What kind of disease is chorea? Chorea disease: symptoms and treatment of the disease. How to avoid developing the disease

A hereditary, slowly progressive disease of the nervous system, characterized by choreic hyperkinesis, mental disorders and progressive dementia. The concept of “Huntington's chorea” also corresponds to: Huntington's disease, hereditary chorea, degenerative chorea, progressive chronic chorea. Typically, Huntington's chorea begins to manifest clinically between the ages of 20 and 50 years. Patients with Huntington's chorea undergo symptomatic therapy aimed at suppressing hyperkinesis. The disease has an unfavorable prognosis, with death occurring on average 10-13 years after the onset of the disease.

General information

Etiology and pathogenesis of Huntington's chorea

The Huntington's chorea gene is located on the short arm of chromosome 4p16.3. It encodes the huntingtin protein, the function of which is not fully understood. It has been proven that Huntington's chorea develops as a result of an increase in the number of trinucleotide repeats - cytosine-adenine-guanine, located in the first exon of the gene. The cytosine-adenine-guanine triplet encodes the amino acid glutamine, so an elongated polyglutamine tract is formed in the protein. By forming something like a zipper, the extended polyglutamine region of the huntingtin protein changes its own information and binds tightly to other proteins. As a result, protein aggregation occurs, protein-protein interactions are disrupted, which leads to cell apoptosis.

Clinical picture of Huntington's chorea

Huntington's chorea usually manifests itself between the ages of 20 and 50. Cases of the juvenile form of the disease are quite rare (no more than 10%); the earliest onset of the disease known to date is 3 years. The typical manifestation of Huntington's chorea in adults is chorea syndrome; it is rare in adolescence. The localization of choreic hyperkinesis occurs in the facial muscles, which causes expressive grimaces with protruding tongue, twitching of the cheeks, alternate frowning and/or raising of the eyebrows.

In a number of cases, hyperkinesis was observed in the arms in the form of rapid flexion and extension of the fingers, in the legs in the form of alternately crossing and spreading the legs to the side. The movements are usually not as rapid as with minor chorea, but more complex, sometimes slow (like athetoid ones). With the progression of Huntington's chorea, hyperkinesis intensifies, acquiring the character of athetosis and pronounced dystonia, which subsequently turns into rigidity.

In juvenile forms of Huntington's chorea, in 50% of cases the disease manifests itself in the form of bradykinesia and rigidity. Seizures occur in 30-50% of cases (unlike in adult patients). As the disease progresses, patients experience speech dysfunction. First of all, problems arise with sound pronunciation; the semantic and syntactic structure of speech remains intact until the last stage of the disease. Over time, the speed of speech and its rhythm change.

Oculomotor disturbances are observed in most cases in the early stages of Huntington's chorea. In patients, the automation of saccadic movements of the eyeballs is disrupted: the latent period for the onset of saccadic eye movements is prolonged, the speed of gaze translation and tracking accuracy are reduced. With the development of the disease, most patients experience vertical, less often horizontal, sometimes combined nystagmus.

Diagnosis and treatment of Huntington's chorea

CT or MRI of the brain reveals atrophy of the heads of the caudate nuclei, which increases as the disease progresses. The diagnosis of Huntington's chorea is verified at the molecular genetic level. The polymerase chain reaction is used to determine the number of turns of the cytosine-adenine-guanine triplet in the HD gene. In adult patients, the number of repeats exceeds 36, in the juvenile form of the disease - 50.

To date, no specific treatment for Huntington's chorea has been developed. Symptomatic treatment by a neurologist is indicated, the main goal of which is to combat choreic hyperkinesis. Prescribed drugs that reduce the activity of dopaminergic systems of the brain (haloperidol, reserpine). The dose of the drug is increased every 2-3 days. The effectiveness of stereotactic surgery for the treatment of Huntington's chorea has not been proven.

Forecast and prevention of Huntington's chorea

In most cases of Huntington's chorea, the prognosis for life is poor. Death due to various complications (pneumonia, congestive cardiac activity) occurs after 10-13 years of the disease. The life expectancy of patients ranges from 45 to 55 years.

In the absence of examination methods that make it possible to identify carriers of the pathogen before the manifestation of clinical signs of Huntington's chorea, medical genetic consultation presents certain difficulties. Families of patients are not recommended to have children in the future.

Chorea is a form of hyperkinesis and is a pathology of the nervous system, which is accompanied by problems in the subcortical nodes of the brain and is expressed by chaotic, aimless and episodic twitching mainly in the legs and arms (less often in the torso).

This term has a dual application. It denotes both independent diseases from this group (such as Huntington's chorea or minor chorea), and some syndromes that occur in various pathologies. The name “trochea” is also not accidental: translated from Greek it means a certain type of dance. A sick patient during an attack looks really awkward: fast, abrupt, uncoordinated and jerky movements of the limbs and torso create the impression of a chaotic, somewhat sweeping and involuntary dance. Therefore, chorea acquired another “historical” name - “dance of St. Vitus,” which came to us from the deep Middle Ages. By the way, many people who are in no way involved in neurology have heard about this extraordinary term. The fact is that Saint Vitus, who lived in Sicily, was at one time martyred by the Romans as an active propagandist of Christianity. And later a belief spread that every person who dances in front of the statue of this Saint on his birthday (June 15) will receive as a reward a colossal supply of energy and vigor for at least a year. So, on this day, superstitious citizens began to crowd around the statue, who, for the benefit of their health, did not hesitate to “perform” ridiculously expressive dances. This is where the roots of the expression “St. Vitus’ dance” grow, which over time was dubbed chorea.

The causes of chorea can vary, but are often hereditary. There are four varieties of this pathology, which have become “hostages” of bad genetics (the so-called primary forms). We are talking about Huntington's chorea, Lesch-Nyhan disease, neuroacancytosis and benign hereditary chorea.

Among other provoking factors for chorea, doctors point to the following reasons:

Diseases of an infectious nature (whooping cough, borreliosis, neurosyphilis, HIV, viral encephalitis, tuberculous meningitis).

Metabolic disorders. In this group, a number of “culprit” pathologies are even richer: Sturge-Weber disease, hyperthyroidism, glutaric aciduria, Hallervorden-Spatz disease, hypocalcemia, methochromatic leukodystrophy, Wilson-Konovalov disease, mucopolysaccharidosis, gangliosidosis, Leigh disease, homocystinuria, Merzbacher-Pelitzeus disease , hyperglycemia, Fabry disease, etc.

Intoxication. Poisoning with levodopa, various antipsychotics, digoxin, lithium, mercury, and even oral contraceptives can be fatal.

Autoimmune pathologies. The cause of chorea can be multiple sclerosis, systemic lupus erythematosus, a reaction to immunization, antiphospholipid syndrome, etc.

Structural brain damage. Among them are strokes, various types of traumatic brain injuries, hypoxic encephalopathy and tumor formations.

All types of chorea, provoked by any factor from this group, belong to the secondary forms of the disease. In addition, there is another type of chorea - psychogenic (a type of psychogenic movement disorder).

General signs

Chorea is manifested by short-term chaotic and seemingly random bodily movements, especially in the limbs. Sometimes they resemble the fast and completely normal movements of a healthy, but alarmed person, but they are not part of any adequate planned actions. In other cases, voluntary tremors during chorea are similar to an uncontrollable and emotional “dance.” These jerky twitches can be unilateral or bilateral, and even with the “participation” of both sides of the body, they are not synchronized.

Manifestations of chorea vary depending on the form of pathology. Thus, with mild choreic hyperkinesis, there is slight motor restlessness, which may be accompanied by inappropriate gestures, unexpected fussy movements, some antics, increased emotionality and motor disinhibition. As for clearly defined forms of chorea, they are usually manifested by peculiar movements of a “jack on a string” or a loose, violent “dance”. Severe choreic hyperkinesis distorts not only speech and facial expressions, but even walking movements. The gait of such a sick person can be described as strange and somewhat “clown-like.” Patients with extremely severe chorea, on the other hand, are unable to perform any movements at all. It is difficult for them to move due to constant falls, they are not able to fully take care of themselves in everyday life, and therefore they are dependent on loved ones. Choreic twitching in the facial and oral muscles of the face (including the larynx and tongue) interferes with both verbal communication and food intake. Such patients can easily carry a fork with food past their mouth or cannot “get” a napkin into their nostrils in order to blow their stuffy nose.

Types of chorea and their features

1. Primary forms:

Huntington's chorea. This disease can appear at almost any age, but usually develops between 35 and 45 years of age. It is characterized not only by typical hyperkinesis, but also by dementia (decreased intelligence) and personality disorders. The development of the disease is gradual, sometimes it is even difficult to detect the appearance of the first violent movements. As a rule, they occur in the facial area and look like random motor automatisms (opening the mouth, licking lips, frowning, sticking out the tongue, etc.). As the pathology progresses, hyperkinesis develops in the upper extremities (the so-called “fingers playing the piano”), and also spreads to the torso, disrupting static behavior and gait. Speech and swallowing processes, memory and level of self-care deteriorate even further. As a consequence, dementia occurs.

Sometimes Huntington's chorea starts with mental disorders in the form of behavioral, affective or hallucinatory-paranoid disorders.

Neuroacanthocytosis. In addition to choreic hyperkinesis, it is also manifested by acanthocytosis (i.e. changes in the shape of red blood cells). The main difference between this disease and the previous one is that it causes weakness and atrophy in the muscles of the arms and legs. It is also characterized by oral hyperkinesis with chewing movements, tongue protruding, lip twitching and other grimaces. Another distinctive feature of neuroacanthocytosis is involuntary biting of the lips, tongue and inner surfaces of the cheeks (even bleeding). As a rule, this type of chorea is complicated by attacks of epilepsy and dementia as it progresses.

Lesch-Nyhan disease. This is a congenital pathology, which is caused by a hereditary deficiency of hypoxanthine-guanine phosphoribosyltransferase, which leads to severe disturbances in the functioning of the nervous system and increased production of uric acid. Delayed motor development in a child is noticeable already in the first months of his life, then rigidity of the limbs appears. The first facial grimaces, as a rule, appear already in the second year of life, and signs of damage to the pyramidal tract and mental retardation are also observed. One of the threats of this pathology is that children tend to cause physical harm to themselves by biting their fingers or lips.

Benign (or non-progressive) hereditary chorea. This type of disease manifests itself in early childhood or even infancy. The child has generalized hyperkinesis, which “subsides” only during sleep. The main difference between the disease and Huntington's chorea lies in the following two points: the normal development of intelligence and the non-progressive course of the disease (on the contrary, with benign chorea it is even possible to reduce hyperkinesis in older age).

2. Secondary forms. There are many of them, but the most common are chorea of pregnancy and minor chorea.

Chorea in pregnancy, as a rule, appears in those women who suffered from minor chorea in childhood. This pathology often manifests itself in primiparous women. It manifests itself during the 2-5th month of pregnancy and can be repeated in subsequent “interesting” positions. Signs of the disease, as a rule, go away within a couple of months after childbirth or termination of pregnancy.

Minor chorea (synonymous name - Sydenham's chorea). It often occurs a couple of months after an exacerbation of rheumatism or steptococcal infection. In mild forms, disinhibited movements with expressive gestures and exaggerated grimaces are noted. In more complex forms, choreic hyperkinesis throughout the body deprives the patient of the ability to move normally, serve himself, communicate, and even breathe. Muscular hypotonia, emotional and affective disorders, and a “freezing” or “tonic” knee reflex are also observed.

Treatment

Therapeutic actions depend on the specific type of disease. Thus, for Huntington's chorea, drugs that reduce the activity of dopaminergic systems of the brain are effective: reserpine, haloperidol, phenothiazine derivatives, etc. Tranquilizers and antipsychotics also help the patient cope with depression and internal discomfort. For minor chorea, you should go to the hospital. In addition to bed rest, antibiotics (peni- and novocellin), glucocorticoid hormones, salicylates, calcium supplements, heart medications, and multivitamins are prescribed. Physiotherapy treatments include pine baths, electrosleep, and Shcherbak’s galvanic collar with calcium chloride.

For chorea in pregnant women, magnesium, calcium, salicylates, bromine and other agents that calm the central nervous system are used.

Nervous system diseases, especially those accompanied by hyperkinesis (involuntary pathological movements), are very painfully endured by both the patients themselves and their relatives.

In severe cases, such diseases can lead to patient disability and even death. The accompanying mental disorders can make the patient’s relationship with relatives difficult and painful, and push him towards suicide. Chorea is one such disease.

Huntington's chorea disease - what is it?

Under the term "chorea", especially when it comes to children, often imply any hyperkinesis that occurs as a result of a previous injury or infection of the brain, as well as congenital diseases, for example, cerebral palsy.

Huntington's disease- This is one of the types of chorea that occurs as an independent disease, and not as a symptom of other lesions.

Refers to hereditary hyperkinesis, with it the development of motor and mental disorders.

It manifests itself:

in the form of obsessive movements, which the patient does not control;
decreased muscle tone and development of paresis;
mood swings, depression and other severe symptoms.

Your name Huntington's chorea received in honor of the American psychiatrist who first described her symptoms. The disease is inherited; according to statistics, the disease appears more often in children if their fathers suffered from chorea, and less often in mothers.

The basis of pathogenesis chorea According to modern medicine, there is a violation of DNA synthesis in neurons - the appearance of extra sequences of three nucleic acids. As a consequence, in one of the proteins synthesized in the nervous tissue, additional glutamine molecules appear in the amino acid sequence.

Defective protein does not perform its function and leads to the death of the neuron. As a result of massive death of neurons, motor and mental disorders are formed.

It affects the striatum - the brain structures responsible for the tone of skeletal muscles and the coordination of involuntary movements. These same structures are involved in the implementation of motor stereotypes, for example, walking or other actions that a person performs without thinking. It is in the striatum that the concentration of pathological proteins sharply arises.

The disease carries chronic progressive nature, that is, the patient’s condition deteriorates more and more over time, restoration of damaged functions does not occur, but on the contrary, new symptoms appear.

Huntington's chorea disease in children

Although chorea– a hereditary disease, its manifestations in children are quite rare. In children, other types of chorea are more common, caused by congenital or acquired disorders in the functioning of the brain.

Chorea can be caused in children by:

cerebral palsy, previous encephalitis, including tick-borne encephalitis;
injuries brain;
rheumatic diseases;
quite rare congenital defect - Wilson-Konovalov disease;
copper metabolism disorder, which is accompanied by other symptoms besides chorea.

If the child develops Huntington's chorea, then it tends to be more severe, with a rapid increase in symptoms. In addition, a child, unlike an adult, cannot control the manifestations of the disease through willpower, so in him these manifestations are much more noticeable.

One of the characteristic symptoms is periodic convulsive seizures, which, unlike epileptic seizures, are not accompanied by loss of consciousness and amnesia.

Some drugs used in adults, for children with Huntington's chorea This is not possible, so it is more important for children to follow a regimen and diet that does not allow the course of the disease to worsen. It is also important to take medications strictly as scheduled.

Child, sick chorea, may attend school only with the permission of his attending physician. If the course is severe, he is transferred to home schooling.

Huntington's chorea minor

Small chorea is called hyperkinesis, arising as one of the manifestations of rheumatism. Despite the similarity of symptoms, it is very indirectly related to Huntington’s disease.

Chorea, unlike Huntington's disease, develops in children and adolescents, less often in young men suffering from rheumatism.

The basis of the disease is not genetic mechanisms, but autoimmune– rheumatism develops when the body’s own tissues are damaged by the body’s immune system after a staphylococcal infection. Minor chorea is not present all the time, but only during an exacerbation of rheumatism.

Symptoms of minor chorea– sweeping involuntary movements of the limbs, torso, head, an important feature – facial muscles are usually not involved.

The intensity of attacks of minor chorea does not change or decreases; in most patients, attacks stop several years after puberty. Mental disorders do not occur. In general, chorea minor is much less dangerous to the health and life of the patient than Henryton's disease.

Ask your doctor about your situation

Mental disorders accompanying Huntington's disease

Main danger chorea is a mental disorder.

Along with hyperkinesis, they are the most characteristic sign of the disease:

Emotional lability, unstable mood, low mood – this is symptoms, which are caused by a decrease in the amount of excitatory neurotransmitters.
Memory impairment in the form of anterograde amnesia - the patient has difficulty remembering new information and has difficulty distinguishing faces.
Hyperkinesis of facial muscles makes speech slurred, filled with extraneous sounds. It is often impossible to understand what the patient is talking about. Changes may also affect the patient’s thinking - the inability to clearly formulate one’s thoughts makes communication with him very difficult, sometimes almost impossible.
Depression with chorea wears a pronounced progressive in nature, accompanied by suicidal thoughts and attempts, so strong that suicide often becomes the cause of death of the patient. Apathy, delusional ideas of self-blame, and unmotivated aggression may also develop.
Dementia develops in later stages when there are already pronounced hyperkinesis and mental disorders. Memory impairment occurs, the patient stops remembering people’s faces, loses the ability to care for himself, feed himself, dress, and maintain personal hygiene.
Bad habits such as alcoholism, with chorea intensify and lead to even greater destruction of the patient’s personality.

Causes of Huntington's chorea

Chorea– a genetic disease, it is inherited according to an autosomal dominant principle, that is, the pathological gene that determines the disease chorea is not related to gender and always appears if the patient has inherited it.

If one of the parents is sick with chorea, then in about half of the cases the children will also be sick. The risk is much higher if both parents are sick. It is believed that children of sick fathers get sick more often than children of sick mothers, but there is no explanation for this.

The affected gene encodes development pathological squirrel, which causes the death of neurons in the striatum of the brain, as a result, the functions for which these subcortical structures are responsible begin to fall out.

Despite the fact that the disease is inherited, it usually begins to manifest itself in adulthood, less often in adolescence. The occurrence of chorea in children is an extremely rare situation, and in this case its course is much more severe than usual.

Symptoms

The first symptoms of chorea arehyperkinesis:

Involuntary movements at first appear only in one of the limbs, they occur in paroxysms, and the patient is able to suppress them by force of will.
Over time, violent movements become more and more frequent, then permanent, they involve more and more muscle groups - limbs, torso, neck, facial muscles.
Over time, hyperkinesis takes over most of the skeletal muscles, the patient’s gait becomes dancing, accompanied by unnecessary movements, involuntary gestures, and grimaces.
Hyperkinesis of the hands does not allow the patient perform precise manipulations, then deprive him of the ability to dress, eat and perform basic hygiene procedures independently.
Constant grimaces make speech extremely illegible. The larynx can also be involved in hyperkinesis, and in this case, not only speech, but also breathing is impaired.
In addition to hyperkinesis, there is another important motor symptom – muscle tone steadily decreases, which, in combination with involuntary movements, leads to disability of the patient.
In later stages, the patient cannot move independently and must use a wheelchair or remain bedridden.

Types of disease

There are two main types of disease:

classical;
juvenile

The difference between them is not only in the age of onset of the disease, but also in the predominant symptoms:

with classical chorea hyperkinesis comes first;
with juvenile– muscle hypotonicity.

Mental abnormalities occur in both types and always progress steadily.

Main forms of the disease

Depending on which of the three groups of symptoms (hyperkinesis, hypotonicity, mental abnormalities) is most pronounced, several forms of chorea are distinguished:

Classic or hyperkinetic form. The disease develops in adults after 35 years of age; hyperkinesis predominates among the symptoms.
Akinetic-rigid, Westphalian or juvenile form. Develops in young people after 20 years of age or earlier, hyperkinesis is mild, symptoms of decreased muscle tone predominate. When analyzing, a higher concentration of pathological proteins is found than in the classical form.
Mental. It develops at the same age as the classic one; symptoms are dominated by memory and thinking disorders and mood swings. Motor symptoms may be mild or almost absent.

Inheritance of Huntington's chorea

As already mentioned, chorea is inherited according to an autosomal dominant principle, and sick children are born in half the cases if one of the parents is sick, and in 75% if both are sick.

Since the chorea gene is dominant, sooner or later it manifests itself each has its own carrier. With the classic version of chorea, there is a possibility that the patient will die from other causes before he develops chorea, but his children may be sick.

Diagnostics

Preliminary diagnosis Huntington's disease diagnosed based on characteristic external signs - a combination of hyperkinesis, hypotonicity and mental disorders.

Laboratory and instrumental methods that allow you to confirm and clarify the diagnosis:

MRI allows you to visualize brain lesions and determine their location (with chorea, these are always the striatum);
CT reveals lesions of the myelin sheath of the brain. It is carried out to exclude demyelinating diseases;
Positron emission tomography. This type of tomography allows you to determine how metabolic processes occur in the brain and see their disruption;
Genetic testing identifies a defective gene in a patient;

Treatment of Huntington's chorea

Chorea– a chronic disease that is characterized by steady progression, so it cannot be completely cured. The use of medications can slow down the development of the disease and preserve the patient’s ability to work longer.

The most effective medications for chorea are considered neuroleptics– they prevent the development of hyperkinesis and have an antipsychotic effect. It is also recommended to undergo sanatorium-resort treatment and perform physical exercises that allow the patient to better control hyperkinesis.

Prevention

It is impossible to prevent the development of chorea because it is a genetic disease. Genetic testing can identify the defective gene in a patient who has a close relative with chorea before he or she develops the disease.

If the gene is identified, the doctor may recommend to the patient don't have children. Similarly, if the chorea gene is detected in the fetus during intrauterine examination, termination of pregnancy is recommended. In each of these cases, the final word remains with the patient.

Chorea is a disease in which hyperkinesis of various muscles occurs and progresses. The patient often makes chaotic, sudden movements with his limbs. Moreover, they can be both one-sided and two-sided. In the latter case, with pathology, there is no synchronization, that is, the arms and legs “live their own lives” and are not connected to each other.

Pathogenesis of the disease

Due to the aggressive influence of various factors, the basal ganglia of the brain, as well as the dentate nuclei of the cerebellum, are damaged and deformed. This is the basic principle of the formation of a pathological condition.

Almost always these destructions are accompanied reticular formation of the brain, which leads to disruption of the physiological release of dopamine and the appearance of chaotic muscle movements. Chorea disease takes a long and difficult time to treat, so contacting a specialist at the first symptoms and timely treatment will give a favorable prognosis.

With minor pathological hyperkinesis, weak motor excitement occurs, accompanied by excessive movements, motor liveliness, grimaces, abnormal gestures. During severe choreic hyperkinesis, facial expressions are distorted, speech, walking, standing are disrupted, and an unnatural gait appears that cannot be described normally.

At a severe stage of the disease, various voluntary active actions cannot be performed; due to falls, the patient is unable to move. Due to choreic activity of facial, oral, and respiratory muscles, a person cannot speak normally or even eat food.

The occurrence of slow choreoathetoid movements of a twisting nature is explained by the superposition of dystonia on the fast pathological activity, in which agonists and antagonists simultaneously contract for a long time. The sudden development of chorea occurs due to an existing vascular, metabolic or autoimmune disease.

Gradual pathology with subsequent progression indicates the presence of a neurodegenerative disease in the body. Forced movements are focal in oral neuroleptic hyperkinesis, generalized, and also having the appearance of hemisyndrome.

Classification

Pathology can be primary and secondary. The first type includes:

chorea Huntington;
choreoacanthocytosis or neuroacancytosis;
benign hereditary disease without progress;
disease Lesha-Naykhana.

Secondary forms develop in the presence of autoimmune pathologies, various infections, metabolic failures, intoxication, and brain injuries. According to another classification, chorea is of the following types:

hereditary, non-progressive early and chronic late;
arising from extrapyramidal diseases;
secondary.

Despite the variety of forms, almost all types of this pathological condition have the same clinical manifestations. Huntington's chorea can occur at any age, but most often affects people between 35 and 42 years of age. Classic choreic hyperkinesis develops in stages, the first unnatural movements are sometimes difficult to catch.

As the pathology progresses, licking of lips, frowning, and tongue protruding are accompanied by abnormal hand activity, deterioration of gait, speech, swallowing, memory impairment, complication of banal household self-care, and the development of dementia.

Sometimes, in the first stages of the disease, mental disorders occur, for example, depression, hallucinations, behavioral changes, and after a few years a hyperkinetic syndrome is formed.

With neuroacanthocytosis, in addition to chorea, they change their shape red blood cells. As a rule, the pathology affects middle-aged people. At the initial stage of the disease, the patient suffers from oral hyperkinesis, that is, he sticks out his tongue, moves his lips, chews, and makes various grimaces that are similar to tardive dyskinesia.

The characteristic of this form of chorea is that with it chaotic biting the inner surfaces of the cheeks and other areas of the oral cavity lead to damage. Due to damage to the peripheral nerves, weakness and atrophy occur in the muscles of the limbs. As neuroacanthocytosis progresses, epileptic seizures occur more frequently.

With benign hereditary chorea developing in children, there is no dementia, and generalized pathology occurs only during the day. This form of the disease is characterized by the absence of further progression with a possible decrease in manifestations, as well as natural mental development.

During Lesch-Nyhan disease, uric acid levels rise and the nervous system is significantly affected. During the first few months of their life, children begin to suffer from delayed improvement of motor skills and developing rigidity in the arms and legs. Then the pyramidal tract is affected, grimaces occur, lips, cheeks, and fingers are damaged after biting.

Secondary Sydenham's chorea affects children and adolescents and occurs several months after a relapse of rheumatism or streptococcal infection. The incidence in girls is 2 times higher than in boys. The first stages or mild degrees of this chorea manifest themselves in the form of motor disinhibition, various gestures and grimaces.

In severe cases of the disease, the patient is unable to care for himself, move, or communicate; speech and breathing are also impaired. Almost always within six months there is a sudden regression of hyperkinesis.

Chorea of pregnancy affects first-time mothers who suffered a minor form of the pathology in childhood. Usually the disease develops before the fifth month of pregnancy with exacerbations during subsequent “positions”.

After childbirth or abortion, clinical manifestations suddenly regress. Extrapyramidal symptoms do not include chorea major, which is a psychogenic movement disorder.

Causes

The main factor in the development of chorea is heredity. Other causes of the disease include:

violations in immune system;
mechanical injuries brain;
children's cerebral paralysis;
Availability infectious pathologies of bacterial or viral form, for example, encephalitis, meningitis;
vascular Problems;
intoxication;
metabolic failures;
rheumatism with the subsequent appearance of rheumatic chorea;
system red lupus;
tonsillitis in a chronic form.

Sometimes the provoking factor is pregnancy if a woman suffered from minor chorea in childhood. Dopamine D1 receptor antagonists used for a long time cause a drug form of pathology.

Clinical signs

The disease does not always manifest itself immediately, but its symptoms are pronounced and practically do not resemble the manifestations of other lesions of the nervous system. Choreic hyperkinesis manifests itself in the form of sweeping, chaotic movements of the limbs.

During a visual examination, decreased muscle tone is revealed. The patient often involuntarily makes various grimaces and gesticulates vigorously. When speaking, the inability to move the hands is noted.

Chorea is also characterized by deterioration in coordination of activity, the appearance of a “dancing” gait, smacking or sighing when communicating. Even at rest, the patient's head twitches. During sleep, clinical manifestations usually disappear, but after awakening or during emotional stress they increase significantly.

The patient also suffers from dementia, impaired memory, attention, speech, general anxiety, aggressiveness, changes in handwriting, as well as significant difficulty in performing controlled movements. In children, the symptoms are identical to adult chorea, but are somewhat smoothed out.

Diagnosis of the disease

The diagnosis of chorea is influenced by patient complaints and clinical manifestations of pathology. A blood test is done to determine the level of white blood cells, as well as the presence of streptococcal infection.

It can also be used to recognize rheumatoid chorea factor, which is determined by C-reactive protein levels. During the diagnostic process, a specialist must necessarily study the diseases of the parents of the suffering child to identify heredity.

To detect the slightest changes in brain activity, an electroencephalogram is performed. For a thorough study of muscle biopotentials, innovative electromyography is performed. Computer and magnetic resonance imaging are used as additional instrumental examinations.

Treatment process

Some forms of the disease, for example, Henington's chorea, often worsen, so you should strictly adhere to the treatment prescribed by your specialist. Children with rheumatism should be registered at the dispensary even before the development of the pathological condition. This reduces the chance of severe illness.

Drug therapy for chorea consists of taking a whole group of drugs - anti-inflammatory, antibacterial, sedatives, neuroleptics, as well as antihistamines, vitamins, vasodilators and to improve brain activity.

Severe Henington's chorea is treated with antibiotics. Auxiliary treatment methods include healing radon baths or with pine needles, and physiotherapy is also used.

The result of eliminating chorea depends from the correct diagnosis and timely detection of the main cause of the disease. If there is a family history of chorea, adults are not recommended to plan children. The appearance of symptoms of pathology in pregnant women significantly reduces the chances of giving birth to a healthy child, and it is generally better to abandon the idea of conceiving a second baby.

Parents of sick children should be attentive and extremely careful in their behavior and communication. The child’s nervous system should not be irritated, so it is better to avoid provoking screams and negative emotions.

Huntington's disease (Huntington's chorea, Huntington's syndrome) is a genetic neurodegenerative disease that is accompanied by mental disorders and progressive choreic hyperkinesis.

ICD-10	G10, F02.2
ICD-9	333.4, 294.1
DiseasesDB	6060
OMIM	143100
MedlinePlus	000770

general information

Huntington's disease is diagnosed in 3-7 people out of 100,000 among Caucasians and 1 person out of 1,000,000 among other races. Most often it appears between the ages of 30-50 years. Cases have been recorded (about 7%) of early onset of the disease - up to 20 years of age (juvenile form). Sometimes the first symptoms appear late - after 70 years.

It is believed that the mutant gene that causes Huntington's disease was introduced to the United States in 1630. The pathology is named after the doctor from Connecticut who first described its classic symptoms in 1872.

The basis for compiling a clinical picture was observations of representatives of a family living in Long Island. Doctors, including George Huntington, monitored the health of three generations of this family for 75 years. Later, the disease was described by doctors from other countries.

The study of the causes of Huntington's disease and the processes occurring in the body during its development is ongoing to this day. The main goal of scientific research is the development of pharmacological agents that can prevent the occurrence of pathology, as well as significantly influence its course.

Causes

Huntington's disease is caused by a mutation in the Htt gene (IT-15). Since it is dominant, the probability of developing pathology in a child, one of whose parents is its carrier, is 50%. For unknown reasons, the risk of juvenile Huntington's disease is higher in people whose fathers pass the altered genome on.

The Htt gene is located on the fourth chromosome. It is present in all humans and contains a region with a repeating sequence of three components: cytosine, adenine and guanine (CAG triplet). These nitrogenous bases encode glutamine amino acid molecules, which then combine in a specific order to form the polyglutamine tract, which is part of the huntingtin (Htt) protein.

Normally, the number of repeats of CAG triplets ranges from 11 to 35. Exceeding this number leads to the synthesis of mutant huntingtin protein (mHtt) with an extended polyglutamine tract. It has a toxic effect on nerve cells and provokes Huntington's disease.

The severity of the disease depends on the number of repetitions. If it exceeds the norm by 36-40%, then the symptoms of the pathology appear at a late age and slowly progress. With the number of repetitions being 60% higher than normal, Huntington's disease begins to develop before the age of 50.

Huntingtin protein is present in all cells, but its greatest concentration is found in the brain and testes. It interacts with various proteins that:

participate in transcription - the process of RKN synthesis in all living cells, in which DNA is used as a template;
transmit signals and transport nutrients inside cells.

In addition, experiments with mice showed that huntingtin:

plays a certain role in the development of the embryo - without it, fading occurs;
prevents apoptosis (programmed cell death);
regulates the formation of a protein that protects brain neurons and controls their formation.

The mechanism of action of the mutant protein on the body in Huntington's disease is not fully understood. It is assumed that when the polyglutamine tract is lengthened, the work of some proteins involved in the functioning of the nervous system is disrupted, the activity of mitochondria (the energy stations of cells) decreases, and the death of neurons increases.

Pathogenesis

At the cellular level, Huntington's disease has the following developmental features. The mutant huntingtin protein combines with other proteins, which leads to its accumulation and the formation of intracellular inclusion bodies. These bodies mechanically interfere with the transport of nutrients and neurotransmitters within cells. As a result, signal transmission in neurons is disrupted. In addition, the following ways of negative influence of mHtt on cells are distinguished:

impact on chaperones - substances responsible for restoring the normal structure of proteins, as well as the formation and breakdown of protein complexes;
reactions with caspases - compounds that are involved in apoptosis;
suppression of energy synthesis in cells;
toxic damage to nerve cells by glutamine;
disruption of gene expression - the process of converting information contained in DNA into RNA or protein.

The destructive effect of the mutant protein is most pronounced when it is combined with the RASD2 protein, which is mainly produced in the striatum. Therefore, in Huntington's disease, it is he who is primarily affected.

The striatum (striatum) is a part of the brain that belongs to the basal ganglia of the hemispheres. Its structure includes the caudate and lenticular nuclei. Functions of the striatum:

control of muscle tone;
planning and correction of movements;
regulation of the functioning of internal organs;
participation in various behavioral reactions;
formation of conditioned reflexes.

In Huntington's disease, gliosis is detected (replacement of damaged areas of nervous tissue by cells called glia), as well as the death of GABAergic neurons in the caudate nucleus. In the basal ganglia, the concentration of gamma-aminobutyric acid, which is a neurotransmitter, and glutamate decarboxylase, an enzyme involved in its production, decreases, while the level of lactate (lactic acid) increases.

As Huntington's disease progresses, other areas of the brain are damaged: the substantia nigra, some layers of the cortex, Purkinje cells in the cerebellum, the hippocampus, and certain areas of the hypothalamus and thalamus. Mutant huntingtin provokes a decrease in these sections due to cell death. There is also an increase in the number of astrocytes - neuroglial cells with many processes. They surround neurons, performing protective, support and other functions.

Symptoms

Symptoms of Huntington's disease differ in different patients in terms of onset, rate of increase and degree. Usually the clinical picture is very similar, especially in terms of physical disorders.

The primary manifestation of Huntington's disease most often occurs at 35-40 years of age, but earlier/later periods are possible. The main sign of the first stage is the gradual development of chorea - a syndrome that is accompanied by erratic, jerky movements reminiscent of dancing, and grotesque facial expressions (grimacing).

At first, the patient's coordination is slightly impaired: he makes minimal movements against his will and does not complete some manipulations. In this case, gestures can be either inhibited or accelerated (more often). At this stage, Huntington's disease is difficult to detect because many patients pass off involuntary movements as intentional. Another symptom of the first stage is a slowdown in saccadic eye movements.

As the disease progresses, symptoms increase:

grimacing appears associated with spasms of the facial muscles;
speech becomes unintelligible;
limbs and torso move convulsively even at rest;
problems with chewing and swallowing occur;
due to loss of coordination while walking, the gait becomes “dancing”;
the patient has difficulty dressing, combing his hair, eating, and so on;
sleep deteriorates;
epileptic seizures are observed (characteristic of the juvenile form).

Gradually, cognitive (behavioral) disorders join physical disorders. Their specificity is individual. The most common mental disorders associated with Huntington's disease are:

at the initial stages - irritability, excitability, loss of interest in usual activities, impaired abstract thinking, causing difficulties in planning and evaluating actions;
as it progresses - aggressiveness, memory problems, irresponsibility, self-centeredness, inability to think rationally.

Many patients experience apathy or depression, increased addiction (to alcohol, drugs, gambling), and develop hypersexuality (sexual intercourse is promiscuous). All this leads to suicide attempts. Some suffer from phobias and obsessive states that resemble schizophrenia.

Diagnostics

Huntington's disease is diagnosed using genetic and clinical methods. Genetic studies can be carried out:

in the perinatal period - analysis of fetal DNA during pregnancy using invasive techniques;
before implantation of an embryo obtained by in vitro fertilization;
after the birth of the child.

Genetic diagnosis in the postnatal period is carried out either when characteristic symptoms occur or in individuals with a family history. In the latter case, preliminary medical and genetic counseling is carried out, including a thorough analysis of family history. This is necessary to assess the likelihood of developing the disease, since a high risk of Huntington's disease, confirmed by a DNA test, is a psychological trauma.

For the study, blood is drawn, then the number of repeats of the CAG triplet in the Htt gene (IT-15) is determined. If there are 36 or more of them, then the possibility of Huntington’s chorea occurring is 100%, but the diagnosis is not made until symptoms appear. A negative result of genetic testing (the number of CAG triplets in the Htt gene is less than 36) indicates the absence of pathology and the risk of its development in the future.

Genetic testing can predict the age at which symptoms of Huntington's disease will first appear. It depends on the number of repetitions: the more there are, the earlier brain damage will begin. In most patients, the number of CAG triplets is 40-49; this interval is considered average and does not provide information about the timing of the onset of the disease.

Clinical diagnosis includes:

physical examination;
psychological testing;
positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) – show changes in brain activity before symptoms appear;
computed tomography (CT) and magnetic resonance imaging (MRI) demonstrate brain atrophy at the stage of pathology progression.

Genetic research, instrumental methods, physical examination and psychological testing can reliably diagnose Huntington's disease and determine the degree of impairment. The pathology is differentiated from Alzheimer's disease, ataxia, benign chorea, schizophrenia and abetalipoproteinemia.

Treatment

Huntington's disease has no specific treatment. The use of medications is aimed at eliminating its symptoms. As a rule, patients are observed in, and. Doctors prescribe complex treatment, including several groups of drugs.

To reduce the severity of muscle tension (rigidity), myoclonic hyperkensia (twitching) and hypokinesia (involuntary movements), antiparkinsonian drugs are used:

levodol;
valproic acid;
pergolide;
bromocriptine.

Treatment of depression and elimination of sleep disorders is carried out with the help of selective substances that suppress (inhibit) the reuptake of the neurotransmitter serotononin. Among them: Prozac, Zoloft and citalopram. Mirtazapine is also used.

For anxiety, aggression, psychosis and cognitive impairment, atypical antipsychotics are prescribed - amisulpride, clozapine and risperidone.

There is a constant search for effective pharmacological agents that can comprehensively influence the manifestations of Huntington's disease. In 2008, the drug tetrabenazine was approved for market in the United States. It reduces the degree of physical impairment, but has side effects: it can cause depression, drowsiness, dizziness, anxiety, akatasia (the inability to remain at rest for a long time).

Cognitive disorders require correction with the help of psychotherapy and training. A person with Huntington's disease needs emotional support.

In the terminal stage of the disease, it is important to provide proper care for the patient, since he completely loses the ability to make independent decisions and actions. If necessary, hospitalization is carried out.

Currently, studies are being carried out on the effectiveness and safety of drugs aimed at the preventive treatment of Huntington's disease: glutamate receptor antagonists and substances that activate the functions of the mitochondrial electrical transport chain. The action of these drugs is to protect neurons from the toxic effects of the mutant huntingtin protein. It is assumed that their use will produce positive results: delaying the onset of the disease and reducing the rate of its progression.

Forecast

Huntington's disease has a poor prognosis. The average life expectancy after the first signs appear is 15 years. Sometimes it is 20-25 years. The juvenile form is characterized by the fastest progression of symptoms - a person dies on average 8 years after the initial manifestation of the pathology.

In most cases, the cause of death is not the direct toxic effect of the mutant huntingtin protein on brain cells. As a rule, death occurs as a result of complications:

pneumonia;
heart failure;
suffocation;
a sharp weakening of the immune system;
severe dehydration and so on.

Suicides and physical injuries are common causes of life interruption.

Prevention

Huntington's disease is a genetic hereditary disease, so it cannot be prevented. If there are cases of pathology in the family history, it is recommended to carry out early genetic diagnosis - at the perinatal stage or in infancy. Detection of a mutation in the Htt gene is a reason for periodic checking of the condition of the brain and implementation of preventive treatment.