诱发电位在多发性硬化诊断中的价值

目的：评价诱发电位在多发性硬化(MS)诊断中的价值，并为临床提供MS的诱发电位(EP)资料。方法：本课题采用临床病例分析统计方法，对164例MS患者的3项EP资料进行分析。结果：MS患者的3项EP中，视觉诱发电位(VEP)的异常率最高，其次为体感诱发电位(SEP)，脑干听觉诱发电位(BAEP)最低；这3项EP联合检查可使异常率提高，EP发现病灶的敏感性较临床检查高，其不仅可以发现中枢神经系统的病灶，而且还能够发现外周神经系统的病灶。结论：联合应用3项EP检查有助于MS诊断以及亚临床病灶的发现。     

Neurogenic vestibular evoked potentials in the diagnosis of multiple sclerosis

OBJECTIVES: To determine the value of neurogenic vesibular evoked potential (NVESTEP) studies in comparison with other paraclinical tests in demonstrating dissemination in time and space in Multiple Sclerosis (MS) and in identifying clinically silent lesions. METHOD: All patients in whom MS was suspected but the diagnosis of MS was not possible based on the McDonald criteria were included in this study. We studied 14 patients and performed visual, brainstem auditory, somatosensory and neurogenic vestibular evoked potentials in all patients, together with MRI and CSF analysis of oligoclonal bands (OB). RESULTS: Two out of the thirteen patients could be movedfrom the category of "possible MS" to "MS" using the McDonald criteria based on an abnormal NVESTEP result. CONCLUSION: Neurogenic vestibular evoked potentials are potentially useful in identifying clinically silent lesions in patients with possible MS.     

Cytoimmunological profile of cerebrospinal fluid in diagnosis of multiple sclerosis

The purpose of this paper is to report cerebrospinal fluid (CSF) findings in multiple sclerosis (MS) from our laboratory, to discuss the implications of CSF abnormalities in terms of diagnosis. Paired CSF-serum samples from of 1533 on 3893 patients with suspected neurological diseases over a 10 year period were analysed by routine laboratory microscopy and assays of immunoglobulin G by isoelectric focusing for the detection of intrathecal oligoclonal IgG. Patients were grouped further into four headings according to their disorders: MS (625 cases), definite (246 cases) probable (123 cases) and possible (256 cases) according to Poser, others inflammatory neurological diseases (91 cases), various non-inflammatory neurological disorders (732 cases) and uncertain neurological disorders (85 cases). Definite MS group (16%) was compared to non-inflammatory neurological disorders (48%). Important signs for activity of multiple sclerosis are observed. Cell counts were 10/microl in 71% (N < or =2/microl). Inflammatory cytology is observed after concentration and cytocentrifugation on slides with activated B-lymphocytes, lymphoplasmocytes and/or plasmocytes (76%), total protein concentration is increased in 37% (N < 0.40g/l), CSF/serum albumin quotient with age dependent references for the blood-CSF barrier dysfunction is increased in 26% (N < 0.65 x 10(-2)), IgG index for intrathecal synthesis of IgG is increased in 69% (N < 0.70), sensitive detection of oligoclonal IgG restricted to CSF by isoelectric focusing is positive in 91% (86-96%) with a specificity of 96% (93-99%).     

Cannabis for the treatment of multiple sclerosis

Conventional myeloablative conditioning regimens prior to hematopoietic cell transplantation (HCT) are associated with significant transplant-related morbidity and mortality in children affected by primary immunodeficiency disorders. Reduced-intensity conditioning regimens have been extensively used without severe acute toxicity in patients with pre-HCT comorbidities, with the additional advantage of reducing or avoiding long-term sequelae such as infertility and growth retardation. Compared with myeloablative HCT, reduced-intensity conditioning regimens are associated with an increased incidence of mixed donor chimerism and graft rejection. While mixed donor engraftment is likely to correct the phenotypic expression of most children with primary immunodeficiency disorders, the use of donor lymphocyte infusion to increase donor chimerism or second HCT procedures may be required in some cases. Here we discuss the most recent data on the use of different reduced-intensity conditioning protocols in children with primary immunodeficiency disorders, highlighting significant clinical lessons and areas that need additional study.     

Elevated serum levels of lysophosphatidic acid in patients with multiple sclerosis

A plethora of studies have shown that lysophosphatidic acid (LPA) is involved both in inflammation and T cell apoptosis evasion. The aim of this study was to measure the concentrations of LPA in serum of patients with multiple sclerosis (MS). Twenty MS patients along with 20 age–sex matched healthy individuals were recruited for this investigation. By employment of ELISA method, we demonstrated that MS patients had higher levels of LPA in serum than control group (P = 0.006). This study is the first report of LPA elevation in MS disease.     

Genetic predisposition for multiple sclerosis

Although the clinical manifestations and neuropathological signs of multiple sclerosis (MS) have been known for a century, the cause of this disease has not yet been determined. The epidemiological studies indicate that MS is of multifactorial etiology, including both environmental and inherited (genetic predisposition) factors. The role of the HLA system in genetic predisposition to MS has been known since the 1970s. As a result of the progress made in human genetics, it is now possible to study genetic predisposition to MS.     

Subcutaneous alemtuzumab for multiple sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS that is heterogeneous in its clinical manifestation and progression, as well as in its pathological mechanisms. Animal models, in particular the various forms of experimental autoimmune encephalomyelitis, have been highly valuable for studying both disease pathology and drug development. Novel technologies, such as advanced imaging systems, as well as systematic research of CNS biopsies and postmortem samples from MS patients, have brought major progress in disease understanding. Consequently, in addition to the sclerotic demyelinated plaques in the white matter, changes in normal-appearing white matter tissue (‘pre-plaque’) and gray matter pathology are currently regarded as central disease components. This review aims to provide current insights on several central aspects in MS research. In particular, the interplay between inflammation and neurodegeneration mediating the disease, and therapeutic strategies attempting to induce immunomodulation and neuroprotective repair processes, are discussed.     

Experimental immunotherapies for multiple sclerosis

Summary Multiple sclerosis (MS) is a chronic demyelinating disease affecting the central nervous system (CNS) principally in young adults. Although its etiology is as yet unknown current evidence suggests that tissue damage is mediated by autoimmune T cells. The examination of an experimental animal model for MS, experimental allergic encephalomyelitis (EAE), has demonstrated that myelin basic protein (MBP)- or proteolipid protein (PLP)-specific T cells mediate the destruction of CNS myelin. In recent years, elegant studies in EAE have shown that encephalitogenic T cells recognize short peptides of MBP or PLP in the context of MHC/HLA-class II molecules, express a restricted number of T cell receptor (TCR) molecules and secrete interferon- and tumor necrosis factor-a/. Understanding the pathogenetic steps in lesion development at the molecular level led to highly specific immunotherapies for EAE targeting each individual molecule. It has been the hope of many investigators that immunological events resembling those in EAE can be found in patients with MS and that the specific immunotherapies effective in EAE could also be applied to MS. However, to date, the evidence for a unique immunological abnormality in MS is notstrong. Although MBP- and PLP-specific T cells with properties similar to those that are encephalitogenic in animals can be isolated from patients, they are not specific for MS and occur with similar frequency in controls. In addition, the variability in specificity and TCR usage has raised questions regarding the relevance of these cells in patients. The importance of the T cell responses to myelin antigens in MS may not be established until the effects of abrogating their activity through specific therapies targeting the trimolecular complex (TMC) have been demonstrated. Consequently, attention has begun to focus on modifying the biology of the MS lesion rather than targeting the initiating event at the level of the TMC, and the success of this approach is reflected by the effect of interferon- on lesion development in MS. The recent approval for the use of interferon- for the treatment of relapsing-remitting MS has raised great interest in examining novel strategies for immunotherapies in MS. The basic concepts as well as the current candidates for such new immunotherapies will be outlined in this short review.     

Differential diagnosis of HTLV-I-associated myelopathy and multiple sclerosis in Iranian patients

Summary Two Iranian patients with chronic progressive spastic paraparesis and urinary dysfunction were referred to our hospital with the presumptive diagnosis of multiple sclerosis (MS). Routine CSF analysis and magnetic resonance imaging of the two patients were only partially characteristic of MS. Testing for antibodies to human T-cell leukemia virus type I [HTLV-1] in serum using a radioimmune precipitation assay revealed antibodies to HTLV-I in both patients. The infection with HTLV-I was confirmed by polymerase chain reaction (PCR) and liquid hybridization analysis using primers to the tax/rex region and a corresponding probe, demonstrating proviral DNA in peripheral blood mononuclear cells of both patients. On the basis of these findings demonstrating the presence of proviral HTLV-1 DNA in the two Iranian patients, the initial diagnosis of MS was corrected to that of HTLV-I-associated myelopathy (HAM). In contrast, several patients with definite MS (nine from Germany, two from Iran) with a relapsing and remitting form of the disease were tested for HTLV-1 infection by enzyme-linked immunosorbent assay and PCR, which yielded negative results. However, the mother of one HAM patient was found to be infected with HTLV-I. To support an association between HTLV-I infection and CNS disease in the two HAM patients, we analyzed the production of specific IgG antibodies within the CNS based on a simple enzyme immunoassay for viral IgG antibodies in CSF and serum. In the two HAM patients there was significant intrathecal antibody production directed against HTLV-I, but this was not found in any of the samples from MS patients. These findings demonstrate an immune reaction to HTLV-I in the CNS of HAM patients, thus confirming the association of infection and CNS disease. The demonstration of intrathecal HTLV-I antibody production also proved useful for the differential diagnosis of MS or HAM, especially in patients from areas endemic for HTLV-I.Abbreviations DTPA diethylenetriaminepentaacetic acid - ELISA enzyme-linked immunosorbent assay - HAM HTLV-I-associated myelopathy - HTLV-I human T-cell leukemia virus type I - MRI magnetic resonance imaging - MS multiple sclerosis - PBMC peripheral blood mononuclear cells - PCR polymerase chain reaction - RIPA radioimmune precipitation assay - SDS sodium dodecyl sulfate - TSP tropical spastic paraparesis     

Validation and meta-analysis of kappa index biomarker in multiple sclerosis diagnosis

The importance of studying the cerebrospinal fluid (CSF) in Multiple Sclerosis (MS) is included in the last McDonald criteria (2018). The study of oligoclonal IgG bands (OCGB) assay is strongly recommended in some situations in which MS diagnosis is uncertain. New biomarkers are developed during the last years. Kappa free light chains (FLC) can predict conversion to MS in patients with Clinically Isolated Syndrome (CIS).The aim of this work is to validate the clinical usefulness of the kappa index, and to establish the actual state of knowledge for kappa index as a biomarker of conversion in CIS patients by a meta-analysis. Kappa index seems more relevant than the mere concentration of kappa FLC in CSF.In the validation study, 334 patients were included; in which 100 were CIS patients. Patients were divided in two groups according kappa index cut-off of 10.62: group 1 (kappa index>10.62); group 2 (kappa index<10.62). In group 1 more patients had positive OCGB, IgG index>0.56 and fulfilled magnetic resonance imaging (MRI) criteria. In contrast, in group 2, more patients showed negative OCGB, IgG index<0.56 and did not fulfilled MRI criteria. While 67.6% of patients from group 1 converted to MS, only 12.5% of patients from group 2 converted to MS. An HR of 6.02 was obtained in the Kaplan-Meier analysis.In the meta-analysis, 8 studies were finally included. The SROC curve revealed a high diagnostic performance for the kappa index as a MS diagnostic biomarker. Despite heterogeneity found between studies, the global OR revealed a good discriminatory capacity of kappa index.In conclusion, kappa index has a great clinical sensitivity and specificity as a support in MS diagnosis. High kappa index increase the probability of CIS to MS conversion. A correct sample processing in the preanalytical stage is key to obtain right results and to allow establishing comparison between laboratories.