title: Parkinsonism in cirrhosis: pathogenesis and current therapeutic options.
abstract: Acquired hepatolenticular degeneration, also known as "Parkinsonism in cirrhosis" is characterized by extrapyramidal symptoms including hypokinesia, dystonia and rigidity that are rapidly progressive and may be independent of the severity of cognitive dysfunction. Magnetic resonance imaging reveals T1-weighted hyperintense signals in both globus pallidus and substantia nigra. Estimates of the prevalence of Parkinsonism in cirrhosis have been reported as high as 21 %. The cause of Parkinsonism in cirrhosis has been attributed to manganese deposition in basal ganglia structures, leading to the dysfunction of the dopaminergic neurotransmitter system. In particular, there is evidence from both spectroscopic and biochemical investigations for damage to (or dysfunction of) presynaptic dopamine transporters together with a loss of post-synaptic dopamine receptors in basal ganglia of affected patients. Therapeutic options are limited; ammonia-lowering strategies are without substantial benefit, and an effective manganese chelator is not available. In many patients, L-Dopa replacement therapy and the dopamine receptor agonist bromocriptine are beneficial, and liver transplantation is generally effective. However, reports of post-transplant residual extrapyramidal symptoms suggest an element of irreversibility in some cases.
authors.affiliation: Unité de recherche en neurosciences, Hôpital Saint-Luc (CHUM), Université de Montréal, Montréal, Canada. roger.butterworth@umontreal.ca
authors.forename: Roger F
authors.initials: RF
authors.lastname: Butterworth
mesh_terms: D000978:Antiparkinson Agents / Q000627:therapeutic use; D001923:Brain Chemistry / Q000502:physiology; D002614:Chelating Agents / Q000627:therapeutic use; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000627:therapeutic use; D006801:Humans; D022124:Hyperammonemia / Q000188:drug therapy; D007980:Levodopa / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000150:complications* / Q000473:pathology; D016031:Liver Transplantation; D020149:Manganese Poisoning / Q000209:etiology / Q000473:pathology; D010300:Parkinson Disease / Q000209:etiology* / Q000473:pathology / Q000628:therapy*
chemical_list: D000978:Antiparkinson Agents; D002614:Chelating Agents; D015259:Dopamine Agents; D007980:Levodopa; D004298:Dopamine