Huntington's chorea: symptoms and treatment, methods of diagnosis

Huntington Horea is a progressive hereditary disease of the central nervous system. In the literature it occurs under the name of Huntington's disease, degenerative chorea, hereditary chorea, chorea progressive chronic, choreic dementia. All this is the same disease. It is manifested by spontaneous violent movements, mental and mental disorders. Although the disease was described as far back as 1872. American doctor Huntington, a special interest in the philistine to him appeared after the release of the series "Doctor House the main character of which had a high risk of developing this serious illness.

Causes of the disease

Chorea is a Greek term, literally translated as "dancing". Physicians call this word disorderly, involuntary, rapidly changing each other arrhythmic movements in various muscles of the human body. This symptom often appears one of the first in Huntington's disease, which was the name. Frequency of occurrence is 3-10 cases per 10, 00 population. The disease is based on genetic pathology.

The short shoulder of the 4th human chromosome is responsible for the synthesis of the protein of hentingtin, which contains the amino acid glutamine. Normally, this region contains a certain number of repeats of the trinucleotide sequence of cytosine-adenine-guanine (CAG), the gene record responsible for the amino acid glutamine. When the gene mutates, an increase in the number of repeats of the CAG occurs, which leads to an extension of the amino acid chain and a violation of the structure of the protein of hentingtine. "Wrong" protein, built into the metabolism, leads to the death of nerve cells located in the brain. And there are symptoms that are characteristic of Huntington's disease.

The rule is a sequence length of 36 CAGs, if more often their number increases from 37 to 121. To date, it has been proven that the higher the number of CAGs in a mutated gene, the earlier at an earlier age the disease will manifest itself (it is proved for repeats of CAGs over 60). Another feature of Huntington's chorea is the possibility of increasing the repetition of the CAG (increasing the length of repetition) in the transmission on the paternal line, i.e. among men. When the gene is transmitted from the mother, both growth and decrease in the repetitions of the CAG are possible. An extremely high incidence of pathological gene expression is characteristic - by the age of 70 the disease manifests itself in 100% of cases. T. e. carriers of the mutation must fall ill. These features are taken into account when conducting genetic counseling in families with Huntington's chorea.

The death of nerve cells is diffuse, changes are observed both in the deep structures of the brain and in its cortex. Gradually diminish the volume and mass of the brain due to the atrophy of the brain substance. Instead of nerve cells, connective tissue proliferates. All this leads to the emergence of choreic movements, mental retardation and mental disorders.

Symptoms

Unreasonable grimacing during a conversation can be a sign of chorea.

To date, two forms of Huntington's disease have been studied:

• Huntington's typical chorea (classical): develops usually after 40 years. In the clinical picture, excessive movements with a decrease in muscle tone prevail;
• juvenile form (variant of Westphalus) - appears early, in the first-second decade of the patient's life (the earliest case, described in medicine - at 3 years).

The juvenile form is about 10% of all cases of Huntington's disease. With this form, the muscle tone is increased, and involuntary movements are less pronounced. Despite this, has a very unfavorable course with an early fatal outcome.

The typical form of the disease has the following features. The disease creeps up to the patient gradually. There are "small" strangeness in mimicry:

• grimacing in conversation;
• smacking lips;
• sniff;
• frowning of the eyebrows;
• frequent unmotivated sighs;
• the publication of various sounds that do not correspond to place and time (for example, grunting);
• sticking out a tongue and the like.

Gradually, the chorea progresses, the movements on the face are joined by "unnecessary" movements in everything body: nodding, dancing, waving hands, swaying to the sides, crossing hands or feet. Developed a violation of swallowing, speech becomes incomprehensible. Motor disorders also manifest themselves in the form of inability to maintain a given time pose: a person can not fix the look on the subject for more than 20 seconds, can not hold a compressed fist. At the beginning of the disease, it is possible to arbitrarily suppress unnecessary movements and facial expressions, gradually volitional control is lost.
Disturbance of swallowing can lead to ingestion of food into the broncho-pulmonary system and contribute to the development of pneumonia.

At the initial stage of the disease, "extra" movements can be provoked by the following tests:

• put Romberg in a pose: legs together, arms raised up to the horizontal, palms facing down, eyes at first open, and then closed;
• in the supine position on the back with arms outstretched;
• talk with the patient about these movements.

Over time, pathological movements may disappear, there is a general slow motion, muscle tone rises, is broken ability to self-service and even the most primitive skills are lost: fastening buttons, the ability to use a spoon and fork and and so forth.

Muscular strength with Huntington's chorea is not disturbed, sensitivity does not suffer. As the disease develops, most patients develop nystagmus: involuntary eye movements of a rhythmic nature. Disorders of urination can appear already at later stages of the disease.

Another characteristic feature of Huntington's chorea is a disturbance of the psyche. Usually these symptoms occur against the background of "unnecessary" movements. In the beginning, it's just increased emotionality, short temper, sleep disturbance, decreased attention, memory impairment. There is a tendency to bad habits: alcoholism, drug addiction, gambling, the emergence of hypersexuality. Gradually, mental disorders progress: there are unmotivated aggression, delusions, suicidal thoughts and hallucinations. Criticism to its condition is reduced, the patients become completely inadequate.

Intellectual indicators are falling, patients are not oriented in the environment, they do not recognize their relatives. Such a patient is a great grief for the family. All this ultimately leads to the development of dementia (dementia), total lack of intelligence. Of course, patients with Huntington's chorea require constant care at this stage.

Usually from the onset of the disease to the fatal outcome is 10-20 years. Such patients die of joining infection, pneumonia. Sometimes suicidal attempts cause death.

The version of Westphalus has a more malignant course. Excessive movements are less pronounced, but epileptic seizures may additionally occur. Early speech disorders occur. The lethal outcome occurs in 8-10 years.

Huntington's disease is always hereditary, autosomal dominant. This means that in a family where a disease is detected, the risk for the next generation is very high.

Diagnostics

To date, there is only one method that allows you to diagnose a disease with a probability 99% (in medicine there is nothing to say about any phenomenon of 100%) - it is molecular-genetic. After collection of blood from the vein, a polymerase chain reaction is carried out. During this reaction, the genes are "scanned the number of repetitions of the CAG is counted. The number of repetitions over 36 indicates Huntington's chorea. Some researchers consider the result of 37-39 repeats of the CAG to be questionable.

Chorea Huntington is a hereditary disease, and is usually clearly traced through the genetic tree. The probability of inheriting the disease in children is 50%. The method of molecular genetic diagnosis can be used for in vitro fertilization (IVF) for the purpose of producing healthy children at the stage of embryo selection for implantation. It is also possible to conduct a study at a later date, naturally occurring pregnancy, but taking the fetal biomaterial is a very risky exercise.

Of the additional research methods that can detect changes in the brain with Huntington's chorea, use computed tomography (CT), magnetic resonance imaging (MRI). There is an atrophy of the brain, an expansion of the cerebrospinal spaces (external and internal hydrocephalus), however these changes are nonspecific. Positron emission tomography (PET), functional MRI can help in the search for pathology even before clinical manifestations.

Treatment

Unfortunately, to date, Huntington's chorea is incurable. The entire spectrum of medications used can reduce individual symptoms of the disease, but can not stop the progression of the process. Usually, you need constant medication. Can be applied:

• tetrabenazine (tetmodis) - synthesized specifically to reducemotor disorders in Huntington's chorea. It is used in a dose of 1, mg 1-3 r / d. The maximum permissible dose is 25 mg 3 r / d;
• neuroleptics (haloperidol, ridazine, moden, pimozide, eglonil, sonapax, azaleptin) - to reduce involuntary movements and mental disorders. Haloperidol is applied to, mg 3 r / d, gradually increasing the dose to achieve the effect, usually 10-15 mg / day;
• antidepressants - tricyclic antidepressants (amitriptyline) or selective serotonin reuptake inhibitors (eg, fluoxetine). Amitriptyline prescribed for 25-50 mg at night with a subsequent increase in dose to achieve the effect, the maximum possible dose 300 mg / day in several doses, fluoxetine 20 mg / day (10 mg 2 r / d or 20 mg in the morning), the maximum dose of 80 mg / day;
• with convulsions - drugs valproic acid (sodium valproate). Begin with 300 mg of 2 r / d, the dose is gradually increased until the cessation of convulsive syndrome;
• with an increase in muscle tone and in the late stages of the disease, antiparkinsonian drugs (levodopa) can be used.

Previously, there were attempts at surgical treatment of Huntington's chorea. Carried out the so-called stereotaxic operations. However, they did not have an effect, so at present operative treatment is not used.

Today, molecular genetics research is being conducted, aimed at creating drugs that will stop the synthesis of long chains of the gene for hentington. And then patients with Huntington's chorea will receive hope for healing.

Educational program on neurology, lecture on "Huntington's disease". Reads Alexey Kotov.