Papilledema refers to swelling of the optic nerves secondary to elevated intracranial pressure (ICP). Profound, permanent vision loss may occur in pediatric patients with papilledema because of irreversible damage to the optic nerves.1–6 The underlying etiologies for elevated ICP that may result in papilledema in children are numerous but in general there are 2 main categories: idiopathic [ie, idiopathic intracranial hypertension (IIH) or pseudotumor cerebri] and secondary causes of elevated ICP. Secondary causes of intracranial hypertension in children which may result in papilledema are myriad and include space occupying tumor, obstructive hydrocephalus from a structural anomaly (eg, aqueductal stenosis), infection, dural venous sinus thrombosis, or iatrogenic (eg, medication related). The diagnosis of papilledema is made clinically through documentation of pathologic optic nerve edema by direct examination coupled with documentation of elevated ICP through either lumbar puncture or direct measurement of ICP intracranially; when there is an etiology, such as with a space occupying tumor, which is associated with elevated ICP, direct measurement of ICP may not be necessary to establish the diagnosis of papilledema. Current limitations in the treatment of papilledema include the lack of a uniform approach toward evaluation, the absence of standardized guidelines for clinical management, and the lack of a standardized mechanism by which an interdisciplinary approach to these patients may ensue. The purpose of this review is to examine pediatric papilledema in the acute setting with respect to etiology and initial evaluation. Further, this review will propose an approach to management with an emphasis on the role of the ophthalmologist to monitor and treat for the visual morbidity associated with the presence of papilledema.
The diagnosis of papilledema requires direct examination of the optic nerve head to clarify whether or not disc edema is present and pathologic, that is, distinguishing papilledema from pseudopapilledema. This can be challenging if the optic nerve appearance is asymmetrical or when there is mild edema that is hard to distinguish from buried optic nerve head drusen or congenitally crowded optic nerves.7 Ancillary testing using B-scan ultrasonography, fundus autofluorescence, optical coherence tomography, and/or fluorescein angiography are all methods that may be utilized to distinguish pseudopapilledema from true optic nerve edema.8–11 In their prospective, comparative study of 19 children evaluating methods for distinguishing papilledema from pseudopapilledema, Chang et al9 found that fluorescein angiography was the most accurate modality among the methods described above. Although optic nerve head drusen may be apparent on computed tomography images of the orbits, and historically may have been used to identify optic nerve head drusen, computed tomography is generally avoided as a diagnostic tool in this case to limit exposure of children to radiation.
The clinical criteria that corroborate pathologic optic nerve edema include position dependent headaches, blurred vision, transient loss of vision (transient visual obscurations), diplopia (secondary to a paresis of the fourth cranial nerve or the sixth cranial nerve).1,3,4,6
Once optic disc edema is established and elevated ICP is suspected, an evaluation ensues to determine etiology. In our practice we generally recommend neuroimaging including both magnetic resonance imaging (MRI) of the brain and orbits and magnetic resonance venography (MRV) of the head. MRI allows for proper evaluation of secondary causes of elevated ICP. In the setting of IIH, MRI may highlight “soft signs” of elevated ICP including enlargement of the subarachnoid perioptic space, protrusion of the optic nerves into the vitreous cavity, or an empty sella turcica.12–14 The utility of MRV in addition to MRI for the primary evaluation of children with papilledema is not well established. Standridge and O’Brien,15 in their retrospective study of pediatric patients with papilledema, found that 11% had an occult cerebral venous thrombosis, an etiology which is not seen on standard MRI sequences and which warrants a distinct management. Importantly, these patients did not have other clinical findings which would have heralded this diagnosis. Given the possibility of occult venous sinus thrombosis and the implications for treatment, at Boston Children’s Hospital, the neuroophthalmology service includes MRV of the head as part of our initial diagnostic evaluation in pediatric patients with papilledema.
When appropriate, elevation of the ICP is confirmed through lumbar puncture if the etiology is unclear from the neuroimaging (eg, as in IIH). Historically in pediatric patients, the accepted threshold for an elevated ICP had been 20 cm H2O.16 In 2010, Avery and colleagues undertook a prospective, single institution study to establish a reference range for opening pressure using standard manometry in the lateral decubitus position for pediatric patients aged 1 year to 18 years. In this study, the authors operationally defined an elevated opening pressure as above the 90th percentile, which for this cohort was 28 cm H2O.17 This value was supported by comparison of ICP in pediatric patients with documented papilledema versus aged-matched controls.18 When the authors excluded those patients who had been sedated or who were obese, both entities of which may elevate ICP, the 90th percentile threshold was 25 cm H2O.18 A threshold of 28 cm H2O is now utilized in the revised diagnostic criteria for pseudotumor cerebri in children who have undergone a sedated lumbar puncture; in those children who are not obese and whose lumbar puncture opening pressure was obtained without sedation, the threshold of 25 cm H2O is accepted for elevated ICP.19 A subsequent prospective study validating these thresholds has not yet been performed. Although the opening pressure is an important aspect of the diagnostic criteria for pediatric IIH, clinicians must consider the presentation in its entirety, and consider treatment if there are no plausible alternative explanations for the observed optic nerve findings. Some patients may not have all of the radiographic findings to support IIH, and others may have an opening pressure which is close to the accepted threshold but does not meet it and yet the clinical presentation is consistent with IIH.20,21
At Boston Children’s Hospital, in 2011 the neuroophthalmology service developed a papilledema clinical care algorithm as part of a hospital-based focus on standardization of best clinical practices. Data from existing studies on papilledema with respect to diagnosis, etiology, and outcomes were collated and analyzed toward the development of the algorithm. The goal in proposing this guideline was to promote a more uniform approach to initial evaluation and documentation within the Department of Ophthalmology, and to codify the subsequent evaluation so as to standardize management of papilledema. The algorithm is shown in Figure 1. As new data emerge regarding papilledema and management of this condition, the clinical care guideline may be further updated. Nevertheless, we believe that having this fundamental framework has provided a successful tool toward the prevention of treatable vision loss in children at our institution.
Epidemiology and Etiology
The incidence of the acute presentation of papilledema in pediatric patients is essentially unknown. At Boston Children’s Hospital, we have undertaken several retrospective studies to determine how frequently patients with papilledema are seen in the Department of Ophthalmology. We performed 1 retrospective 11-year study which sought to identify patients below 20 years of age who had at least 1 ophthalmological examination in the Department of Ophthalmology at Boston Children’s Hospital for the diagnosis of IIH with papilledema. In this cohort, a total of 86 patients were identified which yielded a rate of ∼8 IIH patients per year during the study period (unpublished data). Separately, we conducted a retrospective 5-year study evaluating the incidence and etiology of secondary causes of pediatric papilledema in those patients who had at least 1 ophthalmological examination in the Department of Ophthalmology at Boston Children’s Hospital. We identified 84 patients with an average incidence of 17 patients per year during the study period. Of the 84 patients who were seen, the most common cause of papilledema was obstructive hydrocephalus from brain tumor in 37% of the cohort.22 The interpretation of this number must take into account the referral bias of those children who present to a large, tertiary care children’s hospital. In their prospective study of pediatric patients referred for an assessment of papilledema, Kovarik and colleagues found a much smaller percentage of patients with papilledema in their outpatient clinics. This study excluded those patients with a known central nervous system disease or other secondary causes of elevated ICP. Over a 2-year study period, 2 of 34 patients referred for possible papilledema had a confirmed diagnosis of true papilledema; the majority of referred patients had pseudopapilledema conferred by optic disc drusen.23 Although the incidence of pediatric papilledema in general has not been systematically studied, the ophthalmologist must recognize those etiologies which are associated with pediatric papilledema, initiate the appropriate diagnostic work up, and guide the long-term management of this ophthalmic finding. A familiarity with etiologies associated with pediatric papilledema is therefore important.
Etiologies of Pediatric Intracranial Hypertension and Papilledema
IIH or Pseudotumor Cerebri Syndrome
In adults, the incidence of IIH is estimated at 0.9 in 100,000 and rises to 19.3/100,000 in obese women.24 In their analysis of incidence of elevated ICP in children 18 years and younger, Gillson and colleagues evaluated a cohort in central Ohio who presented to a dedicated pediatric intracranial hypertension clinic and estimated the incidence of primary intracranial hypertension to be 0.63 per 100,000 children and secondary intracranial hypertension to be 0.33 per 100,000 children.25 In their retrospective evaluation of 203 patients under 18 years of age in the intracranial hypertension registry, Aylward et al26 found that papilledema occurred in 89.3% of patients with IIH and 78.7% of children with secondary causes of elevated ICP.
Although in adults for IIH there is an association with female sex and higher body mass index, this association does not seem to exist for prepubertal children. In their study of 40 pediatric patients with IIH at Children’s Hospital of Philadelphia, Balcer et al27 found that there was an equal distribution of female and male patients and near equal distribution of obese versus nonobese (defined as 120% ideal body weight) in patients aged 3 to 11; however in presumed postpubertal patients, age 15 to 17, all were female and 91% overweight consistent with the common adult presentation. In adults, the potential for more severe vision loss is more common in African American IIH patients but the impact of race has not been evaluated in pediatric patients.28 A recent analysis suggested that the overall health care costs for IIH patients exceeds $444 million per year given the number of hospital admissions, evaluation and treatment, and lost productivity in younger patients reflective of the burden that this process places on our families and the health care community at large.29
Secondary Causes of Papilledema
Secondary ICP elevation with papilledema may be caused and may be a presenting sign of a myriad of etiologies including but not limited to space occupying tumor, hydrocephalus, an abnormality of the cerebral spinal fluid outflow tract, dural venous sinus thrombosis, meningitis, iatrogenically induced by medication, or in association with a systemic disorder such as with craniosynostosis. The clinical care algorithm highlights the need to initiate a multidisciplinary evaluation with neurology, neurosurgery, and emergency room colleagues if the eye care team is the first to identify pathologic optic disc edema. Alternatively, if the ophthalmology team serves as a consultant, then they should emphasize the need to continue to participate in clinical care when papilledema is present.
Treatment and Management
Management is guided by the degree of visual impairment at initial presentation as determined by visual acuity assessment and visual field examination. The degree of papilledema at presentation has also been suggested to correlate with a worse visual outcome.30,31 In pediatric patients, evaluation can be complicated by an inability of the patient to participate in visual acuity testing or visual field testing and therefore the papilledema grade may be the only finding that can guide treatment. In consideration of this limitation, protocols that use alternative quantitative measures that may be used as an adjunct to the subjective assessment such as with optical coherence tomography, may be helpful in the long-term monitoring of pediatric patients.32
While historically it was believed that papilledema in children did not result in vision loss,33 this notion has been rejected. Many reports in children corroborate the potential for severe, permanent vision loss from papilledema,1–6 although the risk factors for a more fulminant course have yet to be defined. For secondary causes of papilledema, the underlying etiology is addressed by the primary team. However, the ophthalmologist should play an active role in monitoring for visual morbidity from papilledema. In some cases, although the ophthalmologist is consulted to acutely diagnose papilledema, follow-up with the eye care team may not occur and vision loss ensues. Our service stresses with the interdisciplinary team the importance of continued care by ophthalmology and incorporates follow-up in the clinical care algorithm to emphasize the continued role for the eye specialist beyond establishing the initial diagnosis of papilledema.
For papilledema, treatment is initiated with the use of ICP-lowering drugs. Acetazolamide at 15 mg/kg divided bid-tid is often the first-line medication.16 Furosemide and topiramate have also been utilized.34
For IIH, surgical treatment may be recommended when the presentation at initial diagnosis is severe; however, the threshold vision which would warrant such treatment has not been established.35 Specifically, in aggressive, fulminant presentations, neurosurgical shunting (ie, lumboperitoneal or ventriculo-peritoneal) procedures may be offered; placement of a lumbar drain to temporize the clinical course until medication may be more effective has been proposed as an alternative to a permanent neurosurgical shunting procedure.36 In the only published case series specifically looking at pediatric patients, Thuente and Buckley37 found that optic nerve sheath fenestration was an effective treatment for papilledema with excellent visual outcome, improvement of systemic symptoms, and avoidance of the morbidity of a neurosurgical procedure in all but 1 of their treated patients. A prospective comparison of each of these techniques has not been performed to date in pediatric patients.
In summary, pediatric patients with papilledema are at risk for irreversible vision loss. In the majority of cases, this is preventable with prompt diagnosis and appropriate treatment. We have developed a clinical care algorithm at our institution to standardize an approach to evaluation, provide guidelines for clinical management, and recognize the relevance of the ophthalmologist in the continued management of papilledema so as to maximize visual outcomes for our pediatric patients.
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