Abstract & Commentary
Synopsis: 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.
Source: Burkhard PR, et al. Arch Neurol. 2003;60:521-528.
The neurological manifestations of chronic cirrhosis and hepatic failure are protean. Myoclonus (often negative), chorea, and dystonia may occur in these patients, often accompanied by pyramidal dysfunction and dementia. More than three-quarters of patients with chronic cirrhosis have abnormalities in the basal ganglia on MRI, typically bilateral pallidal hyperintensity on T1 images. Other studies have shown that patients with cirrhosis develop manganese deposits in the basal ganglia. The density of D2-receptors is depressed as well.
Burkhard and colleagues have studied all consecutive patients with cirrhosis who were evaluated as candidates for liver transplantation over a 1-year period in the University Hospital of Switzerland. A total of 51 patients were evaluated, and 11 were found to have clinical parkinsonism with extrapyramidal symptoms and signs. Those 11 were then carefully examined using a battery of tests that included the Unified Parkinson’s Disease Rating Scale (UPDRS), a neuropsychological exam, an MRI (interpreted by a neuroradiologist blinded to patients’ status), and measurements of copper and whole blood manganese. Cerebrospinal fluid levels of manganese were determined in 3 patients.
The clinical picture of cirrhosis-induced parkinsonism was very uniform. In the 11 patients, symptoms of parkinsonism began slowly and progressed rapidly over an average of 7 months. Symptoms and signs were symmetric, with generalized bradykinesia, dysarthria, postural instability, and prominent action tremor (not rest tremor). Six patients exhibited dystonia, typically involving the face and/or the feet. Mental status was reasonably preserved, but frontal lobe dysfunction developed on neuropsychological testing. Two patients were treated with levodopa, with significant improvement in parkinsonism as measured by the UPDRS. In all 11 patients, whole-blood manganese levels were elevated above normal. Cerebrospinal fluid manganese levels were also elevated in the 3 patients in whom it was measured. All patients had an abnormal MRI, with bilateral symmetric T1 hyperintensities in the substantia nigra and globus pallidus.
Comment by Steven Frucht, MD
In this careful study, Burkhard et al have defined the clinical and radiologic features of parkinsonism associated with cirrhosis. The disorder is common and probably under-recognized. The clinical presentation is one of a rapid, progressive, symmetric parkinsonian state, unaccompanied by pyramidal dysfunction, cerebellar signs, or cognitive decline. Involvement of the substantia nigra on MRI contributes a partial presynaptic deficit in these patients, as does the response to treatment with levodopa.
The etiology of cirrhosis-induced parkinsonism is unknown, but Burkhard et al’s results argue that the role of abnormal manganese deposition may be a critical factor. Unlike patients with acute manganism, neuropsychiatric features were absent in this cohort, save for evidence of frontal lobe dysfunction. Manganese deposition in the substantia nigra and globus pallidus has been previously demonstrated in patients with acute mangan ism. Liver transplantation in cirrhotic patients reverses the abnormalities seen on MRI. These factors suggest that manganese deposition causes cirrhotic parkinson ism. For patients who might not qualify for liver transplant, chelating agents might provide an alternate treatment to help slow this process. It certainly seems worthwhile treating these patients with levodopa. This disorder thus provides a compelling example of an extrapyramidal syndrome resulting indirectly from a serious medical illness.
Dr. Frucht is Assistant Professor of Neurology, New York Presbyterian Hospital-Cornell Campus, New York, NY.