Klinik und Pathologie einer übertragbaren granulomatösen Meningoencephalomyelitis (gMEM) bei der Hausziege

Summary During the past five years a disease involving mainly the CNS was observed among adult and older animals in a flock of goats. Debilitating factors appear to favour the onset of the clinical manifestation. These are usually ushered in by a short febrile episode. The course, as a rule, is chronic with frequent recurrences. Clinical signs include ataxia, coarse tremor, nystagmus, torticollis, trismus, excess salivation, weakness of the hindquarters or complete paralysis. The serum globulins are abnormally elevated, particularly the gamma fraction. High levels of total protein, glucose and transaminases are common in the CSF. Neuropathologically, two types of changes are found, often blending together in a smooth fashion, namely, a chiefly granulomatous lesion in periventricular, paraventricular regions and meningeal spaces respectively and a predominantly demyelinating process reaching out from the paraventricular areas into the adjacent nervous parenchyma. A neurologic illness of the domestic goat—clinically and pathologically very similar to the spontaneous gMEM—was repeatedly obtained by injection of a cell-free filtrate into the cisterna magna prepared from a saline suspension of organ-material of a gMEM-animal. Final etiologic elucidation of this affection in goats, however, is yet to be accomplished.

     

The intercellular gaps of the neuropil as possible pathways for virus spread in viral encephalomyelitides

Summary An encephalomyelitis was produced in adult albino mice by intracerebral infection with the Zimmern virus, which is a group B arbovirus belonging to the TBE complex. Ultrastructural studies of this process showed some interesting results. Zimmern virus particles, which measure about 400 to 450 Å in diameter, could be observed, not only inside numerous neurons, but also repeatedly within the intercellular gaps of the neuropil. This finding makes it very likely that the extracellular spaces of the CNS are considerably wider in the intravital state than they appear to be after employing the conventional electron microscopic preparatory techniques. One may also conclude, therefore, that the intercellular clefts can serve as pathways for the spread of at least smaller virions (e. g., picorna viruses and group B arboviruses) throughout the parenchyma of the brain and spinal cord.

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Zusammenfassung Bei erwachsenen weißen Mäusen wurde durch intracerebrale Infektion mit dem Zimmern-Virus, ein dem TBE-Komplex angehörendes Arbovirus der Gruppe B, eine Encephalomyelitis erzeugt. Bei ultrastrukturellen Untersuchungen dieses Prozesses konnten einige interessante Beobachtungen gemacht werden. Zimmern-Viruspartikel, welche einen Durchmesser von etwa 400–450 Å haben, wurden nicht nur innerhalb zahlreicher Nervenzellen, sondern wiederholt auch in den Intercellularfugen des Neuropils angetroffen. Aufgrund dieses Befundes ist es sehr wahrscheinlich, daß die extracellulären Räume im ZNS intra vitam wesentlich weiter sind als man sie nach Anwendung der üblichen elektronenmikroskopischen Präparationsverfahren zu Gesicht bekommt. Es liegt somit auch die Annahme nahe, daß die Intercellularspalten als Wege für die Ausbreitung zumindest von kleineren Viren (z. B. Picornaviren und Arboviren der Gruppe B) im eigentlichen Hirn- und Rückenmarksgewebe dienen können.

     

一起病毒性脑炎的血清学分析

目的从脑炎患者脑脊液标本中分离病毒、传代增殖制备抗原,用ELISA方法检测特异性IgG、IgM,研究其在人群中的流行状况。方法采集脑炎患者脑脊液进行病毒分离培养,将出现病变的细胞培养物传代扩增,收获后制备抗原,用交叉稀释ELISA方法以患者恢复期血清滴定抗原工作浓度,将调查对象之血清稀释后(根据交叉稀释法滴定至适当浓度)进行ELISA检测。结果脑炎患者恢复期血清IgM和IgG阳性率分别为67%和8%;发热患者分别为13%和29%;呼吸系统感染患者分别为10%和31%;健康查体人群的平均阳性率分别为9%和31%。非脑炎人群IgM和IgG阳性率与脑炎患者比较,差别具有显著性意义(P(0.01)。一般发热、呼吸系统感染患者IgM阳性率与健康人群比较,无明显差异(P(0.05)。结论脑炎患者脑脊液中分离到的病毒与脑炎发病关系密切。     

柯萨奇病毒B3感染的病毒性脑炎小鼠模型的建立

目的建立柯萨奇病毒B3（CVB3）感染的病毒性脑炎小鼠模型。方法BALB/c纯系小鼠分两组,实验组小鼠颅内直接注射滴度为4.5×10^8pfu的柯萨奇病毒B3悬液20μl,对照组颅内注射生理盐水20μl,应用逆转录酶聚合酶链反应（RT-PCR）法测定脑组织中CVB3RNA含量,HE染色观察脑组织病理学的改变。结果与对照组相比,模型组动物于注射后1d开始出现病毒性脑炎的表现;另外脑组织观察到CVB3的阳性条带,并出现大量的炎细胞浸润、充血水肿和片状坏死,皮质细胞排列紊乱,形态不规则,有空泡样改变,出现核固缩、碎裂、溶解等。结论颅内直接注射柯萨奇病毒B3悬液,可快速建立柯萨奇病毒B3感染的病毒性脑炎小鼠模型。     

Electron microscopic studies of rabbit central and peripheral nervous system in experimental Borna disease

Summary The CNS and posterior root ganglia of rabbits experimentally infected with Borna virus were studied by electron microscopy. Intracytoplasmic crystalline arrays were common in the non-neuronal cell elements of the central and peripheral nervous tissues of all infected animals. Peculiar filamentous collections were seen occasionally in the central and peripheral neurons of one third of the inoculated rabbits. Control animals showed no such changes. In the affected tissues the nuclear density was increased. There were numerous cells grouped around the vessels or scattered singly or in clusters in the parenchyma. Amongst them plasma cells could be recognized as well as mononuclear cells of hematogenous origin, microglia cells in various reactive stages and macrophages derived from either of the latter cell types.The nonspecific character of the crystalline aggregates is emphasized. The questionable viral nature of the filamentous bundles is considered briefly; other explanations as to their nature are also mentioned. Finally, attention is drawn to the heterogeneous composition of the glial nodules and to the ultrastructural variability of the various cell types found in the inflamed tissues.The preliminary results of this work were presented in part at the 16th combined Meeting of the Vereinigung Deutscher Neuropathologen und Neuroanatomen e.V. and the British Neuropathological Society, Heidelberg, September 9–11, 1971.     

Restricted expression of viral surface proteins in canine distemper encephalitis

Summary Sixteen dogs with naturally occurring acute and chronic canine distemper virus (CDV) encephalitis were examined immunohistochemically for the presence of the five major CDV-specific proteins in the central nervous system. Monoclonal antibodies (mAbs) directed against two, three, four and five epitopes of the nucleo-(N), phospho- (P), fusion (F), and hemagglutinin (H) protein, respectively, and a polyclonal monospecific antibody recognizing the matrix (M) protein were used. Both core proteins and their epitopes, three F protein epitopes and the M protein were demonstrated in all animals examined. A fourth F protein epitope was found only in 13 animals. The H-2 and H-3 epitope of the H protein were detected in 15, the H-1 and H-5 epitope in 14, and the H-4 epitope in 3 animals. All viral proteins were observed in the same types of brain cells including neurons and astrocytes. The N and P protein were demonstrated in nucleus, cytoplasm and cell processes, whereas M, H and F protein were observed in the cytoplasm only and rarely in cell processes. In addition, the M protein was detected occasionally in the nucleus of neurons and reactive astrocytes. Intralesional distribution of CDV-specific proteins varied between core and surface proteins. In acute and subacute lesions without associated inflammation, expression of the M, H and F protein was only slightly diminished compared to the N and P protein. However, plaques with severe inflammation were either devoid of viral antigen or exhibited N-and P protein-specific immunoreactivity exclusively at the periphery, whereas expression of surface proteins was severely reduced or absent. These results are suggestive of restricted synthesis of CDV envelope proteins in acute, and more prominent in chronic, distemper encephalitis.Supported by the Gemeinnützige Hertie-Stiftung (grant no. GHS 203/91)     

Pathogenesis of experimental rabies in mice: an immunohistochemical study

Summary The spread of rabies virus in the central nervous system of mice was examined after hindlimb footpad and intracerebral inoculation of the CVS strain of fixed rabies virus. All mice developed paralytic rabies. After intracerebral inoculation there was early simultaneous infection of neurons in the cerebral cortex and pyramidal neurons of the hippocampus, and later there was spread to the cerebellum. After high-dose intracerebral inoculation there was early infection ependymal cells lining the lateral ventricles and neurons adjacent to the central canal of the spinal cord, suggesting that rabies virus entry into the CNS occurs, at least in part, by a cerebrospinal fluid pathway. The sequence of involvement was different after hindlimb footpad inoculation. Infection became established in the cerebellum on day 5, in the cerebral cortex on day 6, and in the hippocampus on day 8. CA3 was initially affected, CA1 became infected 2 days later, and there was much less involvement of the dentate gyrus. Hippocampal infection occurred late relative to the rest of the brain after peripheral inoculation, but not after intracerebral inoculation. The hippocampus is not a good location for the detection of early brain infection after peripheral inoculation, although it may be involved when a natural rabies vector has the ability to transmit infection. These findings also raise questions about the mechanisms for the limbic dysfunction observed in clinical rabies.Supported by grant MA-10068 from the Medical Research Council of Canada     

病毒性脑炎患者Borna病病毒P24基因片段的检测

目的探讨Borna病病毒(BDV)感染与人类病毒性脑炎的关系。方法采用荧光定量套式逆转录酶聚合酶链反应(FQ nRT PCR)检测了59例临床诊断的原因未明的病毒性脑炎及112名健康人外周血单个核细胞(PBMC)中BDVP24基因片段。结果59例原因未明的病毒性脑炎患者中有3例PBMC中检出BDVP24基因片段,而112名健康对照均未检出。病毒性脑炎患者BDV阳性率(5.08%)高于健康对照,差异有统计学意义(P<0.05),且BDVP24基因片段检测阳性病例的脑脊液中其他常见致脑炎病毒(单纯疱疹病毒、带状疱疹病毒、腮腺炎病毒、柯萨奇病毒和巨细胞病毒)检查均为阴性。结论中国的部分病毒性脑炎患者中存在BDV感染,BDV感染与病毒性脑炎的发病可能有关。     

Ultrastructure of herpes simplex virus infection of the nervous system of mice

Summary The nervous system and small intestine of mice infected with herpes simplex virus were examined by electron microscopy from the viewpoint of virus-host interaction.The host cells examined included the neuron, astrocyte, oligodendrocyte, and Schwann cell. The susceptibility of the latter was not less than that of the neuron. The endothelial cell, perineural fibrocyte and smooth muscle cell were also host cells. Replication of herpes virus in the nervous system was proven to be identical to that occurringin vitro; initial reproduction of nucleocapsids in the nucleus and subsequent maturation at the nuclear membrane with envelope formation, followed by discharge into the cytoplasmic reticular cavities and finally release from the host cell. Inconsistency in the distribution of virus particles and viral antigen was chiefly concerned with the host cell nucleus and the glial cytoplasm.Herpes virions, though few, were identified in the axons of peripheral nerves, and in the periaxonal space of myelinated fibres in the brain and the nerve ganglia. Virions were present in tiny vesicles in the perikarya or as naked particles. In the distal parts of peripheral nerve, there was marked dissociation in the amount of virions between Schwann cells and the axon. The significance of the endoneural space and the axon in the neural speread of infection is discussed briefly.     

^18F-FDG PETCT在抗NMDA受体脑炎及病毒性脑炎诊断中的价值

抗N-甲基-D-天冬氨酸(NMDA)受体脑炎及病毒性脑炎的临床表现相似但治疗方法及预后不同,故早期鉴别至关重要。抗体检测及病原学检测存在延时、假阴性等不足,常规辅助检查缺乏特异性,鉴别价值有限。^18F脱氧葡萄糖(FDG)标记的正电子发射计算机断层显像(PETCT)检查对于抗NMDA受体脑炎早期代谢异常敏感性高,存在特征性的枕叶低代谢和额颞叶高代谢。病毒性脑炎行^18F-FDG PETCT检查研究病例数较少,不同病毒性脑炎的脑代谢表现不同,但均无特征性的枕叶代谢减退。本文现围绕NMDA受体脑炎及病毒性脑炎行^18F-FDG PETCT检查时的脑代谢特点综述如下。     

病毒性脑炎患者血液和脑脊液博尔纳病病毒p24的检测

目的探讨博尔纳病病毒（BDV）与病毒性脑炎（VE）的关系。方法采用巢式逆转录聚合酶链反应（RT-PCR）结合荧光定量（FQ）PCR检测了52例VE患者和32例外科手术患者外周血液（PBMC）和脑脊液有核细胞（CSFMC）中的BDV p24基因片段，对阳性产物进行了基因序列测定、同源性和氨基酸顺序分析。结果VE患者PBMC和CSFMC中BDV p24基因片段阳性率（分别为9．6％和11．5％）明显高于对照组（0，P〈0．05）；PBMC和CSFMC中BDV p24基因片段拷贝数的对数值呈显著正相关（r=0．653，P〈0．05）；CSFMC所含目的基因片段阳性产物测序后，与BDV标准病毒株V核苷酸序列比较同源性为96．5％，在3个位点出现突变（nt1649T→C，nt1670C→T，nt1673C→T），突变率为3．5％。从系统发生树图形可以看出，该目的基因片段与澳大利亚马脑组织分离的S88和德国绵羊血液分离的H544病毒株亲缘关系最近。结论宁夏及其周边地区部分VE患者中可能存在BDV感染。     

病毒性脑炎的诊断与治疗

病毒性脑炎是常见的中枢神经系统感染性疾病,由不同的病毒引起,在免疫能力正常的人群中单纯疱疹病毒（HSV-1）,水痘带状疱疹病毒（VZV）,EB病毒（EBV）,流行性腮腺炎病毒,麻疹病毒,肠道病毒感染引起的最为常见。病毒的种类、宿主的免疫状态和环境因素决定了受累的脑区以及疾病的预后。尽管目前特异的治疗仅限于几种病毒,但正确的诊断、对症支持治疗对预后极为重要。     

Experimental Chandipura virus infection in mice

Summary Chandipura virus was inoculated intraperitoneally into 9-day old mice. Rising viral titers were detected in blood, skeletal muscle and viscera, beginning 3 to 6 h post-inoculation. Significant quantities of virus were initially noted in the brain at 24 h, and titers in that region rose precipitously during the succeeding 72 h. Detectable clinical signs, including neurologic dysfunctions began 48 h post-inoculation. Death was common at 72 and 96 h. The most significant and consistently observed lesions were in the central nervous system and included necrosis of neurons and ependymal cells.Supported by U.S. Public Health Service Grants PHS-FR-05358-08 and PHS 2 PO 6 RR 00393.     

130例病毒性脑膜炎患者的脑电图临床分析

目的探讨病毒性脑膜炎在临床治疗前和治疗后患者的脑电图变化。方法脑电图对病毒性脑膜炎患者进行疗效的分析。结果130例患者的脑电图，都有不同程度的恢复和改变结论经有效的临床治疗后，患者在临床上症状的好转与脑电图的结果基本是相符的。     

病毒性脑炎患者肠道病毒RT-PCR检测的临床意义初探

目的探讨对病毒性脑炎患者的脑脊液(CSF)进行肠道病毒(EV)逆转录-聚合酶链式反应(RT-PCR)检测的临床诊断和治疗意义。方法用1对针对EV多数血清型的特异性通用引物组建的逆转录-聚合酶链式反应对43例临床诊断为病毒性脑炎患者的CSF进行临床检测,同时观察这些患者的临床症状、体征、脑脊液生化常规及病毒其他病原体检查,头颅影像学和脑电图检查,用t检验进行统计学分析。结果CSF肠道病毒逆转录-聚合酶链式反应(EVRT-PCR)阳性者18人,占41.9%,临床症状、病情轻重与阴性者无明显差异,CSF蛋白和细胞数较高,可同时合并血中其他病毒(单纯疱疹病毒、巨细胞病毒)抗体阳性。结论EV引起的病毒性脑炎发病率高,并可合并其他病毒感染,EVRT-PCR与血清学检查结果存在不一致性,EVRT-PCR检查结果可指导临床诊断和针对性用药。     

Chronic Localized Encephalitis (Rasmussen's Syndrome) Preceded by Ipsilateral Uveitis: A Case Report

Summary: Chronic localized encephalitis (Rasmussen's syndrome) developed in an 11-year-old girl 1 month after operation for residual cataract due to chronic uveitis that had appeared at age 9 years ipsilateral to the affected cerebral hemisphere. Although the pathogenesis of Rasmussen's syndrome remains unknown, our case provides additional evidence indicating that a viral ocular infection is a possible cause or part of the disorder.     

Glycogenosis of the central nervous system in the cat

Summary A case of glycogenosis in the cat involving the central nervous system is reported. The electron microscopic picture is highly suggestive of Pompe's disease.Glycogen storage disease in an animal has not been reported before. From the present study it appears to be possible to achieve a strain of cats with this disease, which would greatly facilitate further research.

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Zusammenfassung Ein Fall von Glykogenose bei der Katze wird beschrieben. Die Krankheit hat das Zentralnervensystem befallen und zeigt das gleiche ultrastrukturelle Aussehen wie die Pompesche Krankheit.Glycogenosis bei einem Tier ist bisher nicht beschrieben worden. Als Erleichterung zukünftiger Forschungen dürfte es nunmehr möglich sein, einen Katzenstamm mit dieser Krankheit zu züchten.

     

Chronic daily intrathecal injections of a large volume of fluid increase mast cells in the thalamus of mice

Mast cells are found in the central nervous system (CNS) as well as in the periphery. In the brain of mice, they are localized primarily in the thalamus and meninges. Although their numbers increase in response to stress, the mediator of their recruitment is not known. During studies in which drugs were delivered intrathecally in a volume sufficiently large to distribute to the brain, we discovered that repeated daily injections of this large volume increased the number of mast cells in the thalamus. The increase was not due to changes in electrolyte composition of the cerebrospinal fluid (CSF) as chronically administered artificial CSF produced similar effects. Repeated injections of even small volumes (2 mul) increased mast cells in the medial intralaminar (Med), ventral posterior (VP) and posterior (Po) nuclei. Increasing the volume injected daily to 20 mul increased mast cells in the lateral intralaminar (Lat), laterodorsal (LD), ventrolateral (VL) and lateral geniculate (LG) nuclei and further increased those in the lateral extension of the Po nucleus. Thus, small and large volumes augment distinct populations of mast cells. While stem cell factor (SCF) is abundant in the CNS and is chemotactic to mast cells in the periphery, thalamic mast cells in the rodent do not express c-kit, the SCF receptor, suggesting that this factor may not be responsible for the effect. Consistent with this, centrally injected SCF was incapable of increasing thalamic mast cell populations after either single or chronic (21 days) daily injections compared to the effect of saline alone. Although the mechanism is not known, repeated injections of a large volume of fluid dramatically increase mast cells in the CNS, a phenomenon that may be relevant to clinical conditions of increased CSF pressure or volume.     

小儿病毒性脑炎86例临床分析

目的 探讨小儿病毒性脑炎的诊断及治疗方法.方法 对86例小儿病毒性脑炎的临床表现、辅助检查及治疗方法和治疗效果做回顾性分析.结果 小儿病毒性脑炎大多于2～3周完全恢复.脑脊液检查、头颅MRI、脑电图（EEG）有助于病毒性脑炎的诊断.综合治疗基础上分别合用激素、干扰素、静脉注射用丙种球蛋白（IVIG）疗效好.结论 小儿病毒性脑炎病程呈自限性.确诊主要靠脑脊液检查.激素、干扰素、IVIG值得临床推广应用.