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

Abstract

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.

Minimal hepatic encephalopathy characterized by parallel use of the continuous reaction time and portosystemic encephalopathy tests

“…Therefore, encephalopathy in these patients likely was MHE. In accordance with earlier reports from us and from others we found a high proportion of patients with abnormal psychometric tests (Lauridsen et al 2012;Patidar et al 2014;Nabi et al 2014;Bajaj et al 2014;Li et al 2013). Also, more patients had abnormal results when more than one psychometric test was applied; a phenomenon also present in our earlier study on the CRT and the Critical Flicker Frequency Method (Lauridsen et al 2011) and in reports on the use of a battery of tests (Montagnese et al 2011;Goldbecker et al 2013;Sharma et al 2010;Maldonado-Garza et al 2011).…”

“…One hundred and twenty-nine patients were prospectively included and underwent CRT, PSE and blood tests on the same occasion between February 2013 and August 2014. The included patients also filled out the Sickness Impact Profile questionnaire on quality of life and Epworth Sleepiness Scale and Sleep Timing Sleep Quality questionnaires for sleep assessment as described in detail elsewhere (Groeneweg et al 1998;Lauridsen et al 2014). A Dutch reference population sets the SIP baseline (Groeneweg et al 1998).…”

“…A value below 1.9 is considered abnormal and may indicate minimal HE. The method measures and combines motor reaction speed, sustained attention, and inhibitory control, which are all key abilities of daily life functioning (Lauridsen et al 2013).…”

“…Mounting evidence supports is use: we and others have shown that more than half of liver patients with no other cause of brain involvement have an abnormal test result; that there is no learning or tiring effect; that the test result is not age or gender dependent; not related to educational or social status; and that it is not disturbed by sleep deprivation (Elsass 1986;Jakobsen et al 2010;Lauridsen et al 2014;Lauridsen et al 2012;Lauridsen et al 2013;Elsass et al 1985). However, the CRT test has not been systematically conducted in parallel with the PSE test and consequently has not been compared with a test of other cognitive domains.…”

Brain edema: a valid endpoint for measuring hepatic encephalopathy?

“…In humans, diagnosing HE, in particular minimal/covert HE, involves using sophisticated neuropsychometric and neurophysiological tests, such as the psychometric hepatic encephalopathy score (PHES) (Weissenborn et al 2001;Ferenci et al 2002;Amodio et al 2008), the inhibitory control test (ICT) (Bajaj et al 2007), the critical flicker frequency (CFF) test (Kircheis et al 2002), the continuous reaction time (CRT) (Lauridsen et al 2013) and the EncephalApp (Smartphone based Stroop test) (Bajaj et al 2013). Overall, these tests evaluate cognition, psychomotor processing speed, visuomotor coordination, memory, attention as well as motor function.…”