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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 4/2008

01-04-2008 | Original article

Brain MRI and SPECT in the diagnosis of early neurological involvement in Wilson’s disease

Authors: Mario Piga, Alessandra Murru, Loredana Satta, Alessandra Serra, Alessandro Sias, Gianluigi Loi, Francesco Marrosu, Luigi Demelia

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2008

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Abstract

Purpose

To evaluate the impact of brain MRI and single-photon emission computed tomography (SPECT) in early detection of central nervous system abnormalities in patients affected by Wilson’s disease (WD) with or without neurological involvement.

Methods

Out of 25 consecutive WD patients, 13 showed hepatic involvement, ten hepatic and neurological manifestations, and twp hepatic, neurological, and psychiatric symptoms, including mainly movement disorders, major depression, and psychosis. Twenty-four healthy, age-gender matched subjects served as controls. All patients underwent brain MRI and 99mTc-ethyl-cysteinate dimer (ECD) SPECT before starting specific therapy. Voxel-by-voxel analyses were performed using statistical parametric mapping to compare differences in 99mTc-ECD brain uptake between the two groups.

Results

Brain MRI showed T2-weighted hyperintensities in seven patients (28%), six of whom were affected by hepatic and neurological forms. Brain perfusion SPECT showed pathological data in 19 patients (76%), revealing diffuse or focal hypoperfusion in superior frontal (Brodmann area (BA) 6), prefrontal (BA 9), parietal (BA 40), and occipital (BA 18, BA 39) cortices in temporal gyri (BA 37, BA 21) and in caudatus and putamen. Moreover, hepatic involvement was detected in nine subjects; eight presented both hepatic and neurological signs, while two exhibited WD-correlated hepatic, neurological, and psychiatric alterations. All but one patient with abnormal MRI matched with abnormal ECD SPECT. Pathologic MRI findings were obtained in six out of ten patients with hepatic and neurological involvement while abnormal ECD SPECT was revealed in eight patients. Both patients with hepatic, neurological, and psychiatric involvement displayed abnormal ECD SPECT and one displayed an altered MRI.

Discussion

These findings suggest that ECD SPECT might be useful in detecting early brain damage in WD, not only in the perspective of assessing and treating motor impairment but also in evaluating better the less investigated disorders in the cognitive domain.
Literature
1.
Scheinberg IH, Sternlieb I. Wilson’s disease. Major problems in internal medicine, vol XXIII. Philadelphia: Saunders; 1984.
2.
Olsson C, Waldenstrom E, Westermark K, Landegre U, Syvanen AC. Determination of the frequencies of ten allelic variants of the Wilson disease gene (ATP7B), in pooled DNA samples. Eur J Hum Genet. 2000;8:933-8.CrossRefPubMed
3.
Giagheddu A, Demelia L, Puggioni G, Nurchi AM, Contu L, Pirari G, et al. Epidemiologic study of hepatolenticular degeneration (Wilson’s disease) in Sardinia (1902-1983). Acta Neurol Scand. 1985;72:43-55.CrossRefPubMed
4.
Figus A, Angius A, Loudianos G, Bertini C, Dessi V, Loi A, et al. Molecular pathology and haplotype analysis of Wilson’s disease in Mediterranean populations. Am J Hum Genet. 1995;57:1318-24.PubMedPubMedCentral
5.
Loudianos G, Dessi V, Lovicu M, Angius A, Figus A, Lilliu F, et al. Molecular characterization of Wilson disease in the Sardinian population-evidence of a founder effect. Hum Mut. 1999;14:294-303.CrossRefPubMed
6.
Roberts EA, Schilsky ML. A practice guideline on Wilson’s disease. Hepatology 2003;l37:75-92.
7.
Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet. 1993;5:327-37.CrossRefPubMed
8.
Petrukhin K, Lutsenko S, Chernov I, Ross BM, Kaplan JH, Gilliam TC. Characterization of the Wilson’s disease gene encoding a P-type copper transporting ATPase: genomic organization, alternative splicing and structure/function predictions. Hum Mol Genet. 1994;3:1647-56.CrossRefPubMed
9.
Cullen LM, Prat L, Cox DW. Genetic variation in the promoter and 5′ UTR of the copper transporter, ATP7B, in patients with Wilson disease. Clin Genet. 2003;64:429-32.CrossRefPubMed
10.
Ferenci P. Regional distribution of mutations of the ATP7B gene in patients with Wilson disease: impact on genetic testing. Hum Genet. 2006;120:151-9.CrossRefPubMed
11.
Angius A, Dessì V, Lovicu M, De Virgiliis S, Pirastu M, Cao A. Early and severe neurological features in a Wilson disease patient compound heterozygous for two frameshift mutations. Eur J Pediatr. 1998;157:128-9.CrossRefPubMed
12.
Jeon B, Kim JM, Jeong JM, Kim KM, Chang YS, Lee DS, et al. Dopamine transporter imaging with (123)CIT demonstrates presynaptic nigrostriatal dopaminergic damage in Wilson’s disease. J Neurol Psych. 1998;65:60-4.CrossRef
13.
Demirkiran M, Jankovic J, Lewis RA, Cox DW. Neurologic presentation of Wilson disease without Kaiser-Fleischer rings. Neurology. 1996;46:1040-3.CrossRefPubMed
14.
Bono W, Moutie O, Benomar A, Aidi S, el Alaoui-Faris M, Yahyaoui M, et al. Wilson’s disease. Clinical presentation, treatment and evolution in 21 cases. Rev Med Interne. 2002;23:419-31.CrossRefPubMed
15.
Akil M, Brewer GJ. Psychiatric and behavioural abnormalities in Wilson’s disease. Adv Neurol. 1995;65:171-8.PubMed
16.
Duchen LW, Jacobs JM. Nutritional deficiencies and metabolic disorders. Greenfield’s neuropathology. 5th ed. London: Edward Arnold; 1992. p. 838.
17.
Nazer H, Brismar J, Al Kawi MZ, Gunasekaran TS, Jorulf KH. Magnetic resonance imaging of the brain in Wilson’s disease. Neuroradiology. 1993;35:130-3.CrossRefPubMed
18.
Thuomas KA, Aquilonius SM, Bergstrom K, Westermark K. Magnetic resonance imaging of the brain in Wilson’s disease. Neuroradiology. 1993;35:134-41.CrossRefPubMed
19.
Giagheddu M, Tamburini G, Piga M, Tacconi P, Giagheddu A, Serra A, et al. Comparison of MRI, EEG, EPs and ED-SPECT in Wilson’s disease. Acta Neurol Scand. 2001;103:71-81.CrossRefPubMed
20.
21.
Starosta-Rubinstein S, Young AB, Kluin K, Hill G, Aisen AM, Gabrielsen T, et al. Clinical assessment of 31 patients with Wilson’s disease: correlations with structural changes on magnetic resonance imaging. Arch Neurol. 1987;44:365-70.CrossRefPubMed
22.
Magalhaes AC, Caramelli P, Menezes JR, Lo LS, Bacheschi LA, Barbosa ER, et al. Wilson’s disease: MRI with clinical correlation. Neuroradiology. 1994;36:97-100.CrossRefPubMed
23.
King AD, Walshe JM, Kendall BE, Chinn RJ, Paley MN, Wilkinson ID, et al. Cranial MR imaging in Wilson’s disease. Am J Roentgenol. 1996;167:1579-84.CrossRef
24.
Van Wassenaer-van Hall HN, den Heuvel AG, Algra A, Hoogenraad TU, Mali WPTM. Wilson’s disease: findings at MR imaging and CT of the brain with clinical correlation. Radiology. 1996;198:531-6.CrossRefPubMed
25.
Watanabe N, Seto H, Shimizu M, Kageyama M, Morijiri M, Nomura K, et al. Brain SPECT in Wilson’s disease. Clin Nucl Med. 1995;20:1028-30.CrossRef
26.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders DSM-IV-TR. 3rd ed. Washington DC: American Psychiatric Publishing Inc.; 2000.
27.
Morbelli S, Rodriguez G, Mignone A, Altrinetti V, Brugnolo A, Piccardo A, et al. The need of appropriate brain SPECT templates for SPM comparisons. Q J Nucl Med Mol Imaging. 2007; in press.
28.
Acton PD, Friston KJ. Statistical parametric mapping in functional neuroimaging: beyond PET and fMRI activation studies. Eur J Nucl Med. 1998;25:663-7.PubMed
29.
Imram MB, Kawashima R, Awata S, Sato K, Kinomura S, Ono S, et al. Parametric mapping of cerebral blood flow deficits in Alzheimer’s disease: a SPECT study using HMPAO and image standardization technique. J Nucl Med. 1999;40:244-9.
30.
Roh JK, Lee TG, Wie BA, Lee SB, Park SH, Chang KH. Initial and follow-up in brain MRI findings and correlation with the clinical course in Wilson’s disease. Neurology. 1994;44:1064-8.CrossRefPubMed
31.
Prayer L, Wimberger D, Kramer J, Grimm G, Oder W, Imhof H. Cranial MRI in Wilson’s disease. Neuroradiology. 1990;32:211-4.CrossRefPubMed
32.
Imai N, Nozaki H, Miyata K, Terayama Y, Ishihara N. Short interval change of 99mTc-ethyl cysteinate dimer single photon emission computed tomography in Wilson’s disease. No To Shinkei. 1999;51:785-9.PubMed
33.
Guizzetti MP. Per l’anatomia patologica della degenerazione lenticolare progressiva con cirrosi epatica (malattia del Wilson). Riv Pat Nerv Ment. 1925;30:89-130.
34.
Konovalov NW. Histopathologie der hepatolentikularen Degeneration. II Histopathologie der Rindenerweichungen. Z ges Neurol Psychiat. 1941;171:200-28.CrossRef
35.
Ishino H, Takashi M, Havashi Y, Saito A, Otsuki S. A case of Wilson’s disease with enormous cavity formation of cerebral white matter. Neurology. 1972;22:905-9.CrossRefPubMed
36.
Tejada I, Barreiro P, Diez Tejedor E, Frank A. Enfermedad de Wilson: imagen en tomografia computadorizada y resonancia magnética. Neurologia. 1990;5:328-31.PubMed
37.
Berard-Badier M, Lowenthal A, Bernard R, Payan H, Gastaut H. Degenerescence hepatolenticulaire. Etude anatomo-clinique, electroencephalografique et biochimique à propos de trois cas dont deux jumeaux. Psychiat Neurol. 1960;140:445-75.CrossRef
38.
Miyakawa T, Murayama E. An autopsy case of the « demyelinating type » of Wilson’s disease. Acta Neuropath. 1976;35:235-41.CrossRefPubMed
39.
De Lisi L. Sulla degenerazione lenticolare progressiva (Malattia di Wilson). Riv Pat Nerv Ment. 1914;19:577-644.
40.
Pollock LI. The pathology of the nervous system in a case of progressive lenticular degeneration. J Nerv Ment Dis. 1917;46:401-20.CrossRef
41.
Spielmever W. Die histopathologische Zusammengehorig keit der Wilsonschen Krankheit und der Pseudosklerose. Zschr ges Neurol Psychiat. 1920;57:312-51.CrossRef
42.
Braunmohl A. Die Rinden-Markkomponente in anatomischen Bild der Wilson-Pseudosklerosegruppe. Z Ges Neurol Psychiat. 1930;130:1-65.CrossRef
43.
Bielschowskv M, Hallervorden J. Symmetrische Einschmelzungsherde im Stirnhirn beim Wilson-Pseudosklero-sekomplex. J Psych NeuroI. 1931;42:177-209.
44.
Sjòwall E, Walgren A. Some aspects of hepatolenticular degeneration and its pathogenesis. Acta Psychiat Neurol. 1934;9:435-64.CrossRef
45.
Van Bogaert L, Willock E. “Etudes anatomo-cliniques sur la dégénérescence hépatolenticulaire. Forme portale de la maladie de Wilson. Forme familiale de lapseudosclérose de Westphal-Strumpell. Rev Neurol. 1936;66:461-97.
46.
Rabiner AM, Joachim H, Freiman IS. Hepatolenticular degeneration (Wilson’s disease) following splenectomy; interrelationship of the reticuloendothelial and central nervous system. Ann Intern Med. 1941;14:1781-801.CrossRef
47.
Jervis GA, Notkin J, Freiman IS, Moore J. Progressive lenticular degeneration (Wilson’s disease). Psychiat Quart. 1942;16:357-72.CrossRef
48.
Gysin WM, Cooke ET. Unusual mental symptoms in a case of hepatolenticular degeneration. Dis Nerv Syst. 1950;11:305-9.PubMed
49.
Schulman S, Barbeau A. Wilson’s disease: a case with almost total loss of cerebral white matter. J Neuropath Exper Neurol. 1963;22:105-19.CrossRef
50.
Fukuda K. Clinical and pathological aspects of Wilson’s disease in cases of one and the same family. Tohoku J Exp Med. 1965;85:55-71.CrossRefPubMed
51.
Miller GJ, Persaud V. Hereditary hepatolenticular degeneration (Wilson’s disease). Report of the first case in Jamaica. Trop Geogr Med. 1968;20:225-32.PubMed
52.
Chen JJ, Shiau YC, Wang JJ, Ho ST, Kao A. Abnormal regional cerebral blood flow in primary antiphospholipid antibody syndrome patients with normal magnetic resonance imaging findings. Scand J Rheumatol. 2002;31:89-93.CrossRefPubMed
53.
Chang CP, Shiau YC, Wang JJ, Ho ST, Kao A. Abnormal regional cerebral flow on 99mTc ECD brain SPECT in patients with primary Sjögren’s syndrome and normal findings on brain resonance imaging. Ann Rheum Dis. 2002;61:774-8.CrossRefPubMedPubMedCentral
54.
Hawkins RA, Mazziotta JC, Pelps ME. Wilson’s disease studied with FDG and positron emission tomography. Neurology. 1987;37:1707-11.CrossRefPubMed
55.
Hermann W, Barthel H, Hesse S, Grahmann F, Kuhn HJ, Wagner A, et al. Comparison of clinical types of Wilson’s disease and glucose metabolism in extrapyramidal motor brain regions. J Neurol. 2002;249:896-901.CrossRefPubMed
56.
Jacquier-Sarlin M, Polla BS, Slosman DO. Cellular basis of ECD brain retention. J Nucl Med. 1996;37:1694-7.PubMed
57.
Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989;12:366-75.CrossRefPubMed
58.
Hirsch EC, Graybiel AM, Hersh LB, Duyckaerts C, Agid Y. Striosomes and extrastriosomal matrix contain different amounts of immunoreactive choline acetyltransferase in the human striatum. Neurosci Lett. 1989;96:145-50.CrossRefPubMed
59.
Oder W, Grimm G, Kollegger H, Ferenci P, Schneider B, Deecke L. Neurological and neuropsychiatric spectrum of Wilson’s disease: a prospective study of 45 cases. J Neurol. 1991;238:281-7.PubMed
Metadata
Title
Brain MRI and SPECT in the diagnosis of early neurological involvement in Wilson’s disease
Authors
Mario Piga
Alessandra Murru
Loredana Satta
Alessandra Serra
Alessandro Sias
Gianluigi Loi
Francesco Marrosu
Luigi Demelia
Publication date
01-04-2008
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2008
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-007-0681-1

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