JAK2 Variant and Parkinsonian Syndromes: Coincidence or Pathophysiological Link?

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.

To describe parkinsonian phenotypes in patients with JAK2-mutated MPNs and explore possible pathophysiological links.

We identified five patients with a JAK2-mutated MPNs and parkinsonism and reviewed their demographic and clinical features, neuroimaging, and levodopa response.

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.

Although JAK2-mutated MPNs and parkinsonism may coexist coincidentally, recent evidence suggests plausible pathophysiological links, including vascular, inflammatory, immune-mediated, and treatment-related mechanisms.