, CSF细胞学能够更敏感地显示CSF的炎性状态, 因此对于GBS也更具诊断意义。     

牙龈和舌组织活检在淀粉样变性病诊断中的应用和比较

  目的  比较牙龈和舌组织活检对淀粉样变性的诊断价值。  方法  回顾性分析2012年5月至2013年7月在北京协和医院口腔科同时行牙龈及舌组织活检的32例淀粉样变性患者临床资料。其中24例同期由外科行腹壁脂肪组织活检。活检标本由病理科常规制片, 行HE染色和刚果红特染。  结果  组织活检病理示淀粉样变性在光镜下HE染色呈粉红色, 刚果红染色呈砖红色; 在偏振光显微镜下呈苹果绿双折射性。牙龈组织活检阳性22例, 舌组织活检阳性23例, 腹壁脂肪组织活检阳性19例。共29例经牙龈和舌组织活检确诊淀粉样变性, 口腔组织活检阳性率为90.63%。经卡方检验, 牙龈和舌组织活检对于淀粉样变性的检出结果差异无统计学意义(P > 0.05)。  结论  牙龈和舌组织活检均可提供淀粉样变性病诊断重要依据。     

超声引导组织活检对甲状腺病变的诊断价值

  目的  评价超声引导组织活检(core-needle biopsy, CNB)对甲状腺病变的诊断价值。  方法  选取2004年11月至2011年6月在北京协和医院就诊的117例进行CNB、有完整手术病理或随访资料的甲状腺病变患者, 回顾性分析其甲状腺病灶的CNB及病理结果。  结果  CNB结果显示, 117例甲状腺病变中良性85例, 恶性28例, 可疑恶性2例, 取材不满意2例, 取材成功率98.3%;弥漫性病变37例, 甲状腺结节80例。29例手术患者术后病理显示恶性24例(22例乳头状癌, 2例淋巴瘤), 其中5例CNB为良性(假阴性); 良性5例。80例甲状腺结节中小于1 cm者2例, 1~2 cm者21例, 大于2 cm者57例。  结论  超声引导CNB取材成功率高, 安全可靠, 可作为超声引导细针抽吸活检(fine needle aspiration, FNA)的有效补充手段, 并可用于特殊甲状腺病理类型, 如淋巴瘤的首选诊断方式。     

胎儿完全性大动脉转位产前超声诊断

  目的  探讨超声对胎儿完全性大动脉转位的诊断价值。  方法  回顾性分析2010年3月至2013年7月北京协和医院4例胎儿完全性大动脉转位的产前超声表现, 并与病理结果进行比较。  结果  4例完全性大动脉转位胎儿中, 3例四腔心切面正常, 1例可见室间隔缺损。左室及右室流出道切面4例胎儿可见心室与大动脉连接关系异常, 2例可见室间隔膜部缺损。三血管气管切面4例均仅可见2条血管。  结论  完全性大动脉转位具有特征性超声表现, 重点观察心室流出道切面及三血管气管切面有助于产前正确诊断。     

蝶鞍区疑难病变临床特点及活检安全性分析

  目的  总结蝶鞍区疑难病变的临床特点, 探讨神经内镜下经鼻蝶窦鞍区病变活检术的临床价值及安全性。  方法  回顾性收集2011年7月1日至2019年7月1日于北京协和医院神经外科接受神经内镜下经鼻蝶窦入路(endoscopic transsphenoidal approach, ETA)鞍内占位活检术或神经内镜下扩大经鼻蝶窦入路(endoscopic extended transsphenoidal approach, EETA)鞍上占位活检术的所有蝶鞍区病变患者临床资料, 分析其病因构成、临床表现、实验室检查、影像学表现及术后并发症情况。  结果  共142例符合纳入标准的患者入选本研究, 其中115例(81.0%, 115/142)接受ETA鞍内占位活检术, 27例(19.0%, 27/142)接受EETA鞍上占位活检术。142例蝶鞍区病变的病因包括囊性病变12例(8.5%, 12/142)、炎症/感染性疾病30例(21.1%, 30/142)和肿瘤100例(70.4%, 100/142), 最常见的诊断依次是生殖细胞肿瘤(79例)、朗格汉斯细胞组织细胞增生症(8例)、Rathke's囊肿(8例)和淋巴细胞垂体炎(7例)。142例患者中, 最常见的临床表现为中枢性尿崩相关症状; 无脑脊液甲胎蛋白升高; 29例脑脊液β人绒毛膜促性腺激素升高, 其中27例(93.1%)为生殖细胞肿瘤, 2例(6.9%)为颅咽管瘤; 肿瘤和炎症/感染性疾病最常同时累及鞍内和垂体柄(25.0%和33.3%), 其次为鞍内或由鞍内延伸至鞍上(21.0%和30.0%), 囊性病变则最常累及鞍内/由鞍内延伸至鞍上(75.0%)。97.0%病例的头颅MRI表现为垂体后叶亮斑缺失。活检术后1个月内, 7例(4.9%, 7/142)患者出现中枢神经系统感染, 3例(2.1%, 3/142)出现脑脊液漏(其中2例行二次手术修补后恢复), 3例(2.1%, 3/142)出现眼球运动功能障碍, 2例(1.4%, 2/142)出现视力下降, 2例(1.4%, 2/142)出现视野缺损或较术前加重, 经治疗后均基本恢复正常。  结论  蝶鞍区病变临床表现常缺乏特异性, 组织病理学检查是诊断的金标准。ETA鞍内和EETA鞍上占位活检术安全可靠。     

炎性肌纤维母细胞瘤计算机断层摄影表现

  目的  探讨炎性肌纤维母细胞瘤的计算机断层摄影(computed tomography, CT)表现, 以提高对该病CT表现的认识。  方法  选择本院9例经病理证实的炎性肌纤维母细胞瘤患者, 回顾性分析其CT平扫及增强表现。  结果  CT示肺内肌纤维母细胞瘤3例, 2例表现为界限清楚的肿块, 1例仅表现为支气管阻塞, 未见肿块; 纵隔肌纤维母细胞瘤3例, CT均表现为软组织密度肿块, 1例界限清楚, 2例与周围结构分界不清; 鼻根部、颈部及盆腔肌纤维母细胞瘤各1例, 表现为囊实性或实性肿块, 部分病变界限不清, 侵犯周围组织; 3例病变增强扫描后呈明显不均匀强化。  结论  炎性肌纤维母细胞瘤CT表现具有一定的特点, 但最终确诊仍需依靠病理学。     

肌萎缩侧索硬化症的周围神经损害

目的 阐明肌萎缩侧索硬化症患者腓肠神经的病理改变特点。方法 选择已确诊的肌萎缩侧索硬化症患者行周围神经活检。取其腓肠神经进行光镜及电镜检查，观察其病理改变。结果 周围神经的改变以轴索损害为主，伴有髓鞘的脱失。根据病理改变可分为4组：正常；轻度轴索变性及髓鞘脱失；有髓神经纤维轻度脱失，轴索变性及脱髓鞘；有髓神经纤维严重脱失，轴索变性及脱髓鞘。结论 肌萎缩侧索硬化症患者常常早期即出现周围神经的损害，其中以轴索性的改变为主，同时可伴有不同程度的髓鞘脱失。     

Ultrastructural pathology of peripheral nerves in patients with diabetic neuropathy

Sural nerve lesions in patients with clinically manifest diabetic neuropathy were investigated electron microscopically. Myelinated nerve fibers were reduced in all the diabetic patients. Axonal degeneration of both myelinated and unmyelinated nerve fibers was most conspicuous finding in the diabetic sural nerves. Structural changes of the axons were represented by axonal dwindling, depletion of axoplasmic organelles, vacuolarization and an increase in neurofilaments. Accumulation of glycogen-like particles and deposition of electron homogeneous amorphous materials were noted within a few axons. On the other hand, there could also be found degenerative changes of myelin sheaths, various kinds of cytoplasmic inclusion bodies (crystalloid, lamellar inclusion bodies and lipids-like droplets), aggregates of glycogen particles in the Schwann cell cytoplasm and basement membrane hyperplasia of Schwann cells in all the subjects. Furthermore, multiplication and thickening of the basement membrane of vasa nervorum were constant findings of the diabetic sural nerves. The vascular changes, demyelination and axonal degeneration of the cases were not apparently correlated with each other. There was no special relationship between nerve tissue changes and clinical symptoms or laboratory findings. These results indicated that the peripheral nerve lesions in human diabetics were mainly due to metabolic impairment of nerve fibers, accompanying dysmetabolism of Schwann cells and diabetic microangiopathy, and that these changes proceeded independently.     

Histopathological heterogeneity of neuropathy in insulin-dependent and non-insulin-dependent diabetes, and demonstration of axo-glial dysjunction in human diabetic neuropathy.

Altered sorbitol and myo-inositol metabolism, (Na,K)-ATPase function, electrochemical sodium gradients, axonal swelling, and distortion and disruption of the node of Ranvier ("axo-glial dysjunction") directly implicate hyperglycemia in the pathogenesis of neuropathy in diabetic rats, but the relevance of this sequence to clinical neuropathy in heterogeneous groups of diabetic patients remains to be established. Fascicular sural nerve morphometry in 11 patients with neuropathy complicating insulin-dependent diabetes revealed a pattern of interrelated structural changes strikingly similar to that of the diabetic rat when compared to age-matched controls. 17 older non-insulin-dependent diabetic patients with comparable duration and severity of hyperglycemia and severity of neuropathy, displayed similar nerve fiber loss, paranodal demyelination, paranodal remyelination and segmental demyelination compared to age-matched controls, but axo-glial dysjunction was replaced by Wallerian degeneration as the primary manifestation of fiber damage, and fiber loss occurred in a spatial pattern consistent with an ischemic component. The mechanistic model developed from the diabetic rat does indeed appear to apply to human diabetic neuropathy, but superimposed hormonal, metabolic, vascular, and/or age-related effects alter the morphologic expression of the neuropathy in non-insulin dependent diabetes.     

Acute and remitting painful diabetic polyneuropathy: a comparison of peripheral nerve fibre pathology.

The cause of the neuropathic pain that is experienced by some patients with diabetic neuropathy remains to be established. Early neuropathological reports, based on comparisons between diabetic patients and non-diabetic control subjects, emphasised associations between pathological changes in specific classes of peripheral nerve fibre and the presence of pain. By making comparisons with more appropriate control subjects, namely diabetic patients without neuropathic pain, more recent studies have found that there are few clear morphological correlates for this type of pain. To investigate this further, we have conducted a detailed morphometric study of sural nerve biopsies from six diabetic patients, four with active acute painful neuropathy and two with recent remission from the same condition. Normal values for the neuropathological parameters were obtained from six non-diabetic control subjects. Teased fibre analysis showed that similar axonal and Schwann cell abnormalities were present in both groups of diabetic patients. Electron microscopical studies revealed that evidence of both myelinated and unmyelinated fibre degeneration and regeneration was also present in the nerves of all diabetic patients, irrespective of whether they had pain. Within the constraints of interpreting results from small numbers of patients, our observations suggested that remission from pain might be associated with a less abnormal axon/Schwann cell calibre ratio, more successful myelinated fibre regeneration and less active unmyelinated fibre regeneration. However, the inescapable finding of this study was, in fact, the similarity in the nerve fibre pathology in diabetic patients with active and remitting painful neuropathy. We conclude that the occurrence of nerve fibre degeneration and regeneration is in itself unlikely to be sufficient to account fully for diabetic neuropathic pain. However, it is conceivable that events occurring during certain stages in the pathological cycle of degeneration and regeneration create the necessary circumstances which lead to pain.     

Fulminant Guillain-Barré syndrome mimicking cerebral death: case report and literature review

A 45-year-old woman was admitted to the intensive care unit (ICU) for respiratory arrest. One day prior to admission, she had been nauseated and in a state of total exhaustion. On the night of admission she was unresponsive and developed gasping respiration. The patient was comatose with absent brainstem reflexes and appeared brain dead. Blood chemistry findings and brain magnetic resonance imaging were normal. Electroencephalogram revealed an alpha rhythmical activity unresponsive to painful or visual stimuli. The cerebrospinal fluid showed an albuminocytological dissociation. Guillain-Barré syndrome (GBS) was suspected. The electrophysiological evaluation revealed an inexcitability of all nerves. The pathological findings of the sural nerve biopsy indicated an axonal degeneration secondary to severe demyelination. GBS can very rarely present with coma and absent brainstem reflexes. This case illustrates the importance of electrophysiological tests and laboratory and imaging studies in patients with suspected brain death where a cause is not clearly determined. Received: 13 August 1999 Final revision received: 27 January 2000 Accepted: 1 February 2000     

Endocrinopathy in POEMS syndrome: the Mayo Clinic experience

OBJECTIVE: To determine the prevalence and characteristics of endocrinopathies at diagnosis of POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. PATIENTS AND METHODS: From January 1, 1960, through June 30, 2006, we identified 170 patients with POEMS syndrome in the Mayo Clinic dysproteinemia database. We abstracted information about endocrine abnormalities from their medical records. RESULTS: Of the 170 patients with POEMS syndrome during the entire study period, the 64 patients seen after 2000 had more complete endocrine evaluations; of these 64 patients, 54 (84%) had a recognized endocrinopathy (38 men; median age, 50 years; interquartile range, 43-59 years). Hypogonadism was the most common endocrine abnormality; 26 (79%) of 33 men had subnormal total testosterone levels, and 10 men had gynecomastia. Among the 35 patients with measured prolactin levels, 7 men and 3 women had elevated levels. Hypothyroidism was noted in 17 men and 11 women. Abnormalities in glucose metabolism were present in 24 (48%) of 50 patients; 16 patients had impaired fasting glucose levels, and 8 were diagnosed as having diabetes. Adrenal insufficiency (defined by an abnormal response of cortisol to stimulation with standard high-dose [250 microg] synthetic adrenocorticotropic hormone) was noted in 6 of 9 patients tested. Fourteen (27%) of 51 patients tested had hypocalcemia. Twenty-nine (54%) of 54 patients had evidence of multiple endocrinopathies in the 4 major endocrine axes (gonadal, thyroid, glucose, and adrenal). CONCLUSION: The high prevalence of endocrinopathy in our study, to our knowledge the largest published series of POEMS cases, calls for a thorough endocrine investigation in patients presenting with this syndrome.     

POEMS综合征425例临床分析

目的总结425例POEMS综合征的临床特点及诊治.方法荟萃总结分析POEMS综合征临床表现的特点并与国外文献相比较.结果 POEMS综合征多见于中年男性,发病年龄11～74岁,平均43岁;临床表现以多发性周围神经病、脏器肿大、内分泌病、M-蛋白和皮肤改变为特征,常与多发性骨髓瘤并存;死因多见于严重感染、呼吸衰竭或心力衰竭等,发病机制不详;激素疗法短期疗效尚可.结论国内POEMS综合征患者周围神经损害、皮肤改变、肢端水肿等较常见,其次为肝脾肿大、阳痿、男性女性化乳房、闭经、胸腹水等.     

POEMS综合征9例临床分析

【目的】总结POEMS综合征的临床特征,加深临床医师对POEMS综合征的认识。【方法】回顾分析9例POEMS综合征的一般资料、临床表现、辅助检查、治疗和预后。【结果】患者平均年龄44岁,男女比例为3．5：1,9例患者均有多发性神经病、脏器肿大和内分泌改变,M蛋白阳性率55．6％,88．9％的患者有皮肤改变。治疗以激素为主（8／9）,1例患者激素联合化疗,1例患者放疗联合化疗,1例患者死于心源性猝死,出院时3例神经症状减轻,1例皮肤改变缓解。【结论IPOEMS综合征是一种少见的多系统损害疾病,临床表现复杂,临床诊疗水平有待提高。     

Chronic inflammatory polyradiculoneuropathy.

The diagnostic criteria, natural history, nerve conduction characteristics, pathology, laboratory features, and efficacy of corticosteroid treatment have been evaluated personally in 53 patients with chronic inflammatory polyradiculoneuropathy (CIP) who were followed up for an average of about 7.5 years. These were patients whose monophasic neurologic deficit had not crested by 6 months, patients with recurrences, and patients with a steady or stepwise progression. The typical features of CIP include absence of an associated disease, frequent history of preceding infection or receipt of foreign protein, and tendency to involve cranial, truncal, and proximal as well as distal limb structures and to have diffusely slow conduction velocity of peripheral nerves. The most marked slowing is often very proximal. The pathologic features include serous edema, mononuclear cell infiltrates (especially in perivascular areas, but without evidence of vasculitis), macrophage-induced segmental demyelination, and hypertrophic neuritis. If our patients are representative, complete recovery occurs only infrequently; about 60% of patients are able to be ambulatory and work, 25% become confined to a wheelchair or become bedridden, and approximately 10% die from their disease. Although the bulk of the pathologic changes affect spinal roots and proximal nerves, the brain and spinal cord may be involved also. Degeneration into linear rows of myelin ovoids is the predominant type of myelinated fiber degeneration of the sural nerve at the ankle.