Huntington舞蹈病大脑免疫病理改变及其和痴呆精神异常的关系

目的：研究Huntington舞蹈病的组织病理改变特点,观察泛素阳性营养不良性神经突起和神经细胞核内包涵体在大脑不同部位的分布规律,探讨痴呆和精神异常的病理基础,方法：先症者为－49岁的男性病人,表现为进行性痴呆、舞蹈和精神异常,于病后17年死亡。家族中连续5代人中15例出现类似临床表现,先症者死亡后进行部头解剖和组织学检查,对大脑皮层和基底节不同区域进行tau蛋白和泛素免疫比喻杂色,分析不同区域的病理改变规律。结果：脑病理改变特点为新纹状体显著萎缩,神经细胞脱失伴胶质细胞增生,泛素阳性的营养不良性神经突起和神经细胞核包涵体主要出现在大脑皮层的Ⅲ-Ⅳ层,神经细胞核内泛素阳性包涵体在大脑额叶前区皮层达22％,依次为顶叶7％、枕叶3％、颞叶1％和哲带回1％。相就细胞核出现变性改变,包涵体不含有tau蛋白。泛素阳性营养不良性神经突起在大脑额叶前区皮层最多,每低倍视野达5个以上,其次为顶叶、颞叶和扣带回的皮层,低倍视野在1－5个之间,海马和纹状体仅偶见营养不性神经突起,没有神经细胞核内包涵体,结论：大脑皮层出现泛素阳性神经细胞内包涵体和营养不良神经突起在大脑不同区域的分布存在很大的差异,由于额极也存在明显的病理改变,所以此病的智能减退属于额叶皮层－皮层下性痴呆。额叶、颞叶和扣带皮层出现神经细胞核内包涵体或营养不良性神经突起可能是精神异常的病理学基础。     

伴有周围神经损害的强直性肌营养不良

目的探讨强直性肌营养不良(DM)的临床表现和病理改变。方法通过1例确诊的DM病例的临床表现和神经肌肉的病理改变来系统回顾本病的发病机理、分类、临床表现、病理改变、诊断和治疗。结果该例患者的临床表型和肌肉病理改变符合DM1型,腓肠神经主要病理改变为轴索变性,伴有轻度脱髓鞘。结论DM是一组遗传性疾病,临床表现为骨骼肌萎缩、力弱、强直和多种骨骼肌以外的症状,可伴有以轴索变性为主的周围神经损害。     

4例亚急性海绵状脑病的临床与病理

目的探讨Creutafeldt-Jakob(CJD)病的临床与病理特点。方法分析4例脑活检证实的Creutafeldt-Jakob患者的临床资料、脑电图及脑活检的病理特点。结果CJD病的临床表现进行性痴呆、共济失调、锥体系症状、锥体外系症状,视觉障碍和肌阵挛发作;病理改变大脑组织呈海绵状变性,大脑神经细胞脱失,星形胶质细胞增生;脑电图的特征性改变周期性尖慢波发放(PSWC)。结论临床表现和脑电图对CJD的诊断具有重要意义,确诊依靠病理检查。     

亚急性硬化性全脑炎临床与病理分析

目的　通过分析已确诊的亚急性硬化性全脑炎 (SSPE)病例 ,探讨其临床特点及早期诊断要点。方法　回顾分析 5例经病理或免疫学检查证实的SSPE的临床资料及病理结果。结果　 5例均有高级神经系统损害的表现、肌阵挛、锥体束损害及特征性脑电图改变 ,早期临床表现常为智能减退。病理改变为脑的灰质和白质均广泛受累 ,血管周围淋巴细胞和浆细胞袖套状浸润 ,胶质细胞增生 ,白质片状脱髓鞘改变 ,神经细胞和胶质细胞核及胞浆内可见嗜伊红包涵体。本组 4例符合以上改变 ,部分电镜下见可疑病毒颗粒。血清及脑脊液麻疹抗体阳性可助生前诊断SSPE。本组 4例死亡 ,1例呈缄默状态。结论　有上述临床特点的患者应尽早行血清及脑脊液麻疹病毒免疫学检查以明确诊断。本病预后差 ,加强支持治疗可延长生命     

Duchenne型肌营养不良的临床和病理及抗肌萎缩蛋白表达

目的：归纳总结Duchenne型肌营养不良（DMD）的临床表现,组织病理特点及抗肌萎缩蛋白表达情况。方法：通过临床、病理及免疫组化染色方法,对16例DMD患者的临床表现,肌肉病理改变和肌肉抗肌萎缩蛋白表达情况进行观察分析。结果：年龄〉4岁的14例患儿均有比较典型的DMD临床表现;而年龄〈4岁的2例患儿症状较轻。肌肉病理显示2例为早期改变、11例为中期改变、3例为晚期改变,病理改变严重程度与年龄相关。免疫组化染色显示16例患者的肌肉标本抗肌萎缩蛋白均完全缺失。结论：DMD患者的临床和病理表现的严重程度与年龄有关,检查抗肌萎缩蛋白在肌纤维膜上表达是诊断DMD的金标准。     

dysferlinopathy患者八例临床及分子病理学特点

目的探讨中国dysferlinopathy患者的临床及分子病理学特点。方法分析已确诊的4例肢带型肌营养不良2B型、4例Miyoshi远位型肌营养不良患者的临床、骨骼肌活体组织检查和免疫组织化学染色病理特点。并以Duchenne肌营养不良4例，多发性肌炎和包涵体肌炎各2例作为对照。结果dysferlinopathy患者均以进行性加重的肌无力、萎缩为主要症状，符合进行性肌营养不良的临床表现。组织化学染色示dysferlinopathy患者出现不同程度的肌纤维变性、坏死、再生，结缔组织增生；多数病例可见炎性细胞浸润；抗dysferlin单克隆抗体免疫组织化学染色显示8例dysferlinopathy患者均出现dysferlin蛋自在肌纤维膜上和胞质内的缺失。结论（1）dysferlinopathy符合进行性肌营养不良的临床、病理表现；（2）抗dysferlin单克隆抗体免疫组织化学染色病理分析是诊断dysferlinopathy的可靠方法，值得临床推广应用。     

线粒体肌病与线粒体脑肌病的临床分析

目的探讨神经肌肉系统线粒体病的发病机制、临床与病理特征及诊断。方法对7例确诊为线粒体病患者的临床表现、病理检查、实验室与影像学资料进行了回顾性分析。结果该组患者诊断为线粒体肌病3例,线粒体脑肌病4例;其中2例患者血乳酸水平升高;7例患者肌电图均有异常发现,肌肉活检均有特征性的改变;4例线粒体脑肌病患者头部影像学均有异常改变。结论线粒体病主要累及肌肉及中枢神经系统,诊断要求多种手段结合,以临床和病理表现为主,近年来基因方面的研究及影像学诊断发展迅速,目前对本病主要采取对症治疗。     

Creutzfeldt—Jakob病的临床及病理分析

目的 探讨Creutzfeldt-Jakob病（CJD）的临床特点及诊断，提高生前确诊率。方法 对4例经病理证实的CJD患者的临床表现、光镜及电镜所见进行分析。结果 4例均具有典型的临床表现，病理可见神经细胞变性死亡，胶质细胞增生，无炎性改变，电镜除可见上述改变外，还可见部分髓鞘及轴索的肿胀、变性。结论 此病多为散发性，无特殊有效治疗，预后差。临床病理检查是确诊CJD的最佳检查方法。     

70例颞叶癫痫的病理与临床研究

对７０例颞叶癫痫切除病灶作了病理学观察。其中肿瘤６例，血管畸形１３例．疤痕７例，外伤等脑损伤５例。蛛网膜囊肿及囊虫病各１例。以上同时伴有海马硬化者２３例；仅有海马硬化者３７例，其中７例有局部脑组织结构不良，４例有神经细胞增生灶，２例白质内灰质异位。表现为神经细胞变性脱失和胶质增生的海马硬化，主要波及齿状回、Ａｍｍｏｒｉｓ角和下托。还讨论病理诊断和鉴别诊断、病因病灶和致癫灶的确立。原发病变与继发病变的区分。     

南京地区多发性硬化的临床与病理

对４例多发性硬化的临床和病理进行了研究。男、女各２例；年龄分别为２０岁、２６岁、２８岁及６２岁。病程分别为３２天、４５天、８年及２０年。临床表现多发病灶，主要症状和体征是视力障碍、肢体瘫痪及截瘫等，缓解复发１～４次不等。研究发现其病理改变为中枢神经系统白质多发性脱髓鞘病灶，视神经、视交叉及脊髓损害严重，脊髓又以后索及侧索损害为多见，有对称倾向。在较新鲜的病灶中发现明显的星形胶质增生，而在陈旧性病灶扩展的边缘部可见到血管周围淋巴细胞浸润。对此病的诊断标准、命名及临床病理特征等进行了讨论     

Neuropathologic features of amnestic mild cognitive impairment

BACKGROUND: The neuropathologic substrate of amnestic mild cognitive impairment (aMCI) is not known. OBJECTIVE: To determine the neuropathologic features of patients who died while their clinical classification was aMCI. DESIGN: Cohort study. SETTING: Community based. PARTICIPANTS: Sixty-six individuals, including 15 who had memory impairment beyond that allowed for aging but who were not demented, were studied along with 28 clinically healthy individuals and 23 patients with probable Alzheimer disease (AD) for comparison. MAIN OUTCOME MEASURES: Standard neuropathologic techniques and classification according to Khachaturian, Consortium to Establish a Registry for Alzheimer Disease, and National Institute on Aging-Reagan criteria were used to analyze autopsy tissue from 15 individuals who died while their clinical diagnosis was aMCI. For comparison, autopsy data on age-matched groups of clinically healthy individuals and patients with probable AD were analyzed. RESULTS: Most patients with aMCI did not meet the neuropathologic criteria for AD, but their pathologic findings suggest a transitional state of evolving AD. All the patients with aMCI had pathologic findings involving medial temporal lobe structures, likely accounting for their memory impairment. In addition, there were many concomitant pathologic abnormalities, including argyrophilic grain disease, hippocampal sclerosis, and vascular lesions. CONCLUSIONS: The neuropathologic features of aMCI matched the clinical features and seemed to be intermediate between the neurofibrillary changes of aging and the pathologic features of very early AD.     

Cerebrovascular and Degenerative Changes in the Brain; A Study of 233 Japanese 50 or More Years of Age

Abstract: A neuropathologic study, chiefly cerebrovascular lesions and degenerative changes, was conducted on the brains of 233 subjects 50 years of age and over among 557 autopsy cases of RERF-ABCC Hiroshima in 1972–1974. There were some discrepancies between the principal clinical diagnosis and principal pathologic diagnosis in cerebrovascular disease. For cerebral hemorrhage, 8.6% were accounted for in the clinical diagnosis of the entire subjects while only 2.1% were accounted for in the pathologic diagnosis of the same subjects. The degenerative changes in the central nervous system have been increasing with age and these changes were seen more in the females than in the males. Intracerebral arteriosclerosis of a moderate extension or more existed in 36.5% of the subjects and the frequency of this disease increased with age. The frequency of cerebral infarct increased with age. The location of the infarcts was most often seen in the basal ganglia and cortex of cerebrum, the size of the cortical infarct was within 0.5 cm in diameter and multiple. The vascular lesions or degenerative changes were seen in about 74% of the brains of 50 years and over.     

Topographic distribution and severity of brain lesions in Wernicke's encephalopathy

The distribution and severity of the brain lesions were studied in 45 cases (age range: 26-84 years) of Wernicke's encephalopathy. The process was acute or subacute (active) in 24 cases and chronic (inactive) in 21. Cases with acute and subacute disease had more extensive and severe lesions than the chronic ones. The majority of the acute cases had lesions involving the mammillary bodies and thalamus and the subependymal structures along the third and fourth ventricles and the aqueduct. Only three acute cases had lesions restricted to the mammillary bodies. Among the chronic cases, the majority of the lesions were restricted to the mammillary bodies and the thalamus. Only two lesions extended as far down as the inferior collicles. Eleven out of 21 chronic cases has isolated lesions of the mammillary bodies. The affection of the mammillary bodies in chronic cases varied from barely visible to subtotal destruction of the tissue. Similarly, the lesions in the thalamus varied from slight gliosis in the dorsomedial nucleus to extensive nerve cell loss in several nuclei. There were similar variations in the severity of the clinical picture. Memory loss was recorded in three cases with isolated lesions of the mammillary bodies.     

Phenotypic Variability Within the Inclusion Body Spectrum of Basophilic Inclusion Body Disease and Neuronal Intermediate Filament Inclusion Disease in Frontotemporal Lobar Degenerations With FUS-Positive Inclusions

ABSTRACT: Basophilic inclusion body disease and neuronal intermediate filament inclusion disease (NIFID) are rare diseases included among frontotemporal lobar degenerations with FUS-positive inclusions (FTLD-FUS). We report clinical and pathologic features of 2 new patients and reevaluate neuropathologic characteristics of 2 previouslydescribed cases, including an early-onset case of basophilic inclusion body disease (aged 38 years) with a 5-year disease course and abundant FUS-positive inclusion bodies and 3 NIFID cases. One NIFID case (aged 37 years) presented with early-onset psychiatric disturbances and rapidly progressive cognitive decline. Two NIFID cases had later onset (aged 64 years and 70 years) and complex neurologic deficits. Postmortem neuropathologic studies in late-onset NIFID cases disclosed α-internexin-positive "hyaline conglomerate"-type inclusions that were positive with 1 commercial anti-FUS antibody directed to residues 200 and 250, but these were negative to amino acids 90 and220 of human FUS. Early-onset NIFID had similar inclusions that werepositive with both commercial anti-FUS antibodies. Genetic testing performed on all cases revealed no FUS gene mutations. These findings indicate that phenotypic variability in NIFID, including clinical manifestations and particular neuropathologic findings, may be related to the age at onset and individual differences in the evolution of lesions.     

Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia

BACKGROUND: The pathologic outcome of patients diagnosed with mild cognitive impairment (MCI) following progression to dementia is poorly understood. OBJECTIVE: To determine the pathologic substrates of dementia in cases with prior diagnosis of amnestic MCI. DESIGN AND SETTING: Community-based cohort. PATIENTS: Thirty-four subjects followed up prospectively as part of a community-based study who were diagnosed with amnestic MCI, progressed to clinical dementia, and underwent subsequent postmortem brain analysis. MAIN OUTCOME MEASURES: Neuropathologic analyses resulted in assignment of a primary pathologic diagnosis and included staging of Alzheimer pathologic abnormalities and identification of contributing vascular disease, Lewy bodies, and argyrophilic grains. RESULTS: Although the majority of subjects progressed both clinically and pathologically to Alzheimer disease (AD), 10 (29%) of them developed non-AD primary pathologic abnormalities. All of the cases were found to have sufficient pathologic abnormalities in mesial temporal lobe structures to account for their amnestic symptoms regardless of the cause. Most subjects were found to have secondary contributing pathologic abnormalities in addition to primary pathologic diagnoses. No significant differences between subjects with and without neuropathologically proven AD were detected in demographic variables, apolipoprotein E genotype, or cognitive test measures at onset of MCI, onset of dementia, or last clinical evaluation. CONCLUSIONS: The neuropathologic outcome of amnestic MCI following progression to dementia is heterogeneous, and it includes AD at a high frequency. Complex neuropathologic findings including 2 or more distinct pathologic entities contributing to dementia may be common in community-based cohorts. Neither demographic variables nor cognitive measures had predictive value in determining which patients diagnosed with MCI will develop the neuropathologic features of AD.     

Clinicopathologic observations in essential tremor: report of six cases

Essential tremor (ET) is the most common pathologic tremor, but only eight cases have been studied pathologically. We report detailed clinical and neuropathologic studies of six additional patients. We did not find any neuropathologic lesions that might be specific for ET. Moreover, there were no abnormalities of the substantia nigra consistent with Parkinson's disease. The neuropathologic substrate of ET remains unknown.     

Case Report: neuropathology of methyl bromide intoxication

The neuropathological findings in a man and his dog both of whom died after acute exposure to methyl bromide are presented. The dog had cerebral oedema, most marked in the depths of cortical sulci. The man survived 30 days after the initial illness and his brain contained well-defined symmetrical lesions in the mammillary bodies and inferior colliculi. He also had a peripheral neuropathy and lymphocytic thyroiditis. The pathology in the central nervous system has features resembling Wernicke's encephalopathology; the mechanism by which methyl bromide may produce such lesions is discussed.     

Impairment of the peripheral nervous system in Creutzfeldt-Jakob disease

BACKGROUND: The clinical manifestations of Creutzfeldt-Jakob disease (CJD) primarily reflect involvement of the central nervous system. The coexistence of CJD with peripheral nervous system involvement has also been reported. OBJECTIVE: To analyze peripheral neuron electrophysiologic changes and to compare these data with neuropathologic features of spinal motor neurons in patients with definite CJD. DESIGN AND PATIENTS: Electrophysiologic examinations were performed on 16 patients with sporadic CJD. The diagnosis was confirmed by neuropathologic examinations (15 patients) or by intravital detection of the 14-3-3 protein in the cerebrospinal fluid (1 patient). The spinal cord was neuropathologically examined in 8 patients. SETTING: Department of Clinical Neurophysiology, I Neurological Department, Institute of Psychiatry and Neurology, Warsaw, Poland. MAIN OUTCOME MEASURES: Electromyography, compound muscle and sensory nerve action potentials, distal latencies, F waves, peripheral motor and sensory conduction velocity, and spinal motor neuron numbers and morphologic characteristics. RESULTS: All patients had signs of central nervous system damage typical of sporadic CJD. Only 3 patients had clinical signs of peripheral nervous system involvement. Electrophysiologic examinations confirmed peripheral nervous system damage in these patients and revealed preclinical peripheral nervous system impairment in 11 more patients. In 1 patient, electrophysiologic examination revealed features of motor neuron disease; in 9, axonal disease; and in 4, axonal-demyelinating neuropathy. Neuropathologic examination results confirmed severe loss of spinal motor neurons in 1 patient with motor neuron disease and revealed the features of motor neuron chronic disease in 4. In 2 of them, electrophysiologic data were normal. CONCLUSION: In sporadic cases of CJD, peripheral nervous system impairment should be considered to be an integral component of disease.     

Pathologic findings in nerve and muscle biopsies from 47 women with silicone breast implants.

OBJECTIVE: To describe the pathologic findings in 47 consecutively received nerve and muscle biopsies from patients with silicone breast implants (SBI). BACKGROUND: The controversial proposal that systemic illness may result from SBI includes diseases of the central and peripheral nervous system. METHODS: All of the biopsies were processed in full according to current standard methodologies in nerve and muscle pathology. Myelinated fiber histograms were prepared in 40 of the 47 cases. RESULTS: Eight of the 47 nerves showed pathologic changes likely to be symptomatic: 7 with an axonal neuropathy, including 1 with a granulomatous neuritis and myositis and 1 with diabetic neuropathy, and the eighth with a hypertrophic onion bulb neuropathy. Eleven showed minor morphologic or morphometric alterations of uncertain clinical significance. The remaining 28 nerve biopsies were normal, including 1 in which the accompanying muscle showed an inflammatory myopathy typical of polymyositis. CONCLUSIONS: These findings represent the largest set of reported pathologic data derived from women with SBI. Within this highly selected cohort of women with SBI, the majority of the biopsies were normal, and in 9 of 47 diverse abnormalities were detected including axonal and demyelinating neuropathies and inflammatory myopathies. These findings do not support a consistent association between SBI and any neuropathologic entity.     

Alzheimer's disease or plaque disease? Two cases at the frontier of a definition.

Atypical dementias confront the adequacy of current diagnostic concepts. The two patients with atypical dementia syndromes described here shared common postmortem features of numerous neocortical neuritic (senile) plaques and microvascular amyloid, sparing of hippocampus and substantia nigra, and the virtual absence of neurofibrillary tangles. Microscopically, the two differed only by the presence of a few subcortical Lewy bodies in case 1. These similar morphologic features were associated with dramatically different clinical presentations. In the first patient, visual hallucinations, Capgras' syndrome, cognitive slowing, myoclonus, parkinsonism, and primitive reflexes evolved over 3 years. Memory and language were relatively spared. In the second, dysphagia, nonfluent aphasia, hypophonia, motor perseveration, and a severe disorder of attention developed during this 18-month illness. At autopsy, an unrecognized colon malignancy was found. Despite high neuritic plaque counts in cortex, neither the clinical nor the pathologic criteria for Alzheimer's disease adequately describe either case. The cases will be examined first as clinical, then as neuropathologic, entities. From this approach, we conclude that a specific clinical dementia syndrome may be expressed by several neuropathologic "diseases" and that a variety of clinical syndromes may represent a single neuropathologic diagnosis. This strategy identifies a conceptual dichotomy between Alzheimer's syndrome and postmortem Alzheimer's disease. Meticulous clinical and neuropathologic observation is essential in advancing an understanding of the relationship between the two.