Clinical Review & Education
JAMA Clinical Challenge
A 55-Year-Old Man With Severe Papilledema Jonathan A. Micieli, MD, CM; Edward Margolin, MD
Right eye
Left eye
Figure 1. Optic nerve photographs demonstrating severe bilateral optic disc edema with peripapillary hemorrhages.
A 55-year-old man presenting to the emergency department reported blurry vision in his right eye during the past week. He also noticed rhythmic pulsing sounds in both ears during the past month. Past medical history was significant only for well-controlled hypertension treated with irbesartan (300 mg daily) and poor vision in the left eye for many years attributable to presumed inactive ocular histoplasmosis. On presentation, the patient appeared well, with blood pressure of 140/70 mm Hg and a regular heart rate of 75/min. Best corrected visual acuity was 20/200 (right eye) and counting fingers at 1 foot (left eye). Direct ophthalmoscopy revealed severe bilateral optic disc edema, peripapillary hemorrhages, and absent spontaneous venous pulsations (Figure 1). Quiz at jama.com Findings from a full neurologic examination were otherwise normal. Findings from a plain computed tomography (CT) scan of the head were normal apart from multiple bony sclerotic lesions seen in the calvarium, skull base, and C1 vertebra.
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WHAT WOULD YOU DO NEXT?
A. Perform skeletal survey B. Perform lumbar puncture with patient in upright position to measure opening pressure and examine cerebrospinal f luid (CSF) components C. Order magnetic resonance imaging (MRI) or magnetic resonance venography (MRV) of the brain and orbits D. Perform serum and urine protein electrophoresis
(Reprinted) JAMA March 3, 2015 Volume 313, Number 9
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/15/2015
963
Clinical Review & Education JAMA Clinical Challenge
Diagnosis Papilledema due to cerebral venous sinus thrombosis (CVST)
What to Do Next? C. Order magnetic resonance imaging (MRI) or magnetic resonance venography (MRV) of the brain and orbits Papilledema is defined as edema of the optic nerve heads due to increased intracranial pressure.1 The etiology can be broadly categorized into entities that cause an increase in brain volume, blood volume, or cerebrospinal fluid (CSF) volume.2 In this patient, after a plain CT scan of the head demonstrated no signs of hemorrhagic stroke or an intracranial mass, the next most appropriate step in the diagnosis was an MRI and MRV to assess the optic nerves and to rule out venous obstruction, most commonly caused by CVST. Computed tomography does not provide enough information about the details of the orbital and intracranial anatomy but is a useful imaging modality to assess the dural venous sinuses. Magnetic resonance imaging is important to rule out subtle compressive lesions and assess for enhancement of the optic nerves, which can occur with inflammatory processes that cause breakdown of the blood-brain barrier. If no cause can be found on neuroimaging, the next step in the diagnostic workup of patients with suspected papilledema is a lumbar puncture performed in the lateral decubitus position (because normative data exist only for this position) to measure the opening pressure and assess CSF constituents. An elevated opening pressure (>25 cm H2O) would confirm papilledema; an opening pressure that is not elevated would point to other causes of bilateral optic disc edema. These causes include inflammatory optic neuropathies such as idiopathic demyelinating optic neuritis, infiltrative optic neuropathies such as central nervous system lymphoma, and ischemic optic neuropathies such as that caused by giant cell arteritis. Choices A and D may be important in a subsequent metastatic workup but are not as critical as obtaining neuroimaging in this patient.
Discussion Cerebral venous sinus thrombosis occurs when thrombosis is present intheduralvenoussinuses,whichdrainbloodfromthebrain.3 Inamultinational prospective observational study the most common causes of CVST were thrombophilia, either genetic or acquired, and oral contraceptives.4 Other less common causes include hematologic conditions (anemia, polycythemia, or thrombocythemia), central nervous system infections, pregnancy, and malignancy.4,5 Isolated intracranial hypertension is often the presenting manifestation of CVST.6 Therefore, all patients presenting with symptoms and signs of increased intracranial pressure, such as papilledema, should be carefully evaluated withaneuroimagingstudythatincludesvenography.Patientswhohave long-standing papilledema may lose vision because of atrophy of the
retinal ganglion cells, which underscores the importance of early detection and treatment. This patient’s MRV imaging revealed the presence of CVST (Figure 2), and a lumbar puncture revealed an elevated opening pressure greater than 50 cm H2O with normal CSF constituents. The bony sclerotic lesions seen on the initial CT scan of the head raised concern for metastatic prostate cancer, and further testing revealed an elevated prostate-specific antigen level (751 ng/mL). Computed tomography urography demonstrated an irregular filling defect within the distal right ureter, which was later confirmed to be adenocarcinoma of the prostate. A thrombophilia panel was negative. Thus, the patient’s venous sinus thrombosis was likely the result of a hypercoaguable state secondary to malignancy. Dilated fundus examination revealed findings of macular edema and diffuse retinal hemorrhages in addition to papilledema. Patients with recent-onset papilledema usually have normal central visual acuity unless there is associated macular edema. In this patient, central visual acuity in his right eye was decreased due to macular edema related to extension of fluid from the optic nerve head. His hypercoaguable state also led to retinal vein occlusions confirmed with intravenous fluorescein angiography, which was responsible for the diffuse retinal hemorrhages.
Patient Outcome The patient was prescribed a therapeutic dose of enoxaparin as well as acetazolamide to help reduce his intracranial pressure. He was referred to oncology and began treatment with degarelix for metastatic prostate cancer.
ARTICLE INFORMATION
REFERENCES
Author Affiliations: Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada.
1. Trobe JD. Papilledema: the vexing issues. J Neuroophthalmol. 2011;31(2):175-186.
Corresponding Author: Jonathan A. Micieli, MD, CM, 340 College St, Ste 400, Toronto, Ontario, M5T 3A9, Canada ([email protected]). Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
964
Figure 2. Magnetic resonance venography demonstrating filling defects in the right transverse sinus (white arrowhead) and in the superior sagittal (yellow arrowhead) and right sigmoid (blue arrowhead) sinuses.
2. Mokri B. The Monro-Kellie hypothesis: applications in CSF volume depletion. Neurology. 2001;56(12):1746-1748. 3. Bushnell C, Saposnik G. Evaluation and management of cerebral venous thrombosis. Continuum (Minneap Minn). 2014;20(2 Cerebrovascular Disease):335-351.
4. Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F; ISCVT Investigators. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke. 2004;35(3):664-670. 5. Biousse V, Ameri A, Bousser MG. Isolated intracranial hypertension as the only sign of cerebral venous thrombosis. Neurology. 1999;53(7):1537-1542. 6. Biousse V, Rucker JC, Vignal C, Crassard I, Katz BJ, Newman NJ. Anemia and papilledema. Am J Ophthalmol. 2003;135(4):437-446.
JAMA March 3, 2015 Volume 313, Number 9 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/15/2015
jama.com
JAMA Clinical Challenge
A 55-Year-Old Man With Severe Papilledema Jonathan A. Micieli, MD, CM; Edward Margolin, MD
Right eye
Left eye
Figure 1. Optic nerve photographs demonstrating severe bilateral optic disc edema with peripapillary hemorrhages.
A 55-year-old man presenting to the emergency department reported blurry vision in his right eye during the past week. He also noticed rhythmic pulsing sounds in both ears during the past month. Past medical history was significant only for well-controlled hypertension treated with irbesartan (300 mg daily) and poor vision in the left eye for many years attributable to presumed inactive ocular histoplasmosis. On presentation, the patient appeared well, with blood pressure of 140/70 mm Hg and a regular heart rate of 75/min. Best corrected visual acuity was 20/200 (right eye) and counting fingers at 1 foot (left eye). Direct ophthalmoscopy revealed severe bilateral optic disc edema, peripapillary hemorrhages, and absent spontaneous venous pulsations (Figure 1). Quiz at jama.com Findings from a full neurologic examination were otherwise normal. Findings from a plain computed tomography (CT) scan of the head were normal apart from multiple bony sclerotic lesions seen in the calvarium, skull base, and C1 vertebra.
jama.com
WHAT WOULD YOU DO NEXT?
A. Perform skeletal survey B. Perform lumbar puncture with patient in upright position to measure opening pressure and examine cerebrospinal f luid (CSF) components C. Order magnetic resonance imaging (MRI) or magnetic resonance venography (MRV) of the brain and orbits D. Perform serum and urine protein electrophoresis
(Reprinted) JAMA March 3, 2015 Volume 313, Number 9
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/15/2015
963
Clinical Review & Education JAMA Clinical Challenge
Diagnosis Papilledema due to cerebral venous sinus thrombosis (CVST)
What to Do Next? C. Order magnetic resonance imaging (MRI) or magnetic resonance venography (MRV) of the brain and orbits Papilledema is defined as edema of the optic nerve heads due to increased intracranial pressure.1 The etiology can be broadly categorized into entities that cause an increase in brain volume, blood volume, or cerebrospinal fluid (CSF) volume.2 In this patient, after a plain CT scan of the head demonstrated no signs of hemorrhagic stroke or an intracranial mass, the next most appropriate step in the diagnosis was an MRI and MRV to assess the optic nerves and to rule out venous obstruction, most commonly caused by CVST. Computed tomography does not provide enough information about the details of the orbital and intracranial anatomy but is a useful imaging modality to assess the dural venous sinuses. Magnetic resonance imaging is important to rule out subtle compressive lesions and assess for enhancement of the optic nerves, which can occur with inflammatory processes that cause breakdown of the blood-brain barrier. If no cause can be found on neuroimaging, the next step in the diagnostic workup of patients with suspected papilledema is a lumbar puncture performed in the lateral decubitus position (because normative data exist only for this position) to measure the opening pressure and assess CSF constituents. An elevated opening pressure (>25 cm H2O) would confirm papilledema; an opening pressure that is not elevated would point to other causes of bilateral optic disc edema. These causes include inflammatory optic neuropathies such as idiopathic demyelinating optic neuritis, infiltrative optic neuropathies such as central nervous system lymphoma, and ischemic optic neuropathies such as that caused by giant cell arteritis. Choices A and D may be important in a subsequent metastatic workup but are not as critical as obtaining neuroimaging in this patient.
Discussion Cerebral venous sinus thrombosis occurs when thrombosis is present intheduralvenoussinuses,whichdrainbloodfromthebrain.3 Inamultinational prospective observational study the most common causes of CVST were thrombophilia, either genetic or acquired, and oral contraceptives.4 Other less common causes include hematologic conditions (anemia, polycythemia, or thrombocythemia), central nervous system infections, pregnancy, and malignancy.4,5 Isolated intracranial hypertension is often the presenting manifestation of CVST.6 Therefore, all patients presenting with symptoms and signs of increased intracranial pressure, such as papilledema, should be carefully evaluated withaneuroimagingstudythatincludesvenography.Patientswhohave long-standing papilledema may lose vision because of atrophy of the
retinal ganglion cells, which underscores the importance of early detection and treatment. This patient’s MRV imaging revealed the presence of CVST (Figure 2), and a lumbar puncture revealed an elevated opening pressure greater than 50 cm H2O with normal CSF constituents. The bony sclerotic lesions seen on the initial CT scan of the head raised concern for metastatic prostate cancer, and further testing revealed an elevated prostate-specific antigen level (751 ng/mL). Computed tomography urography demonstrated an irregular filling defect within the distal right ureter, which was later confirmed to be adenocarcinoma of the prostate. A thrombophilia panel was negative. Thus, the patient’s venous sinus thrombosis was likely the result of a hypercoaguable state secondary to malignancy. Dilated fundus examination revealed findings of macular edema and diffuse retinal hemorrhages in addition to papilledema. Patients with recent-onset papilledema usually have normal central visual acuity unless there is associated macular edema. In this patient, central visual acuity in his right eye was decreased due to macular edema related to extension of fluid from the optic nerve head. His hypercoaguable state also led to retinal vein occlusions confirmed with intravenous fluorescein angiography, which was responsible for the diffuse retinal hemorrhages.
Patient Outcome The patient was prescribed a therapeutic dose of enoxaparin as well as acetazolamide to help reduce his intracranial pressure. He was referred to oncology and began treatment with degarelix for metastatic prostate cancer.
ARTICLE INFORMATION
REFERENCES
Author Affiliations: Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada.
1. Trobe JD. Papilledema: the vexing issues. J Neuroophthalmol. 2011;31(2):175-186.
Corresponding Author: Jonathan A. Micieli, MD, CM, 340 College St, Ste 400, Toronto, Ontario, M5T 3A9, Canada ([email protected]). Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
964
Figure 2. Magnetic resonance venography demonstrating filling defects in the right transverse sinus (white arrowhead) and in the superior sagittal (yellow arrowhead) and right sigmoid (blue arrowhead) sinuses.
2. Mokri B. The Monro-Kellie hypothesis: applications in CSF volume depletion. Neurology. 2001;56(12):1746-1748. 3. Bushnell C, Saposnik G. Evaluation and management of cerebral venous thrombosis. Continuum (Minneap Minn). 2014;20(2 Cerebrovascular Disease):335-351.
4. Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F; ISCVT Investigators. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke. 2004;35(3):664-670. 5. Biousse V, Ameri A, Bousser MG. Isolated intracranial hypertension as the only sign of cerebral venous thrombosis. Neurology. 1999;53(7):1537-1542. 6. Biousse V, Rucker JC, Vignal C, Crassard I, Katz BJ, Newman NJ. Anemia and papilledema. Am J Ophthalmol. 2003;135(4):437-446.
JAMA March 3, 2015 Volume 313, Number 9 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/15/2015
jama.com
