Torticollis as a side effect of cisapride treatment in an infant.

Abstract

To the Editor: Cisapride is a widely employed, usually well-tolerated drug for the treatment of gastroesophageal reflux (GER) of infants. Trimebutine is a prokinetic drug employed for irritable bowel syndrome with abdominal pain (1,2). We report the case of a 7-week-old infant who experienced torticollis during cisapride and trimebutine treatment. The patient was born at 40 weeks' gestation. Her weight at birth was 2.95 kg, her length was 47 cm, and her head circumference was 33 cm. Delivery was normal without the use of forceps. The Apgar scores were 10 at 1 and 5 min of life. The patient received daily supplementation of 800 IU of vitamin D from the first days of life. At the age of 5 weeks, cisapride treatment (0.2 mg/kg/day) was prescribed along with trimebutine (5.4 mg/kg/day) because of her frequent crying and the suspected presence of esophagitis. Two weeks after beginning cisapride therapy, the patient was examined for torticollis at the children's hospital. Clinical examination showed left lateral deviation of the head and neck, and mobilization of the neck seemed to be painful. There was no hematoma of the sternocleidomastoid muscle or adenopathy in the cervical region. The patient's temperature was 37.4°C. Examination of the joints and pharynx was normal. Radiography of the cervical spine and clavicles showed no anomaly. C-reactive protein was 1.2 mg/L, white blood count was 16,600/mm3, hemoglobin was 11.2 mg/100 ml, hematocrit was 33.3%, platelet count was 583,000/mm3. Trimebutine and cisapride therapy were stopped at admission. The last administration of cisapride had been at 11 a.m. the same day; trimebutine treatment had not been given on that day. Six hours after admission, clinical examination showed no evidence of torticollis. The patient was discharged the next day. Cisapride and trimebutine treatment were not reinstituted. Transient torticollis during cisapride and trimebutine treatment has not been described in the literature. Cisapride acts by an indirect mechanism to facilitate acetylcholine release through a process mediated by postganglionic nerve endings in the myenteric plexus of the gut (3). A cholinergic effect in rats (salivation, lacrimation) has been observed only at doses much greater than those required for gastrokinetic activity (4). The mechanism of action of cisapride is believed to be an indirect cholinomimetic type (5). The molecular mechanism is unknown, but transmembranal calcium movement may be involved (6). Cisapride is believed to be devoid of dopaminergic effect (5). This drug is largely used in pediatrics for the treatment of GER and is well tolerated in most cases. The most common side effects are diarrhea or transient abdominal cramping (5). Tachycardia has been reported in seven cases (7,8). The occurrence of tachycardia with cisapride treatment was not noted in a large study by Inman and Kubota (9). Central nervous side effects, such as somnolence or fatigue, have been reported during cisapride treatment, but they occur much less frequently in patients treated with cisapride than in patients treated with metoclopramide (1.6% versus 15.2%). Headache and dizziness were not seen more often with cisapride than with placebo (10). Trimebutine is a peripheral enkephalinic agonist. Its effects are obtained by association with endogenous opioid receptors (1). Trimebutine is considered to be a prokinetic drug acting by competitive opposition to acetylcholine on the intrinsic nervous system. It increases the tone of the lower esophageal sphincter, enhances gastric emptying, and regulates the migrant motor complexes. Sleepiness is one of the most usual side effects (11). Maximal blood concentration is obtained in 1-2 h after absorption, and 70% is eliminated after 24 h (12). In our case the torticollis occurred 2 weeks after the start of cisapride and trimebutine therapy and disappeared completely after its withdrawal without the need for any other therapy. It seems unlikely that trimebutine is responsible for the torticollis, but the possibility cannot be excluded. Total regression of symptoms after withdrawal of treatment suggests the responsibility of cisapride therapy or the combination of cisapride and trimebutine therapy for the symptoms, but it is not possible to know whether the symptoms would have disappeared if cisapride and trimebutine treatment had been continued. Ultrasound on the sternocleidomastoid muscle was not performed in our patient. The syndrome of Sandifer during GER consists of transient torticollis during acid reflux and esophagitis. In our patient, symptoms appeared during medical treatment of GER and regressed promptly after withdrawal. Endoscopy of the esophagus was not performed because of the spontaneous favorable evolution. In our patient drug therapy was likely responsible for the torticollis, but it cannot be confirmed. Further data are necessary to support the possibility of torticollis or extrapyramidal side effects during cisapride therapy. K. Dieckmann; C. Maurage; J. C. Rolland Department of Pediatric Gastroenterology and Nutrition CHU Clocheville Tours, France N. Ramponi; A. P. Jonville Department of Pharmacology CHU Bretonneau Tours, France