Hepatic Encephalopathy (HE) is a well-recognized complication of cirrhosis. These patients display a variety of neuropsychological deficits as well as clinical and serum ammonia abnormalities. Sub-clinical hepatic Encephalopathy (SHE) is a subtler accompaniment of cirrhosis that is associated with neuropsychological abnormalities without significant neurologic findings such as asterixis. Although neuropsychological tests are the current standard for diagnosing SHE, the results are non-specific and reveal little about the underlying neurochemical processes. Cerebral Magnetic Resonance Spectroscopic (MRS) metabolic alterations and MRI signal abnormalities in the basal ganglia reveal a relationship between neuropsychological functioning and biochemical abnormalities found in patients with SHE. This study will involve collaboration among hematologists, radiologists, psychiatrists, MR physicists and neuropsychologists. We will identify a total of 60 liver failure patietns who have SHE and compare them to 60 healthy control subjects. These patients and healthy controls will undergo clinical assessment by hepatologists and neuropsychiatric evaluation by psychiatrists. Subsequently, they will undergo a comprehensive series of neuropsychological tests to characterize the nature of their neurocognitive deficits. Following these tests, all subjects will undergo MR Imaging and Spectroscopic (MRI/MRS) examinations.
We aim to use 1H MRS to meare and compare absolute cerebral metabolite levels of myo-inositol, choline, and glutamine/glutamate in the frontal lobe, parietal lobe and basal ganglia of a matched group of SHE patients and healthy controls. The resulting MRS and MRI data will be quantitatively analyzed and correlated with the results of neuropsychological testing and clinical examination. Multivariate methods and correlational analysis will be used to test hypotheses regarding differences between SHE patients and controls. We hypothesize that myo-inositol will be decreased, glutamine/glutamate will be increased and choline will be decreased in patietns with SHE. We propose that these underlying biochemical abnormalities will be correlated with clinical, neuropsychiatric and neuropsychological aspects of SHE. If these relationships are found, they will provide an improved biochemical understanding of the underlined aspects of SHE as characterized y clinical and neuropsychological testing. This enhanced understanding of pathophysiology will improve our ability to diagnose and treat this condition, resulting in improved patient outcomes.
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