POLYCYTEMIA VERA PRESENTING AS SUDDEN‐ONSET COGNITIVE IMPAIRMENT

Abstract

To the Editor: A 67-year-old woman was presented at our outpatient clinic for analysis of recent-onset cognitive impairment. Her medical history was unremarkable, and except for sporadic acetaminophen, she did not use any medication. Until 2 months before presentation, she had lived independently and enjoyed her work serving coffee at an auction. Over several weeks, she developed rapid progressive cognitive impairment with loss of memory and the inability to perform activities of daily living, including her job. She met the criteria for clinical dementia. Her son and daughter also noticed agitation and trivialization. In the previous 2 months, she had fallen occasionally during biking because of “balance difficulties.” Upon questioning, she reported generalized itching complains. She did not suffer from fatigue, headaches, lightheadedness, burning sensation of the palms or soles, visual disturbances, gout, or gastrointestinal complaints. Upon physical examination, her attention was neither diminished nor fluctuating. There was a remarkable redness of the face, with strong red-injected conjunctivae. Her skin showed generalized scratch marks, and her fingertips were cyanotic. Physical examination of heart, lungs, and abdomen was unremarkable. Neurological examination revealed a slight gait disturbance (widened base) but no focal abnormalities. Laboratory results showed prominent erythrocytosis: hemoglobin (Hb) 22.05 g/dL, mild leukocytosis (9.2×109/L), and no thrombocytosis (198×109/L). Her general practitioner had also found erythrocytosis (Hb 20.64 g/dL) 4 months earlier. Magnetic resonance imaging of her cerebrum showed extensive generalized white matter lesions and several hemorrhagic infarct lesions in the anterior and posterior border zones of both hemispheres, with cortical necrosis (Figure 1). Duplex testing of her carotid arteries was normal. Fluid-attenuated inversion recovery image of the brain, showing bilateral, symmetric white matter hyperintensities (leukoaraiosis) and bilateral infarcts in the parietal lobes in the watershed territories of the posterior and middle cerebral arteries. Neuropsychological testing was performed, with a Mini-Mental State Examination score of 12 out of 30 (normal≥25), a Cambridge Cognitive Examination score of 47 out of 101 (normal>80), and an inability to perform the Trails Making Tests. There were no signs of delirium. The clinical diagnosis of cognitive dysfunction due to watershed infarction caused by polycythemia vera (PV) was confirmed by genetic screening for the JAK2 mutation, low serum erythropoietin level, and tri-linear hyperplasia of the three different cell lines in her bone marrow, in the absence of stainable iron. She was treated immediately with frequent phlebotomies and started taking acetylcystein 100 mg once daily. After the first phlebotomy, pruritus disappeared, as did congestion of the face, conjunctivae, and finger tips. After 6 weeks of treatment, global cognitive function and executive function improved, and she was able to perform her daily tasks at a reasonable, although not the preexisting, level. Long-term follow-up will show to what extend cognitive symptoms are fully reversible. Watershed infarctions of the cerebral cortex occur at the intersection of the outflow trajectories of two major cerebral arteries. These infarctions are usually secondary to stenosis of the carotid artery or to cardiac arrest.1 Watershed infarction due to hyperviscosity caused by PV is a rare medical condition, and sudden cognitive impairment is even less often reported. Improvement of cognitive impairment in patients with PV after phlebotomies has been described, but these patients did not suffer from stroke.2 Focal cognitive and behavioral dysfunction are often seen after watershed infarctions. The precise pathophysiology of these neuropsychiatric symptoms remains unclear but may be the result of disruption of cortical projection pathways, impairment of cortical blood flow, or both.3 Other typical neurological presentations include hemiparesis, sparing the face, and mood disturbances such as apathy or euphoria in non-dominant hemisphere anterior lesions. In posterior watershed infarctions, hemi-anopsia is common. Watershed infarctions in the bilateral frontal lobes can cause severe dementia.4 PV is a chronic, myeloproliferatieve disorder, predominantly presenting in elderly patients with an incidence rate of 23.5 per 100,000 person-years.5 Symptoms are due to hyperviscocity. A feared complication of PV is thrombosis (venous or arterial). Together with transformation into myelofibrosis, acute leukemia, or both, thrombosis is the main cause of death.6 The median survival of treated patients exceeds 10 year.7 This case history illustrates that an unusual course of cognitive impairment necessitates in-depth clinical investigation. We thank Professor R. G. J. Westendorp for thoroughly reading this manuscript. We also thank Dr. L. van der Wiel, neuropsychologist, Dr. W. Bollen, clinical neurologist, and Professor M. A. van Buchem, neuroradiologist, for their contributions. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this letter. Author Contributions: Both authors contributed equally to the preparation of this letter. Sponsor's Role: None.