Critical flicker frequency and continuous reaction times for the diagnosis of minimal hepatic encephalopathy. A comparative study of 154 patients with liver disease

Abstract

Minimal hepatic encephalopathy (MHE) is intermittently present in up to 2/3 of patients with chronic liver disease. It impairs their daily living and can be treated. However, there is no consensus on diagnostic criteria except that psychometric methods are required. We compared two easy-to-perform reproducible bedside methods: the critical flicker frequency (CFF) and continuous reaction times (CRT) tests. A CFF <39 Hz and CRT-index <1.9 (index: the ratio 50/(90 minus 10) percentiles of reaction times) indicates cerebral dysfunction. 154 patients with acute or chronic liver disease with out overt hepatic encephalopathy (HE) underwent both tests at the same occasion. Both tests were abnormal in 20% of the patients and both tests were normal in 40% of the patients. In more than 1/3 the two tests were not in agreement as CFF classified 32% and CRT-index classified 48% of the patients as having MHE (p < 0.005). The two tests were weakly linearly correlated (r(2) = 0.14, p < 0.001) and neither test correlated with the metabolic liver function measured by the Galactose Elimination Capacity (GEC), nor with the blood ammonia concentration. Both tests identified a large fraction of the patients as having MHE and cleared only 40%. The two tests did not show concordant results, likely because they describe different aspects of MHE: the CFF gives a measure of astrocytic metabolic state and hence pathogenic aspects of MHE, whereas the CRT measures a composite key performance, viz. the ability of reacting appropriately to a sensory stimulus. The choice of test depends on the information needed in the clinical and scientific care and study of the patients.

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

“…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). This seems not necessarily to imply that all patients would be afflicted if enough tests were applied.…”

Minimal Hepatic Encephalopathy: The Reality Beyond Our Eyes

“…33,34 Several tools to detect MHE have been proposed, including neuropsychological testing (such as Psychometric Hepatic Encephalopathy Score (PHES), 33 Repeatable Battery for Assessment of Neuropsychological Status (RBANS), 33 Inhibitory Control Test, 35 Continuous Reaction Time Test 34,36 ), electroencephalogram spectral analysis/evoked potentials 33,[37][38][39][40] and critical flicker frequency. 33,34,36,41,42 Comparing with the other approaches, the psychometric testing is the most robust diagnostic method because it directly assesses the cognitive functions which are impaired in MHE and is more extensively validated. 33,36 The PHES has been recently recommended by the International Society on Hepatic Encephalopathy and Nitrogen Metabolism for the neuropsychological assessment of patients with liver disease.…”

“…33,34,36,41,42 Comparing with the other approaches, the psychometric testing is the most robust diagnostic method because it directly assesses the cognitive functions which are impaired in MHE and is more extensively validated. 33,36 The PHES has been recently recommended by the International Society on Hepatic Encephalopathy and Nitrogen Metabolism for the neuropsychological assessment of patients with liver disease. 33 Only this battery has been specifically developed for the diagnosis of MHE.…”

Diagnosis and Treatment of Low-Grade Hepatic Encephalopathy

“…From the reaction times a continuous reaction time (CRT) index is generated which allows comparison of the reaction time to a control. A CRT index of <1.9 is suggestive of mHE [14]. …”