嗜人T淋巴细胞病毒I型（HTLV—I）相关HAM／TSP病

本文报道了应用田间免疫荧光法，从汕头地区９７例神经系统疾病患者血清中，检出嗜人Ｔ淋巴细胞病毒Ｉ型（ＨＴＬＶ－Ｉ）抗体阳性的ＨＴＬＶ－Ｉ相关ＨＡＭ／ＴＳＰ病患者５例，阳性率为５．１５％。并对ＨＴＬＶ－Ｉ相关ＨＡＭ／ＴＳＰ病的临床特点，伴发疾病，病理及发病机制，治疗等进行了讨论，认为国内进一步开展对ＨＴＬＶ－Ｉ相关ＨＡＭ／ＴＳＰ病的检测和研究是非常必要的。     

HTLV-Ⅰ相关性HAM/TSP患者血浆及脑脊液sFas、sFasL的测定及意义

目的探讨人嗜T淋巴细胞病毒Ⅰ型相关性脊髓病/热带痉挛性瘫痪(humanT-lymphotropicvirustypeⅠassociatedmyelopathy/tropicalspasticparaparesis,HAM/TSP)患者血浆及中可溶性Fas(sFas)和Fas配体(sFasL)表达水平及其与HAM/TSP病发病机制的关系。方法应用ELISA方法检测HAM/TSP患者血浆及脑脊液(CSF)中sFas和sFasL水平。结果HAM/TSP患者血浆sFas表达水平[(1.08±0.26)ng/mL]与其他神经系统疾病(otherinflammatoryneurologicdiseases,OIND)[(0.29±0.05)ng/mL]及正常对照组[(0.18±0.07)ng/mL]相比显著增高(P<0.05),血浆sFasL表达水平[(0.26±0.11)ng/mL]与OIND组[(0.22±0.04)ng/mL]及正常对照组[(0.21±0.05)ng/mL]比较差异无显著性(P>0.05);CSFsFas与sFasL表达水平[(0.19±0.07)ng/mL与(0.24±0.08)ng/mL]均高于OIND组[(0.11±0.06)ng/mL与(0.01±0.01)ng/mL](P<0.05)。结论sFas、sFasL蛋白可能在HAM/TSP发病机制中起重要作用。     

人类T细胞白血病病毒I型相关脊髓病四例报告

报道在日本经治的４个例人类Ｔ细胞白血病病毒Ｉ型（ＨＴＬＶ－Ｉ）相关脊髓病（ＨＡＭ），介绍了ＨＡＭ极流行学病学资料，认为在世界范围的ＨＴＬＶ－１多发区寻找ＨＡＭ是必要的，国内是否存在ＨＡＭ实应考虑。建议在国内在ＨＴＬＶ－１流行区注意切断各种传染作，这对预防我国ＨＡＭ发生及防止人类Ｔ细胞白血病扩散是非有价值的。     

重症肌无力与人类嗜T淋巴细胞I型病毒抗原的关系

采用免疫荧光法检测２５例重症肌无力患者外周血细胞中人类嗜Ｔ淋巴细胞Ｉ型病毒（ＨＴＬＶ－１）抗原。结果显示，２０％（５／２５）的重症肌无力患者血细胞中ＨＴＬＶＩ抗原阳性，而对照组７１例全部为阴性。两组比较差异有极显著性意义。提示重症肌无力的发病可能与ＨＴＬＶ－１的感染有关。     

人T淋巴细胞白血病Ⅰ型病毒致HAM／TSP一例报告

人Ｔ淋巴细胞白血病Ⅰ型病毒致ＨＡＭ／ＴＳＰ一例报告郑璇庄伟端陈显光杜登青我们于１９９５年５月检测１例人Ｔ淋巴细胞白血病Ⅰ型病毒（ＨＴＬＶ－１）抗体阳性及聚合酶链反应（ＰＣＲ）阳性的神经系统疾病患者，现报道如下。患者男，３４岁。因进行性双下肢乏力，行走...     

人T淋巴细胞白血病Ⅰ型病毒相关脊髓病一例报告

人Ｔ淋巴细胞白血病Ⅰ型病毒相关脊髓病一例报告许楚芸郭幼宝患者女性，３０岁，广东人，已婚。因尿潴留半个月于１９９４年１０月３日入院。患者３个月前左眼视物欠清，２０天前头晕，腰骶部酸痛伴右下肢乏力，数天后不能自行排尿，当地给导尿和抗生素治疗症状未减而转来...     

人类T细胞白血病病毒Ⅰ型相关脊髓病四例报告

报道在日本经治的４例人类Ｔ细胞白血病病毒１型（ＨＴＬＶ－Ⅰ）相关脊髓病（ＨＡＭ），介绍了ＨＡＭ临床及流行病学资料，认为在世界范围的ＨＴＬＶ－１多发区寻找ＨＡＭ是必要的，国内是否存在ＨＡＭ实应考虑。建议在国内ＨＴＬＶ－１流行区注意切断各种传染途径，这对预防我国ＨＡＭ发生及防止人类Ｔ细胞白血病扩散是非常有价值的。     

重症肌无力与人类嗜T淋巴细胞：I型病毒抗原的关系

采用免疫荧光法检测２５例重症肌无力患者外周血细胞中人类嗜Ｔ淋巴细胞Ｉ型病毒（ＨＴＬＶ－１）抗原。结果显示，２０％（５／２５）的重症肌无力患者血细胞中ＨＴＬＶ－１抗原阳性，而对照组７１例全部为阴性。两组比较差异有极显著性意义。提示重症肌无力的发病可能与ＨＴＬＶ－１的感染有关。     

癌性脊髓病（附5例报告）

癌性脊髓病属癌性非转移性神经疾病。1964年Mamcall首先报告本病,多发于肺癌,其次是胃癌、前列腺癌、甲状腺癌和乳腺癌等。几年来,我们先后收治5例,均在原发癌肿发现以前出现脊髓横贯性损害,脊髓经造影或CT等检查无癌转移表现,符合本病的特征,现报告如下。病例报告例1 女,54岁。因突然腰以下感觉丧失,双下肢瘫痪伴人小便障碍3天于1985年4月入院,即往健康。检查:T37度,BP(?)6/12kpa,肥胖,神志、语言清。心、肺、腹部正常。     

HTLV-1相关性脊髓病/热带痉挛性瘫痪病的研究进展

人嗜T淋巴细胞病毒1型(HTLV-1)是第1个被发现的人类逆转录病毒，是HTLV-1相关性脊髓病(HAM)或热带痉挛性瘫痪病(TSP)的病原体。迄今为止，HAM／TSP的发病机制尚未清楚，也缺乏有效的治疗方法。现就近年来对HAM／TSP病所进行的流行病学、传播途径、发病机制、实验室检查、临床表现及治疗等方面的研究作一概述。希望对HTLV—1病毒的认识及HAM／TSP的防治起一定的作用。     

Clinical and demographic features of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Rio de Janeiro, Brazil

In Rio de Janeiro (RJ) most cases of paraparesis of obscure origin are associated with the human T-cell lymphotropic virus type I (HTLV-I). Thirty-four consecutive patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) from RJ were evaluated. Most patients came from low socio-economic levels. There was no difference in terms of gender. The main affected racial group was white. A history of sexually transmitted diseases was a major risk factor for HAM/TSP and a positive serology for syphilis was found in 26.5% of the patients. The major clinical findings were of a spastic paraparesis with generalized brisk tendon jerks and bilateral Babinki's sign. Sensation was abnormal in 25 patients (73.5%) and five (14.7%) had a sensory level. Three patients (8.8%) had optic atrophy. The cerebrospinal fluid showed a lymphocytic pleocytosis with a mean total protein content of 0.4 g/litre, and an increased intrathecal IgG synthesis in 59.4% of patients. HAM/TSP and multiple sclerosis (MS) occur indigenously in RJ and some HAM/TSP cases can be sometimes confused with MS. Therefore we propose that, in places where MS coexist with HAM/TSP, HTLV-I antibodies should be sought routinely in those MS suspected cases with prominent spastic paraparesis.     

Neuroaxonal dystrophy in HTLV-1-associated myelopathy/tropical spastic paraparesis: neuropathologic and neuroimmunologic correlations

Summary Detailed neuropathologic and immunohistologic analysis of a case of serologically and polymerase chain reaction-confirmed human immunodeficiency virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is reported in a 73-year-old North American black woman. In addition to the usual neuropathologic features of HAM/TSP, including tractal degeneration of the spinal cord, leptomeningeal and perivascular fibrosis, perivascular demyelination and chronic inflammation, neuroaxonal spheroids were prominent in the spinal cord. Neuroaxonal dystrophy was characterized by neurofilamentous masses that were immunoreactive for phosphorylated neurofilament epitopes, but not ubiquitin. Neuroimmunologic analysis of the inflammatory reaction revealed a prevalence of CD8⁺ T cells and class I major histocompatibility molecules (MHC) (HLA-ABC and 2-microglobulin), but very few CD4⁺ T cells. Microglia were highly reactive for class II MHC (HLA-DR) and this was attributed to activation, rather than CD4 interaction, since CD4 presence was minimal. Inflammatory cytokine immunoreactivity was also detected in glia. It is concluded that the cumulative effects of cytotoxic T cell (CD8) infiltration and the possible involvement of cytokines were responsible for the unusual degree of neuroaxonal dystrophy and vascular fibrosis, as well as the observed demyelination in this case.Supported in part by grants NS 07098, NS 08952, NS 11920 and MH 47667 from the NIH; and RG 1001-G-7 from the National Multiple Sclerosis Society.     

Human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis: Clinical presentation and pathophysiology

Human T-cell lymphotropic virus type 1(HTLV-1)-associated myelopathy/tropical spastic paraparesis(HAM/TSP) is a slowly progressive neurodegenerative disorder in which lesions of the central nervous system cause progressive weakness, stiffness, and a lower limb spastic paraparesis. In some cases, polymyositis, inclusion bodymyositis, or amyotrophic lateral sclerosis-like syndromes are associated with HTLV-1. TSP was first described in Jamaica in 1888 and known as Jamaican peripheral neuritis before TSP was related to HTLV-1 virus, the first retrovirus being identified, and the disease is since named HAM/TSP. There is no established treatment program for HAM/TSP. Prevention is difficult in lowincome patients(i.e., HTLV-1 infected breast feeding mothers in rural areas, sex workers). Thus, there is a need for new therapeutic avenues. Therapeutic approaches must be based on a better understanding, not only of clinical and clinicopathological data, but also of the pathophysiology of the affection. Consequently, a better understanding of existing or newly developed animal models of HAM/TSP is a prerequisite step in the development of new treatments.     

Viral specific IgG and IgM antibodies in the CSF of patients with tropical spastic paraparesis

Summary The cerebrospinal fluid (CSF) from seven West Indian migrants to the United Kingdom with tropical spastic paraparesis were studied by antigen immunoblotting for specific anti-HTLV1 oligoclonal IgG and IgM. Eight CSFs from five patients were positive for specific IgG and negative for IgM; three CSFs from two patients were positive for IgM and negative for IgG. No patient had both IgG- and IgM-positive CSF. Those patients with IgM only had disease of the shortest duration. When looking for evidence that neurological damage is caused by HTLV1, both IgM and IgG should be examined.     

Chronic paraparesis associated with human T-lymphotropic virus type I beginning after dental extraction

We report a patient with a chronic paraparesis associated with human T-lymphotropic virus I infection (HTLV-I antibodies were present in blood and CSF), which began after a dental extraction. We suggest the possible relation of the dental procedure with the triggering of the disease.     

Histopathological analysis of four autopsy cases of HTLV-I-associated myelopathy/tropical spastic paraparesis: inflammatory changes occur simultaneously in the entire central nervous system

Although brain lesions have been described in some cases with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), little is known about the nature of brain lesion and its relation to the spinal cord lesion. In the present study, we performed histopathological analysis of the brain and the spinal cord of four autopsied cases with HAM/TSP to clarify the relationship between the brain and the spinal cord lesions. In two cases with active-chronic inflammation in the spinal cord, perivascular inflammatory infiltration was also seen in the brain, and the composition of cell subsets was similar both in the spinal cord and in the brain. No active inflammatory change was seen in the brain in two cases with inactive-chronic spinal cord lesions. Inflamed vessels were distributed mainly in the deep white matter and in the area between cerebral cortex and white matter of the brain. In the spinal cord inflamed vessels were mainly seen in the bilateral lateral and the ventral posterior columns. Parenchymal infiltration was diffused in the spinal cord but very sparse in the brain, suggesting the importance of parenchymal infiltration in the destruction of tissues. These results suggest that inflammatory changes occurred simultaneously in the spinal cord and in the brain, and that distribution of inflamed vessels closely correlated with the characteristics of vascular architecture of the brain and the spinal cord, which lead to a slow blood flow. This study may help promote a better understanding of the pathogenesis of HAM/TSP. Received: 9 July 1999 / Revised, accepted: 9 November 1999     

Does testing of brainstem auditory response aid diagnosis in progressive spastic paraparesis?

40 patients with progressive spastic paraparesis of uncertain cause were studied in order to assess the outcome of their investigations. Abnormalities of the visual evoked response (VER) were found in 33%, indicating a second lesion in the nervous system. An additional 15% had abnormalities of the brainstem auditory evoked potentials (BAEP), indicating an supra-spinal, though not necessarily a second lesion. Qualitative CSF examinations for oligoclonal IgG banding showed abnormality in 30%, and considerable overlap (83%) with the patients who had abnormal VER, but not in those with an abnormal BAEP alone. It is concluded that the BAEP is of value when the VER and CSF are normal.     

A novel presenilin 1 mutation (V261L) associated with presenile Alzheimer's disease and spastic paraparesis

Background and purpose:  We report a novel mutation in exon 8 of the presenilin 1 (PSEN1) gene (V261L) associated with early-onset autosomal dominant Alzheimer's disease and spastic paraparesis.
Methods and results:  The proband was a woman who developed insidious cognitive decline with predominant memory loss and gait disorder secondary to spasticity at the age of 40. Her brother and her mother had a similar disease in the fifth decade of life. The feature of amnestic presentation with spastic paraparesis is consistent with the majority of mutations in the exon 8 of the PSEN1 1 gene.
Conclusions:  Screening for PSEN1 mutations is especially likely to be productive when directed toward persons with positive family history and with age at onset of under 60.     

Hereditary spastic paraparesis with dementia, amyotrophy and peripheral neuropathy. A neuropathological study

Hereditary, probably autosomal recessive, spastic paraparesis in two siblings was associated with dementia of frontal lobe type, amyotrophy and peripheral sensory and motor polyneuropathy. Neuropathological findings correlate with neurological deficits, although neuron loss in the caudate and putamen, substantia nigra, and loss of Purkinje cells were clinically silent. Loss of neurons occurred in all cortical layers of the prefrontal lobe and superior temporal gyrus. Immunohistochemical studies showed reduced parvalbumin immunoreactivity in dendrites, and reduced numbers of calbindin D28k-immunoreactive cells, thus suggesting involvement of cortical local-circuit neurons. Myelin loss, ubiquitin-immunoreactive granular deposits, and nerve fibre degeneration in the white matter of the frontal lobes and corpus callosum were also observed. Cerebral and sub-cortical white matter abnormalities, together with atrophy of the thalamic dorsomedial complex and anterior nucleus, may have accounted for the development of severe dementia in this patient.