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CASE REPORT
Year : 2022 | Volume
: 8
| Issue : 4 | Page : 225-227
Isolated cerebellar infarction in a case of JAK 2 mutation-negative polycythemia vera: A case report
Prasad Krishnan
Department of Neurosurgery, National Neurosciences Centre, Kolkata, West Bengal, India
Correspondence Address:
Prasad Krishnan
Department of Neurosurgery, National Neurosciences Centre, 2nd Floor, Peerless Hospital Campus, 360, Pancha Sayar, Garia, Kolkata - 700 094, West Bengal
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/bc.bc_37_22
Polycythemia vera is a myeloproliferative disorder caused by clonal expansion of erythroid precursors in the bone marrow commonly due to a mutation in the Janus kinase 2 (JAK2) gene located in the short arm of chromosome 9. Hyperviscosity of blood due to high hematocrit causes a low flow state that may predispose to infarct. These commonly occur in the supratentorial compartment. The case of a 46-year-old man who had an isolated cerebellar infarct with high hematocrit and hemoglobin levels and low serum erythropoietin levels is described. Further investigations eventually led to the unmasking of a JAK2 mutation-negative polycythemia vera.
Keywords: Cerebellum, Infarction, JAK 2 mutation, Low flow infarction, Polycythemia vera
Polycythemia vera (PV) also called primary polycythemia is a myeloproliferative disorder due to clonal proliferation of erythrocyte, leukocyte, and megakaryocyte precursors in the bone marrow[1] and may present with isolated erythrocytosis, isolated thrombocytosis, isolated leukocytosis, or any combination of these.[2] Among the myeloproliferative disorders, PV has the highest incidence of thromboembolic complications and these usually occur early in the course of the disease.[2] Thrombotic occlusion of cerebral arteries occurs in 10–20% of patients with PV.[1]
Case ReportA 46-year-old nondiabetic, nonhypertensive male patient presented with sudden-onset ataxia and slurred speech of 7-day duration along with severe headache and multiple episodes of vomiting for 3 days. On examination, he was moving all four limbs, left cerebellar signs were present and plantars were bilaterally flexor. Computed tomography (CT) scan of the brain showed a hypodensity in the left cerebellar hemisphere with compression of the 4th ventricle [Figure 1]a and hydrocephalus [Figure 1]b. Magnetic resonance (MR) imaging of the brain revealed an acute infarct in the left cerebellar hemisphere with diffusion restriction and hemorrhagic transformation [Figure 1]c and [Figure 1]d. MR angiography revealed no obvious abnormality or thrombosis in the vertebral arteries or circle of Willis and vertebral artery dissection had also been ruled out [Figure 1]e, [Figure 1]f, [Figure 1]g. His serum glucose and lipid profile were normal and investigations revealed he was euthyroid. Thrombophilia profile test too showed no abnormality. Transesophageal echocardiogram showed no patent foramen ovale and Holter monitoring was also normal.
Figure 1: CT scan of brain (a) showing a large left cerebellar hypodensity with effacement of the 4th ventricle; (b) cerebellar infarct seen causing supratentotrial hydrocephalus; (c) axial T2 weighted MRI showing hyperintense left cerebellum with mildly compressed brainstem and effaced 4th ventricle and (d) restriction on corresponding MR DWI showing the extent of the infarct. MR angiogram images (e-g) showing no evidence of vertebral artery dissection of any thrombosis or narrowing of major vessels. CT: Computed tomography, MR: Magnetic resonance, MRI: MR imaging, DWI: Diffusion weighted imagesHematological investigations revealed hemoglobin of 23 g% with a packed cell volume (PCV) of 70. Platelet counts were normal. He was not a smoker, was not obese, and had no history of chronic lung disease or sleep apnea. His serum erythropoietin was low (1 mU/L). PV was provisionally diagnosed. He underwent serial phlebotomies every few days till his hemoglobin was 14.5 g% and PCV was 47. PV Janus kinase 2 (JAK2) mutation panel study was negative for mutations at V617F and exon 12. Ultrasound abdomen revealed splenomegaly and a contrast-enhanced CT scan of the abdomen revealed no adrenal, renal, or liver tumors. Bone marrow aspirate and biopsy revealed a myeloid: erythroid ratio of 5:1 and hypercellularity with normal trilineage maturation was seen.
Initially, the patient was planned for a suboccipital decompressive craniectomy in view of his hydrocephalus and 4th ventricular compression but this was deferred as his sensorium was preserved, and with conservative treatment, his headache and vomiting subsided. Serial CT scans showed resolving hydrocephalus and opening up of the 4th ventricle. At discharge, he was able to stand with support but remained ataxic. He was then put on aspirin to prevent further strokes.
DiscussionBoth transient ischemic attacks and strokes have been documented in PV.[1] These usually involve the basal ganglia, thalamus, corona radiata, and subcortical white matter.[3] However, cerebellar infarction in these patients is rare[4] and there is only one previous report of isolated cerebellar infarction where too it was the presenting symptom of PV (in a 72-year-old woman who too was treated with serial phlebotomies).[4]
Infarction in these patients is commonly attributed to decreased cerebral blood flow as a consequence of hyperviscocity[1] and also to associated thrombocytosis if present.[1],[5] Furthermore, persistently high hematocrit has been speculated to cause vascular endothelial damage and increase susceptibility to cerebrovascular thrombosis[3] which was not found in our patient. Rarely, emboli may be the cause of infarction in these patients too.[5] Strangely, in contrast to PV, secondary polycythemias (occurring in smokers, patients with congenital cyanotic heart disease, high altitude, etc.) are less frequently associated with ischemic stroke[1] and there the treatment consists in addressing the cause causing elevated hematocrit.[6],[7]
Clonal expansion of cells in PV occurs due to a mutation of the JAK2 gene located in the short arm of chromosome 9.[8] The most common mutation is in the V617F locus that is found in approximately 95% of patients.[9] In those who lack the V617F mutation, mutations affecting exon 12 are found and the presence of any of these mutations with elevated hematocrit is now considered diagnostic of PV.[8],[9] Our case is novel in that though our patient had raised hemoglobin and elevated hematocrit, he was JAK2 mutation negative. While this is an extremely uncommon occurrence in PV,[8] such patients are also considered to have PV (JAK2-negative PV) if they fulfill the 2016 revised World Health Organization criteria[9][Table 1].
Table 1: World Health Organization criteria to diagnose polycythemia veraThe mainstay of management once PV is diagnosed is periodic phlebotomy to reduce hematocrit to a level normal for the sex of the patient.[2] Chemotherapy (with agents such as hydroxyurea or anagrelide)[2],[8] does not eradicate the disease but can be used in patients who are unwilling to undergo periodic phlebotomy. Prophylactic treatment of PV patients with aspirin and dipyridamole is not recommended due to the risk of hemorrhage but may be given if previous strokes have occurred[1] as in this patient.
ConclusionIschemic strokes in PV are commonly reported in the supratentorial compartment. Isolated cerebellar infarction has been reported only once previously in PV and in this instance, the neurological event unmasked the hitherto hidden disease. Our case was also peculiar in that it was both JAKV617F and exon 12 mutation negative, and in such patients, workup is needed to rule out other causes of stroke and also secondary polycythemia. Once the diagnosis of PV is established by the WHO criteria, periodic phlebotomy is needed to prevent a recurrence.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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