Diagnosis and treatment of dementia with Huntington's chorea

What is Huntington's disease?

Huntington's disease (Huntington syndrome, Huntington's chorea, or Huntington's chorea) is a genetic, progressive neurodegenerative disease characterized by the gradual development of involuntary muscle movements affecting the arms, legs, face, and trunk, and the progressive decline of cognitive processes and memory (dementia).

Neurological movement abnormalities may include uncontrolled, irregular, fast, jerking movements (chorea, choreic hyperkinesis) and athetosis, a condition characterized by relatively slow, writhing, involuntary movements. Dementia is usually associated with progressive disorientation and confusion, personality disintegration, impaired memory control, anxiety, agitation, and other symptoms and signs. In patients with the disorder, the duration of the disease can vary from approximately 10 to 25 years or more. Life-threatening complications may occur as a result of pneumonia or other infections, injuries associated with falls, or other related processes as a result of the disease.

Huntington's chorea is transmitted as an autosomal dominant trait. The disease occurs as a result of changes (mutations) in the HTT gene. The HTT gene, located on the short arm (p) of chromosome 4 (4p16.3), encodes a protein known as “Huntingtin.” This gene contains a region with a repeating sequence of three nucleotide bases - cytosine-adenine-guanine (i.e., CAGCAGCAG...). The length of expanded repeats may influence the age at onset of symptoms. The specific symptoms and physical signs associated with Huntington's disease result from the degeneration of nerve cells (neurons) in certain areas of the brain (eg, basal ganglia, cerebral cortex).

Treatment of Huntington's chorea

Modern medicine does not have clear treatment tactics; this disease is considered incurable. In some cases, the following are prescribed as a treatment for hyperkinesis in children:

• Tetmodis – reduces movement disorders;
• neuroleptics (Haloperidol, Azaleptin and others) – reduce muscle tone, inhibit the progression of mental disorders;
• Amitriptyline is an antidepressant that reduces the intensity of motor and facial disorders.

No other therapeutic prescriptions are made because any intervention does not produce any results. Patients are literally doomed, because as a result they become completely uncontrollable, do not orient themselves in space and time, lose their memory and do not recognize any of their relatives. They must be under constant supervision, which is why they are most often placed in specialized psychiatric clinics.

Huntington's chorea is a genetic disorder. Therefore, when such a patient appears in the family, all family members must be examined, and pregnancy planning is best done under the strict supervision of geneticists. Modern scientists can offer people who are at risk of having such a baby to undergo IVF or ICSI - it will be possible to implant a healthy fertilized egg into the mother.

More complete information about the pathology and the disease rheumatic chorea can be found on the pages of our website.

Related services: Consultation with a neurologist

Signs and symptoms

Signs and symptoms of the disease (see video) most often appear in adults aged 30-50 years, but can appear at any age. Symptoms tend to worsen over 10-25 years.

Over time, Huntington's disease or its complications are fatal.

According to the Huntington's Disease Society of America, symptoms of the disorder can be similar to amyotrophic lateral sclerosis (ALS), Parkinson's disease and Alzheimer's disease all rolled into one.

Main symptoms include:

• personality changes, mood swings and depression;
• problems with memory and judgment;
• unsteady walking and uncontrolled movements (choreic hyperkinesis);
• difficulty speaking and swallowing;
• weight loss.

How the signs and symptoms of the disease progress depends on the individual. In some patients, depression occurs before motor skills are affected. Mood swings and unusual behavior are usually the first to appear.

— Early signs and symptoms.

Early symptoms may not be recognized if the disease has not previously run in the family. It may take a long time to establish a diagnosis.

Initial signs and symptoms include:

• slight uncontrolled movements;
• minor changes in coordination;
• minor mood changes;
• lack of attention, slight problems with concentration and difficulties at work;
• lapses in short-term memory;
• depression;
• irritability.

Symptoms

The first symptoms of the disease appear after 30 years of age (early onset is much less common).

Signs of Huntington's chorea include:

• Restlessness, fussiness and strange, frequently repeated movements (manifest in the first stages of the disease and are usually not regarded as pathology).
• Involuntary facial expressions, grimacing: clicking the tongue, smacking, opening the mouth, etc.
• A swaying gait accompanied by dancing movements and twitching movements.
• Disorders of motor activity of the eyes, development of nystagmus (rhythmic involuntary eye movements).
• Hyperkinesis, or uncontrolled movements (sudden swings of the limbs, jerking of the neck), which may disappear during sleep, but intensify during stressful situations.
• Slow speech with unnecessary sounds.
• Intellectual disorders: the patient ceases to recognize loved ones, he experiences memory impairment and dementia.
• Decreased muscle tone.
• Loss of ability to eat and care for oneself.
• Mental disorders: apathy, irritability, panic, delusional ideas, sometimes hypersexuality and alcoholism.

In the initial stages, a person can suppress the manifestations of the disease through willpower, but subsequently control weakens, and the steady progression of the pathology leads to disability.

The last stage is characterized by inappropriate behavior of patients: they do not navigate the environment, become absolutely helpless and require constant care.

In addition, they exhibit unmotivated aggression, hallucinations and suicidal thoughts.

Causes of Huntington's disease

The disease is inherited as an autosomal dominant trait. Human traits, including classical genetic diseases, are the product of the interaction of two genes, one passed on from the father and the other from the mother.

In dominant disorders, one copy of the disease gene (obtained from the mother or father) will be expressed as “dominant” over the other normal gene and result in the disease. The risk of passing the disorder from the affected parent to the offspring is 50% in each pregnancy, regardless of the sex of the child.

Huntington's chorea is caused by changes (mutations) in a gene located on the short arm (p) of chromosome 4 (4p16.3). Chromosomes are found in the nucleus of all cells in the body. They carry the genetic characteristics of every person. Pairs of human chromosomes are numbered 1 to 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm (arm), designated by the letter "p", and a long arm, designated by the letter "q". The chromosomes are further divided into numbered bands.

This gene, known as HTT, controls the production of the protein Huntingtin, found in nerve cells (neurons) throughout the brain. However, the specific function of the protein is unknown. In patients, the HTT gene contains errors in the encoded “building blocks” that carry its specific genetic instructions.

The instructions in each gene consist of different patterns of four basic chemicals (nucleotide bases) called adenine (A), cytosine (C), guanine (G) and thymine (T). In people with the disease, the HTT gene contains abnormally long repeats of cytosine-adenine-guanine encoded instructions (trinucleotide CAG (CAG) repeat expansions). For example, people with the disorder have more than 35 CAG repeats in the HTT gene, with most having more than 39. However, people without the disorder have about 20 repeats in the gene.

Diagnostics

Because symptoms are mild in the early stages of Huntington's disease, it can be difficult to recognize its onset. Suspicion may be based on symptoms and the presence of this disease in the patient's relatives. The doctor should be told about relatives who have had mental disorders or who have been diagnosed with a neurological or mental illness (for example, Parkinson's disease or schizophrenia), since the illness in these relatives may have been confused with another nervous or mental illness.

Computed tomography (CT) or magnetic resonance imaging (MRI) is done to rule out other diseases and to look for degeneration of the basal ganglia and other areas of the brain that the disease typically affects.

Additionally, genetic analysis is performed to confirm the diagnosis. It is important for people who do not have symptoms of Huntington's disease but have a family history of the disease to undergo genetic testing and counseling. The fact is that such people may have children before the first symptoms appear. Genetic counseling should precede genetic testing. For consultation, such people are referred to a center that specializes in solving complex ethical and psychological problems associated with genetic research.

How to treat?

Today, Huntington's chorea is considered an incurable disease, so treatment is aimed at improving the patient's condition.

To combat the disease, medications are used that are aimed at reducing the main symptoms and manifestations of the pathology.

1. "Tetrabenazine" ("Tetmodis") . A drug that was created to reduce the intensity of involuntary movements in patients with Huntington's chorea.
2. Neuroleptics (Haloperidol, Moditen, Sonapax) are used to reduce the mental manifestations of the disease. Modern doctors recommend new generation antipsychotics (Olanzapine, Risperidone) to patients due to the minimal number of side effects.
3. Antidepressants and anxiolytics . For Huntington's chorea, tricyclic antidepressants and selective inhibitors are used predominantly - Amitriptyline, Fluoxetine. They ease a person’s psychological state, reduce anxiety, irritability and other manifestations of depression.
4. Valproic acid preparations. Sodium valproate and other similar drugs are prescribed for seizures.
5. Antiparkinsonian drugs. In the later stages of the disease and when muscle tone increases, patients are recommended to take Levodopa and other medications prescribed for Parkinson's disease.

To reduce psychological symptoms and prolong working capacity, patients are recommended to attend training on the development of thinking and engage in some kind of intellectual activity.

Previously, there were attempts to treat Huntington's chorea surgically through so-called stereotactic operations (the introduction of electrodes or microinstruments into certain areas of the brain), but due to the lack of effect, such methods are no longer used.

The only way out for patients is long-term use of medications that can improve the length and quality of life.

Disorders with similar symptoms

Symptoms of the following disorders may be similar to those of Huntington's chorea. Comparisons can be useful for differential diagnosis:

• Hallervorden-Spatz disease is a rare, progressive disease that affects muscle movement. The disorder is associated with degeneration of the nervous system. Hallervorden-Spatz disease is characterized by uncontrolled muscle movements (dystonia), muscle rigidity and loss of cognitive abilities (dementia). Symptoms of the disease usually begin in childhood, although sometimes the disease begins in adulthood.
• Multiple system atrophy (MSA) is a group of rare inherited diseases characterized by progressive degeneration of the cerebellar cortex and other brain tissues. Several different types of systemic atrophy have been identified, with symptoms varying widely depending on the type of MSA. Typically, these disorders are characterized by impaired ability to coordinate muscle movements, tremors, involuntary muscle jerks, speech impairment (dysphasia), loss of cognitive abilities and mental deterioration.
• Rheumatic chorea (Sydenham's chorea) is a nervous system disorder that occurs suddenly after a streptococcal infection, such as scarlet fever, pharyngitis or rheumatic fever. The disorder usually affects young children and teenagers. Sydenham's chorea is characterized by rapid, involuntary, non-repetitive muscle movements that may gradually become more severe and frequent. The muscles of the arms and legs are most severely affected. Speech may also be impaired. Other common symptoms may include a clumsy gait. Chore-like muscle movements tend to disappear with sleep. The disorder usually resolves in 3-6 months without permanent neurological or muscle damage.
• Wilson's disease is a rare genetic disorder characterized by excess copper in various tissues of the body, especially the liver, brain and corneas of the eyes. The disease is progressive and, if left untreated, can cause liver disease, central nervous system dysfunction, and death.
• Tourette syndrome is a neurological movement disorder that usually first appears between the ages of 2 and 16 years. Initial symptoms are often rapid eye blinking (nystagmus) or facial tics. Tourette syndrome is not a progressive or degenerative disease, and patients live a normal life expectancy.

Forecasts and statistics

According to medical statistics, Huntington's chorea is considered a rare disease - from 2 to 7 cases per 100 thousand population, and it is most widespread in the Scandinavian countries.

There are no preventive measures to prevent the development of the disease (since Huntington's chorea tends to get worse from generation to generation, people with this diagnosis are not recommended to have children).

The prognosis for life is unfavorable - death occurs 10-13 years after the onset of the first symptoms at the age of 45-55 years from complications of the disease (pneumonia, cardiac disorders).

About 20% of patients die due to suicide.

Today in Western countries, research is being conducted on the use of stem cells and the creation of drugs that can block the synthesis of pathological proteins, which will give patients diagnosed with Huntington's chorea hope for recovery.

Treatment of Huntington's disease

Once Huntington's disease is diagnosed, it is advisable for the patient to complete advance directives in the event of disability as soon as possible. In these instructions, the patient can explain what type of care he would like to receive at the end of his life.

Huntington's disease has no cure. However, some medications, including antipsychotics (such as chlorpromazine, haloperidol, risperidone, and olanzapine) and dopamine-reducing drugs (such as tetrabenazine and the high blood pressure drug reserpine), may help relieve symptoms such as abnormal movements and restlessness. .

If you have depression, antidepressants can be used.

Forecast

Huntington's disease is a progressive disease leading to disability and death, usually from intercurrent illness.

The average age at death in all major categories ranges from 51 to 57 years, but the range can be wider. The duration of the disease varies considerably, with an average of about 19 years. Most patients survive 10-25 years after the onset of the disease. In a large study, pneumonia and cardiovascular disease were the most common primary causes of death.

The juvenile form of the disease (i.e., onset of the disease in patients younger than 20 years of age) accounts for approximately 5-10% of all patients. Most patients with juvenile Huntington's chorea inherit the disease from their father, while patients with onset after age 20 are more likely to inherit the gene from their mother.

Clinical symptoms

The onset of the disease occurs between the ages of 20 and 50 years. The teenage form of Huntington's disease accounts for no more than 10% of cases of overall morbidity. To date, one case of early onset of disease symptoms in a 3-year-old child has been described. At the age of 13-17 years, the appearance of choreic syndrome is recorded very rarely. This syndrome is a typical feature of Huntington's chorea in adult patients.

Patients experience facial hyperkinesis of the facial muscles, which manifests itself in the form of expressive facial expressions, grimaces with protruding tongue, involuntary trembling of the cheeks, alternating raising, frowning of the eyebrows.

Involuntary obsessive movements of the hands are expressed by rapid flexion and extension of the fingers. Hyperkinesis of the legs is manifested by crossing or spreading. If with minor chorea motor acts are fast and sudden, then with Huntington's chorea the movements are complex and slow. The movements belong to the athetoid group.

The longer the disease progresses, the more severe hyperkinesis it is accompanied by. Motor acts acquire the character of athetosis with pronounced dystonia and further muscle rigidity.

The juvenile form of Huntington's disease manifests itself as rigidity and bradykinesia in 50% of clinical cases. Seizures occur in 30-50% of patients. Sick adolescents experience speech disorders in the form of difficulty pronouncing sounds and constructing syntactically and semantically correct sentences.

These disorders persist throughout the entire period of the disease. The listed signs include slow speech speed and rhythm disturbances during conversation.

Early symptoms include oculomotor pathologies. Patients are characterized by automatic scanning eye movements. Experts record an increase in the latent interval of repeated oculomotor acts, a decrease in the speed of gaze movement, and a decrease in the accuracy of object tracking. With a long course of the disease, vertical nystagmus occurs, less often - horizontal or combined.

Clinical signs of Huntington's chorea include:

• motor coordination disorders;
• sudden fussy twitching;
• involuntary sweeping movements of arms and legs;
• erratic head movements;
• pathological facial expressions;
• lack of confidence when walking;
• emotional instability;
• convulsions;
• memory disorders;
• slurred, slow speech;
• dementia;
• suicidal tendencies;
• indifference bordering on apathy;
• visual and auditory hallucinations;
• endocrine system disorders;
• sleep disorders.