Acute cerebral ischemic stroke as a presentation of polycythemia vera: a case report and a review of literature

Introduction: Polycythemia vera (PV) is a disease of stem cells characterized by pan hyperplastic, malignant, and neoplastic bone marrow conditions. It is characterized by an increased absolute red blood cell count due to uncontrolled red blood cell synthesis, as well as excessive white blood cell and platelet production. Although the relationship between PV and stroke, especially ischemic stroke, is widely known around the world, no previous cases have been reported from Somalia. Case presentation: In the presenting study, we report a 60-year-old male patient who presented with a right-side weakness for 3 days. After laboratory and brain imaging, he was diagnosed with an acute cerebral infarct affecting the left basal ganglion secondary to PV. Conclusions: PV as the cause of ischemic stroke is a rare condition but can be encountered in clinical practice, and clinicians should be familiar with this combination.


Introduction
Polycythemia vera (PV) is the most prominent myeloproliferative neoplasm (MPN), the final phenotypic effect of Janus kinase-2 (JAK2) somatic gene mutations, and the most frequently MPN accompanied by arterial and venous thrombosis [1] . It was first identified by a French doctor named Louis Henri Vaquez in 1892 [2] . It is caused by signaling deficiency which will cause an aberrant response to growth stimuli, and the defective clonal line interferes with the proliferation of normal lineages. The intracellular signaling gene JAK2 is mutated in 90% of PV cases [3] . It is characterized by an increased absolute red blood cell count (RBC) due to uncontrolled RBC synthesis, as well as excessive white blood cell (WBC) and platelet production [4] . The relationship between PV and stroke, especially ischemic stroke, is widely known around the world. There are numerous populations with a higher incidence of stroke; however, patients with PV are unique, both in terms of pathophysiology and the treatment of the disease [5] . Cerebral ischemia occurrences are triggered by elevated blood viscosity and platelet activation in the arteries of the central nervous system [6] . Here we report a 60-year-old male patient with ischemic stroke resulting from PV.

Case presentation
A 60-year-old male was admitted from the emergency with a complaint of right-sided weakness for 3 days. Noncontrast brain computed tomography was inconclusive and did not reveal any focal lesion. Subsequent diffusion MRI showed left basal ganglion hyperintensity consistent with acute cerebral infarct (see Fig. 1). The patient had no history of cerebrovascular risk factors such as hypertension, hyperlipidemia, diabetes, coronary heart disease, or smoking. There was no recent history of trauma, poisoning, surgery, blood transfusion, infection, or a family history of a similar condition. There was no seizure, recent headache, or visual disturbance. Vital signs were normal. Despite basal ganglion infarct, the patient's cognitive function was preserved. There was no apparent restriction of eye movements. Other systemic examinations, including those of the respiratory and cardiovascular systems, were unremarkable.

HIGHLIGHTS
• Cerebral ischemia occurrences are triggered by elevated blood viscosity and platelet activation in the arteries of the central nervous system. • Arterial ischemic consequences of polycythemia vera are widespread, typically occurring early in the disease cycle, spanning from 15% in the 2 years before diagnosis to up to 40% throughout the illness course. • Polycythemia vera may be more commonly affected in the left hemisphere of the brain. The results of laboratory investigations on admission were as follows: whole blood cell analysis revealed WBC count, 37.09 × 10 9 /l; lymphocyte percentage, 2.5%; neutrophil percentage, 89.4%; monocyte absolute value, 1.10 × 10 9 /l; eosinophil absolute value, 0.3 × 10 9 /l; basophil absolute value, 0.02 × 10 9 /l; and basophil percentage, 0.1%. The RBC count was 9.89 × 10 12 / l; hemoglobin level, 21.3 g/dl; platelet count, 258 × 10 9 /l. The absolute value of neutrophils was 33.17 × 10 9 /l and the platelet volume was 9.7%. The liver function test, renal function test, glucose, and electrolytes were normal. There was no obvious abnormality among the results for the remaining blood sampling: abdominal ultrasonography showed no abnormalities. A 24-h dynamic electrocardiogram did not reveal atrial fibrillation or arrhythmia. Echocardiography did not show any potential cardioembolic source. Carotid and vertebral arteries Doppler ultrasound examination did not show intravascular thickening, thrombus, or stenosis. Peripheral blood smear showed erythrocytosis, and neutrophilia features suggestive of polycythemia (see Fig. 2).
Based on the case summary and the lack of capacity in our hospital to perform bone marrow aspiration and JAK2 gene analysis, this patient's cerebral infarction was diagnosed due to PV. The patient was treated with low molecular weight heparin 60 mg twice daily, aspirin at a dose of 100 mg, and hydroxyurea at a dose of 500 mg twice daily.

Discussion
PV is a disease of stem cells characterized by pan hyperplastic, malignant, and neoplastic bone marrow conditions [7] . According to 2016 revised WHO recommendations, the diagnosis of PV requires either the presence of all three major criteria or the presence of the first two major criteria and the minor criterion. The major WHO criteria include hemoglobin greater than 16.5 g/dl in men and greater than 16 g/dl in women, or hematocrit greater than 49% in men and greater than 48% in women, or red cell mass greater than 25% above mean normal predicted value, bone marrow biopsy demonstrating hypercellularity for age with trilineage growth (panmyelosis) consisting of prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, and the presence of JAK2V617F or JAK2 exon 12 mutations. A serum erythropoietin level below the normal range constitutes the minor criterion [8] . The peak incidence of PV is found between the ages of 50 and 70, correlating with the incidence rate of stroke at these ages [9] .
Arterial ischemic consequences of PV are widespread, typically occurring early in the disease cycle, spanning from 15% in the 2 years before diagnosis to up to 40% throughout the illness course [10] . The high hematocrit level, which is a determinant of blood hyperviscosity, may also initiate an attack on the arterial endothelium, equivalent to atheromatous lesions, leading to platelet activation and also activation of the inflammation response that contributes to arterial blockage  and in situ thrombus formation [11] . In 20% of individuals with PV, thrombotic events are the presenting symptoms, and they are the leading cause of morbidity and mortality in untreated patients [12] .
To the extent of our knowledge, this is the first case of ischemic stroke caused by PV to be documented in Somalia. Our patient presented with right-sided weakness without a history of cerebrovascular risk factors such as hypertension, hyperlipidemia, diabetes, coronary heart disease, or smoking. His subsequent evaluations, which included blood testing and brain imaging, revealed acute cerebral infarction in the basal ganglion caused by PV. The patient was admitted to our hospital, and low molecular weight heparin, aspirin, and hydroxyurea were administered.
Gaye et al. [13] described a case report of a 66-year-old male patient with recurrent ischemic stroke in 2022. They concluded that the cause of the recurrent ischemic stroke was identified as PV and was treated with hydroxyurea, aspirin, and allopurinol. Corse and Kurtis also described a case of a 51-year-old male patient in 2018 who presented with right-sided weakness and slurred speech. They diagnosed the patient with an ischemic stroke caused by secondary polycythemia due to erythropoietin-secreting renal cell carcinoma [14] . In 2013, Zoraster and Rison reported a case of a 57-year-old man with right-side clumsiness. PV was found to be the perpetrator of this condition, and the patient's symptoms were relieved with hydration and phlebotomy [9] . As in our case report, all of the aforementioned cases presented to the hospital with right-side weakness, which could be interpreted as meaning that the left hemisphere is the most commonly affected hemisphere in PV cases. This needs to be the spotlight for future research to identify which hemisphere of the brain is most commonly affected by an ischemic stroke caused by PV.
Our work has been reported in line with the SCARE (Surgical CAse REport) 2020 criteria [15] .

Conclusion
PV as the cause of ischemic stroke is a rare condition but can be encountered in clinical practice, and clinicians should be familiar with this combination. It seems that ischemic stroke patients with PV tend to be above the age of 50 and may always affect the left hemisphere of the brain.

Ethical approval
Mogadishu Somali Turkish Training and Research Hospital ethics committee waived approval for this case report.

Patient consent
Written informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.