Postural hand tremor before and following liver transplantation and immunosuppression with cyclosporine or tacrolimus in patients without clinical signs of hepatic encephalopathy

Objective: To assess tremor characteristics and severity in patients with severe liver disease without hepatic encephalopathy and following orthotopic liver transplantation (LTX) and immunosuppresion (IS) with cyclosporin A (CsA) or tacrolimus (FK 506). Methods: A total of 35 consecutive patients were included into the prospective study and serum levels of CsA (n = 29) or FK 506 (n = 6) were monitored following LTX. Tremor characteristics and severity were assessed by two-blinded raters before and following LTX. In addition, accelerometric recordings were taken before and after LTX, and compared with 16 normal controls without tremor and without clinical signs of hepatic encephalopathy or liver disease. Accelerometry was performed while sitting in a comfortable chair with the forearms supported and included rest and postural condition with and without weight load (500 g) on each hand. Kolmogorov-Smirnov test, paired t-test and t-test for independent samples were used for statistical analysis. Results: The clinical rating revealed no rest but a mild postural hand tremor before LTX with a significant increase following LTX (p < 0.001). After LTX the mean score of postural tremor was significantly (p < 0.05) higher in patients with plasma levels of >850 ng CsA/ml compared with patients with lower levels. Patients and normal controls showed comparable mean peak frequencies of rest and postural hand tremor. The mean amplitude of postural hand tremor was significantly higher in patients before and after LTX compared with controls. In the majority of patients (89%) and controls (88%), the dominant tremor frequency decreased significantly (>1.5 Hz) when applying a weight load on each hand. Conclusion: The present study is the first to describe hand tremor characteristics in patients with severe liver disease without clinical signs of hepatic encephalopathy and in patients following LTX and IS. Compared with normal controls the patients showed a significant postural hand tremor prior and post-LTX and an increase of mean tremor amplitude following LTX and CsA/FK 506 treatment. The decrease of the dominant tremor frequency with weight load and an increase of tremor amplitude with higher plasma levels of CsA are both indicative of an enhanced physiological or toxic tremor.