Our knowledge on the clinical efficacy of intravenous immunoglobulins (IVIg) in neurological diseases has greatly increased in the last 5 years. Liquid formulations with a higher concentration of IVIg have simplified administration. Despite a worldwide increase in plasma production it is still a valuable biological product which is why current indications must be continuously validated.
View Article and Find Full Text PDFIn this study, we investigated the potential of minocycline to influence cuprizone induced demyelination in the grey and white matter. To induce demyelination C57BL/6 mice were fed with cuprizone for up to 6 weeks and were analysed at different timepoints (week 0, 4, 5, 6). Mice treated with minocycline had less demyelination of the cortex and corpus callosum compared with sham treated animals.
View Article and Find Full Text PDFMultiple sclerosis (MS) is considered to be an autoimmune disease leading to inflammatory demyelination and axonal damage in the central nervous system (CNS). Current treatments involve non-specific immunosuppression and immunomodulation. The development of monoclonal antibodies for therapeutic use allows targeting of specific immune mechanisms.
View Article and Find Full Text PDFWe report herein a clinical case of a patient with meningeal carcinomatosis from penile squamous cell carcinoma. A 68-year-old man presented with mental changes, headaches, and unstable gait. Examinations revealed brain metastases and infiltration of the leptomeninges and subarachnoid space by carcinoma cells.
View Article and Find Full Text PDFJ Neuroimmunol
December 2009
In multiple sclerosis (MS) matrix metalloproteinases (MMP) are believed to be involved in the disruption of the blood brain barrier and demyelination. MMP-9 is increased in the cerebrospinal fluid of MS patients and expressed in MS lesions, indicating an involvement in MS pathogenesis. It is known that activated microglia secrete MMP.
View Article and Find Full Text PDFA 45-year-old man presented with a progressive transverse spinal cord syndrome. MRI scanning revealed bitemporal and multiple spinal lesions with significant enhancement after gadolinium administration mimicking an acute disseminated encephalomyelitis. CSF analyses showed a lymphocytic pleocytosis.
View Article and Find Full Text PDFCurr Neuropharmacol
March 2009
Fumaric acid is an intermediate product of the citric acid cycle that is a source of intracellular energy in the form of adenosine triphosphate (ATP). It is generated by oxidation of adenylsuccinate by the enzyme succinate dehydrogenase and is then converted to maleate by the enzyme fumarase. At present, fumaric acid esters (FAE) are licensed for the treatment of psoriasis.
View Article and Find Full Text PDFCuprizone feeding is a commonly used model to study experimental de- and remyelination, with the corpus callosum being the most frequently investigated white matter tract. We have previously shown that demyelination is also extensive in the cerebral cortex in the cuprizone model. In the current study, we have performed a detailed analysis of the dynamics of demyelination in the cortex in comparison to the corpus callosum.
View Article and Find Full Text PDFBackground: Plasma exchange (PE) is well established for conditions such as rapid progressive vasculitis associated with autoantibodies against neutrophil cytoplasmic antigens (ANCA), anti-glomerular basement membrane (GBM) antibody disease, or thrombotic thrombocytopenic purpura (TTP). Also, several neurological disorders, such as acute worsening in myasthenia gravis, Guillan-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), can successfully be treated with PE. Only small case series have previously shown that PE is also effective in relapses in patients with multiple sclerosis (MS).
View Article and Find Full Text PDFNat Rev Neurol
June 2009
A trial of autologous hematopoietic stem cell transplantation to treat multiple sclerosis has yielded promising results, generating considerable interest within both the clinical literature and the mainstream press.the findings should, however, be interpreted with some caution, and larger, randomized trials will be required to establish the true efficacy of the approach.
View Article and Find Full Text PDFIn multiple sclerosis, demyelination occurs beside the white-matter structures and in the cerebral and cerebellar cortex. We have previously shown that, in the cuprizone model, demyelination is present not only in the corpus callosum but also in the cerebral cortex. Here, we have performed a detailed analysis of the dynamics of de- and remyelination in the cerebellar cortex and white matter at nine timepoints in two cerebellar regions.
View Article and Find Full Text PDFThe majority of multiple sclerosis lesions fail to remyelinate after chronic demyelinating episodes resulting in neurologic disability. In the current study, chronic demyelination was investigated by using the cuprizone model, a toxic demyelination model. C57BL/6 mice were administered a 0.
View Article and Find Full Text PDFChronic dysregulation of the intracellular Ca(2+) homeostasis (excitotoxicity) is thought to contribute to the development of motor neuron diseases. Valproic acid (VPA) is widely used as an antiepileptic drug and acts mainly by inhibition of sodium channels and by enhancing the level of the inhibitory neurotransmitter gamma-aminobutyric acid. Neuroprotective capacities of VPA are supposed to arise also from the inhibition of histone deacetylases.
View Article and Find Full Text PDFCurrent treatments for multiple sclerosis (MS) include immunomodulatory or immunosuppressive agents but no neuroprotective or regenerative therapy is available. From various animal models, we have learned that remyelination in the CNS is a potent neuroprotective mechanism. The knowledge about oligodendrocyte biology and the process of remyelination has greatly increased in recent years; however, the precise mechanisms are far from being understood.
View Article and Find Full Text PDFLong-term treatment of immune-mediated polyneuropathies remains difficult. For acute polyneuritis, or Guillain-Barré syndrome, the established standard therapy utilizes high doses of polyvalent intravenous immunoglobulins (IVIG). A recently published randomized placebo-controlled study of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) showed IVIG to be clinically effective also for this disorder in both short and long term.
View Article and Find Full Text PDFIn multiple sclerosis demyelination not only affects the white matter, but also the grey matter of the brain. We have previously reported that in the murine cuprizone model for demyelination lesions occur in addition to the corpus callosum also in the neocortex and hippocampus. In the current study, we provide a detailed characterization of hippocampal demyelination in the cuprizone model.
View Article and Find Full Text PDFWhether differences in diet composition may influence demyelinating diseases remains controversial. The aim of this study was to analyse if diets with a different composition of polyunsaturated fatty acids (PUFAs) could influence demyelination and remyelination in cuprizone fed mice, a widely used animal model for de- and remyelination. C57Bl/6 mice were fed with 0.
View Article and Find Full Text PDFExpert Rev Neurother
November 2008
All licensed disease-modifying drugs for the treatment of relapsing-remitting multiple sclerosis (MS) only display partial efficacy and hitherto require parenteral administration. Thus, there is a high demand for innovative and at the same time orally available MS therapeutics. Fumaric acids and their esters (FAE) may represent such a new class of compounds.
View Article and Find Full Text PDFIn multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), impairment of glial "Excitatory Amino Acid Transporters" (EAATs) together with an excess glutamate-release by invading immune cells causes excitotoxic damage of the central nervous system (CNS). In order to identify pathways to dampen excitotoxic inflammatory CNS damage, we assessed the effects of a beta-lactam antibiotic, ceftriaxone, reported to enhance expression of glial EAAT2, in "Myelin Oligodendrocyte Glycoprotein" (MOG)-induced EAE. Ceftriaxone profoundly ameliorated the clinical course of murine MOG-induced EAE both under preventive and therapeutic regimens.
View Article and Find Full Text PDFTher Adv Neurol Disord
September 2008
Since the incidental discovery in 1981 that intravenous immunoglobulins (IVIg) are immunomodulatory, they have been investigated in a large number of putative autoimmune diseases. This has led to licensing for idiopathic thrombocytopenic purpura, Kawasaki disease, and in neurological disorders for Guillain-Barré syndrome (GBS). Although not licensed, randomized controlled trials have also shown IVIg efficacy in other neuroimmunological diseases such as multifocal motor neuropathy (MMN), chronic inflammatory demyelinating neuropathy (CIDP), myasthenia gravis, dermatomyositis, and stiff-person syndrome.
View Article and Find Full Text PDFBackground: Intravenous immunoglobulins (IVIg) have been proven in the past two decades to be potent immunomodulators. This led to the licensing and recommendation of IVIg as first-line treatment for Kawasaki disease, idiopathic thrombocytopenic purpura and Guillain-Barré syndrome.
Objective: To review the evidence and indications for the use of IVIg in the treatment of muscular diseases.
Remyelination in multiple sclerosis (MS) occurs spontaneously and extensively. The underlying mechanisms, however, are only partly understood. Findings in experimental animal settings suggest that inflammation promotes remyelination and repair.
View Article and Find Full Text PDFUnravelling the factors that can positively influence remyelination is one of the major challenges in multiple sclerosis research. Expression of the chemokine receptor CXCR2 on oligodendrocytes both in vitro and in MS lesions has suggested a possible role for CXCR2 in the recruitment of oligodendrocyte precursor cells (OPC). To investigate the function of CXCR2 during remyelination in vivo, we studied this receptor in cuprizone-induced demyelination and subsequent remyelination.
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