循环抗原、抗体和MRI在脑囊虫病程演变中的变化

囊虫病系绦虫的幼虫即囊尾蚴寄生于人体所致,全世界每年约有5万人因此而死亡。它可以寄生于人的皮下、肌肉、眼睛等,其中对健康危害最大的是寄生于中枢神经系统犤1犦。在本研究中,用单克隆抗体采用ELISA方法检测脑囊虫病人血清、脑脊液中循环抗原(CAg)和抗体(Ab)在MRI影像学的不同时期的变化,以进一步明确脑囊虫病人的病程演变情况。资料与方法1.一般资料:45例患者,男29例,女16例,年龄4.6～75岁,平均35.6岁。2.临床诊断:45例患者中,21例为神经外科收住并经手术病检证实,24例经神经内科确诊为脑囊虫并治疗有效。3.影像学检查:对脑囊虫病…     

脑囊尾蚴病神经影像学表现与循环抗原相关性研究

目的探讨脑囊虫病血清循环抗原（CAg）与神经影像学（CT、MRI）的关系。方法根据诊断脑囊虫病的四个标准,对确诊的36例脑囊虫病病人行CAg定量测定及神经影像学检查并分期。结果根据神经影像学检查,36例脑囊虫病人在活虫期、变性死亡早期、变性死亡后期及钙化期之间的CAg水平有显著性差异（P〈0.01）。相关性分析表明血清中CAg的含量与脑囊虫病的神经影像学表现具有正相关性,其相关系数为0.871。结论（1）脑囊虫病人循环抗原与神经影像学（CT、MRI）表现具有相关性;（2）血清循环抗原的检查可用于对脑囊虫病的早期诊断和指导临床治疗。     

同时检测脑囊虫病患者血清和脑脊液循环抗原的临床研究

我院自lop年4月以来应用抗猪囊虫CA单克隆抗体以EIJS双抗体夹心法同时检测脑囊虫病患者血清和脑清液。现报告如下：1资料和方法11临床资料脑囊虫病组：叨例，男力冽，女9例，年龄18－65岁，平均38．3t13．7岁。均系初诊患者，按1986年中华神经精神科杂志编委会制定的诊断标准。f’］全部病人均行头颅CT检查示典型多发囊虫影像。同时采取血清，脑脊液各班倒。非脑囊虫病组：血清，脑脊液各41例。1．2方法步骤①加检样将洗浴后的脑脊液或已经预处理的被检血清加入反应孔，0．IInl／孔，每板记阳，阴性孔和空白孔各回个，43℃叨分钟后置4℃…     

50例脑囊虫病的临床、MRI与囊虫抗原、抗体测定

目的：探索脑囊虫病早期诊断的可能性及治疗的前景。方法：对我院１９９４年９月￣１９９８年９月期间住院确诊为脑囊虫病的５０例进行回顾性分析,着重对其诊断,治疗,实验室及预后作一探讨。结果;脑囊虫病在ＭＲＩ上具有特征性改变,在脑囊虫病的诊断上价值远高于ＣＴ。     

脑囊虫病的临床与脑电图、CT改变的研究

脑囊虫病的临床表现复杂多变 ,目前国内外对其的分型种类较多 ,各有不同侧重。现将我院近几年收治的 6 5例脑囊虫病患者的临床、脑电图、CT等资料结合分型分析如下 :1　临床资料患者 6 5例 ,男 37例 ,女 2 5例 ,男女之比为 1∶ 0 .76 ,年龄 7～ 72岁 ,平均 43岁。临床分癫痫型 33例 ,高颅压型 18例 ,混合型 14例。全部患者均经脑电图、CT、免疫学检查 ,结合临床病史、腰穿确诊 ,符合 1986年制定的脑囊虫病诊断标准 [1 ]。6 5例患者中脑电图异常 49例 (75 % ) ,其中界限异常 8例 ,轻度异常 2 5例 ,中度异常 12例 ,重度异常 2例。癫痫型患者…     

脑囊虫病人的EEG、BEAM与CT的对比研究

目的:探讨EEG、BEAM和CT在诊断脑囊虫病中的应用价值。方法 对263例脑囊虫病人的检查结果进行对比分析。结果 该组病人的EEG、BEAM和CT异常率分别为63.9％、79.1％和84.0％。BEAM比EEG提高阳性检出率15.2％,提示BEAM优于目测EEG,它能分辨出目测中不易识别的的EEG微细变化,显示出不同导联及频段的能量分布,有定量分析价值。CT和BEAM的诊断符合率为86.4％,定侧或定位符合率为82.5％。结论 BEAM和CT从脑功能和形态结构上为脑囊虫病的诊断提供重要依据。     

脑囊虫病患者的智力、记忆力和情感的研究

本文对９３例脑囊虫病患者进行了情感测验，其中４３例进行了记忆测验，４０例进行了智力测验。分别与正常人对照组相比，脑囊虫病可造成患者的记忆、智力水平明显下降（Ｐ＜０．００１：Ｐ＜０．０５）；并给患者造成了明显的焦虑和抑郁情感（Ｐ＜０．００１），女性病人的情感更易受影响，男性病人中伴发癫痫或高颅压者的焦虑成绩均明显高于无相应指标者。     

脑囊虫病不同分期的影像学表现

目的 探讨囊虫病的分型、分期的影像学表现特征.方法 回顾性分析94例脑囊虫病患者的CT及MRI的特点.结果 94例中脑实质型74例,脑室型8例,混合型11例,软脑膜炎型1例;处于活动期25例,退变死亡期29例,钙化期4例,混合期36例.各期CT与MRI表现均不同.结论 不同脑囊虫病的病理学过程和影像学表现不同,它的分型、分期对指导临床治疗有着重要意义.     

脑囊尾蚴病患者脑脊液特异性IgG、一氧化氮含量与高颅压和癫(癎)的关系

目的探讨脑囊尾蚴病患者脑脊液（CSF）特异性IgG含量和一氧化氮（NO）水平与高颅压和癫痫的关系。方法检测40例脑囊尾蚴病患者CSF特异性IgG的含量和NO的水平,并对有无高颅内压征及癫痫的患者进行比较、分析。另外,检测23例大隐静脉曲张患者（对照组）CSFNO水平作对照。结果与对照组相比,脑囊尾蚴病组CSF中NO值明显增高（P〈0.01）。脑囊尾蚴病组特异性IgG与NO水平呈正相关（r=0.579,P〈0.05）;高颅内压患者CSF中特异性IgG与NO水平显著高于无高颅内压患者（P〈0.05-0.01）;癫痫患者CSF中NO值与无癫痫患者相比明显升高（P〈0.05）,而特异性IgG含量虽然升高但差异无统计学意义（P〉0.05）。结论脑囊尾蚴病致颅内高压征患者CSF中NO和特异性IgG水平明显增高;脑囊尾蚴病致癫痫患者CSFNO水平亦增高。     

脑囊虫病所致癫痫与影像学及囊尾蚴生存状态之间关系的研究

目的 探讨脑囊虫病引起的癞痫与CT、MRI特征及囊尾蚴生存状态之间的关系。材料与方法 回顾性研究1985年8月～1996年1月经寄生虫组织病理学证实的148例以癫痫为主要表现的脑囊虫病患者临床、CT、MRI及组织病理学资料,观察其癫痫发作类型、次数及程度与CT、MRI表现及囊虫生存状态之间的关系。结果 本组以部分性发展至全身强直阵挛发作为多,占82.5％,单纯部分性发作占17.5％。发作类型与病灶所在部位及周围组织水肿程度有关,而发作频率及程度只与CT、MRI所示病灶周围、水肿范围有关。同时发现水肿程度又与囊尾坳在脑组织内的生存状态有关。结论囊尾蚴在脑组织内的不同时期,在影像学上均有其对应特征,癫痫发作及与否及程度与囊虫生存状态密切相关。这对正确全面诊断,特别是制订恰当的治疗方案有重要意义。     

多发性硬化患者IgG指数、24 h合成率、组分区带检测的比较

目的 研究IgG指数，24h合成率，组分区带对多发性硬化（MS）患者的临床意义。方法 应用免疫比浊法，等电点聚焦及银染色法进行检测。结果 103例经临床诊断为MS患者中IgG组分区带阳性占90.3%，IgG24h合成率异常占19.4%,IgG指数异常占17.5%。结论 MS患者IgG组分区带阳性率比IgG指数，IgG24h合成率高，对MS有辅助性诊断意义。     

Autoimmune Neurological Disorders with IgG4 Antibodies: a Distinct Disease Spectrum with Unique IgG4 Functions Responding to Anti-B Cell Therapies

The main IgG4 antibody–mediated neurological disorders (IgG4-ND) include MuSK myasthenia; CIDP with nodal/paranodal antibodies to Neurofascin-155, contactin-1/caspr-1, or pan-neurofascins; anti-LGI1 and CASPR2-associated limbic encephalitis, Morvan syndrome, or neuromyotonia; and several cases of the anti-IgLON5 and anti-DPPX-spectrum CNS diseases. The paper is centered on the clinical spectrum of IgG4-ND and their immunopathogenesis highlighting the unique functional effects of the IgG4 subclass compared to IgG1-3 antibody subclasses. The IgG4 antibodies exert pathogenic effects on their targeted antigens by blocking enzymatic activity or disrupting protein–protein interactions affecting signal transduction pathways, but not by activating complement, binding to inhibitory FcγRIIb receptor or engaging in cross-linking of the targeted antigen with immune complex formation as the IgG1-IgG3 antibody subclasses do. IgG4 can even inhibit the classical complement pathway by affecting the affinity of IgG1-2 subclasses to C1q binding. Because the IgG4 antibodies do not trigger inflammatory processes or complement-mediated immune responses, the conventional anti-inflammatory therapies, especially with IVIg, immunosuppressants, and plasmapheresis, are ineffective or not sufficiently effective in inducing long-term remissions. In contrast, aiming at the activated plasmablasts connected with IgG4 antibody production is a meaningful therapeutic target in IgG4-ND. Indeed, data from large series of patients with MuSK myasthenia, CIDP with nodal/paranodal antibodies, and anti-LGI1 and CASPR2-associated syndromes indicate that B cell depletion therapy with rituximab exerts long-lasting clinical remissions by targeting memory B cells and IgG4-producing CD20-positive short-lived plasma cells. Because IgG4 antibody titers seem reduced in remissions and increased in exacerbation, they may serve as potential biomarkers of treatment response supporting further the pathogenic role of self-reacting B cells. Controlled trials are needed in IgG4-ND not only with rituximab but also with the other anti-B cell agents that target CD19/20, especially those like obexelimab and obinutuzumab, that concurrently activate the inhibitory FcγRIIb receptors which have low binding affinity to IgG4, exerting a more prolonged anti-B cell action affecting also antigen presentation and cytotoxic T cells. Antibody therapies targeting FcRn, testing those anti-FcRn inhibitors that effectively catabolize the IgG4 antibody subclass, may be especially promising.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01210-1.     

Specific IgG subclass reactivity in herpes simplex encephalitis

Summary Serum and cerebrospinal fluid (CSF) samples from 19 patients with a previous diagnosis of herpes simplex virus encephalitis (HSVE), from 14 patients with a previous diagnosis of non HSVE encephalitis and from 21 healthy subjects were examined to detect IgG subclasses 1–4 reactive with herpes simplex virus (HSV), cytomegalovirus (CMV) and varicella zoster virus (VZV). Antibodies to HSV were detected in CSF and serum from the 14 HSVE-patients with a reactivated HSV infection and from 3 of the 5 patients with a primary HSV infection. The predominant subclass pattern was an early HSV-specific IgG1 rise, followed by IgG3 and, more seldom, IgG4; HSV IgG2 was rarely seen. In HSVE patients, HSV IgG3 was absent in early samples and usually appeared 10–20 days after onset of disease. In 14 out of 16 seropositive healthy controls, on the other hand, HSV IgG3 was present in the CSF. Rising VZV IgG levels in serum and CSF were found in 11 HSVE patients. Eight of them showed signs of intrathecal VZV IgG1 synthesis. The VZV IgG reactivity was restricted to IgG1 in 7 of these whereas the HSV IgG subclass response also included IgG3 or 4. The appearance of several HSV IgG subclasses appeared to serve as a marker of HSV infection in spite of the serological VZV reaction, usually restricted to VZV IgG1. Intrathecal synthesis of the quantitatively minor HSV IgG3 and 4 subclasses was detected earlier than intrathecal synthesis of total HSV IgG, dominated by IgG1 in 4 patients with HSVE.     

Clinical fluctuations in MuSK myasthenia gravis are related to antigen-specific IgG4 instead of IgG1

We studied the longitudinal relation between disease severity and titers of antigen-specific IgG subclasses in sera of patients with myasthenia gravis and antibodies to Muscle Specific Kinase (MuSK MG). Six patients were included of whom 55 samples had been collected during 2.5–13.4 years. Anti-MuSK antibodies were determined by ELISA and with a cell-based immunofluorescence assay. Disease severity was scored on a semi continuous scale. Only antigen-specific IgG4, and not IgG1, titers were significantly associated with disease severity in a linear mixed effect model (p = 0.036). Levels of IgG4 antibodies were above IgG1 in all samples except in one patient who went into clinical remission while switching from IgG4 to IgG1. The results support an important role for IgG4 in the pathogenesis of MuSK MG, in contrast to MG with anti-acetylcholine receptor antibodies.     

Intracranial hypertension related to cerebral venous thrombosis; and acute ischemic stroke with micro-infarcts associated with IgG4-related disease

ABSTRACT

IgG4-related systemic disease (IgG4-RD) is characterized by an inflammatory reaction rich in IgG4-positive plasma cells, affecting multiple organs. This report describes a case who was diagnosed with IgG4-RD, having cerebral venous thrombosis and a subsequent acute ischemic stroke of undetermined cause. A 47-year-old woman presented with headache, visual disturbance and eyelid swelling and two years later she was admitted with acute attacks of mild left lower limb sensory-motor monoparesis. Indirect immunohistochemistry assay showed elevated level of IgG4, labeling neurons of the central nervous system, suggesting an immunological process possibly affecting vascular structures. Our experience suggests that IgG4-RD may be considered in patients with ischemic stroke and cerebral venous system involvement.     

IgG4-Related Intracranial Hypertrophic Pachymeningitis : A Case Report and Review of the Literature

Hypertrophic pachymeningitis is an uncommon disorder that causes a localized or diffuse thickening of the dura mater. Recently, the possibility that IgG4-related sclerosing disease may underlie some cases of intracranial hypertrophic pachymeningitis has been suggested. We herein report the tenth case of IgG4-related intracranial hypertrophic pachymeningitis and review the previous literature. A 45-year-old male presented with left-sided focal seizures with generalization. Magnetic resonance imaging (MRI) revealed a diffuse thickening and enhancement of the right convexity dura matter and falx with focal nodularity. The surgically resected specimens exhibited the proliferation of fibroblast-like spindle cells and an infiltration of mononuclear cells, including predominantly plasma cells. The ratio of IgG4-positive plasma cells to the overall IgG-positive cells was 45% in the area containing the highest infiltration of plasma cells. On the basis of the above findings, IgG4-related sclerosing disease arising from the dura mater was suspected. IgG4-related sclerosing disease should be added to the pachymeningitis spectrum.     

Serum IgG,IgA and IgM concentration in 1,038 patients with various neurological disorders

Summary Concentration of serum IgG, IgA and IgM in 1,038 unselected patients with various neurological diseases was determined. In 521 instances, the levels of CSF IgG, IgA and IgM were also established. In serum, the most frequent selective quantitative abnormality was found in the IgA concentration. In CSF, an increased level of IgG with normal IgA concentration and undetectable IgM was established about 8 times more frequently than isolated increase of CSF IgA. Selective quantitative abnormalities in serum IgG were observed in 35% of patients with subacute sclerosing panencephalitis as compared to 5% in instances in the definite MS group. Abnormal bands in the serum gamma-globulin field were most frequently seen in electropherograms from patients with subacute sclerosing panencephalitis, in cases of malignant lymphoproliferative disorders and in patients with definite MS. No correlation between the concentration of serum and CSF immunoglobulins could be established. Most frequent quantitative abnormalities in serum IgG, IgA and/or IgM were established in malignant lymphoproliferative disorders, in patients with myopathies including myositides and in subacute or chronic inflammatory CNS disorders. Highest incidence of increased CSF IgG, IgA and/or IgM concentration was detected in patients with inflammatory CNS disease, in instances of definite MS and in malignant lymphoproliferative disorders with CNS symptomatology. Increased CSF IgG and IgA concentration with detectable levels of IgM in patients with elevated CSF total proteins indicated alterations in the blood/CNS barrier structures.Supported by PHS grants NB05450 and 06793.     

A unique case of isolated thoracic spinal Rosai-Dorfman disease related to IgG4

Rosai-Dorfman disease (RDD) is a rare benign histiocytosis usually characterized by massive cervical lymphadenopathy and systemic manifestations. Extranodal, especially spinal involvement, is extremely rare. Our case was deemed worthy of presentation because it was the first reported isolated case of spinal RDD related to IgG4 and mimicked meningioma clinically and radiologically. A case with an intradural extramedullary mass causing neurological compression findings in the thoracic spinal region and radiologically mimicking meningioma is presented. In the histomorphological examination of the resection material, polymorphonuclear leukocytes in the dura, histiocytes showing emperipolesis, an increase in collagenized fibrous connective tissue, and intense lymphoplasmacytic cell infiltration accompanied by obliterative phlebitis were observed. Immunohistochemically, the histiocytic cells were found to be S-100 protein, CD68, and CD163 positive and CD1a and langerin negative, and more than half of the plasma cells were immunoglobulin-G4 (IgG4) positive. Although rare, RDD or IgG4-related meningeal disease should be considered in the differential diagnosis of dural-based spinal masses that radiologically suggest meningioma. The pathologist should be aware that these two histopathological entities may coexist. To our knowledge, this is the first case of “isolated spinal RDD related to IgG4” reported in the literature.     

TLR4, IL‐6, IL‐18, MyD88 and HMGB1 are highly expressed in intracranial inflammatory lesions and the IgG4/IgG ratio correlates with TLR4 and IL‐6

We determined distribution of plasma cells and IgG4/IgG index and factors associated with the index in intracranial inflammatory lesions. Specimens of nine patients were analyzed immunohistochemically using antibodies against CD45, CD68, CD3, CD4, CD8, CD20, CD138, lambda chain, kappa chain, IgG, IgG4, IL‐1α, IL‐6, IL‐18, toll‐like receptor (TLR) 2, TLR4, high‐mobility group box 1 (HMGB1), tumor necrosis factor‐alpha (TNF‐α), myeloid differentiation factor 88 (MyD88), and anaplastic lymphoma kinase (ALK). The relationship between all the factors was assessed using Spearman's rank correlation coefficient (ρ). Negative ALK staining was observed in all the patients. Plasma cells were detected in eight patients with varying degrees. The highest number of neutrophils, but no plasma cells, was observed in a patient with the shortest history of inflammation. IgG4/IgG index was independent of the number of plasma cells. The index was relatively highly correlated with IL‐6 (ρ = 0.7271) and TLR4 expression (ρ = 0.7246). IL‐6 expression was highly correlated with TLR4 expression (ρ = 0.8042). IL‐18 was maximally expressed in all the patients. TLR4 expression was strong, but TRL2 expression was weak. Positive HMGB1 staining was observed in all the patients, predominantly in the nuclei, but also in the cytoplasm in four patients. The cytoplasmic expression strongly correlated with IL‐1α expression (ρ = 0.9583). The cytoplasmic colocalization of HMGB1 and IL‐1α was histologically confirmed in cells with collapsing nuclei by the double‐staining method. The IgG4/IgG indexes varied case by case. IL‐6 and TLR4 expressions may influence IgG4/IgG index. The nuclei of cells with both IL‐1α and HMGB1 expressions in the cytoplasm collapse in the cell death stage. The cooperative high expression of TLR4, IL‐6, IL‐18, MyD88 and HMGB1 suggest their critical roles in the inflammation circuit.