Clinical investigations in hepatic encephalopathy: Applications of proton nuclear magnetic resonance spectroscopy

Abstract

A primary goal of this work was to demonstrate that 1 H magnetic resonancespectroscopic techniques can be used to understand the neurochemistry noninvasively in hepatic encephalopathy. In Phase I, cerebral metabolite levels were quantified relative to creatine in patients (n=17) with sub clinical and mild hepatic encephalopathy using a GE 1.5T MRI scanner with a standard head MRI coil. A STEAM sequence was used to localize a voxel in the parietal white matter. Some of these patients were scanned again after they received a liver transplantation (n=9). Neuropsychological assessment was done with a battery of neuropsychologic tests. In Phase II, the absolute levels of cerebral metabolite levels were measured in ambulant patients awaiting liver transplantation (n=21). In addition to the parietal white matter, the prefrontal cortex was also localized for the MRS study using a PRESS sequence with TR=3 s, TE=30 ms, and NS=128. Phase I results showed a significant reduction in mI/Cr, a small decline in Cho/Cr, and an increase in Glx/Cr in patients when compared to healthy controls. The patients did not return to normal cerebral metabolic states within 60 days of liver transplantation. The absolute levels in Phase II results showed an increase in creatine, and glutamine/glutamate, a decrease in myoinositol, and no significant change in choline in patients compared to healthy controls. A significant correlation was found between the magnetic resonancespectroscopy findings and the neuropsychologic tests in both Phase I and Phase II studies. The results emphasize the role of multiple neurotransmitter systems in the pathogenesis of hepatic encephalopathy.