Successful Treatment of Rheumatic Chorea
With Carbamazepine
Liora Harel, MD*, Abraham Zecharia, MD†, Rachel Straussberg, MD*,
Benjamin Volovitz, MD*, and Jacob Amir, MD*
Carbamazepine has been used successfully in the treat-
ment of different movement disorders and was recently
reported to be effective for nonhereditary chorea. In
view of the significant side effects associated with the
drugs currently used to treat chorea, we sought to
further evaluate the efficacy of carbamazepine in chil-
dren with rheumatic chorea. The study was prospec-
tive and included 10 children with chorea (eight fe-
males and two males; age range ⴝ 7-16 years) referred
to our Pediatric Rheumatology Clinic between 1995
and 1999. Nine had rheumatic fever and one had
antiphospholipid antibody syndrome that later evolved
to systemic lupus erythematosus. All were treated with
carbamazepine. Improvement was evident within 2-14
days of initiation of low doses of carbamazepine (4-10
mg/kg daily). The plasma drug levels were 2.8-8.2
␮g/mL (therapeutic antiepileptic range ⴝ 8-12 ␮g/
mL). The chorea disappeared within 2-12 weeks. The
duration of treatment was 1-15 months. No side effects
were observed. Recurrence was observed in three
patients who received a second trial of carbamazepine
with a good response. We suggest that carbamazepine
may serve as a first-line treatment for rheumatic
chorea. © 2000 by Elsevier Science Inc. All rights
reserved.
Harel L, Zecharia A, Straussberg R, Volovitz B, Amir J.
Successful treatment of rheumatic chorea with
carbamazepine. Pediatr Neurol 2000;23:147-151.
Introduction
Chorea is a disease of the central nervous system
characterized by rapid, involuntary, jerky movements of
the extremities, face, and trunk. It may be caused by
several hereditary or acquired conditions. The rheumatic
(immune-related) causes include rheumatic fever, sys-
From the Departments of *Pediatrics “C”; and †Emergency and Day
Care Pediatrics; Schneider Children’s Medical Center of Israel;
Sackler School of Medicine; Tel Aviv University; Petach Tikvah,
Israel.
© 2000 by Elsevier Science Inc. All rights reserved.
PII S0887-8994(00)00177-6 ● 0887-8994/00/$20.00
temic lupus erythematosus (SLE), antiphospholipid anti-
body syndrome (APS), and Lyme disease [1].
Sydenham’s chorea (St. Vitus’s dance) is a major
manifestation of rheumatic fever. Several medications
have been used to treat Sydenham’s chorea, such as
chlorpromazine, phenobarbital, haloperidol, and sodium
valproate, but their side effects have limited their use.
Roig et al. [2] found that carbamazepine (CBZ), an
antiepileptic drug, was effective in treating five children
with nonhereditary chorea. On the basis of their promising
results, and in view of the significant side effects of the
currently used medications, we sought to further evaluate
the efficacy and side effects of CBZ in children with
rheumatic chorea.
Methods
The study was prospective and included 10 children with rheumatic
chorea who were referred to our Pediatric Rheumatology Clinic between
1995 and 1999. The diagnostic evaluation included determination of
antistreptolysin O titers and levels of copper and ceruloplasmin, antinu-
clear antibodies, complement, anticardiolipin antibodies, and lupus
anticoagulant, electrocardiography, electroencephalography, and cranial
computed tomography (CT) scan. All patients were treated with CBZ at
relatively low doses (4-10 mg/kg daily) according to the data from the
study by Roig et al. [2]. Patients with a diagnosis of rheumatic fever were
also given prophylactic penicillin. The response to treatment was
assessed by history taking and clinical evaluation, including handwriting
and spiral drawings before and periodically during treatment. Drug levels
were determined as was the hemogram and liver function to monitor for
side effects.
Results
Eight females and two males, aged 7-16 years, partici-
pated in the study. Nine had Sydenham’s chorea with
concomitant carditis (mitral or aortic regurgitation, or
both). The diagnosis was determined according to the
echocardiographic findings, an elevated erythrocyte sedi-
Communications should be addressed to:
Dr. Harel; Department of Pediatrics “C”; Schneider Children’s
Medical Center of Israel; Petach Tikvah, Israel 49202.
Received January 21, 2000; accepted April 3, 2000.
Harel et al: Rheumatic Chorea and Carbamazepine 147
mentation rate and antistreptolysin O titers, or by exclud-
ing other causes. Nine patients were negative for antiphos-
pholipid antibodies. In the remaining patient (Patient 6),
the chorea was the presenting sign of APS. The diagnosis
was based on the findings of thrombocytopenia (90,000-
130,000/m3), positive anticardiolipin antibodies (IgG
greater than 100 GPL U/mL, normal less than 12; IGM
greater than 60 MPL U/mL, normal less than 6), lupus
anticoagulant (17%, normal ⫽ 0-15%), and prolonged
partial thromboplastin time (41 seconds). SLE developed 1
year later and was characterized by Coombs-positive
hemolytic anemia, rash, positive antinuclear antibodies
(1:320), and low complement levels (C3 ⫽ 77 mg/dL,
C4 ⫽ 15 mg/dL, CH100 ⫽ 42 U/mL). Cranial CT,
magnetic resonance imaging, and single-photon emission
computed tomography (SPECT) revealed no abnormali-
ties. Electroencephalography exhibited generalized dis-
charges.
None of the patients had been treated for the chorea
with other drugs before the initiation of CBZ, except for
Patient 7, who had received haloperidol during previous
chorea attacks. She was the only patient with recurrent
Sydenham’s chorea; the recurrences may have been
caused by her refusal of prophylactic penicillin.
The response to treatment and outcome are presented in
Table 1. The number of symptomatic days before treat-
ment was 7-240. The CBZ dosage was between 4 and 10
mg/kg daily. The plasma drug levels were 2.8-8.2 ␮g/mL
(therapeutic antiepileptic range ⫽ 8-12). Improvement
was observed within 2-14 days, with the disappearance of
the chorea in seven of the patients within 2-4 weeks; in the
other two patients, the disappearance was reported at 8 and
12 weeks. The patient with APS and SLE (Patient 6)
responded to CBZ without the addition of steroids (only
additional low doses of aspirin).
The duration of treatment was 1-15 months. Patient 8
discontinued CBZ after 1 month because of parental
refusal of treatment (not because of side effects).
A recurrence was observed in Patients 5, 6, and 8 within
2 months, 8 months, and 10 days, respectively. Treatment
was reinstituted in Patients 5 and 6 at the same dose as
before and was equally successful (chorea improved
within 2 weeks). The duration of retreatment was 4 and 12
months.
The duration of follow-up was 3 weeks to 41 months.
No side effects occurred, except for an itchy maculopap-
ular rash in Patient 9 that responded to antihistamine
drugs.
Discussion
Sydenham’s chorea is a major manifestation of rheu-
matic fever, and according to the criteria of Jones, is
sufficient for a diagnosis of rheumatic fever [3]. It occurs
in 10-20% of patients with rheumatic fever who are 7-14
years old, with a peak incidence at 8 years and a female
predominance of 2:1 [4]. The early clinical picture is
148 PEDIATRIC NEUROLOGY Vol. 23 No. 2
distinguished by marked deterioration in handwriting and
emotional lability. Movements are jerky and uncoordi-
nated and disappear during sleep, and speech is slurred or
jerky. The duration of the disease is 2-3 months or longer,
and recurrences are not unusual [5]. The diagnosis is based
on the elimination of other causes of chorea. The findings
from cerebrospinal fluid analysis and cranial CT, magnetic
resonance imaging, and SPECT will reveal no abnormal-
ities [6,7]; electroencephalography [8,9] will exhibit tran-
sient changes. The pathogenesis may involve antineuronal
antibodies that increase in response to streptococcal infec-
tion and cross-react with neurons within the basal ganglia
[10].
Chorea is rare in SLE, occurring in only 1-4% of
patients, although it is more frequent in childhood lupus.
Chorea may precede the other manifestations of SLE and
may even be the sole presentation in childhood. The
choreiformic movements may last several weeks, and
repeated episodes have been reported. No basal ganglia
infarcts have been demonstrated on CT or magnetic
resonance imaging in most patients. The pathogenesis is
multifactorial, with vascular involvement in the minority
of cases or functional disturbances, possibly antiphospho-
lipid antibody-mediated, in others [11,12].
Although Sydenham’s chorea is self-limited, it is desir-
able to treat patients promptly because of the accompany-
ing anxiety, emotional lability, obsessive-compulsive
signs, and other concomitant psychologic dysfunction
[13]. Several modes of therapy have been used to treat
Sydenham’s chorea [5]. Simple measures, such as bed rest,
a quiet environment, and avoidance of stress, will alleviate
signs. Sedatives, such as phenobarbital, diazepam or
chlorpromazine, dopaminergic receptor antagonists, such
as haloperidol or pimozide [14], and valproic acid [15]
have all been used, with varying degrees of success.
Treatment of chorea in SLE also includes moderate to high
doses of corticosteroids and antiaggregants or anticoagu-
lant agents (in patients with APS) [12]. The major disad-
vantages of these drugs are their significant side effects
(e.g., extrapyramidal [haloperidol] and liver toxicity [val-
proic acid]).
CBZ, a structural analog of the tricyclic antidepressants
and phenothiazine, is frequently used as an antiepileptic
drug. CBZ is relatively rarely associated with significant
side effects, although some investigators have described
CBZ-induced choreoathetoid dyskinesis [16,17]. CBZ in-
toxication may cause choreiformic movements in addition
to manifestations such as coma, seizure, hallucinations, or
ataxia. A few therapeutic trials with CBZ for different
movement disorders have been reported. CBZ was bene-
ficial for familial and sporadic paroxysmal kinesigenic
choreoathetosis [18-23], in nocturnal paroxysmal dystonia
[24], and in painful tonic spasms associated with putami-
nal infarction caused by SLE [25].
In 1988, Roig et al. [2] reported the successful use of
CBZ in the treatment of five patients with nonhereditary
chorea, two of them with Sydenham’s chorea. CBZ was
 Table 1. Response to treatment with carbamazepine in 10 children with rheumatic chorea

Duration of
Symptoms Plasma Onset of Disappearance Duration of Time to Duration of
Pt. Age (yr)/ Before CBZ Dose CBZ Level Improvement of Chorea Treatment Recurrence Follow-up
No. Sex Etiology (days) (mg/kg daily) (␮g/mL) (days) (wk) (mo) (mo) Retreatment (mo)

1 12/F Rheumatic fever 60 8 4.1 7 12 11 — — 12

2 14/F Rheumatic fever 9 10 5.2 3 2 7 — — 23
3 10/F Rheumatic fever 7 4 2.8 10 8 3 — — 17
4 9/M Rheumatic fever 12 6 8.2 6 2 7 — — 12
5 7/F Rheumatic fever 15 7 3.0 7 4 3 2 5 mg/kg; improvement in 2-3 12
wk; therapy duration 4 mo; no
recurrence
6 12/F APS, SLE 240 10 4.4 14 4 15 8 10 mg/kg; improvement in 2 wk; 41
therapy duration 12 mo; no
recurrence
7 16/F Rheumatic fever 7 7 — 7 2 1.5 21
8 8/M Rheumatic fever 18 7 — 2 2 1* 10 days — 21
9 9/F Rheumatic fever 21 7 5.2 2 4 4 — — 12
10 10/F Rheumatic fever 7 7 — 7 — 5 — — 11

* Parents refused medication.

Abbreviations:
APS ⫽ Antiphospholipid antibody syndrome M ⫽ Male
CBZ ⫽ Carbamazepine Pt. No. ⫽ Patient number
F ⫽ Female SLE ⫽ Systemic lupus erythematosus

Harel et al: Rheumatic Chorea and Carbamazepine 149

given at low doses (15-25 mg/kg), and improvement was
evident within 4-15 days with no major side effects.
One year later, Pallares et al. [26] reported patients with
Sydenham’s chorea responding within 1 week to CBZ (20
mg/kg daily) with no recurrence after 3 months of therapy.
Roulet et al. [27] administered low-dose CBZ (less than 1
mg/kg) to a patient with hereditary chorea, with a rapid
response within 1 week. To the best of our knowledge, no
studies have yet been done of CBZ treatment for chorea in
SLE.
In our study, all 10 children had rheumatic chorea (nine
with Sydenham’s chorea and one with SLE). All were
treated with CBZ for 1-27 months at relatively low doses
(4-10 mg/kg daily). The time to improvement was very
short (2-4 days), and none of the patients experienced
significant side effects. The CBZ dosage used in our
patients was lower than that previously reported [2,26].
The plasma drug levels were lower than required for
antiepileptic effect and yet all patients responded.
The mechanism by which CBZ alleviates chorea is
unknown. Two possible explanations are blockade of the
dopaminergic postsynaptic receptors and a stimulation of
the cholinergic pathways [28,29].
Because CBZ is currently used to treat psychiatric
conditions, such as bipolar disorders [30,31], and was even
reported to be helpful in obsessive-compulsive disorders
[32,33], its therapeutic benefit in chorea may be combined.
We are aware that our study was uncontrolled, but so
were all the other drug studies of chorea. That rheumatic
fever and especially chorea is uncommon is an obstacle in
conducting controlled studies. However, these results may
encourage others to plan a multicenter controlled trial.
In conclusion, CBZ proved highly effective in the
treatment of rheumatic chorea in all our patients. Because
Sydenham’s chorea is a self-limited disease, pediatricians
are reluctant to treat children, thus avoiding drug toxicity.
They should remember, however, that chorea affects
children and adolescents during the school years and may
severely interfere with school performance, especially if it
persists for several months. Therefore, on the basis of our
experience, we suggest the use of CBZ, an efficient and
relatively nontoxic drug, for the treatment of rheumatic
chorea.
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CONNECTIONS—Web Site Update

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site is the Genetic/Rare Conditions Support Groups & Information Site, run by the Medical Genetics
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Harel et al: Rheumatic Chorea and Carbamazepine 151