Papilledema and Vision Loss Caused by Jugular Paragangliomas

Cyclic oculomotor nerve paresis is a rare and usually congenital disorder. It is characterized by unilateral third nerve paresis with periodic spasms causing eyelid elevation, miosis, and contraction of 1 or more of the extraocular muscles innervated by the third nerve. We report a 20-month-old girl who presented initially with a congenital partial right third nerve paresis without ptosis. She subsequently developed isolated cyclic spasms of the pupil followed several months later by permanent partial ptosis.

Original Contribution Papilledema and Vision Loss Caused by Jugular Paragangliomas Paweena Lertakyamanee, MD, Ashok Srinivasan, MD, Lindsey B. De Lott, MD, Jonathan D. Trobe, MD Abstract: Paragangliomas that arise from the jugular bulb are known to present as masses in the neck or with hearing loss, pulsatile tinnitus, and lower cranial nerve palsies. Much less recognized is their tendency to cause increased intracranial pressure and papilledema by obstructing jugular venous outflow. Only 7 such cases have been reported and with minimal ophthalmic documentation. We describe 3 more cases to provide additional documentation and to emphasize that paragangliomas are a potential cause of the pseudotumor cerebri syndrome, and that papilledema may be overlooked when a jugular paraganglioma is diagnosed or after it has been treated. Such lapses have led to disabling vision loss from damage to the optic nerves in long-standing papilledema. Journal of Neuro-Ophthalmology 2015;35:364-370 doi: 10.1097/WNO.0000000000000281 © 2015 by North American Neuro-Ophthalmology Society P aragangliomas of the head and neck [also known as glomus tumors, chemodectomas, nonchromaffin tumors, carotid body tumors, glomerocytomas, tympanic body tumors, and receptomas (1,2)] are chromaffin cell tumors originating from the sympathetic and parasympathetic ganglia (3). They arise from the jugular bulb (jugular paragangliomas or glomus jugulare tumors), along the tympanic branch of the glossopharyngeal nerve or the auricular branch of the vagus nerve (tympanic paragangliomas or glomus tympanicum tumors), along the vagus nerve (vagal paragangliomas or glomus vagale tumors), or from the carotid body (carotid paragangliomas or carotid body tumors) (2,4). Their incidence ranges from 1 in 30,000 Departments of Ophthalmology (PL, LBDL, JDT), Neurology (LBDL, JDT), and Radiology (Neuroradiology) (AS), Kellogg Eye Center, University of Michigan. The authors report no conflicts of interest. Address correspondence to Jonathan D. Trobe, MD, Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105; E-mail: jdtrobe@ umich.edu 364 to 1 in 100,000 (4). Most paragangliomas are benign, but malignant behavior is seen in 4% of jugulotympanic and laryngeal paragangliomas, 10% of carotid body paragangliomas, and 16% of vagal paragangliomas (5). One study indicated that malignancy was present in only 3.5% of all cases (4). Management includes observation, surgical resection with preoperative embolization, radiotherapy, and radiosurgery (4,6). Paragangliomas often are discovered incidentally on imaging studies or in patients who present with neck masses, hearing loss, pulsatile tinnitus, or lower cranial nerve palsies (4,7-9). Because head and neck paragangliomas are usually nonsecreting tumors (4), signs of catecholamine hypersecretion, such as rapid pulse, pallor, tremor, headache, and diaphoresis, are not often seen (10). But these tumors may obstruct jugular venous outflow enough to cause increased intracranial pressure and vision loss secondary to long-standing papilledema. This phenomenon has been reported in only 7 patients (11-15) and with minimal ophthalmic documentation. Standard references to paragangliomas do not mention this clinical presentation (7,9,16). We present 3 additional cases to emphasize that these tumors may be an overlooked cause of papilledema in patients who have no brain imaging abnormalities, and that papilledema may not be identified at the time of tumor diagnosis or after its management, leading to permanent vision loss. CASE REPORTS Case 1 A 44-year-old woman presented to an optometrist for presbyopic symptoms. Bilateral optic disc edema was present. An ophthalmic examination 4 years earlier had been normal. Pulsatile tinnitus had begun 18 months earlier, but otolaryngological examination was nondiagnostic. Lertakyamanee et al: J Neuro-Ophthalmol 2015; 35: 364-370 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Case 1. A. Axial computed tomographic venogram demonstrates a mass in the left jugular fossa (arrows) with nonopacification of the left sigmoid sinus, suggesting no significant venous flow. There is opacification of the right jugular vein (arrowhead), consistent with normal venous flow. Postcontrast T1 axial (B) and coronal (C) images acquired on the same date demonstrate an enhancing mass (arrows) in the left jugular fossa and nonopacification of the left sigmoid sinus. However, opacification of the jugular vein is present more inferiorly in the neck, suggesting reconstitution of flow from venous collaterals (arrowheads). Shortly after the detection of optic disc edema, she was referred to an ophthalmologist, who confirmed the findings and ordered a computed tomographic (CT) scan of the head. This study showed no abnormalities of the brain, but an astute radiologist detected a mass in the left jugular foramen. CT venography revealed compression and nonopacification of the distal left sigmoid sinus and jugular vein at the level of the jugular foramen (Fig. 1A). Magnetic resonance imaging (MRI) of the neck demonstrated an enhancing mass in the same region (Fig. 1B, C). The imaging findings were consistent with a jugular paraganglioma. Two months later, our examination disclosed visual acuity of 20/20 in both eyes. Pupils were normal. Ophthalmoscopy disclosed bilateral optic disc edema (Fig. 2). Automated visual fields showed enlarged blind spots with mean deviations of 22.3 dB in the right eye and 22.1 dB in the left eye. Otolaryngologic examination revealed a mass behind the left tympanic membrane and moderate sensorineural hearing loss in the left ear. No intervention took place. Six months later, the patient remained visually asymptomatic, and ophthalmic signs and brain MRI were unchanged. Case 2 A 41-year-old woman reported transient obscurations of vision in both eyes. Visual acuity was 20/25 in the right eye and 20/20 in the left eye. Optic discs were moderately swollen. Automated visual field examination showed severe arcuate visual field loss in the right eye and mild arcuate loss in the left eye. CT showed no brain abnormalities, but venography disclosed that both jugular veins were compressed by masses that had imaging features of paraganglioma. Lumbar puncture yielded an opening pressure of 55 cmH2O with a normal cerebrospinal fluid (CSF) formula. The patient was diagnosed as having increased intracranial pressure from impeded cranial venous outflow and treated with acetazolamide. She underwent 4,500 cGy external beam radiation therapy for the presumed paragangliomas. At 4-year follow-up, visual acuity was unchanged and visual fields had improved but not normalized. The right optic disc was pale; the left optic disc appeared normal. An afferent pupil defect was present in the right eye. Repeat CT showed minimal shrinkage in the size of the tumors [This case was briefly reported in (17)]. FIG. 2. Case 1. Bilateral papilledema is present 2 months following the diagnosis of a left jugular paraganglioma. Lertakyamanee et al: J Neuro-Ophthalmol 2015; 35: 364-370 365 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 3. Case 3. A. Preoperative postcontrast T1 axial magnetic resonance imaging (MRI) demonstrates a large paraganglioma (arrow) in the right jugular foramen. There is no left jugular vein opacification identified at the level of the foramen, but there is slow flow within the right distal sigmoid sinus (arrowhead). B. Preoperative T2 axial MRI shows normal flow in the right transverse sinus (arrow). C. T2 axial MRI performed 4 years after resection of the right paraganglioma shows postoperative signal changes in the right jugular foramen (arrow). D. There is now intermediate-to-high signal intensity in the right transverse sinus (arrow), in contrast to the previously seen flow void preoperatively, a finding that may be attributed to slower blood flow in the right transverse sinus. Case 3 A 51-year-old woman with diabetes mellitus complained of painless reduced hearing in her right ear. A family physician diagnosed otitis media and prescribed several rounds of antibiotics to no avail. Brain MRI demonstrated a mass in the right jugular foramen with slowed flow in the right transverse sinus (Fig. 3A). There was normal flow in the right transverse sinus (Fig. 3B). In addition, the patient was found to have an extracranial left carotid sheath mass, but cerebral venous sinus flow on the left was normal. The patient was diagnosed with bilateral paragangliomas and underwent resection of the right jugular foramen mass. Pathologic examination confirmed paraganglioma. Within 2 months of surgery, the patient reported frequent transient visual obscurations precipitated by standing. Visual acuity was 20/20 in each eye, visual fields showed nasal field loss bilaterally (Fig. 4), and both optic discs were swollen (Fig. 5A). Repeat MRI demonstrated postoperative changes in the right jugular fossa (Fig. 3C) with interval development of intermediate-tohigh signal intensity in the right transverse sinus (Fig. 3D), suggesting slower flow in this sinus compared with the preoperative study. Lumbar puncture revealed 366 an opening pressure of 36 cmH2O with normal CSF analysis. She was treated with acetazolamide in escalating doses. When the dose reached 1,500 mg/d, the visual obscurations stopped. Twenty-four months later, visual acuities were 20/15 in the right eye and 20/20 in the left eye with a left relative afferent pupillary defect. Ophthalmoscopy disclosed mild residual optic disc edema in both eyes (Fig. 5B). Automated visual fields were improved, and brain MRI disclosed no change in the size or extent of the tumors. At 36-month follow-up, the patient remained stable with resolution of papilledema. DISCUSSION Our 3 patients had jugular paragangliomas that caused enough cranial venous outflow obstruction to produce increased intracranial pressure and papilledema. These cases add to the reported profile of papilledema and jugular paragangliomas (Table 1). Our Case 1, in which papilledema found on routine optometric examination led to the discovery of a paraganglioma, has no exact match in the reported literature. Our Case 2, of a patient presenting with visual symptoms, is Lertakyamanee et al: J Neuro-Ophthalmol 2015; 35: 364-370 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 4. Case 3. Automated visual fields show enlarged blind spots with nasal field loss in each eye (mean deviation: 23.6 dB, right eye; 24.3 dB, left eye). similar to that of a 27-year-old man with visual symptoms and headache whose ophthalmologic examination showed severe visual impairment and papilledema (11). Brain CT revealed a right jugular paraganglioma. Corticosteroids resolved the headache, but 1 month later, he developed ipsilateral sixth and seventh nerve paralysis. Vision deteriorated to no light perception bilaterally with optic disc pallor. Embolization and surgery of the paraganglioma did not reverse the blindness. Our Case 2 also resembles a patient who presented with blurred vision and was found to have papilledema, normal brain imaging, and elevated CSF pressure (12). She was misdiagnosed as having idiopathic intracranial hypertension (IIH) and received treatment with acetazolamide, optic nerve sheath fenestration, and a ventriculoperitoneal shunt, but she eventually developed no light perception in 1 eye. Years later, she complained of pulsatile tinnitus and was found to have a mass behind both tympanic membranes. Neuroimaging revealed enhancing masses in both jugular foramina with stagnant blood flow due to tumorous compression of the jugular veins. Retrospective examination of the original brain imaging disclosed that these tumors had been present at the time of the diagnosis of IIH and had not enlarged in the interval. Preoperative embolization and surgical removal eventually obliterated the tumors and relieved headache and disequilibrium but did not improve visual acuity, which remained no light perception in 1 eye and 20/25 in the other. Our Case 3, of a patient who developed visual symptoms within months of treatment of a paraganglioma on 1 side, is similar to 4 reported cases in which visual symptoms developed after intervention for paraganglioma (11,13-15). The first case involved a 30-year-old woman who developed headache, blurred vision, and diplopia 2 days after excision of a right jugular bulb paraganglioma (13). She had bilateral papilledema and a sixth nerve palsy. Lumbar puncture revealed a high opening pressure. Preoperative imaging had disclosed a large right transverse venous sinus and a small left transverse sinus. The patient was treated with dexamethasone and acetazolamide, but later required a lumboperitoneal shunt. The second case is that of a 56-year-old woman who developed blurred vision and papilledema 9 days after surgery for a right FIG. 5. Case 3. A. Two months after excision of a right jugular paraganglioma, there is bilateral papilledema. B. After treatment with oral acetazolamide for 24 months, the optic disc edema has markedly decreased. Lertakyamanee et al: J Neuro-Ophthalmol 2015; 35: 364-370 367 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Age/Gender/ Location of Reference Paraganglioma Presenting Manifestations Ophthalmologic Findings Lertakyamanee et al: J Neuro-Ophthalmol 2015; 35: 364-370 Blurred vision; headache; nausea; vomiting before diagnosis of paraganglioma Blurred vision starts 9 d after paraganglioma surgery "Total loss of vision" OU; bilateral papilledema; optic nerve "atrophy" Marked papilledema OU Increasing headache, new diplopia, blurred vision after diagnosis of paraganglioma but before intervention Pulsatile tinnitus; headache (misdiagnosed as "benign intracranial hypertension") with later diagnosis of paraganglioma Headache, blurred vision starts 48 h after paraganglioma surgery; diplopia starts 5 d later Blurred vision, headache start several days after paraganglioma embolization, surgery Blurred vision and TOVs start several months after paraganglioma embolization Bilateral papilledema; sixth nerve palsy 27/M/(11) Right 56/F/(11) Right 24/M/(11) Bilateral 39/F/(12) Bilateral 30/F/(13) Right 2/M/(14) Left 51/F/(15) Right 44/F/(Our Case 1) Left 41/F/(Our Case 2) Bilateral Transient obscurations of vision OU before diagnosis of paraganglioma 51/F/(Our Case 3) Bilateral Transient obscurations of vision both eyes starting 2 mo after paraganglioma surgery Pulsatile tinnitus before diagnosis of paraganglioma Management Visual Outcome Embolization, surgery of paraganglioma "Remained blind" Heparin, methylprednisolone, lumboperitoneal shunt for high ICP Corticosteroids, lumboperitoneal shunt for high ICP "Decreased papilledema"; "vision was restored" Papilledema, headache "improved" 20/40 OD, no light perception OS; Embolization, surgery of chronic papilledema paraganglioma 20/25 OD, no light perception OS Papilledema OU; sixth nerve palsy "Symptoms of elevated ICP quickly improved"; vision data not reported 20/15 right eye, 20/30 left eye; reduced color vision OS; bilateral marked papilledema Finger counting OD, light perception OS; bilateral marked papilledema Corticosteroids, acetazolamide, lumboperitoneal shunt for high ICP Anticoagulation for dural venous thrombosis "Remained well"; vision data not reported Drainage of cerebrospinal fluid, "Reads fine newspaper print with corticosteroids, for high ICP; magnifying glasses" OD, light paraganglioma excised perception OS; papilledema resolved No intervention All findings stable after 6 mo 20/20 OU; bilateral chronic papilledema; enlarged blind spots, mild decreased mean deviation OU 20/25 OD, 20/20 OS; moderate Acetazolamide for high ICP; radiotherapy for papilledema; marked arcuate paraganglioma visual field loss OD, mild arcuate loss OS 20/20 OU; papilledema OU; Acetazolamide for high ICP enlarged blind spots OU Visual acuity unchanged; visual fields improved but still very abnormal; pale optic disc OD 20/15-1 OD, 20/20-2 OS; left afferent pupil defect; mild optic disc edema OU; decreased mean deviations OU ICP, intracranial pressure; OD, right eye; OS, left eye; OU, both eyes; TOV, transient obscuration of vision. Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution 368 TABLE 1. Clinical features of reported cases of paragangliomas causing papilledema Original Contribution jugulotympanic paraganglioma (11). Imaging revealed thrombosis that extended from the right jugular vein to the right transverse sinus with poor venous flow through a hypoplastic left transverse sinus. The patient's visual manifestations did not improve after medical treatment, and she underwent placement of a lumboperitoneal shunt. One month later, papilledema had decreased and "vision was restored." Six months later, imaging revealed "satisfactory venous outflow." The third case involved a 42-yearold man with a left jugular paraganglioma who presented with tinnitus (14). Blurred vision and headache developed within days after embolization and surgery. Visual acuities were 20/20 in the right eye and 20/30 in the left eye without afferent pupil defect, but reduced color vision in the left eye, a "superior altitudinal defect" in the right eye, and "few central defects" in the left eye. Bilateral papilledema was present. Magnetic resonance venography showed a "fresh thrombus within the left lateral sinus, which was occluded." The right lateral sinus was "slightly narrowed." The patient underwent anticoagulation, but there was no documentation of the visual outcome. The fourth case (15) concerned a 51-year-old woman who presented with tinnitus, deafness, and mild ipsilateral peripheral facial weakness (15). She was found to have a vascular lesion in the right petrous bone with enlargement of the jugular foramen. Several months after embolization, the patient reported transient visual obscurations. She had finger counting visual acuity in the right eye, light perception in the left eye, and bilateral papilledema. She was treated with dexamethasone without visual improvement, so she underwent tumor removal. Papilledema resolved, and vision was reported as "reading fine newspaper print with magnifying glasses" in the right eye but remained light perception in the left eye. Reduced vision from papilledema has also been detected after the diagnosis of paraganglioma but before intervention (10). A 24-year-old man presented with headache and a cervical mass suggestive of a left carotid body tumor. Otoscopy revealed a reddish retrotympanic tumor in the left middle ear. There was no cranial nerve involvement. Neuroimaging disclosed multiple neck paragangliomas. While awaiting genetic test results, the patient developed headache, trigeminal pain, diplopia, and blurred vision. Physical examination revealed a sixth cranial nerve palsy and bilateral papilledema with normal visual acuity. Magnetic resonance angiogram revealed marked impairment of jugular venous outflow on both sides. The papilledema and headache did not improve with corticosteroid therapy but did improve after lumboperitoneal shunt. The visual outcome was not reported. In our cases and in those previously reported, the ophthalmic manifestations of jugular paragangliomas (blurred vision, transient obscurations, and papilledema) resulted from impaired venous drainage. The impaired venous drainage raises pressure in the dural venous sinuses and across the arachnoid granulations, where CSF outflow Lertakyamanee et al: J Neuro-Ophthalmol 2015; 35: 364-370 is governed by a pressure differential between the subarachnoid and dural venous sinus spaces. In cases where symptoms develop gradually, venous compression is probably the mechanism. In cases where symptoms arise suddenly, especially after surgery, venous thrombosis has been noted on imaging. Most reported cases have involved either bilateral or right paragangliomas. Predominance of right paragangliomas can be explained by the fact that the right transverse-sigmoid-jugular drainage system is usually dominant (18,19). In summary, we emphasize 3 points: 1. Paragangliomas may be an occult cause of the "pseudotumor cerebri syndrome." A diagnosis of pseudotumor cerebri should not be tendered without attention to the neck, where paragangliomas, sometimes small but usually conspicuous because of avid enhancement, could be the cause. 2. Increased intracranial pressure and papilledema may be overlooked at the time of diagnosis of the paraganglioma. 3. Increased intracranial pressure and papilledema may arise or become exacerbated after treatment of paraganglioma. Embolization, extirpative surgery, radiosurgery, and x-irradiation have all been documented to produce ophthalmic manifestations of high intracranial pressure within days to months of intervention by causing further compromise of venous outflow. These interventions may reduce venous outflow which, hopefully, will normalize with development of collateral vessels. Treating physicians should anticipate these consequences, alert patients to them, and arrange for ophthalmologic examination. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: P. Lertakyamanee, A. Srinivasan, J. D. Trobe; b. Acquisition of data: P. Lertakyamanee, A. Srinivasan, L. B. De Lott, J. D. Trobe c. Analysis and interpretation of data: P. Lertakyamanee, A. Srinivasan, L. B. De Lott, J. D. Trobe. Category 2: a. Drafting the manuscript: P. Lertakyamanee, A. Srinivasan, J. D. Trobe b. Revising it for intellectual content: P. Lertakyamanee, A. Srinivasan, L. B. De Lott, J. D. Trobe. Category 3: a. Final approval of the completed manuscript: P. Lertakyamanee, A. Srinivasan, L. B. De Lott, J. D. Trobe. REFERENCES 1. Forbes JA, Brock AA, Ghiassi M, Thompson RC, Haynes DS, Tsai BS. Jugulotympanic paragangliomas: 75 years of evolution in understanding. 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Lertakyamanee et al: J Neuro-Ophthalmol 2015; 35: 364-370 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.