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

M.V. Ronchezel, Assistent Professor, Division of Rheumatology, Department of Pediatrics, Santa Casa de Misericórdia de São Paulo: M.O.Hilário, Associate Professor, Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics; L.H.A. Forléo, Post Graduate; C. A. Len and M.T. Terreri, Assistent Professor, Division of Allergy, Clinical Immunology and Rheumatology, Departament of Pediatrics, L.C.P Vilanova, Associate Professor, Division of Pediatric Neurology, Department of Medicine; D. Solé, Associate Professor, Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Escola Paulista de Medicina, Universidade Federal de São Paulo.

Address reprint requests and correspondence to:
Dra. M.O.E Hilário,
Alameda dos Anapurús, 1370 ap 144
São Paulo, SP, 04087-004, Brazil

We studied the efficacy and side effects of haloperidol and valproate in the treatment of 65 patients with Sydenham Chorea. 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. Greater frequency of side effects related to haloperidol was detected.

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 described our experience with haloperidol and valproate in SC considering the efficacy and frequency of side effects.

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 come 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, muscular weakness, and walking 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 reavaluated within a period of on average, 72 hours. In this reavaluation, we maintained the dose in the cases that presented 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 from a clinical and laboratory point of view with aspartate 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. The significant improvement was defined by the desapparance 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.

RESULTS

Of the 65 children who took part in the study, 45 (69.3%) were female and 20 (30.7%) were male; 33 (50.7%) caucasoid and 32 (49.3%) non-caucasoid. The age at which symptoms began varied from 5 to 14 years old (mean = 9.7 years). Ten children presented recurrences, that took place 10 months at least 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%), disturbed walking (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 lack of efficacy, 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 efficacy (Table 1). The evident control of choreic movements took place, on 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 (m=3.5 months) for haloperidol and from 2 to 21 months (m=3 months) for valproate. The follow-up time varied from 2 to 72 months(m=24.7 months) for haloperidol and from 2 to 60 months (m=18.6 months) for valproate (Table 1). In 9 patients (8 with haloperidol and 1 with valproate), the reduction of dosage or withdrawn of the drug became necessary because of side effects (Table 2).

DISCUSSION

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 (1,2,3). 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, with positive results being demonstrated at the end of the 60’s and beginning of the 70’s, up to the present (4,5,6). 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, with three of our patients a favourable response was not obtained, and in these cases, given the need to control the choreic manifestations, the alternative was the utilization of sodium valproate with improvement.

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 and for the authors, this would be an effective therapeutic option for the symptomatic control of chorea (8,9,10). In our study we have proved the efficacy of 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 utilization of the medication, were similar to those of the Daoud et al study (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 efficacy, a favourable response being obtained with the introduction of haloperidol.

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 symptons 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 patient reevaluation. 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.

TABLE 1 - Clinical and Therapeutic Response Characteristics of 65 patients and 75 episodes of Sydenham Chorea.

cauc.=caucasoid; n.cauc.=no caucasoid

Gen = generalized           Hem = hemichorea

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