Chorea

Chorea is irregular, jerky, disorderly, chaotic, sometimes sweeping, aimless movements that occur mainly in the limbs. Mild choreic hyperkinesis may manifest itself as mild motor restlessness with excessive fussy movements, motor disinhibition, exaggerated expression, grimaces and inadequate gestures. Severe choreic hyperkinesis resembles the movements of a "devil on a string" (or a modern youth dance with "loose" motor skills and "frantic" movements). Severe hyperkinesis distorts facial movements, speech, standing and walking, leading to a strange, fanciful, "clown" gait that is difficult to adequately describe. In extremely severe cases, chorea makes it impossible to perform any voluntary movements. Such patients cannot move due to falls, they are unable to take care of themselves and become dependent on others. Choreic movements of the face, involving the facial and oral muscles (including the tongue and larynx), as well as the respiratory muscles, interfere not only with food intake, but also with verbal communication.

Chorea is a term used to describe short-term, involuntary, chaotic elementary movements of the limbs. Chorea is characterized by simple, rapid movements that may resemble normal movements performed by a distressed person, but are not part of any planned actions. The movements may be bilateral or unilateral, but even when both sides of the body are involved, their movements are not synchronized. Slower choreoathetotic movements occur due to the imposition of a dystonia element on a rapid choreic movement with a prolonged simultaneous contraction of agonists and antagonists. As a result, the movements acquire a twisting character. Depending on the etiology, chorea may develop gradually or suddenly. Sudden, or subacute, onset usually indicates a vascular, autoimmune, or metabolic disease. While gradual onset and progressive course usually indicate a neurodegenerative disease.

Forced choreic movements can be either focal, as, for example, in oral hyperkinesis of neuroleptic origin, or generalized (which is observed more often), and in some cases they manifest as a hemisyndrome (for example, hemichorea in stroke).

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Classification and causes of chorea

• Primary forms.
  • Huntington's chorea.
  • Neuroacanthocytosis (choreoacanthocytosis).
  • Benign (non-progressive) hereditary chorea.
  • Lesch-Nyhan disease.
• Secondary forms.
  • Infectious diseases (viral encephalitis, neurosyphilis, whooping cough, tuberculous meningitis, HIV infection, borreliosis).
  • Autoimmune diseases (systemic lupus erythematosus, antiphospholipid syndrome, chorea of pregnancy, reaction to immunization, Sydenham's chorea, multiple sclerosis).
  • Metabolic disorders (hyperthyroidism, Leigh disease, hypocalcemia, Fabry disease, hypo-, hyperglycemia, Wilson-Konovalov disease, Niemann-Pick disease, Hallervorden-Spatz disease, homocystinuria, phenylketonuria, Hartnapp disease, glutaric aciduria, gangliosidosis, metachromatic leukodystrophy, Merzbacher-Pelizaeus disease, mucopolysaccharidoses, Sturge-Weber disease, etc.).
  • Structural brain damage (TBI, tumors, hypoxic encephalopathy, strokes).
  • Intoxications (neuroleptics, mercury, lithium, levodopa, digoxin, oral contraceptives).
• Psychogenic chorea.

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Primary forms of chorea

Huntington's chorea usually begins at the age of 35-42 (but can appear at any age - from childhood to old age) and is characterized by very typical choreic hyperkinesis, personality disorders and dementia. The type of inheritance is autosomal dominant. The disease begins gradually, the appearance of the first violent movements is sometimes difficult to catch. Most often they appear in the face, resembling voluntary motor automatisms (frowning, opening the mouth, sticking out the tongue, licking the lips, etc.). As the disease progresses, hyperkinesis in the hands ("fingers playing the piano") joins in with its subsequent generalization, statics and gait disorders. The accompanying speech disorders (hyperkinetic dysarthria) and swallowing make proper nutrition and communication impossible. Short-term and long-term memory deteriorates, criticism of one's condition decreases, basic everyday self-care becomes difficult, dementia develops and progresses. Deep reflexes are usually brisk on the legs, in a third of cases clonus is detected, muscle hypotonia is typical.

The akinetic-rigid form (without chorea) is most typical for the early-onset variant (Westphal variant), but it is sometimes observed with a later onset (at 20 years of age or older).

Sometimes the disease begins with mental disorders in the form of affective (most often in the form of depression), hallucinatory-paranoid and behavioral disorders, and only after 1.5-2 years or later hyperkinetic syndrome joins in. In the terminal stage, patients most often die from aspiration pneumonia.

Differential diagnosis of Huntington's chorea involves excluding such diseases as Alzheimer's disease, Creutzfeldt-Jakob disease, benign hereditary chorea, Wilson-Konovalov disease, hereditary cerebellar ataxia, choreoacanthocytosis, basal ganglia infarctions, tardive dyskinesia, and in some cases also schizophrenia and Parkinson's disease.

Neuroacanthocytosis is manifested by chorea and acanthocytosis (change in the shape of red blood cells). Both autosomal recessive and sporadic cases of the disease have been described. The disease usually begins in the 3rd or 4th decade of life (sometimes in the 1st). Initial manifestations are oral hyperkinesis with protruding tongue, lip movements, chewing and other grimaces, very reminiscent of tardive dyskinesia. Inarticulate vocalization is quite common, cases of echolalia (but not coprolalia) have been described. A distinctive feature is self-harm in the form of involuntary biting of the tongue, lips and inner surfaces of the cheeks. Choreic hyperkinesis of the limbs and trunk is often noted; dystonic postural phenomena and tics may also appear.

The disease differs from Huntington's chorea by the presence of weakness and atrophy in the muscles of the limbs, caused by damage to the cells of the anterior horns and peripheral nerves (axonal neuropathy with a decrease in deep reflexes). Later, dementia and epileptic seizures are often (but not always) observed. The level of lipoproteins in the blood is normal. For diagnosis, it is important to identify acanthocytosis, accompanied by progressive neurological deficit with a normal level of lipoproteins.

Benign (non-progressive) hereditary chorea without dementia begins in infancy or early childhood with the appearance of generalized chorea, which stops only during sleep. The disease is inherited in an autosomal dominant manner. Normal intellectual development is typical. Another difference from juvenile Huntington's chorea is the non-progressive course (on the contrary, even a decrease in the severity of choreic hyperkinesis in adulthood is possible).

Lesch-Nyhan disease is caused by a hereditary deficiency of hypoxanthine-guanine phosphoribosyltransferase, which leads to increased uric acid production and severe damage to the nervous system. Inheritance is X-linked recessive (hence, males are affected). Children are born normal, except for mild hypotonia, but motor development delay develops during the first 3 months of life. Progressive limb rigidity and torticollis (or retrocollis) then develop. Facial grimaces and generalized choreic hyperkinesis, as well as symptoms of pyramidal tract damage, appear in the 2nd year of life.

Later, children show a tendency to self-harm (they begin to bite their fingers, lips, and cheeks). These compulsive self-harms (resulting in disfigurement) are quite typical (but not pathognomonic) for Lesch-Nyhan disease. Mental retardation of varying degrees of severity is observed.

The uric acid content in the blood and urine is elevated. The diagnosis is confirmed by a decrease in the activity of hypoxanthine-guanine-phosphoribosyltransferase in erythrocytes or fibroblast culture.

Secondary forms of chorea

Secondary forms of chorea can develop in many diseases: infectious, tumor, vascular, autoimmune, metabolic, toxic, traumatic. Diagnostics of secondary choreic syndrome in these diseases usually does not cause difficulties. Recognition of the nature of the primary lesion is usually based on a complex of clinical and paraclinical methods, including biochemical, molecular genetic, neuroimaging and many other studies.

The most common secondary forms are Sydenham's chorea (observed almost exclusively in childhood and adolescence) and chorea of pregnancy.

• Chorea minor (Sydenham's chorea) usually develops several months after a streptococcal infection or exacerbation of rheumatism, when there are no longer any symptoms of the acute period, and is associated not with vasculitis, as was previously thought, but with autoimmune processes and the formation of antineuronal antibodies. Girls get sick 2 times more often than boys. In the initial stages or in mild cases, motor disinhibition with grimacing and exaggerated gestures is observed. In severe cases, generalized choreic hyperkinesis deprives the patient of the ability to perform basic self-care, disrupts speech (dysarthria) and even breathing, and makes movement and communication impossible. In most cases, generalization of hyperkinesis goes through the stage of hemichorea. Muscle hypotonia is characteristic, sometimes creating the impression of muscle weakness, a "tonic" or "freezing" knee reflex (Gordon phenomenon), emotional-affective and transient cognitive disorders. In most cases, hyperkinesis spontaneously regresses within 3-6 months.
• Chorea of pregnancy usually develops in primiparous women who suffered from minor chorea in childhood. Chorea of pregnancy is currently associated with antiphospholipid syndrome (primary or in the context of systemic lupus erythematosus). Chorea usually begins in the 2nd to 5th month of pregnancy, rarely in the postpartum period, and sometimes recurs in subsequent pregnancies. Symptoms usually regress spontaneously within a few months or soon after childbirth or abortion. Most authors currently classify so-called senile (senile) chorea as a dubious diagnosis and, as a rule, are absent from classification schemes.

Psychogenic chorea (“major chorea” - according to the terminology of older authors) does not belong to extrapyramidal syndromes and is one of the variants of psychogenic movement disorders.

Differential diagnosis of chorea

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Drug-induced chorea

Drug-induced chorea most often develops as a result of long-term use of dopamine D1 receptor antagonists. Chorea usually appears several months or years after the start of drug administration and may be combined with other dyskinesias or dystonia. Since hyperkinesia occurs after long-term use of the drug, it is called tardive dyskinesia (tardive chorea) or tardive dystonia. If the drug is stopped at the first signs of dyskinesia, then its reversal usually, although not always, occurs. If the drug is continued, then the dyskinesia becomes persistent, irreversible, and does not decrease after discontinuation of the drug that caused it. Although older people are more prone to the development of tardive dyskinesia, it can occur at any age. Tardive dyskinesia is most often observed during the treatment of mental illness with neuroleptics, but it can also occur in patients taking neuroleptics or other dopamine receptor antagonists for nausea or decreased gastric motility.

Chorea may also occur in patients with Parkinsonism who are taking levodopa. Muscarinic cholinergic receptor antagonists (anticholinergics) may also induce chorea, especially in individuals with organic basal ganglia disease. Chorea caused by levodopa or anticholinergics is reversible with dose reduction or drug withdrawal.

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Metabolic diseases

A large number of acquired or inherited metabolic disorders can cause chorea. Frequently, it is caused by metabolic disorders during pregnancy (or estrogen therapy) or thyrotoxicosis. After resolution of pregnancy, discontinuation of estrogen therapy, or adequate treatment of thyrotoxicosis, the symptoms usually regress completely.

Autoimmune diseases

Chorea in autoimmune disorders probably results from the production of antibodies to the caudate nucleus. Sydenham's chorea usually begins weeks to months after a group A streptococcal infection and worsens over several days. Hyperkinesia may be severe and may be accompanied by tics and personality changes. Reversal is usually gradual over several weeks and is sometimes incomplete. Some individuals who had Sydenham's chorea as children or young adults develop chorea again in old age. Similarly, estrogen use or thyrotoxicosis sometimes cause chorea in patients who have had Sydenham's chorea.

In systemic lupus erythematosus or other collagenoses, chorea may be an initial manifestation or occur against the background of a developed clinical picture of the disease. Chorea may also be a remote manifestation of a malignant neoplasm, arising as a result of the production of anti-bullet antibodies capable of cross-reacting with striatal antigens.

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Vascular diseases and other structural damage

Hemiballismus or hemichorea usually results from structural damage to the subthalamic nucleus caused by ischemia, tumor, or infection. The disease manifests itself in sweeping choreic or ballistic movements of the limbs on one side of the body. Dyskinesia often involves the face. The movements are of such great amplitude that they can cause physical exhaustion of the patient. Fortunately, if the patient survives the acute period, their intensity weakens over time and hyperkinesis gradually transforms into unilateral chorea.

Although the subthalamic nucleus is not directly connected to the dopaminergic system, dopamine receptor antagonists can be very effective in the treatment of ballistic hyperkinesis. Benzodiazepines, valproic acid preparations, and barbiturates are also sometimes used to reduce violent movements. No specific therapy has been developed for this disease.

Genetic diseases

Recessive, with onset in childhood. There are many hereditary diseases associated with amino acid, lipid, and mitochondrial metabolism disorders that cause chorea and dystonia. They are relatively rare, but are fairly easy to diagnose with laboratory tests. Chorea in these cases typically develops against the background of other neurological or systemic manifestations.

Dominant, adult-onset: Huntington's disease.