Chorea, Sydenham

Article Author:
Kevin Beier
Article Editor:
Dyveke Pratt
Updated:
10/27/2018 12:31:54 PM
PubMed Link:
Chorea, Sydenham

Introduction

Sydenham Chorea (SD), also referred to as St. Vitus dance, is a manifestation of rheumatic fever (RF), occurring in up to 40% of patients with RF. It is uncommon in the United States but occurs at a much higher frequency in developing countries. It is thought to be an autoimmune process that is the result of antigenic mimicry between central nervous system basal ganglia cells and Group A B-hemolytic Streptococci antigens. Anti-basal ganglia antibodies that result from the antigenic mimicry attack portions of the brain and are responsible for the pathological findings and symptoms. 

SD is much less common today than in the past, but when it does occur, the symptoms are less severe and the relapses are less frequent. This may be partially due to aggressive treatment of Group A Streptococcal infections, improved general hygiene practices, and a reduction in the strain of Gp A Streptococcus that causes the antigenic mimicry that triggers the disease. The Jones Criteria proposed by TD Jones for the diagnosis of RF included SD as major criteria when diagnosing RF. A very high proportion of RF patients who develop SD suffer from carditis and develop valvular heart disease.

Etiology

SD is believed to be an autoimmune disorder typically occurring after a Group A B-Hemolytic streptococcal infection. The immune system is stimulated to produce antibodies against the streptococcal bacterial infection. These antibodies cross-react to cells of the basal ganglia, which have important roles in controlling motor movements. Death and damage to these cells considered to be responsible for the manifestations of the disease.

Epidemiology

The disease typically is delayed 6 to 8 weeks after Group A B-hemolytic streptococcal pharyngitis. It does not occur after skin infections. SD is more prevalent in females than males (3:1). It is largely a childhood disease with most affected patients between the ages of five and 18 years. It is almost never reported in children less than five years old, and the peak age is eight to nine years old. Adult onset of SD is uncommon, and most adult cases usually are secondary to recurrence following childhood illness. The incidence is higher in developing countries due to beta-hemolytic streptococci infection and inadequate treatment of streptococci infection which is exacerbated by overcrowding and poor hygienic conditions. Chorea gravidarum (CG) is a pregnancy-related variant. Most cases are a recurrence of SD and are considered due to the hormonal changes of pregnancy, but it also can be precipitated by the use of oral contraceptives. Symptoms often resolve quickly immediately after delivery.

Pathophysiology

Most authorities believe SD to be an autoimmune disease that is triggered by a streptococci infection, subsequently resulting in a hypersensitivity humoral reaction to the infection and cross-reactivity streptococci antigens and human tissue antigens through antigen mimicry. The stimulated antibodies target the basal ganglia brain cells in the host and cause a diffuse inflammatory process in the corpus striatum, mainly the caudate nucleus. The symptoms of SD are caused by an imbalance between the dopaminergic system, intrastriatal cholinergic system, and the inhibitory gamma-aminobutyric acid (GABA) system.

Histopathology

SD is caused by a hypersensitivity humoral response that is triggered by an infection with group A beta-hemolytic streptococci. The subsequent immune response attacks and destroys cells of the basal ganglia.

History and Physical

SD often presents following other symptoms and signs of RF, but it can occur alone. Isolated attacks, without other RF symptoms, are common in recurrent Chorea attacks. Typically, the first episode occurs 6 to 8 weeks after an episode of GABHS pharyngitis. The features of the chorea include involuntary movements, poor tone and muscular weakness, and psychological features. The involuntary movements are the cardinal signs of SD and are characterized by the abrupt onset of symptoms that usually affect all four limbs. Other motor symptoms include gait disturbances, loss of motor control, deterioration of handwriting, development of cognitive or emotional disorders. Facial grimacing or tongue chorea may develop as well as the "milkmaid sign" which is a relapsing grip such as occurs with the hand grip while milking a cow. Tics are common in SD. Vocal tics occur in 70% of patients and are believed to be related to chorea of the pharynx and larynx. Dysarthria is common as well as decreased verbal fluency due to the involvement of bulbar muscles. Deep tendon reflexes can either be sustained due to chorea or pendular secondary to hypotonia.

Behavioral problems are common, with obsessions and compulsions present in up to 70% of patients and 16.7% meeting the criteria for obsessive-compulsive disorder. Hyperactivity and attention deficit disorder has been found in up to 45% of patients. Psychosis has been reported in the acute phase of the illness. Carditis occurs in up to 80% of patients. PANDAS (pediatric autoimmune neuropsychiatric disorders associated with strep) is a controversial diagnosis in which patients develop a rather acute onset of OCD and tics that persist despite treatment.

Evaluation

There are no specific ancillary tests to provide a definitive diagnosis of the illness. All patients with chorea need a detailed neurologic and cardiac evaluation. Routine blood tests should include complete blood count (CBC), complete metabolic panel (CMP), liver function test (LFT), B12 (deficiency in children can lead to chorea), thyroid-stimulating hormone (TSH), and drug screens. Anti DNAse-B titers may be elevated up to one year after group A streptococcal pharyngitis. Due to the latency between the initial pharyngeal infection and the onset of the chorea, there is a limited utility of acute phase reactants such as C-reactive protein, erythrocyte sedimentation rates, rheumatoid factor, and antistreptolysin-O titers. Echocardiograms are indicated to evaluate for carditis, as up to 80% of patients with SD have a concurrent cardiac disease.

Brain MRI and CT scans typically are normal, although there may be an occasional reversible hyperintensity in the basal ganglia.  In children, obtaining MRI is of questionable use given requirements for sedation, and careful consideration should be made on a case by case basis. PET scans and SPECT imaging have demonstrated hypermetabolism and hyperperfusion of the basal ganglia in case reports; whereas, other chorea disorders are associated with hypometabolism.

Treatment / Management

In the past, the illness was considered benign and typically would remit after a few months.  More recent studies have found that up to half of patients have chorea lasting up to 2 years. Recurrences of movement disorders occur in up to 50% of patients regardless of prophylaxis.  Many of these recurrences have not been associated with Streptococcus infection or anti-basal ganglia antibodies. A significant concern for patients with the illness is the development of valvular heart disease as a component of RF. There is a very strong correlation between SD and the development of carditis and valvular heart disease.

Prevention of the SD by aggressively treating Group A B-hemolytic streptococcal pharyngeal infection and reducing the likelihood of rheumatic heart disease is effective. Once SD is diagnosed, secondary antibiotic prophylaxis is indicated to decrease the risk of neurologic and cardiac problems with future streptococcal infections. The World Health Organization (WHO) recommends secondary prophylaxis up to the age of 21 years.

Symptomatic treatment of the illness has not been well-studied.  Typically valproic acid has been used in escalating doses, first starting at 250 mg per day and rapidly increasing up to 1500 mg per day or until symptoms abate.  Valproic acid does have a slow onset of action thus at least 2 weeks should be allowed before abandoning as ineffective.  Second line treatment if valproic acid fails are neuroleptics.  Risperidone 1 mg to 2 mg per day have been found effective in controlling the chorea. However, they increase the risk of tardive dyskinesia. More recently tetrabenazine, a dopamine depleting agent with fewer potential side effects, has been suggested. Its effectiveness is not well studied. Immunosuppression has not been found to be effective in the management of the illness.

Pearls and Other Issues

Chorea Sydenham should be differentiated from other causes of chorea, including auto-immune, toxic, vascular, and genetic causes. The acuity of onset can assist in diagnosis. The toxic/vascular causes are more acute to sub-acute versus, and the genetic causes are more gradual. Family is typically, but not always, present in the latter.

Drugs including dopaminergic and anti-dopaminergic and cholinergic, among others, have been identified in the cause of chorea (often referred to as dyskinesia or tardive dyskinesia). Cocaine and amphetamines have also been implicated.

Stroke, demyelinating disease, hypoglycemia or hyperglycemia (diabetic striatopathy), liver disease, and anoxia should be included in the differential, although these typically present in older age.

Huntington's disease presents with a slow onset with a progressive course, is typically associated with family history and ultimately leads to dementia and death. Other, rarer genetic causes can be considered if clinical or familiar history is suggestive.