One gene but different proteins and diseases: the complexity of dystonin and bullous pemphigoid antigen 1.

Since the immunochemical identification of the bullous pemphigoid antigen 230 (BP230) as one of the major target autoantigens of bullous pemphigoid (BP) in 1981, our understanding of this protein has significantly increased. Cloning of its gene, development and characterization of animal models with engineered gene mutations or spontaneous mouse mutations have revealed an unexpected complexity of the gene encoding BP230. The latter, now called dystonin (DST), is composed of at least 100 exons and gives rise to three major isoforms, an epithelial, a neuronal and a muscular isoform, named BPAG1e (corresponding to the original BP230), BPAG1a and BPAG1b, respectively.

Dual-task assessment in natalizumab-treated multiple sclerosis patients.

Background: To study the 1-year evolution of quantitative dual-task gait parameters in comparison with single-task gait parameters and detailed neuropsychological assessment in patients with multiple sclerosis (MS) treated with natalizumab.

Methods: Walking speed, stride length and stride time during a dual task (walking while forward counting, backward counting, semantic fluency, and phonemic fluency), a single walking task, and a detailed neuropsychological assessment were prospectively measured and assessed twice at the 1-year interval in 9 consecutive patients with MS treated with natalizumab.

Results: Dual-task-related gait changes (walking speed, stride length and stride time while performing semantic fluency and walking speed, and stride time while performing phonemic fluency) showed a significant improvement after 1 year of treatment with natalizumab.

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.

Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease.

Background: The envelope protein from multiple sclerosis (MS) associated retroviral element (MSRV), a member of the Human Endogenous Retroviral family 'W' (HERV-W), induces dysimmunity and inflammation.

Objective: The objective of this study was to confirm and specify the association between HERV-W/MSRV envelope (Env) expression and MS.

Methods: 103 MS, 199 healthy controls (HC) and controls with other neurological diseases (28), chronic infections (30) or autoimmunity (30) were analysed with an immunoassay detecting Env in serum.

Adapted timed up and go: a rapid clinical test to assess gait and cognition in multiple sclerosis.

Background/aims: To measure the Timed Up and Go (TUG), imagined TUG (iTUG), and the difference of time between these two tests (delta time) in 20 patients with relapsing-remitting multiple sclerosis (RRMS) and 20 healthy age-matched controls and to examine whether an association with cognitive functions, motor impairment, and behavioral changes can be determined.

Methods: The mean ± SD of TUG, iTUG and delta time were used as outcomes. Spatiotemporal gait parameters were recorded by a 12-camera optoelectronic system during straight walking at usual self-selected speed.

Hypereosinophilia in patients with multiple sclerosis treated with natalizumab.

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

Methods: A case series of 3 patients treated with natalizumab for relapsing-remitting multiple sclerosis including functional and phenotypic characterization of their peripheral blood lymphocytes and eosinophils is presented.

Results: Marked peripheral blood eosinophilia with more than 2,000 cells/mm(3) emerged in all 3 patients after the fourth natalizumab infusion and was asymptomatic.

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).

Magnetic resonance imaging in multiple sclerosis.

Objectives: multiple sclerosis (MS) is an inflammatory disease of unknown origin affecting the central nervous system. Magnetic resonance imaging (MRI) plays an increasingly important role in its diagnosis and further monitoring of disease progress.

Methods: the typical MRI appearance of MS on conventional MRI sequences and current diagnostic criteria for MS are discussed.

Hepatocyte growth factor inhibits CNS autoimmunity by inducing tolerogenic dendritic cells and CD25+Foxp3+ regulatory T cells.

Immune-mediated diseases of the CNS, such as multiple sclerosis and its animal model, experimental autoimmune encephalitis (EAE), are characterized by the activation of antigen-presenting cells and the infiltration of autoreactive lymphocytes within the CNS, leading to demyelination, axonal damage, and neurological deficits. Hepatocyte growth factor (HGF) is a pleiotropic factor known for both neuronal and oligodendrocytic protective properties. Here, we assess the effect of a selective overexpression of HGF by neurons in the CNS of C57BL/6 mice carrying an HGF transgene (HGF-Tg mice).

[Inflammatory neuropathies and multineuritis].

Inflammatory neuropathies include those neuropathies in which the diagnosis, outcome and type of treatment are badly known, the reason of this review. They are expressed as diffuse (such as CIDP and ganglionopathies), multifocal (vasculitic neuropathy) or focal (MMN; plexopathies; immune reconstitution inflammatory syndrome). These forms of neuropathies are important to be known because the beneficial therapeutic possibilities of immunosuppression.

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

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.

[Autoantibodies in neurological diseases: clinical implications].

Autoantibodies are defined as antibodies directed against self antigens, i.e., against a normal antigenic endogenous tissue constituent.

[Multiple sclerosis and pregnancy].

Mulltiple sclerosis and pregnancy Multiple sclerosis (MS) is diagnosed between the second and fourth decade. More than 2/3 of patients are women and are often in childbearing age. We may ask two main questions: Which implication of pregnancy on the evolution of MS has to be considered ? Which influence of MS on the pregnancy is expected? In other words could the pregnancy worsen MS and could MS represent specific risks for the pregnancy?

Glatiramer acetate increases IL-1 receptor antagonist but decreases T cell-induced IL-1beta in human monocytes and multiple sclerosis.

Mechanisms of action as well as cellular targets of glatiramer acetate (GA) in multiple sclerosis (MS) are still not entirely understood. IL-1beta is present in CNS-infiltrating macrophages and microglial cells and is an important mediator of inflammation in experimental autoimmune encephalitis (EAE), the MS animal model. A natural inhibitor of IL-1beta, the secreted form of IL-1 receptor antagonist (sIL-1Ra) improves EAE disease course.

[The painful multiple sclerosis].

"What are you doing today? I'm suffering." So expressed himself Alphonse Daudet the French writer. The pain he had gave him the spirit when he wrote a text entitled "La Doulou" a word from the South of France meaning "The pain".

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.

Integrating an evidence-based assessment of benefit and risk in disease-modifying treatment of multiple sclerosis.

Background: As results from an increasing number of clinical trials with disease-modifying drugs (DMDs) in multiple sclerosis (MS) become available, the challenge for the treating neurologist is how to decide on the appropriate therapy for an individual patient.

Objective: An International Working Group for Treatment Optimization in MS met to consider how the principles of evidence-based medicine (EBM) should be used to assess the current best evidence regarding the treatment of MS. This report summarizes the outcome from the workshop at which this topic was addressed.

[Neuromyelitis optica/Devic's syndrome: new perspectives].

Neuromyelitis optica (NMO) or Devic's syndrome is a severe demyelinating disease of the central nervous system involving preferentially the optic nerves and the spinal cord. Until recently, NMO was described as an atypical multiple sclerosis IMS), characterized by an unusual clinical presentation, a severe relapsing progression, and a poor response to usual MS treatments. The recent discovery of the so-called NMO-IgG, a highly NMO-specific antibody directed against the blood brain barrier and the aquaporine-4, allowed to refine diagnostic criteria and to classify this disease as an autoimmune channelopathy.

Inhibition of naive Th1 CD4+ T cells by glatiramer acetate in multiple sclerosis.

We investigated whether glatiramer acetate (GA) treatment may affect Th1 differentiation at various T-cell maturation stages. Specifically, we analyzed the effect of in vivo GA treatment on intracellular synthesis of IL-2 and TNF-alpha by naive, memory and effector CD4(+) and CD8(+) T cells by five-colour flow cytometry. Our data indicate that GA treatment downregulates/normalizes an accelerated Th1 differentiation of CD4(+) T cells in RRMS patients at all stages of T-cell maturation.

Cerebrospinal fluid anti-SSA autoantibodies in primary Sjogren's syndrome with central nervous system involvement.

Background: Central nervous system involvement in primary Sjogren's syndrome is a matter of controversy, and its diagnosis remains difficult.

Methods: We report 3 patients with primary Sjogren's syndrome and central nervous system involvement in whom we assessed intrathecal immunoglobulin G synthesis and the presence of cerebrospinal fluid anti-SSA and anti-SSB autoantibodies.

Results: We found intrathecal immunoglobulin G synthesis and presence of cerebrospinal fluid anti-SSA autoantibodies in all patients, with demonstration for the first time of specific anti-SSA autoantibody intrathecal synthesis in 2 patients.

[Immunity and neurodegeneration: new concepts in multiple sclerosis].

Multiple sclerosis is an autoimmune demyelinating disease of the central nervous system that leads to a progressive deterioration of the neurological functions. The concept of primary myelin and oligodendrocyte damage with axon sparing (axon-myelin dissociation) has been recently reconsidered with the demonstration that neuro-axonal lesions are an early phenomenon, linked to the inflammatory process, observed outside demyelinated areas, and correlated with the progression of the disease. Neurodegeneration in MS, long considered as a late process following recurrent episodes of demyelination, is now accepted as an early and major trigger of MS pathogenesis on which research should focus in the

A recommended treatment algorithm in relapsing multiple sclerosis: report of an international consensus meeting.

An International Working Group for Treatment Optimization in MS met to recommend evidence-based therapeutic options for the management of suboptimal responses or intolerable side-effects in patients treated with disease-modifying drugs (DMDs) for multiple sclerosis (MS). Several DMDs are now available for the treatment of MS that have been shown to alter the clinical course of the disease by decreasing disease activity and delaying the progression of disability. Nevertheless, many patients continue to experience disease activity whilst on treatment, and recommendations have been made on how the success of therapy in an individual patient can be assessed.

Mechanisms of action for treatments in multiple sclerosis: Does a heterogeneous disease demand a multi-targeted therapeutic approach?

The etiology of multiple sclerosis (MS) is incompletely understood, and evidence suggests there may be more than one underlying cause in this disorder. Furthermore, this complex and heterogeneous autoimmune disease shows a high degree of clinical variability between patients. Therefore, in the absence of a single therapeutic target for MS, it is difficult to apply conventional drug design strategies in the search for new treatments.

[Immunomodulatory/suppressive treatments in neurology].

Immunomodulatory/suppressive treatments are frequently used in neurological disorders affecting the central and peripheral nervous system. Demyelinating disorders are a good example of a wide application of the various types of existing therapies. Although these therapies are still mostly not disease specific, their combination with more targeted molecules appears most relevant for diseases with multiple pathogenic mechanisms.