Concepts concerning the cause and the pathogenesis of Wilson's hepatolenticular degeneration have undergone a slow and tortuous evolution.<sup>49 Wilson S.A.K. Progressive lenticular degeneration: A familial nervous disease associated with cirrhosis of the liver Brain 1912 ;  34 : 295

Cliccare qui per andare alla sezione Riferimenti</sup> Hints regarding the presence of excess copper in the tissues of a patient were obtained as early as 1913, 1 year after Wilson's publication, but Rumpel believed that silver was the principal toxin.<sup>24 Rumpel A. Ueber das Wesen und die Bedeutung der Leberveränderungen und der Pigmentierungen bei den damit verbundenen Fällen von Pseudosklerose, Zugleich ein Beitrag zur Lehre von der Pseudosklerose (Westphal-Strümpell) Dtsch Z Nervenheilk 1913 ;  49 : 54

Cliccare qui per andare alla sezione Riferimenti</sup> A decade later, ophthalmologists noted the similarity of Kayser-Fleischer rings and the copper-induced corneal rings encountered in patients with chalcosis but failed to appreciate the significance of these isolated observations. Only toward the middle of the century did Cumings<sup>5 Cumings J.N. The copper and iron content of brain and liver in the normal and in hepato-lenticular degeneration Brain 1948 ;  71 : 410

Cliccare qui per andare alla sezione Riferimenti</sup> establish that Wilson's disease is the result of copper toxicity, concluding that removal of copper from the tissues may be therapeutic. At that time British Anti-Lewisite, 2,3-dimercaptopropanol (BAL) was the only chelating agent used to treat patients with neurologic Wilson's disease. A few years later, Scheinberg and Gitlin discovered the pathognomonic deficiency of ceruloplasmin in plasma.<sup>26 Scheinberg I.H., Gitlin D. Deficiency of ceruloplasmin in patients with hepatolenticular degeneration Science 1952 ;  116 : 484

Cliccare qui per andare alla sezione Riferimenti</sup> Soon thereafter, Walshe introduced two oral therapies: first penicillamine, and later trientine, which revolutionized patient management and drastically improved the prognosis of patients diagnosed before irreversible damage to liver and brain had taken place.<sup>44 Walshe J.M. Wilson's disease. New oral therapy Lancet 1956 ;  1 : 25  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 45 Walshe J.M. Treatment of Wilson's disease with trientine (triethylene tetramine) dihydrochloride Lancet 1982 ;  1 : 643  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 47 Walshe J.M., Yealland M. Chelation treatment of neurological Wilson's disease QJM 1993 ;  86 : 197

Cliccare qui per andare alla sezione Riferimenti</sup> Several years later, zinc salts were found to be effective in the management of certain patients.<sup>2 Brewer G.J., Dick R.D., Johnson V.D. , e al. Treatment of Wilson's disease with zinc: XV. Long-term follow-up studies J Lab Clin Med 1998 ;  132 : 264  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 33 Schouwink G.   De hepato-cerebrale degeneratie [MD thesis] Arnheim: University of Amsterdam, GW Van der Wiel and Co (1961). 

Cliccare qui per andare alla sezione Riferimenti, 50 Yuzbasiyan-Gurkan V., Grider A., Nostrant T. , e al. Treatment of Wilson's disease with zinc: X. Intestinal metallothionein induction J Lab Clin Med 1992 ;  120 : 380

Cliccare qui per andare alla sezione Riferimenti</sup>