Demyelinating disease are a large group of diseases in which the myelin sheaths of the structures of the central and peripheral nervous system are destroyed. They have a multifactorial nature, occur with a combination of burdened heredity and external risk factors. The most common nosologies are multiple sclerosis, various clinical forms of multiple encephalomyelitis and polyneuropathies. Diagnosis of demyelinating pathologies requires MRI, neurophysiological and immunological studies. Treatment includes hormone therapy, immunosuppression, extracorporeal hemocorrection, multidisciplinary rehabilitation.
G35-G37 Demyelinating diseases of the central nervous system
More than 500 thousand patients with various demyelinating pathologies have been registered in the USA, of which 30% are people with multiple sclerosis. The incidence rate ranges from 30-70 cases per 100 thousand population in different regions of the country. Demyelinating disease are a serious health problem, because they reduce the quality of life and ability to work, and require high treatment costs. Specialists in the field of experimental and practical neurology are constantly working on new therapies that give hope for achieving a stable remission or a complete cure.
The multifactorial theory of demyelinating disease is generally accepted, according to which they occur with a combination of external and internal provoking factors. Most pathologies are associated with hereditary causes. These patterns are best studied in patients with multiple sclerosis (MS), for the development of which at least 2 genes from the HLA complex are responsible. Exogenous risk factors include the following:
- Infections. The specific causative agent of multiple encephalomyelitis is the ADEM virus. Often, demyelination is provoked by measles, rubella, and infectious mononucleosis viruses. HIV infection deserves special attention: encephalopathy and dementia develop in 15-20% of patients at the AIDS stage.
- Metabolic disorders. Demyelinating processes by the type of myelinolysis develop with the accumulation of nitrogen metabolism products against the background of CRF, decompensated diabetes mellitus, pathology of the urea metabolism cycle.
- Cerebral ischemia. The defeat of the myelin sheaths is provoked by episodes of impaired cerebral circulation. They are typical for people with complicated hypertension, recurrent hypertensive crises, severe arrhythmias.
- Intoxication. Poisoning with chemical solvents, paint and varnish products, and carbon monoxide play a role in the development of demyelinating disease. Provoking factors include overdoses of medications that affect the regulation of cardiorespiratory activity and cause hypoxia.
- Vaccination. Isolated cases of CNS damage after immunization, with optional vaccination against influenza and rabies are described. Such pathologies are caused by the individual reaction of the body to vaccination and more often develop in patients with burdened heredity.
Myelin is the outer shell of nerve fibers and consists of several layers of plasmolemma. It provides electrical insulation and nerve power so that impulses can quickly reach different structures of the nervous system. Demyelination is a pathological process of loss of myelin with relative preservation of axons. It should be distinguished from myelinopathies – a disease in which the primary processes of formation of myelin sheaths are disrupted.
Depending on the type of damage, there are 4 types of demyelination: dizimmuninflammatory, viral, metabolic and hypoxic-ischemic. Dizimmuninflammatory forms occur in multiple sclerosis and pathologies close to it. It is manifested by selective focal destruction of myelin, the appearance of lipophytes and proliferation of microgliocytes. At the same time, most axons in the central nervous system continue to function.
Viral demyelinating disease develop when pathogens accumulate in the nervous tissue, which gradually destroy the myelin sheaths. Hypoxic-ischemic injury is associated with chronic episodes of hypoperfusion of the brain or with damage to the central nervous system by neurotoxic agents. Metabolic demyelination may be associated with sudden fluctuations in sodium levels. In this case, central pontine myelinolysis develops.
Taking into account etiopathogenesis, demyelinating disease are divided into primary, which occur without a clear cause under the influence of autoimmune mechanisms, and secondary – the result of the damaging action of viral or toxic agents. In practical neurology, classification by lesion localization and clinical course is widely used. According to her, there are such variants of demyelinating diseases:
1. CNS lesions. In this case, the damage is localized in the white matter of the brain and spinal cord. The diseases are characterized by a severe course, steady progression and violation of all neurological functions. According to the rate of development , they are divided into subgroups:
- Sharp. This category includes primary multiple encephalomyelitis and its individual forms: opticomyelitis, disseminated myelitis, polioencephalitis. The acute course is typical for parainfective and vaccinal encephalopathies.
- Subacute. This type of course is characteristic of multiple sclerosis, which manifests itself in the form of cerebrospinal, cerebral, optical and other clinical forms.
- Chronic. This group of demyelinating diseases includes Dawson’s encephalitis, Pette-Dering, diffuse Schilder leukoencephalitis.
2. Peripheral nerve damage. Primary polyradiculoneuritis is most often diagnosed in Guillain-Barre disease. Also, the group of peripheral demyelinating pathologies includes infectious and toxic neuropathies, diabetic polyneuropathy.
The debut takes place at a young age. Initial symptoms are represented by paresthesia in one or more limbs, muscle weakness in the arms and legs, periodic visual disturbances. Patients note a slight discoordination of movements, instability of gait. Sometimes, at the beginning of the disease, disorders of the functions of the pelvic organs manifest themselves: urinary incontinence, frequent urge to urinate.
As multiple sclerosis progresses, paresis or paralysis of the extremities occur, the functions of the cranial nerves (CN) are disrupted, lesions of sensitive nerve fibers are intensified. Muscle spasticity is added, which increases with the patient’s verticalization and during walking. Dissociation syndrome is typical for MS: a discrepancy between internal organ lesions and clinical symptoms.
Acute multiple encephalomyelitis
Clinical manifestations of demyelinating disease correspond to encephalopathy. Pathology manifests itself with disorders of consciousness of varying severity – from deafness to coma. Patients are concerned about severe headaches, nausea, vomiting, which does not bring relief. Neurological symptoms reach a maximum within a few days, which is why patients are hospitalized in the intensive care unit.
Focal manifestations are variable and depend on the localization of the lesion. Demyelinating pathology is manifested by coordination disorders, paralysis of half of the case, impaired vision, speech and other functions that are controlled by the PMN. Up to 35% of cases are accompanied by epileptic seizures, about 25% of patients suffer from radicular pain syndrome, pelvic organ dysfunction.
The main sign of the disease is symmetrical muscle weakness, which begins in the legs and gradually spreads to the muscles of the trunk, upper limbs, face and neck. It is accompanied by unsteadiness of gait, tingling in the arms and legs, back pain. The muscles responsible for swallowing and articulation are involved in the process, therefore dysphagia and dysarthria develop. With paralysis of the respiratory muscles, asphyxia is possible.
Other types of polyneuropathies
Peripheral nerve damage is manifested by a combination of motor, sensory and autonomic symptoms. Most cases of demyelinating disease begin with muscle weakness in the distal extremities, which gradually spreads to the overlying parts of the body and can reach the respiratory muscles. Characterized by depression or complete absence of tendon reflexes.
At the onset of polyneuropathy, patients complain of a symmetrical violation of sensitivity by the type of “socks” and “gloves”. In the distal parts, there is increased pain and tactile sensitivity, some patients complain of a crawling sensation of goosebumps and numbness of the skin. Gradually, the symptoms of irritation are replaced by signs of loss of neurological function, temperature and pain sensitivity are disturbed.
Demyelinating disease are accompanied by neurological deficiency, which is inexorably progressing. In the later stages, the patient is assigned a disability group due to motor or cognitive impairments. In acute diseases (concentric sclerosis, multiple encephalomyelitis), a fatal outcome is possible in the first months. Diffuse-disseminated sclerosis ends in death 3-7 years after the onset of symptoms.
Demyelination is characterized by total muscle damage, so at least a third of patients develop respiratory failure, impaired chewing and swallowing of food, disorders of speech function. Bulbar syndrome caused by a lesion (PMN) is especially severe. Disorders of the autonomic nervous system are joined, which are manifested by arrhythmias, fluctuations in blood pressure. violations of peristalsis and pelvic organs.
To detect demyelinating disease, the patient needs a full examination by a neurologist. At the initial consultation, much attention is paid to the collection of anamnesis, since 80% of people have risk factors in the form of past infections, iatrogenic interventions, intoxication and other exogenous hazards. The examination is supplemented by an assessment of the neurological status. The diagnostic program consists of the following methods:
- Brain MRI. Neuroimaging of the brain and spinal cord is the main method for diagnosing demyelination in the central nervous system, determining its topography and size. The doctors’ attention is attracted by the combination of foci accumulating and not accumulating contrast agent within the framework of one MRI image.
- Neurophysiological diagnostics. In case of convulsive syndrome, classical electroencephalography and EEG with sleep deprivation are necessarily performed to detect epileptiform activity. Signs of peripheral nerve pathology requires electroneuromyography, which determines the localization of pathology and the rate of passage of nerve impulses.
- Immunological tests. Mandatory for MS is the examination of blood and cerebrospinal fluid for IgG oligoclonal antibodies. To determine possible provoking factors, an analysis is performed for antibodies to native DNA, cardiolipin, lupus anticoagulant. To distinguish MS from opticoneuromyelitis, a study on antibodies to aquaporin-4 allows.
- Additional methods. The basic diagnostic program includes general blood and urine tests, advanced biochemical blood analysis, determination of acute phase parameters. Serological and molecular genetic reactions are performed to exclude chronic infections.
- Consultations of specialists. Visual disorders require consultation with an ophthalmologist, ophthalmoscopy, biomicroscopy of the eye and visometry. With hearing loss, the patient is referred for consultation to an otolaryngologist with mandatory audiometry, a study of auditory evoked potentials.
Differential diagnosis of demyelinating processes is difficult due to the diversity of the clinical picture, the lack of clear clinical and morphological criteria. During the examination, viral and bacterial encephalitis, systemic connective tissue diseases, paraneoplastic syndrome are excluded. In complex cases, the symptoms are differentiated with the manifestations of mitochondrial diseases, for which a muscle biopsy and DNA diagnostics are prescribed.
The treatment regimen is selected individually for each patient, taking into account the type of disease, its stage, severity and clinical features. Patients with moderate manifestations of neurological deficit and stable development of the disease are treated at home under the supervision of a doctor. In more severe forms, hospitalization in a neurological hospital or intensive care unit is required. In demyelinating disease, several directions of conservative therapy are indicated:
- Immunosuppression. Since the pathology is autoimmune in nature, treatment with glucocorticosteroids is prescribed to relieve symptoms. Hormonal pulse therapy with parenteral administration of medications is indicated for rapid relief of exacerbation. If they are ineffective, cytostatics, interferons, monoclonal antibodies are used.
- Correction of neurological symptoms. To eliminate muscle spasticity, muscle relaxants of central action, anticonvulsants are used. To reduce coordination disorders, drugs are used against systemic dizziness. Correction of psychoemotional status is carried out with antidepressants and anxiolytics.
- Extracorporeal methods. To remove circulating antibodies and immune complexes, cascade plasma filtration, cryoaferesis, lymphocytapheresis and other methods of hemocorrection are performed. Therapy accelerates the onset of remission and increases its duration.
With secondary forms of demyelinating processes associated with a specific etiological factor, the root cause is eliminated if possible. Patients are prescribed antiviral or antibacterial therapy of neuroinfections, rational hypoglycemic therapy, medicinal and extracorporeal methods of treatment of CRF. In case of toxic forms of polyneuropathy, it is necessary to stop contact with the toxic substance and introduce appropriate antidotes.
Clinical trials of a calcium ion blocker (4-amidopyrine) are underway to relieve the symptoms of demyelinating processes in the central nervous system. It has been proven that the drug accelerates conduction through myelin nerve fibers and reduces the phenomena of neurological deficit. It acts on the calcium channels of the axolemma of the fibers, thereby regulating the action potential.
In 2017, a group of American scientists presented a unique method of gene therapy, which is based on suppressing the activity of immune cells and eliminating autoimmune damage to myelin. Researchers have created a safe virus with the genetic code MOG, which is embedded in the DNA of the liver and reduces the aggression of T-killers on the brain. The therapy is under development and requires long-term preparation for clinical trials.
Patients require comprehensive care and medical and social rehabilitation. These measures are aimed at improving the quality of life, normalizing the physical and intellectual functioning of a person. Physical therapy improves the strength of skeletal muscles, trains the cardiovascular and respiratory systems. Cognitive training, classes with a speech therapist and a clinical psychologist are recommended.
Prognosis and prevention
Despite the improvement of knowledge about etiopathogenesis and treatment options, demyelinating disease are still an unsolvable problem for neurology. Complex therapy slows down or stops their progression, but methods of complete cure have not been developed. Cautious optimism is inspired by the directions of immunotherapy and gene therapy, which affect the root cause of the development of diseases.
There are no effective primary prevention measures. In order to reduce the risk of activation of autoimmune processes, patients with genetic risk factors are advised to avoid toxic effects, neuroinfections, polypragmasia of drugs. A rational approach to routine vaccination is needed, which prevents measles, rubella and other infections that act as triggers of demyelinating disease.