Etiology and pathogenesis
The exact cause of the disease has not yet been established. Multiple sclerosis is considered multifactorial: its development requires a combination of external triggers (for example, viral infections, geographical and environmental features), endocrine changes, and genetic predisposition, which determines a specific type of immune response.
For a long time, the disease was considered exclusively a demyelinating pathology of the white matter. However, it is now proven that axons and the gray matter of the hemispheres are actively involved in the pathological process.
The disease is based on two parallel processes:
- Multifocal inflammation: an attack by the body's own immune system destroys the myelin sheaths of nerve fibers.
- Neurodegeneration: irreversible damage to central axons and the death of neurons themselves.
Demyelination plaques vary in size from millimeters to several centimeters. They are most often localized around the brain ventricles, in the white matter of the spinal cord, cerebellum, brainstem, and optic nerves.
Clinical presentation and types of course
In 90% of cases, the onset is characterized by a relapsing-remitting course — an alternation of exacerbation and remission periods. The first attacks of the disease often end with complete restoration of functions, but over time, neurological deficits accumulate due to irreversible damage to conducting pathways. Subsequently, the disease may transition into a secondary progressive stage. About 10% of patients initially have a primary progressive form, in which impairments steadily increase from day one.
Symptoms during an exacerbation increase gradually, over several days. The most typical manifestations:
- Motor disturbances: central paresis, predominantly affecting the legs.
- Coordination disorders: cerebellar ataxia.
- Visual disturbances: unilateral or bilateral retrobulbar neuritis (vision loss), double vision (diplopia), nystagmus, strabismus.
- Sensory disturbances: impairment of deep and superficial sensation of the pathway type.
- Pelvic disorders: urinary urgency, incontinence or urinary retention, constipation, impotence.
An important clinical feature is the "flickering" of symptoms throughout the day. Psychoemotional changes are also characteristic: depression, euphoria, reduced self-awareness, pronounced fatigue, and memory impairment.
Prognosis
A benign variant of the course is observed in only 20% of patients (they maintain the ability to work for 10–20 years or longer). In typical cases, the patient gradually loses independence: 10 years after the onset of the disease, half of the patients cannot walk without support or use a wheelchair.
Average life expectancy is reduced by 10 years. The main cause of fatal outcomes is secondary infections (pneumonia, urinary tract infections) against the background of severe pelvic disorders and immobility.
Diagnostics
Making a diagnosis requires two conditions: confirmation of dissemination in space (multiple lesions) and dissemination in time (chronic wave-like progression). Infections and tumors with similar symptoms must be ruled out.
- MRI (magnetic resonance imaging): the leading instrumental method. Allows visualization of multiple lesions in the white matter. The use of contrast (gadolinium) helps detect active inflammation — fresh lesions uptake the agent in T1 mode.
- Evoked potentials (EP): examination of auditory, visual, and somatosensory pathways confirms multifocality of the lesion by recording slowed impulse conduction.
- Cerebrospinal fluid analysis: during an exacerbation, 80% of patients show mild pleocytosis (from 5 to 50 lymphocytes per 1 µL) and an elevated gamma-globulin level. Detecting oligoclonal immunoglobulin bands by electrophoresis is of critical diagnostic importance.
Principles of treatment
Therapy is divided into the management of acute attacks and long-term prevention.
Management of exacerbations: Corticosteroids are the drugs of choice. The gold standard is intravenous methylprednisolone pulse therapy (500–1000 mg/day for 3–5 days). Then the patient is switched to oral forms (60–80 mg/day) for 5–7 days, followed by a gradual dose reduction (by 5 mg every 2 days) until complete discontinuation.
Disease-modifying therapy (prevention): Aimed at reducing the number of relapses, preventing the formation of new MRI lesions, and slowing down disability. Immunomodulators are used:
- Interferon beta-1b (subcutaneously every other day).
- Interferon beta-1a (intramuscularly once a week or subcutaneously 3 times a week).
- Glatiramer acetate (subcutaneously daily).
These drugs require regular administration.
In progressive course, cytostatics (methotrexate, azathioprine, cyclophosphamide) and mitoxantrone are prescribed.
Briefly: answers to topical questions
What drugs are classified as disease-modifying therapies for multiple sclerosis (DMTs), including second-line ones?
Sources classify the following as disease-modifying therapies for multiple sclerosis (DMTs):
- Interferons — interferon beta-1a, interferon beta-1b, peginterferon beta-1a, sampeginterferon beta-1a.
- Other drugs — glatiramer acetate.
- Oral drugs — teriflunomide, dimethyl fumarate, fingolimod.
- Monoclonal antibodies and other DMTs indicated when switching therapy — natalizumab, ocrelizumab, alemtuzumab, cladribine, ozanimod, divozilimab, ofatumumab.
In steadily progressive multiple sclerosis, cytostatics are used: azathioprine, methotrexate, cyclophosphamide, as well as mitoxantrone.
What types of multiple sclerosis course are distinguished in modern classification?
Modern classification distinguishes three main types of multiple sclerosis course.
- Relapsing-remitting multiple sclerosis — characterized by the presence of relapses, with no progression of disability during the interictal period.
- Secondary progressive multiple sclerosis — develops after a period of relapsing-remitting course and is characterized by confirmed progression of disability independent of relapses.
- Primary progressive multiple sclerosis — manifests with confirmed progression of disability from the onset of the first symptoms of the disease.
What diagnostic criteria are used to confirm the diagnosis of multiple sclerosis?
To confirm the diagnosis of multiple sclerosis, criteria based on proving the dissemination of lesions in space and in time are used.
- McDonald criteria — 2017 revision is used for adult patients and children without encephalopathy at onset. For an atypical onset, the 2010 criteria can be used.
- International Pediatric MS Study Group criteria — 2013 revision is used for patients under 18 years of age in the presence of encephalopathy or general cerebral symptoms.
- MAGNIMS criteria — 2016 revision allows establishing a diagnosis at earlier stages.
What scale is used by neurologists to assess the degree of disability in patients with multiple sclerosis?
To assess the degree of disability and severity of neurological disorders in patients with multiple sclerosis, standardized scales are used.
- Expanded Disability Status Scale (Expanded Disability Status Scale) — assesses the severity of neurological disorders. High scores on the scale (7.0–10.0) correspond to severe disability, loss of the ability to move and care for oneself.
- Kurtzke Functional Systems Scale — used during a neurological examination to assess functional systems.
The key to the diagnosis is "Dissemination in space and time." Space refers to multiple lesions on MRI (brainstem, spinal cord, optic nerve), and time refers to the alternation of relapses and remissions.
Class and exam questions
What is the difference between a primary progressive course and a secondary progressive course?
Primary progressive course (about 10% of cases) means that symptoms steadily worsen from the very beginning of the disease. Secondary progressive develops later, when the classic relapsing-remitting course transitions into a stage of continuous worsening.
Why is a contrast agent (gadolinium) used in MRI?
Gadolinium enhancement on T1-weighted images marks fresh demyelinating lesions. This indicates an active ongoing pathological process at the current time.
What cerebrospinal fluid changes are characteristic of multiple sclerosis?
During an exacerbation, cerebrospinal fluid analysis reveals a mild lymphocytic pleocytosis (5–50 cells), elevated gamma-globulins, and, most importantly, oligoclonal immunoglobulin bands (on electrophoresis).
What is the most common cause of death in patients with multiple sclerosis?
The main cause of death is secondary infections (pneumonia, urinary tract infections leading to renal failure). These develop against the background of profound immobility and severe pelvic sphincter dysfunction in the late stages.
What else to study on this topic
- Acute disseminated encephalomyelitis: differentiation from multiple sclerosis
- Differential diagnosis of multiple sclerosis with infectious and neoplastic lesions of the CNS
- Methodology for studying visual, brainstem auditory, and somatosensory evoked potentials (EP)
- Pharmacology of disease-modifying therapies for multiple sclerosis (DMTs)
- Management algorithms for patients with severe pelvic sphincter dysfunction
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