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A Distinct Subset of Acquired Hepatocerebral Degeneration

Pierre R. Burkhard, MD; Jacqueline Delavelle, MD; Renaud Du Pasquier, MD; Laurent Spahr, MD

Arch Neurol. 2003;60:521-528.

Context  The clinical, neuroradiological, and biological characteristics of the so-called acquired hepatocerebral degeneration have not yet been fully determined and its frequency remains largely uncertain.

Objectives  To prospectively study the prevalence of extrapyramidal symptoms in patients with moderate to severe cirrhosis of various causes, to delineate the main neurological features of the condition, and to establish correlations with neuroradiological and biological findings.

Patients and Methods  During a 1-year period, all consecutive patients with cirrhosis who were potential candidates for liver transplantation were screened for extrapyramidal features. When extrapyramidal features were present, further workup included a detailed neurological examination, magnetic resonance imaging of the brain, a comprehensive battery of neuropsychological tests, extensive blood tests, and, in some cases, cerebrospinal fluid analysis.

Setting  A community-based hospital.

Results  From 51 patients screened, 11 (21.6%) exhibited moderate to severe parkinsonism sometimes associated with focal dystonia. Typical features included rapid progression over months, symmetric akinetic-rigid syndrome, postural but not resting tremor, and early postural and gait impairment. Neuropsychiatric manifestations were minimal. Some patients were responsive to levodopa therapy. In all patients, magnetic resonance imaging scans showed striking hyperintensities on T1-weighted images typically involving the substantia nigra and the globus pallidus bilaterally. Whole blood and cerebrospinal fluid manganese concentrations were severalfold above the reference range.

Conclusions  Cirrhosis-related parkinsonism may represent a unique, consistent, and common subset of acquired hepatocerebral degeneration, whose features are permanent and entirely different from acute hepatic encephalopathy episodes. This form of parkinsonism can be clearly distinguished from other forms of parkinsonism of middle to advanced age, based on a suggestive association of clinical, neuroradiological, and biological abnormalities. Our findings support the concept of the toxic effects of manganese being the major determinant of basal ganglia dysfunction leading to the predominantly extrapyramidal central nervous system manifestations of cirrhosis observed in these patients.

From the Departments of Neurology (Drs Burkhard and Du Pasquier), Neuroradiology (Dr Delavelle), and Gastroenterology and Hepatology (Dr Spahr), University Hospital, Geneva, Switzerland.

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