多系统萎缩17例临床分析和一例尸检报告

目的分析多系统萎缩的临床、病理特点和诊断标准.方法按Gilman诊断标准,回顾性分析了17例多系统萎缩的临床资料和其中1例病理资料.结果按Gilman诊断标准,本组17例中,确诊多系统萎缩1例,拟诊12例,可疑者4例.首发症状表现为植物神经功能障碍者8例,锥体外系体征8例.病程中出现姿位性低血压的有12例;排尿障碍16例,阳痿9例;帕金森综合征症状12例;共济失调13例;皮质脊髓束损害12例.头颅MRI发现10例脑萎缩.1例经尸检证实存在少突胶质细胞包涵体.结论多系统萎缩是累及植物神经、锥体外系、小脑和皮质脊髓束,并具少突胶质细胞包涵体等特定神经病理表现的变性疾病.Gilman诊断标准具有较强的临床可操作性.     

多系统萎缩17例临床分析和一例尸检报告

目的 分析多系统萎缩的临床、病理特点和诊断标准。方法 按Gilman诊断标准,回顾性分析了17例多系统萎缩的临床资料和其中1例病理资料。结果 按Gilman诊断标准,本组17例中,确诊多系统萎缩1例,拟诊12例,可疑者4例。首发症状表现为植物神经功能障碍者8例,锥体外系体征8例。病程中出现姿位性低血压的有12例;排尿障碍16例,阳痿9例;帕金森综合征症状12例;共济失调13例;皮质兴髓束损害12例。头颅MRI发现10例脑萎缩。1例经尸检证实存在少突胶质细胞包涵体。结论 多系统萎缩是累及植物神经、锥体外系、小脑和皮质脊髓束,并具少突胶质细胞包涵体等特定神经病理表现的变性疾病。Gilman诊断标准具有较强的临床可操作性。     

帕金森病和帕金森叠加综合征11例黑质纹状体病理观察

目的 认识帕金森病（PD）和帕金森叠加综合征黑质纹状体组织细胞病变及异常蛋白质表达特征.方法 对尸检证实的5例PD,3例进行性核上性麻痹（PSP）和3例多系统萎缩（MSA）脑组织标本,进行Gallyas-Braak银染色,tau、α-synuclein、ubiquitin免疫组化染色.观察黑质纹状体组织神经细胞和胶质细胞变性特征及蛋白质表达特性.结果 PD、PSP及MSA的黑质腹外侧区及腹内侧区神经细胞均存在严重脱失.PD黑质神经细胞见α-synuclein和ubiquitin蛋白阳性路易小体.PSP黑质和苍白球神经细胞胞质内存在tau蛋白阳性球状神经原纤维缠结,同时黑质、苍白球还存在tau蛋白阳性葱状星形细胞及线团样少突胶质细胞变性.MSA纹状体神经细胞中至重度脱失,并在黑质、纹状体见大量α-synuclein和ubiquitin蛋白阳性、嗜银少突胶质细胞包涵体.结论 PD路易小体和MSA少突胶质细胞包涵体均表达α-synuclein和ubiquitin蛋白,提示这两组疾病存在相同的蛋白质病理基础;PSP黑质纹状体组织存在特征性的神经细胞和星形胶质变性,但其蛋白质病理属于与tau蛋白相关的变性疾病.     

HSV-2感染小鼠导致脊髓白质髓鞘脱失的研究

该实验为了解人类Ⅱ型单纯疮疹病毒（HSV－2）所致中枢神经系统（CNS）白质的脱髓鞘机制,将病毒经阴道感染小鼠。在感染前用环磷酸胺腹腔注射抑制小鼠免疫力,在病毒感染后第8天取小鼠脊髓制作样本分别进行光镜和电镜观察。结果显示,在机体免疫力抑制的条件下,病毒引起的髓鞘脱失率高于单独病毒感染所致。认为髓鞘脱失是由于病毒直接作用于少突胶质细胞及与其有关的髓鞘所致,而非自身免疫所引起。在讨论中认为由于免疫力降低,增加了病毒对少突胶质细胞及与其有关的髓鞘的毒性攻击能力,以致脱髓鞘频率增高。本实验的电镜中观察显示了少突细胞线粒体变性及髓鞘水肿变性,此时神经纤维轴索未受损伤。随后纤维断裂、崩解、被吞噬细胞吞噬,其时胞浆中内含有大量的次级溶酶体,其中的变性髓鞘处于不同的消化阶段。     

进行性多灶性白质脑病

正进行性多灶性白质脑病是一种中枢神经系统脱髓鞘性疾病,由JC病毒机会性感染所致。病变常位于灰白质交界处,髓鞘染色可见髓鞘脱失,病灶内特别是活动性病灶内有大量泡沫细胞,仅可见散在淋巴细胞浸润。受感染的少突胶质细胞胞核较大、深染,"毛玻璃"样改变的少突胶质细胞多见于病灶周边(图1a),病灶内及周围脑组织可见体积增大、深染、异形性或多核、     

影响多发性硬化髓鞘再生的因素及其机制

多发性硬化(MS)是常见的中枢神经系统(CNS)炎性脱髓鞘性疾病,目前认为MS是一种自身免疫性疾病,是细胞免疫与体液免疫共同参与导致的以脑和脊髓白质损伤为主的疾病.由于在人类成体前脑有大量少突胶质细胞前体细胞(OPC),另外在MS脱髓鞘斑内亦存在OPC,少突胶质细胞及其前体OPC是MS中髓鞘再生的主要来源.目前越来越多的研究认为髓鞘再生是MS治疗中非常有前景的方向,但是要达到有效的、有治疗作用的髓鞘再生,首先必须了解影响髓鞘再生的各种因素,理解控制髓鞘形成和髓鞘再生的确切机制.现就近年来这方面的研究进展综述如下.     

多发性硬化康复治疗

<正>多发性硬化(MS)是一种以中枢神经系统白质脱髓鞘为主要病理改变的自身免疫性疾病,常见病变部位位于脑或脊髓,临床表现为病变多发和反复复发-缓解病程,即空间和时间多发性,以髓鞘脱失、神经胶质增生、不同程度轴索病变和进行性神经功能障碍为主要特点,常累及脑室周围白质、视神经、脊髓、脑干和小脑,尤以侧脑室体部和脊髓前角多     

进行性多灶性白质脑病(附1例临床病理报告)

报告我国首例进行性多灶性白质脑病,临床上表现为精神症状后出现以锥体外系及锥体束损害为主的进行性弥漫性脑部病变,两大脑半球白质有散在众多与血管分布无关的脱髓鞘小病灶,并具有正常少突胶质细胞消失和星形胶质细胞增生肥大的病理特征,未发现核内包涵体的存在。     

慢性实验性变应性猴脑脊髓炎的超微结构改变

目的：探讨自身免疫性中枢神经系统脱髓鞘疾病慢性型的病理特点及其可能机制。方法：成功建立猴实验性态反应性脑脊髓炎模型数年后，根据MR摄片结果位病灶并作分类，然后进行病理取材和电镜观察超微结构。结果：（1）活动性病灶内成片的髓鞘松解、断裂或融合，轴突空泡样变性，皱缩或消失，少突胶质细胞变性，未见淋巴细胞浸润，仅见散在巨噬细胞，伴明显的间质水肿；（2）可疑活动性病灶内见部分髓鞘内板松解，其内轴突有较度空泡样变，亦见少突胶质细胞变性，散在巨噬细胞，未见淋巴瘤浸润，结论：慢性EAE的病理改变不仅有髓鞘的变性，同时轴突的病变也十分明显。     

JC病毒感染与进行性多灶性白质脑病

进行性多灶性白质脑病(progressive multifocal leukoencephalopathy,PML)是一种由JC病毒(JCV)感染少突胶质细胞引起的致命性中枢神经系统脱髓鞘疾病.1958年,美国麻省总医院的Richardson总结了2例慢性淋巴细胞白血病及1例霍奇金病患者尸检中发现的特殊脑病理改变,指出其白质内均存在众多大小不等的脱髓鞘病灶,而且小病灶有相互融合形成大病灶的趋势.当时,他推测这种融合趋势是疾病进展的表现,故将其命名为PML.翌年,Rubinstein在PML病灶中的少突胶质细胞核内发现了包涵体,推测PML可能与病毒感染有关.1965年,Zu Rhein使用电镜在上述包涵体中发现了类似多瘤病毒的病毒颗粒,证实了前人的推测.     

Study on argyrophilic inclusions of multisystem atrophy (Oppenheimer)]

Non-hereditary olivo-ponto-cerebellar atrophy (OPCA) and striato-nigral degeneration (SND) have been looked upon as a single disease entity called multisystem atrophy (MSA) by Oppenheimer. This study revealed that both intracytoplasmic argyrophilic inclusions (AI) in pontine neurons and glial (argyrophilic) cytoplasmic inclusions (GCIs) widely distributed in the CNS are characteristics of MSA. MATERIALS: a) 12 cases with MSA, b) 16 cases with autosomal dominant (AD) form of spinocerebellar degeneration (SCD): AD form of OPCA 5 cases, Joseph disease 4 cases, AD-dentatorubropallidoluysian atrophy (Naitoh & Oyanagi's form) 6 cases, AD-spastic ataxia (Brown) 1 case, c) 4 cases with autosomal recessive (AR) form of SCD: AR form of OPCA 1 case, myoclonic epilepsy with ragged-red fibers (MERRF) 1 case, complicated form of spastic paraplegia 2 cases, d) 6 cases with non-hereditary SCD including intoxications: late cortical cerebellar atrophy 1 case, alcoholic cerebellar degeneration 2 cases, phenytoin-induced cerebellar degeneration 1 case, neuroleptic malignant syndrome 1 case, and e) 27 cases with other neuropsychiatric diseases: Alzheimer disease 20 cases, progressive supranuclear palsy 5 cases, schizophrenia 2 cases. METHOD: We examined 10 mu-thick paraffin sections stained with HE, Klüver-Barrera, Bodian, Holzer, Gallyas, and Bielschowski methods. RESULTS: AI in pontine neurons were found only in two cases of MSA. Interestingly no AI could be detected even in cases with AD form of OPCA showing mild degeneration in the pontocerebellar system. On the other hand, GCIs were found in all cases with MSA irrespective of the degree of degeneration in the olivo-ponto-cerebellar or striato-nigral system. However, there was no GCIs in cases with other form of SCD and other neuropsychiatric diseases. Gallyas stain was the best method for detecting GCIs. GCIs were widely distributed in the CNS except for superficial layers of the cerebral cortex, the cerebellar cortex, and the dorsal column of the spinal cord. There were also many GCIs in the putamen, pontine base, and cerebellar white matter, even though these sites were well preserved.     

原发性干燥综合征继发中枢神经系统血管炎临床及影像分析

目的   探讨原发性干燥综合征继发中枢神经系统血管炎的临床和影像特征。 方法   回顾性分析35例原发性干燥综合征继发中枢神经系统血管炎患者临床表现和影像学资料。 结果  男性5例,女性30例;年龄18～76［平均（52±14）］岁;中枢神经系统首发症状24例（68.57%）。其中以急性脑血管病发病患者8例（22.86%）,表现为蛛网膜下腔出血2例（5.71%）,短暂性脑缺血发作2例（5.71%）,动静脉瘘2例（5.71%）,脑出血1例（2.86%）,静脉窦血栓1例（2.86%）,其余的患者临床表现形式分别为：脑白质病变10例（28.57%）,视神经脊髓炎6例（17.14%）,脊髓炎5例（14.29%）,帕金森综合征3例（5.57%）,三叉神经痛2例（5.71%）,脑脊髓炎1例（2.86%）。影像学表现动脉瘤3例（8.57%）（2例蛛网膜下腔出血）;动脉狭窄2例（5.71%）,其中椎动脉狭窄1例（2.86%）,大脑中动脉狭窄1例（2.86%）;颞顶枕动静脉瘘2例（占5.71%,三叉神经痛合并动静脉瘘1例）;上矢状窦血栓1例（2.86%）。室旁白质受累20例（57.14%）,皮层下白质受累16例（45.71%）,脑干8例（22.86%）,脊髓11例（31.43%）;脑室扩大2例（5.71%）;其中脊髓/脑干单病灶累及多个脊髓阶段（≥3个脊髓阶段）患者10例（28.57%）。 结论  中枢神经系统原发性干燥综合征可以急性脑血管病形式起病,但以急慢性小血管受累的脑白质病和脊髓病最常见;单病灶多个脊髓阶段是脊髓病变的影像特点。     

Widespread spinal cord involvement in progressive supranuclear palsy

We describe the histopathologic features of spinal cord lesions in 10 cases of progressive supranuclear palsy (PSP) and review the literature. Histologic examination revealed atrophy with myelin pallor in the anterior funiculus and anterolateral funiculus in the cervical and thoracic segments in eight of the 10 cases, whereas the posterior funiculus was well preserved. The degrees of atrophy of the anterior funiculus and the anterolateral funiculus correlated with that of the tegmentum of the medulla oblongata. Myelin pallor of the lateral corticospinal tract was observed in two of the 10 cases. Microscopic observation of the spinal white matter, particularly the cervical segment, revealed a few to several neuropil threads, particularly in the white matter surrounding the anterior horn after Gallyas‐Braak (GB) staining or AT‐8 tau immunostaining. However, the posterior funiculus was completely preserved from the presence of argyrophilic or tau‐positive structures. In the spinal gray matter, widespread distribution of neurons with cytoplasmic inclusions and neuropil threads was observed, particularly in the medial division of the anterior horn and intermediate gray matter, especially in the cervical segment. Globose‐type neurofibrillary tangles and pretangles were found. The distribution of GB‐ or AT‐8 tau‐positive small neurons and neuropil threads resembled that of the spinal interneurons. In conclusion, the spinal cord, especially the cervical segment, is constantly involved in the pathologic process of PSP. We speculate that spinal interneurons and their neuronal processes, particularly in the medial division of the anterior horn and intermediate gray matter of the cervical segment, are most severely damaged in the PSP spinal cord.     

Conventional magnetic resonance imaging features in patients with tropical spastic paraparesis

Conventional brain and spinal cord magnetic resonance images were performed in 21 patients with human T-cell lymphotropic virus (HTLV)-1 associated myelopathy/tropical spastic paraparesis, to assess the role of conventional magnetic resonance imaging (MRI) in the disease diagnosis. These patients had no other central nervous system conditions or related risk factors at the time of tropical spastic paraparesis diagnosis. Eleven (52.4%) patients showed nonspecific brain abnormalities on T2-weighted images. The majority (77.2%) of brain abnormalities were located in the deep white matter. A transient contrast-enhancing lesion was identified in the brain of only one patient. In the brain of another patient, 9.0% of the T2-hyperintense lesion load was hypointense on the correspondent T1-weighted images. No differences in terms of demographic, biological, or clinical variables were present between patients with abnormal brain images and those with normal brain magnetic resonance images. Spinal cord T2-weighted images were abnormal in three (14.3%) patients. In one of these three patients, a diffuse but transient edema was found along the entire tract of the spinal cord. White matter lesions were present in the central nervous system of 60% of the cases in this study. However, no correlations between magnetic resonance imaging and clinical findings, and no specificity of lesions were observed. Hence, conventional magnetic resonance imaging is a sensitive but not highly specific tool for diagnosis of tropical spastic paraparesis.     

Amyotrophic lateral sclerosis: early contributions of Jean-Martin Charcot

Amyotrophic lateral sclerosis is historically an important entity because its manifestations involve distinct signs that can be correlated with gray and white matter lesions at specific sites within the central nervous system. Working at the end of the nineteenth century, the celebrated neurologist, Jean-Martin Charcot, used this disorder as a prototypic example of the power of his research method, termed "méthode anatomoclinique." Using clinical cases and autopsy material, he showed how anatomical lesions in the nervous system could be accurately determined by the presence of carefully analyzed clinical signs. Charcot's work on amyotrophic lateral sclerosis brought together neurological entities formerly considered as disparate disorders, primary amyotrophy and primary lateral sclerosis. In addition, these studies contributed to the understanding of spinal cord and brain stem anatomy and the organization of the normal nervous system. Because of Charcot's fundamental contributions, the eponym "Charcot's disease" has been used internationally in association with amyotrophic lateral sclerosis.     

Spinal cord lesions of progressive multifocal leukoencephalopathy in an acquired immunodeficiency syndrome patient

Progressive multifocal leukoencephalopathy (PML) is a deadly demyelinating disease of the central nervous system, which occurs in immunosuppressed individuals. This disease is caused by a reactivation of the polyomavirus JC (JCV). Clinical presentation can be variable from patient to patient as lesions can occur anywhere in the CNS white matter; however, they appear to spare the optic nerves and the spinal cord. The authors present a case of PML in the setting of acquired immunodeficiency syndrome (AIDS) who developed PML lesions in the spinal cord, discovered during the postmortem examination. This finding is significant because PML has recently been diagnosed in patients with multiple sclerosis (MS) treated with the novel immunomodulatory medication natalizumab. Indeed, spinal cord lesions are frequent in MS. Therefore clinicians should be aware that in addition to the brain, PML may also affect the spinal cord white matter.     

Magnetic resonance imaging of spinal cord lesions in multiple sclerosis.

The clinical and pathological manifestations of multiple sclerosis are due to areas of demyelination which occur throughout the white matter of the central nervous system. MRI of the brain frequently shows abnormalities in the hemispheric subcortical white matter; these are demonstrable in the majority of patients and support the clinical diagnosis of multiple sclerosis. Our studies have shown that while MRI identifies such cerebral lesions in nearly all clinically definite multiple sclerosis patients with illness of duration greater than 10 years, these areas of abnormal T2 signal are present less often in the brains of patients studied within 3 years of disease onset. However, symptoms referable to the long tracts of the spinal cord are prominent in many of these patients. Imaging of the spinal cord has presented technical problems because of the small size of the cord, patient body, heart and respiratory movements, and limitations of surface coil technology. The spinal cord of 77 patients with multiple sclerosis have been imaged, revealing three types of abnormalities: (1) approximately half the cords show regions of abnormal T2 weighted signal; (2) during acute exacerbation, spinal cord enlargement (swelling) may be observed; (3) spinal cord atrophy (narrowing) is found particularly in patients with disease of longer duration and greater disability. Unlike the presence of brain lesions, the existence of spinal cord lesions of high T2 signal is not associated with increasing duration of disease but is correlated with disability status. Of patients with such lesions about one fifth did not exhibit brain lesions discernible by MRI.     

New concepts on progressive multiple sclerosis

Multiple sclerosis is generally regarded as a putative autoimmune disease of the central nervous system in which a chronic T-cell-mediated inflammation leads to focal plaques of demyelination in the white matter of the central nervous system. This plaque-centered view of the disease, however, fails to explain clinical deterioration of the patients when they have reached the progressive stage of the disease. It was thus postulated during the past few years that besides inflammation there is a neurodegenerative component of the disease that leads to progressive and global brain damage. This article reviews recent findings that suggest a different explanation. It describes that in the early stage of acute and relapsing multiple sclerosis, focal plaques in the white matter are formed by relapsing waves of inflammation. With chronicity, however, the inflammatory response becomes trapped behind the blood-brain barrier, giving rise to slowly progressive inflammatory damage that affects the brain and spinal cord in a global sense. This is mainly reflected by extensive cortical demyelination and diffuse axonal injury within the normal-appearing white matter. This process seems to be driven by the aberrant formation of ectopic lymphatic tissue within the brain compartment.     

Relapsing-remitting inflammatory disease of the central nervous system with normal MRI: multiple sclerosis or phenocopy in a series of 15 patients

Multiple sclerosis is a demyelinating disease of central nervous system. Although many sub-types and clinical forms are identified, diagnosis is clearly related to the detection of MS lesions on brain MRI. We report data of 15 patients admitted in Nice for suspicion of MS after clinical relapsing-remitting or progressive symptoms. Extensive screening tests (i.e blood sample, CSF, MRI, spectroscopy) were performed at onset and at each relapse. All patients had normal-appearing white matter on spinal cord and brain MRI. Nevertheless, 11 patients can be considered as MS according to McDonald criteria.     

Arrested maturation of cerebral neurons, axons and myelin: a new familial syndrome of newborns.

A new lethal familial syndrome of unknown etiology is described in two male siblings who died in the newborn period. Both had corneal edema and were hypotonic, requiring assisted ventilation at birth. Neuropathological findings included an immature appearance of neocortical neurons, with cortical architecture similar to that normally seen in an infant of 5 months gestational age. Axons and myelin were absent in the cerebral and cerebellar white matter, and also in descending white matter tracts of brainstem and spinal cord. Subacute inflammation was seen in the anterior horns of the spinal cord in both cases, although there was no evidence of inflammation elsewhere in the nervous system. Electron microscopy of endothelial cells from brain, spinal cord and a number of other tissues of the second sibling showed tubuloreticular inclusions (TRIs). There are no known previous reports of similar neuropathology. Future recognition of this condition will be important for genetic counselling.