CASE 4427 Published on 14.05.2006

MRI of the brain in a patient affected by Wilson Disease

Section

Neuroradiology

Case Type

Clinical Cases

Authors

I. Pesaresi¹, C. Michelassi¹, G. Lazzarotti¹, M. Cosottini² (¹) Departement of Oncology, Transplants and New Technologies in Medicine (²) Department of Neuroscience

Patient

29 years, male

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Clinical History

The patient was admitted to hospital for rigidity and involuntary movements. Since one year he suffered from behavioral disturbance (irritability and aggressiveness) , for which he was treated with haloperidol. The patient was also affected by cirrhosis, previously classified as alcoholic.

Imaging Findings

The neurological examination revealed plastic rigidity, reduced arm movements during walking and reduced facial expressions. The neuropsychologic tests documented a mild cognitive impairement (Mini Mental State 26/30) and reduced abstractive capacity. The MRI study of the brain demonstrated symmetric bilateral abnormal signal involving both gray matter and white matter, highly suggestive for Wilson Disease (WD): T2-weighted images at basal ganglia level showed high signal in external capsule and internal medullary lamina of the thalamus and low signal in lenticular nucleus and ventroposterior nucleus of the thalamus; at midbrain level, features similar to the classical 'face of the giant panda' sign (formed by high signal intensity in the tegmentum except for the red nucleus, preserved signal intensity of the lateral portion of the pars reticulata of the substantia nigra and hypointensity of the superior colliculus) were present; DP-T2 weighted images showed high signal in dorsal pons. MR imaging of the liver revealed a micronodular aspect on T1-weighted images, in relation to cirrhosis. On T2-weighted images the nodules didn't show a significant signal drop, suggesting a relatively low iron deposition. The WD diagnosis was confirmed by laboratory exams (serum copper <80mcg/100ml and urinary copper excretion >100µg/24h; caeruloplasmin value: not detectable) and by liver biopsy (hepatic copper concentration>250µg/g of dry weight).

Discussion

Wilson Disease (WD) is a rare autosomal inherited disorder. The mutant gene (ATP7B) encodes for the hepatic copper-transporting ATPase which regulates the copper metabolism. In WD copper accumulates in the liver and in other organs, such as the brain, and causes cellular damage by promoting the production of free radicals. The main criteria for the diagnosis of WD are: neuropsychiatric symptoms of unknown origin, hepatitis or cirrhosis of unknown origin, caeruloplasmin <20mg/dl, serum copper < 80mcg/100ml, urinary copper excretion >100µg/24h, hepatic copper concentration>250µg/g of dry weight. Usually, WD manifests as liver pathology in children-adolescents and as neuropsychiatric illness in young adults. The severity of the liver damage varies from a simple fatty infiltration to an advanced cirrhosis with portosystemic shunts. The brain damage can be present even without a severe hepatic damage. The neurologic symptoms can be grouped in parkinsonian, pseudosclerotic, dystonic and choreic. The psychiatric manifestations include behavioral, affective, schizophrenic-like and cognitive disorders. Moreover WD causes ophthalmologic (Kayser-Fleischer rings for copper deposits within Descemet membrane), hematological (hemolytic anemia), musculoskeletal (osteopenia, arthropathy) and renal illness (Fanconi-like syndrome). Although not pathognomonic, neuroimaging can help in the diagnosis of this rare disorder. CT imaging is much less sensitive then MRI in detecting the brain damage. MRI studies of the brain report bilateral symmetric alterations and identify different types of signal abnormalities: white matter presents abnormal high signal intensity on T2 weighted images (probably related to mielinolysis and gliosis). Gray matter presents either abnormal high signal intensity on T2 weighted images (probably related to spongy-cystic degeneration and cell loss) or low signal intensity in both T1 and T2 weighted images (probably related to iron deposits). Indeed the caeruloplasmin deficit in WD is responsible for a secondary alteration of iron metabolism, and, on the other hand, copper deposits cannot be responsible for the T2 signal decay because Cu ¹⁺ is diamagnetic. Moreover in patients with liver failure and portosystemic shunts MRI studies report a T1-hyperintensity of the globus pallidus. MR imaging has also an important role to monitor the therapy response infact some pathological MRI findings has been demonstrated to be reversible after somministration of chelating agents (e.g. penicillamina) .

Differential Diagnosis List

Wilson Disease or Hepatolenticular Degeneration.

Final Diagnosis

Wilson Disease or Hepatolenticular Degeneration.

References

[1] van Wassenaer-van Hall HN, van den Heuvel AG, Algra A, Hoogenraad TU, Mali WP. Wilson Disease: finding at MR Imaging and CT of the brain with clinical correlation. Radiology, vol 198, pp 531-536 (1996). (PMID: 8596862)

[2] Aisen AM, Martel W, Gabrielsen TO, Glazer GM, Brewer G, Young AB, Hill G. Wilson Disease of the Brain: MR imaging. Radiology, vol147, pp 1137-141 (1985). (PMID: 4034959)

[3] Askwith C, Kaplan J. Iron and copper transport in yeast and its relevance to human disease. TIBS 23, pp135-138 (1998). (PMID: 9584616)

[4] Arredondo M, Nunez MT. Iron and copper metabolism. Molecular apect of medecine, vol 26, pp 313-327 (2005). (PMID: 16112186)

[5] Liebeskind DS, Wong S, Hamilton RH. Faces of the giant panda and her cub: MRI correlates of Wilson\'s Disease. J.Neurol. Neurosurg. Psychiatry, vol 74, pp 682 (2003). (PMID: 12700322)

Case information

URL:	https://www.eurorad.org/case/4427
DOI:	10.1594/EURORAD/CASE.4427
ISSN:	1563-4086

Figure 1

Axial MR images at basal ganglia level

SE T2-weighted image in the axial plane at level of the basal ganglia. High signal intensity of the external capsules and internal medullary lamina of the thalamus; low signal intensity of lenticular and caudate nuclei.

Figure 2

Axial MR images at pons level

SE PD-weighted image in the axial plane at pons level. High signal intensity in the dorsal pontine region.

Figure 3

Hepatic copper transporting ATPase

The hepatic copper transporting ATPase mediates the copper transport inside the Golgi vescicular system and thus allows copper incorporation in ceruloplasmin and its excretion in bile when in excess. Ceruloplasmin mediates iron mobilization by acting as ferroxidase and converting ferrous iron to ferric iron, which is then bound by transferrin. WDN: copper transporting ATPase whose mutation is responsible for Wilson Disease. CP: ceruloplasmin.

Figure 4

MR imaging of the liver

GRE T1-weighted image in the axial plane of the upper abdomen. Micronodular aspect of the liver, in relation to cirrhosis.

FSE T2-weighted image in the axial plane of the upper abdomen. The nodules do not show a significant signal intensity decay, suggesting a relatively low iron deposition.