Multiple sclerosis: treatment and prognosis

For the treatment of multiple sclerosis, drugs with anti-inflammatory and immunosuppressive action are used. The goal of immunotherapy for multiple sclerosis is to improve the outcome of exacerbations, reduce the risk of repeated exacerbations, prevent or slow the progression of the disease. Glucocorticoids and adrenocorticotropic hormone preparations 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, when exacerbated, accelerates recovery and improves the functional state in the short term. However, neither this method nor the long-term use of glucocorticoids by mouth improves the functional state in the long term, although a very small proportion of patients develop a steroid dependence, and when an attempt is made to cancel glucocorticoids, there is an exacerbation of multiple sclerosis.

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

The extended scale of disability Kurtzke (Kurtzke Extended Disabi1ity Status Sca1e - EDSS)

• 0 - normal neurological status
• 1-2,5 - minimal defect in one or several functional systems (for example, pyramidal, trunk, sensory, cerebral / psychic, cerebellar, intestinal and urinary, visual, others)
• 3-4.5 - moderate or severe defect in one or more functional systems, but is capable of self-movement at least within 300 m
• 5-5,5 - a pronounced defect in one or more functional systems; It is capable of moving without additional support within a minimum of 100 m.
• 6 - one-sided support is required (for example, a crutch or walking stick for at least 100 m)
• 6.5 - two-sided support is required (for example, a walker, two crutches or two walking sticks within a minimum of 20 m)
• 7-7,5 - chained to a wheelchair
• 8-8,5 - bedridden
• 10 - death due to multiple sclerosis

In recent years, new immunomodulatory agents have appeared to treat multiple sclerosis. Non-selective agents include the antiviral cytokine INFBb. Currently, 2 drugs of INFB are allowed 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.

The determination of the effectiveness of drugs in multiple sclerosis is based mainly on the data of a neurological examination, supported by a quantitative neuroimaging assessment of the number of foci and their activity. To assess the functional defect, the Kurtzke Functiona1 Status Sca1e (FSS) and the Kurtzke Extended Disabi1ity Status Sca1e (EDSS) scale created more than 30 years ago are most often used. Both scales are assessed in terms of the state of neurological functions most often associated with multiple sclerosis

[1], [2], [3], [4]

Problems of treatment of multiple sclerosis

Early Therapy

Currently, these drugs are usually prescribed for patients with clinically reliable multiple sclerosis, which has signs of an active process. At the same time, they are not used in cases of probable multiple sclerosis, when the patient had only one exacerbation. However, there is no consensus on when to start long-term therapy. A study was completed showing that the early use of INFB1a after the first attack of demyelinating disease allows delaying the development of a second attack and, consequently, clinically significant multiple sclerosis. Currently, the cost of treatment is high (about $ 10,000 per year), but it is potentially counterbalanced by the cost of treating exacerbations or complications of the disease, as well as maintaining the economic productivity of the patient.

[5], [6], [7], [8], [9]

Combination Therapy

Another problem, which is being intensively studied, is the possibility of combining drugs with different mechanisms of action. For example, a combination of in vitro glatiramer acetate and INFbeta1b exerted additive effect, reducing proliferation infu-activated MBP-reactive cells obtained from healthy volunteers. To date, there is no data on the use of a combination of glatiramer acetate and INFBb in clinical settings. In some centers, in patients with progressive multiple sclerosis, a treatment method was tested, which included bolus administration of cyclophosphamide and methylprednisolone as an induction therapy followed by maintenance therapy of the INFB to stabilize the patients. Currently, any reports of the beneficial effects of combination therapy should be considered preliminary, since the efficacy and safety of such methods have not been investigated in adequate controlled clinical trials.

[10], [11], [12],

New strategies for treating multiple sclerosis

There are a number of other possible directions of immunotherapy, potentially capable of having a beneficial effect in multiple sclerosis. In the future, this series is likely to expand as knowledge on the immunopathogenesis of the disease deepens. Some drugs have undergone preliminary clinical trials (eg, transformed growth factor P, T cell vaccine, antibodies to a4 integrin, phosphodiesterase inhibitors, anti-CD4 antibodies, T-cell antagonists). Sometimes the results of these studies differ from the expectations, which reflects an incomplete understanding of the pathogenesis of multiple sclerosis. For example, treatment with antibodies to TNF in two patients with rapidly progressive multiple sclerosis did not affect the clinical status, but caused a transient increase in the number of active, contrast-accumulating focuses on MPT.

Prognosis of Multiple Sclerosis

A survey of 1,099 patients noted that 51% of them retained the ability to move independently. In this study, 66% of patients had a relapsing course at the onset of the disease, while 34% had a tendency to progress. The frequency of transformation of the remitting flow into a second progression in the first 5 years after the diagnosis was 12%. Within 10 years, this transformation was noted in 41% of patients, for 25 years - in 66% of patients.

In other studies, there was a trend toward steady, albeit slow, progression, with the proportion of patients with mild disease declining over time. In the study Weinshenker et a1. (1989), it was noted that the average for the group from the moment of diagnosis to the time when the movement of the patient becomes impossible without some outside help, is 15 years, but in patients with progressive course this period averaged 4.5 years. Similar data were obtained by observing 308 patients with a remitting disease within 25 years. In both studies, it was noted that the female sex and early onset of the disease are favorable prognostic signs, as well as the onset of the disease from sensory disorders (including optic neuritis) followed by complete recovery, a rare exacerbation in the first years of the disease, a minimal restriction of function after the first 5 years of illness.

Biological factors, which predetermine the variability of the onset of the disease and the transformation of the remitting current into a progressive one, are the focus of scientific research. Their detection will allow more rational planning of treatment in specific patients.

MRI studies. The study of MRI in dynamics allows to deepen understanding of the pathogenesis of multiple sclerosis and the course of the disease. Although in cross-section studies the relationship between the volume of foci measured by MRI and the degree of functional impairment is variable, in prospective studies, an increase in the volume of the affected tissue is accompanied by an increase in functional defect. In addition, a relationship was established between the clinical activity of the disease and the appearance of new active foci produced by contrasting gadolinium on T1-weighted images. The size of the foci usually increases within 2-4 weeks, and then decreases over a period of 6 weeks. Clinical significance has foci, which are both hyperintensive on T2-weighted images and hypo-intensive on T1-weighted images. These foci correspond to zones of gliosis, more severe demyelination or more significant axonal degeneration.

The study of MRI in dynamics in patients with a remitting current reveals new active foci from month to month and the increase in the total volume of the affected white matter over time, even in the absence of clinical signs of progression. It is believed that the transformation of the remitting flow into a secondary progressive is associated with the accumulation of similar foci of demyelination.

Another important indicator is the degree of involvement of the spinal cord. In patients with spinal cord injury, the degree of functional defect is higher. In the study of MRI in dynamics in patients with remittent and secondarily progressive course, a comparable rate of increase in lesion volume is observed. At the same time, with a primarily progressive course, the volume of damage to the brain tissue is usually lower than in the secondarily progressing course, and the foci are less contrasted with gadolinium.