Carlos Jacas

The development of low-grade cerebral edema in cirrhosis is supported by the evolution of 1H-magnetic resonance abnormalities after liver transplantation

BACKGROUND/AIMS Liver failure may cause brain edema through an increase in brain glutamine. However, usually standard neuroimaging techniques do not detect brain edema in cirrhosis. We assessed magnetization transfer ratio and (1)H-magnetic resonance (MR) spectroscopy before and after liver transplantation to investigate changes in brain water content in cirrhosis. METHODS Non-alcoholic cirrhotics without overt hepatic encephalopathy (n=24) underwent (1)H-MR of the brain and neuropsychological tests. (1)H-MR results were compared with those of healthy controls (n=10). In a subgroup of patients (n=11), the study was repeated after liver transplantation. RESULTS Cirrhotic patients showed a decrease in magnetization transfer ratio (31.5+/-3.1 vs. 37.1+/-1.1, P<0.01) and an increase in glutamine/glutamate signal (2.22+/-0.47 vs. 1.46+/-0.26, P<0.01). The increase in glutamine/glutamate signal was correlated to the decrease in magnetization transfer ratio and to neuropsychological function. Following liver transplantation, there was a progressive normalization of magnetization transfer ratio, glutamine/glutamate signal and neuropsychological function. Accordingly, correlations between these variables were lost after liver transplantation. CONCLUSIONS Cirrhotic patients show reversible changes in magnetization transfer ratio that are compatible with the development of low-grade cerebral edema. Minimal hepatic encephalopathy and low-grade cerebral edema appear to be the consequences of the metabolism of ammonia in the brain.

Quality of life and cognitive function in hepatitis C at different stages of liver disease

BACKGROUND/AIMS Hepatitis C has been associated with a decrease in quality of life and with neurological abnormalities. The aim of our study was to investigate the relationship between quality of life and cognitive function. METHODS Quality of life, clinical variables and neuropsychological function were evaluated in 120 patients with hepatitis C (mild chronic hepatitis, compensated cirrhosis and decompensated cirrhosis) and in healthy controls (n=40, in each group). RESULTS Patients with chronic hepatitis or compensated cirrhosis showed a decrease in quality of life, in spite of unimpaired neuropsychological tests. Patients with decompensated cirrhosis exhibited a further decrease in quality of life and neuropsychological abnormalities. The decrease in quality of life was associated with the severity of liver failure, neuropsychological abnormalities and treatment with beta-blockers or diuretics. However, in the multivariable analysis, only treatment with beta-blockers or diuretics (which was limited to decompensated cirrhosis) was independently associated with quality of life. CONCLUSIONS Hepatitis C causes a decrease in quality of life even in the absence of major cognitive impairment. The mechanisms that worsen quality of life are unknown. However, in cirrhotic outpatients with prior decompensations, treatment with beta-blockers or diuretics appears to have an important effect on quality of life.

Quality of life in cirrhosis is related to potentially treatable factors.

Objective Improvement of prognosis and availability of diverse therapeutic options for complications of advanced liver disease highlight the importance of health-related quality of life (HRQOL) in cirrhosis. The aim of this study was to identify factors that influence HRQOL and may be potentially treatable in patients with cirrhosis. Methods HRQOL was measured in 212 outpatients with cirrhosis using a generic questionnaire (Medical Outcomes Study Form, SF-36) and a liver-specific questionnaire (Chronic Liver Disease Questionnaire, CLDQ). All patients underwent a systematic clinical and neuropsychological assessment. Independent factors associated with poor HRQOL were identified by multiple linear regression. Results HRQOL scores exhibited by patients were: global CLDQ: 4.8±1.2; Physical Component Score of SF-36: 38.5±10.7; Mental Component Score of SF-36: 45.3±14.3. The independent variables for global CLDQ were female sex, nonalcoholic etiology, current ascites, and a decrease in albumin (R2 = 0.22). For Physical Component Score of SF-36, the independent variables were prior hepatic encephalopathy, current ascites, and a decrease in hemoglobin (R2 = 0.22). For Mental Component Score of SF-36, the independent variables were nonalcoholic etiology, the Grooved Pegboard test, and a decrease in hemoglobin (R2 = 0.14). Conclusion Several clinical variables, potentially treatable, may alter particular aspects of HRQOL. Correction of ascites, hypoalbuminemia, minimal hepatic encephalopathy, and anemia may cause a positive impact on HRQOL of patients with cirrhosis.

Hepatic encephalopathy is associated with posttransplant cognitive function and brain volume

Hepatic encephalopathy (HE) is a common complication of cirrhosis that is associated with brain atrophy and may participate in impaired cognitive function after liver transplantation. This study analyzes the relationship of HE with cognitive function and brain volume after transplantation. A total of 52 consecutive patients with cirrhosis (24 alcohol abuse, 24 prior HE, 14 diabetes mellitus) completed a neuropsychological assessment before liver transplantation and again, 6 to 12 months after transplantation. In 24 patients who underwent the posttransplant assessment, magnetic resonance imaging was performed in addition, with measurement of brain volume and relative concentration of N‐acetylaspartate (NAA) and creatine/phosphocreatine (Cr), a neuronal marker, by magnetic resonance spectroscopy. Neuropsychological assessment prior to transplantation identified minimal HE in 28 patients. All cognitive indexes improved after liver transplantation, but 7 patients (13%) showed persistent mild cognitive impairment. Global cognitive function after transplantation was poorer in patients with the following variables before liver transplantation: alcohol etiology, diabetes mellitus, and HE. Brain volume after transplantation was smaller in patients with prior HE. Brain volume correlated to NAA/Cr values (r = 0.498, P = 0.013) and poor motor function (r = 0.41, P = 0.049). In conclusion, the association of HE with cognitive function and brain volume suggests that having experienced HE before liver transplantation impairs the posttransplantation neurological outcome. Liver Transpl 17:38–46, 2011.

Development of a clinical hepatic encephalopathy staging scale.

To develop a scale to assess the severity of hepatic encephalopathy using simple dichotomic items.

Decreased White Matter Lesion Volume and Improved Cognitive Function After Liver Transplantation

Focal T2‐weighted white matter lesions (WML) on brain magnetic resonance imaging (MRI), mimicking those seen in cerebrovascular small‐vessel disease described in patients with persistent hepatic encephalopathy, decreased in volume with the improvement of hepatic encephalopathy. This outcome has been interpreted as a decrease in the edema that it is proposed to be involved in the pathogenesis of hepatic encephalopathy. We designed a study to further investigate potential changes in focal WML in the brains of patients with cirrhosis following liver transplantation and to study the relationship between these changes and overall cognitive function. We used MRI to measure the volume of supratentorial focal WML and a neuropsychological examination to assess cognitive function before and after liver transplantation in 27 patients with cirrhosis without signs of overt hepatic encephalopathy. Baseline MRI identified focal T2‐weighted lesions in 19 patients (70.3%). The presence of WML was associated with older age but not with vascular risk factors, severity of liver function, or psychometric tests. A significant reduction in lesion volume was observed after liver transplantation (from a median of 1.306 cm3 to 0.671 cm3, P = 0.001). This decrease correlated with an improvement in an index of global cognitive function (r = −0.663; P < 0.001). This evolution indicates that lesion volume is partially related to a reversible type of tissue damage, which is compatible with brain edema. Conclusion: Focal WML probably induced by age‐related microvascular injury can decrease their volume with liver transplantation. The associated improvement of cognitive function supports a relationship between brain edema and minimal hepatic encephalopathy. (HEPATOLOGY 2007.)

Brain dysfunction in multiple chemical sensitivity.

Multiple Chemical Sensitivity (MCS) is a chronic acquired disorder of unknown pathogenesis. The aim of this study was to ascertain whether MCS patients present brain single photon emission computed tomography (SPECT) and psychometric scale changes after a chemical challenge. This procedure was performed with chemical products at non-toxic concentrations in 8 patients diagnosed with MCS and in their healthy controls. In comparison to controls, cases presented basal brain SPECT hypoperfusion in small cortical areas of the right parietal and both temporal and fronto-orbital lobes. After chemical challenge, cases showed hypoperfusion in the olfactory, right and left hippocampus, right parahippocampus, right amygdala, right thalamus, right and left Rolandic and right temporal cortex regions(p<or=0.01). By contrast, controls showed hyperperfusion in the cingulus, right parahippocampus, left thalamus and some cortex regions (p<or=0.01). The clustered deactivation pattern in cases was stronger than in controls (p=0.012) and the clustered activation pattern in controls was higher than in cases (p=0.012). In comparison to controls, cases presented poorer quality of life and neurocognitive function at baseline, and neurocognitive worsening after chemical exposure. Chemical exposure caused neurocognitive impairment, and SPECT brain dysfunction particularly in odor-processing areas, thereby suggesting a neurogenic origin of MCS.

Long-Term Treatment with Citicoline May Improve Poststroke Vascular Cognitive Impairment

Background: Cognitive decline after stroke is more common than stroke recurrence. Stroke doubles the risk of dementia and is a major contributor to vascular cognitive impairment and vascular dementia. Nonetheless, few pharmacological studies have addressed vascular cognitive impairment after stroke. We assessed the safety of long-term administration and its possible efficacy of citicoline in preventing poststroke cognitive decline in patients with first-ever ischemic stroke. Methods: Open-label, randomized, parallel study of citicoline vs. usual treatment. All subjects were selected 6 weeks after suffering a qualifying stroke and randomized by age, gender, education and stroke type into parallel arms of citicoline (1 g/day) for 12 months vs. no citicoline (control group). Medical management was similar otherwise. All patients underwent neuropsychological evaluation at 1 month, 6 months and 1 year after stroke. Tests results were combined to give indexes of 6 neurocognitive domains: attention and executive function, memory, language, spatial perception, motor speed and temporal orientation. Using adjusted logistic regression models we determined the association between citicoline treatment and cognitive decline for each neurocognitive domain at 6 and 12 months. Results: We recruited 347 subjects (mean age 67.2 years, 186 male (56.6%), mean education 5.7 years); 172 (49.6%) received citicoline for 12 months (no significant differences from controls n = 175). Demographic data, risk factors, initial stroke severity (NIHSS), clinical and etiological classification were similar in both groups. Only 37 subjects (10.7%) discontinued treatment (10.5% citicoline vs. 10.9% control) at 6 months; 30 (8.6%) due to death (16 (9.3%) citicoline vs. 14 (8.0%) control, p = 0.740), 7 lost to follow-up or incorrect treatment, and 4 (2.3%) had adverse events from citicoline without discontinuation. 199 patients underwent neuropsychological evaluation at 1 year. Cognitive functions improved 6 and 12 months after stroke in the entire group but in comparison with controls, citicoline-treated patients showed better outcome in attention-executive functions (OR 1.721, 95% CI 1.065–2.781, p = 0.027 at 6 months; OR 2.379, 95% CI 1.269–4.462, p = 0.007 at 12 months) and temporal orientation (OR 1.780, 95% CI 1.020–3.104, p = 0.042 at 6 months; OR 2.155, 95% CI 1.017–4.566, p = 0.045 at 12 months) during the follow-up. Moreover, citicoline group showed a better functional outcome (modified Rankin scale ≤2) at 12 months (57.3 vs. 48.7%) without statistically significant differences (p = 0.186). Conclusions: Citicoline treatment for 12 months in patients with first-ever ischemic stroke is safe and probably effective in improving poststroke cognitive decline. Citicoline appears to be a promising agent to improve recovery after stroke. Large clinical trials are needed to confirm the net benefit of this therapeutic approach.

A long-term study of changes in the volume of brain ventricles and white matter lesions after successful liver transplantation.

Background. A prolonged survival in liver transplant recipients due to a better management exposes them to multiple factors that can impair neurologic function in the long term. Methods. Twenty-two patients were studied by brain magnetic resonance and completed a neuropsychologic assessment shortly before liver transplant, 6 to 12 months after (short term), and 6 to 9 years (long term) after liver transplant. Thirteen healthy controls matched by age were studied in parallel. Results. An enlargement in the ventricular size (an indirect measure of brain volume) was observed in the short term (+8%) and in the long term after liver transplant (+22%); the size of ventricles was larger than in healthy controls. In addition, a progression in the volume of focal T2 white matter lesions (an index of small vessel cerebrovascular disease) was detected in the long term (+49%) and was related to vascular risk factors in those with larger increases (>12.5% per year). Neuropsychologic function showed a significant improvement after liver transplant and remained stable in the long term, except for memory loss in those patients with larger increases in white matter lesions. Conclusions. Improvement in neuropsychologic function after successful liver transplant can be demonstrated up to 9 years. However, these patients experience a progressive accumulation of focal T2 brain lesions and show a smaller brain volume than controls, which can be related to their previous cirrhosis. A good management to minimize brain injury before transplantation and an accurate treatment of vascular risk factors may be important to prevent consequences on cognitive function.

Relationship between poor decision-making process and fatigue perception in Parkinson's disease patients.

BACKGROUND Fatigue is a common non-motor symptom in Parkinsons disease patients. The reasons for its perception are not completely understood. One suggested possibility might be that perceived fatigue is related with abnormal interpretation of somatic symptoms. It has been described that somatic markers misinterpretation leads to poor decision-making. We hypothesized that fatigued Parkinsons disease patients would show poorer performance than non-fatigued in a decision-making task. METHODS To test our hypothesis, 89 Parkinsons disease patients were assessed for the presence of fatigue using the Parkinson Fatigue Scale. All patients were also administered scales evaluating psychopathology and neuropsychological tests, including the Iowa Gambling Task. RESULTS 33 (37.1%) patients fulfilled the established criteria for fatigue. In the univariate analysis, fatigued patients showed higher levels of anxiety (state: p = 0.001, trait: p < 0.001), impulsivity (p = 0.051), and depression (p < 0.001) than non-fatigued patients. No statistically significant differences in other neuropsychological test results (Stroop, Trail Making Test, Tower of London) were found between fatigued and non-fatigued patients except for the Iowa Gambling Task, in which fatigued patients showed poorer performance (p = 0.001) after controlling for confounding factors. CONCLUSIONS These results suggest that fatigued Parkinsons disease patients may present abnormal decision-making process, which may reflect abnormal processing of somatic markers when faced with an activity that requires effort.