Chorea Associated with JAK2^V617F‐Positive Essential Thrombocythemia

Chorea and Cognitive Impairment in JAK2V617F-Positive Myeloproliferative Disorders: A Case Report and Literature Review

“…Unexpectedly, functional neuroimaging and pathological studies have, until now, failed to find differences in the neostriatal structures of patients presenting with or without chorea in PV [14]. Therefore, with the current level of evidence, hematological abnormalities, hyperviscosity, and cerebral hypoperfusion can explain only partially the presence of chorea [13]. Additionally, hyperviscosity is present in multiple myeloma and Walderstrom's macroglobulinemia, but, until now, there are no reported cases associating this with chorea [2].…”

“…Seldomly, it can occur as a complication of some myeloproliferative neoplasms. In our review of the literature, there are some cases of polycythemia vera, a few essential cases of thrombocythemia, and only one case of secondary myelofibrosis with associated chorea [1,2,4,[11][12][13][14][15]. We present a rare case of chorea with progressive cognitive impairment in a patient with a history of JAK2V617F prePMF.…”

“…JAK2 is also expressed in vivo by striatal progenitor cells in the central nervous system [18]. The JAK2V617F mutation disturbs JAK2 ′ s auto-inhibitory activity, leading to increased neuroinflammation, astrogliosis, and the intensification of cell proliferation, differentiation, and migration [13,18,19].…”

“…Another proposed mechanism for chorea is a direct effect of the JAK2V617F mutation, postulating a chronic neuroinflammatory effect, with the cytokinic hyper-activation of the neostriatum [14]. Other studies have suggested dopamine circuit dysfunction as a potential mechanism for chorea: either through increased dopamine receptor sensitivity in the context of reduced levels of catecholamines and serotonin, increased dopamine release in the platelets and its accumulation in the basal ganglia, or the altered metabolic turnover of dopamine in the striatum [2,13,14]. The latter mechanism could be sustained by the response to tetrabenazine [13].…”

“…This was also the case in two of the three patients with ET. Notably, one of them developed chorea after self-stopping the cytoreducing treatment [13].…”