Wilhelm Nolte

Bright basal ganglia in T1-weighted magnetic resonance images are frequent in patients with portal vein thrombosis without liver cirrhosis and not suggestive of hepatic encephalopathy.

BACKGROUND/AIMS Deposition of paramagnetic substances in basal ganglia, resulting in increased signals in T1-weighted magnetic resonance images (bright basal ganglia), is frequently seen in liver cirrhosis. The present study describes the prevalence of bright basal ganglia and its clinical significance in patients with long-standing portal vein thrombosis in the absence of liver cirrhosis. METHODS Six patients with angiographically proven complete portal vein thrombosis and cavernomatous transformation without signs of acute or chronic liver disease were studied by magnetic resonance imaging of the brain, neuropsychiatric evaluation, psychometric tests, electroencephalography, and determination of arterial ammonia levels and of serum manganese concentrations from peripheral venous blood. RESULTS Five out of six patients demonstrated increased signal intensity in the basal ganglia. Overt portal-systemic encephalopathy was not noted prior to or at the time of evaluation. Normal EEG results were recorded in all patients. Only one of the six patients had pathological results in at least two out of four psychometric tests. This latter patient had had a large right-sided brain infarction. Arterial ammonia concentrations were normal in four of the six patients; one patient with increased ammonia levels had concomitant renal insufficiency with azotemia. The other four patients had no relevant concomitant diseases. Serum manganese levels were non-significantly increased compared with a control group (p=0.06), but they were significantly correlated to basal ganglia signal intensity (R=0.88; p=0.02). CONCLUSIONS Our results demonstrate that bright basal ganglia primarily represent shunt-induced alterations. They are not directly associated with disturbed liver function nor with portal-systemic encephalopathy.

Elevated Serum Levels of Astroglial S100β in Patients with Liver Cirrhosis Indicate Early and Subclinical Portal-Systemic Encephalopathy

Portal-systemic encephalopathy is the prototype among the neuropsychiatric disorders that fall under the term Hepatic Encephalopathies. Ammonia toxicity is central to the pathophysiology of Portal-systemic encephalopathy, and neuronal ammonia toxicity is modulated by activated astrocytes. The calcium-binding astroglial key protein S100β is released in response to glial activation, and its measurement in serum only recently became possible. Serum S100β was determined by an ultrasensitive ELISA in patients (n=36) with liver cirrhosis and transjugular intrahepatic portosystemic stent-shunt. Subclinical portal-systemic encephalopathy and overt portal-systemic encephalopathy were determined by age-adjusted psychometric tests and clinical staging, respectively. Serum S100β was specifically elevated in the presence of subclinical or early portal-systemic encephalopathy, but not arterial ammonia. S100β levels elevated above a reference value (S100β ≤ 110pg/ml) or the cut off value determined in our group of patients (112pg/ml) predicted subclinical portal-systemic encephalopathy with a specificity and sensitivity of 100 and 56.5%, respectively. Serum S100β was significantly dependent on liver dysfunction (Child-Pugh score), but was more closely related to cognitive impairments than the score. Serum S100β seems to be a promising biochemical surrogate marker for mild cognitive impairments due to portal-systemic encephalopathy.

Psychiatric Aspects of Portal-Systemic Encephalopathy

This paper focuses on psychiatric aspects of portal-systemic encephalopathy (PSE) due to chronic liver disease and/or portal-systemic shunting. Clinical syndromes of PSE are discussed from the point of view of biological psychiatry, but, psychological consequences of concomitant cognitive disorders are also addressed. Psychiatric symptoms of early PSE and sleep disorders in patients with chronic liver disease are of specific interest.

Polysomnographic findings in five adult patients with pituitary insufficiency before and after cessation of human growth hormone replacement therapy

objective We observed the new onset of severe obstructive sleep apnoea syndrome (OSAS) in an adult male patient during human growth hormone (hGH) replacement therapy. This prompted us to evaluate the potential influence of hGH substitution therapy on sleep in middle‐aged men.

Increase of serum estradiol in cirrhotic men treated by transjugular intrahepatic portosystemic stent shunt

BACKGROUND/AIMS Liver cirrhosis is frequently associated with sexual dysfunction and hormonal abnormalities. To evaluate the effect of portosystemic shunting on sex steroid serum concentrations, a prospective study was performed in cirrhotic patients treated consecutively and electively by transjugular intrahepatic portosystemic stent shunt (TIPS). METHODS In 27 patients with liver cirrhosis we measured serum levels of testosterone (T), sexual hormone binding globulin (SHBG), luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone sulfate, androstenedione (A), estradiol (E2), 17-OH-progesterone and the T/SHBG ratio before and 3 months after TIPS. RESULTS In men (n = 17) 3 months after TIPS, A and E2 significantly increased, with mean serum levels rising from 4.4 +/- 2.5 to 5.6 +/- 2.9 ng/ml (P = 0.04) and from 27 +/- 9 to 40 +/- 19 pg/ml (P = 0.003), respectively. In contrast to A the increase of E2 persisted at 9 and 15 months after TIPS. Erectile dysfunction increased from 30% before TIPS to 70% after TIPS. In women (n = 10) A and E2 levels did not change significantly after TIPS. CONCLUSIONS TIPS aggravated hormonal dysbalance of sex steroids in favor of estrogens (hyperestrogenism) in men.

Quantification of the electroencephalographic theta/alpha ratio for the assessment of portal-systemic encephalopathy following implantation of transjugular intrahepatic portosystemic stent shunt (TIPSS).

The aim of the study was the quantification of metabolically caused electroencephalographic changes of portal-systemic encephalopathy, a prototype of hepatic encephalopathy. We examined 12 patients with liver cirrhosis before and after implantation of a transjugular intrahepatic portosystemic stent shunt (TIPSS) by means of quantitative digital electroencephalography (EEG). One month after TIPSS implantation, all patients showed an increase in the power of the theta frequency band as well as a decrease in the power of the alpha frequency band. To reduce the error variance, we formed the quotient of the relative power of the theta and alpha frequency band. Theta/alpha quotient values over 0.7 indicate a general change of the EEG with a sensitivity of 93% and a specificity of 87%. The results we have to hand indicate a correlation between the albumin concentration and the theta/alpha quotient 1 and 3 months after TIPSS. No significant correlation was revealed with regard to the Child-Pugh score or the liver function parameters cholinesterase, bilirubin, and prothrombin time. Neither the arterial ammonia concentration nor the performance in the psychometric test showed significance in relation to the theta/alpha quotient. Substances with a high albumin bond and potential neurotoxicity may—in the case of lower albumin levels—be absorbed with increased frequency in the CNS and may be responsible for the observed EEG change.

Quality of life and outcome of ultrasound-guided laser interstitial thermo-therapy for non-resectable liver metastases of colorectal cancer

Objective Patients with non-resectable liver metastases of colorectal cancer have poor prognosis and are mainly treated by palliative chemotherapy. Laser interstitial thermo-therapy is an innovative minimal invasive procedure for local tumour destruction within solid organs. The aim of the study was to investigate quality of life and outcome of ultrasound-guided laser interstitial thermo-therapy (US-LITT) in patients with liver metastases of colorectal cancer. Methods In this prospective non-randomized study, 45 patients with liver metastases of colorectal cancer were palliatively treated by US-LITT. Patient survival was analysed by the Kaplan–Meier method and the quality of life by questionnaire C30 of the European Organisation for Research and Treatment of Cancer before, and 1 week, 1 month, and 6 months after initiation of US-LITT. Results Median survival after initiation of US-LITT was 8.5 ± 0.7 months with a range of 1.5–18 months. Body weight was constant 1 month after US-LITT. In the multivariate analyses, quality-of-life symptoms and functioning scales did not deteriorate in patients alive at 6 months after initiation of US-LITT. Univariate analyses outlined a significant increase of the pain subscale before and at 1 week after US-LITT. Conclusions This study first describes the quality of life in patients with liver metastases of colorectal cancer treated by US-LITT. Potential benefits of the minimal invasive procedure could be prolonged survival time by preserved quality of life, but this first impression needs to be verified in a comparative study.

Recurrent episodes of acute hepatitis associated with LKM-1 (cytochrome P450 2D6) antibodies in identical twin brothers

BACKGROUND/AIMS Liver/kidney microsomal antibodies have been noted in liver disease of different etiology, e.g. in autoimmune hepatitis, chronic hepatitis C and D virus infection and in drug-induced liver disease. Unlike these, acute hepatitis of unknown etiology associated with high-titer liver/kidney microsomal-1 antibodies (cytochrome P450 2D6) is reported in identical twin brothers. METHODS Patients were studied using clinical, biochemical, serological and immunological methods, as well as liver biopsy. RESULTS The acute icteric episodes were followed by spontaneous remission with complete normalization of liver function tests and liver histology. During the acute phase, serum titer for liver/kidney microsomal-1 antibodies (detected by indirect immunofluorescence, ELISA and Western blot analysis) was exceedingly high and decreased gradually thereafter. Hepatitis C and D virus infection were excluded by repeated serological testing; exposure to drugs or chemicals was not evident. Concomitant autoimmune disease was not detectable. HLA typing for class 1 and 2 antigens was positive for the HLA haplotype DQ2, but negative for HLA B4, B8, DR3 and DR4. CONCLUSIONS The present observations might suggest a hitherto unreported form of acute hepatitis of unknown etiology, distinct from other liver diseases in which liver/kidney microsomal antibodies have been described so far.

Quantification of changes in electroencephalographic power spectra in a patient with Budd-Chiari-syndrome after implantation of a transjugular intrahepatic portosystemic stent shunt (TIPSS).

We examined a 41-year-old female with a subacute Budd-Chiari Syndrome (BCS) before and after implantation of a transjugular intrahepatic portosystemic stent shunt (TIPSS) by means of digital electroencephalography (EEG). After TIPSS implantation hepatic decompression had been achieved and the liver function as well as the clinical status improved daily. Simultaneously, the digital EEG showed a decrease in the power of the theta band and an increase in the physiological alpha frequency band. The theta/alpha ratio decreased after TIPSS, despite an elevated arterial ammonia level. The patient had a well-preserved liver parenchyma before the occurrence of the BCS. After portal decompression by TIPSS, the liver function normalized and the liver resumed efficient synthesis and parts of its detoxification task. This regeneration capacity was documented by a rise in cholinesterase after TIPSS. After temporary substitution of albumin the serum albumin concentration returned to normal. Thus, some neurotoxic substances with high albumin-binding capacity may not be absorbed by the central nervous system (CNS). Furthermore, it appears likely that the length of time the brain is exposed to neurotoxic substances plays a role in the clinical and electroencephalographic changes. Compared to the conventional EEG the theta/alpha ratio reflected better metabolically conditioned electroencephalographic changes after TIPSS.

Gyriform Liver Foci in Chronic Hepatic Porphyria

A patient with suspected liver metastases detected by routine sonography of the abdomen was admitted to our clinic for further testing. Liver sonography disclosed multiple irregular gyriform foci of a hyperechoic structure with a maximum diameter of 3.5 cm. In magnetic resonance imaging, these foci appeared as hyperintense in T1-weighted images and isointense in T2-weighted images. A biopsy showed a discrete portal and periportal fibrosis. UV light fluorescence of the specimen was negative. Analysis of urine revealed an almost fourfold el-evation of total porphyrin of 591 µg/24 h, proving the diagnosis of chronic hepatic porphyria. Characteristic liver foci in hepatic porphyria are detected by sonography in some affected patients. Usually, they can also be depicted by magnetic resonance imaging and computed tomography. These foci often appear before any other symptoms of the disease and are reversible when triggering factors, such as certain drugs or alcohol, are discontinued.