This article includes discussion of acquired hepatocerebral degeneration, chronic acquired hepatocerebral degeneration, and non-Wilsonian hepatocerebral degeneration. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
A minority of patients with chronic liver disease develop acquired hepatocerebral degeneration – a progressive neurologic disorder characterized by extrapyramidal signs, ataxia, and cognitive decline. Although the pathogenesis of acquired hepatocerebral degeneration is not known, diversion of portal blood into the systemic circulation appears to underlie the syndrome. In this article, the authors review the clinical, radiological, and pathological features of acquired hepatocerebral degeneration along with current treatment strategies. Evidence supporting and opposing the potential role of manganese in acquired hepatocerebral degeneration’s pathogenesis is discussed, as well as outcomes following liver transplantation.
• Acquired hepatocerebral degeneration is a neurologic disorder that is clinically distinct from hepatic encephalopathy and characterized by extrapyramidal signs, ataxia, and cognitive dysfunction.
• The pathogenesis of acquired hepatocerebral degeneration is not known, but portosystemic shunting likely plays a central role.
• Acquired hepatocerebral degeneration is not a contraindication to liver transplantation; indeed, in some cases transplantation may be the only effective therapy.
Historical note and terminology
In 1912, S A Kinnear Wilson’s manuscript on hepatolenticular degeneration aroused new interest in a possible association between liver dysfunction and neurologic disease (147). The progress that followed marks one of neurology’s greatest successes in translating a clinical observation into molecular understanding and cure of an otherwise fatal neurodegenerative disorder. Wilson disease is now recognized to be a hereditary disorder of biliary copper excretion. Once inescapably fatal, it is now readily treatable—and often reversible (71). In contrast to Wilson disease, most cirrhotic patients with progressive neurologic dysfunction have non-inherited (acquired) types of hepatic failure that do not respond to copper-lowering drugs. Acquired hepatocerebral degeneration, first described by vanWoerkem in 1914 (141), was largely unrecognized until the landmark review by Victor, Adams, and Cole in 1965 (142).
The pathogenesis of acquired hepatocerebral degeneration is not known, and treatment strategies are lacking, making it a suitable research topic, yet surprisingly little has been published on the condition. Interest in the disorder, however, is growing based largely on three observations: (1) extrapyramidal signs may be much more common in cirrhotic patients than previously recognized (107; 125; 07); (2) the majority of patients with advanced liver disease have an abnormal signal in their basal ganglia on T1-weighted magnetic resonance imaging (25; 69); and (3) this signal appears to result from manganese deposition (25; 39; 59; 104).