The continuous reaction times method for diagnosing, grading, and monitoring minimal/covert hepatic encephalopathy

Existing tests for minimal/covert hepatic encephalopathy (m/cHE) are time- and expertise consuming and primarily useable for research purposes. An easy-to-use, fast and reliable diagnostic and grading tool is needed. We here report on the background, experience, and ongoing research regarding the continuous reaction times (CRT) method. The method has been in clinical use for decades in Denmark for the stated purpose. The method is a 10-minutes, computerised registration of a series of motor reaction times to an auditory stimulus, with results reported as the CRTindex (50 percentile/(90-10) percentile) as a parameter of reaction time variability. The index is a measure of alertness stability and is used to assess attention and cognition deficits. The CRTindex identifies half of patients in a Danish cohort with chronic liver disease, as having m/cHE, a normal value safely precludes HE, it has a broad outcome span reflecting the degree of brain impairment, it shows no learning effect, and it is independent on age and gender. The CRTindex is, therefore, a candidate tool for routine screening, detecting, grading, and monitoring m/cHE. Still, however, further methodological and clinical validation trials are required and are currently being conducted.