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Recent Updates on Acquired Hepatocerebral Degeneration Cover

Recent Updates on Acquired Hepatocerebral Degeneration

Tremor and Other Hyperkinetic Movements
Volume 7 (2017): Issue 0
By: Hae-Won Shin and  Hee Kyung Park  
Open Access
|Sep 2017

Figures & Tables

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Figure 1

Pathology of AHD. Alzheimer type II astrocyte showing large pale nuclei with basophilic nuclei. Reproduced with permission from Ferrara et al.12 AHD, Acquired Hepatocerebral Degeneration.

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Figure 2

The Putative Pathomechanism in AHD. The exact pathomechanism in AHD remains unclear, but the putative pathomechanism includes complex actions between toxic substance accumulation, neuroinflammation, oxidative stress, and inducible nitric oxide (nitrosative stress). AHD, Acquired Hepatocerebral Degeneration.

Video 1

Case 1: A 63-Year-Old Male with a 3-Year History of Tremor. He presented with masked face, hypophonia, micrographia, mild action tremor of hands, and mild rigidity and bradykinesia. With levodopa 300 mg/day, there was marked improvement of tremor, micrographia, and bradykinesia.

Video 2

Case 2: A 38-Year-Old Male with Severe Tremors of the Tongue, Jaw, and Both Hands. He presented with severe resting and postural tremors in the arms, masked face, mild bradykinesia, and rigidity, which were not responsive to levodopa.

Table 1

Comparison between Wilson disease, AHD, and Chronic Manganism

Wilson DiseaseAHDChronic Manganism
Etiology or risk factorsCausative gene: ATP7B (Family history)Chronic liver failure, portosystemic shuntOccupational exposures: welders, miners
Possible pathomechanismAccumulation of copperSynergistic actions of multiple mechanisms

  1. Accumulation of toxic substances: ammonia, manganese

  2. Neuroinflammation

  3. Oxidative and nitrosative stress

Accumulation of manganese
Clinical characteristics

  1. Age at onset: <30

  2. Ophthalmic: K-F rings

  3. Hepatic: hepatic dysfunction

  4. Movement disorders: parkinsonism, dystonia, wing-beating tremor, ataxia, dysarthria, and chorea

  5. Cognition: impaired executive function and attention deficits

  6. Psychiatric: depression, personality changes, psychosis

  1. Age at onset: variable

  2. Ophthalmic: absence of K-F ring

  3. Hepatic: advanced hepatobiliary diseases

  4. Movement disorders: ataxia, tremor, parkinsonism, chorea, dystonia, and myoclonus

  5. Cognition: inattentiveness, apathy, and psychomotor slowness

  6. Psychiatric: apathy, disinhibition, aggression

  1. Age at onset: variable, mostly adulthood

  2. Ophthalmic: absence of K-F ring

  3. Hepatic: normal function

  4. Movement disorders: parkinsonism, dystonia, and gait disturbance

  5. Cognitive dysfunction

  6. Psychiatric changes: compulsive behaviors, psychosis

Laboratory findings

  1. Serum ceruloplasmin: ↓

  2. 24-hour urinary copper: ↑

  3. Abnormal liver function tests

  4. Hemolytic anemia: present

  5. Genetic testing: ATP7B mutations

  1. Abnormal liver function tests

  2. Normal to slightly increased ammonia level

  3. Increased manganese levels in whole blood and CSF may be shown

  1. Increased manganese levels in whole blood

Neuroimaging findings

  1. T2-MRI (m/c): hyperintensities in the thalamus, lentiform and caudate nuclei, midbrain (“face of the giant panda”), and cerebellum

  2. T1-MRI: hyperintensities in the globus pallidus

  1. T1-MRI (m/c): hyperintensities in the globus pallidus, putamen, and substantia nigra

  2. T2-MRI: MCP and cerebellum

  3. F-DOPA and DAT scan: conflicting results (normal uptake and reduced uptake of F-DOPA and DAT)

  1. T1-MRI hyperintensities in the globus pallidus and substantia nigra

  2. F-DOPA and DAT scan: conflicting results (normal uptake and reduced uptake of F-DOPA and DAT)

PathologyOpalski cells, Alzheimer type II astrocyte, cavitationsAlzheimer type II astrocyte, polymicrocavitation, CPM/EPMAlzheimer type II astrocyte
Management

  1. Chelating agent: zinc, penicillamine, trientine (effective)

  2. Hepatic failure: liver transplantation (controversial)

  3. Symptomatic therapy

    • Parkinsonism: levodopa (may be beneficial)

    • Tremor: beta-blocker

    • Dystonia: anticholinergics, botulinum toxin

No established treatments

  1. Liver transplantation for liver failure (may reverse neurologic manifestations)

  2. Symptomatic therapy:

    • Parkinsonism: levodopa (may be beneficial)

    • Tremor: beta-blocker, anticholinergics (limited)

    • Chorea: tetrabenazine (limited)

  3. Other treatments: trientine, BCAA, and BRTO (controversial)

  1. Chelating agent: CaNa2EDTA, PAS

  2. Symptomatic therapy:

    • Parkinsonism: levodopa (limited)

[i] Abbreviations: BCAA, Branched-Chain Amino Acid; BRTO, Balloon-Occluded Retrograde Transvenous Obliteration; CaNa2EDTA, Calcium Disodium Salt Ethylene Diamine Tetraacetic Acid; CPM, Central Pontine Myelinolysis; CSF, Cerebrospinal Fluid; DAT, Dopamine Transporter; EPM, Extrapontine Myelinolysis; F-DOPA, Fluorodopa; K-F rings, Kayser-Fleischer Rings; MCP, Middle Cerebellar Peduncles; m/c, Most Common; PAS, Para-Aminosalicylic Acid; T1-MRI, T1-Weighted Magnetic Resonance Imaging; T2-MRI, T2-Weighted Magnetic Resonance Imaging.

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Figure 3

Neuroimaging Studies in AHD with Parkinsonism. (A) Brain MRI in AHD. High signal intensities in the bilateral globus pallidus on T1-weighted images, (B-E) (18F FP-CIT PET findings. (B) Normal controls; (C) AHD patients with parkinsonism; (D) AHD patients with parkinsonism; (E) Idiopathic Parkinson diseases. AHD, Acquired Hepatocerebral Degeneration; 18F FP-CIT PET, 18F-N-3-Fluoropropyl-2β-Carboxymethoxy-3β-(4-iodophenyl)-Nortropane Positron Emission Tomography; MRI, Magnetic Resonance Imaging.

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Figure 4

Brain MRI findings in AHD with Ataxia-Plus Syndrome. (A) High signal lesion on T2-weighted image and (B) low signal lesion on T1-weighted image in the middle cerebellar peduncles Reproduced with permission from Ishii K et al.75 AHD, Acquired Hepatocerebral Degeneration; MRI, Magnetic Resonance Imaging.

DOI: https://doi.org/10.5334/tohm.379 | Journal eISSN: 2160-8288
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Language: English
Submitted on: Mar 11, 2017
Accepted on: Jul 24, 2017
Published on: Sep 5, 2017
Published by: Columbia University Libraries/Information Services
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year
Keywords:
Acquired hepatocerebral degeneration,
liver cirrhosis,
manganese,
parkinsonism,
neuroinflammation,
dopamine transporter imaging

© 2017 Hae-Won Shin, Hee Kyung Park, published by Columbia University Libraries/Information Services
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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