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Brain metal concentrations in chronic liver failure patients with pallidal T1 MRI hyperintensity
Klos KJ, Ahlskog JE, Kumar N, Cambern S, Butz J, Burritt M, Fealey RD, Cowl CT et al.. Neurology, 2006-12-01
Topic: Brain proteins, microglia and lab models
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.
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APA 7th
Klos, K. J., Ahlskog, J. E., Kumar, N., Cambern, S., Butz, J., Burritt, M., et al. (2006). Brain metal concentrations in chronic liver failure patients with pallidal T1 MRI hyperintensity. Neurology. https://doi.org/10.1212/01.wnl.0000247037.37807.76
Vancouver
Klos KJ, Ahlskog JE, Kumar N, Cambern S, Butz J, Burritt M, et al. Brain metal concentrations in chronic liver failure patients with pallidal T1 MRI hyperintensity. Neurology. 2006. doi:10.1212/01.wnl.0000247037.37807.76. PMID: 17159105.
BibTeX
@article{klos2006-17159105,
author = {Klos, K. J. and Ahlskog, J. E. and Kumar, N. and Cambern, S. and Butz, J. and Burritt, M. and Fealey, R. D. and Cowl, C. T. and others},
title = {{Brain metal concentrations in chronic liver failure patients with pallidal T1 MRI hyperintensity}},
journal = {Neurology},
year = {2006},
doi = {10.1212/01.wnl.0000247037.37807.76},
pmid = {17159105},
url = {https://doi.org/10.1212/01.wnl.0000247037.37807.76}
}
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Key findings
- Background Chronic liver failure may be associated with pallidal MRI T1 hyperintensity and heterogeneous neurologic syndromes, including parkinsonism, cognitive impairment, and others.
- 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.
- 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).
Why it matters
In seven chronic liver failure cases, pallidal T1 hyperintensity was linked to sevenfold higher pallidal manganese concentrations, with manganese also elevated in other brain regions and mostly negative alpha-synuclein and tau staining. This concerns manganese accumulation in liver failure rather than Alzheimer's disease, and offers no treatment, cure or prevention for it.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2006 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 91 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.1 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 3 / 6 | Cited 3.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Keith A. Josephs: h-index 119 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 17159105) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 43 / 100 | — |
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