Dokument: Magnetic resonance spectroscopy and quantitative brain water imaging in patients with hepatic encephalopathy

Titel:Magnetic resonance spectroscopy and quantitative brain water imaging in patients with hepatic encephalopathy
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URN (NBN):urn:nbn:de:hbz:061-20160111-100929-3
Dokumententyp:Wissenschaftliche Abschlussarbeiten » Dissertation
Autor: Oeltzschner, Georg [Autor]
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Dateien vom 05.01.2016 / geändert 05.01.2016
Beitragende:Prof. Dr. Schnitzler, Alfons [Gutachter]
Prof. Dr. Heinzel, Thomas [Gutachter]
Dewey Dezimal-Klassifikation:500 Naturwissenschaften und Mathematik » 530 Physik
Beschreibung:Hepatic encephalopathy (HE) is a set of neurological symptoms frequently occurring as a consequence of liver cirrhosis. HE affects many functional entities of the brain, including cognitive, executive and perceptive systems. Patients with HE exhibit an impaired performance of cognitive tasks, abnormal perception of temperature stimuli, behavioural changes, and motor dysfunctions. The severity of these symptoms is highly volatile and can range from subtle alterations to stupor and coma hepaticum.

The accumulation of neurotoxic ammonia in the brain due to impaired liver activity has been identified as a key feature of HE, triggering manifold responses such as neuroinflammation, oxidative stress, and formation of low-grade oedema. Recent magnetoencephalography (MEG) studies have provided evidence that HE symptoms are consistently associated with slowing of neural oscillations in their respective functional systems, but the underlying mechanisms remain elusive. While these and numerous other processes behind HE have been identified on microscopic and mesoscopic scales, they are yet to be integrated
into a coherent pathophysiological concept, and at this point, it remains unclear how they contribute to pathological neural activity.

The present work investigated the role of the main inhibitory neurotransmitter gamma-aminobutyric acid (GABA) for the pathogenesis of HE. As local GABA levels had previously
been shown to influence the frequency of oscillations in the visual and the motor gamma frequency band, it was hypothesized that altered GABA concentrations contribute to HE symptoms via modulation of neural oscillations.

To test this hypothesis, magnetic resonance spectroscopy (MRS) was employed to determine in vivo levels of GABA in a cohort of 16 healthy controls and 30 HE patients. Results showed a decrease of GABA in the visual cortex in HE. Further, individual GABA levels correlated with the critical flicker frequency (CFF), a singular experimental parameter reliably reflecting HE severity. Low GABA was also linked to elevated blood ammonia levels. Beyond this, GABA was coupled to concentrations of glutamine and myo-inositole, two compounds that are highly involved in astrocytic regulation of hyperammonemia. However, none of these relationships became evident in the sensorimotor region, giving rise to the assumption that the mechanisms mediating pathological behaviour are substantially different across brain regions.

In a second MRS investigation, the interplay of the major cerebral antioxidant glutathione, magnetic resonance imaging (MRI) measures of brain water content and HE characteristics was studied. Glutathione was elevated in HE, correlated with blood ammonia levels and closely followed alterations of glutamine and myo-inositol, suggesting an involvement in the interception of oxidative stress induced by ammonia. In contrast, measures
of brain water content were not influenced by HE severity, blood ammonia or metabolite concentrations. This may imply that, at least in early stages of HE, the pathological impact of cerebral oedema may be smaller than previously assumed.

In conclusion, the novel findings presented in this work may help improve the understanding of the emergence of HE. GABA concentrations are presumably relevant for the development of HE symptoms in certain functional systems, but evidence prompts the
notion that the exact pathways mediating abnormal oscillatory behaviour are highly region-specific. Further, glutathione appears to participate in the adaptation to hyperammonemia, whereas the relationship of brain water content and HE severity may be of more complex nature than previously expected.
Fachbereich / Einrichtung:Mathematisch- Naturwissenschaftliche Fakultät
Dokument erstellt am:11.01.2016
Dateien geändert am:11.01.2016
Promotionsantrag am:06.11.2015
Datum der Promotion:16.12.2015
Status: Gast