- Department of Neurosurgery, Medical College of Wisconsin, Riley Children's Hospital/Indiana University, Indianapolis, IN
- Department of Opthalmology, Riley Children's Hospital/Indiana University, Indianapolis, IN
- Department of Neurological Surgery, Riley Children's Hospital/Indiana University, Indianapolis, IN
- Department of Neurological Surgery, Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN
Laurie L. Ackerman
Department of Neurological Surgery, Riley Children's Hospital/Indiana University, Indianapolis, IN
Department of Neurological Surgery, Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN
DOI:10.4103/2152-7806.110686Copyright: © 2013 Nguyen HS. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Nguyen HS, Haider KM, Ackerman LL. Unusual causes of papilledema: Two illustrative cases. Surg Neurol Int 18-Apr-2013;4:60
How to cite this URL: Nguyen HS, Haider KM, Ackerman LL. Unusual causes of papilledema: Two illustrative cases. Surg Neurol Int 18-Apr-2013;4:60. Available from: http://sni.wpengine.com/surgicalint_articles/unusual-causes-of-papilledema-two-illustrative-cases/
Background:Neurosurgeons are frequently among the first physicians asked to evaluate patients with papilledema, and the patient is often referred with the implication that they may require shunting. After an initial evaluation to exclude potential neurosurgical emergencies, the physician should carefully consider various etiologies of papilledema to prevent unnecessary neurosurgical operations.
Case Description:The authors report two illustrative cases of unusual causes of papilledema: Anemia and leukemic infiltration of the central nervous system. In each case, a complete blood count provided clues for the diagnosis. A review of the literature is also included.
Conclusions:Both patients responded to medical management/treatment of the underlying disease and did not require neurosurgical operative intervention. Papilledema may be caused by other etiologies besides increased intracranial pressure. The authors present two unusual cases leading to papilledema and provide an outline for the workup of these conditions.
Keywords: Anemia, cerebrospinal fluid shunt, idiopathic intracranial hypertension, papilledema
Papilledema is clinically defined as optic disc swelling secondary to increased intracranial pressure (ICP).[
We report two unusual etiologies of papilledema—one due to anemia and the other due to leukemic infiltration of the central nervous system. Both patients had abnormal bloodwork results shown on an initial complete blood count. Both patients responded to medical management and treatment of the underlying disease and operative intervention was not required. We also conducted a literature review to highlight the work-up for papilledema in an attempt to create a roadmap for diagnosis of papilledema.
A 14-year-old boy with Crohn's disease complained of “spots” in his vision for a 24-hour period and severe headaches during the prior several weeks. An initial evaluation revealed bilateral retinal hemorrhages and disc edema. Laboratory studies demonstrated severe anemia with hemoglobin of 3.0 mg/dL, white blood cells (WBC) of 1.8 × 103/mm3, and platelets of 101 × 103/mm3. He was transfused with packed red blood cells (RBC) and referred to our facility.
One to two days before admission, the headaches were described as retro-orbital and bilateral, accompanied by multiple spots in both visual fields. On admission, the spots had consolidated into one large spot in the center of his vision. The patient also admitted to intermittent diplopia, pulsatile tinnitus, and several episode of emesis over the previous 2 weeks. He had noted bloody stools the previous day. His medications before admission included 6-mercaptopurine (6-MP), mesalamine, and vitamin D supplements. He had been taking 6-MP to treat Crohn's disease for several months. On retrospective chart review, we noted that the patient's blood counts had gradually declined since 6-MP therapy had been initiated.
An ophthalmologic assessment at our institution demonstrated visual acuity of 20/800 right eye and 20/400 left eye, bilateral 4+ optic disc edema, bilateral central scotomas, nerve fiber layer hemorrhages, and bilateral scattered peripheral intraretinal hemorrhages. Computed tomography (CT) scan and magnetic resonance imaging/magnetic resonance venography (MRI/MRV) were unremarkable [
We postulated that the patient's severe anemia may have precipitated the elevated ICP, causing his symptoms. He was placed on oral acetazolamide 5 mg/kg/dose daily to reduce ICP. His 6-MP was discontinued as this was thought to be the proximate cause of anemia, and he received a transfusion of packed RBC to increase his hemoglobin to 8.5 g/dL.
The patient's clinical course showed improvement by hospital day 3 [
A 16-year-old obese girl presented with a 2-week history of jaw pain, headaches, sore throat, and tactile fevers. One week after the onset of symptoms, she was diagnosed with acute sinusitis and treated with amoxicillin-clavulinate. Due to persistent symptoms, further tests were performed that revealed anemia (Hgb of 7.8 mg/dL) and thrombocytopenia (platelets of 15 × 103/mm3). Blasts were noted on the smear. A monospot test was negative. Leukemia was suspected and she was referred to our facility for further management.
A review of the patient's systems revealed diffuse headaches, which were moderated by acetaminophen, mild neck pain, nausea with three episodes of emesis for 2 days, and bleeding when brushing her teeth. Bone marrow biopsy results were consistent with acute promyelocytic leukemia. She underwent induction therapy that consisted of all-transretinoic acid (ATRA) on days 1 through 28, daunomycin on days 3 through 6, and cytarabine (Ara-C) intravenously on days 3 through 9, and she also received four doses of intrathecal Ara-C. Her blood cell counts were monitored daily and transfusions of packed RBC and platelets were provided as needed.
Two days into her chemotherapy, the patient complained of progressive vision loss. An ophthalmology evaluation revealed visual acuity of 20/200 right eye and 20/200 left eye, bilateral 4+ optic nerve edema, and macular exudates. Intravenous acetazolamide (500 mg twice daily) was administered.
A “high” opening pressure during lumbar puncture was reported. CSF studies revealed RBC of 16/mm3, WBC of 1/mm3, bands of 18%, neutrophils of 59%, lymphocytes of 14%, monocytes of 4%, and other cells of 2% (myelocytes, metamyelocytes). Myeloid cells were also noted in the cytopathology specimen consistent with the diagnosis of leukemia. MRI demonstrated multifocal irregular nodules, dural thickening, and gyral enhancement in the posterior fossa. In addition, the patient's optic nerve sheaths were dilated and demonstrated thick nodular enhancement diffusely [
Acetazolamide did not lead to any improvement in the patient's condition. She urgently underwent a course of palliative craniospinal radiation therapy (12 daily treatments of 2160 cGy). Notably, her headaches and vision improved by the end of radiation treatment as evident by interval improvement in her papilledema with ongoing resolution of nerve hemorrhages and macula exudates. The patient continued taking acetazolamide until her papilledema resolved. A follow-up appointment at 8 months revealed visual acuity of 20/30 bilaterally and full ocular motility. Color plates continued to be decreased bilaterally, but were stable compared with prior exams. Mild optic nerve pallor was seen bilaterally, with no sign of optic nerve edema.
When a patient presents with optic disc swelling, it is important to obtain a thorough history, physical exam, and directed testing to determine if neurosurgical intervention is required. Optic disc swelling should distinguish between true disc edema and pseudo-edema via an ophthalmologic exam[
Etiologies leading to papilledema include PTC/IIH, hydrocephalus, shunt failure, mass lesions, trauma, venous sinus obstruction, and infection.[
Once serious neurosurgical causes are excluded, the physician should consider more unusual causes of optic disc edema. If the patient has increased ICP with no clear etiology, PTC/IIH is a potential diagnosis. Classically, PTC/IIH is diagnosed in the setting of papilledema when the following conditions are met: (1) Normal imaging studies (usually MRI); (2) normal CSF studies; (3) elevated opening pressure; and (4) other signs and symptoms secondary to elevated ICP (such as uni-or bilateral disc edema or a sixth nerve palsy).[
Although PTC/IIH is considered idiopathic, it has been associated with many conditions, including nutrition (such as hypervitaminosis A and vitamin deficiencies), drugs (such as phenytoin and anabolic steroids), hormonal regulation (such as thyroid disease, Addison's disease, and hypoparathyroidism), systemic illness (such as lupus, malignancies, and renal failure), and infections (such as HIV and Lyme disease).[
In Case 1, it is important to note that the patient had significant anemia, and to consider the role of medications in inducing anemia. This patient was taking 6-MP, which acts as a false metabolite of the purine hypoxanthine. It has been used as an immunosuppressive drug for inflammatory bowel disease (IBD)[
In a review of 77 patients with clinical evidence of intracranial hypertension, Mollan et al.[
The mechanism between anemia and intracranial hypertension has remained rather nebulous. Iron-deficiency anemia has been regarded as a hypercoagulable condition and linked to cerebral venous thrombosis.[
Hypercoagulability has also been reported in various conditions related to hemolytic anemia, including beta-thalassemia,[
Regarding Case 2, papilledema is a relatively rare complication of leukemia. Several reports exist concerning the relationship between papilledema and acute myeloid leukemia,[
Headache is the most frequent side effect of ATRA therapy.[
Moreover, the administration of intrathecal Ara-C has been associated with papilledema. Sommer et al.[
Shunt placement and operative intervention are not always mandated in the treatment of papilledema. Nonsurgical causes for papilledema should be considered in the differential diagnosis.
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