A double‐blind randomized controlled trial to assess efficacy of bromocriptine in cirrhotic patients with hepatic parkinsonism

Abstract

Background Parkinsonism like features can be seen in cirrhotics, possibly related to alterations in brain dopamine metabolism, transport and receptor integrity at basal ganglia. Hepatic parkinsonism [HP] is often not suspected and only ammonia reducing therapies are given to such patients. We investigated the efficacy and safety of bromocriptine, a dopaminergic agent, in patients with HP. Patients and Methods Cirrhotics were screened for presence of extrapyramidal symptoms and were diagnosed as HP if any two of tremor, bradykinesia and/or rigidity were present, supported by MRI brain showing T1 hyperintensities in basal ganglia and substantia nigra. Patients were randomized to receive placebo (Gr A, n=22) or bromocriptine (Gr B, n=24) for 12 weeks. Complete, partial and non‐response were defined as 30%, 10%‐30% and <10% reduction respectively in Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Results Of 1016 cirrhotics, 50 (4.9%) had HP. Patients in two treatment groups were comparable for MELD score, arterial NH3 and frequency of porto‐systemic shunts. Bromocriptine therapy for 12 weeks resulted in improvement in rigidity, tremors, bradykinesia and gait compared to placebo with complete and partial response in 7 versus none (29.1%, 0%, p<0.01) and 12 versus one (50%, 4.5%, p<0.01) patients. Prolonged and more severe motor symptoms were associated with non‐response to bromocriptine therapy. There were no major side‐effects in either treatment group. Conclusions Hepatic parkinsonism is seen in ~5% cirrhotics. Bromocriptine is a safe and effective therapy for these patients and is more effective in mild to moderate hepatic parkinsonism.