干燥综合征神经系统损伤的临床病理分析

目的探讨原发性干燥综合征(Sjgren综合征)神经系统损伤的临床病理特征及其机制。方法8例患者均符合欧洲原发性Sjgren综合征的诊断标准,其中唇黏膜活检5例,腓肠神经活检5例,肱二头肌活检1例,全部标本均进行了组织和免疫病理学检查。结果对称性感觉运动性周围神经病2例,多发性单神经病2例,感觉性周围神经病1例,脑神经损伤2例,累及中枢神经2例。唇黏膜活检示部分腺体萎缩,腺泡及间质内可见淋巴、单核吞噬细胞浸润,主要为CD8阳性的毒性和抑制性T细胞。腓肠神经活检示1例有典型血管炎改变,4例无血管炎性改变。可见有髓纤维丢失、轴索和髓鞘断裂,小静脉周围可见CD68阳性单核吞噬细胞及CD45RO阳性T细胞。肌活检示肌纤维有轻度变性坏死,间质内可见少量淋巴及吞噬细胞。结论Sjgren综合征导致的神经损伤呈多样性,且常先于Sjgren综合征的诊断之前出现,因此追述有无眼干、口干症状对诊断有重要价值。血管炎及非血管炎性免疫介导的炎性细胞浸润可能是Sjgren综合征神经损伤的重要机制。     

干燥综合征患者伴神经系统损害7例临床及病理变化

目的 探讨干燥综合征患者伴神经系统损害患者的临床及其肌肉和周围神经病理改变。方法 对7例患者的临床表现、实验室检查进行系统描述,对肌肉及神经组织进行组织学及组织化学染色,并行电子显微镜检查。结果 2例神经组织活检可见有髓神经纤维严重脱失,有髓神经纤维数目严重减少,轻度轴索变性。5例肌肉活检可见肌纤维萎缩、坏死,血管周围有单核样细胞浸润,肌内衣有微血管炎的病理改变。结论 干燥综合征患者的肌肉或周围神经并发症在疾病的早期即可出现,肌肉或神经活检可证实有无损害及其严重程度,早期诊断及早期治疗对改善干燥综合征患者伴神经系统损害者的预后是很有 必要的。     

15例慢性炎性脱髓鞘性多发性神经根神经病的病理和临床研究

目的 探讨慢性炎性脱髓鞘性多发性神经根神经病(CIDP)的病理和I临床特点。方法 对15例CIDP患者均进行腓肠神经活检和临床分析。结果15例腓肠神经活检显示以脱髓鞘为主要表现，其中6例伴有轻度轴索变性；15例均有不同程度的雪旺氏细胞增生，其中3例合并有洋葱样肥大神经改变。结论 CIDP病理诊断一定要结合有髓纤维和无髓纤维的改变，以及血管和结缔组织的改变和临床综合判断。     

血管炎性周围神经病临床病理学研究

目的总结不同类型血管炎性周围神经病临床和病理学特点,提出病理诊断要点以指导临床诊断。方法回顾分析11例血管炎性周围神经病患者之临床表现、实验室检查和神经肌肉组织活检特点,观察神经、肌肉和皮肤组织病变。通过免疫组织化学染色检测神经微丝蛋白、髓鞘碱性蛋白、外周髓鞘蛋白22、S-100蛋白,以及人类白细胞抗原DR、CD68、CD3、CD20表达变化,分别观察神经轴索、髓鞘、施万细胞病变和炎性细胞浸润情况;免疫荧光染色检测免疫球蛋白IgA、IgM、IgG和补体C3在血管壁沉积情况;特殊染色检测肌肉病变程度。结果血管病变以神经束周和外膜小血管CD3+T细胞浸润为主,呈活动性血管炎(3例)或非活动性血管炎(8例)改变,8例中4例呈血管纤维闭塞性改变严重、炎性细胞浸润较轻,4例以血管周围炎为主、血管壁本身病变不明显。神经病变以轴索变性为主(6例)或轴索变性伴髓鞘松解和脱失(5例),大直径有髓纤维明显减少,甚至呈终末期改变。肌肉组织活检呈神经源性萎缩。病理诊断为系统性血管炎性周围神经病8例[原发性系统性血管炎5例(抗中性粒细胞胞质抗体相关性小血管炎2例、Churg-Strauss综合征1例、免疫相关性间质性肺疾病2例)和继发性系统性血管炎3例(干燥综合征)],以及非系统性血管炎性周围神经病3例。结论血管炎性周围神经病的神经改变以轴索病变为主,血管炎病理改变呈多样性,不能仅以活动性血管炎作为唯一的病理诊断标准。因此对于临床可疑血管炎性周围神经病患者应完善血液免疫学指标检查和神经组织活检,必要时联合肌肉组织活检以明确诊断。     

腊肠体样周围神经病的临床、电生理和病理特点

目的总结腊肠体样周围神经病的临床、电生理和病理特点。方法收集3例患者病史、体格检查以及电生理检查及病理检查资料。结果3例患者中男2例、女1例,13～28岁发病,阳性家族史2例;机械性压迫或牵拉后导致双侧腓总神经麻痹1例,隐袭和慢性起病各1例。电生理检查可见广泛的周围神经损伤,正中神经运动传导远端潜伏期（DML）均延长。腓肠神经活检均可见少数明显增粗的有髓神经纤维,电镜下可见髓鞘板层数增多。1例患者肌肉活检示轻微病理改变。结论腊肠体样周围神经病为周围神经髓鞘发育障碍所致,神经电生理和神经病理对诊断有特异性。     

肌痛、肌无力、肌萎缩与血管炎(附79例报告)

目的探讨血管炎与肌痛、肌无力、肌萎缩的关系。方法观察了７９例表现为肌痛、肌无力、肌萎缩，经病理证实为血管炎之患者的临床、有关实验室检查、肌电图及肌肉神经病理活检情况。结果血管炎可仅累及周围神经、肌肉而无其它器官及系统损害；其免疫学指标有异常改变；肌电图可表现为肌病性改变和／或周围神经性改变；腓肠神经、肌肉活检可见束周肌纤维萎缩，少量炎性细胞浸润；神经原性损害者可见神经髓鞘或轴索的病理改变以及肌肉的小群组化、角形纤维、靶纤维等改变。结论血管炎是肌痛、肌无力、肌萎缩一个较常见的病因     

变应性肉芽肿性血管炎的神经系统表现

目的研究变应性肉芽肿性血管炎(AGA,亦称ChurgStrauss综合征,CSS)相关神经病的发病率、临床类型、发病机制、诊断和治疗。方法14例确诊为CSS的患者从临床表现、实验室检查、神经电生理检查和活检病理检查等方面予以分析,并观察治疗效果。结果14例CSS患者中有12例累及周围神经系统,其中5例以周围神经病为首发症状。12例周围神经受累的患者中5例表现为多发性单神经病,4例表现为远端不对称的多发性神经病,2例表现为对称的多发性神经病。腓肠神经活检可见有髓神经纤维丢失,轴索变性。电生理检查发现感觉和运动传导波幅显著降低或消失。CSS的诊断应结合临床与病理所见。除1例患者外,激素治疗对CSS相关神经病有效。结论CSS患者中周围神经病很常见,早期诊断可改善预后。     

伴有炎性改变的腓骨肌萎缩症二例病理报告

目的 报道2例经基因诊断明确的腓骨肌萎缩症患者的病理特点.方法 对2例经基因诊断明确为连接蛋白32（connexin 32,Cx32）基因突变所致的腓骨肌萎缩症患者进行腓肠神经和腓肠肌活检,肌肉切片采用HE染色,腓肠神经半薄切片采用美蓝染色,另采用免疫组织化学（SP法）检测腓肠神经是否有炎症细胞浸润.所用抗体为抗CD68抗体和抗白细胞共同抗原（LCA）抗体.结果 2例患者腓肠肌活检均可见肌间质大量炎性细胞浸润,脂肪增生.腓肠神经半薄切片未见明显洋葱球样结构形成,可见有髓纤维密度明显减少,大量薄髓鞘有髓神经纤维和有髓神经纤维再生簇形成.免疫组织化学见2例患者腓肠神经CD68和LCA表达均呈阳性.结论 腓骨肌萎缩症患者可表现为炎性病理改变,临床上要注意与慢性炎症性脱髓鞘性多发性神经病等鉴别.     

类淀粉变性多神经病

目的　探讨类淀粉性周围神经病的临床特点及病理改变。方法　报告 3例经腓肠神经和皮肤活检证实的病例 ,结合文献分析其临床特点、病理改变及治疗。结果　本病为慢性进行性周围神经病 ,可伴有心、胃肠、肾等损伤。病理改变示刚果红染色阳性 ,可见类淀粉物沉积于神经内膜、束膜及血管壁外膜 ,有髓及无髓纤维减少 ,节段性脱髓鞘。结论　根据临床特点及周围神经皮肤活检进行诊断 ,肝移植是治疗本病最有前途的方法     

慢性特发性轴索性多神经病的病理及免疫组化研究

目的 研究慢性特发性轴索性多神经病(chronic idiopathic axonal polyneuropathy,CIAP)病理改变特点,并探索腓肠神经炎细胞CD3、CD20、CD68抗体及其微小血管内皮细胞膜结合性血栓调节蛋白(thrombomodulin,TM)、内皮源性一氧化氮合酶(endothelial-nitricoxide synthase,e NOS)的表达规律。方法 10例经过临床、电生理、腓肠神经活检病理检查证实的CIAP患者,均进行腓肠神经活检标本的常规病理组织学染色以及以抗CD3、CD20、CD68、TM、e NOS、v WF(von Willebrand factor,v WF)抗体作为第一抗体的免疫组织化学染色。结果 10例患者腓肠神经病理检查显示有髓神经纤维轻-中度减少,伴随轴索变性和再生,部分可见轻微脱髓鞘改变,4例患者出现毛细血管基底膜肥厚。4例患者腓肠神经神经束衣间小血管周围有散在分布的CD68阳性单核细胞浸润。所有患者血管内皮细胞v WF、e NOS、TM均正常表达。结论 CIAP病理特点为轴索损害为主,发病可能和体液免疫异常有关,部分患者毛细血管基底膜肥厚提示血管内皮细胞可能受损,但内皮细胞功能相关蛋白表达初步提示正常。     

Schwann cell remyelination of demyelinated axons in spinal cord multiple sclerosis lesions

To investigate remyelination in multiple sclerosis lesions, we immunostained spinal cord sections from patients with multiple sclerosis and neurological normal (control) patients with antisera to P0 protein, a major constituent of peripheral nervous system myelin, and myelin basic protein, which is found in both central and peripheral nervous system myelin. In sections from five of the eight patients with no clinical or pathological evidence of neurological disease, P0 immunostaining was confined to peripheral myelin sheaths in dorsal and ventral roots. They were intensely stained, and peripheral--central nervous system transition zones were clearly demarcated. Sections from the other three control patients contained a few P0-stained sheaths in the central nervous system near root entry zones or among marginal glia near the dorsal sulcus. Spinal cord sections from six of the ten patients with multiple sclerosis contained clusters of myelin sheaths immunostained by P0 antiserum. These regenerating sheaths of peripheral nervous system origin were most numerous in large lesions and were commonly located in central areas or peripherally near root entry zones. The sheaths were observed frequently in areas of active demyelination and appeared morphologically normal even when surrounded by debris-filled macrophages. Near margins of small inactive plaques were a few basic protein--stained oligodendroglia extending processes to thin basic protein--stained sheaths.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lupus-related myelopathy: report of three cases and review of the literature.

Transverse myelopathy is an uncommon complication of systemic lupus erythematosus (SLE). Three patients with SLE are reported who developed transverse myelopathy, including the neuropathological findings in one patient on whom necropsy was performed. Paraparesis was present in all three cases, but definite sensory changes were present in only one patient. In two patients, the CSF findings were remarkable for elevated protein and depressed glucose concentrations. Microscopic examination of the brain demonstrated small, scattered foci of recent necrosis consistent with microinfarctions. Striking abnormalities were found in the spinal cord at all levels, including multiple foci of vacuolar spongy degeneration in the peripheral white matter, as well as ballooning of myelin sheaths, swollen axons, myelin pallor, and loss of glial nuclei. The pathological findings in previously reported cases of SLE-related transverse myelopathy are reviewed, and the possible pathogenesis of the findings in our case are discussed.     

Polymyositis associated with peripheral nerve lesion: clinico-pathological investigation of 8 cases

Polymyositis with peripheral nerve lesion are rare. The study of eight cases of polymyositis with some peripheral lesion, pathologic investigation of muscle biopsy of all patients and biopsy of sural nerve in six cases were reported. Age: 19-52 (average 34) yrs. Course: 4mo-10 (average 4) yrs. They showed symmetric weakness and tenderness of the proximal muscles, peripheral hypoesthesia and hypo even areflexia. Electrophysiological parameters showed myogenic lesion in 8 cases and neurogenic in 3 cases. Pathological (light and electron-microscopic) findings coincide with acute and chronic myositis, consisting of focal necrosis of muscle fiber, monocyte infiltration, myofibril regeneration, hyperplasia of interstitial vessels and fibrous tissue in muscle biopsy of 8 cases; mild to moderate loss of density of myelinated fibers, mostly thin myelin sheath and demyelinating changes, axonal degeneration also, mainly loss of unmyelinated fiber, perivascular monocyte and macrophages in sural nerve biopsy of six cases. The aforementioned clinical and pathological findings suggest that involving both muscle and nerve be able to primary. No primary course involving nerve has been found, except in only one case with coexisting SLE, another case six months later carcinomatous myositis was diagnosed, but there are no evidence of vasculitis and ischemic neuropathy.     

Neurogenic muscular atrophy and low density of large myelinated fibres of sural nerve in chorea-acanthocytosis.

In three cases of chorea-acanthocytosis (acanthocytosis and neurological disease, or familial degeneration of the basal ganglia with acanthocytosis), biopsies of short peroneal muscles and sural nerves were studied histologically. The muscles showed groups of atrophic fibres with clumping of sarcolemmal nuclei in all cases. It was concluded that neurogenic muscular atrophy should be included as one of the main pathological findings in chorea-acanthocytosis. The sural nerves showed a small number of large myelinated fibres in two cases. This finding remains to be confirmed in other cases.     

The peripheral neuropathy of vitamin B12 deficiency

Nerve conduction studies and sural nerve biopsy were performed on three patients with vitamin B12 deficiency and symptoms of peripheral neuropathy. The pathological findings were those of axonal degeneration; there was no evidence of demyelination. The patients were reviewed at intervals of 5-15 years commencement of treatment; progression of the neuropathy had been arrested by treatment, but in all cases residual neurological abnormalities persisted. In one patient with autonomic neuropathy, the postural hypotension resolved rapidly and fully with treatment.     

Sensorimotor and autonomic neuropathy associated with systemic lupus erythematosus

In this article, one described 7 patients with systemic lupus erythematosus (SLE) and the pathological findings of their sural nerves. In 4 of the 7 cases the criteria for diagnosis of SLE were satisfied and in 3 cases there was serological evidence of an undifferentiated connective tissue disease, most likely to be SLE. The peripheral neuropathy was of a chronic sensorimotor type with predominantly sensory features and gradual onset. In 2 cases the presentation was asymmetrical. One patient had autonomic dysfunction. There was ischemic neuropathy in 2 cases, segmental demyelination in 2 cases, and axonal degeneration with demyelination in 3 cases. In 6 cases there was increased expression of Ia antigen within the nerve fascicle, perineurium and endothelial cells.     

Sural nerve morphology in asymptomatic uremia

This study evaluates morphologically the sural nerves of two patients with acute and another pair with chronic uremia, both of whom had neither clinical nor electrophysiologic evidence of neuropathy. Morphometric changes indicative of myelin repair were noted in the chronic uremic case who had a shorter duration of renal failure but required dialysis. Also, changes suggestive of axonal degeneration were found in the case who had chronic uremia of long duration. Both cases of acute uremia did not reveal significant abnormalities. Structural changes in the sural nerves may precede clinical and nerve conduction derangements in uremia, specifically in chronic cases.     

Neuropathology of multiple sclerosis—new concepts

Multiple sclerosis is a chronic inflammatory disease of the central nervous system with profound heterogeneity in clinical course, neuroradiological presentation and response to therapy. The pathological analysis of 235 actively demyelinating lesions coming from three centers revealed different structural and immunological features suggesting that different pathogenetic mechanisms are involved in lesion formation. On the basis of the presence or absence of immunoglobulin and complement deposition, myelin protein loss and the patterns of oligodendrocyte degeneration beside a T cell- and macrophage-dominated immune response, four distinct patterns of demyelination have been identified. In this short review, possible paraclinical markers for tissue destruction on the basis of the main features of myelin destruction are discussed. Furthermore, the importance of early axonal damage in multiple sclerosis is highlighted.     

Neuropathology of multiple sclerosis-new concepts

Multiple sclerosis is a chronic inflammatory disease of the central nervous system with profound heterogeneity in clinical course, neuroradiological presentation and response to therapy. The pathological analysis of 235 actively demyelinating lesions coming from three centers revealed different structural and immunological features suggesting that different pathogenetic mechanisms are involved in lesion formation. On the basis of the presence or absence of immunoglobulin and complement deposition, myelin protein loss and the patterns of oligodendrocyte degeneration beside a T cell- and macrophage-dominated immune response, four distinct patterns of demyelination have been identified. In this short review, possible paraclinical markers for tissue destruction on the basis of the main features of myelin destruction are discussed. Furthermore, the importance of early axonal damage in multiple sclerosis is highlighted.     

Leber's disease with spastic paraplegia and peripheral neuropathy. Case report with nerve biopsy study

A 43-year-old patient with familial Leber's optic atrophy suffered from spastic paraplegia. Physical examination disclosed cerebellar and pyramidal signs and signs of peripheral neuropathy. On sural nerve biopsy, there were few large myelinated fibers, signs of axonal degeneration and thin myelin sheets. This case suggests an overlap syndrome with central and peripheral nervous system features of Leber's disease, spinocerebellar degeneration and peroneal muscular atrophy.