childhood hypertonia of central origin: a trial of anticholinergic treatment effects

Conditions: Dystonia

Summary: 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

Keywords: childhood cerebral palsy dystonia secondary trihexyphenidyl pediatric dystonia