Background
Chorea gravidarum (CG) is the term given to chorea occurring during pregnancy. This is not an etiologically or pathologically distinct entity but rather a generic term for chorea of any cause starting during pregnancy. Therefore, CG is regarded as a syndrome rather than a specific disease entity. Chorea is an involuntary abnormal movement, characterized by abrupt, brief, nonrhythmic, nonrepetitive movement of any limb, often associated with nonpatterned facial grimaces. [1, 2, 3]
Pathophysiology
Rheumatic fever is no longer a major cause of chorea gravidarum (CG) and the pathophysiology of CG in current times is unclear. Several pathogenetic mechanisms for CG have been proposed, but none have been proven.
In regard to rheumatic fever, the pathologic changes in the brain reported in CG are similar to those found in rheumatic cardiac disease. These changes include nonspecific arteritis with endothelial swelling, perivascular lymphocytic infiltration, and petechial hemorrhages. [4] Of note, Aschoff bodies, found in the rheumatic heart disease, are not found in the brain. [5, 6] These pathologic changes in the brain are most prominent in the corpus striatum and associated with severe neuronal loss. The corpus striatum is considered to be the largest structure present in the basal ganglia. Classically, the corpus striatum is divided in two parts: dorsal striatum (caudate nucleus and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle). The corpus striatum preforms a variety of different functions from cognitive process and behavior reinforcement to motor functions. It is the dorsal striatum, however, which is most significant in motor activity and commonly involved in hyperkinetic and hypokinetic movement disorders.
In CG patients with autoimmune pathology, postmortem studies show diffuse foci of small hemorrhages present throughout the brain. These hemorrhages are most evident in basal ganglia and caudate nucleus with associated widespread vasculitis. [7, 8] Presumably, as the inflammation resolves, the chorea disappears, and degenerative changes are left in small arterioles.
Another pathologic hypothesis is related to hormonal mediation, particularly estrogen, given there is an increase in chorea cases among young women on oral contraceptives. Nausuda et al reported that modification of postsynaptic dopamine receptors produces dopamine hypersensitivity in high estrogen states. [9] Lee et al suggested that estrogen augments the neuronal function by increasing the expression of active D5 receptors. [10] Estrogen acts as a dopamine agonist on the striatal D2 receptors in the medial part of corpus striatum. In normal estrogen states there does not appear to be any effect on the striatal dopamine receptor expression. [11, 12] Oral contraceptives may activate the same high estrogen state mechanism of CG leading to chorea and further supporting the role of estrogen in CG. In 1950, Beresford and Graham postulated that, “It may be that pregnancy lowers the resistance of a patient who is inherently susceptible to chorea.” [13] Therefore, it has been hypothesized that another cause of CG may be from the reactivation of previous subclinical damage to the basal ganglia during high estrogen states including pregnancy.
In 2004, Miranda et al reported of a case of chorea associated with the use of the oral contraceptives, in which anti-basal ganglia antibodies were detected, suggesting a possible immunological basis to the pathogenesis of this disorder. [14] However, the presence of antibodies in serum does not necessarily infer pathogenicity; the antibodies could be produced as part of tissue damage. [15] To demonstrate that a disorder is autoimmune, 5 criteria must be fulfilled. [16] The criteria are (1) the presence of autoantibodies, (2) the presence of antibodies in target tissue, (3) the induction of disease in an animal model by passive transfer of the antibody, (4) the induction of disease in an animal model by autoantigen immunization, and (5) improvement of clinical symptoms after removal of the antibodies with plasma exchange.
Epidemiology
Incidence
Movement disorders rarely occur during reproductive years, therefore, clinicians are not very familiar with chorea gravidarum (CG). Willson and Preece found that the overall incidence of CG was approximately 1 case per 300 deliveries. According to them, the first description of chorea with onset during pregnancy was made by Horstius in 1661. Rheumatic fever secondary to untreated streptococcal pharyngitis was a major cause of CG at the time of Willson and Preece’s publication. They noted that nearly 70% of their patients had a previous history of either rheumatic fever or chorea. [4] Since the widespread use of antibiotics for streptococcal pharyngitis, CG has become very uncommon.
Calculating the current incidence of CG is not possible given the rarity of the syndrome and lack of more recent published studies. However, a study by Zegart and Schwartz found that one patient with CG had been encountered among 139,000 deliveries in 3 major Philadelphia hospitals. [17] In general, about half the cases of CG are idiopathic, with rheumatic fever and antiphospholipid syndrome (APS) responsible for the reminder of cases. [18]
Demographics
Most patients with CG are young; the average age of onset is 22 years old. [4] Almost all reported patients have been Caucasians, although this may be due to a bias in the older literature, in which the vast majority of reported cases are among patients of European descent.
Of afflicted women, 60% previously had chorea and a family history of transient chorea is not unusual. When occurring with first pregnancies, 50% of CG cases occur in the first trimester and 30% of cases occur in the second trimester. Recurrence of CG in subsequent pregnancies may occur, particularly when associated with antiphospholipid syndrome. [4]
Prognosis
General prognosis
Chorea gravidarum (CG) seldom persists indefinitely. Without treatment, the disease abates in about one third of patients before child delivery. In almost two thirds of patients, the chorea lasts up to 6 weeks postpartum, also known as puerperium. Symptoms often dramatically improve and disappear in the days after childbirth. In some patients, however, neurological sequelae may continue in the form of various degrees of incoordination, tremor, and clumsiness.
Mortality in patients with CG is now rare [7] but, again, difficult to calculate given the scarcity of data. Willson and Preece reported a mortality rate of 12%. [4] However, this likely reflects death due to underlying rheumatic heart disease rather than CG. Beresford and Graham's 1950 analysis of CG reported that death occurred in 1.5% of pregnancies, fetal death in 3.3%, and premature labor in 6.6%, [13] However, due to the absence of a control group it is impossible to interpret this data. Additionally, advances in maternal-fetal medicine since 1950 would also likely improve these statistics.
In the case of drug-induced CG and contraceptive-induced chorea, movements typically resolve after cessation of the drug; and specific therapeutic interventions are not often needed. Individual susceptibility for adverse effects from these drugs may be due to preexisting basal ganglia abnormalities, such as prior vascular insults, Sydenham chorea, or hypoxic encephalopathy.
Fetal prognosis
In view of the paucity of CG, fetal mortality is difficult to assess. Willson and Preece mentioned two 19th-century cases of neonatal chorea. One case involved a microcephalic child with athetoid cerebral palsy. The other case was said to involve transient chorea, but the movements were not described further. [4] It is not clear that these cases were related to CG and no further data is available since their 1932 report.
There is no increased risk of spontaneous abortion in CG [17] and children are generally born healthy and there are not reports on delivery complications. There is no data to indicate significant fetal complications and the 1950 Beresford and Graham report is unclear as noted above.
Future pregnancy
It is unclear what the recurrence rate of CG is in modern times. Willson and Preece reported 21% of women with CG have recurrent chorea with subsequent pregnancies. [4] Several cases have been described in which attacks occurred in the third, fourth, and even fifth pregnancy. [19, 20]
Tables
| Primary differential diagnosis |
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| Secondary differential diagnosis | |
|---|---|
| Drugs/toxicity |
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| Infectious |
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| Genetic |
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| Inherited disorders of metabolism |
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| Metabolic/endocrine disorders |
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| Vascular/trauma |
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| Other systemic disorders |
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| Miscellaneous |
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