Georg Funk

Subclinical impairment of brain function in chronic hepatitis C infection.

BACKGROUND/AIMS Central nervous system abnormalities such as fatigue and depression occur more frequently in chronic hepatitis C virus (HCV) infection than in many other causes of chronic liver disease. The finding that fatigue is unrelated to activity of hepatitis or mode of infection could indicate an independent effect of HCV on brain function. This study tested the hypothesis of a subclinical cognitive dysfunction in HCV-infected patients. METHODS One-hundred untreated HCV-RNA positive biopsy-proven patients were investigated by P300 event-related potentials, a sensitive electrophysiologic test of cognitive processing. Health-related quality of life and fatigue were assessed using the SF-36 questionnaire and the Fatigue Impact Scale, respectively. RESULTS Cognitive brain function was subclinically impaired in the cohort of HCV-infected patients as indicated by significantly prolonged P300 latencies (P=0.01 for comparison to matched healthy subjects) and reduced P300 amplitudes (P<0.001, respectively). Seventeen of the 100 HCV-infected patients had P300 latencies outside the age-adjusted normal range. Abnormal P300 characteristics were not related to the degree of histologic or biochemical activity of hepatitis, severity of fatigue or mental health impairment. CONCLUSIONS This study demonstrates that patients with HCV infection showed a slight but significant neurocognitive impairment, possibly indicating a further extrahepatic manifestation of chronic hepatitis C.

Impaired subcortical and cortical sensory evoked potential pathways in septic patients.

ObjectiveSensory evoked potential (SEP) peak latencies were recorded in order to evaluate the incidence and severity of septic encephalopathy, testing the hypothesis that the occurrence of septic encephalopathy is more frequent than generally assumed. DesignProspective cohort study. SettingMedical intensive care unit of a university hospital. PatientsSixty-eight critically ill patients were studied within 48 hrs after the development of severe sepsis (n = 41) or septic shock (n = 27). InterventionsNone. Measurements and Main ResultsSeptic encephalopathy was defined as prolongation of SEP peak latencies beyond the upper limit of the reference range of subcortical (N13–N20 interpeak latency) and cortical SEP pathways (N20–N70 interpeak latency), as well as asymmetry of peak latencies marked by the presence of subclinical cerebral focal signs. Subcortical SEP pathways were impaired in 34% and cortical SEP pathways in 84% of all patients. The prolongation of the cortical SEP pathway correlated with the Acute Physiology and Chronic Health Evaluation III score (r = 0.23;p < .0001). SEP peak latencies did not differ in patients with severe sepsis compared with those with septic shock. Subclinical cerebral focal signs were present in 24% of the subcortical SEP pathways and in 6% of the cortical SEP pathways. ConclusionsSeptic encephalopathy occurs more frequently than generally assumed, and its severity is associated with the severity of illness. The impairment of subcortical and cortical SEP pathways was not different between patients with severe sepsis and those with septic shock.

Relative impact of fatigue and subclinical cognitive brain dysfunction on health-related quality of life in chronic hepatitis C infection.

Objectives:To assess the relative impact of fatigue and subclinical cognitive brain dysfunction on the impairment of health-related quality of life (HRQL) in hepatitis C virus (HCV) infection. Design and methods:We performed a cross-sectional study in 120 patients with untreated chronic HCV infection to test the hypothesis that the severity of fatigue had an independent effect on HCV-associated impairment of HRQL. Patients were investigated using the short-form-36 questionnaire, the fatigue impact scale, the brief fatigue inventory, and P300 event-related potentials, as an objective correlate of neurocognitive function. Patients with decompensated cirrhosis or clinical depression were excluded. Results:Relative to healthy controls, HCV-infected patients showed significant levels of fatigue (Fatigue Impact Scale, 49 versus 26 points, brief fatigue inventory, 3.0 versus 1.6 points, P < 0.001). Fatigue impact scale and brief fatigue inventory scores were highly correlated (r = 0.77, P < 0.001), demonstrating concurrent validity. Severity of fatigue and age were the only factors independently associated with the impairment of HRQL (P < 0.001). Fatigue was not related to the severity of hepatitis or the degree of subclinical brain dysfunction. Conclusion:In untreated patients with chronic HCV infection, fatigue severity and age but not neurocognitive dysfunction or hepatic function are independently associated with impaired HRQL. Both the fatigue impact scale and the brief fatigue inventory are suitable tools to assess the subjective burden of fatigue. Our findings stress the need for effective therapeutic interventions to reduce the burden of fatigue in patients with HCV infection.

Neurophysiological evidence of cognitive impairment in patients without hepatic encephalopathy after transjugular intrahepatic portosystemic shunts

OBJECTIVE:We aimed to test the hypothesis that subclinical cognitive brain dysfunction in cirrhotic patients would deteriorate after a transjugular intrahepatic portosystemic shunt (TIPS) in the absence of clinically detectable hepatic encephalopathy.METHODS:Out of 49 consecutive cirrhotic patients receiving elective TIPS for recurrent variceal hemorrhage, we identified 22 patients who were not encephalopathic and had not undergone liver transplantation at 6-month follow-up and confirmed TIPS patency by Doppler ultrasound. Patients were tested before and 6 months after TIPS implantation using event-related (P300) cognitive evoked potentials, late somatosensory median nerve (N70) potentials, and standard psychometric tests (Mini-Mental State and trailmaking test A). Twenty-two age-matched healthy subjects served as controls.RESULTS:Relative to controls, patients showed significantly impaired P300 and N70 latencies and abnormal psychometric test results at baseline. Six months after the TIPS, a further impairment of P300 latency was observed (p = 0.005), whereas no relevant changes in N70 latency and psychometric test results occurred.CONCLUSIONS:In cirrhotic patients with portal hypertension, neurophysiological signs of cognitive brain dysfunction are detectable in the absence of hepatic encephalopathy. A further subclinical deterioration of cognitive processing was observed 6 months after the TIPS. These findings demonstrate an aggravation of subclinical hepatic encephalopathy after a TIPS.

Prognostic accuracy of sensory evoked potentials (SEP) and arterial ammonia in predicting development of cerebral edema and death by cerebral herniation in patients with fulminant hepatic failure (FHF)

Cerebral edema, leading to cerebral herniation, is still a major clinical complication and a common cause of death in patients with FHF. Recording of SEP, an objective parameter of cerebral function, has been proposed to predict the neurological course in patients with FHF. Recently, it has been demonstrated that high arterial ammonia is associated with later death by cerebral herniation. We compared the prognostic accuracy of SEP and arterial ammonia in predicting development of cerebral edema and death from cerebral herniation. We included 54 patients (31 females,aged 36:!:19 years) with FHF. The worst N70 peak latency of SEP and the highest arterial ammonia level within 72 hours after emerge of hepatic encephalopathy grade no was used for analysis. Critical cutoff points were defined as 1.) presence or absence of cortical N70 peaks and 2.) arterial ammonia levels below or above 145 ILmoIIL. 21 patients (39%) developed a loss of the N70 peak and 27 patients (50%) had arterial ammonia levels> 145 ILmoIIL. 26 patients (48%) developed cerebral edema and 16 of those (62%) died from cerebral herniation. Out of 21 patients without N70 peak, all but one developed cerebral edema, but only 13 patients died from cerebral herniation. In contrast, out of 27 patients with arterial ammonia < 145 ILmoIIL, 4 patients developed cerebral edema and only 2 patients died from cerebral herniation. Patients who died from cerebral herniation had higher arterial ammonia concentrations (259:!:167 vs 130:!:106 ILmoIIL; p=O.OOI). The prognostic values of SEP and arterial ammonia are shown in the table. In FHF, recording of SEP has a high predictive accuracy to detect patients at risk of developing cerebral edema but fails to predict later death from cerebral herniation. In contrast, assessment of arterial ammonia fails to identify patients at risk of developing cerebral edema but allows detection of patients without risk of cerebral herniation.