Critical flicker frequency for quantification of low‐grade hepatic encephalopathy

Subclinical hepatic encephalopathy (SHE) is currently diagnosed by psychometric tests or neurophysiologic techniques. In view of its sociomedical relevance, simple and reproducible tests for routine diagnosis are required. This study evaluates critical flicker‐frequency thresholds for quantification of low‐grade hepatic encephalopathy. A total of 115 patients (92 with cirrhosis, 23 controls) were analyzed for HE severity (mental state, computerized psychometric tests), and the threshold frequencies at which light pulses are perceived as fused (fusion frequency) or flickering light (critical flicker frequency [CFF]). CFF was a highly reproducible parameter with little age, day‐time, and training dependency. CFFs in cirrhotic patients without HE (HE 0) were not different from those found in noncirrhotic controls. Significantly lower CFFs were found in cirrhotic patients with subclinical or manifest HE, and the various HE groups separated from each other at a high level of significance (P < .01). By using a CFF cut‐off value of 39 Hz, a 100% separation of patients with manifest HE from noncirrhotic controls and HE 0 cirrhotic patients was obtained. SHE patients separated from HE 0 cirrhotic patients with high sensitivity (55%) and specificity (100%). The HE severity–dependent differences were found in both, alcoholic and posthepatitic cirrhosis. Statistically significant correlations (P < .01) were found between CFFs and individual psychometric tests. Aggravation of preexisting HE after transjugular intrahepatic portosystemic stent shunt (TIPS) implantation was accompanied by a corresponding decrease of CFF, whereas improvement of HE increased CFF. In conclusion, CFF is a sensitive, simple, and reliable parameter for quantification of low‐grade HE severity in cirrhotic patients and may be useful for the detection and monitoring of SHE.

[1]  H. Misiak,et al.  Critical flicker frequency (CFF) and psychotropic drugs in normal human subjects—A review , 1976, Psychopharmacology.

[2]  A. Reichenbach,et al.  Hepatic retinopathy: morphological features of retinal glial (Müller) cells accompanying hepatic failure , 2004, Acta Neuropathologica.

[3]  K Weissenborn,et al.  Neuropsychological characterization of hepatic encephalopathy. , 2001, Journal of hepatology.

[4]  G. Marchesini,et al.  Factors associated with poor health-related quality of life of patients with cirrhosis. , 2001, Gastroenterology.

[5]  R. Silberstein,et al.  Serotonin, noradrenaline and cognitive function: a preliminary investigation of the acute pharmacodynamic effects of a serotonin versus a serotonin and noradrenaline reuptake inhibitor , 2000, Behavioural pharmacology.

[6]  R Fischer,et al.  Hepatic encephalopathy in chronic liver disease: a clinical manifestation of astrocyte swelling and low-grade cerebral edema? , 2000, Journal of hepatology.

[7]  W. Hop,et al.  Screening of subclinical hepatic encephalopathy. , 2000, Journal of hepatology.

[8]  R. Butterworth Complications of cirrhosis III. Hepatic encephalopathy. , 2000, Journal of hepatology.

[9]  W. Cevallos,et al.  A comparison of the residual effects of zaleplon and zolpidem following administration 5 to 2 h before awakening. , 2001, British journal of clinical pharmacology.

[10]  A. Blei,et al.  Pathophysiology of cerebral edema in fulminant hepatic failure. , 1999, Journal of hepatology.

[11]  I. Hindmarch,et al.  A double-blind, placebo-controlled investigation of the effects of fexofenadine, loratadine and promethazine on cognitive and psychomotor function. , 1999, British journal of clinical pharmacology.

[12]  P. Angeli,et al.  Clinical features and survivial of cirrhotic patients with subclinical cognitive alterations detected by the number connection test and computerized psychometric tests , 1999, Hepatology.

[13]  W. Hop,et al.  Subclinical hepatic encephalopathy impairs daily functioning , 1998, Hepatology.

[14]  H. Scheinin,et al.  The Effects of Branched Chain Amino Acid Infusion on Pain Perception and Plasma Concentrations of Monoamines , 1998, Pharmacology Biochemistry and Behavior.

[15]  I. Anderson,et al.  Information processing in anxiety: a pilot study of the effect of manipulating 5-HT function , 1998, Journal of psychopharmacology.

[16]  E. Zrenner,et al.  Hepatic Retinopathia. Changes in Retinal Function , 1997, Vision Research.

[17]  S W Schalm,et al.  Subclinical Hepatic Encephalopathy , 1996, Seminars in liver disease.

[18]  G. Pomier‐Layrargues TIPS and hepatic encephalopathy. , 1996, Seminars in liver disease.

[19]  A. Herneth,et al.  Newer Approaches to Therapy of Hepatic Encephalopathy , 1996, Seminars in liver disease.

[20]  S. Bluml,et al.  Proton magnetic resonance spectroscopy: the new gold standard for diagnosis of clinical and subclinical hepatic encephalopathy? , 1996, Digestive diseases.

[21]  J. Schölmerich,et al.  Subclinical hepatic encephalopathy: the diagnostic value of evoked potentials. , 1995, Journal of hepatology.

[22]  A. Rademaker,et al.  Fitness to drive in patients with cirrhosis and portal-systemic shunting: a pilot study evaluating driving performance. , 1994, Journal of hepatology.

[23]  H. Schomerus,et al.  Prevalence of latent portasystemic encephalopathy in an unselected population of patients with liver cirrhosis in general practice. , 1993, Zeitschrift fur Gastroenterologie.

[24]  K. D. Kubinger Testtheoretische Probleme der Computerdiagnostik , 1993 .

[25]  Suzanne Corkin,et al.  Visual dysfunction in Alzheimer's disease: Relation to normal aging , 1991, Annals of neurology.

[26]  R. Butterworth,et al.  Subclinical Hepatic Encephalopathy in Cirrhotic Patients: Prevalence and Relationship to Liver Function , 1991 .

[27]  M. Mehndiratta,et al.  Comparative evaluation of visual, somatosensory, and auditory evoked potentials in the detection of subclinical hepatic encephalopathy in patients with nonalcoholic cirrhosis. , 1990, The American journal of gastroenterology.

[28]  Y. Liaw,et al.  Somatosensory evoked potentials and number connection test in the detection of subclinical hepatic encephalopathy. , 1990, Hepato-gastroenterology.

[29]  R. Hawkins,et al.  Cerebral function in hepatic encephalopathy. , 1990, Advances in experimental medicine and biology.

[30]  P. Angeli,et al.  Prognostic indicators of survival in patients with cirrhosis and esophageal varices, without previous bleeding. , 1989, The American journal of gastroenterology.

[31]  N. Gitlin,et al.  The diagnosis and prevalence of subclinical hepatic encephalopathy in apparently healthy, ambulant, non-shunted patients with cirrhosis. , 1986, Journal of hepatology.

[32]  T. Salmi Critical flicker frequencies in MS patients with normal or abnormal pattern VEP , 1985, Acta neurologica Scandinavica.

[33]  T E Starzl,et al.  Nonalcoholic cirrhosis associated with neuropsychological dysfunction in the absence of overt evidence of hepatic encephalopathy. , 1984, Gastroenterology.

[34]  D. Freides,et al.  Subclinical hepatic encephalopathy: detection, prevalence, and relationship to nitrogen metabolism. , 1978, Gastroenterology.

[35]  E. Lewis,et al.  The effect of alcohol on sensory phenomena and cognitive and motor tasks. , 1969, Quarterly journal of studies on alcohol.

[36]  A. Mahneke FLICKER‐FUSION THRESHOLDS , 1957, Acta ophthalmologica.

[37]  A. Mahneke FLICKER FUSION THRESHOLDS , 1956 .

[38]  A. Ivy,et al.  Effect of analeptic drugs on the somnifacient effect of seconal and antihistaminics as measured by the flicker fusion threshold. , 1952, Journal of applied physiology.