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Optic neuritis usually presents with rapid and gradual loss of vision that is either complete or incomplete, and typically associated with retro-orbital pain. To our knowledge there have been no documented reports of optic neuritis presenting with multiple episodes of amaurosis fugax, the sudden and transient loss of vision lasting seconds to minutes. We report here the case of a young woman with a possible diagnosis of demyelinating left optic neuritis that presented solely with multiple episodes of brief and transient sudden loss of vision. Ophthalmological exams were normal between episodes of vision loss. The patient’s magnetic resonance imaging of the brain showed a subtle enhancement of the left optic nerve along with multiple periventricular lesions, highly suggestive of a demyelinating disease. The frequent episodes of visual loss resolved completely with high dose parenteral steroids. Neurologists and other clinicians should be aware of this unusual presentation of optic neuritis as treatment modalities differ greatly from other causes of amaurosis fugax. [ABSTRACT FROM AUTHOR]

Context: DNA beta-amyloid(1-42) (Abeta42) trimer immunization was developed to produce specific T helper 2 cell (T(H)2)-type antibodies to provide an effective and safe therapy for Alzheimer disease (AD) by reducing elevated levels of Abeta42 peptide that occur in the brain of patients with AD.Objective: To compare the immune response in wild-type mice after immunization with DNA Abeta42 trimer and Abeta42 peptide.Design and Intervention: Wild-type mice received either 4 microg of DNA Abeta42 trimer immunization administered with gene gun (n = 8) or intraperitoneal injection of 100 microg of human Abeta42 peptide with the adjuvant Quil A (n = 8). Titers, epitope mapping, and isotypes of the Abeta42-specific antibodies were analyzed.Main Outcome Measures: Antibody titers, mapping of binding sites (epitopes), isotype profiles of the Abeta42-specific antibodies, and T-cell activation.Results: DNA Abeta42 trimer immunization resulted in antibody titers with a mean of 15 microg per milliliter of plasma. The isotype profile of the antibodies differed markedly. A predominant IgG1 antibody response was found in the DNA-immunized mice, indicating a T(H)2 type of immune response (IgG1/IgG2a ratio of 10). The peptide-immunized mice showed a mixed T(H)1/T(H)2 immune response (IgG1/IgG2a ratio of 1) (P < .001). No increased T-cell proliferation was observed in the DNA-immunized mice (P = .03).Conclusion: In this preliminary study in a wild-type mouse model, DNA Abeta42 trimer immunization protocol produced a T(H)2 immune response and appeared to have low potential to cause an inflammatory T-cell response. [ABSTRACT FROM AUTHOR]

The article discusses a study which compared the immune response in wild-type mice following vaccination with DNA β-amyloid1-42 (Aβ42) trimer and Aβ42 peptide. The laboratory animals were randomly assigned to receive either 4 microgram of DNA Aβ42 trimer delivered with gene gun or intraperitoneal injection of 100 microgram of human Aβ42 peptide with the adjuvant Quil A. Main outcome measures determined in the study included antibody titers, mapping of binding sites, isotype profiles of the A&beta42;-specific antibodies and T-cell activation. Details of the research findings are presented.

The objective of this study was to evaluate immune cytokine expression in cerebrospinal fluid (CSF) of patients with human immunodeficiency virus-1 (HIV-1)–associated dementia (HAD) using a novel cytokine array assay. HIV-1 induces a condition resembling classical subcortical dementia, known as HAD. The immune mechanisms contributing to HAD have not been elucidated. Cytokine expression in CSF was determined by solid-phase protein array in 33 neurologically asymptomatic HIV-positive male patients and were compared to levels in non-HIV controls and patients with HAD. Neurological examinations and lumbar and venous punctures were conducted in all patients and controls. Interleukin (IL)-1, IL-4, and IL-10, were up-regulated in all treated acquired immunodeficiency syndrome (AIDS) patients independent of neurological status compared to controls. In contrast, interferon gamma (IFN-γ), IL-1α, IL-15, and tumor necrosis factor alpha (TNF-α) were highly expressed in patients with HAD compared to undemented HIV-positive patients. These results show that solid-phase protein array can detect immunological changes in patients infected with HIV. Cytokine expression levels differ in different disease stages and in patients on different treatment paradigms. Pending further validation on a larger number of patients, this method may be a useful tool in CSF diagnostics and the longitudinal evaluation of patient with HAD. [ABSTRACT FROM AUTHOR]

Background: Rituximab is a recombinant chimeric monoclonal antibody against CD20, a molecule expressed on cells of the B-cell lineage. A phase 2 clinical trial recently provided strong evidence of the beneficial effects of rituximab in patients with relapsing-remitting multiple sclerosis. We and other investigators previously demonstrated that rituximab therapy depletes B lymphocytes from peripheral blood and cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis. Objective: To determine the effect of rituximab on the presence of B cells in cerebral perivascular spaces. Design, Setting, and Patients: Case report from a tertiary academic medical center. Cerebral white matter from autopsy material of a patient with gastrointestinal mantle-cell lymphoma who developed progressive multifocal leukoencephalopathy following rituximab therapy was evaluated by immunohistochemistry. Locationmatched brain sections of patients with multiple sclerosis not treated with rituximab, patients without central nervous system disease, and patients with progressive multifocal leukoencephalopathy not associated with rituximab were used as controls. Main Outcome Measures: Assessment of the number of B lymphocytes in cerebral perivascular spaces in a patient with gastrointestinal mantle-cell lymphoma treated with rituximab, patients with multiple sclerosis, patients with progressive multifocal leukoencephalopathy not associated with rituximab, and healthy control subjects. Results:Wewere unable to detect B cells in cerebral perivascular spaces of the patient who developed progressive multifocal leukoencephalopathy following rituximab therapy 8 months after her last dose. In contrast, B cells were detectable in all control brain tissues. Conclusions: To our knowledge, this is the first report to show B-lymphocyte depletion from brain tissue following rituximab therapy. A reduction in B-cell numbers may be an important contributing factor in the pathogenesis of central nervous system infections. [ABSTRACT FROM AUTHOR]

We report the first case of primary non-Hodgkin lymphoma of the central nervous system in a 69-year-old patient with chronic inflammatory demyelinating polyneuropathy (CIDP) on long-termimmunosuppression. CIDPwas diagnosed 4 years earlier and treated with plasma exchange, corticosteroids, azathioprine andmycophenolate mofetil. The patient developed an organic brain syndrome and cerebralMRIrevealed multiple enhancingT1 lesions in the periventricular parenchyma. A stereotactic biopsy was not diagnostic, but Epstein-Barr virus (EBV) was detected in the cerebrospinal fluid. After a fulminant course of an illness resembling an encephalitis the patient died. Postmortem analysis confirmed the diagnosis of EBVassociated diffuse large B cell lymphoma. This case illustrates the risks of life-threatening infections associated with continuous immunosuppression, and emphasizes the need for an extensive diagnostic work-up in patients who present with signs and symptoms of an unexpected encephalopathy. [ABSTRACT FROM AUTHOR]

Background: Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS). Minocycline, a potent inhibitor of matrix metalloproteinase (MMP)-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG) minocycline liposomes are effective in treating EAE. Findings: Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs), we determined that PEG minocycline-liposome preparations stabilized with CaCl2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNSinfiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number. Conclusions: Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS. [ABSTRACT FROM AUTHOR]

Based on the results of two phase III clinical trials, the humanized recombinant monoclonal antibody natalizumab was approved for the treatment of relapsing forms of multiple sclerosis (MS). Since its initial approval in November 2004, it has been announced that six patients who received natalizumab in the context of clinical studies acquired an infection with the human polyoma virus JC and were diagnosed with progressive multifocal leukoencephalopathy (PML). Two of these individuals had a fatal outcome. Our groups recently showed that natalizumab therapy results in a reduction of CD4+ T cells within the cerebrospinal fluid (CSF) that is ten-fold more pronounced than the reduction in the number of CD8+ T lymphocytes. Interestingly, it appears that the effect of natalizumab on cell numbers in the CSF persists for at least 6 months after cessation of treatment. More recently, we studied the expression of major histocompatibility complex (MHC) I and II, and the number and phenotypes of leukocytes in cerebral perivascular spaces (CPVS). We observed that natalizumab therapy was associated with a significant decrease in the cell surface expression of MHC class II molecules, and the numbers of dendritic cells in CPVS. In addition, no CD4+ T cells were detectable in this compartment. Our observations may explain the differential and prolonged effects of natalizumab therapy on different leukocyte subsets in the central nervous system. They also suggest that natalizumab treatment may result in prolonged immunosuppression in peripheral organs, and the delayed onset of adverse events. [ABSTRACT FROM AUTHOR]

Despite novel immunoactive agents, immunosuppressants still play a considerable role in the treatment of MS, especially in rapidly progressive cases. Given the limited tolerability and potentially severe side effects of most immunosuppressive drugs, identification of patients with a favorable benefit-risk profile is essential. A narrow therapeutic index, with sometimes high interindividual variability in terms of response and side effects may partially be explained by genetic factors affecting different metabolic pathways. Here, we will review practical aspects in the clinical use of immunosuppressants in MS and discuss approaches to individualized treatment schemes, including novel pharmacogenetic strategies. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) represents the prototypic inflammatory autoimmune disorder of the central nervous system and the most common cause of neurological disability in young adults. The mainstays in the immunomodulatory therapy of MS are currently interferon beta and glatiramer acetate, both of which have proven to be clinically and paraclinically effective. Current clinical evidence indicates that treatment should be initiated as early as possible. In this review we summarize available data from clinical studies on clinical efficacy of immunomodulatory drugs for treating patients with multiple sclerosis. [ABSTRACT FROM AUTHOR]

Objective: To extend our studies on the prolonged and differential effect of natalizumab on T lymphocyte numbers in the cerebrospinal fluid, we investigated the number and phenotypes of leukocytes and the expression of major histocompatibility complex (MHC) classes I and II in cerebral perivascular spaces (CPVS). We hypothesized that natalizumab reduces the number of antigen presenting cells in CPVS. Design: A case-control study in which inflammatory cell numbers in the CPVS of cerebral tissue were assessed by immunohistochemical staining. Subjects: A patient with multiple sclerosis (MS) who developed progressive multifocal leukoencephalopathy (PML) during natalizumab therapy. Controls included location-matched cerebral autopsy material of patients without disease of the central nervous system, patients with MS not treated with natalizumab, and patients with PML not associated with natalizumab therapy. Results: The absolute number of CPVSin the patient with MS treated with natalizumab was significantly lower than in the control groups owing to extensive destruction of the tissue architecture. The expression of MHC class II molecules and the number of CD209+ dendritic cells were significantly decreased in the CPVS of the patient with MS treated with natalizumab. No CD4+ T cells were detectable. Conclusions: Our observations may explain the differential and prolonged effects of natalizumab therapy on leukocyte numbers in the cerebrospinal fluid. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic autoimmune disease of the CNS. Currently, six medications are approved for immunmodulatory and immunosuppressive treatment of the relapsing disease course and secondary-progressive MS. In the first part of this review, the pathogenesis of MS and its current treatment options are discussed. During the last decade, our understanding of autoimmunity and the pathogenesis of MS has advanced substantially. This has led to the development of a number of compounds, several of which are currently undergoing clinical testing in phase II and III studies. While current treatment options are only available for parenteral administration, several oral compounds are now in clinical trials, including the immunosuppressive agents cladribine and laquinimod. A novel mode of action has been described for fingolimod, another orally available agent, which inhibits egress of activated lymphocytes from draining lymph nodes. Dimethylfumarate exhibits immunomodulatory as well as immunosuppressive activity when given orally. All of these compounds have successfully shown efficacy, at least in regards to the surrogate marker contrast-enhancing lesions on magnetic resonance imaging. Another class of agents that is highlighted in this review are biological agents, namely monoclonal antibodies (mAb) and recombinant fusion proteins. The humanized mAb daclizumab inhibits T-lymphocyte activation via blockade of the interleukin-2 receptor. Alemtuzumab and rituximab deplete leukocytes and B cells, respectively; the fusion protein atacicept inhibits specific B-cell growth factors resulting in reductions in B-cells and plasma cells. These compounds are currently being tested in phase II and III studies in patients with relapsing MS. The concept of neuro-protection and -regeneration has not advanced to a level where specific compounds have entered clinical testing. However, several agents approved for conditions other than MS are highlighted. Finally, with the advent of these highly potent novel therapies, rare, but potentially serious adverse effects have been noted, namely infections and malignancies. These are critically reviewed and put into perspective. [ABSTRACT FROM AUTHOR]

Six disease-modifying therapies are approved for the treatment of multiple sclerosis: glatiramer acetate, 2 formulations of interferon (IFN) β-1α (one administered by subcutaneous injection and one administered by intramuscular injection), IFNβ-1b, natalizumab, and mitoxantrone. These agents are thought to act primarily by suppressing central nervous system (CNS) inflammation, which may also produce secondary neuroprotective effects. Inflammatory CNS demyelination requires a sequence of tightly controlled immune processes, including antigen presentation to T cells, additional cell-cell contacts between antigen-presenting cells and T cells that are required for full T-cell activation, the migration of T cells through the endothelial lining, and the release of several proinflammatory or anti-inflammatory chemical mediators. IFNβ and glatiramer acetate (GA) interrupt several of these process, resulting in decreased CNS infiltration of lymphocytes and inflammation. GA may also produce neuroprotective effects by modulating the release of neurotrophic factors, chemical mediators that are produced by several cell populations that promote neuronal development and survival. Natalizumab blocks specific cell-surface receptor molecules that are required for lymphocytes to migrate from the circulation to the CNS, producing long-lasting suppression of the infiltration of CD4+ and CD8+ T lymphocytes. Natalizumab may produce a rebound increase in the number of T2 lesions on magnetic resonance imaging after discontinuation. Mitoxantrone is an antineoplastic agent that interferes with DNA replication in rapidly dividing cells, resulting in lymphocyte depletion. It is not known to produce neuroprotective effects. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is the most common human inflammatory, demyelinating and degenerative disorder of the CNS. Based mostly on work in experimental autoimmune encephalomyelitis, CD4+ T cells were long thought to play the crucial role in MS pathogenesis. Only more recently has it been recognized that other effector cell types, including CD8+ T cells, γδ-T cells and B lymphocytes may also have an important role in disease initiation and perpetuation. The expression of soluble inflammatory mediators, including cytokines and free radicals, may be one of the late pathways mediating CNS tissue damage. In addition, in virtually all patients with MS, an oligoclonal banding pattern of antibodies can be detected in the cerebrospinal fluid (CSF). However, the cause of MS still remains unknown. Specifically, no single foreign or self antigen has been identified to account for clinical disease activity or the presence of surrogate disease markers. All approved pharmacotherapies have anti-inflammatory or immunoregulatory properties and work in early stages of the disease. In a recent clinical trial, BHT-3009, a DNA vaccine encoding full-length human myelin basic protein, was tested in patient with MS. BHT-3009 was safe and well tolerated. In addition, immunization with BHT-3009 induced anti-inflammatory antigen-specific immune changes consisting of a marked decrease in T-cell proliferation of IFNγ production and a reduction in titers of myelin-specific autoantibodies in the CSF. This review will discuss these intriguing observations and the overall potential of DNA vaccination in MS. [ABSTRACT FROM AUTHOR]

Currently, six medications are approved by the US FDA for the treatment of relapsing forms of multiple sclerosis (MS). In contrast, no pharmacological agent has proved to be effective in patients with secondary-progressive MS without relapses, or in patients with primary-progressive MS. One of the principal issues concerning an optimal pharmacotherapy for relapsing forms of MS is the optimal time of treatment initiation. There is now an almost universal consensus among MS experts that many patients will benefit from early therapy. However, several formidable challenges exist in identifying individuals who will benefit versus those who will do well without intervention. How do we define early MS and what clinical and paraclinical markers may be useful in defining the timing and nature of therapy? Do patients with a benign form of MS require therapy or are they exposed unnecessarily to adverse effects of our currently available medications? How do we identify disease progression and treatment failures? This review discusses these issues and outlines the evidence for application of 'early' treatment in patients with relapsing forms of MS. [ABSTRACT FROM AUTHOR]

atalizumab (Tysabri) is an effective therapy for multiple sclerosis. Recently, 3 patients who were treated with natalizumab developed progressive multifocal leukoencephalopathy (PML), an opportunistic infection of the brain with the polyomavirus JC. The pathogenesis of natalizumab-associated PML may be different from that of PML not associated with the drug. We reviewed biologically feasible interventions for patients diagnosed as having PML or other infections while receiving natalizumab therapy. Existing interventions include antiviral treatment, immunomodulatory therapies, hematopoietic growth factors, plasma exchange, intravenous immunoglobulins, and leukapheresis and autotransfusion of leukocytes. In addition, we examined the feasibility of experimental therapies, including small interfering RNA, the in vivo use of antiserum, and recombinant natalizumab-blocking molecules. There is only circumstantial evidence that any of the proposed treatments will benefit patients with multiple sclerosis treated with natalizumab who may develop PML. In addition, the expected incidence of PML in this patient population will likely be too low to test any of the proposed interventions in a controlled manner. Because it is currently impossible to identify patients at risk, and thus to prevent PML as a consequence of natalizumab therapy, it is important that neurologists be aware of possible therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Damage of the blood-brain barrier and invasion of immunocompetent cells into the central nervous system represent key events in the immunopathogenesis of multiple sclerosis. Mitoxantrone hydrochloride reduces progression of disability and clinical exacerbations in patients with multiple sclerosis. Its precise mode of action is unclear. Objective: To investigate the effects of mitoxantrone on the migratory capacity of immunocompetent cells ex vivo and in vitro. Design: Case-control study. Setting: Department of Neurology, Heinrich Heine University, Düsseldorf, Germany. Participants: Peripheral blood mononuclear cells (PBMCs) were obtained from 11 patients with multiple sclerosis before and after intravenous mitoxantrone treatment; PBMCs from 5 healthy control donors were treated with mitoxantrone in vitro. Main Outcome Measures: The migratory capacity was studied in an in vitro Boyden chamber assay; cells and their rates of migration were analyzed by light microscopy and flow cytometry. To determine the specificity of our findings, PBMCs were treated with perfosfamide in vitro. Results: Mitoxantrone decreased the migratory capacity of CD14+ monocytes and (to a lesser degree) of CD4+ and CD8+ T lymphocytes. These observations were confirmed when control PBMCs were treated with an equivalent dose of mitoxantrone in vitro. Similar effects were seen when PBMCs were preincubated with perfosfamide. The inhibitory effects of mitoxantrone on the migratory capacity of PBMCs were mediated by reduced matrix metalloproteinase 9 activity, as demonstrated by zymography, polymerase chain reaction, and inhibitory studies. Conclusion: Mitoxantrone may inhibit the migration of inflammatory cells into and within the central nervous system. [ABSTRACT FROM AUTHOR]

Background: Treatment with natalizumab, a monoclonal antibody against the adhesion molecule very late activation antigen 4, an α4β1 integrin, was recently associated with the development of progressive multifocal leukoencephalopathy, a demyelinating disorder of the central nervous system caused by JC virus infection Objective: To test the effect of natalizumab treatment on the CD4+/CD8+ T-cell ratios in cerebrospinal fluid (CSF) and peripheral blood. Design: Prospective longitudinal study. Setting: Academic and private multiple sclerosis centers. Patients: Patients with multiple sclerosis (MS) treated with natalizumab, untreated patients with MS, patients with other neurologic diseases, and human immunodeficiency virus-infected patients. Main Outcome Measures: CD4+ and CD8+ T cells were enumerated in CSF and peripheral blood. The mean fluorescence intensity of unbound a 4 integrin on peripheral blood CD4+ and CD8+ T cells was analyzed before and after natalizumab therapy. Results: Natalizumab therapy decreased the CSF CD4+/CD8+ ratio of patients with MS to levels similar to those of human immunodeficiency virus-infected patients. CD4+/CD8+ ratios in peripheral blood in patients with MS progressively decreased with the number of natalizumab doses, but they remained within normal limits. Six months after the cessation of natalizumab therapy, CSF CD4+/CD8+ ratios normalized. The expression of unbound a 4 integrin on peripheral blood T cells decreases with natalizumab therapy and was significantly lower on CD4+ vs CD8+ T cells. Conclusions: Natalizumab treatment alters the CSF CD4+/CD8+ ratio. Lower expression of unbound α4 integrin on CD4+ T cells is one possible mechanism. These results may have implications for the observation that some natalizumab-treated patients with MS developed progressive multifocal leukoencephalopathy. [ABSTRACT FROM AUTHOR]

Summary: Interferon beta was the first therapy to be approved for the treatment of relapsing-remitting multiple sclerosis (MS) more than 10 years ago. Interferon beta reduces relapse rates and disease burden and activity, and it may have beneficial effects on the progression of long-term disease disability. The occurrence of neutralising interferon-beta antibodies has been postulated as a possible cause of the failure of interferon beta in some patients with MS. Here we discuss the basic mechanisms that may account for the generation of an interferon-beta antibody response and its biological implications. We review the evidence for neutralising antibodies as a consequence of interferon-beta treatment, and discuss the implications for the treatment of MS. Strategies to assess and manage the long-term impact of neutralising antibodies will be outlined. [Copyright &y& Elsevier]

Abstract: Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and are widely prescribed as cholesterol-lowering agents. They are promising candidates for future treatment in multiple sclerosis (MS) as they have been shown to exhibit immunomodulatory effects. Recent reports have demonstrated that statins are effective in preventing and reversing chronic and relapsing experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Furthermore, in vitro experiments with human immune cells have documented an immunomodulatory mode of action of statins comparable to that of interferon (IFN)-β. An open label clinical trial assessing simvastatin in MS revealed a significant decrease in the number and volume of new MRI lesions and a favourable safety profile. This article reviews data thus far present on the putative mechanisms of action of statins in the immunopathogenesis of MS. Furthermore, the role of statins as potential pharmacotherapy for MS is discussed in the context of the mechanisms of approved immunotherapies in MS, namely IFN-β and glatiramer acetate (GA). [Copyright &y& Elsevier]

'Statins' are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors-oral cholesterol-lowering drugs that are used to treat hypercholesterolaemia. It is widely accepted that statins have anti-inflammatory effects that are independent of their ability to lower cholesterol. Animal studies and observational clinical studies have indicated that statins might also be effective in treating certain neurological diseases-in particular, multiple sclerosis, Alzheimer's disease and ischaemic stroke. At present, however, results from ongoing prospective, randomized clinical trials are not available. [ABSTRACT FROM AUTHOR]

3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ( ie, statins) are oral cholesterol-lowering drugs. Statins are well tolerated and have an excellent safety record. These agents competitively inhibit HMG CoA reductase, which is the enzyme that catalyzes the conversion of HMG CoA to L-mevalonate. Although L-mevalonate is a key intermediate in cholesterol synthesis, several of its metabolites are involved in post-translational modification of specific proteins involved in cell proliferation and differentiation. Thus, independent of their cholesterol-reducing properties, statins have important pleiotropic biologic effects. Recent reports indicate that statins have anti-inflammatory and neuroprotective properties. Whether statins will be of clinical benefit for patients with multiple sclerosis and other neurodegenerative diseases of the central nervous system will only be known after they are evaluated in prospective randomized clinical trials. [ABSTRACT FROM AUTHOR]

In this article, the author discusses association of antileucine- rich glioma-inactivated1 (anti-LGI1) encephalitis with the major histocompatibility complex (MHC) II haplotype human leukocyte antigen (HLA). Topics discussed include observation of human leukocyte antigen (HLA) in several human immunemediated disorders; expression of MHC II on all nucleated cells; and therapeutic interventions in patients with anti-LGI1 encephalitis.

The FDA approvals of siponimod and cladribine for secondary progressive multiple sclerosis raise questions about the diagnostic criteria for multiple sclerosis phenotypes and their applicability to clinical trials. A simpler classification for the disease could be the answer. [ABSTRACT FROM AUTHOR]

Objective: To describe 2 patients with relapsingremitting multiple sclerosis (RRMS) receiving longterm treatment with the monoclonal antibody rituximab. The clinical and paraclinical efficacy of rituximab was demonstrated recently in a phase 2 clinical trial in patients with RRMS. Design: Case series. Setting: Tertiary care university medical center. Patients: Two young patients with highly active RRMS in whom standard therapy had failed before receiving rituximab for up to 48 months. Main Outcome Measures: Relapse rate, clinical disability, and results of magnetic resonance imaging. Results: Both patients tolerated rituximab treatment well and have been clinically stable throughout the study period. Conclusion: Long-term therapy with rituximab appears safe and effective in some patients with RRMS. Our observation should be confirmed in controlled longterm trials. [ABSTRACT FROM AUTHOR]

Abstract: Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS). Natalizumab (®Tysabri) is a humanized recombinant monoclonal antibody that binds to the alpha (α)4 chain of the α4 beta (β)1 integrin (very late activation antigen 4; VLA-4), and α4β7 integrin. Recently, two patients with MS and one patient with Crohn’s disease who were treated with natalizumab in the setting of clinical trials developed progressive multifocal leukoencephalopathy (PML), an opportunistic infection of the brain with the polyoma virus JC. We recently showed that natalizumab decreases the numbers of CD4+ and CD8+ T lymphocytes, CD19+ B cells, and CD138+ plasma cells in the cerebrospinal fluid (CSF) of patients with MS on natalizumab therapy. In addition, we demonstrated that the cell numbers in CSF remained unchanged even 6 months after cessation of natalizumab treatment. [Copyright &y& Elsevier]

The article discusses a recent study published in "The Lancet Neurology," which reported negative results of combination therapy in multiple sclerosis (MS). The study has demonstrated that simvastatin as an add-on therapy has no beneficial clinical or paraclinical effect on the treatment of MS. It presents an overview of the simvastatin as add-on therapy to interferon (IFN) β-1ba for relapsing-remitting MS (RRMS) (SIMCOMBIN) trial.

A letter to the editor is presented which discusses a case study of a 53-year-old man with vestibular hypofunction, and Chinese restaurant syndrome caused by the ingestion of monosodium glutamate.