JAK2 Variant and Parkinsonian Syndromes: Coincidence or Pathophysiological Link?

Abstract

Abstract Background JAK2 variants are a hallmark of myeloproliferative neoplasms (MPNs), including polycythemia vera and essential thrombocythemia. These disorders are often associated with thrombotic and inflammatory complications. From a movement disorder perspective, chorea is a rare but well‐recognized neurological occurrence in this context, whereas parkinsonism has received limited attention. Objectives To describe parkinsonian phenotypes in patients with JAK2‐mutated MPNs and explore possible pathophysiological links. Methods We identified five patients with a JAK2‐mutated MPNs and parkinsonism and reviewed their demographic and clinical features, neuroimaging, and levodopa response. Results Parkinsonian phenotypes were heterogeneous, including Parkinson's disease (n = 2), atypical parkinsonism (n = 1), motor neuron disease with parkinsonism (n = 1), and chorea followed by parkinsonism (n = 1). The latter patient developed parkinsonism approximately 22 months after onset of generalized chorea. When available (n = 2), DaTscan was abnormal. Levodopa responsiveness was variable. Conclusion Although JAK2‐mutated MPNs and parkinsonism may coexist coincidentally, recent evidence suggests plausible pathophysiological links, including vascular, inflammatory, immune‐mediated, and treatment‐related mechanisms.