Advanced
liver disease has long been associated with cerebral abnormalities. These abnormalities, termed acquired
hepatocerebral degeneration, are typically visualized as T1 weighted hyperintensity on MRI in the deep gray matter of the basal ganglia. Recent reports, however, have demonstrated that a subset of patients with chronic
alcoholic liver disease may also develop white matter abnormalities. Thus far, the morphology of these changes is not well characterized. Previous studies have described these changes as patchy, sporadic white matter abnormalities but have not posited localization of these changes to any particular white matter tracts. This paper hypothesizes that the white matter findings associated with advanced
alcoholic liver disease localize to the corticocerebellar tracts. As an initial investigation of this hypothesis, 78 patients with a diagnosis of
liver cirrhosis and an MRI showing clearly abnormal T1 weighted hyperintensity in the bilateral globus pallidus, characteristic of chronic
liver disease, were examined for white matter signal abnormalities in the corticocerebellar tracts using FLAIR and T2 weighted images. The corticocerebellar tracts were subdivided into two regions: periventricular white matter (consisting of the sum of the centrum-semiovale and corona radiata), and lower white matter (consisting of the corona radiata, internal capsules, middle cerebral peduncles, middle cerebellar peduncles and cerebellum). As compared to matched controls, significantly greater signal abnormalities in both the periventricular white matter and lower white matter regions of the corticocerebellar tracts were observed in patients with known
liver cirrhosis and abnormal T1 W hyperintensity in the globi pallidi. This difference was most pronounced in the lower white matter region of the corticocerebellar tract, with statistical significance of p<0.0005. Furthermore, the pathophysiologic mechanism underlying these changes remains unknown. This paper hypothesizes that the etiology of white matter changes associated with advanced
liver disease may resemble that of white matter findings in
subacute combined degeneration secondary to
vitamin B12 deficiency. Specifically, significant evidence suggests that dysfunctional
methionine metabolism as well as dysregulated
cytokine production secondary to B12 deficiency play a major role in the development of
subacute combined degeneration. Similar dysfunction of
methionine metabolism and
cytokine regulation is seen in
alcoholic liver disease and is hypothesized in this paper to, at least in part, lead to white matter findings associated with
alcoholic liver disease.