Evidence for an Intrathecal Immunoglobulin Synthesis by Kappa Free Light Chains in Neurological Patients with an Isolated Band in Isoelectric Focusing.

The gold standard for detecting intrathecal immunoglobulin synthesis is the determination of the oligoclonal band (OCB) in the cerebrospinal fluid (CSF) using isoelectric focusing (IEF). Controversy still exists regarding the significance of an isolated band in the CSF. A highly promising alternative method for the assessment of intrathecal inflammation is the quantification of kappa free light chains (k-FLC).

Decreased Cerebrospinal Fluid Antioxidative Capacity Is Related to Disease Severity and Progression in Early Multiple Sclerosis.

Oxidative stress-induced neuronal damage in multiple sclerosis (MS) results from an imbalance between toxic free radicals and counteracting antioxidants, i.e., antioxidative capacity (AOC).

Serum netrin-1 in relation to gadolinium-enhanced magnetic resonance imaging in early multiple sclerosis.

Background: Netrin-1, a secreted laminin-related protein, is known to regulate not only axonal guidance and neuronal cell migration, but also blood-brain barrier integrity and inflammation. Two preliminary studies reported altered serum netrin-1 levels in multiple sclerosis; however, associations with longitudinal clinical and magnetic resonance imaging activity have not been investigated.

Objectives: We aimed to assess serum netrin-1 in multiple sclerosis and controls with respect to disease activity and its temporal dynamics.

Prognostic value of free light chains lambda and kappa in early multiple sclerosis.

Background: Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) have been suggested as quantitative alternative to oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS). However, little is known on their role in predicting clinical and paraclinical disease progression, particularly in early stages.

Objective: To assess the prognostic value of FLC in OCB-positive patients with clinically isolated syndrome (CIS) suggestive of MS and early MS.

Cerebrospinal fluid lipocalin 2 in patients with clinically isolated syndromes and early multiple sclerosis.

Background: Lipocalin 2 (LCN2) may be involved in the immunopathogenesis of multiple sclerosis (MS) and might further impact on iron homoeostasis. Brain iron accumulates in MS; however, the association to iron-related proteins is still unsolved.

Objective: To investigate cerebrospinal fluid (CSF) and serum LCN2, transferrin (Trf) and ferritin in early MS in relation to disease evolution and longitudinal brain iron accumulation.

Laboratory diagnosis of Lyme neuroborreliosis is influenced by the test used: comparison of two ELISAs, immunoblot and CXCL13 testing.

Purpose: To compare Borrelia-specific intrathecal antibodies by two different ELISAs, an immunoblot (IB) and CXCL13.

Methods: Twenty-seven adults and 23 children with clinical symptoms compatible with NB were tested for Borrelia-specific intrathecal antibodies by flagellum ELISA-AI (flELISA), a recombinant ELISA-AI (rELISA) and by IB. Patients were classified according to the European Federation of Neurological Societies (EFNS) criteria as definite NB, possible NB, or non-NB.

Cerebrospinal fluid transferrin levels are reduced in patients with early multiple sclerosis.

Background: Previous magnetic resonance imaging (MRI) studies have demonstrated increased iron deposition in the basal ganglia of multiple sclerosis (MS) patients. However, it is not clear whether these alterations are associated with changes of iron metabolism in body fluids.

Objectives: The purpose of this study was to investigate if iron metabolism markers in cerebrospinal fluid (CSF) and serum of clinically isolated syndrome (CIS) and MS patients differ from controls and how they relate to clinical and imaging parameters.

CSF neurofilament and N-acetylaspartate related brain changes in clinically isolated syndrome.

Background: Axonal damage is considered a major cause of disability in multiple sclerosis (MS) and may start early in the disease. Specific biomarkers for this process are of great interest.

Objective: To study if cerebrospinal fluid (CSF) biomarkers for axonal damage reflect and predict disease progression already in the earliest stages of the disease, that is, in clinically isolated syndrome (CIS).

[Treatment options in painful diabetic polyneuropathy].

Distal symmetrical polyneuropathy is the most frequent manifestation of diabetic neuropathy and crucially contributes to the development of diabetic foot and subsequent amputation in 70 to 80% of all cases. In 10 to 15% of affected patients considerable pain is present, in particular in early diabetic polyneuropathy. This review summarizes evidence based data on prevention, neuroregenerative, and symptomatic treatment of painful diabetic polyneuropathy.

IVIG therapy in neurological disorders of childhood.

There is growing evidence that intravenous immunoglobulins (IVIG) are effective in some neuroimmunological disorders of childhood. This short review summarizes the evidence-based indications and recommendations of IVIG therapy in these disorders. Despite considerable efforts to define the role and mechanisms of IVIG, more clinical studies are needed to further explore the therapeutic potential of IVIG in childhood diseases of the nervous system and muscle.

Multiple sclerosis: Mitoxantrone promotes differential effects on immunocompetent cells in vitro.

Mitoxantrone is an anti-neoplastic anthracenedione derivative that, based on its immunosuppressive properties, is approved for the treatment of severe forms of relapsing-remitting or secondary progressive multiple sclerosis (MS). Whether the beneficial clinical effects of mitoxantrone in MS are due to a broad immunosuppression, or whether there is a specific mechanism of action remains unknown. Peripheral blood mononuclear cells (PBMCs) from untreated or interferon-beta-treated patients with MS or from healthy donors were stimulated in the presence or absence of mitoxantrone.

Glomerular permeability is altered by loss of P0, a myelin protein expressed in glomerular epithelial cells.

The myelin protein 0 (MPZ or P0) is a transmembrane glycoprotein that represents the most abundant myelin component. Mutations in the P0 gene are associated with one form of autosomal dominant demyelinating peripheral neuropathy, Charcot-Marie-Tooth disease type 1B (CMT1B). Because CMT1 may be associated with renal involvement, mostly focal segmental glomerulosclerosis, we hypothesized that P0 could be expressed in the kidney.

Putative mechanisms of action of statins in multiple sclerosis--comparison to interferon-beta and glatiramer acetate.

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.

Different effects of simvastatin and interferon beta on the proteolytic activity of matrix metalloproteinases.

Background: Interferon beta and statins are known to exert immunomodulatory actions by inhibiting gene transcription and translation of various proinflammatory molecules. Although interferon beta represents a mainstay in therapy for multiple sclerosis (MS), statins are considered a potential new approach in treating MS.

Objective: To investigate the effect of interferon beta and statins on the posttranslational activity of matrix metalloproteinases (MMPs) released from mononuclear cells in vitro that were obtained from patients with MS and healthy donors.

Tau protein and 14-3-3 are elevated in the cerebrospinal fluid of patients with multiple sclerosis and correlate with intrathecal synthesis of IgG.

Recently it has been shown that axonal damage occurs in all stages of multiple sclerosis (MS) and can be detected very early in the course of the disease. Axonal pathology has been related to the inflammatory demyelinating environment, but its dependence on inflammation is still unknown. We measured tau protein and 14-3-3, two intracellular proteins expressed in neurons and glial cells, in the cerebrospinal fluid (CSF) of 114 patients with MS, in 79 patients with other inflammatory neurological diseases (IND) and in the CSF of 60 patients with non-inflammatory neurological diseases (NIND) as controls.

Comparative proteomics of the Mycobacterium leprae binding protein myelin P0: its implication in leprosy and other neurodegenerative diseases.

Mycobacterium leprae, the causative agent of leprosy invades Schwann cells of the peripheral nerves leading to nerve damage and disfigurement, which is the hallmark of the disease. Wet experiments have shown that M. leprae binds to a major peripheral nerve protein, the myelin P zero (P0).

Mycobacterium leprae binds to a major human peripheral nerve glycoprotein myelin P zero (P0).

We have previously shown that a major phosphorylated 25-kDa glycoprotein of the human peripheral nerve binds to Mycobacterium leprae. In the present study, we confirm that the 25-kDa glycoprotein of the human peripheral nerve is myelin P zero (P0) by immunoprecipitation and Western blot experiments using monoclonal antibodies to myelin P0. Immunohistochemical studies on human nerve using these antibodies to myelin P0 exhibited a strong immunoreactivity to the myelin and Schwann cells.

[Cholesterol-reducing medications-a new therapeutic option for multiple sclerosis? Statins as immunomodulators].

Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is crucial for cholesterol biosynthesis, and are widely used as lipid-lowering agents. These drugs greatly reduce atherosclerosis and cardiovascular morbidity, which in the past was mainly attributed to their cholesterol-lowering properties. However, recent evidence suggests that statins are also potent immunomodulators.

Prevalence of autoimmune thyroiditis and non-immune thyroid disease in multiple sclerosis.

Since multiple sclerosis (MS) and autoimmune thyroiditis (AIT) are presumed to be of autoimmune origin the correlation of these two diseases is of special interest. The aim of this study was to determine whether there are differences in the prevalence of thyroid disease with special emphasis on AIT compared with MS and normal subjects and whether the presence of thyroid disease correlates with disability, disease course, age, and disease duration. 353 consecutive patients with clinically definite MS, without interferon-beta treatment and 308 patients with low back pain or headache were extensively examined for the presence of non-immune or autoimmune thyroid disease.

Immunomodulation in multiple sclerosis: from immunosuppression to neuroprotection.

Multiple sclerosis (MS) is the most common disabling neurological disease of young adulthood. Following advances in the understanding of the immunological mechanisms that underlie the pathogenesis of MS, a growing arsenal of immunomodulatory agents is available. Two classes of immunomodulators are approved for long-term treatment of MS, the efficacy of several promising new concepts is being tested in clinical trials and classical immunosuppressive agents used in MS treatment have been shown to exert specific, immunomodulatory effects.

Statins as immunomodulators: comparison with interferon-beta 1b in MS.

Background: Recent data suggest that statins may be potent immunomodulatory agents. In order to evaluate the potential role of statins as immunomodulators in MS, the authors studied their immunologic effects in vitro and compared them to interferon (IFN)beta-1b.

Methods: Peripheral blood mononuclear cells (PBMC) obtained from untreated or IFN beta-1-treated patients with relapsing-remitting MS or from healthy donors (HD) and T cells were stimulated with concanavalin A, phytohemagglutinin, or antibody to CD3 in the presence of lovastatin, simvastatin, mevastatin, IFN beta-1b, or statins plus IFN beta-1b.

P0 protein is a target antigen in chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is widely regarded as an autoimmune disorder, although the autoantigen remains unknown. In this study, the sera of 21 CIDP patients were examined by immunofluorescence for antimyelin activity and by Western blotting for binding to myelin proteins. Six sera contained anti-P0 immunoglobulin G antibodies, and four of these caused conduction block and demyelination following intraneural injection in experimental animals.