Chorea and a Frontal Lobe Syndrome: A Rare Neurological Presentation of Polycythemia Vera; A Case Report

A 73-year-old nonsmoking woman presented with attacks of involuntary movements of her arms and head, an awkward feeling in her mouth and tongue, numbness of the left upper quadrant of her face, and an inability to speak. The attacks had occurred several times a day and had increased in frequency. Six months previously, she had demonstrated progressive behavioral change, which family members described as social disinhibitive behavior that included a number of unrestrained and inappropriate verbal comments and increasing motor restlessness. Initially, her changed behavior was attributed to psychological stress, because her husband had been hospitalized, possibly in combination with a neurodegenerative disease such as dementia. Referral to the geriatrician took place only when the daily attacks of involuntary movements became unbearable. Her medical history included osteoporosis, for which she was prescribed alendronate and calcium carbonate with cholecalciferol; recurrent urinary tract infections; and polymyalgia rheumatica, for which she took prednisolone 5 mg/d. On general physical examination, she appeared euvolemic; her face was plethoric. There were no signs of spleno- or hepatomegaly. Neurological examination revealed gross involuntary movements, automatisms of the mouth and lips, and choreatic movements of the arms. Positive snout, glabellar, and right palmomental reflexes were found. Psychiatric evaluation showed no signs of delirium. Neuropsychological testing showed mild cognitive impairment with predominantly extensive frontal symptomatology, resulting in social disinhibition, distractibility, utilization behavior, and a tendency to imitate. On hospital admission, laboratory testing showed high hemoglobin (Hb; 18.7 g/dL, reference 12–16 g/dL) and hematocrit (Ht; 0.57 L/L, reference 0.35–0.45 L/L) and a mean corpuscular volume of 88 fL (reference 80–98 fL). Other laboratory tests showed normal values. In retrospect, Hb and Ht had been rising since 6 months before presentation. Apart from mild ischemic white matter lesions, no abnormalities were seen on magnetic resonance imaging. Electroencephalogram and cerebral spinal fluid analysis revealed no specific pathology. The finding of a JAK2 mutation confirmed the diagnosis of polycythemia vera (PV), and phlebotomy was initiated at 500 mL twice a week. After her fourth phlebotomy, she was feeling better, the chorea attacks disappeared, and the motor restlessness declined significantly. Her Hb dropped to 13.1 g/dL and Ht to 0.40 L/L. Neuropsychological retesting revealed a significant improvement in frontal characteristics; 6 months later she was still in remission. Neurological manifestations of PV such as headache, dizziness, paresthesias, and transient ischaemic attacks occur frequently,1 but chorea, with a prevalence of 1% to 2.5%, is a rare manifestation of PV. Although PV is predominantly found in men, only a case series has suggested that polycythemic chorea manifests mainly in women aged 50 and older.2 The pathophysiology of the development of chorea in PV is not fully understood. Hyperviscosity, measured using the Ht, seems to be the determining factor in the pathophysiology.3 In the case of chorea, one assumes that neostriatal hyperviscosity in the brain leads to venous stasis, low brain blood flow, and impaired oxygen and glucose metabolism, causing the chorea.3 The frontal lobe syndrome as such in PV has not yet been described, but cognitive impairment in PV with partial reversibility upon lowering of the Ht has been reported once.4 It is possible that the pathophysiology of frontal lobe syndrome is based on the same principle as polycythemic chorea but manifests in the frontal lobe region. The target Ht value for PV therapy is 0.45.1 Because low cerebral blood flow may predispose to the development of cerebral infarction, the Ht should be reduced and maintained at lower levels than generally accepted.5 This can be achieved by phlebotomy, which as previous case reports have described, can also result in a decrease in chorea.2, 4, 6 In addition low-dose aspirin is recommended to reduce the incidence of thrombotic events.1 Although chorea as a presenting symptom of PV is uncommon, in the case of a high Ht, PV should be considered as a potential cause. The existence of frontal lobe syndrome in PV with significant reversibility after phlebotomy is even more remarkable because it has not been described before. This case demonstrates not only a rare presentation of PV, but also the risk of delay in diagnosis and therapy in elderly adults. Their symptoms can easily be attributed to (frequently coexisting) psychosocial stress or degenerative disease. This case shows the importance of a complete geriatric assessment including internal evaluation for every elderly adult with behavioral changes. Conflict of Interest: None. Author Contributions: M. Severs: Wrote the first draft of the paper and contributed to revising the paper. H.M. Boelens, S.B. Diraoui, and J. Schuur: Revised the manuscript and contributed to concept and design. Sponsor's Role: None.