Diagnosis, Pathophysiology, and Management of Papilledema

Educational Objectives

The goal of this program is to improve management of papilledema. After hearing and assimilating this program, the clinician will be better able to:

1. Provide prompt workup of papilledema based on clinical presentation.
2. Select appropriate medical or surgical treatment for pseudotumor cerebri.

Summary

Definition: optic disc (OD) swelling due to increased intracranial pressure (ICP), secondary to axonal swelling and blocked transport; generally painless; loss of visual field (VF) and visual acuity (VA) typically occur during advanced stages of disease, upon which there is severe and sudden loss of vision; loss of central vision generally occurs at the end of the disease process

Grading

Frisen scale: most common; very early papilledema (grade 1) — mild hyperemia of the optic disc (OD) with blurring of some disc margins (temporal margin is typically normal); early papilledema (grade 2) — OD hyperemia and blurring of all margins with clear view of vessels; moderate papilledema (grade 3) — clear elevation of the OD, disc hyperemia, blurring of all margins, and obscurity of some major vessels leaving the disc; marked papilledema (grade 4) — includes features of grade 3, obscurity of some vessels overlying the disc surface, and pseudodrusen; severe papilledema (grade 5) — involves disc elevation, blurring and rounding of margins, and obscurity of all major vessels

Retinal nerve fiber layer (RNFL) measurements: favorably comparable at lower grades of Frisen staging, but less reliable for higher grades (at which point total retinal thickness should be used)

VF and VA: Frisen grades 1 and 2 — VF and VA are normal; grade 3 — enlarged blind spot may be visible, though VA is normal; Frisen grade 4 — some VF loss may be visible; VA is generally normal; Frisen grade 5 — there may be nasal field loss, constricted VF, and decreased VA; permanent vision loss occurs with postpapilledema optic atrophy (characterized by minimal disc elevation, pallor, halo around the disc, and remnants of Patton lines without hemorrhage or exudates)

Rate of progression: the minimum time to develop papilledema may develop ≈2 hr following trauma, and atrophic papilledema develops in 1 wk; earlier VA loss can occur secondary to macular hemorrhage or exudate, submacular edema, tumor (causes hydrocephalus [secondary to occlusion of the third ventricle], compression of the optic nerves (ONs) or chiasm, or involvement of the visual pathway), or ischemic optic neuropathy; a patient with papilledema is presumed to have a brain tumor until proven otherwise; provide same-day patient referral to the emergency department (ED); patients with organic VF constriction require emergency treatment; other etiologies of papilledema include inflammatory mass, abscess, hemorrhage, infarction, reduced outflow of cerebrospinal fluid (CSF) due to arteriovenous (AV) malformation or dural AV fistula, venous sinus thrombosis or stenosis, increased CSF production, and trauma; children with craniosynostosis or sclerosteosis have papilledema secondary to compression of the brain

Treatment: dependent on etiology; may involve, eg, tumor resection, CSF diversion (ventriculoatrial [VA], ventriculoperitoneal [VP], or lumboperitoneal [LP] shunt), optic nerve sheath fenestration (ONSF), posterior fossa decompression (to treat a Chiari malformation), venous sinus reconstruction, venous sinus stenting (VSS), medication discontinuation (for, eg, vitamin A, lithium), anticoagulation

Primary Pseudotumor Cerebri

Etiology, demographics, and risk: ie, idiopathic intracranial hypertension (IIH); the most common etiology of papilledema; primarily occurs in women in the second to fourth decades of life; in the United States, pseudotumor cerebri (PTC) occurs in ≈1 per 100,000 women among the general population and ≈3.5 per 100,000 women of childbearing age; proposed mechanisms include hypersecretion of CSF, obstruction of CSF outflow, and increased venous sinus pressure; Daniels et al (2007) found that patients with obesity have a 6-fold increased risk to develop PTC, compared with patients without obesity

Diagnosis: magnetic resonance imaging and magnetic resonance venography or computed tomography (CT) and CT venography are ideal for suspected PTC; perform a lumbar puncture (LP) if no mass lesion is identified; perform LP under fluoroscopy in the prone position (for patients with extreme obesity) or lateral decubitus position (offers similar results as prone position), as ICP may read abnormally high if LP is performed in the seated position (common in the ED) due to pressure in the vertical column of the CSF above the needle; LP performed in the lateral decubitus or prone position is more reliable, compared with the seated position; PTC can only be diagnosed if ICP is elevated but CSF contents are normal (ie, normal protein and glucose concentrations and no cells); rule out thrombosis, occlusion, or stenosis of the superior sagittal, lateral, or straight sinuses, plus inferior tonsillar displacement (ie, cerebellar tonsillar ectopia; secondary to, eg, Chiari malformation); inquire about exogenous agents (eg, vitamin A, tetracyclines); consider sleep apnea or anemia in children and adults

Management: monitoring is reasonable for a patient with mild papilledema and no headaches or with mild headaches that respond to analgesics; otherwise, consider weight loss or acetazolamide; patients with sleep apnea may require continuous positive airway pressure, bilevel positive airway pressure, mandibular advancement device, or surgery; weight loss — the only consistently effective treatment; weight loss of 7% to 10% eliminates or speeds resolution of papilledema and headache; acetazolamide — reduces ICP better than weight loss alone; start with 1 g/day in divided doses; severe papilledema may require higher doses; dose tolerance is limited by side effects (include, eg, tingling of fingers and toes, insomnia, lethargy, reduced appetite, mood changes, metallic taste); sulfa allergy and pregnancy are not contraindications; furosemide — less effective than acetazolamide; steroids — generally not indicated; can worsen obesity and hypertension; topiramate — improves headache, suppresses appetite, and reduces CSF, though is ineffective for PTC and may be teratogenic; the IIHTT trial (Wall et al, 2014) — found that long-term treatment of mild to moderate PTC with weight loss and ≤4 g/day of acetazolamide (highest tolerable dose) is more successful than weight loss alone; these findings can only be applied to mild or moderate PTC

Surgical management: reserved for patients with optic neuropathy at presentation, who experience worsening despite maximum medical therapy, or who cannot tolerate medical therapy

Subtemporal decompression: rarely performed; highly effective, has lower risk for infection (since no foreign objects are introduced), cannot become obstructed, and carries no risk to vision; risks include infection, dural tear, or hemorrhage

VP and VA shunting: effective at improving VF and reducing ICP, papilledema, and headaches in adults and children; risk for tonsillar herniation is lower vs LP shunting; visual outcomes are similar to that following ONSF; VA shunting is preferable to VP shunting as there is less risk for obstruction; however, VA shunting must be performed with a stereotactic apparatus and there is risk for hemorrhage, cerebral injury, malposition of the catheter, and infection; in ≈50% of cases, VA or VP shunts must be replaced or revised

LP shunting: directly treats elevated ICP, carries little to no risk to vision, and improves papilledema, VFs, and RNFL thickness; may be performed under general or regional anesthesia; some studies show that LP shunts have a failure rate of 60% over 5 yr; risk of infection is present; there is a risk for low pressure (Toma et al, 2010), though most new valves reduce the risk for overdrainage; cerebellar tonsillar herniation is possible (risk is low); Eggenberger et al (1996) found that most LP shunt revisions are performed <12 mo; McGirt et al (2004) showed that LP shunts require revisions more often than VA or VP shunts

Optic nerve sheath fenestration: immediately improves vision, eliminates pressure on the ON without need for implantation of foreign material, yields similar visual outcomes as shunting, and improves contralateral papilledema (with unilateral ONSF); disadvantages include risk to vision due to manipulation of the ON, diplopia due to alteration of the medial rectus muscle, and higher risk of failure (dependent on ICP level)

Venous sinus stenting (VSS): venous sinus stenosis is likely a risk factor for PTC; while all patients studied by Radvany et al (2013) improved following VSS, many patients who had normal ICP still experienced headaches responsive to antimigraine medications; Satti et al (2015) found greater improvement in vision, headache, and papilledema with VSS over ONSF or shunting; Aguilar-Pérez et al (2017) found that VSS yields improvement or resolution of papilledema in ≈90% of patients and of headaches in 84%; Dinkin et al (2017) followed 13 patients who were refractory to medical therapy or presented with fulminant VF loss and underwent VSS and noted improvement or resolution of headaches in 80% of patients, tinnitus in 100% of patients, transient visual obscuration in 100% of patients, and improvement in mean deviation and papilledema; advantages — results in immediate reduction of ICP, yields rapid resolution of signs and symptoms, is more cost-effective than shunting, and has a better prognosis than shunting or ONSF; disadvantages — include the need for an experienced interventionalist, risks of the procedure itself, and lack of data regarding long-term safety and efficacy

Prognosis: prognosis for visual function is best when visual loss is associated with subretinal fluid vs ON damage; prognosis is better if treatment occurs before significant VF constriction or reduction in vision occurs; PTC can recur after resolution, especially following recent weight gain; men tend to have a poorer prognosis than women, possibly due to a higher risk for obstructive sleep apnea or delay in examination and diagnosis; children typically have a good prognosis, but poorer in pubescence; younger age may be a risk factor for treatment failure

Readings

Chen J, Wall M. Epidemiology and risk factors for idiopathic intracranial hypertension. Int Ophthalmol Clin. 2014;54(1):1-11. doi: 10.1097/iio.0b013e3182aabf11; Daniels AB, Liu GT, Volpe NJ, et al. Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol. 2007;143(4):635-41. doi: 10.1016/j.ajo.2006.12.040; Dinkin MJ, Patsalides A. Venous sinus stenting in idiopathic intracranial hypertension: results of a prospective trial. J Neuroophthalmol. 2017;37(2):113-121. doi: 10.1097/WNO.0000000000000426; Eggenberger ER, Miller NR, Vitale S. Lumboperitoneal shunt for the treatment of pseudotumor cerebri. Neurology. 1996;46(6):1524-1530. doi:10.1212/wnl.46.6.1524; Fonseca PL, Rigamonti D, Miller NR, Subramanian PS. Visual outcomes of surgical intervention for pseudotumour cerebri: optic nerve sheath fenestration versus cerebrospinal fluid diversion. Br J Ophthalmol. 2014;98(10):1360-1363. doi:10.1136/bjophthalmol-2014-304953; Radvany MG, Solomon D, Nijjar S, et al. Visual and neurological outcomes following endovascular stenting for pseudotumor cerebri associated with transverse sinus stenosis. J Neuroophthalmol. 2013;33(2):117-122. doi:10.1097/WNO.0b013e31827f18eb; Sandoval M, Shestak W, Stürmann K, et al. Optimal patient position for lumbar puncture, measured by ultrasonography. Emerg Radiol. 2004;10(4):179–181. doi: 10.1007/s10140-003-0286-3; Satti SR, Leishangthem L, Chaudry MI. Meta-analysis of CSF diversion procedures and dural venous sinus stenting in the setting of medically refractory idiopathic intracranial hypertension. AJNR Am J Neuroradiol. 2015;36(10):1899-904. doi: 10.3174/ajnr.A4377; Scott CJ, Kardon RH, Lee AG, et al. Diagnosis and grading of papilledema in patients with raised intracranial pressure using optical coherence tomography vs clinical expert assessment using a clinical staging scale. Arch Ophthalmol. 2010;128(6):705-711. doi:10.1001/archophthalmol.2010.94; Wall M, Kupersmith MJ, Thurtell MJ, et al. The longitudinal idiopathic intracranial hypertension trial: outcomes from months 6-12. Am J Ophthalmol. 2017;176:102-107. doi:10.1016/j.ajo.2017.01.004.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Miller’s lecture includes information related to the off-label or investigative use of a therapy, product, or device.

Acknowledgements

Dr. Miller was recorded exclusively for Audio Digest. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.25 CE contact hours.

Lecture ID:

OP610402

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.