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.
Similar content being viewed by others
References
Bankhead I, MacKay DN (1982) Fine motor performance in subjects of subnormal, normal and superior intelligence. I. Reaction time and task complexity. J Ment Defic Res 26(Pt 2):73–89
Bianchi G, Giovagnoli M, Sasdelli AS, Marchesini G (2012) Hepatic encephalopathy and health-related quality of life. Clin Liver Dis 16(1):159–170. doi:10.1016/j.cld.2011.12.003
Bruhn P, Parsons OA (1971) Continuous reaction time in brain damage. Cortex 7(3):278–291
Dam G, Keiding S, Munk OL, Ott P, Vilstrup H, Bak LK, Waagepetersen HS, Schousboe A, Sorensen M (2012) Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake. Hepatology. doi:10.1002/hep.25995
Elsass P (1984) Number connection test and continuous reaction times in assesment of organic and metabolic encephalopathy: a comparative study. Acta Pharmacol Toxicol 54:115–119
Elsass P (1986a) Continuous reaction times in cerebral dysfunction. Acta Neurol Scand 73:225–246
Elsass P (1986b) Continuous reaction times in cerebral dysfunction. Acta Neurol Scand 73(3):225–246
Elsass P, Hartelius H (1985) Reaction time and brain disease: relations to location, etiology and progression of cerebral dysfunction. Acta Neurol Scand 71(1):11–19
Elsass P, Zeeberg I (1983) Reaction time deficit in multiple sclerosis. Acta Neurol Scand 68(4):257–261
Elsass P, Lund Y, Ranek L (1978) Encephalopathy in patients with cirrhosis of the liver. A neuropsychological study. Scand J Gastroenterol 13(2):241–247
Elsass P, Christensen SE, Ranek L, Theilgaard A, Tygstrup N (1981) Continuous reaction time in patients with hepatic encephalopathy. A quantitative measure of changes in consciousness. Scand J Gastroenterol 16(3):441–447
Elsass P, Christensen SE, Mortensen EL, Vilstrup H (1985) Discrimination between organic and hepatic encephalopathy by means of continuous reaction times. Liver 5(1):29–34
Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT (2002) Hepatic encephalopathy–definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology 35(3):716–721. doi:10.1053/jhep.2002.31250
Frijns CJ, Laman DM, van Duijn MA, van Duijn H (1997) Normal values of patellar and ankle tendon reflex latencies. Clin Neurol Neurosurg 99(1):31–36
Harder F, Elsass P, Hvidberg EF, Hjorting-Hansen E, Hendel J (1976) Clinical and psychological effects of intravenous diazepam related to plasma levels. A controlled, double-blind, cross-over study in oral surgery involving local analgesia. Int J Oral Surg 5(5):226–239
Haussinger D, Schliess F, Kircheis G (2002) Pathogenesis of hepatic encephalopathy. J Gastroenterol Hepatol 17(Suppl 3):S256–S259
Iversen P, Keiding S, Mouridsen K, Ott P, Vilstrup H (2011) Transjugular intrahepatic portosystemic shunt does not alter cerebral blood flow. Clin Gastroenterol Hepatol 9(11):1001–1003. doi:10.1016/j.cgh.2011.07.015
Jakobsen LH, Sorensen JM, Rask IK, Jensen BS, Kondrup J (2010) Validation of reaction time as a measure of cognitive function and quality of life in healthy subjects and patients. Nutrition. doi:10.1016/j.nut.2010.08.003
Lally M, Nettelbeck T (1977) Intelligence, reaction time, and inspection time. Am J Ment Defic 82(3):273–281
Lauridsen MM, Jepsen P, Vilstrup H (2011) Critical flicker frequency and continuous reaction times for the diagnosis of minimal hepatic encephalopathy: a comparative study of 154 patients with liver disease. Metab Brain Dis 26(2):135–139. doi:10.1007/s11011-011-9242-1
Lauridsen MM, Gronbaek H, Naeser EB, Leth ST, Vilstrup H (2012) Gender and age effects on the continuous reaction times method in volunteers and patients with cirrhosis. Metab Brain Dis. doi:10.1007/s11011-012-9318-6
Miller E (1970) Simple and choice reaction time following severe head injury. Cortex 6(1):121–127
Montagnese S (2012) Validation of a computerized psychometric test for minimal hepatic encephalopathy (MHE): the scan test. Preliminary results from a multicentre study. In: 15th ISHEN Symposium, Grenaa, Denmark, June 2012 2012. ISHEN, SHEN Program and abctract book, pp 73–74
Reichenbach A, Stolzenburg JU, Wolburg H, Hartig W, el-Hifnawi E, Martin H (1995) Effects of enhanced extracellular ammonia concentration on cultured mammalian retinal glial (Muller) cells. Glia 13(3):195–208. doi:10.1002/glia.440130306
Renzi D (1965) The comparative efficiency of intelligence and vigilance tests in detecting hemispheric cerebral damage. Cortex 1:410–433
Sharma P, Sharma BC, Puri V, Sarin SK (2007) Critical flicker frequency: diagnostic tool for minimal hepatic encephalopathy. J Hepatol 47(1):67–73. doi:10.1016/j.jhep.2007.02.022
Weissenborn K (2012) Psychometric tests for diagnosing minimal hepatic encephalopathy. Metab Brain Dis. doi:10.1007/s11011-012-9336-4
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lauridsen, M.M., Thiele, M., Kimer, N. et al. The continuous reaction times method for diagnosing, grading, and monitoring minimal/covert hepatic encephalopathy. Metab Brain Dis 28, 231–234 (2013). https://doi.org/10.1007/s11011-012-9373-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-012-9373-z