Multiple sclerosis is a neurological pathology with a progressive course caused by the demyelination of the pathways with the subsequent formation of sclerotic plaques in the foci of myelin destruction. Among the symptoms of multiple sclerosis, motor disorders, sensitivity disorders, optic neuritis, pelvic organ dysfunction, neuropsychic changes predominate. The diagnosis is confirmed by MRI of the brain, electrophysiological studies, neurological and ophthalmological examination. Drug pathogenetic therapy of multiple sclerosis is carried out with glucocorticoids, immunomodulators, immunosuppressants
ICD 10
G35 Multiple sclerosis
General information
Multiple sclerosis is a chronic progressive disease characterized by multiple lesions in the central and to a lesser extent peripheral nervous system. The concept of “multiple sclerosis” in neurology also corresponds to: plaque sclerosis, multiple sclerosis, spotted sclerosis, multiple sclerosing periaxial encephalomyelitis.
The onset of the disease usually occurs at a young, active age (20-45 years); in most cases, multiple sclerosis develops in persons engaged in the intellectual field. Multiple sclerosis often affects residents of countries with a temperate climate, where the incidence rate can reach 50-100 cases per 100 thousand population.
Causes and pathogenesis
The development of multiple sclerosis, related to multifocal diseases, is due to the interaction of environmental factors (geographical, environmental, viruses and other microorganisms) and hereditary predisposition, which is realized by a polygenic system that determines the features of the immune response and metabolism. Immunopathological reactions play a leading role in the pathogenesis of multiple sclerosis.
One of the first events in the pathogenesis of this disease is the activation of anergic autoreactive CD4+ T cells with respect to myelin antigens on the periphery (outside the central nervous system). During this process, the interaction of the T-cell receptor and the antigen associated with class II molecules of the main histocompressibility complex on antigen-presenting cells, which are dendritic cells. In this case, the antigen may be a persistent infectious agent.
As a result, T cells proliferate and differentiate mainly into type 1 T helper cells, which produce pro-inflammatory cytokines, which contributes to the activation of other immune cells. At the next stage, T-helpers migrate through the blood-brain barrier. Reactivation of T cells by antigen-presenting cells (microglia, macrophages) occurs in the central nervous system.
An inflammatory reaction develops caused by an increase in the level of proinflammatory cytokines. The permeability of the blood-brain barrier increases. B-cell tolerance is disrupted with an increase in antibody titers to various structures of oligodendroglia and myelin. The level of reactive oxygen species increases, the activity of the complement system increases. As a result of these events, demyelination develops with damage to the nerve fiber already at the early stages of the pathological process, the death of oligodendrogliocytes and the formation of plaques.
Classification
Currently, multiple sclerosis is classified according to the type of course of the disease. There are basic and rare variants of the development of the disease. The first include: remitting course, secondary-progressive (with or without exacerbations), primary-progressive.
- The remitting course of multiple sclerosis is most typical (up to 90% of cases). There is a period of the appearance of the first symptoms or a significant increase in existing ones lasting at least a day (exacerbation) and a period of their regression (remission). The first remission is more often longer than the subsequent ones, so this period is designated as a stabilization stage.
- The secondary progressive course of multiple sclerosis occurs after the remitting course, the duration of which is individual for each patient. There comes a stage of chronic progression with periods of exacerbation and stabilization. The increase in neurological deficit is caused by progressive degeneration of axons and a decrease in the compensatory capabilities of the brain.
- With the primary progressive course of multiple sclerosis (12-15% of cases), there is a steady increase in signs of damage to the nervous system without exacerbations and remissions throughout the disease. This course of the disease is mainly due to the neurodegenerative nature of the development of the pathological process. The spinal form of multiple sclerosis is extremely rare, with a possible debut before the age of 16 or after 50 years.
Multiple sclerosis symptoms
The clinical picture of multiple sclerosis is characterized by extreme polymorphism, especially in the onset of the disease, which can be both poly- and monosymptomatic. Often the disease begins with weakness in the legs, less often with sensory and visual disturbances. Sensitivity disorders are manifested by a feeling of numbness in various parts of the body, paresthesia, radicular pain, a symptom of Lermitt, and visual — optical neuritis with a pronounced decrease in vision, which later, as a rule, is restored.
In some cases, multiple sclerosis debuts with a shaky gait, dizziness, vomiting, nystagmus. Sometimes, at the beginning of the disease, the function of the pelvic organs may be impaired in the form of delays or frequent urge to urinate. For the early stages of multiple sclerosis, the fragmented appearance of individual symptoms is typical.
With the development of multiple sclerosis in the clinical picture, symptoms of damage to the pyramidal, cerebellar and sensory pathways, individual CN and pelvic organ dysfunction are most often detected with varying degrees of severity. The severity of individual symptoms can vary not only for several days, but even hours. Among the typical clinical manifestations of multiple sclerosis, paresis occupies a leading place. Lower spastic paraparesis is especially often observed, less often tetraparesis. The severity of spasticity depends on the patient’s posture. So, in the supine position, muscle hypertonus is less intense than in the vertical position, which is especially noticeable when walking.
Signs caused by damage to the cerebellum and its connections — dynamic and static ataxia, dysmetria, asinergia, intentional trembling, megalography, chanted speech. When the dentate-red-nuclear pathways are affected, the intentional tremor takes on the character of hyperkinesis, which sharply increases with the redirection of movement, and in severe cases spreads to the head and trunk. In most patients, foot pathological reflexes of flexor and extensor types are caused, in rare cases, carpal pathological reflexes, clonus of the feet and patella. In 30% of cases, reflexes of oral automatism are detected. Often there is a pathology of CN in the form of optical neuritis and internuclear ophthalmoplegia.
A distinctive feature of multiple sclerosis is the so-called “dissociation” syndrome, which reflects the discrepancy between the symptoms of damage to one or more systems. For example, a significant decrease in vision in the absence of changes in the fundus in the presence of optic neuritis or, conversely, significant changes in the fundus, changes in visual fields and the presence of scotoma with normal visual acuity. In some cases, in the late stages of the disease, involvement of the peripheral nervous system in the process in the form of radiculopathy and polyneuropathy is revealed. Among neuropsychological disorders, affective disorders (euphoria, depressive syndrome), a kind of organic dementia, neurosis-like states (hysterical and hysteroform reactions, asthenic syndrome) are most common.
Diagnostics
There are certain criteria for diagnosing multiple sclerosis:
- the presence of signs of a multi-focal lesion of the central nervous system (mainly white matter of the brain and spinal cord)
- gradual appearance of various symptoms of the disease
- instability of some symptoms
- remitting or progressive course of the disease
- additional research data
Laboratory and instrumental diagnostic methods are used to identify subclinical lesions, as well as to assess the activity of the pathological process. The main method confirming the diagnosis of “multiple sclerosis” is an MRI of the brain, which allows you to identify the presence and topographic distribution of suspected foci of demyelination.
When the relevant afferent systems are involved in the process at the subclinical level, studies of SSVP, SVP and auditory evoked potentials are carried out. To register clinically pronounced static disorders, as well as hearing and nystagmus, stabilography and audiometry are performed, respectively. In the early stages of multiple sclerosis, an ophthalmological examination is required to identify disorders typical of optical neuritis.
Differential diagnosis
Multiple sclerosis must be differentiated primarily from diseases accompanied by a multi—focal lesion of the central nervous system – collagenoses and systemic vasculitis (Sjogren’s syndrome and Behcet’s disease, systemic lupus erythematosus (SLE), nodular periarteritis, Wegener’s granulomatosis) and infectious diseases with primary multi-systemic lesion (HIV infection, brucellosis, syphilis). It should be remembered that for all of the above diseases, a combination with the pathology of other organs and systems is typical. In addition, with multiple sclerosis, differential diagnosis is carried out with diseases of the nervous system — Wilson’s disease, various types of ataxia, familial spastic paralysis, which differ from multiple sclerosis by sluggish progression or prolonged stabilization of the pathological process.
Multiple sclerosis treatment
Patients with multiple sclerosis should always be under the constant supervision of a neurologist. The goals of treatment for multiple sclerosis include: relief and prevention of exacerbations, slowing the progression of the pathological process.
To relieve exacerbations of multiple sclerosis, pulse therapy with methylprednisolone is most often used for 4-7 days. With little effectiveness of this pulse therapy, after its completion, methylprednisolone is prescribed orally every other day with a gradual dose reduction over a month. Before starting treatment, it is necessary to exclude contraindications to the use of glucocorticoids, and in the course of treatment, add accompanying therapy (potassium preparations, gastroprotectors). In case of exacerbation, plasmapheresis may be performed (from 3 to 5 sessions), followed by the administration of methylprednisolone.
The most important direction of pathogenetic therapy of multiple sclerosis is to modulate the course of the disease in order to prevent exacerbations, stabilize the patient’s condition and, if possible, prevent the transformation of the remitting course of the disease into a progressive one. The components of the pathogenetic therapy of multiple sclerosis — immunosuppressants and immunomodulators — have a single name “DCCMS” (drugs that change the course of multiple sclerosis). immunomodulators containing interferon beta (interferon beta-1a for subcutaneous and intravenous administration) and glatiramer acetate are used. These drugs alter the immune balance in the direction of an anti-inflammatory response.
Second—line drugs — immunosuppressants – block many immune responses and prevent the penetration of lymphocytes through the blood-brain barrier. The clinical efficacy of immunomodulators is evaluated at least once every three months. Annual MRI is shown. When using interferon beta, regular blood tests (platelets, leukocytes) and liver functional tests (ALT, AST, bilirubin) are necessary. From the group of immunosuppressants, in addition to natalizumab and mitoxantrone, cyclosporine and azathioprine are used in some cases.
The aim of symptomatic therapy is to relieve and weaken the main manifestations of multiple sclerosis. Antidepressants (fluoxetine), amantadine and CNS stimulants are used to relieve chronic fatigue. With postural tremor, non-selective beta—blockers (propranolol) and barbiturates (phenobarbital, primidone) are used, with intentional tremor – carbamazepine, clonazepam, with resting tremor — levodopa preparations. Carbamazepine or other anticonvulsants and barbiturates are used to relieve paraxysmal symptoms.
Depression responds well to treatment with amitriptyline (tricyclic antidepressant). However, it should be remembered about the ability of amitriptyline to delay urination. Pelvic disorders in multiple sclerosis are caused by a change in the nature of urination. In case of urinary incontinence, anticholinergic drugs, calcium channel antagonists are used. In case of violation of emptying of the bladder, muscle relaxants, stimulants of contractile activity of the detrusor of the bladder, cholinergic agents and intermittent catheterization are used.
Prognosis and prevention
With multiple sclerosis, the prognosis for further life is generally favorable. The possibility of a fatal outcome can be minimized with the help of adequate treatment of the underlying disease and timely resuscitation measures (including ventilation). The natural course of multiple sclerosis implies disability of patients during the first 8-10 years of the disease.
Methods of primary prevention of multiple sclerosis do not exist today. The main component of secondary prevention of multiple sclerosis is long-term immunomodulatory therapy.
