Hemichorea in a patient with JAK2V617F blood cells

To the editor:

Chorea has been reported in patients with polycythemia vera (PV). JAK2V617F is a molecular marker used for the diagnosis of PV.^1,2  Occasionally, patients have insufficient clinical criteria to establish a diagnosis of PV or only possess some disease features without having overt hematologic manifestations. We present a case of an elderly woman with subacute hemichorea who was found to have normal hematologic profile and JAK2V617F⁺ hematopoiesis. Hemichorea completely resolved after therapeutic phlebotomy and hydroxyurea therapy.

A previously active, healthy 87-year-old woman experienced an episode of dizziness and a week later dysarthria and facial asymmetry. An MRI/MRA of the brain was unrevealing. Three weeks later, she developed involuntary movements of the left arm, face, and leg that progressively worsened in intensity and frequency. Neurologic examination revealed left hemichorea with motor impersistence and “milkmaid's grip.” Chorea was activated by rapid alternating movements and walking. There were no signs of Parkinsonism or dystonia.

Palpable splenomegaly was absent on examination. Blood work was notable for a hemoglobin of 15.6 g/dL, hematocrit of 44.2%, WBC count of 8.6 × 10⁹/L, platelet count of 281 × 10⁹/L, mean corpuscular volume of 95.7 fL, normal iron studies, and a serum erythropoietin of 12.7 mIU/mL. Her peripheral blood JAK2V617F granulocyte allele burden was 35% as determined by allele-specific PCR. The patient refused a BM biopsy.

The patient was phlebotomized to a hematocrit less than 42% and started on daily hydroxyurea 500 mg and aspirin 81 mg. Treatment with venesection and hydroxyurea achieved resolution of chorea within 4 weeks.

Neurologic complications have been reported in up to 80% of untreated PV patients.³  PV-associated chorea (PVC) has been reported as the presenting complaint, primarily in older females, which typically involves the orofaciolingual and appendicular musculature and often resolves with phlebotomy or cytoreductive therapy.^4-6  The exact mechanism underlying PVC is not known and there are no specific neuroimaging abnormalities or pathologic findings.^7,8 

Chorea in this patient represents a possible forme fruste of an MPN in that the patient's clinical features did not allow for a definitive diagnosis of PV even though she was JAK2V617F⁺. A similar situation has been documented in patients who present with splanchnic vein thrombosis and are found to be JAK2V617F⁺. These patients lack overt signs of an MPN and in some cases have normal BM morphology.⁹  More than 50% of such JAK2V617F⁺ patients with splanchnic vein thrombosis eventually develop clinical features of MPN.¹⁰ 

Based on this report, patients over the age of 50 years presenting with chorea should be tested for JAK2V617F even if they have a normal hematologic profile. This case highlights the possibility that chorea might represent a forme fruste of an MPN that will be responsive to venesection and cytoreductive therapy. The natural history of an unclassifiable JAK2V617F⁺ MPN presenting with neurologic complications is not yet known and will require further study.