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Wilson Disease Presenting as Opsoclonus-Myoclonus Syndrome

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Movement Disorder Emergencies

Part of the book series: Current Clinical Neurology ((CCNEU))

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Abstract

Wilson disease (WD) is a rare autosomal recessive inborn error of copper metabolism, caused by mutations in ATP7B which encodes a transmembrane copper-transporting ATPase. This leads to copper overload in the liver, brain, cornea, and other tissues, often presenting with a hepatolenticular syndrome. Hepatic dysfunction varies from mild asymptomatic transaminase elevation to acute fulminant hepatic failure. The most frequent neurological manifestations include dysarthria, dystonia, tremor, parkinsonism, choreoathetosis, and ataxia. Probably the most prototypical findings are wing-beating tremor, risus sardonicus, and Kayser-Fleischer (KF) rings seen on slit lamp examination. In the midbrain a “face of a giant panda” sign can be seen in the MRI of some WD patients. The diagnosis can be challenging because of its protean manifestations. According to the European Association for the Study of the Liver (EASL) guidelines, based on the Leipzig Score, the combination of typical clinical symptoms plus KF rings and a serum ceruloplasmin level less than 0.1 g/L is sufficient to establish the diagnosis. However, when this triad is not fulfilled, it is often necessary to perform a liver biopsy or genetic testing. Early diagnosis and treatment are critical as they may prevent serious disability and life-threatening complications. The aim of treatment is to remove the accumulated copper and prevent further copper accumulation. Trientine and D-penicillamine are first-line chelators for the treatment of WD, although both are associated with several adverse events that require close monitoring.

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Authors and Affiliations

  1. Department of Neuroscience, Clínica Dávila, Santiago, Chile

    Philippe A. Salles, Valentina Besa-Lehmann, Carolina Pelayo-Varela, Prudencio Lozano-Iraguen & Andrés De la Cerda

  2. CETRAM, Santiago, Chile

    Philippe A. Salles, Valentina Besa-Lehmann & Andrés De la Cerda

  3. Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA

    Philippe A. Salles & Hubert H. Fernandez

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  1. Philippe A. Salles
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Correspondence to Hubert H. Fernandez .

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  1. Department of Neurology, NYU Langone Health, New York, NY, USA

    Steven J. Frucht

Electronic Supplementary Material

A 31-year-old previously healthy man presented with an insidious 3-month history of anxiety and agoraphobia, and recent upper limb action tremor and balance difficulties. On examination, he was very apathetic and almost mute. Smooth pursuit and saccadic ocular movements were intact, but he had bouts of ocular flutter. Mini-myoclonus in both hands and negative myoclonus in all four limbs interfered with smooth movements. He was slightly dysarthric, had mild dysmetria, intention tremor, dysdiadochokinesia, and difficulties with tandem gait. Strength, reflexes, and sensation were intact. Signs of chronic liver disease were seen in the abdominal CT and brain MRI showed poorly delineated T2-hyperintensity in the brainstem, ascending to diencephalic structures. Serum ceruloplasmin level was borderline (19.3 mg/dL; normal value >20 mg/dL) but no Kayser-Fleischer rings were found. His family history was remarkable for a sister who was admitted to a psychiatric unit with a history of delusions and later experienced dystonia, tremor, and seizures. Her MRI also showed nonspecific T2-hyperintensities in the brainstem and thalamus. Although an extensive workup was done, she died without a diagnosis. With this information, a genetic disease was suspected in our patient and additional investigations were obtained. Finally, an increase in the 24-hour urinary copper (1145 μg; normal value 10–30 μg) and genetic testing showing a homozygous mutation (c.3207C>A) in the ATP7B gene confirmed the diagnosis of Wilson’s disease (MP4 91958 kb)

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Salles, P.A., Besa-Lehmann, V., Pelayo-Varela, C., Lozano-Iraguen, P., Fernandez, H.H., De la Cerda, A. (2022). Wilson Disease Presenting as Opsoclonus-Myoclonus Syndrome. In: Frucht, S.J. (eds) Movement Disorder Emergencies. Current Clinical Neurology. Humana, Cham. https://doi.org/10.1007/978-3-030-75898-1_26

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