A 60-year-old woman with a medical history of type 2 diabetes mellitus, papillary thyroid cancer status post resection, and hypertension presented to a referring hospital with worsening headaches and visual disturbances. For four months prior to her presentation, she had experienced intermittent unilateral, pulsating headaches as well as visual disturbances in the right eye. Upon arrival to the emergency department, she was febrile and noted to have meningismus. CBC revealed white blood cells at 9,800/L, hemoglobin at 12.9 g/dL, and platelets at 223,000/uL. Lumbar puncture was performed with a cerebrospinal fluid (CSF) profile demonstrating colorless fluid, total nucleated cells 43/mm3, red blood cells 4/mm3, glucose 134 mg/dL, total protein 50 mg/dL, and an opening pressure of 21 cm H20. CSF herpes simplex virus 1/2, West Nile virus, cytomegalovirus, enterovirus, varicella zoster virus PCRs, venereal disease research laboratory (VDRL), and coccidioides antibodies were negative or nonreactive, respectively. Serum HIV 1/2 antibodies, QuantiFERON-TB Gold, and autoimmune panel consisting of antinuclear antibody, rheumatoid factor, anti-mitochondrial antibody, and macrophage 2 antibodies were also nonrevealing. Magnetic resonance imaging (MRI) of the brain was obtained at the time which showed acute-to-subacute thrombosis of the right transverse sinuses (Figure 1). Given her constellation of symptoms and negative infectious and autoimmune workup, she was initially treated for aseptic meningitis and discharged home with warfarin anticoagulation for the thrombosis. Her symptoms did not fully resolve, however, and she was readmitted one week later to the hospital for further evaluation and workup.
On readmission, her CBC demonstrated elevated white blood cells at 17,000/L (38% polymorphonuclear cells, 34% lymphocytes, and 23% variant lymphocytes). Due to the presence of variant lymphocytes noted at that time, a peripheral blood smear was obtained which revealed precursor B-cells and 30% circulating blasts consistent with B-cell acute lymphoblastic leukemia (ALL). A repeat lumbar puncture was performed with CSF profile demonstrating total nucleated cells 728/mm3, red blood cells 0/mm3, glucose 93 mg/dL, and total protein 42 mg/dL. CSF flow cytometry demonstrated 97% blasts expressing CD34, CD19, bright CD10, and dim CD33 consistent with CNS involvement. After consultation with hematology, the patient was started on the ALL202 protocol with cyclophosphamide, daunorubicin, vincristine, methotrexate, cytarabine, and imatinib (given Ph chromosome positivity) as well as intrathecal methotrexate. During her hospitalization, her dural sinus thrombosis was treated with therapeutic-dosing enoxaparin at 1.5 mg/kg/day (100 mg).
During the course of her ALL treatment, the patient experienced repeated episodes of thrombocytopenia with clinical concerns for subarachnoid hemorrhage. After a year and a half of anticoagulation with enoxaparin, a follow-up MRI was obtained which demonstrated stability in the thrombosis since initial diagnosis. Because of the chronicity of the thrombus and the ongoing bleeding concerns, enoxaparin was discontinued. The patient underwent subsequent brain imaging during the course of her ALL treatment which did not demonstrate any increase in size of the dural sinus thrombosis despite lack of anticoagulation.