Interferon-ß1a Treatment Modulates Th1 Expression In R/R Multiple Sclerosis delta+ T-Cells
Elliott CL, El-Touny SY, Filipi ML, Healey KM, Leuschen MP
J Clin Immunol 2001 May;21(3):200-9
Nebraska Medical Center, Dept of Internal Medicine, Omaha 68198-1205, USA
PMID# 11403227; UI# 21295851
A paradigm exists that Multiple Sclerosis is causally related to dysregulation of Th1 Inflammatory Cytokines and Th2 AntiInflammatory Cytokines. The Cytokine source(s) that initiate the imbalances are unknown.
In this study, delta, CD4+, and CD8+ T-Cell receptor-positive Cells (TCR+) were isolated from the blood.
Of 26 Definitive Relapsing/Remitting Multiple Sclerosis patients prior to Interferon-beta-1a (IFN-ß-1a) therapy and following 8-10 weeks of this therapy.
The bioactivities of Interferon-gamma (IFN-), InterLeukin-10 (IL-10), and InterLeukin-12 (IL-12) were determined.
The concentrations of IFN-, IL-10, and IL-12 from each cell type did not change significantly with IFN-ß-1a treatment.
The IL-10 secreted by delta+ TCR Cells strongly correlated with the IL12 secreted by the same delta+ TCR Cells, supporting the paradigm.
Furthermore, IFN-ß-1a therapy decreased the delta+ TCR Cell secretion of Th1 Cytokines after 8-10 weeks of therapy.
von Budingen HC, Tanuma N, Villoslada P, Ouallet JC, Hauser SL, Genain CP
J Clin Immunol 2001 May;21(3):155-70
Univ of California, Dept of Neurology, San Francisco 94143, USA
PMID# 11403222; UI# 21295846
Myelin/Oligodendrocyte GlycoProtein (MOG) is a surface-exposed Antigen of Myelin and an important target for AutoImmune responses which mediate inflammatory DeMyelination in the Central Nervous System.
Experimentally, MOG induces strong pathogenic T-Cell responses in many strains of laboratory animals.
Immunological studies in humans also identify MOG as a surprisingly prevalent antigenic molecule among the Myelin proteins.
In addition, the Encephalitogenic properties of MOG are linked to the induction of AntiBody responses which have been demonstrated to directly promote Central Nervous System DeMyelination.
A hallmark NeuroPathological feature in disorders such as human Multiple Sclerosis.
Factors responsible for AutoImmunity to MOG likely include Genetic influences as well as other mechanisms, which are the subject of intense investigation.
This article reviews experimental data currently available on specificity and pathogenic roles of T-Cell and AntiBody responses against MOG, which have implications relevant to Multiple Sclerosis and related disorders.
Ciccarelli O, Werring DJ, Wheeler-Kingshott CA, Barker GJ, Parker GJ, Thompson AJ, Miller DH
Neurology 2001 Apr 10;56(7):926-33
Institute of Neurology, NMR Research Unit, National Hospital for Neurology and NeuroSurgery, London, United Kingdom
PMID# 11294931; UI# 21192592
To quantitatively investigate water Diffusion changes in Normal-Appearing White Matter (NAWM) and Gray Matter in patients with MS, and to evaluate whether these changes are correlated with clinical disability and disease duration.
Diffusion Tensor Imaging provides quantitative information about the magnitude and directionality (Anisotropy) of water Diffusion in vivo and detects pathologic changes in MS Brain tissue.
Diffusion Tensor imaging was performed in 39 patients with MS and in 21 age-matched control subjects.
Quantitative indices, including Fractional Anisotropy, Volume Ratio, and Mean Diffusion, were obtained in 30 regions of interest located in Normal-Appearing Basal Ganglia, Cerebellar Gray Matter, and SupraTentorial and InfraTentorial NAWM.
Patients with MS showed significantly reduced Anisotropy and a trend toward increased Diffusivity in the InfraTentorial and SupraTentorial NAWM, and significantly increased Anisotropy in the Basal Ganglia.
In all patients with MS, both Fractional Anisotropy and Mean Diffusivity in the Cerebral Peduncles were inversely correlated with the Expanded Disability Status Scale and Pyramidal Functional scores.
In patients with Relapsing/Remitting MS, there was a strong correlation between Expanded Disability Status Scale score and Fractional Anisotropy in both SupraTentorial and InfraTentorial NAWM.
In Primary and Secondary/Progressive MS, disease duration correlated strongly with Mean Diffusivity in InfraTentorial NAWM and Fractional Anisotropy in the Cerebral Peduncles, respectively.
The most striking finding of decreased Fractional Anisotropy in SupraTentorial and InfraTentorial NAWM and increased Fractional Anisotropy in Basal Ganglia may result from Axonal Degeneration due to transected Axons in remote Focal lesions.
Diffusion Tensor Imaging indices, in particular Fractional Anisotropy, appear sensitive to structural damage in NAWM that is associated with Disability and progression in MS.
Gabapentin But Not Vigabatrin Is Effective In The Treatment Of Acquired Nystagmus In Multiple Sclerosis: How Valid Is The GABAergic Hypothesis?
Bandini F, Castello E, Mazzella L, Mancardi GL, Solaro C
J Neurol NeuroSurg Psychiatry 2001 Jul;71(1):107-10
Univ of Genoa, Dept of Neurological Sciences and Vision, via De Toni 5, 16132 Genoa, Italy
PMID# 11413274; UI# 21306293
Acquired Nystagmus occurs frequently in patients with Multiple Sclerosis and is often the cause of illusory motion of the environment (Oscillopsia), and blurring of vision.
Based primarily on the beneficial effect of Gabapentin on Acquired Pendular Nystagmus (APN), a GABAergic mechanism in controlling Nystagmus has been hypothesised.
If increasing GABA concentrations in the CNS are critical for the treatment of Nystagmus, then a selective GABAergic drug should be highly successful.
However, as Gabapentin is not a selective GABAergic agent, Vigabatrin, a "pure" GABAergic medication, and Gabapentin, were compared in a single blind cross over trial in eight patients with Definite Multiple Sclerosis.
Patients were randomly assigned to begin with Gabapentin (1200 mg daily) or Vigabatrin (2000 mg daily).
Neuro-Ophthalmological and Electro-OculoGraphic (EOG) evaluations were performed four and three times, respectively.
Treatment efficacy was based on improving Visual Acuity and EOG indices (amplitude or frequency of Nystagmus, or both) by at least 50% of pretreatment values. Three out of eight patients dropped out due to adverse effects.
In the remaining five patients Gabapentin improved symptomatic Pendular or Gaze Evoked Jerk Nystagmus in four. Three patients decided to continue Gabapentin therapy.
Importantly, Vigabatrin proved useful in only one out of five patients, suggesting that Gabapentin effectiveness may be related to additional non-GABAergic mechanisms of action.
Interaction with Cerebral Glutamate transmission by inhibition of NMDA receptor might be an alternative hypothesis for the therapeutic action of Gabapentin.