Abstract

We have investigated the efficacy of pulse-therapy with glucocorticoids (GC) at different time stages (in debuts, at the recurrent stage and at the stage of progression) of secondary progressive course (SPC) of multiple sclerosis (MS) in 70 patients (57 women and 13 men) at the ages from 28 to 67 years (mean age 45±2.5 years). The duration of the disease accounted for 7 up to 34 years (average duration was 19.8±2.3 years). We have conducted 438 courses of GC therapy: at the onsets – 11, at the recurrent stage (RS) – 178 and at the stage of secondary progression-249. The efficacy of hormonal therapy was assessed taking into account the following criteria: the dynamics of regression of neurological symptoms under the influence of the first course of GC therapy at the stage of onsets; a comparative evaluation of remission’s duration after admission and without taking GC at the onsets; duration of RS depending on the duration of remissions after the first course of GC therapy; a comparative evaluation of remissions’ duration after the 1st (at the stage of onset and/or on the RS), and the period of stabilization on the SPS before the last courses of GC; the variants of secondary progression under the influence of GC courses; scores according the EDSS disability scale after the 1st and before the last course of GC therapy; the rate of progression under the influence of the repeated courses of GC therapy. We have defined the three categories of efficacy at the repeated courses of pulse therapy with GC: the moderate efficacy, the low efficacy, the lack of efficacy. We have not observed the high efficacy in patients with SPC. The patients with MFR <1.0, among which the pulse therapy with GC promoted the prolongation of RS, relieved the severe (less often) and moderate (more often) relapses, the outcome of which was accompanied by a moderate and stable neurologic deficit, were subsumed under the subgroup with moderate efficacy (21 individuals). The most favorable progressive variant of progression prevailed in these patients after transformation of RS into SPS. The patients with different rate of MFR (9 – with MFR <1.0 and 12 – with MFR>1.0), with short (more often) and moderate (less often) RS, during which the accumulation of neurological deficit due to the frequent and heavy relapses had occurred, were subsumed under the subgroup with low efficiency (21 individuals). After transformation into SPS, the recurrent variant of progression prevailed in these patients. The patients who were characterized by short RS, by predominance of severe and prolonged relapses, the MFR value greater than 1.0, the steady accumulation of a pronounced and persistent neurologic deficit, a high rate of progression and high scores on the EDSS disability scale more than 6.5 points) were subsumed under the subgroup with the lack of efficacy (28 individuals). After transformation in the SPC, the most unfavorable variant of progression prevailed (21 patients); significantly less frequent were the recurrent (5 patients) and a combination of a steady and recurrent (2 patients) progression. The persistent lack of efficacy of the hormonal therapy in this subgroup of patients was most likely associated with the genetically determined low individual sensitivity to GC. Therefore, the results of our study showed that the efficacy of GC therapy in SPC of MS is determined by the complex interaction of clinical indicators having the prognostic value, as well as by the number of the genetic factors, which require their further observation.

Highlights

  • IntroductionThe modern algorithm for the treatment of multiple sclerosis (MS) is based on “four whales”: relief of exacerbations with the help of glucocorticoids (GC); immunotherapy with drugs that change the course of MS (PITRS), symptomatic therapy, which removes various clinical manifestations of the disease and a complex of rehabilitation measures, including the development of adaptive strategies for reducing disability [1, 2].As first-line drugs that relieve exacerbations of MS, are GC (prednisolone, methylprednisolone), the clinical effect of which is due to immunosuppressive and anti-inflammatory action

  • The modern algorithm for the treatment of multiple sclerosis (MS) is based on “four whales”: relief of exacerbations with the help of glucocorticoids (GC); immunotherapy with drugs that change the course of MS (PITRS), symptomatic therapy, which removes various clinical manifestations of the disease and a complex of rehabilitation measures, including the development of adaptive strategies for reducing disability [1, 2].As first-line drugs that relieve exacerbations of MS, are GC, the clinical effect of which is due to immunosuppressive and anti-inflammatory action

  • We have investigated the efficacy of pulse-therapy with glucocorticoids (GC) at different time stages of secondary progressive course (SPC) of multiple sclerosis (MS) in 70 patients (57 women and 13 men) at the ages from 28 to 67 years

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Summary

Introduction

The modern algorithm for the treatment of multiple sclerosis (MS) is based on “four whales”: relief of exacerbations with the help of glucocorticoids (GC); immunotherapy with drugs that change the course of MS (PITRS), symptomatic therapy, which removes various clinical manifestations of the disease and a complex of rehabilitation measures, including the development of adaptive strategies for reducing disability [1, 2].As first-line drugs that relieve exacerbations of MS, are GC (prednisolone, methylprednisolone), the clinical effect of which is due to immunosuppressive and anti-inflammatory action. Hormone therapy in MS is important as a factor that suppresses the autoimmune process, and as a form of replacement therapy in connection with the development of glucocorticoid insufficiency in this disease, which changes immunological reactivity in the direction of enhancing allergic manifestations and contributes to the demyelination process [4]. As it known, the secondary progressive course (SPC), in contrast to the recurrent course (RC), is characterized by a more unfavorable course due to the progression of the process leading to accumulation of a neurological deficit and persistent disability [5, 6]. Timely and adequate appointment of GC in the early stages of the disease, i.e. in debuts and on the recurrent stage (RS), can postpone further progression of the process [7]

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