Alexander's disease (Rosental's leukodystrophy, Rosenthal's disease) is a fairly rare disease of the nervous system caused by a gene mutation. Symptoms develop as a result of malnutrition of nerve cells and a block of conduction of nerve impulses along myelin fibers. The clinical picture of the disease is very diverse. Effective methods of treatment do not exist yet. In this article you can get acquainted with the causes, symptoms, methods of diagnosing Alexander's disease, as well as the possibilities of providing medical care to such patients.
For the first time the disease was described by the pathologist Aleksander in 1949. The disease is characterized by a steadily progressing course. The prevalence of Alexander's disease has not been reliably studied due to the low occurrence of this pathology. About 500 cases of the disease in the USA are described; A study in Japan found the presence of 1 case of a disease for , 0, 00 people. The probability of occurrence of Alexander's disease in the human population is estimated theoretically: - 000 000. It is precisely known that the onset of the disease does not depend on race, sex, or place of residence on the Earth.
Content
- 1Causes
- 2Symptoms
- 3Diagnostics
- 4Treatment
Causes
In 95% of cases, Alexander's disease develops as a result of a mutation in a gene located on the 17th chromosome. Usually the mutation arises spontaneously, that is, the parents are perfectly healthy, their genotype does not have such changes. Most likely, the change in the gene occurs in the paternal chromosome during spermatogenesis, and if such an "abnormal" sperm fertilizes the egg, then the disease develops in the child.
The gene is responsible for the production of glial fibrillar acidic protein GFAP. In the case of mutation, the altered GFAP protein accumulates in the neuronal auxiliary cells (neuroglia), which prevents the supply of neurons with nutrients. In addition, with Alexander's disease in the most altered GFAP protein, nodules are formed, which are called Rosenthal fibers. The latter interfere with the normal conduct of nerve impulses along myelinated fibers.
In 5% of people who are diagnosed with Alexander's disease, such or other genetic defect is not detected, that is, the cause of development remains unknown.
Symptoms
The disease first manifests itself in people of different ages. Depending on this, it is customary to distinguish several clinical forms:
- infantile (infantile);
- juvenile (youthful);
- adult.
It is assumed that there is a so-called neonatal form of the disease, when the child is born with manifestations of the disease. In such children, usually from the first days of life, there is increased intracranial pressure, an abnormally large skull. Characterized by a convulsive syndrome, a marked delay in neuropsychic development. Unfortunately, the life expectancy of such children is not even a year. Some scientists attribute this form to infantile, but with a very early onset.
Infantile formdevelops in early childhood, on average - after reaching 6 months. These children have a bad appetite, they often regurgitate until vomiting. There is a pathologically rapid increase in the size of the head, an increase in intracranial pressure. Naturally, this affects the pace of physical and neuropsychic development. Children badly gain weight, late start to keep their head (after 3 months), sit down and crawl. As the child grows and develops, muscle weakness in the limbs (paresis) develops along with increased muscle tone (spasticity), which manifests itself by limiting the volume and strength of arbitrary movements. Against the background of paresis in the limbs, involuntary movements appear: twisting, vermiform movements in the fingers, turning the head with fixation of the posture and the like. These phenomena are called hyperkinesis, in particular, choreoathetosis. Possible convulsive epileptic seizures. The intellect suffers: children do not recognize their loved ones, they are not pleased with toys, they do not master skills (for example, they can not string rings on a pyramid at the appropriate age). Also, coordination of movements is disturbed, twitchings of eyeballs (nystagmus) are observed. Independent walking is almost impossible. The disease progresses steadily and ends with death within 2-3 years.
Juvenile formmanifests itself somewhat later, at the age of 4 to 14 years, on average - about 9 years. Although some signs of the disease may appear earlier - in 2-3 years, but they are usually not associated with Alexander's disease. Such children lag somewhat behind in neuropsychological development, suffer from seizures. They have a larger head in comparison with their peers (but not so much larger than the infantile form). Somewhat later, speech disorders (blur, fuzziness), popperation at ingestion of food, and then during swallowing of water are added. The voice acquires a nasal hue. Movements in the language are difficult. All these changes form bulbar and pseudobulbar disorders, and arise as a result of damage to the brainstem. In the mornings, patients are disturbed by indomitable vomiting. Just like in the infantile form, there is a muscle weakness in the limbs, which gradually builds up.
Muscular tone increases, muscles become dense and firm to the touch, pathological stop signs appear (Babinsky's symptom and others). Gradually, these changes cover all four limbs, which is the cause of movement disorders and self-care. Possible disturbance of balance, behavioral disorders. Usually intellectual disorders are expressed little or none, although cases of a sharp decrease in cognitive abilities are described. In patients with juvenile form, a reflex stopping of respiration is periodically recorded: apnea. In the end, the progressive defeat of the nervous system ends in death, on average, 10 years from the appearance of the initial clinical signs of the disease.
Adult formdevelops in the period from 20 to 70 years. Clinical symptoms are quite diverse, as they can be a reflection of the pathology of any part of the brain. Most often these are pareses and paralysis with increased muscle tone, impaired coordination of movements and balance, involuntary uncontrolled movements, speech and swallowing disorders. Decreased intelligence is insignificant. Often there is nystagmus and violation of friendly (simultaneous and unidirectional) movements of the eyeballs. The disease progresses and inevitably ends with a lethal outcome (usually from the attachment of intercurrent infections).
Diagnostics
Diagnosis of the disease in vivo is rather difficult, because there are no clinical symptoms peculiar only to Alexander's disease. And none of the research methods reveal any specific changes (not counting the genetic analysis, which, nevertheless, it is still necessary to prescribe, suspecting this disease).
When magnetic resonance imaging of the brain (MRI) with Alexander's disease, demyelination of various parts of the brain is detected (when infantile and youthful forms - mainly in the frontal with the spread to other areas, with the adult - more pronounced in the cerebellum and the brain stem).
In electroencephalography, changes in the bioelectrical activity of the brain in the frontal regions are recorded.
Genetic analysis most accurately confirms the diagnosis of Alexander's disease: find a mutation in the gene GFAP on the 17th chromosome (in 95% of cases). It should be remembered that 5% of patients with this disease did not have a genetic defect to this day.
Confirmation of the disease is the detection of Rosenthal fibers (which is possible with brain biopsy or after death at autopsy).
Treatment
Today, medicine does not have effective methods of treating Alexander's disease. Perhaps the future in this direction belongs to genetic engineering.
After the diagnosis is established, symptomatic therapy is usually performed, which makes it possible to facilitate and prolong the life of the patient:
- at pareses prescribe stimulators of neuromuscular conduction (Neurromidine);
- with spasticity of muscles - muscle relaxants (Baclofen, Sirdalud, Midokalm);
- with epileptic seizures - anticonvulsant drugs (Valproate, Sibazon and others);
- Neuroleptics (Haloperidol, Azaleptin and others) can be used to reduce involuntary movements.
For movement use special devices, including orthopedic. The peak of the disease allows you to move only with the help of a wheelchair. Of course, in the terminal stages of the disease, patients need constant external care.
Alexander's disease is a rare, mainly, genetically determined disease. His detailed clinical picture represents movement, coordination disorders, problems with speech and eating. Almost all adult patients live no more than 10 years from the moment of the disease development. The most accurate method of diagnosis is genetic. Methods of treatment are under development, patients are currently being helped only by symptomatic means.
