Childhood chronic inflammatory demyelinating polyneuropathy with central nervous system demyelination resembling multiple sclerosis

Central nervous system demyelination has been described in adults but not in children with chronic inflammatory demyelinating polyneuropathy. We describe a patient with clinical and electrophysiological features consistent with chronic inflammatory demyelinating polyneuropathy who presented at age 5 with an intramedullary spinal cord tumor-like lesion and at age 8, represented with cerebral and spinal demyelinating lesions. Her clinical course and magnetic resonance imaging features were atypical for multiphasic disseminated encephalomyelitis and indistinguishable from multiple sclerosis. To our knowledge, this association has not been previously described in the English literature in childhood.     

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.     

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.     

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.     

Chronic inflammatory demyelinating polyradiculoneuropathy associated with central nervous system involvement--as compared to multiple sclerosis

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with central nervous system (CNS) demyelinating lesions has recently been reported to mimic multiple sclerosis (MS). In this paper, a series of patients with CIDP were examined to see if they had CNS involvement. CIDP patients with CNS lesions were then compared to patients with MS with peripheral nervous system (PNS) involvement for similarities. CNS and PNS involvement were detected by clinical symptoms, neurological findings, neuro-otological and neuro-ophthalmological tests, electrophysiological examinations such as electroencephalography, evoked potentials, blink reflex, conventional peripheral nerve conduction studies and electromyography, as well as computed tomography and magnetic resonance imaging (MRI). There were 7 of 17 CIDP patients with CNS involvement, but only 2 of 59 MS patients with PNS lesions were found. The rate of CIDP with CNS involvement (41.2%) was higher than that of MS with PNS lesions (3.4%). The CNS signs and symptoms of 7 CIDP patients were not so constant as their PNS symptoms, and consisted of 1 case with optic neuritis, 4 cases with cerebellar atxia and/or nystagmus, and 3 cases with spinal symptoms. These signs and symptoms are all well known in MS. Prolonged latencies on evoked potentials and high signal white matter lesions on T2 weighted MRI, indicating demyelinating CNS lesions were also similar to those found in MS. The CNS involvement in those patients with CIDP was therefore similar in character to those found in MS, but was far less severe than the PNS finding.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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     

FGF/FGFR system in the central nervous system demyelinating disease: Recent progress and implications for multiple sclerosis

Background

With millions of victims worldwide, multiple sclerosis is the second most common cause of disability among young adults. Although formidable advancements have been made in understanding the disease, the neurodegeneration associated with multiple sclerosis is only partially counteracted by current treatments, and effective therapy for progressive multiple sclerosis remains an unmet need. Therefore, new approaches are required to delay demyelination and the resulting disability and to restore neural function by promoting remyelination and neuronal repair.

Aims

The article reviews the latest literature in this field.

Materials and methods

The fibroblast growth factor (FGF) signaling pathway is a promising target in progressive multiple sclerosis.

Discussion

FGF signal transduction contributes to establishing the oligodendrocyte lineage, neural stem cell proliferation and differentiation, and myelination of the central nervous system. Furthermore, FGF signaling is implicated in the control of neuroinflammation. In recent years, interventions targeting FGF, and its receptor (FGFR) have been shown to ameliorate autoimmune encephalomyelitis symptoms in multiple sclerosis animal models moderately.

Conclusion

Here, we summarize the recent findings and investigate the role of FGF/FGFR signaling in the onset and progression, discuss the potential therapeutic advances, and offer fresh insights into managing multiple sclerosis.     

Idiopathic inflammatory demyelinating diseases of the central nervous system: differentiating between acute disseminated encephalomyelitis and malignant multiple sclerosis

Multiple sclerosis (MS) is the most frequent demyelinating disorder of the central nervous system (CNS). However, at presentation, it is frequently difficult to differentiate between malignant MS (MMS) and other fulminant CNS demyelinating diseases like acute disseminated encephalomyelitis (ADEM). The literature contains many case reports of ADEM but few series. We report on four representative cases of acute demyelinating diseases, together with evaluation of treatment, course and follow-up. We also present clinical, laboratory, neuropathologic, neuroimaging and data on therapeutic options, including follow-up, in order to establish distinguishing characteristics of MMS and ADEM. Good clinical outcome from a postinfectious, monophasic episode, correlating with regressive demyelinating lesions on MRI, after more than 2 years differentiate best. Therapeutic efficacy, prior infection and initial MRI lesions seem to be of limited value. Despite the advances of neuroimaging and laboratory techniques, objective parameters are still missing, but findings on basic immunologic mechanisms of humoral and cellular response might provide further insight.     

Immunohistochemical identification of T-lymphocytes in the central nervous system of patients with multiple sclerosis and subacute sclerosing panencephalitis

T-lymphocytes were identified in frozen brain sections derived from patients with chronic inflammatory disorders of the CNS by using a specific heteroantiserum and the unlabelled antibody enzyme method. Clusters of T-cells were found in post-mortem material of cases with multiple sclerosis (MS) and subacute sclerosing penencephalitis (SSPE). The results suggest that T-lymphocytes are involved in the pathogenesis of both MS and SSPE.     

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.     

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.     

Exercise in multiple sclerosis and its models: Focus on the central nervous system outcomes

Multiple sclerosis (MS) is a central nervous system (CNS) disorder characterized by inflammation, demyelination, and neurodegeneration. Emerging research suggests that exercise has therapeutic benefits for MS patients but the clinical data have focused primarily on non-CNS outcomes. In this review, we discuss evidence in preclinical MS models that exercise influences oligodendrocyte proliferation and repopulation, remyelination, neuroinflammation, neuroprotection, axonal regeneration, and astrogliosis. Evidence for the therapeutic effects of exercise in MS is further supplemented by data from other CNS diseases, including Alzheimer's disease, Parkinson's disease, and spinal cord injury. These results motivate studies into the benefits that exercise confers within the CNS in MS.     

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....