|Year : 2015 | Volume
| Issue : 3 | Page : 411-413
Chronic subdural hematoma-unsual cause of headache in a patient with chronic myeloid leukemia treated with high-dose imatinib mesylate: A rare case report with review of literature
Sanjay M Khaladkar, Dhaval K Thakkar, Mansi N Jantre, Vilas M Kulkarni, Amarjit Singh
Department of Radio-Diagnosis, Dr. D.Y. Patil Medical College, Pimpri, Pune, Maharashtra, India
|Date of Web Publication||15-May-2015|
Sanjay M Khaladkar
Flat No. 5, Plot No. 8, S. No. 26/A, Tejas Bldg, Sahawas Society, Karve Nagar, Pune - 411 052, Maharashtra
Source of Support: None, Conflict of Interest: None
Head injury is considered one of the single most important causes of subdural hematoma. Other cause include bleeding diasthesis. We report here a case of 70-year-old female patient with chronic myeloid leukemia (CML) presenting with bilateral chronic subdural hematoma after an incremental high-dose of imatinib mesylate (IM) due to loss of complete molecular response. IM is useful to treat a wide range of diseases, including Philadelphia chromosome-positive CML, as it has high tolerability and low incidence of minor side effects. Hemorrhage is a rare complication of IM. IM is associated with reduced α2-plasmin inhibitor and platelet dysfunction. This case report emphasizes on the need to consider chronic subdural hematoma as atypical cause of headache in a patient of CML taking high-dose IM.
Keywords: Chronic myeloid leukemia, imatinib mesylate, subdural hematoma
|How to cite this article:|
Khaladkar SM, Thakkar DK, Jantre MN, Kulkarni VM, Singh A. Chronic subdural hematoma-unsual cause of headache in a patient with chronic myeloid leukemia treated with high-dose imatinib mesylate: A rare case report with review of literature. Med J DY Patil Univ 2015;8:411-3
|How to cite this URL:|
Khaladkar SM, Thakkar DK, Jantre MN, Kulkarni VM, Singh A. Chronic subdural hematoma-unsual cause of headache in a patient with chronic myeloid leukemia treated with high-dose imatinib mesylate: A rare case report with review of literature. Med J DY Patil Univ [serial online] 2015 [cited 2023 Dec 5];8:411-3. Available from: https://journals.lww.com/mjdy/pages/default.aspx/text.asp?2015/8/3/411/157113
| Introduction|| |
Chronic myeloid leukemia (CML) a myeloproliferative disease is characterized by the presence of the Philadelphia chromosome resulting from reciprocal chromosomal translocation t (9; 22) (q34; q11). Imatinib mesylate (IM) is a first-generation tyrosine kinase inhibitor that is used in the treatment of CML, gastrointestinal stromal tumors, and other cancers. It selectively targets certain tyrosine kinases, including c-ABL, platelet-derived growth factor receptor, and KIT. In CML, IM inhibits the oncoprotein BCR-ABL, the protein product of the Philadelphia chromosome gene fusion.  It is a standard initial treatment for CML and has revolutionized its treatment. Its common side effects are nausea, emesis, diarrhea, periorbital edema, fluid retention, and myelosuppression. We report here an unusual case of subdural hematoma in a 70-year-old female patient with CML treated with high-dose IM presenting with headache associated with nausea, vomiting and giddiness.
| Case Report|| |
A 70-year-old woman was diagnosed with CML and was initiated IM at a dose of 400 mg daily. The treatment dosage was increased to 800 mg/day 1-year later owing to failure to achieve complete cytogenic response. After 6 months of increased dose, patient complained of a headache associated with nausea, vomiting and giddiness. There was no history of associated trauma. A complete ophthalmoscopic examination was done which revealed no abnormality.
A plain brain computed tomography scan was performed. A hypodense chronic subdural hematoma (maximum thickness 1.6 cm, supero-inferior extent 6.1 cm) was seen in the right fronto-parieto-temporo-occipital region causing mass effect on right lateral ventricle and third ventricle with a marked shift of midline structures towards left (1.7 cm) with obstructive dilatation of left lateral ventricle. Few hyperdense areas noted within hematoma are suggestive of re-bleed [Figure 1]. Contrast study showed mild enhancement of the inner membrane [Figure 2]. Similar chronic hypodense subdural hematoma (maximum thickness 1.1 cm, supero-inferior extent 2.5 cm) was noted in left parietal region. Sulcal spaces and basal cisterns were effaced suggestive of raised intracranial tension. Suprasellar cistern was effaced on right side suggestive of transtentorial descending herniation. No bony fracture was noted at bone window settings.
|Figure 1: Plain axial computed tomography brain images (a, b, c) showing hypodense chronic subdural hematoma in right fronto-temporoparieto- occipital region and left parietal region with areas of re-bleed with ventricular mass effect and signs of raised intracranial tension|
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|Figure 2: Contrast enhanced computed tomography brain (a, b, c) showing hypodense chronic subdural hematoma in right frontotemporo- parieto-occipital region (with mild enhancement of the inner membrane) and left parietal region with areas of re-bleed with ventricular mass effect and signs of raised intracranial tension|
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| Discussion|| |
In the general population, incidence of subdural hematoma is estimated to be 1-15 cases/1,00,000 patients.  Patients treated with IM, central nervous system hemorrhage occurs in 5% of those in blast crisis, 1% in accelerated and 0.6% in chronic phase. 
Our patient detected to have chronic subdural hematoma at an IM does of 800 mg daily without thrombocytopenia or coagulation abnormalities. IM phramacokinetics analysis in IRIS study showed that hemorrhagic complications were not increased by higher IM trough levels at 400 mg daily during steady state.  Song et al. reported that 7 out of 121 advanced CML patients treated with IM, initially at 600 mg/day were diagnosed with nontraumatic subdural hematomas.  All patients developed subdural hematoma at the median of 10 weeks (1-48 weeks) after start of therapy. Our patient was detected to have chronic subdural hematoma after 6 months of increasing IM dose to 800 mg daily.
Radaelli et al. reported that 10 (11%) of 87 patients who took IM at a dose of 300-600 mg daily for a minimum of 3 months developed unilateral or bilateral conjunctival hemorrhage.  During follow-up, no other hemorrhagic events were observed. Hence, the authors decided not to discontinue IM, if only conjunctival hemorrhage occurred in the absence of other major hemorrhagic events.
Our patient was operated for bilateral chronic subdural hematomas due to midline shift of 1.7 cm and was later on put on a maintenance dose of 400 mg daily. This was decided, as the patient previously did not have any adverse events at a dose of 400 mg/day and had developed subdural hematoma at a dose of 800 mg/day.
Matsue et al. reported decrease in the level of α2-plasmin inhibitor (α2-PI) in Philadelphia chromosome - positive lymphoblastyic leukemia patients who had suffered hemorrhagic episodes while on an IM dose of 400 mg/day.  They suggested that other predisposing factors may play a role in the development of hemorrhagic events as abnormal fibrinogenolysis is known to occur when plasma α2-PI levels fall below 60% of normal.  Platelet aggregate dysfunction was reported in CML patients receiving IM or dasatinib. 
Choi et al. also stated that hemorrhage in CML is caused not only by thrombocytopenia but also by leukocyte infiltration in blast crisis stage.  Intracranial hemorrhage in hematological disorders occurs due to thrombocytopenia, leukocytosis, and disseminated intravascular coagulopathy. Intracerebral hemorrhage in hematological disorders tend to be multiple and occur in varying combinations of subcortical lobar hematoma, subarachnoid hemorrhage, subdural hemorrhage and intraventricular hemorrhage. 
Our report describes the occurrence of chronic subdural hematoma in a CML patient treated with IM-800 mg/day with a background of normal coagulation with no history of recent trauma, thrombocytopenia or anticoagulation medication. This suggests that subdural hematoma may be caused by IM by unknown mechanism. IM produces hemostatic abnormalities independent of thrombocytopenia. Further investigations and studies are needed to establish a mechanism of subdural hematoma causation and also to examine the reduction in α2-PI levels and platelet aggregation dysfunction. Physicians and radiologists should be alert to subdural hematoma as atypical cause of headache in patients taking high-dose IM.
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[Figure 1], [Figure 2]