Martin Bokemeyer

Attention, memory, and cognitive function in hepatic encephalopathy.

Deficits in attention and arousal play a major role in the clinical presentation of hepatic encephalopathy. Attention deficits arealso the main components of minimal hepatic encephalopathy. The present paper summarizes some findings about attentional and memory dysfunction in hepatic encephalopathy, with reference to basic knowledgeabout normal attention and memory function and their cerebral representation.

Monoaminergic neurotransmission is altered in hepatitis C virus infected patients with chronic fatigue and cognitive impairment

Background: The majority of patients with hepatitis C virus (HCV) infection suffer from disabling fatigue, cognitive dysfunction, and quality of life reduction. Meanwhile, there is increasing evidence that HCV infection can affect brain function. Recent studies have shown that fatigue and psychomotor slowing may resolve in patients with hepatitis C after treatment with ondansetron. This observation indicates alteration of serotonergic neurotransmission in HCV infected patients with chronic fatigue. Methods: Data from 20 HCV infected patients who were referred to our clinic because of disabling fatigue and cognitive decline of unknown cause were analysed retrospectively. Patients had undergone a diagnostic programme, including clinical and psychometric examination, electroencephalogram (EEG), magnetic resonance imaging of the brain, cerebrospinal fluid analysis, and I-123-beta-CIT (2β-carbomethoxy-3-β-(4-[123I]iodophenyl)tropane) single photon emission computerised tomography (SPECT) studies of serotonin and dopamine transporter binding capacity. Results: All patients had pathological results on the fatigue impact scale. Two thirds of patients showed pathological attention test results. EEG, magnetic resonance imaging, and cerebrospinal fluid analysis were normal. Pathological dopamine transporter binding was present in 12/20 (60%) patients and pathological serotonin transporter binding in 8/19 (50%) patients. Patients with normal SPECT results did not significantly differ from controls with regard to psychometric test results. Interestingly, patients with both decreased serotonin and dopamine transporter binding showed significantly impaired performance in most of the tests applied. Comorbidity that could have impaired cerebral function was excluded in all patients. Conclusion: Our findings indicate alteration of serotonergic and dopaminergic neurotransmission in HCV infected patients with chronic fatigue and cognitive impairment.

Correlations between cerebral glucose metabolism and neuropsychological test performance in nonalcoholic cirrhotics.

Many cirrhotics have abnormal neuropsychological test scores. To define the anatomical–physiological basis for encephalopathy in nonalcoholic cirrhotics, we performed resting-state fluorodeoxyglucose positron emission tomographic scans and administered a neuropsychological test battery to 18 patients and 10 controls. Statistical parametric mapping correlated changes in regional glucose metabolism with performance on the individual tests and a composite battery score. In patients without overt encephalopathy, poor performance correlated with reductions in metabolism in the anterior cingulate. In all patients, poor performance on the battery was positively correlated (p < 0.001) with glucose metabolism in bifrontal and biparietal regions of the cerebral cortex and negatively correlated with metabolism in hippocampal, lingual, and fusiform gyri and the posterior putamen. Similar patterns of abnormal metabolism were found when comparing the patients to 10 controls. Metabolic abnormalities in the anterior attention system and association cortices mediating executive and integrative function form the pathophysiological basis for mild hepatic encephalopathy.

Functional Imaging of the Brain in Patients with Liver Cirrhosis

Brain imaging techniques have provided substantial insight into the pathophysiology of hepatic encephalopathy (HE). Magnetic resonance imaging gave hint to the fact that there is an increased deposition of manganese especially in the basal ganglia. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) showed that the preference of the basal ganglia might be due to differences in regional cerebral blood flow and an additional redistribution of blood flow from the cortex to subcortical regions in cirrhotics. PET studies using ammonia as tracer showed that the cerebral metabolism of ammonia and the permeability of the blood brain barrier for ammonia is increased in cirrhotic patients compared to healthy controls. The regional ammonia supply is in accordance with the regional blood flow. In accordance with these findings fluorodesoxyglucose-PET-studies of the brain in cirrhotics showed characteristic alterations of glucose utilisation in the patients with a relative decrease of the glucose utilisation of the cingulate gyrus, the frontomedial, frontolateral, and parieto-occipital cortex, while the glucose utilisation of the basal ganglia, the hippocampus, and the cerebellum was relatively increased. These findings fit well with the clinical characteristics of early stages of HE such as deficits in attention, visuo-spatial orientation, visuo-constructive abilities, motor speed, and accuracy.

Cerebral glucose utilisation in hepatitis C virus infection-associated encephalopathy

Patients with hepatitis C virus (HCV) infection frequently show neuropsychiatric symptoms. This study aims to help clarify the neurochemical mechanisms behind these symptoms and to add further proof to the hypothesis that HCV may affect brain function. Therefore, 15 patients who reported increasing chronic fatigue, mood alterations, and/or cognitive decline since their HCV infection underwent neurologic and neuropsychological examination, magnetic resonance imaging, 18F-fluoro-deoxy-glucose positron emission tomography of the brain, and single photon emission tomography of striatal dopamine and midbrain serotonin transporter (SERT) availability. None of the patients had liver cirrhosis. Patients’ data were compared with data of age-matched controls. In addition, regression analysis was performed between cognitive deficits, and mood and fatigue scores as dependent variables, and cerebral glucose metabolism, dopamine, or SERT availability as predictors. Patients showed significant cognitive deficits, significantly decreased striatal dopamine and midbrain SERT availability, and significantly reduced glucose metabolism in the limbic association cortex, and in the frontal, parietal, and superior temporal cortices, all of which correlated with dopamine transporter availability and psychometric results. Thus, the study provides further evidence of central nervous system affection in HCV-afflicted patients with neuropsychiatric symptoms. Data indicate alteration of dopaminergic neurotransmission as a possible mechanism of cognitive decline.

Structural brain abnormalities in cervical dystonia

BackgroundIdiopathic cervical dystonia is characterized by involuntary spasms, tremors or jerks. It is not restricted to a disturbance in the basal ganglia system because non-conventional voxel-based MRI morphometry (VBM) and diffusion tensor imaging (DTI) have detected numerous regional changes in the brains of patients.In this study scans of 24 patients with cervical dystonia and 24 age-and sex-matched controls were analysed using VBM, DTI and magnetization transfer imaging (MTI) using a voxel-based approach and a region-of-interest analysis. Results were correlated with UDRS, TWSTRS and disease duration.ResultsWe found structural alterations in the basal ganglia; thalamus; motor cortex; premotor cortex; frontal, temporal and parietal cortices; visual system; cerebellum and brainstem of the patients with dystonia.ConclusionsCervical dystonia is a multisystem disease involving several networks such as the motor, sensory and visual systems.

Video documented follow-up of liver transplantation in Wilson's disease with predominant neurological manifestation

Wilsons disease (WD) is a rare autosomal‐recessive disorder of copper metabolism with predominantly hepatic and extrapyramidal motor symptoms. Copper chelating therapy has proven to be an effective treatment for WD. Yet, if conservative treatment fails, liver transplantation (LT) often is the only remaining therapeutic option. The indication for LT especially in patients with stable liver function but severe neurological manifestation is debated controversially. In this case report, we document the follow up of neurological symptoms in WD after LT for the first time on video.

Imaging studies in hepatic encephalopathy

For decades, insights into the pathophysiology of hepatic encephalopathy (HE) had to be achieved using animal models, such as the portacaval shunted rat, or cell cultures. However, recent developments in brain imaging techniques, such as magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), single photon emission tomography (SPECT) and positron emission tomography (PET) provide new opportunities to study in vivo structural and metabolic changes, or even altered neurotransmission, in the brain of patients with HE.