Childhood Hypertonia of Central Origin: A Trial of Anticholinergic Treatment Effects

This study is an open-label trial of trihexyphenidyl in children with upper extremity dystonia due to cerebral palsy. It is hypothesized that trihexyphenidyl in doses up to 0.75mg/kg/day would be well-tolerated and show significant changes on the Melbourne scale of upper extremity function.

BACKGROUND: Although trihexyphenidyl has been used to treat both primary and secondary dystonia in children, previous studies have not investigated efficacy in secondary dystonia. We describe the results of a prospective, open-label, multi-center trial of high-dose trihexyphenidyl in children with secondary dystonia of the arms due to cerebral palsy.

METHODS: Twenty-six children age 4-15 years with cerebral palsy and dystonia that impairs function of the dominant upper extremity were enrolled. All children were given trihexyphenidyl at increasing doses over 9 weeks up to 0.75mg/kg/day. Trihexyphenidyl was subsequently tapered over 5 weeks. Visits occurred at baseline, 9 weeks, and 15 weeks. The primary outcome measure was the Melbourne assessment of upper extremity function, tested in the dominant arm.

RESULTS: Three children withdrew due to non-serious adverse events (chorea, drug rash, hyperactivity). 3 children reduced dosage due to non-serious adverse events. The 23 children who completed the study showed a significant improvement in arm function at 15 weeks (p=0.045) but not at 9 weeks. Post-hoc analysis showed that a subgroup (N=10) with hyperkinetic dystonia worsened at 9 weeks (p=0.04) but subsequently returned to baseline following taper of the medicine.

CONCLUSIONS: Trihexyphenidyl appears to be safe and effective for treatment of arm dystonia in children with cerebral palsy. Children with hyperkinetic dystonia may worsen. A larger randomized prospective trial is needed to confirm these results.

Eligibility Criteria:
Inclusion Criteria:

* Dystonia in the dominant upper extremity

Exclusion Criteria:

* Complete absence of voluntary movement in the affected hands, wrists, and elbows
* Severe weakness in the dominant upper extremity (MRC grade \< 4)
* Passive range of motion at the hand, wrist or elbow less than 80% of normal
* Current use of medications for dystonia (anticholinergics, L-dopa, baclofen, diazepam, tizanidine, tetrabenazine, reserpine, and others)
* Changes in the subject's physical therapy regimen for the duration of the 15-week study
* Prior use of trihexyphenidyl or other anticholinergic therapy for dystonia.
* History of surgery on the dominant upper extremity or cervical spine
* Botulinum toxin injection in the dominant upper extremity within the previous 6 months
* Current or prior implantation of an intrathecal baclofen pump, deep brain stimulator, or other device to treat dystonia or spasticity
* Concurrent acute or chronic medical condition (such as frequent seizures, heart disease, or asthma) that could adversely affect motor performance or the safety of testing
* Presence of diurnal fluctuations or other clinical signs and symptoms suggesting an inborn error of metabolism, a family history of dystonia suggesting a genetic dystonia, or dystonia due to injury after the neonatal period (including toxin exposure, trauma, or medication-induced)
* History of allergic or adverse reaction to trihexyphenidyl or other anticholinergic medications
* Current complaint of urinary retention requiring treatment.
* History of glaucoma, or family history of glaucoma with onset before age 40