Multiple Sclerosis - Treatment and Prognosis

Multiple sclerosis is treated with drugs with anti-inflammatory and immunosuppressive effects. The goal of immunotherapy in multiple sclerosis is to improve the outcome of exacerbations, reduce the risk of recurrent exacerbations, and prevent or slow down the progression of the disease. Glucocorticoids and adrenocorticotropic hormone drugs have the longest history of use and are most widely used in the treatment of multiple sclerosis. Currently, preference is given to intravenous administration of high doses of methylprednisolone, which accelerates recovery during an exacerbation and improves functional status in the short term. However, neither this method nor long-term oral use of glucocorticoids improves functional status in the long term, although a very small proportion of patients develop steroid dependence, and an attempt to discontinue glucocorticoids results in an exacerbation of multiple sclerosis.

• Treatment of exacerbations of multiple sclerosis
• Interferons and Multiple Sclerosis
• Symptomatic treatment of multiple sclerosis

Kurtzke Extended Disability Status Sca1e (EDSS)

• 0 - normal neurological status
• 1-2.5 - minimal defect in one or more functional systems (e.g. pyramidal, brainstem, sensory, cerebral/mental, cerebellar, intestinal and urinary, visual, others)
• 3-4.5 - moderate or severe impairment in one or more functional systems, but capable of independent movement at least within 300 m
• 5-5.5 - pronounced defect in one or more functional systems; capable of moving without additional support within at least 100 m.
• 6 - one-sided support is required (e.g. crutch or cane for walking at least 100 m)
• 6.5 - requires bilateral support (e.g. walker, two crutches or two canes to walk at least 20 m)
• 7-7.5 - confined to a wheelchair
• 8-8.5 - bedridden
• 10 - death due to multiple sclerosis

In recent years, new immunomodulatory agents have appeared for the treatment of multiple sclerosis. Non-selective agents include the antiviral cytokine INFb. Currently, two INFb drugs are approved for use in multiple sclerosis - INFb1b and INFb1a. A more specific approach to the treatment of multiple sclerosis is based on the use of glatiramer acetate.

Determining the efficacy of drugs in multiple sclerosis is based primarily on neurological examination data, supported by quantitative neuroimaging assessment of the number of lesions and their activity. The Kurtzke Functional Status Scale (FSS) and the Kurtzke Extended Disability Status Scale (EDSS), created more than 30 years ago, are most often used to assess functional impairment. Both scales assess the state of neurological functions most often affected by multiple sclerosis.

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Problems of treatment of multiple sclerosis

Early therapy

Currently, these drugs are usually prescribed to patients with clinically significant multiple sclerosis that has signs of an active process. At the same time, they are not used in probable multiple sclerosis, when the patient has had only one exacerbation. However, there is no consensus on when to start long-term therapy. A study has been completed showing that early use of INFb1a after the first attack of demyelinating disease allows delaying the development of a second attack and, therefore, clinically significant multiple sclerosis. Currently, the cost of treatment is high (about $10,000 per year), but it is potentially balanced by the cost of treating exacerbations or complications of the disease, as well as maintaining the economic productivity of the patient.

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Combination therapy

Another issue that is being increasingly explored is the possibility of combining drugs with different mechanisms of action. For example, in vitro combinations of glatiramer acetate and INFbeta1b had an additive effect, reducing the proliferation of INFγ-activated OMP-reactive cells obtained from healthy volunteers. To date, there are no data on the use of a combination of glatiramer acetate and INFβ in clinical settings. In some centers, a treatment method has been tried in patients with progressive multiple sclerosis that involves bolus administration of cyclophosphamide and methylprednisolone as induction therapy, followed by maintenance therapy with INFβ to stabilize the patients' condition. At present, any reports of a beneficial effect of combination therapy should be considered preliminary, since the efficacy and safety of such methods have not been studied in adequate controlled clinical trials.

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New strategies for treating multiple sclerosis

There are a number of other potential immunotherapies that may have a beneficial effect in MS. This range will likely expand in the future as our understanding of the immunopathogenesis of the disease increases. Several agents have entered preliminary clinical trials (e.g., transformed growth factor β, T-cell vaccine, anti-α4 integrin antibodies, phosphodiesterase inhibitors, anti-CD4 antibodies, T-cell antagonist peptides). Sometimes the results of these studies are at odds with expectations, reflecting our incomplete understanding of the pathogenesis of MS. For example, treatment with anti-TNF antibodies in two patients with rapidly progressive MS had no effect on clinical status but did cause a transient increase in the number of active, contrast-enhancing lesions on MRI.

Prognosis of Multiple Sclerosis

In a study of 1099 patients, it was noted that 51% of them retained the ability to move independently. In this study, 66% of patients had a remitting course at the onset of the disease, while 34% had a tendency to progression. The frequency of transformation of the remitting course into a secondary progressive course in the first 5 years after diagnosis was 12%. Within 10 years, such a transformation was noted in 41% of patients, within 25 years - in 66% of patients.

Other studies have noted a tendency toward steady, albeit slow, progression, with the proportion of patients with mild disease decreasing over time. In a study by Weinshenker et al. (1989), it was noted that on average 15 years pass from the time of diagnosis to the time when the patient's movement becomes impossible without some assistance, but in patients with a progressive course this period averaged 4.5 years. Similar data were obtained in a 25-year follow-up of 308 patients with a remitting course of the disease. Both studies noted that female gender and early onset of the disease are favorable prognostic signs, as well as the onset of the disease with sensory disorders (including optic neuritis) followed by complete recovery, the rarity of exacerbations in the first years of the disease, and minimal limitation of functions after the first 5 years of the disease.

Biological factors that determine the variability of the age of onset of the disease and the transformation of the remitting course into a progressive one are the focus of scientific research. Their identification will allow more rational treatment planning for specific patients.

MRI studies. Dynamic MRI studies provide insight into the pathogenesis of multiple sclerosis and the course of the disease. Although the relationship between the volume of lesions measured by MRI and the degree of functional impairment is variable in cross-sectional studies, in prospective studies an increase in the volume of affected tissue is accompanied by an increase in the functional defect. In addition, a relationship has been established between the clinical activity of the disease and the appearance of new active lesions, which are detected by gadolinium contrast on T1-weighted images. The size of the lesions usually increases over 2-4 weeks and then decreases over 6 weeks. Lesions that are simultaneously hyperintense on T2-weighted images and hypointense on T1-weighted images are of clinical significance. These lesions correspond to areas of gliosis, more severe demyelination, or more significant axonal degeneration.

Dynamic MRI studies in patients with remitting course reveal new active foci from month to month and an increase in the total volume of affected white matter over time, even in the absence of clinical signs of progression. It is assumed that the transformation of remitting course into secondary progressive is associated with the accumulation of such foci of demyelination.

Another important indicator is the degree of spinal cord involvement. In patients with spinal cord damage, the degree of functional defect is higher. In dynamic MRI studies, patients with remitting and secondary progressive disease show a comparable rate of increase in the volume of damage. At the same time, with a primarily progressive disease, the volume of brain tissue damage is usually lower than with a secondary progressive disease, and the lesions are less contrasted with gadolinium.