Increase in mean diffusivity indicates the presence of interstitial brain edema. Mean diffusivity values increase as the grade of HE increases, suggesting that brain edema present in patients with HE may contribute to its pathogenesis.59 Mean diffusivity values decreased significantly and there was a corresponding improvement in neuropsychological test scores in patients with MHE after three weeks of lactulose therapy.59 MR imaging techniques therefore complement neuropsychological evaluation of MHE. 31 MRS, diffusion-weighted BMN 673 cell line imaging, magnetization transfer imaging and diffusion tensor

imaging show abnormalities in cirrhotic patients with or without HE. (1b) By definition, patients with MHE have a normal neurological examination; however they may still be symptomatic. Symptoms relate to disturbances in sleep, memory, attention, concentration and other areas of cognition.60,61 Sleep disturbance is a classic sign of HE. On a sleep questionnaire, disturbance is seen in 47% of cirrhotics and 38% of patients with chronic renal failure compared to 4.5% of controls.60 Studies using HRQOL

questionnaires have confirmed a higher frequency of sleep disturbance in cirrhotic patients with MHE as well.3,14 However, sleep disturbance in cirrhosis is not associated with cognitive impairment; thus it may not truly be an MHE symptom. Unsatisfactory sleep is associated with higher scores for depression and anxiety, raising the possibility that the effects of chronic disease may underlie the pathogenesis of sleep disturbance. Disturbances in cirrhotics may also be related to abnormalities of circadian rhythm. Defective memory has also been shown to be a feature find more of MHE. Weissenborn et al.61 have shown that patients with MHE have impaired short- and long-term memory. This impairment was predominantly related to deficits in attention and visual perception. Memory deficit of MHE seems to comprise short-term but not long-term memory impairment. This can be described as an encoding defect, in which memory recall (or retrieval) is intact.

Several cognitive statements (i.e. complaints), have predictive value for MHE, including impaired psychomotor performance selleck (‘I have difficulty doing handwork; I am not working at all’); impaired sleep or rest (‘I spend much of the day lying down in order to rest’); decreased attention (‘I am confused and start several actions at a time’); and poor memory (‘I forget a lot; for example, things that happened recently, where I put things, etc.’).14 It has been shown conclusively that cognitive functions improve with therapy for MHE.3,62–67 Such therapy may improve HRQOL of patients with MHE3,67 and delay the development of HE.68 Hence all patients with liver cirrhosis should be subjected to testing for MHE. Special attention should be given to those who have cognitive symptoms and high-risk groups such as active drivers, patients handling heavy machines or reporting decline in work performance.