The copper metabolism disorder Wilson's disease was first defined in 1912. Wilson's disease can present with hepatic and neurological deficits, including dystonia and parkinsonism. Early-onset presentations in infancy and late-onset manifestations in adults older than 70 years of age are now well recognised. Direct genetic testing for ATP7B mutations are increasingly available to confirm the clinical diagnosis of Wilson's disease, and results from biochemical and genetic prevalence studies suggest that Wilson's disease might be much more common than previously estimated. Early diagnosis of Wilson's disease is crucial to ensure that patients can be started on adequate treatment, but uncertainty remains about the best possible choice of medication. Furthermore, Wilson's disease needs to be differentiated from other conditions that also present clinically with hepatolenticular degeneration or share biochemical abnormalities with Wilson's disease, such as reduced serum ceruloplasmin concentrations. Disordered copper metabolism is also associated with other neurological conditions, including a subtype of axonal neuropathy due to ATP7A mutations and the late-onset neurodegenerative disorders Alzheimer's disease and Parkinson's disease.

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Wilson's disease and other neurological copper disorders.

Wilson's disease: A 2017 update

Royal college of physicians of london.

Liver pathology in Wilson's disease: From copper overload to cirrhosis.

Wilson disease (WD) is genetically induced failure of copper metabolism which can be successfully treated with pharmacological agents. The prognosis for survival in most WD patients is favorable if diagnosis and anti-copper treatment are provided early. Many observations imply that persistence with drug treatment is generally low in patients with chronic diseases, which impact the treatment effectiveness, but such results are very limited in WD. The aim of our study was to assess persistence with treatment among WD patients, to analyze its effect on patient outcome and to identify factors that might be related to persistence. 170 newly diagnosed, symptomatic patients with WD who started treatment between 1995 and 2005 were analyzed retrospectively to assess treatment non-persistence, which was defined as at least one reported break of more than 3 months or minimum two breaks lasting longer than 2 months. Results were further analyzed according to selected clinical variables. Only 74.1% of patients were persistent with treatment during the mean 11.7 years of follow up. Treatment persistence closely impacted positive clinical outcomes. In patients classified as persistent, improvement and lack of WD progression were observed more often compared to those classified as non-persistent (29.4 and 68.3% vs. 2.3 and 45.5%; p < 0.001, respectively). In contrast, non-persistent patients presented more often with worsening WD than persistent patients (52.3% vs. 2.4%). Type of WD treatment, gender, phenotypic presentation, adverse events and duration of treatment were not related to treatment persistence. Higher or upper/post-secondary education and a supportive family attitude towards treatment were the most important factors related to persistence. One quarter of WD patients were not taking anti-copper treatment regularly and this had an important negative effect on clinical outcome. Family support played an important role in treatment persistence.

/pdf/persistence-with-treatment-for-wilson-disease-a-5g6onwpyuo.pdf

Persistence with treatment for Wilson disease: a retrospective study.

Wilson's disease, 100 years later….

Samuel Alexander Kinnier Wilson. Wilson's disease, Queen Square and neurology.

Supplementary material : Samuel Alexander Kinnier Wilson. Wilson's disease, Queen Square and neurology

Resume Introduction L’observance dans la maladie de Wilson, pathologie genetique rare, est cruciale. Il existe des traitements efficaces si prescrits precocement et pris a vie. Sinon, les consequences sont gravissimes : handicap ou deces. Ce travail vise a determiner le taux et les facteurs de non-observance. Methodes Etude prospective au Centre national de reference de la maladie de Wilson (Paris et Lyon) sur 8 mois. L’observance a ete evaluee a l’inclusion et au 8e mois par un questionnaire quantifiant le nombre de prises manquees, un autoquestionnaire precisant les causes de non-observance et des echelles analogiques evaluant la relation medecin–malade et le rapport au traitement. Au meme moment, un entretien avec la psychologue etait realise et la gravite des symptomes depressifs evaluee par l’inventaire de depression de Beck. Tous les deux mois, une psychologue realisait un entretien telephonique evaluant l’observance et le ressenti des patients. Resultats Trente-neuf patients ont ete inclus, d’un âge moyen de 34 ans (± 9,9). A M0, 84,6 % etaient mal-observants. Ils ne differaient pas pour ce qui est de l’âge, du type de traitement ou de la qualite de la relation au medecin, mais avaient ete diagnostiques plus recemment (p = 0,049) et presentaient plus frequemment des signes neurologiques (p = 0,007). Des symptomes depressifs etaient presents chez 38,5 % d’entre-eux. A M8, la proportion de patients mal-observants etait egale a 56,8 % et 21,6 % presentaient des symptomes de depression. Conclusion Les patients atteints de maladie de Wilson ont des difficultes d’observance, sans etre forcement depressifs. Un suivi multidisciplinaire rapproche semble pouvoir ameliorer l’observance, en particulier pour les patients atteints de troubles neurologiques.

L’observance dans la maladie de Wilson : intérêt d’un suivi rapproché au long cours

This historical article describes the life and work of the British physician Samuel Alexander Kinnier Wilson (1878-1937), who was one of the world's greatest neurologists of the first half of the 20th century. Early in his career, Wilson spent one year in Paris in 1903 where he learned from Pierre-Marie at Bicêtre Hospital. He subsequently retained uninterrupted links with French neurology. He also visited in Leipzig the German anatomist Paul Flechsig. In 1904, Wilson returned to London, where he worked for the rest of his life at the National Hospital for the Paralysed and Epileptic (later the National Hospital for Nervous Diseases, and today the National Hospital for Neurology and Neurosurgery) in Queen Square, and also at Kings' College Hospital. He wrote on 'the old motor system and the new', on disorders of motility and muscle tone, on the epilepsies, on aphasia, apraxia, tics, and pathologic laughing and crying, and most importantly on Wilson's disease. The other objective of our paper is to commemorate the centenary of Wilson's most important work published in 1912 in Brain, and also in Revue Neurologique, on an illness newly recognized and characterized by him entitled "Progressive lenticular degeneration, a familial nervous disease associated with liver cirrhosis". He analyzed 12 clinical cases, four of whom he followed himself, but also four cases previously published by others and a further two that he considered in retrospect had the same disease as he was describing. The pathological profile combined necrotic damage in the lenticular nuclei of the brain and hepatic cirrhosis. This major original work is summarized and discussed in the present paper. Wilson not only delineated what was later called hepato-lenticular degeneration and Wilson's disease, but also introduced for the first time the terms extrapyramidal syndrome and extrapyramidal system, stressing the role of the basal ganglia in motility. The present historical work emphasizes the special contributions made by Wilson to the study of movement disorders, including akinesia and bradykinesia in Parkinson's disease, and their relation to basal ganglia pathology.

F. Woimant

Papers

Wilson's disease, 100 years later….

Samuel Alexander Kinnier Wilson. Wilson's disease, Queen Square and neurology.

Supplementary material : Samuel Alexander Kinnier Wilson. Wilson's disease, Queen Square and neurology

L’observance dans la maladie de Wilson : intérêt d’un suivi rapproché au long cours

Iconography : Samuel Alexander Kinnier Wilson. Wilson's disease, Queen Square and neurology