J Yeungnam Med Sci.  2023 Apr;40(2):136-145. 10.12701/jyms.2022.00689.

Hepatic encephalopathy on magnetic resonance imaging and its uncertain differential diagnoses: a narrative review

• Lim CG
• Hahm MH
• Lee HJ

• KMID: 2541939
• DOI: http://doi.org/10.12701/jyms.2022.00689

Abstract

Hepatic encephalopathy (HE) is a severe neuropsychiatric abnormality in patients with either acute or chronic liver failure. Typical brain magnetic resonance imaging findings of HE are bilateral basal ganglia high signal intensities due to manganese deposition in chronic liver disease and hyperintensity in T2, fluid-attenuated inversion recovery, or diffusion-weighted imaging (DWI) with hemispheric white matter changes including the corticospinal tract. Low values on apparent diffusion coefficient mapping of the affected area on DWI, indicating cytotoxic edema, can be observed in acute HE. However, neuropsychological impairment in HE ranges from mild deficits in psychomotor abilities affecting quality of life to stupor or coma with higher grades of hepatic dysfunction. In particular, the long-lasting compensatory mechanisms for the altered metabolism in chronic liver disease make HE imaging results variable. Therefore, the clinical relevance of imaging findings is uncertain and differentiating HE from other metabolic diseases can be difficult. The recent introduction of concepts such as “acute-on-chronic liver failure (ACLF),” a new clinical entity, has led to a change in the clinical view of HE. Accordingly, there is a need to establish a corresponding concept in the field of neuroimaging diagnosis. Herein, we review HE from a historical and etiological perspective to increase understanding of brain imaging and help establish an imaging approach for advanced new concepts such as ACLF. The purpose of this manuscript is to provide an understanding of HE by reviewing neuroimaging findings based on pathological and clinical concepts of HE, thereby assisting in neuroimaging interpretation.

Keyword

Chronic liver disease; Hepatic encephalopathy; Magnetic resonance imaging

Figure

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  Fig. 1. A 57-year-old male with hepatic encephalopathy. (A–E) T1-weighted imaging shows high signal intensity in the basal ganglia, which is more prominent in the globus pallidus (arrows) and substantia nigra reticulata (short arrows), and to a lesser extent, striatum, portions of the bilateral internal capsules, and cerebellar peduncle (arrowhead).

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  Fig. 2. A 49-year-old male with general weakness. (A) Fluid-attenuated inversion recovery imaging shows diffuse high signal intensity lesions involving subcortical white matter, (B) periventricular white matter, (C) internal capsule, and (D) midbrain crus cerebri in a patient with chronic liver disease.

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  Fig. 3. A 52-year-old male with weakness of upper extremities. (A) Magnetic resonance imaging sequences of T2-weighted imaging, (B) fluid-attenuated inversion recovery, (C) diffusion-weighted imaging, and (D) apparent diffusion coefficient map show signal changes in cortex of precentral gyrus of both frontal lobes (arrows) in a patient with chronic liver disease.

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  Fig. 4. Magnetic resonance (MR) spectroscopy of a 61-year-old male with liver cirrhosis. Compared with (A) the spectrum from the relatively spared right thalamus, (B) the proton MR spectrum of a patient with hepatic encephalopathy shows significant increases (upward pointing arrows) in lipid macromolecular content (Lipid-Macro) and glutamate/glutamine (Glx), and marked decreases in choline (Cho) and myoinositol (mIns) (downward pointing arrows). (C) On a T2-weighted image, MR shows increased signal intensities at the basal ganglia and corpus callosum with periventricular white matter extension with a relatively spared thalamus. Cre, creatine; NAA, N-acetylaspartate.

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  Fig. 5. Proposed pathway of pathophysiology in hepatic encephalopathy. There are two major axes of the pathophysiology pathway: decreased protein synthesis and ammonemia in chronic liver disease. Decreased protein synthesis causes impaired manganese chelation, resulting in manganemia, manganese deposition in globus pallidus, and high T1 signal intensity (SI) observed on brain magnetic resonance imaging (MRI). Arylsulfatase A (ASA) depletion is also believed to trigger axonal degeneration of transcallosal fibers in a metachromatic leukodystrophy-like mechanism, consequently Marchiafava-Bignami disease (MBD). On pathology, ammonemia causes Alzheimer type II astrocytes and spongiform gray matter, which cause acquired chronic hepatocerebral degeneration (ACHD) symptoms. In addition, ammonemia causes a decrease in intracerebral myoinositol, which makes brain cells, especially astrocytes, sensitive to external osmotic pressure changes, resulting in osmotic demyelinating syndrome of central pontine or extrapontine types depending on the anatomical location. Since abnormalities in ion influx eventually lead to edema and death of nerve cells, metronidazole encephalopathy occurs when drugs such as metronidazole are used in these vulnerable patients. GFAP, glial fibrillary acidic protein; DWI, diffusion-weighted imaging; ADC, apparent diffusion coefficient.

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  Fig. 6. Clinical manifestation of hepatic encephalopathy. In both chronic liver disease and liver cirrhosis, residual liver function declines over time. Acute decompensation episodes occur recurrently due to the existence of precipitating factors. In the period of precirrhotic disease, reversible metabolic encephalopathy shows good prognosis due to full recovery after a temporary decrease in liver function. As residual liver function gradually declines into compensatory cirrhosis, intracellular glutamine accumulation and deficiency of choline and myoinositol are observed. When an acute decompensation episode occurs from this period onward, returning liver function to its initial state is challenging. With disease progression, basal ganglia T1 hyperintensity related to manganese accumulation is observed, and after entering decompensated cirrhosis, white matter T2 hypersensitivity is observed on magnetic resonance imaging. Finally, this damages the cortex and induces signal changes in the cortex. If organ failure is accompanied by acute decompensation episodes, it can be clinically classified as acute-on-chronic liver failure (ACLF), with increased mortality with a number of organ failures. CPM, central pontine myelinolysis; EPM, extrapontine myelinolysis; NAA, N-acetylaspartate; MRS, magnetic resonance spectroscopy.

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  Fig. 7. A 52-year-old male with stuporous mentality. (A–D) Extensive involvement of deep gray matter, including globus pallidus (GP), striatum (Str), thalamus (Th), and dentate nucleus (DN) as well as involvement of white matter such as periventricular white matter (PVWM), corpus callosum (CC), internal capsule (IC), tegmentum (Tg), tectum (Tc), and pons, mimicking central pontine myelinolysis and extrapontine myelinolysis.

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  Fig. 8. A 52-year-old male with stuporous drowsy mentality. (A–D) Fluid-attenuated inversion recovery imaging shows reported synchronous involvement of red nucleus (arrow) and dentate nucleus (arrowhead) in a patient with metronidazole encephalopathy.

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