Repetitive Pertussis Toxin Promotes Development of Regulatory T Cells and Prevents Central Nervous System Autoimmune Disease

Bacterial and viral infections have long been implicated in pathogenesis and progression of multiple sclerosis (MS). Incidence and severity of its animal model experimental autoimmune encephalomyelitis (EAE) can be enhanced by concomitant administration of pertussis toxin (PTx), the major virulence factor of Bordetella pertussis. Its adjuvant effect at the time of immunization with myelin antigen is attributed to an unspecific activation and facilitated migration of immune cells across the blood brain barrier into the central nervous system (CNS). In order to evaluate whether recurring exposure to bacterial antigen may have a differential effect on development of CNS autoimmunity, we repetitively administered PTx prior to immunization. Mice weekly injected with PTx were largely protected from subsequent EAE induction which was reflected by a decreased proliferation and pro-inflammatory differentiation of myelin-reactive T cells. Splenocytes isolated from EAE-resistant mice predominantly produced IL-10 upon re-stimulation with PTx, while non-specific immune responses were unchanged. Longitudinal analyses revealed that repetitive exposure of mice to PTx gradually elevated serum levels for TGF-β and IL-10 which was associated with an expansion of peripheral CD4+CD25+FoxP3+ regulatory T cells (Treg). Increased frequency of Treg persisted upon immunization and thereafter. Collectively, these data suggest a scenario in which repetitive PTx treatment protects mice from development of CNS autoimmune disease through upregulation of regulatory cytokines and expansion of CD4+CD25+FoxP3+ Treg. Besides its therapeutic implication, this finding suggests that encounter of the immune system with microbial products may not only be part of CNS autoimmune disease pathogenesis but also of its regulation

Paralysie faciale périphérique isolée et infection à VIH: 7 cas

Human immunodeficiency virus infection frequently involves the peripheral or central nervous system. Seven cases of isolated peripheral facial palsy that occurred at various stages of the disease are reported. The palsy was the first manifestation of the disease in 5 patients, and revealed it in 3 of them. The palsy involved the right side in 6 cases (complete N = 2; incomplete N = 4); it was bilateral in one (complete on both sides). Abnormalities of the cerebrospinal fluid were present in all patients but differed depending on the stage of the retroviral infection. Electroneuromyography defined the type of the palsy, principally due to axonotmesis in 4 patients (including the bilateral one) and principally to neurapraxia in 3 patients. The outcome was good in most cases. The physiopathology remains undetermined

TNF-alpha and psychologically stressful events in healthy subjects: potential relevance for multiple sclerosis relapse

The authors conducted a prospective and descriptive pilot study in 14 healthy medical students, investigating whether a psychologically stressful event (final examination) may modify serum tumor necrosis factor alpha (TNF-alpha) levels. There was a dramatic and sustained decrease of phytohemagglutinin (PHA)-induced TNF-alpha several weeks before and the day of the examination, followed by a significant increase of TNF-alpha starting the next day. Examination-induced stress was confirmed by both elevated urinary cortisol concentration and significant increase in stress scale scores. Extending these results to patients suffering from multiple sclerosis (MS) leads to the hypothesis that psychological stress may influence the course of MS by substantially altering TNF-alpha levels, and suggests the need for further studies in MS patients exposed to stressful conditions

Interferon-beta induces brain-derived neurotrophic factor in peripheral blood mononuclear cells of multiple sclerosis patients

Interferon-beta (IFN-beta) achieves its beneficial effect on multiple sclerosis (MS) via anti-inflammatory properties. In this study, we assessed the expression of the brain-derived neurotrophic factor (BDNF) in peripheral blood mononuclear cells (PBMC) from relapsing-remitting multiple sclerosis (RRMS) patients treated or not with IFN-beta. Intracellular BDNF was measured by Western blot and ELISA and compared with serum BDNF. We found higher levels of BDNF in PBMC of IFN-beta-treated versus non-treated patients, whereas serum levels of BDNF were similar. We hypothesize that the increased intracellular BDNF secondary to IFN-beta is not released in the periphery. This release is probably not tissue specific but in MS patients, BDNF could be specifically delivered by PBMC at the site of re-activation, i.e. within the central nervous system

Illustrating the relevance of updated diagnostic criteria for sporadic Creutzfeldt-Jakob disease: a teaching neurocase

A 75-year-old woman with unremarkable medical history, consulted for a 5-month history of involuntary shaking of left upper limb. Clinical examination revealed polyminimyoclonus of the upper limbs with cogwheel-like rigidity, hyperreflexia, bradykinesia, inconstant spastic-like rigidity in the lower limbs and a stiff and cautious gait. These symptoms, together with the memory impairment found on neuropsychological assessment yielded suspicion for a subacute encephalopathy probably due to a non-conventional infectious agent. There was no 14-3-3 protein found in the cerebrospinal fluid and no periodic sharp wave complexes on EEG. These findings made the diagnosis of Creutzfeldt-Jakob disease (CJD) rather unlikely according to the current WHO diagnostic criteria. However, typical isolated cortical hyperintensity of right temporal, parietal and occipital lobes on MRI suggested a probable CJD and prompted cerebral biopsy which confirmed the diagnosis. This article emphasises the need to update the current WHO criteria by including radiological findings

Increasing the diagnostic value of evoked potentials in multiple sclerosis by quantitative topographic analysis of multichannel recordings

SUMMARY: This study presents a method to record and analyze multichannel visual-evoked potential (VEP) and somatosensory-evoked potential (SEP) in an objective, automatic, and quantitative manner. The intention of this study was to assess their diagnostic value in multiple sclerosis (MS). A 256-channel VEP and SEP were recorded in 44 healthy subjects, 26 patients with MS, and 20 patients with other neurologic diseases. Topographic pattern recognition methods were applied and a normative database was established. Z-score statistics allowed identifying the number of subjects with significant abnormal values in each group. These values were compared with conventional single-channel waveform analysis. The diagnostic value of the new measures for MS reached a sensitivity of 72% and a specificity of 100% for the VEP, which was significantly higher than the conventional analysis. For the SEP, the specificity was also high (93%) but the sensitivity remained low as in the conventional analysis (30%). The quantitative topographic analysis of multichannel VEP revealed high-diagnostic sensitivity and specificity for MS. Moreover, the method reliably identified the most dominant VEP and SEP components in the healthy subject group. The results indicate that objective topographic analysis of multichannel recordings increase the value of VEP as surrogate marker for MS

Autoanticorps en neurologie : implications cliniques

Autoantibodies are defined as antibodies directed against self antigens, i.e., against a normal antigenic endogenous tissue constituent. They can be the immediate cause of the neurological syndrome or be detected as an epiphenomenon of the pathogenic process. Autoantibodies are often considered useful biomarkers for the improvement of diagnostic accuracy, for the staging of disease progression or for the follow up of a biological response to a therapeutic intervention. The purpose of this article is to review the autoantibodies that are available to investigate immune-mediated neurological conditions. The detection of some of these autoantibodies may help the clinician to establish a definite diagnosis which may further facilitate the therapeutic decision

Hypereosinophilia in patients with multiple sclerosis treated with natalizumab

To report asymptomatic hypereosinophilia as a potential side effect in patients treated with natalizumab, an α-4 integrin blocking agent