Multiple sclerosis specific antigens in MS brains

Antigens in MS and non-MS brains were investigated by means of crossed immunoelectrophoresis. Two MS specific antigens were found: a measles antigen which was present in microsomes and cytosole, and an unidentified antigen present only in cytosole.     

Chronic viral infections of the central nervous system: Aspects specific to multiple sclerosis

The involvement of a viral infection in the physiopathology of multiple sclerosis has been said to cause certain viruses to target the central nervous system and induce neuroinflammation leading to cell dysfunction, as seen, for example, by demyelination or neuronal death. The most recent results of the literature have focused on the Herpes family viruses (HHV-6 and HHV-4/Epstein-Barr virus) and their possible role in the development of multiple sclerosis. Even if no virus has been identified so far as the multiple sclerosis etiological agent, our aim here is to show that some viruses may be responsible for triggering or sustaining neurological diseases. This is particularly the case for Paramyxoviruses, in the late appearance of functional alterations, Picornaviruses, in inducing a breakdown of immune tolerance, epitope spreading and demyelination, and Herpes viruses in inducing T and B lymphocyte activation, T lymphocytes dysregulation and autoimmunity after their reactivation. Therefore, “common” viruses can play a role as potential modulators of the immune and nervous systems which, in the specific context of dysimmunity and genetic susceptibility, stimulate a favorable background to the development of multiple sclerosis. Tracing and studying viruses in multiple sclerosis patients may improve our understanding of their actual involvement in multiple sclerosis physiopathology.     

Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis

Our identification of Chlamydia pneumoniae in the cerebrospinal fluid (CSF) of a patient with multiple sclerosis (MS) led us to examine the incidence of this organism in the CSF from 17 patients with relapsing–remitting MS, 20 patients with progressive MS, and 27 patients with other neurological diseases (OND). CSF samples were examined for C pneumoniae by culture, polymerase chain reaction assays, and CSF immunoglobulin (Ig) reactivity with C pneumoniae elementary body antigens. C pneumoniae was isolated from CSF in 64% of MS patients versus 11% of OND controls. Polymerase chain reaction assays demonstrated the presence of C pneumoniae MOMP gene in the CSF of 97% of MS patients versus 18% of OND controls. Finally, 86% of MS patients had increased CSF antibodies to C pneumoniae elementary body antigens as shown by enzyme-linked immunosorbent assay absorbance values that were 3 SD greater than those seen in OND controls. The specificity of this antibody response was confirmed by western blot assays of the CSF, using elementary body antigens. Moreover, CSF isoelectric focusing followed by western blot assays revealed cationic antibodies against C pneumoniae. Infection of the central nervous system with C pneumoniae is a frequent occurrence in MS patients. Although the organism could represent the pathogenetic agent of MS, it may simply represent a secondary infection of damaged central nervous system tissue. A therapeutic trial directed at eliminating C pneumoniae from the central nervous system may provide additional information on its role in MS. Ann Neurol 1999;46:6–14     

Evaluation of central nervous system vaccinia antibody synthesis in multiple sclerosis patients

A serum/cerebrospinal fluid (CSF) ratio method was used to determine whether elevated CSF vaccinia antibody titers in some patients with multiple sclerosis are the result of central nervous system antibody synthesis or of a leak in the blood-brain barrier. Nine of 20 multiple sclerosis patients were noted to have a depressed serum/CSF vaccinia antibody ratio and a normal ratio for poliovirus-I, an agent thought not to be involved in the pathogenesis of multiple sclerosis. These data suggest central nervous system synthesis of vaccinia neutralizing antibody. Vaccinia virus antigens may play an important direct or indirect role in the pathogenesis of multiple sclerosis.     

Magnetization transfer MRI in multiple sclerosis and other central nervous system disorders

The present review summarizes the major contributions given by magnetization transfer-magnetic resonance imaging to provide an accurate in vivo picture of the heterogeneity of central nervous system pathology and, ultimately, to improve our ability to monitor the evolution of various neurological conditions.     

A differential diagnosis of central nervous system demyelination: beyond multiple sclerosis

Although multiple sclerosis (MS) is the most common demyelinating disorder of the central nervous system (CNS), it lacks any definitive diagnostic test. Instead, diagnosis of MS primarily depends upon clinical criteria, supported by abnormalities characteristic of MS on para-clinical investigations including magnetic resonance imaging of the brain and spine, in the absence of an alternative explanation for underlying neurologic symptoms. While many of the potential disorders that may mimic MS in routine clinical practice are either extremely rare, or associated with specific and characteristic distinguishing diagnostic features, some inflammatory demyelinating disorders of the CNS may be particularly challenging to distinguish from MS, especially during initial presentation. In particular, acute disseminated encephalomyelitis, neuromyelitis optica, and idiopathic transverse myelitis may closely resemble MS, impeding prompt and accurate diagnosis. In this review, we describe the clinical features, diagnosis, pathology, and treatment of these other CNS demyelinating disorders. In addition, we review relevant features of other CNS inflammatory disorders that may mimic MS, including Sj?gren's syndrome, systemic lupus erythematosus, Beh?et's disease, and primary CNS vasculitis.     

Chlamydophila pneumoniae infection of the central nervous system in patients with multiple sclerosis

BACKGROUND: Chlamydophila pneumoniae has been postulated as an aetiological agent in the pathophysiology of multiple sclerosis. Previous studies show conflicting results. OBJECTIVE: To investigate patients with multiple sclerosis and other neurological diseases for evidence of past or present infection with C pneumoniae. METHODS: 19 patients with multiple sclerosis and 29 with other neurological diseases were studied. Evidence was sought for past or present infection with C pneumoniae using polymerase chain reaction (PCR) and cell culture of cerebrospinal fluid (CSF), and enzyme linked immunosorbent assay and microimmunofluorescence of serum. RESULTS: C pneumoniae was grown from the CSF of one patient with multiple sclerosis. PCR was negative in all cases. Anti-chlamydial antibodies were detected in the same proportion in each group. CONCLUSIONS: This study does not support the theory of an association between C pneumoniae and multiple sclerosis.     

Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains

The amount of messenger RNA encoding human inducible nitric oxide synthase and the presence and distribution of NADPH diaphorase were determined in tissue sections from multiple sclerosis (MS) and control brains. Levels of human nitric oxide synthase messenger RNA were markedly elevated in MS brains when compared to normal control brains. NADPH diaphorase activity, a histochemical stain reflecting nitric oxide synthase catalytic activity, was detected in reactive astrocytes in active demyelinating MS lesions and at the edge of chronic active demyelinating lesions. Control brains did not contain NADPH diaphorase–positive astrocytes. These results implicate the free radical nitric oxide in the pathogenesis of demyelinating MS lesions.     

Modulating processes within the central nervous system is central to therapeutic control of multiple sclerosis

Journal of Neurology - Historically considered to be an autoimmune demyelinating disease, multiple sclerosis is now recognized to be characterized by significant axonal and neuronal pathology....     

Stimulation of active E-rosette forming lymphocytes by myelin basic protein and specific antigens from multiple sclerosis brains.

Peripheral blood lymphocytes from 30 patients with multiple sclerosis (MS) responded to low doses (i.e. 0.1--5 pg total protein) of crude MS myelin basic protein (BP) as assayed by the active E-rosette test (AER). Of the MS patients studied 20 (65%) responded to control BP. The optimum response of MS lymphocytes to MS BP was obtained at a lower concentration than their response to control BP. Thirty percent of other neurological patients (OND) were stimulated by both MS and control BP. Lymphocytes of all MS patients but none of the OND responded to partially purified protein fraction of MS brain ("peak 2"). Crossed immunoelectrophoresis revealed the presence of one common specific antigen in crude MS BP and MS "peak 2" antigens. The nature of these antigens is discussed.     

多发性硬化的周围神经系统损害

目的 探讨多发性硬化（MS）患者合并周围神经系统（PNS）损害的临床及肌电图特点。方法 回顾性分析14例MS合并PNS损害的临床及肌电图资料。结果 MS合并PNS损害的发生率为12．5％,其临床表现主要为末梢型或神经型根型感觉障碍、根性疼痛、肌肉萎缩,周围神经受损较神经根受损常见。PNS损害并不是每次发病都出现,出现时间较早、持续时间较短,不影响的疾病的病程及患者的功能障碍。肌电图上表现为存在纤颤波、正锐波,轻收缩时波幅增高、时限延长,感觉神经传导速度减慢,末端运动潜伏期延长,神经电位波幅降低,F波潜伏期延长等。结论 MS患者确实可能有PNS损害,出现PNS损害不影响患者的预后,常随着病情的好转很快恢复。     

Peripheral nervous system involvement in multiple sclerosis

Objective: To investigate possible peripheral nervous system (PNS) affection in patients with multiple sclerosis (MS) by standard nerve conduction velocity (SNC) and pain‐related evoked potentials (PREP), a novel electrophysiological method for diagnosing small fibre neuropathy. Background: Former neuropathological and electrophysiological studies demonstrated subtle PNS affection in MS, but routine measurements are mostly normal. Small fibre polyneuropathy is associated with several autoimmune diseases but has not been investigated in MS yet. Design/Methods: Fifty‐four patients with MS (43 relapsing–remitting, 11 secondary progressive MS) underwent SNC of the tibial, sural and peroneal nerve. Twenty‐one patients additionally underwent PREP. Results: SNC abnormalities were observed in 29.6% of all patients and 14.2% of all nerves examined No abnormalities on PREP were found. Conclusions/Relevance: We demonstrated subtle alterations on routine electrophysiological measurements in patients with MS without hints for small fibre pathology.     

A rare case of nonenhancing primary central nervous system lymphoma mimic multiple sclerosis

Primary central nervous system lymphoma (PCNSL) is reported to have increased in the last decades. Early diagnosis is crucial for proper management of this tumor. We report a case of a 48-year-old man who was initially diagnosed with multiple sclerosis. Magnetic resonance imaging of the brain revealed multiple lesions with hypersignals in the bilateral basal ganglia and brain stem in T2-weighted image and non-enhancement, while positron emission tomography showed a low uptake of ¹⁸F-fluorodeoxyglucose in the affected brain, indicative of demyelination. However, this individual was correctly diagnosed with PCNSL after biopsy and further histological analysis. Primary central nervous system lymphoma must be considered even when nonenhancing, diffuse lesions are seen on MRI. A visible tumor on imaging is essential to ensure an early brain biopsy and histological diagnosis.Primary central nervous system lymphoma (PCNSL) accounts for 3.3% of all brain tumors.1 Primary central nervous system lymphoma in immunocompetent patients is non-Hodgkin lymphomas of germinal B-cell origin in the vast majority of cases, which arise from the brain, spinal cord, cerebrospinal fluid (CSF), or eyes in the absence of systemic disease.1,2 Because of its ambiguous clinical manifestation, neuroradiographic, and CSF cytology, PCNSL can be easily misdiagnosed. Our objective in presenting this particular case is to highlight that PCNSL should be considered even when non-enhancing, diffuse lesions are seen on MRI.     

Immunological disturbances in the central nervous system linked to MRI findings in multiple sclerosis

To clarify immunological disturbances in the central nervous system (CNS) in multiple sclerosis (MS) by linking to magnetic resonance imaging (MRI) findings, 22 patients with relapsing remitting MS were studied. Cerebrospinal fluid (CSF) samples were analyzed during a total of 27 independent MS stages (20 active, 7 inactive) on 25 occasions during which gadolinium (Gd)-enhanced MRI scans were performed. The number of Gd-enhanced lesions was significantly correlated with CSF cell counts, as well as the number of CD4(+)CD29(+) helper inducer and IL-2 receptor (CD25)-positive activated helper T cells. In contrast, T(2) lesion load in the brain showed a trend of association with elevated IgG index.     

Monoclonal antibodies to central nervous system antigens

Thirty monoclonal antibodies produced by mouse hybrid myelomas which react with antigens in hamster or mouse nervous system tissues were derived. Using these antibodies as probes with indirect immunofluorescence and immunoperoxidase techniques, we can selectively identify by morphological criteria many of the structural components of the brain seen at a light-microscopic level, including the neuropil, neuronal cytoplasm, nuclei, axons, astrocytes and ependyma. Some of the antibodies display cytoskeletal and filamentous structures, including intermediate filaments, microfilaments, neurofilaments, glial and ependymal filaments. The specificity to neural tissue components of these hybridoma antibodies was assessed by their reactivity to mouse and hamster non-neural tissues and selected mouse, hamster, rat and human cultured cell lines. Of the 30 clones analyzed, specificity ranged from 3 clones reacting only with grey matter of mouse and hamster brain, one clone reacting only with axons in animal and human brain, to 19 clones reactive with both neural and non-neural tissue components.     

Glutamine synthetase immunoreactivity is present in oligodendroglia of various regions of the central nervous system

Glutamine synthetase immunoreactive oligodendrocytes were identified in the cerebral cortex, cerebellum, brain stem, and spinal cord. They were mostly confined to the gray matter, particularly close to neurons and processes. The white matter showed few immunoreactive oligodendroglia. It was suggested that some type of oligodendrocytes, specially those in perineuronal location, might fulfill a functional role more akin to astrocytes than to the normally myelinating oligodendroglia.