Related Experiment Video
Updated: Jul 18, 2026
Assessing Iron Deposition in the Brains of 5xFAD Mice by Perls'/DAB Staining
Published on: May 23, 2025
Brain metal concentrations in chronic liver failure patients with pallidal T1 MRI hyperintensity
K J Klos1, J E Ahlskog, N Kumar
1Department of Neurology, Mayo Clinic, Rochester, MN, USA. kklos@tulsacoxmail.com
Background:
Chronic liver failure may be associated with pallidal MRI T1 hyperintensity and heterogeneous neurologic syndromes, including parkinsonism, cognitive impairment, and others. Manganese accumulation may be responsible for the imaging and clinical findings.
Objective:
To measure manganese plus other metal concentrations in pallidum and additional brain regions and to examine the corresponding neuropathology in cases of chronic liver failure.
Methods:
Regional brain metal concentrations were measured in seven chronic liver failure cases, four with pallidal T1 hyperintensity and three with normal MRI, plus five controls. Neuropathologic examination employed alpha-synuclein and tau immunohistochemistry.
Results:
In patients with pallidal T1 hyperintensity, pallidal manganese concentrations were increased sevenfold over controls and over fourfold vs liver patients with normal MRI; manganese concentrations were also significantly elevated in all other brain regions. Copper was additionally increased in all brain regions, whereas other metal concentrations were similar to control values. Neuropathology revealed mild to moderate Alzheimer type II gliosis in the liver failure groups and negative alpha-synuclein and tau immunostaining except for one case (intermediate Alzheimer disease pathology).
Conclusion:
In chronic liver failure, manganese accumulation is responsible for the pallidal MRI T1 hyperintensity. Pallidal copper was also elevated in affected cases, but copper does not have the paramagnetic properties to generate isolated T1 hyperintensity. Basal ganglia manganese or copper accumulation may be responsible for the parkinsonism sometimes seen in chronic liver failure. Pallidal MRI T1 hyperintensity is a biomarker of manganese overload.
Insights
In chronic liver failure, manganese accumulation causes pallidal MRI T1 hyperintensity and neurological issues like parkinsonism. This T1 hyperintensity serves as a biomarker for manganese overload.
Area of Science:
- Neuroimaging
- Neuropathology
- Toxicology
Background:
- Chronic liver failure can lead to neurological syndromes, including parkinsonism and cognitive impairment.
- Associated MRI findings include pallidal T1 hyperintensity, potentially linked to manganese accumulation.
Purpose of the Study:
- Quantify manganese and other metal concentrations in the basal ganglia and other brain regions in chronic liver failure.
- Correlate metal levels with neuropathological findings, specifically Alzheimer type II gliosis and alpha-synuclein/tau pathology.
Main Methods:
- Metal concentrations in brain tissue were measured using ICP-MS in seven chronic liver failure patients and five controls.
- Neuropathological analysis involved immunohistochemistry for alpha-synuclein and tau proteins.
Main Results:
- Significantly elevated manganese levels were found in the pallidum and other brain regions of patients with chronic liver failure, especially those with T1 hyperintensity.
- Copper levels were also increased in affected brain regions, but manganese accumulation was the primary driver of T1 hyperintensity.
- Mild to moderate Alzheimer type II gliosis was observed, with minimal alpha-synuclein or tau staining.
Conclusions:
- Manganese accumulation is the cause of pallidal MRI T1 hyperintensity in chronic liver failure.
- Pallidal T1 hyperintensity is a reliable biomarker for manganese overload.
- Basal ganglia metal accumulation, particularly manganese, may underlie parkinsonism in chronic liver failure.
