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Brief Report

Indian Pediatrics 1999; 36:1215-1218 

The Use of Haloperidol and Valproate in children with Sydenham Chorea

M.V. Ronchezel
M.O. Hilario
L.H.A. Forleo
C.A. Len
M.T. Terreri
L.C.P. Vilanova
D. Sole

From the Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics,
Escola Paulista de Medicina, Universidade Federal de Sao Paulo (UNIFESP-EPM), Brazil.

Reprint requests: Dr. M.O.E. Hilario, Alameda dos Anapurus, 1370 ap 144 Sao Paulo, SP,
04087- 004, Brazil.

Manuscript received: February 13, 1998; Initial review completed: March 13, 1998;
Revision accepted: July 6, 1998


Sydenham chorea (SC), the principal neurological manifestation of Rheumatic Fever (RF), is characterized by a state consisting of abrupt, involuntary not rhythmic or repetitive movements(1). A variety of drugs have been advocated for treatment of sc. We describe our experience with haloperidol and valproate in SC.

Subjects and Methods

We carried out a retrospective analysis of the medical records of 65 children suffering from RF with isolated or associated SC, from 1990 to 1995, followed-up at the Pediatric Rheumatology Outpatient Clinic. Nineteen of these patients came from the first care unit to our outpatient clinic and
had been taking haloperidol for up to 3 days) The 46 remaining patients were included consecutively in the study. The diagnostic criterion of SC was clinical, after excluding other diseases. In addition to the choreic movements, uni or bilateral, we took into account the presence of emotional imbalance, motor problems and speech disturbance. The patients were clinically evaluated by both a pediatric neurologist and rheumatologist. Haloperidol at an initial dose of 1 or 2 mg/ day up to 5 mg/ day or sodium valproate at an initial dose of 20 mg/kg/ day up to 40 mg/kg/ day were used regardless of the severity of the disease. The patients were revaluated within a period of an average, 72 hours. In this revaluation, we maintained the dose in the cases that showed improvement, or we increased the dose gradually until a favorable clinical response was obtained. To monitor the hepatotoxicity due to the use of valproate, each. patient was periodically evaluated clinically and also by estimation of asparate transaminase (AST) and alanine transaminase (ALT). All patients were evaluated following the same protocol which covered the initial dose, dose modifications, and maximum dosage; lagtime for improvement of the symptoms; side- effects; lack of response to medication; and treatment duration. Significant improve- ment was defined by the disappearance of spontaneous movements, incoordination and weakness. All the children received secondary prophylaxis with benzathine penicillin every 21 days. The patients did not receive steroids during this study.


Of the 65 children who took part in the study, 45 (69.3%) were females and 20 (30.7%) were males and 33 (50.7%) caucasoid and 32 (49.3%) non-caucasoid. The age at which symptoms began ranged
from 5to 14 years (mean = 9.7 years). Ten children presented with recurrences, that took place at least 10 months after evolution without medication, making a total of 75 chorea episodes evaluated. Among the principal clinical manifestations we would draw attention to generalized chorea in the majority of cases (72%). Hemichorea was observed in 21 episodes (28%), 14 on the left and 7 on the right. Slurred speech (77.9%), muscular weakness (71.4%), gait disturbance (70.1%), and emotional imbalance (62.7%) were also found. Haloperidol was used in 47 episodes (62.7%) and in 8 (17%) of these a change to sodium valproate was necessary (5 because of side effects and 3 due to poor response! after three or four weeks of a daily dose of 5 mg of the medication). Valproate was used in 28 episodes (37.3%), in 3 of which (10.7%) it was necessary to change to haloperidol due to lack of response (Table 1). The evident control of choreic movements took place, on an average, 14 days after the introduction of haloperidol and 10 days after the introduction of valproate. The duration of treatment was from 1 to 20 months (mean = 3.5 months) for haloperidol and from 2 to 21 months (mean=3 months) for valproate. The follow-up time varied from 2 to 72 months (mean=24.7 months) for haloperidol and from 2 to 60 months (mean 18.6 months) for valproate (Table I). In 9 patients (8 with haloperidol and 1 with valproate), the reduction of dosage or withdrawal of the drug became necessary because of side effects (Table II).



Clinical and Therapeutic Response

Characteristics Haloperidol
Episodes (n) 47 28
Female (%) 70 67
Caucasoid (%) 46 47
Mean Age (years) 9.6 10.6
Duration of treatment
Mean (mo) (Range)
3.5 (1-20) 3.0 (2-21)
Change of Medication 8 (17%) 3 (10.7%)
No/poor response 3 (6.4%) 3 (10.7%)
Side effects 5 (10.6%) 0
Follow-up time (mo)
Mean (Range)
24.7 (2-72) 18.6 (2-60)


The chorea described by Thomas Sydenham in 1686 is considered one of the main manifestations of RF and continues to be a public health problem in developing countries(I-3). Various drugs are being used for the symptomatic control of the choreic manifestation, with a view to stabilizing cerebral neurotransmitter activity. One of the neuroleptics already widely used in the control of these manifestations is haloperidol(4-6). In 1970, Axley drew attention to the risks of haloperidol and recommended the use of this drug only for children older than 12 years of age(4). In 1974, Franco and Olivares described their success in using haloperidol in 22 cases of chorea, using daily doses of 3 mg(5). In 1976, Shields and Bray described the case of a 5 years old patient diagnosed with SC who, one month after the introduction of haloperidol at 2.8 mg/ day and control of uncoordinated movements, became aphonic, dysphagic, and. developed dystonic posturing(7). As already shown, eight of the patients who used this medication developed side effects, even with low doses, suggesting an individual susceptibility. Furthermore, in three. of our patients a favorable response was not obtained, and these' cases,. responded to sodium valproate.


Side Effects Observed.

Case Sex Age Chorea Drug Dose Side-effects
1* F 12 Gen VAL 40 mg/kg/d Elevation of hepatic
2* F 10 Hemi HAL 3 mg/d Behavioral disturbance
3* M 8 Gen HAL 5 mg/d Vomiting, hypertonia
4* F 9 Hemi HAL 2 mg/d Hypertonia
5 M 10 Gen HAL 3 mg/d Hypertonia, dystonia
6 M 10 Gen HAL 3 mg/d Hypertonia
7 F 9 Gen HAL 3 mg/d Tremor, hypertonia
8 M 5 Hemi HAL 1 mg/d Dystonia
9 F 5 Gen HAL 3 mg/d Tremor, hypertonia
* Side effects ceased when dose was reduced.
Gen = Generalized; Hemi = Hemichorea; HAL = Haloperidol; VAL = Sodium Valproate.

In 1990, Daoud et al. described their results using sodium valproate in the treatment of 15 patients with rheumatic chorea, who received a daily dose of valproate of 15 to 20 mg/kg(8). No side effects attributable to valproate were observed. Sodium valproate appears to be an effective therapeutic option for the symptomatic control of chorea(8-10). In our study we observed good response to valproate in the treatment of patients with SC, using a daily dose which varied from 20 to 40 mg/kg. Our results, in terms of the beginning of the improvement in symptoms and the mean time for the duration of treatment were similar to an earlier repor:t(8), although We detected as a side effect the elevation of hepatic enzymes in one patient, which returned to normal after the drug was reduced. We should emphasize that in three cases a change of medication was necessary due to lack of response.

Our study shows the efficacy of treating SC with the use of haloperidol as well as valproate. We did not observe important differences as to the lagtime when the choreic symptoms began to improve, and the duration of treatment, as between the drugs used. The greater frequency of side effects related to haloperidol must be noted, which must be monitored by periodical clinical evaluation. As for the use of valproate, hepatic function must be evaluated during the treatment. We believe that observation of these points will permit the appropriate and safe use of these medications for the effective symptomatic control of Sc.


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2. Kandil MR, Tohamy AS, Fattah MA. Prevalence of chorea, dystonia and athetosis in Assiut, Egypt: A clinical and epidemiological study. Neuroepidemiology 1994; 13: 202-210.

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5. Franco R, Olivares L. Haloperidol en la corea de Sydenham. Bol Med Hosp Infant 1974; 31: 267-277.

6. Miyakawa M, Ohkubo 0, Fuchigami T. Effectiveness of haloperidol in the treatment of chorea minor. No To Hattatsu 1995; 27: 191-196.

7. Shields WD, Bray PF. A danger of haloperidol therapy in children. Pediatrics 1976; 88: 301-303.

8. Daoud AS, Zaki M, Shakir R. Effectiveness of sodium valproate in the treatment of Sydenham's chorea. Neurology 1990; 40: 1140-1141.

9. Dhanaraj ARM, Radhakrishnan AR, Srinivas K. Sodium valproate in Sydenham's chorea. Neurology 1985; 35: 114-115.

10. McLachlan KS. Valproic acid in Sydenham's chorea. Br Med J 1981; 283: 274-275.


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