Drug-Induced Movement Disorders and Syndenham's Chorea in an Antipsychotic-Treated Young Child

Chief Complaint and Presenting Problem

D. is a 5-year-old boy who lives with his parents and 6-year-old brother. He attends kindergarten at a special school for children with behavioral problems. He was admitted to an acute inpatient treatment facility for aggressive behavior and threats to kill himself and family members.

History of Present Illness

Parents report that D. had developed behavioral problems by age 3 years characterized by defiance, irritability, and hyperactivity. Parents report that D. began to show aggressive and violent behavior during the past year from age 4 to age 5. During this time, he made frequent threats to kill himself and his family members, and he recently attacked his older brother with a sharp object, resulting in a deep cut on his cheek. He was reported to use foul language without provocation, often became very defiant, and developed explosive outbursts over minor issues, both at home and at school. Parents report that D. showed severe separation anxiety, especially with his father who was his primary caregiver, and had significant difficulty with transitions. He was reported to often appear quite irritable and sad and had frequent crying spells. His sleep was described as poor in quality, with frequent awakenings at night resulting in daytime fatigue and nap taking.

Parents report that D. was frequently motorically overactive since age 3 years, including “squirming” movements, more pronounced in his left leg and right arm. Parents report that D. was started on chlorpromazine, 200 mg daily for the behavioral problems. He was reported to subsequently develop involuntary, odd movements of his tongue and jaw. D.'s “squirming” movements also reportedly became more pronounced at this time. Parents noted deterioration in speech and coordination in the past month. One week prior to admission, chlorpromazine was discontinued due to the development of the tongue and jaw movements.

Past Psychiatric History

D. was hospitalized 6–7 times during the past year for disruptive and severely aggressive behavior.

Developmental History

Parents report that the pregnancy was full term and complicated by maternal use of a selective serotonin reuptake inhibitor. Mother denied in-utero exposure to recreational drugs or alcohol. Delivery was uneventful. Mother described D.'s developmental milestones as “slow,” but she was unable to provide details. Parents describe him as “demanding” in temperament since an early age. Mother reported that D. had a history of speech problems for which he received speech therapy at age 2 years with significant improvement. He is reported to be able to perform all daily activities and grooming with some difficulty, but without assistance.

Educational History

D. is reported to be currently in kindergarten in a special behavioral school. He was reportedly expelled from daycare and multiple pre-school programs before kindergarten. Parents report that D. has an individualized education plan including support staff in his kindergarten program.

Social History

D. lives with his biological parents and 6-year-old brother. He has spent most of the last year in hospitals for his behavioral problems. Mother is seriously ill with diabetes-related complications and has required frequent hospitalizations; mother has been hospitalized two or three times per year since D. was 1 year old. Father is employed at two jobs and is the primary caregiver. The family has had limited access to health care as a result of financial and social factors. The extended family is reported to have little to no involvement with D.

There is no known history of abuse. Parents are reported to have difficulty with consistency in setting limits and consequences, so it has been difficult for them to sustain behavior modification techniques at home.

D. is reported to socialize with his brother and one friend outside of school. Generally, he is reported to be more comfortable around adults than other children and does not show an interest in play dates with other children. D. continues to be aggressive with peers in school despite best efforts by the staff.

Family History

D.'s mother is reported to have pulmonary hypertension, diabetes, and depression. Father is reported to have depression and anxiety. D.'s brother has been diagnosed with attention-deficit/hyperactivity disorder (ADHD) but is reported to have no disruptive behavior.

Maternal family history is positive for diabetes, bipolar disorder and substance use. Paternal family history is not known.

There is no known family history of suicide attempts, premature death, mental retardation, movement disorders, or complications of streptococcal infections.

Medical History

D. has a history of frequent, minor untreated pharyngitis and poor oral hygiene. He has a history of rashes on his back and neck several times in the past year, which his parents attributed to “soap allergy.” He also has a history of nonspecific leg pains. Medical care was not sought for these problems, so etiology is unknown. There has been no known exposure to drugs, alcohol, or other substances or toxins.

D. is mildly obese with a body mass index (BMI) of 18.31, in the 95^th percentile of weight for his age. He has no history of seizures, thyroid problems, hypertension, diabetes, or head injury.

Medication History

In the year and a half prior to admission, D. had been reported to have at least 6–8 week trials of amphetamine/dextroamphetamine, lisdexamfetamine, methylphenidate, iloperidone (6 mg), dextroamphetamine, carbamazepine, lithium (150 mg twice per day (BID)), aripiprazole, quetiapine, ziprasidone (40 mg), and chlorpromazine (200 mg). Daily dosages of amphetamine/dextroamphetamine, lisdexamfetamine, methylphenidate, dextroamphetamine, carbamazepine, aripiprazole, and quetiapine were not reported.

Mental Status Examination on Admission to Hospital

D. is a slightly obese Caucasian child who appears his stated age. He looked disheveled, and his clothes were notable for food stains. He was motorically hyperactive, irritable, and defiant during the assessment. Subtle grinding jaw movements were noticeable. He had poor eye contact. A speech impediment was noted; he had difficulty forming words, and his articulation was garbled. His vocabulary appeared to be below average to average for chronological age. He was oriented to month and year. Attention span was short. D. had a behavioral outburst when he tried to run off the unit but was asked to stay to complete the interview.

There was no evidence of psychotic symptoms. He exhibited frequent self-injurious behaviors such as head banging and self-biting. He continued to make threats to kill himself and others, but added that he “didn't mean it.”

Neurological examination conducted by the consulting pediatric neurologist was notable for the following findings: D.'s hands went into a swan neck position when asked to sustain a posture. Milkmaid grasp was demonstrable. Involuntary movements were more pronounced in the distal compared to proximal parts of limbs. Mild facial movements were present.

Hospital Course

D. spent just over 2 weeks in the hospital. Separation anxiety was problematic after every family visit. When D.'s parents would begin to leave, he would physically cling to them in an effort to prevent their departure. After they would leave, D. would have a long and severe outburst, worry about their safety at home, worry about his mother's health unnecessarily, and exhibit sleep disturbances reportedly due to missing them. Upon admission to the hospital, D. was taking valproic acid (125 mg daily in the morning (QAM), lisdexamfetamine (30 mg), and clonidine (0.05 BID). At time of admission, D. was taking valproic acid, 125 mg at bedtime (QHS). Due to frequent mood changes and ongoing insomnia, valproic acid was increased to 125 mg BID, and ultimately 125 mg QAM and 250 mg QHS. Lisdexamfetamine was discontinued for lack of benefit for ADHD symptoms, and replaced with atomoxetine 18 mg QAM. Clonidine was continued at 0.05 mg three times a day (TID). A trial of dextroamphetamine (2.5 mg TID) was associated with worsening in D.'s aggressive behavior and was discontinued. A trial of quetiapine (12.5 mg BID) resulted in an increase in anxiety and was discontinued.

The self- harm threats continued for the first few days and then subsequently decreased. The frequency and severity of his tantrums decreased as well over this time period. D.'s dysphoric mood, compliance with directions, and participation in group activities improved. Tongue and jaw movements eventually resolved. Despite attenuation of D.'s hyperactivity, he continued to exhibit a peculiar gait and odd limb movements, especially pronounced in the left leg and the right arm. He frequently tripped over his own feet, and his hand coordination was poor. He made corrective movements to mask the involuntary movements. This raised concerns of another comorbid movement disorder. Neurology, cardiology, and infectious disease consultations were obtained to investigate potential etiologies of the persistent involuntary movements.

Initial laboratory studies including CBC, CMP, UA, UDS, TSH, T4, and lipid panel, physical examination, and electrocardiogram were unremarkable. ASO and anti-Dnase B titers were ordered due to the symptom cluster suggestive of streptococcal sequelae. The ASO titer was 800 IU [normal range is<100 IU] and anti-DNase B titer was 318 [normal range is 0–70], which indicate an exposure to past streptococcal infection. Rapid strep test and throat culture were negative, which ruled out active infection. Echocardiography was unremarkable. ANA and ESR were both within normal range. Serum copper, ceruloplasmin, and ionized were normal. CKMB was normal. MRI was unremarkable.

D. was subsequently diagnosed with Sydenham's chorea and started on intramuscular (IM) penicillin (PCN) monthly prophylaxis. IM penicillin was chosen over the oral prophylaxis due to concerns about adherence to the oral regimen and the long duration of treatment.

D. was transferred to a residential hospital facility following this admission. While at the residential facility, D. continued to receive PCN prophylaxis. Movements improved but did not completely cease. D.'s family received family therapy and parent-child interaction training (PCIT), but parents continued to be inconsistent in their behavioral management during his short visits to home.

D. was discharged after six months of residential treatment, with ongoing outpatient family and PCIT. At the time of discharge, he was taking valproate 125 mg QAM and 250 mg QHS, clonidine 0.05 mg BID, and atomoxetine18 mg QAM. He has not been readmitted yet, but parents expect his behaviors will worsen after school starts in August.

Brief Formulation

D. is a 5-year-old boy with a complicated, two-year course of symptoms characterized by disruptive and aggressive behavior consistent with ADHD, mood instability, and abnormal movements. There was no apparent significant medical history except for minor episodes of pharyngitis, rash, and nonspecific leg pains. D.'s clinical course was notable for choreic movements predating exposure to neuroleptics and oral-buccal movements post exposure to chlorpromazine. It appeared most likely that D. met criteria for two specific movement disorders:an antipsychotic induced dyskinesia and Sydenhams's chorea. Other etiologies such as genetic causes, drug use, head injury, and other autoimmune causes were ruled out. The chorea had not resolved at the time of discharge, nor had the adventitious movements associated with the ADHD. D.'s response to a feeling of lack of control over his movements is suspected to have exacerbated his behavior problems.

Developmental delays in speech undoubtedly contributed to the clinical picture by intensifying his frustration and disruptive behavior. In addition, stresses related to his mother's illness, frequent hospitalizations, and separation anxiety also contributed to his behavioral problems.

On the side of strengths, D. had an intact family who were able to access and participate in his health care.

Multi-Axial Diagnoses

Discussion

This case represents the challenges in diagnosis at the interface between early onset psychiatric disorders and early onset movement disorders in pediatric patients. Notably, D. had developed the onset of serious behavioral and affective regulation problems at a very young age, which, despite multiple inpatient psychiatric hospitalizations and medication trials, did not significantly improve his course. His clinical picture, including developmental delays, medical and psychiatric disorders, and medication adverse effects were difficult to disentangle. Initial differential diagnosis included treatment-resistant ADHD, mood disorder, drug-induced movement disorders (DIMD), other pediatric onset movement disorders (inherited, immunologic, infections), and pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) (Swedo et al. 1998; Moretti et al. 2008; Pavone et al. 2006)

Although PANDAS was considered, D. did not appear to have an explosive or abrupt onset of tics or obsessive-compulsive symptoms in temporal association with laboratory documented Group A Beta hemolytic streptococcal infection. In addition, he had both persistent chorea (vs. choreiform movements), and thus did not meet Swedo et al. (1998) diagnostic criteria.

DIMD include akathisia, acute dystonia, Parkinsonism, catatonia, dyskinesias, and neuroleptic malignant syndrome (Richardson et al. 1991). Of these, akathisia, tardive or withdrawal dyskinesias, and dystonia may be classified as hyperkinetic. It is important to note that movement disorders may present at the onset, discontinuation, change in dose, or change in type of antipsychotic and are often misinterpreted as symptoms of an underlying neurological or psychiatric disorder (Mejia and Jankovic 2010). In addition to antipsychotic related dyskinesia, akathisia may have also contributed to D.'s hyperactivity and anxiety symptoms. That these symptoms improved after discontinuation of the antipsychotic further supports a drug-induced etiology. Despite this improvement, odd limb movements, gait, and coordination problems, which predated exposure to antipsychotic and persisted following discontinuation, warranted an investigation into other medical causes of hyperkinetic movements in D.

The incidence of rheumatic fever (RF) is 0.5–2 per 100,000 (Gordis 1985). Sydenham's chorea (SC) is present in 10–30% of patients with RF (Miyake et al. 2007). SC is the most common cause of acquired chorea in children and generally affects children ages 5–15 years (Special Writing Group 1992; Nausieda et al. 1980). Streptococcal infections may present without fever, sore throat or malaise, and may precede SC by several months (Bonthius and Karacay 2003). Chorea is considered a major manifestation of rheumatic fever (Mercadante et al. 2000). Other manifestations include polyarthritis, carditis, subcutaneous skin nodules, rash (erythema marginatum), fever, elevated sedimentation rate, and C-reactive protein, and prolonged PR interval on the electrocardiogram. Chorea typically initially involves distal parts of extremities followed by more proximal areas. Although the course is typically variable, antibiotic treatment usually results in improvement over several months.

Penicillin G prophylaxis has been shown to reduce recurrence of acute RF in comparison to no prophylaxis (Gebremarian 1999; Al-Eissa 1993). Bouts of SC, risk of psychiatric effects, and recurrent carditis and progression to heart failure are prevented as well (Oosterveer et al. 2010). Intramuscular penicillin prophylaxis has been suggested as more effective than oral penicillin (Manyemba and Mayosi 2003). This was the treatment of choice for D., both due to the potential for effectiveness, and concern that it would be difficult for him to adhere to oral penicillin. Penicillin has no known drug interactions with his psychotropic medications.

Valproate is the first-line symptomatic treatment for SC, given its generally favorable profile of adverse effects. Antipsychotic agents such as risperidone, haloperidol, and pimozide, however, are most effective for treating severe chorea. (Oosterveer et al. 2010) Given D.'s history of antipsychotic related dyskinesia, possible akathisia, and improvement on valproate, an antipsychotic was felt to be unnecessary.