Pediatric Pseudotumor Cerebri Syndrome

Idiopathic intracranial hypertension, otherwise known as primary pseudotumor cerebri syndrome (PTCS), most frequently occurs in obese women of childbearing age. However, children may be affected as well. This review will address recent findings regarding demographics, diagnosis, and treatment of pediatric PTCS. Prepubertal children with primary PTCS have an equal sex distribution and less frequent obesity compared with adult patients. However, female gender and obesity are risk factors for primary PTCS in postpubertal children. Compared with adults, children with PTCS more frequently present with ocular motility deficits and more often have associated medical conditions that increase the risk of developing PTCS. Visual field testing may be unreliable, and the optimal modality to monitor visual function is unknown. MRI shows signs of elevated intracranial pressure (ICP) in children with PTCS similar to that of adults. It has now been established that elevated ICP in children ≤18 years old is greater than 25 cm H20 in nonobese, nonsedated children, and greater than 28 cm H2O in the remainder. Optical coherence tomography (OCT) may be used to distinguish pseudopapilledema from papilledema, monitor response to treatment in preverbal children, and identify patients with PTCS at risk for permanent visual loss. However, the precise role of OCT in the management of pediatric PTCS remains to be determined.

Original Contribution Pediatric Pseudotumor Cerebri Syndrome Paul H. Phillips, MD, Claire A. Sheldon, MD, PhD Abstract: Idiopathic intracranial hypertension, otherwise known as primary pseudotumor cerebri syndrome (PTCS), most frequently occurs in obese women of childbearing age. However, children may be affected as well. This review will address recent findings regarding demographics, diagnosis, and treatment of pediatric PTCS. Prepubertal children with primary PTCS have an equal sex distribution and less frequent obesity compared with adult patients. However, female gender and obesity are risk factors for primary PTCS in postpubertal children. Compared with adults, children with PTCS more frequently present with ocular motility deficits and more often have associated medical conditions that increase the risk of developing PTCS. Visual field testing may be unreliable, and the optimal modality to monitor visual function is unknown. MRI shows signs of elevated intracranial pressure (ICP) in children with PTCS similar to that of adults. It has now been established that elevated ICP in children #18 years old is greater than 25 cm H20 in nonobese, nonsedated children, and greater than 28 cm H2O in the remainder. Optical coherence tomography (OCT) may be used to distinguish pseudopapilledema from papilledema, monitor response to treatment in preverbal children, and identify patients with PTCS at risk for permanent visual loss. However, the precise role of OCT in the management of pediatric PTCS remains to be determined. Journal of Neuro-Ophthalmology 2017;37(Suppl):S33-S40 doi: 10.1097/WNO.0000000000000548 © 2017 by North American Neuro-Ophthalmology Society I diopathic intracranial hypertension (IIH), otherwise known as primary pseudotumor cerebri syndrome (PTCS), is characterized by symptoms and signs of elevated intracranial pressure (ICP); no mass, structural lesion, hydrocephalus, or meningeal enhancement on neuroimagDepartment of Ophthalmology (PHP), Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Jones Eye Institute, Little Rock, Arkansas; and Department of Ophthalmology and Visual Sciences (CAS), University of British Columbia, Vancouver, British Columbia, Canada. The authors report no conflicts of interest. Address correspondence to Paul H. Phillips, MD, Department of Ophthalmology, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Jones Eye Institute, #1 Children's Way, Slot 111, Little Rock, AR 72202; E-mail: [e-mail] Phillips and Sheldon: J Neuro-Ophthalmol 2017; 37(Suppl): S33-S40 ing; and elevated ICP with a normal cerebrospinal fluid (CSF) composition (1). Although primary PTCS most commonly occurs in adult women of childbearing age, children may be affected as well (2,3). This review will summarize recent findings of PTCS that pertain to pediatric cases (,18 years of age). Similarities between pediatric and adult PTCS will be summarized, followed by a review of recent findings that distinguish pediatric from adult cases of PTCS. In this review, primary PTCS refers to cases with an unclear etiology (IIH). Secondary PTCS refers to cases that are precipitated by an identifiable cause. PSEUDOTUMOR CEREBRI SYNDROME: SIMILARITIES BETWEEN ADULT AND PEDIATRIC CASES In children and adults, papilledema (optic disc edema from elevated ICP) is the hallmark ophthalmologic finding of PTCS, although Friedman et al (1) published revised diagnostic criteria for adults and children that incorporate the rare cases that occur without papilledema (Table 1). At onset, papilledema often spares central visual acuity and color vision and is typically bilateral. Visual field testing shows an enlarged blind spot and peripheral deficits, such as constriction, arcuate defects, and nasal steps (4). Clinical symptoms and signs in children that are similar to adults include headache, nausea, vomiting, transient visual obscurations, diplopia, tinnitus, neck stiffness, papilledema, and cranial nerve deficits (2,4). The differential diagnosis consists of intracranial mass lesions, meningitis, and cerebrospinal drainage abnormalities such as hydrocephalus and venous sinus thrombosis. Diagnostic evaluation typically includes contrast-enhanced MRI of the brain and lumbar puncture with measurement of opening CSF pressure and CSF composition analysis for cells, protein, glucose, gram stain, and culture (1,2). Magnetic resonance venography (MRV) is recommended for atypical cases to detect venous sinus thrombosis (1,2). Similar to adults, children are at risk for permanent visual loss. Gospe et al (5) showed that 19% of 31 pediatric IIH patients developed permanent visual acuity or visual S33 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Diagnostic criteria for pseudotumor cerebri syndrome 1. Required for diagnosis of pseudotumor cerebri syndrome* A. Papilledema B. Normal neurologic examination except for cranial nerve abnormalities C. Neuroimaging: normal brain parenchyma without evidence of hydrocephalus, mass, or structural lesion and no abnormal meningeal enhancement on MRI, with and without gadolinium, for typical patients (female and obese), and MRI, with and without gadolinium, and magnetic resonance venography for others; if MRI is unavailable or contraindicated, contrastenhanced computed tomography may be used D. Normal CSF composition E. Elevated lumbar puncture opening pressure ($250 mm CSF in adults and $280 mm CSF in children [250 mm CSF if the child is not sedated and not obese]) in a properly performed lumbar puncture 2. Diagnosis of pseudotumor cerebri syndrome without papilledema In the absence of papilledema, a diagnosis of pseudotumor cerebri syndrome can be made if B-E from above are satisfied, and in addition, the patient has a unilateral or bilateral abducens nerve palsy In the absence of papilledema or sixth nerve palsy, a diagnosis of pseudotumor cerebri syndrome can be suggested but not made if B-E from above are satisfied, and in addition, at least 3 of the following neuroimaging criteria are satisfied: i. Empty sella ii. Flattening of the posterior aspect of the globe iii. Distention of the perioptic subarachnoid space with or without a tortuous optic nerve iv. Transverse venous sinus stenosis Reprinted from (1) with permission. *A diagnosis of pseudotumor cerebri syndrome is definite if the patient fulfills criteria A-E. The diagnosis is considered probable if criteria A-D are met, but the measured cerebrospinal fluid (CSF) pressure is lower than specified for a definite diagnosis. field loss. In another series of pediatric cases, 33% had optic atrophy and 17% had permanent residual visual field deficits (4). Ideally, automated visual fields and visual acuity are monitored. Treatment consists of discontinuation of associated medications if possible, weight loss in overweight patients, and medications such as acetazolamide and topiramate (2). Surgery such as optic nerve sheath fenestration and shunting procedures is reserved for patients who do not respond to medications or present with severe visual deficits (6). PSEUDOTUMOR CEREBRI SYNDROME: FACTORS UNIQUE TO PEDIATRIC CASES Demographics Patients with primary PTCS are often obese women of childbearing age (mean age: 27 years) (7). However, children with primary PTCS have an equal sex distribution and less frequent obesity compared with adults (2,4,8). These demographics are instrumental in determining what constitutes a pediatric case. Although many studies define pediatric patients as less than 18 years of age, it seems that puberty is the important factor that separates adult from pediatric cases (2). This is demonstrated in the study by Balcer and colleagues (9) that analyzed 45 consecutive cases of IIH with precise definitions of obesity. The data clearly show that children older than 12 years tend to be obese females and children younger than 12 years have less frequent obesity and equal sex distribution, supporting the concept that puberty is the important factor separating adult from pediatric cases. S34 In a multicenter, international study, Sheldon et al (10) used updated pediatric-specific measurements of weight status and evaluated anthropometric features of pediatric IIH. This study identified 3 subgroups: 1) a young cohort (less than approximately 7 years of age in girls and less than 8.5 years of age in boys), of normal height and weight, compared with age- and sex-based reference standards; 2) an early adolescent cohort, typically overweight and taller than age- and sex-matched reference standards; and 3) a late adolescent cohort, typically obese and of normal height, compared with age- and sex-matched reference standards (Fig. 1) (Table 2). Although further studies are required to evaluate whether these subgroups exist on a clinical continuum or represent distinct entities, identifying these subgroups may provide additional insights into the pathogenesis of this condition. Pathophysiology The pathophysiology of pediatric PTCS is complex. In primary PTCS, there may be distinct driving factors, determined by the age, sex, and weight status of the child. In young children, factors other than adiposity seem to contribute to the disease. In early and late adolescence, adiposity is clearly associated with primary PTCS. Pediatric adiposity has complex pathophysiology and includes potential contributions from alterations in growth hormone and gonadal hormones, factors also known to play a role in secondary PTCS (11,12). Salpietro and colleagues (11) have developed a coherent neuroendocrine model of PTCS and with further support from a combined retrospective and prospective study, suggest that the mineralocorticoid pathway, acting through aldosterone, may help explain how Phillips and Sheldon: J Neuro-Ophthalmol 2017; 37(Suppl): S33-S40 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution deficiency within the CSF that through the activities of the enzyme complex of 11-b-hydroxysteroid dehydrogenase type 1 and type 2 act within the choroid plexus to alter CSF production (13,14). Ultimately, abnormal regulation of CSF production may underpin pediatric PTCS. Margeta et al (15) showed that younger, prepubertal children (ages ,13 years) with PTCS often had low CSF protein concentration in contrast to CSF analysis in pubertal children with PTCS. They suggested that increased production of CSF may be responsible for low CSF protein concentration through a dilution effect. Thus, increased CSF production may play a role in the pathophysiology of PTCS, specifically in the prepubertal population. Clinical Symptoms and Signs FIG. 1. Three demographic subgroups of pediatric idiopathic intracranial hypertension: 1) a young cohort (less than approximately 7 years of age in girls and less than 8.5 years in boys) of normal height and weight, compared with age- and sex-based reference standards; 2) an early adolescent cohort, typically overweight and taller than ageand sex-matched reference standards; and 3) a late adolescent cohort, obese and of normal height compared with age- and sex-based reference standards. BMI, body mass index. hypervitaminosis A, pediatric obesity, and recombinant growth hormone trigger PTCS. Other authors have suggested that the pathophysiology of PTCS involves alterations in glucocorticoid metabolism (13). Indeed, withdrawal of chronic steroid use can trigger secondary PTCS. This process may lead to a relative local cortisol Clinical symptoms include headache, nausea, vomiting, tinnitus, neck stiffness, transient visual obscurations, decreased vision, and diplopia (2). As young children may not articulate their symptoms, they may present with less specific symptoms. Parents may describe that the child is irritable. Asymptomatic children may present with ocular misalignment or papilledema detected on a routine examination (16). Children with PTCS have a higher frequency of ocular motility dysfunction compared with adults (2). Sixth nerve palsy is most common, affecting as many as 40% of patients (2,4). However, other ocular motility deficits have often been reported, including third and fourth nerve palsies, skew deviation, comitant esotropia, and complete ophthalmoparesis (2,4,17-23). It is important to document resolution of the ocular motility deficits with normalization of the ICP before attributing one of these less common ocular motility findings to PTCS. Similar to adults, papilledema is the hallmark ophthalmologic sign of PTCS in children. However, it is important TABLE 2. Anthropometric features of pediatric IIH BMI Z-score Height Z-score Young Early Adolescents Late Adolescents ,7 yrs (F) ,8.5 yrs (M) F: 0.41 ± 1.50 M: 0.42 ± 1.50 F: 0.46 ± 1.65 M: 0.22 ± 1.28 7- to 12.5-year M and F Older than 12.5 yrs F: 1.54 ± 1.34 M: 1.78 ± 0.76 F: 0.62 ± 1.39* M: 0.75 ± 1.37* F: 1.89 ± 0.73 M: 1.85 ± 0.99 F: 20.09 ± 1.14 M: 20.10 ± 1.37 Body mass index (BMI) Z-score and height Z-scores in subgroups of pediatric IIH. In both male and female subjects with pediatric IIH, BMI Z-scores increase in older age categories. In female and male subjects with pediatric IIH, only height Z-scores measured in the early adolescent categories were higher than the age- and gender-matched hypothesized values. Cut-offs for young, early adolescents, or late adolescents were empirically determined and based on the relationship between BMI Z-score and age at diagnosis of IIH (10). In the pediatric population, definitions of "overweight" and "obese" are not defined by absolute BMI, as this varies with age. Rather, the U.S. Centers for disease control use percentiles or Z-scores, with Z-scores = 0.00 representing the hypothesized mean (age- and sex-matched), BMI Z-scores .1.04 indicating overweight status while Z-scores .1.64 indicating obese status. Data are reported as a mean ± SD. *Statistical comparisons used 1-way t test analyses to compare mean Z-scores against a hypothesized mean Z-score of 0.00 (e.g., age- and sex-matched normative data). In female subjects, P = 0.28 in those ,7 years, P = 0.004 in those 7-12.5 years, and P = 0.45 in those $12.5 years. In male subjects, P = 0.35 in subjects ,8.5 years, P = 0.03 in subjects 8.5-12.5 years, and P = 0.71 in subjects $12.5 years. F, female; IIH, idiopathic intracranial hypertension; M, male. Phillips and Sheldon: J Neuro-Ophthalmol 2017; 37(Suppl): S33-S40 S35 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution to distinguish papilledema from pseudopapilledema. This is particularly challenging in children as optic disc drusen, if present, are often buried and poor cooperation during the ophthalmologic examination may preclude an accurate assessment of the optic disc. Kovarik et al (24) showed that among 34 children referred for evaluation of suspected papilledema, 26 actually had pseudopapilledema. Only 2 of these 34 children were ultimately diagnosed with papilledema. Similarly, Liu et al (25) showed that among 52 children referred with a diagnosis of PTCS and/or papilledema, 26 actually had pseudopapilledema. Among the 26 children with pseudopapilledema, 19 had MRI, 9 had computed tomography (CT), 14 had lumbar punctures, and 12 were being treated with medications before referral. These studies emphasize the necessity of an accurate evaluation of the optic disc to avoid overdiagnosis of PTCS leading to inappropriate diagnostic testing and treatment (24-26). Noninvasive ancillary testing such as B-scan ultrasonography, autofluorescence fundus photography, and CT may show buried drusen and facilitate the distinction of pseudopapilledema from papilledema (27). B-scan ultrasonography is inexpensive and likely the most sensitive method for the detection of optic disc drusen in children and adults (27). CT is less desirable secondary to radiation exposure. Fluorescein angiography will stain optic disc drusen and show diffuse disc leakage with true papilledema (28). However, obtaining intravenous access for fluorescein injection may be difficult in young children. Optical coherence tomography (OCT) may differentiate true papilledema from pseudopapilledema with buried drusen in children and adults (29). In eyes with papilledema, OCT shows increased peripapillary retinal nerve fiber layer (RNFL) thickness, an inward deflection of the peripapillary Bruch membrane layer toward the vitreous, and a smooth contour of the peripapillary subretinal space (29- 33). Conversely, in eyes with optic disc drusen, OCT shows normal peripapillary RNFL thickness, no inward deflection of Bruch membrane layer, and an irregular contour of the peripapillary subretinal space (32,34). In addition, OCT may enable direct visualization of buried disc drusen (35). Merchant et al (36) showed that enhanced depth imaging OCT detected optic disc drusen with greater sensitivity compared with B-scan ultrasonography. Alternately, several investigators have found that OCT is not reliable in distinguishing mild papilledema from pseudopapilledema (37,38). Karam and Hedges (37) showed that although adult and pediatric patients (age range: 6-35 years) with mild papilledema had greater RNFL thickness than those with pseudopapilledema, the differences were not statistically significant. Similarly, Kulkarni et al (38) showed that OCT was not clinically reliable in differentiating buried optic disc drusen from mild papilledema in children and adults. Quantitatively, OCT showed no significant difference in RNFL thickness between optic discs with buried drusen and those with mild papilledema. Qualitatively, OCT S36 showed focal hyperreflective areas underneath the optic nerve that mimicked disc drusen in many eyes with papilledema. Conversely, OCT did not detect focal hyperreflective masses typical of optic disc drusen in many eyes with buried optic disc drusen. The accuracy of 5 trained clinicians using OCT alone for the diagnosis of optic disc drusen varied from 50% to 64%. Kulkarni et al (38) concluded that B-scan ultrasonography is still the best modality to distinguish mild papilledema from buried optic disc drusen. Diagnostic Evaluation Brain MRI with and without contrast is indicated to rule out hydrocephalus, mass, other structural lesions, and abnormal meningeal enhancement (1,2). MRV is warranted for atypical cases to detect venous sinus thrombosis although some clinicians obtain MRV in all pediatric patients suspected of having PTCS. CT with contrast is obtained if MRI is contraindicated or unavailable but is less desirable secondary to decreased sensitivity for intracranial lesions such as venous sinus thrombosis and associated radiation exposure (Table 1). The primary role of MRI in the evaluation of patients with suspected PTCS is to exclude other causes of elevated ICP. However, Brodsky et al (39) described MRI findings in patients with PTCS that occur secondary to increased ICP. Among their series of 20 patients (including 4 children) with PTCS, MRI disclosed flattening of the posterior sclera in 80%, enhancement of the prelaminar optic nerve in 50%, distention of the perioptic subarachnoid space in 45%, vertical tortuosity of the orbital optic nerve in 40%, intraocular protrusion of the prelaminar optic nerve in 30%, and an empty sella in 70%. Control patients rarely had these neuroimaging signs (#5%). Gorkem et al (40) also showed that these MRI signs were reliable diagnostic markers of PTCS in pediatric patients. In their retrospective analysis of 25 pediatric patients (median age 12 years, range: 1-17 years), MRI showed enlargement of the optic nerve sheath in 88%, posterior globe flattening in 56%, intraocular protrusion of the optic nerve in 40%, horizontal tortuosity of the optic nerve in 68%, and decreased pituitary gland size in 64%. These findings were not as prevalent among 30 control pediatric patients ,17 years of age. Other investigators have reported similar MRI signs of elevated ICP in children with PTCS (41-45). Additional MRI signs of PTCS include cerebellar tonsillar herniation, meningoceles and meningoencephaloceles, spontaneous CSF leaks, and venous sinus stenosis (46). Lumbar puncture is indicated to determine ICP and evaluate CSF composition. The definition of elevated ICP in pediatric patients has been revised (47). In adults, an ICP greater than 25 cm H2O is the criterion for abnormal elevation, and for many years, this was used for children as well (2). However, Avery and colleagues (47) prospectively evaluated 197 children between 1 and 18 years of age undergoing lumbar puncture. These children had no Phillips and Sheldon: J Neuro-Ophthalmol 2017; 37(Suppl): S33-S40 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution medications or medical conditions known to alter ICP. It was shown that an ICP greater than 28 cm H2O exceeded the 90th percentile among these children and suggested that this value should define elevated ICP in this age range. ICP did not correlate with age among these pediatric patients. However, ICP increased with obesity and sedation. Among nonobese, nonsedated children, an ICP greater than 25 cm H2O exceeded the 90th percentile and should be the value that defines abnormal ICP elevation in this subgroup. Secondary Pseudotumor Cerebri Syndrome in Children Primary PTCS refers to cases with an uncertain etiology (1). Secondary PTCS refers to cases that are precipitated by an identifiable cause. Friedman et al (1) published a revised classification scheme of PTCS that incorporates primary and secondary cases (Table 3). Secondary PTCS seems to be more common in children compared with adults accounting for 53%-78% of pediatric cases (4,48,49). Precipitating conditions include medications such as antibiotics (tetracycline, minocycline, and nalidixic acid), vitamin A derivatives, vitamin A intoxication, growth hormone supplementation, and withdrawal from chronic steroid use (50). Other associated conditions include anemia and Down syndrome (Table 3) (50,51). In a retrospective review of pediatric patients with secondary PTCS, Paley et al (50) showed that tetracycline-class antibiotics account for the majority of cases. Patients on these types of antibiotics did not differ in clinical presentation or weight compared to patients with primary pediatric PTCS. Indeed, pediatric patients with secondary PTCS were mid-adolescence and overweight. The possibility remains that factors precipitating secondary PTCS may aggravate an underlying predisposition to the development of PTCS. Currently, it remains important to address weight status as a potential risk factor for PTCS in both primary and secondary PTCS. Lessons From the Idiopathic Intracranial Hypertension Treatment Trial The recent Idiopathic Intracranial Hypertension Treatment Trial (IIHTT), although limited to adults, had important findings applicable to pediatric cases, especially postpubertal patients, who appear to be similar to adults (52). This was a multicenter, randomized, controlled trial in which 86 patients were treated with acetazolamide and diet, and 79 patients in the control group were treated with diet only. The endpoint was the Humphrey visual field (HVF) 24-2 perimetric mean deviation (PMD) after 6 months. Acetazolamide treatment improved HVF 24-2 PMD as well as quality of life scores, papilledema grade, and CSF pressure (52-54). Decreased visual acuity or marked papilledema at presentation was associated with worse outcomes, suggesting Phillips and Sheldon: J Neuro-Ophthalmol 2017; 37(Suppl): S33-S40 TABLE 3. Pseudotumor cerebri syndrome Primary pseudotumor cerebri Idiopathic intracranial hypertension Includes patients with obesity, recent weight gain, polycystic ovarian syndrome, and thin children Secondary pseudotumor cerebri Cerebral venous abnormalities Cerebral venous sinus thrombosis Bilateral jugular vein thrombosis or surgical ligation Middle ear or mastoid infection Increased right heart pressure Superior vena cava syndrome Arteriovenous fistulas Decreased cerebrospinal fluid absorption from previous intracranial infection or subarachnoid hemorrhage Hypercoagulable states Medications and exposures Antibiotics Tetracycline, minocycline, doxycycline, nalidixic acid, sulfa drugs Vitamin A and retinoids Hypervitaminosis A, isotretinoin, all-trans retinoic acid for promyelocytic leukemia, excessive liver ingestion Hormones Human growth hormone, thyroxine (in children), leuprorelin acetate, levonorgestrel (Norplant system), anabolic steroids Withdrawal from chronic corticosteroids Lithium Chlordecone Medical conditions Endocrine disorders Addison disease Hypoparathyroidism Hypercapnia Sleep apnea Pickwickian syndrome Anemia Renal failure Turner syndrome Down syndrome Adapted from (1). that patients with these findings should be monitored and treated aggressively (55). The association of severe papilledema at presentation with permanent vision loss has been described in pediatric patients as well (5). Monitoring of Visual Function One of the challenges in managing children with PTCS is monitoring visual function. Automated visual fields, the primary method used in adults, are not feasible in many young children. Decreased visual acuity and color vision, although important, are late findings of papilledema. In addition, decreased visual acuity alone cannot distinguish reversible visual impairment due to retinal changes from S37 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution permanent visual loss due to optic neuropathy. The optic discs can be monitored for the degree of disc edema and the appearance of disc pallor. However, evaluation of disc appearance is subjective and often lags behind visual changes and is, therefore, not ideal (56). Visual evoked potentials (VEPs) have been used to monitor vision in children with craniosynostosis (57-59). However, obtaining VEPs may be technically difficult, and the reliability of VEPs in monitoring vision in PTCS is controversial (60,61). OCT is a promising, noninvasive test that may facilitate the management of children with PTCS (29). Chen (29) described 3 ways in which OCT contributes to the care of patients with PTCS. First, OCT may be used to distinguish papilledema from pseudopapilledema and detect optic disc drusen. Second, structural changes on OCT can be used as a surrogate to monitor optic nerve function and ICP. However, the optimal OCT parameter that correlates with optic nerve function and ICP remains to be determined. In adult and pediatric patients, OCT of papilledema shows increased peripapillary retinal nerve fiber layer (pRNFL) thickness and inward deflection of Bruch membrane (29,30,62-68). Unfortunately, focusing exclusively on the pRNFL as a reflection of optic nerve function and ICP has potential pitfalls. A progressive decrease in pRNFL thickness may reflect successful reduction of ICP and improvement of papilledema. Alternatively, progressive reduction of the pRNFL thickness may reflect worsening of optic nerve function from axonal death that may occur with severe or chronic papilledema. Focusing on the deflection of Bruch membrane may provide a more accurate assessment of papilledema and ICP (65). OCT measurement of the macular ganglion cell layer-inner plexiform layer (GCL-IPL) thickness in conjunction with the pRNFL thickness may enable more reliable assessment of papilledema and ICP (29). Progressive reduction of the pRNFL thickness with stable macular GCL-IPL layer thickness suggests successful treatment with reduction of ICP and papilledema. Conversely, progressive, simultaneous reduction of pRNFL and macular GCL-IPL thickness suggests worsening optic neuropathy from chronic or severe papilledema. The two-week time lag between optic nerve damage and reduction of the macular GCL-IPL layer limits the utility of this finding on a single examination (69). Third, OCT findings may distinguish visual loss from outer retinal changes vs. optic neuropathy. Chen et al (70) retrospectively analyzed OCT findings in 31 adult and pediatric PTCS patients with a best-corrected visual acuity less than or equal to 20/25, 83% of whom had severe papilledema. Patients with OCT findings limited to the outer retina, such as subretinal fluid, photoreceptor disruption, peripapillary choroidal neovascularization, and chorioretinal folds, often had reversible visual loss. However, patients with a macular GCL-IPL thickness of #70 mm at presentation or progressive thinning of this layer $10 mm within 3 weeks of presentation often had irreversible visual loss, presumably from optic nerve damage. Thus, the degree S38 of irreversible visual loss from optic neuropathy was reflected by macular GCL-IPL thickness. Chen et al (70) suggested that the OCT signs of optic neuropathy can identify patients who require aggressive treatment to preserve vision. The OCT Substudy Committee for the IIHTT showed that OCT measurements of pRNFL thickness, total retinal thickness, and optic nerve head volume correlated with the degree of papilledema and ICP at presentation (30). At the 6-month follow-up examination, the patients randomized to acetazolamide treatment had greater reduction than the control group in all these OCT parameters (68). The treatment and control groups showed minor progressive retinal ganglion cell layer (RGCL) thinning. None of the OCT parameters had a direct correlation with visual function, either at presentation or during follow-up examinations. However, the 14 eyes with an RGCL thickness ,fifth percentile had worse visual field deficits compared with the remainder of study eyes with RGCL thickness $ the fifth percentile. Unlike the study by Chen et al (70), the IIHTT only included adult patients with mild visual loss. However, the patients analyzed by Chen et al (70) included pediatric cases and had more severe visual loss with reduced visual acuity and severe papilledema. CONCLUSION PTCS in young children has a distinct demographic profile as evidenced by an equal gender distribution and less frequent obesity compared with adult patients. The role of puberty in the pathophysiology of pediatric PTCS remains to be determined. Pediatric cases frequently have identifiable associated conditions (secondary PTCS). MRI of pediatric patients with PTCS shows findings of elevated ICP, similar to that of adult patients. The new criteria for an elevated ICP in pediatric cases ,18 years old is greater than 25 cm H2O in nonobese cases without sedation, and greater than 28 cm H2O in the remainder. OCT may facilitate the identification of pseudopapilledema and provide additional parameters to monitor in children with PTCS who are unable to perform visual fields. However, the precise role of OCT remains to be determined. REFERENCES 1. Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013;81:1159-1165. 2. Rangwala LM, Liu GT. Pediatric idiopathic intracranial hypertension. Surv Ophthalmol. 2007;52:597-617. 3. Phillips PH. Pediatric pseudotumor cerebri. Int Ophthalmol Clin. 2012;52:51-59. 4. Phillips PH, Repka MX, Lambert SR. Pseudotumor cerebri in children. J AAPOS. 1998;2:33-38. 5. Gospe SM, Bhatti MT, El-Dairi MA. 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