Pseudotumor Cerebri and Papilledema AN OVERVIEW OF THIS PERPLEXING SYNDROME AND ITS HALLMARK PRESENTATION. BY RUI WANG; ASHWINI KINI, MD; BAYAN AL OTHMAN, MD; AND ANDREW G. LEE, MD seudotumor cerebri, also IIH and secondary intracranial hyper- specific, headaches associated with IIH known as idiopathic intra- tension due to cerebral venous throm- are often daily and are retroocular.9 Pcranial hypertension (IIH), bosis and other causes of obstructed The headaches may resemble migraine describes the perplexing syndrome of venous outflow. headaches with associated symptoms increased intracranial pressure (ICP) Additionally, several systemic dis- of nausea, vomiting, and photophobia. in the absence of a space-occupying eases, drugs, and vitamin deficiencies In fact, many patients with IIH have lesion on neuroimaging or other or excesses have been reported to be coexisting migraine headaches, mak- etiology. Although the disease can associated with IIH. Of medications ing the diagnosis difficult.10 be observed in patients of any age, associated with IIH, growth hormones, Transient visual obscurations IIH classically presents among obese tetracyclines, and retinoids have been (TVOs) have been found to occur (body mass index >30) women of the most often reported.3-5 Other in about two-thirds of patients with childbearing age. Due to the increased systemic illnesses associated with papilledema. TVOs typically last only prevalence of obesity in recent years, pseudotumor cerebri include Addison seconds at a time and may be bilater- a significant increase in cases of IIH disease, hypoparathyroidism, sleep al or unilateral and postural. TVOs are has been noted, and, as such, an abil- apnea, systemic lupus erythematous, likely a manifestation of disc edema ity to recognize and understand the and polycystic ovary syndrome.6-8 leading to transient ischemia of the disease is important.1 optic nerve head.11 CLINICAL MANIFESTATIONS Perhaps the most suggestive clinical PATHOGENESIS Headache is the most common presentation of IIH is pulsatile tin- Although IIH is, by definition, idio- symptom of IIH. Although not nitus, with which patients describe pathic, increased ICP can be caused by increased cerebrospinal fluid (CSF) production, reduced CSF absorption, AT A GLANCE increased cerebral venous pressure, venous sinus stenosis, increased brain s water content, or a combination Papilledema is the hallmark sign of idiopathic intracranial hypertension of these mechanisms.2 One theory and occurs due to raised intracranial pressure transmitted to the optic has postulated elevated intracranial nerve sheath. venous pressure as both the primary mechanism and a final common path- s way for IIH. This theory is supported Patients with papilledema should be evaluated for an intracranial cause. by the similar clinical appearance of 34 GLAUCOMA TODAY | JANUARY/FEBRUARY 2019 DIFFERENTIAL DIAGNOSIS s the setting of IIH may be asymmetric TABLE 1. SYMPTOMS OF IDIOPATHIC INTRACRANIAL HYPERTENSION or frankly unilateral; in one series of Symptoms Frequency 478 IIH patients, 10% had highly asym- Headache 84% metric papilledema and greater visual loss in the eye with the higher grade of Transient visual obscuration 68% papilledema.15 In addition, the absence Back pain 53% of papilledema does not exclude Pulsatile tinnitus 52% elevated ICP. Due to the evolving course of pap- Photopsia 48% illedema, the Frisén scale was devel- Sustained vision loss 32% oped to describe papilledema in clini- Diplopia 18% cally meaningful stages.13 B-scan ultra- Reproduced with permission from Wall et al9 sonography can assist in diagnosis of IIH by measuring the diameter of the optic nerve sheath.16 The diameters in primary gaze and in 30° eccentric gaze are compared, and a 20% reduc- tion in diameter in eccentric gaze (30° test) bilaterally is considered a posi- tive test result, indicating increased subarachnoid fluid surrounding the optic nerve (Figure 1). Additionally, B-scan ultrasonography can aid in dif- ferentiating pseudopapilledema from (Courtesy of Thomas Prager, PhD; Houston Eye Associates) papilledema by identifying optic disc Figure 1. A-scan ultrasonography can be a useful diagnostic tool. Reduction by greater than 20% on eccentric gaze drusen (Figure 2).17 (30° test), as shown above, indicates increased subarachnoid fluid level surrounding the optic nerve. DIAGNOSIS When elevation of ICP is suspected, MRI of the brain with gadolinium and magnetic resonance venography should be promptly conducted to exclude secondary causes of ICP. If no structural abnormality is identified, a lumbar puncture should be performed, documenting the opening pressure, and Figure 2. B- and A-scan ultrasonography of optic disc drusen. Note that the optic nerve head is highly reflective. a CSF sample should be forwarded for Calcified drusen leading to pseudopapilledema maintain high signal intensity, whereas the signal intensity is analysis and culture. IIH is diagnosed decreased in the setting of papilledema. according to the Idiopathic Intracranial Hypertension Treatment Trial modified Dandy criteria (Table 2).18 hearing rushing water or wind. This PAPILLEDEMA symptom can be persistent or inter- Papilledema is the hallmark sign of MEDICAL MANAGEMENT mittent, and it is believed to repre- IIH. It occurs due to raised ICP trans- The goal of treatment for IIH is allevi- sent vascular pulsations transmitted mitted to the optic nerve sheath. The ation of symptoms and preservation of by the CSF under high pressure to the elevated pressure, in turn, disrupts vision. Weight loss in the range of 6% venous sinus.12 Other ocular presen- the axoplasmic flow within the nerve, to 10% has been demonstrated to lead tations include horizontal diplopia, resulting in swelling of the axons and to IIH remission.19 Although a low-sodi- often in association with sixth nerve leakage of water, protein, and other um weight reduction program is rec- palsy; transient episodes of visual loss; cellular content into the extracellular ommended for all obese patients with and visual field disturbance, with pre- space of the optic disc, leading to optic IIH, those unable to lose weight may dilection for inferonasal defect and disc edema.14 Although typically bilat- benefit from bariatric surgery. A meta- arcuate defect (Table 1).9,13 eral and symmetric, papilledema in analysis of bariatric surgery’s effects on JANUARY/FEBRUARY 2019 | GLAUCOMA TODAY 35 s DIFFERENTIAL DIAGNOSIS TABLE 2. IIHTT MODIFIED DANDY CRITERIA final definitive surgical procedure and preoperative evaluation in patients 1. Signs and symptoms of increased intracranial pressure with fulminant IIH and rapidly dete- 2. No localizing findings on neurologic examination riorating vision to prevent further worsening.28 3. No deformity, displacement, or obstruction of the ventricular system and otherwise normal neurodiagnostic studies, except for increased cerebrospinal fluid (CSF) pressure >200 mm H2O (abnormal neuroimaging except for empty sella turcica, optic nerve sheath with filled-out CSF spaces, and smooth- SUMMARY Patients with papilledema should walled, non–flow-related venous sinus stenosis or collapse should lead to another diagnosis) be evaluated for an intracranial cause. 4. Awake and alert patient Negative neuroimaging (eg, cranial, 5. No other known cause of increased intracranial pressure; opening CSF pressure of 200 to 250 mm H2O contrast MRI with magnetic resonance and at least one of the following: venography); normal CSF content; and • Pulse synchronous tinnitus an elevated ICP on opening pressure • Sixth nerve palsy on lumbar puncture establish the diag- • Frisén grade 2 papilledema nosis of IIH. Treatment with weight • Echography negative for drusen and no other disc anomalies mimicking disc edema loss and acetazolamide is the first step • Magnetic resonance venography with lateral sinus collapse or stenosis, preferably using the auto- in the treatment of IIH. Some patients triggered elliptic centric ordered technique who do not respond to maximum • Partially empty sella on coronal or sagittal views and optic nerve sheaths with filled-out CSF spaces medical therapy may require surgery, next to the globe on T2 weighted axial scans such as ONSF, CSF diversion, or venous sinus stenting. n IIH demonstrated 100% papilledema optic nerve function. ONSF has also 1. Friesner D, Rosenman R, Lobb BM, Tanne E. Idiopathic intracranial hyperten- sion in the USA: the role of obesity in establishing prevalence and healthcare resolution and a 90.2% reduction in been shown to be safe and effective in costs. Obes Rev. 2011;12(5):e372-e380. headache symptoms.20 children and could be an option for 2. Biousse V, Bruce BB, Newman NJ. Update on the pathophysiology and Acetazolamide (ACZ) is the most patients with IIH with predominantly management of idiopathic intracranial hypertension. J Neurol Neurosurg 25,26 Psychiatry. 2012;83(5):488-494. effective and the only randomized visual symptoms, especially those 3. Vischi A, Guerriero S, Giancipoli G, Lorusso V, Sborgia G. Delayed onset of control trial–proven therapy for IIH; with fulminant IIH with rapid deterio- pseudotumor cerebri syndrome 7 years after starting human recombinant however, treatment with ACZ led to ration of visual fields. Central acuity growth hormone treatment. Eur J Ophthalmol. 2006;16(1):178-180. 4. Friedman DI, Gordon LK, Egan RA, et al. Doxycycline and intracranial only modest improvement in visual can be preserved until final stages and hypertension. Neurology. 2004;62(12):2297-2299. function