S G Meuth

Publications of S G Meuth

• [Pregabalin and gabapentin in multiple sclerosis: clinical experiences and therapeutic implications].

  Authors: S Bittner, K Höhn, K Göbel, C Kleinschnitz, H Wiendl, S G Meuth

  Der Nervenarzt. 06/2011; 82(10):1273-80.

  Due to a plethora of additional symptoms patients with multiple sclerosis (MS) receive symptomatic treatment besides disease-modifying therapies. Among the substances which are commonly used are ionDue to a plethora of additional symptoms patients with multiple sclerosis (MS) receive symptomatic treatment besides disease-modifying therapies. Among the substances which are commonly used are ion channel modulators (e. g. pregabalin, gabapentin, carbamazepine). The aim of this study was to investigate the use of these drugs in clinical practice in a larger patient cohort. Data from 533 MS patients [439 without and 94 patients with add-on therapy (treatment group)] were evaluated retrospectively. All patients received a detailed neurological examination including evaluation of EDSS scores. Pregabalin and gabapentin are used most commonly. Abnormal sensations are the most frequent reason for therapy initiation. Patients with higher EDSS values and/or under mitoxantrone treatment most frequently receive additional therapy. So far, it is not known whether the investigated agents exert a beneficial influence on the disease course of MS itself beyond a mere symptomatic treatment. Further research efforts and clinical studies are necessary to address this question.

• [Multiple sclerosis - a channelopathy? : Targeting ion channels and transporters in inflammatory neurodegeneration.]

  Authors: S G Meuth, N Melzer, C Kleinschnitz, T Budde, H Wiendl

  Der Nervenarzt. 12/2008;

  Multiple sclerosis (MS) has traditionally been regarded as an inflammatory demyelinating disorder of the CNS in which clinical symptoms result from axon conduction block caused by myelin degradation.Multiple sclerosis (MS) has traditionally been regarded as an inflammatory demyelinating disorder of the CNS in which clinical symptoms result from axon conduction block caused by myelin degradation. However, typical accumulation of permanent neurological deficits during the clinical course of MS cannot be explained solely by de- and remyelinating processes. It is considered to be rather due to neuronal degeneration, for which several reasons could be identified depending on the state of the disease. First, neurons and their axons can be damaged by infiltrating lymphocytes and macrophages either directly by cell-to-cell contact or by the release of harmful mediators such as nitric oxide or glutamate. Second, indirect injury to neurons and axons may occur through the loss of trophic support by neighbouring oligodendrocytes due to destruction of both the myelin sheath and the oligodendrocyte itself. Third, redistribution of certain voltage- and ligand-gated ion channels and transporters along naked demyelinated axons restores axonal conduction but also leads to excessive spatially restricted electrical activity of the axonal membrane, intracellular calcium accumulation, impairment of mitochondrial function, and subsequent neuronal degeneration. The neuroprotective potential of pharmacological modulation of these channels and transporters using already approved drugs has been demonstrated in several animal studies, is the subject of current clinical trials and will be the topic of this review.

• [Update on pathophysiologic and immunotherapeutic approaches for the treatment of multiple sclerosis]

  Authors: C Kleinschnitz, S G Meuth, B C Kieseier, H Wiendl

  Der Nervenarzt. 09/2007; 78(8):883-911.

  Multiple sclerosis (MS) is a chronic disabling disease with significant implications for patients and society. The individual disease course is difficult to predict due to the heterogeneity ofMultiple sclerosis (MS) is a chronic disabling disease with significant implications for patients and society. The individual disease course is difficult to predict due to the heterogeneity of clinical presentation and of radiologic and pathologic findings. Although its etiology still remains unknown, the last decade has brought considerable understanding of the underlying pathophysiology of MS. In addition to its acceptance as a prototypic inflammatory autoimmune disorder, recent data reveal the importance of primary and secondary neurodegenerative mechanisms such as oligodendrocyte death, axonal loss, and ion channel dysfunction. The deepened understanding of its immunopathogenesis and the limited effectiveness of currently approved disease-modifying therapies have led to a tremendous number of trials investigating potential new drugs. Emerging treatments take into account the different immunopathological mechanisms and strategies, to protect against axonal damage and promote remyelination. This review provides a compilation of novel immunotherapeutic strategies and recently uncovered aspects of known immunotherapeutic agents. The pathogenetic rationale of these novel drugs for the treatment of MS and accompanying preclinical and clinical data are highlighted.

• Immunotherapeutic approaches in MS: update on pathophysiology and emerging agents or strategies 2006.

  Authors: C Kleinschnitz, S G Meuth, B C Kieseier, H Wiendl

  Endocrine, metabolic & immune disorders drug targets. 04/2007; 7(1):35-63.

  Multiple sclerosis (MS) is a chronic disabling disease with significant implications for patients and society. The individual disease course is difficult to predict due to the heterogeneity ofMultiple sclerosis (MS) is a chronic disabling disease with significant implications for patients and society. The individual disease course is difficult to predict due to the heterogeneity of clinical presentation as well as radiological and pathological findings. Although its etiology still remains unknown, the last decade has generated considerable success in understanding the underlying pathophysiology of MS. In addition to its view as a prototypic inflammatory autoimmune disorder, recent data support the importance of primary and secondary neurodegenerative mechanisms such as oligodendrocyte death, axonal loss and ion channel dysfunction. The deepened understanding of the immunopathogenesis as well as the limited effectiveness of the currently approved disease modifying therapies have led to a tremendous number of trials investigating potentially new drug targets. Emerging treatments take into account the different immunopathological mechanisms as well as strategies to protect against axonal damage or to promote remyelination. This review provides a compilation of novel immunotherapeutic strategies or new aspects of known immunotherapeutic agents which have evolved recently. The pathogenetic rationale of these novel drug targets for the treatment of MS as well as accompanying preclinical and clinical data are highlighted.

• Why a positive genetic test for myotonic dystrophy type I does not always imply the right diagnosis.

  Authors: S G Meuth, C Kleinschnitz, M Frank, C Wessig, M Bendszus, W Kress, H Wiendl

  Journal of neurology, neurosurgery, and psychiatry. 01/2007; 77(12):1381-2.

• Activity Modes in Thalamocortical Relay Neurons are Modulated by G(q)/G(11) Family G-proteins - Serotonergic and Glutamatergic Signaling

  Authors: P. Coulon, T. Kanyshkova, T. Broicher, T Munsch, N. Wettschureck, T Seidenbecher, S G Meuth, S Offermanns, H C Pape, T Budde

  Front Cell Neurosci, v.4, 132.

  In thalamocortical relay (TC) neurons, G-protein-coupled receptors play an important part in the control of activity modes. A conditional Galpha(q) knockout on the background of a constitutiveIn thalamocortical relay (TC) neurons, G-protein-coupled receptors play an important part in the control of activity modes. A conditional Galpha(q) knockout on the background of a constitutive Galpha(11) knockout (Galpha(q)/Galpha(11) (-/-)) was used to determine the contribution of Gq/G11 family G-proteins to metabotropic serotonin (5-HT) and glutamate (Glu) function in the dorsal part of the lateral geniculate nucleus (dLGN). In control mice, current clamp recordings showed that alpha-m-5-HT induced a depolarization of V(rest) which was sufficient to suppress burst firing. This depolarization was concentration-dependent (100 muM: +6 +/- 1 mV, n = 10; 200 muM: +10 +/- 1 mV, n = 7) and had a conditioning effect on the activation of other Galpha(q)-mediated pathways. The depolarization was significantly reduced in Galpha(q)/Galpha(11) (-/-) (100 muM: 3 +/- 1 mV, n = 11; 200 muM: 5 +/- 1 mV, n = 6) and was apparently insufficient to suppress burst firing. Activating Galpha(q)-coupled muscarinic receptors affected the magnitude of alpha-m-5-HT-induced effects in a reciprocal manner. Furthermore, the depolarizing effect of mGluR1 agonists was significantly reduced in Galpha(q)/Galpha(11) (-/-) mice. Immunohistochemical stainings revealed binding of 5-HT(2C)R- and mGluR1alpha-, but not of 5-HT(2A)R-specific antibodies in the dLGN of Galpha(q)/Galpha(11) (-/-) mice. In conclusion, these findings demonstrate that transmitters of ascending brainstem fibers and corticofugal fibers both signal via a central element in the form of Gq/G11-mediated pathways to control activity modes in the TC system.