When First-Line Therapy for Wilson's Disease Causes Paradoxical Neurological Worsening
Some patients with the neurological presentation of Wilson's disease experience a paradoxical deterioration of neurological symptoms during initial treatment. A structured protocol addresses this specific situation.
Clinical scenario
The patient has neurological symptoms of Wilson's disease. First-line treatment was initiated with either zinc or a chelating agent, following a cautious, gradual escalation approach.
First-line failure — escalation trigger
Initial therapy with zinc or a chelator did not achieve the expected goals: progressive disappearance or attenuation of neurological symptoms, decrease or normalisation of the UWDRS score, progressive vanishing of T2/FLAIR hypersignal on brain MRI, and disappearance of Kayser-Fleischer rings. Instead, paradoxical neurological worsening has occurred — triggering escalation to this protocol.
Next-step approach (partial — full regimen via the link below)
The structured response involves specific modifications to the current chelation regimen, together with changes to certain concomitant medications — the complete individualized algorithm is in the full protocol.
Goal: Resolution of the paradoxical neurological worsening, with progressive improvement of neurological symptoms and decrease or normalisation of the UWDRS score.
References
DOI: 10.1016/j.jhep.2024.11.007
- Either zinc or chelators should be used in patients with a neurological presentation (LoE 2, strong recommendation, consensus).
- In patients with WD who develop paradoxical neurological worsening on first-line therapy, decreasing the dose of chelators and slowing the increase of doses or changing the WD treatment should be considered (chelators to zinc or zinc to chelators) (LoE 2, strong recommendation, consensus).
- For patients experiencing worsening neurological symptoms on first-line therapy, the initial recommendation should involve reducing the chelator dosage and adopting a gradual dose escalation approach (“start low and go slow”), along with discontinuing dopamine receptor antagonists.
- Neurological response to chelators may be delayed and is defined by the progressive disappearance or attenuation of symptoms and the decrease or normalisation of the UWDRS score.
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