Saccadic latency in hepatic encephalopathy: a pilot study

Abstract

Hepatic encephalopathy is a common complication of cirrhosis. The degree of neuro-psychiatric impairment is highly variable and its clinical staging subjective. We investigated whether eye movement response times-saccadic latencies-could serve as an indicator of encephalopathy. We studied the association between saccadic latency, liver function and paper- and pencil tests in 70 patients with cirrhosis and 31 patients after liver transplantation. The tests included the porto-systemic encephalopathy (PSE-) test, critical flicker frequency, MELD score and ammonia concentration. A normal range for saccades was established in 31 control subjects. Clinical and biochemical parameters of liver, blood, and kidney function were also determined. Median saccadic latencies were significantly longer in patients with liver cirrhosis when compared to patients after liver transplantation (244 ms vs. 278 ms p < 0.001). Both patient groups had prolonged saccadic latency when compared to an age matched control group (175 ms). The reciprocal of median saccadic latency (μ) correlated with PSE tests, MELD score and critical flicker frequency. A significant correlation between the saccadic latency parameter early slope (σ(E)) that represents the prevalence of early saccades and partial pressure of ammonia was also noted. Psychometric test performance, but not saccadic latency, correlated with blood urea and sodium concentrations. Saccadic latency represents an objective and quantitative parameter of hepatic encephalopathy. Unlike psychometric test performance, these ocular responses were unaffected by renal function and can be obtained clinically within a matter of minutes by non-trained personnel.

Fig. 1

Box-Whisker blots for individual surrogate markers of hepatic encephalopathy. The median is indicated by a horizontal line. Boxes indicate the 25th and 75th percentile and whiskers the range. Outliers are marked by circles. For saccadic latency the median of 200 individual saccadic latency times in each patient was calculated and for critical flicker frequency the median of 6 individual measurements in each patient was calculated. (Note that the differences in numbers are due to difficulties in obtaining PSE test results, CFF and pNH₃ in some patiens)

Fig. 2

Paired measurements of median saccadic latency before and after transplant in nine patients: the line represents the expected relationship if there is no change. Five patients showed significant reduction in latency, three patients showed a significant increase. (Changes in median saccadic latency were tested for significance in each patient by student’s t-test of log transformed data. Two hundred individual saccadic latency times were recorded for each patient before and 200 after transplantation). Note that a decrease in latency tends to occur in patients whose latencies were longer before the operation, i.e. those whose saccades were more severely affected by cirrhosis

Fig. 3

Scatter blots of surrogate markers of hepatic encephalopathy. Results from correlation tests are shown in Table 4. Individual results are depicted by circles. Regression lines and 95% confidence intervals for linear regression are shown

Fig. 4

Reciprobit plots summarizing the saccadic data from the patient presented in Table 1. The intercept of the 50^th percentile and the best-fit line indicates median saccadic latency (projection to the abscissa indicated by the dashed arrows). The slope of the line corresponds to the LATER parameter σ. Note that improvement of mean saccadic latency after transplantation is associated with a shift of the regression line, implying an increase in the LATER parameter σE