|Year : 2008 | Volume
| Issue : 1 | Page : 18-24
Visual loss at presentation in children with pseudotumor cerebri
Rana Al-Senawi1, Anuradha Ganesh1, Aisha Al-Busaidi1, Amna Al-Futaisi2, Nassra Al-Habsi3, Sana Al-Zuhaibi1
1 Department of Ophthalmology, Sultan Qaboos University Hospital , Muscat, Oman
2 Department of Child Health, Sultan Qaboos University Hospital Muscat, Oman
3 Department of Ophthalmology, Al Nahda Hospital, Muscat, Oman
Department of Ophthalmology, Sultan Qaboos University Hospital, 123/ Al-Khod, Muscat
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Purpose: To describe visual loss at presentation in children with pseudotumor cerebri (PTC), and discuss mechanisms of visual loss and distinguishing features of pediatric PTC.
Materials and Methods: Two children with papilledema and visual complaints were referred for ophthalmic evaluation. Both patients underwent a detailed ophthalmic work-up.
Results: Patient 1, an 8-year-old girl, presented with a 2-week history of headache, vomiting, and visual impairment in both eyes. The child had no previous medical history. Patient 2, a 9-year-old boy, experienced sudden loss of vision in both eyes one week prior to presentation, along with severe headache and vomiting. He had undergone a renal transplantation one year back, and his current medications included cyclosporine A (CsA) and oral prednisolone. Extensive disc swelling, lipid exudation and retinal thickening in the posterior pole were observed in both patients. Lumbar puncture in both showed elevated cerebrospinal fluid pressure. Both were treated with oral acetazolamide. Patient 1 additionally received intravenous methylprednisolone followed by an oral taper. CsA was stopped in patient 2. PTC and papilledema resolved with above measures in both patients, with partial recovery of visual function.
Conclusions: PTC in children may have atypical manifestations. Visual acuity may be compromised acutely due to several factors. Patients with PTC and severe visual loss at presentation mandate an aggressive management approach. Use of intravenous steroids may be considered along with acetazolamide. Despite resolution of PTC, sequelae such as optic atrophy or macular scarring may impede eventual visual recovery. Physicians following patients on CsA need to be aware of the possible neuro-ophthalmic complications of the drug.
Keywords: Pediatric, pseudotumor cerebri, papilledema, visual loss, cyclosporin A
|How to cite this article:|
Al-Senawi R, Ganesh A, Al-Busaidi A, Al-Futaisi A, Al-Habsi N, Al-Zuhaibi S. Visual loss at presentation in children with pseudotumor cerebri. Oman J Ophthalmol 2008;1:18-24
|How to cite this URL:|
Al-Senawi R, Ganesh A, Al-Busaidi A, Al-Futaisi A, Al-Habsi N, Al-Zuhaibi S. Visual loss at presentation in children with pseudotumor cerebri. Oman J Ophthalmol [serial online] 2008 [cited 2021 Oct 19];1:18-24. Available from: https://www.ojoonline.org/text.asp?2008/1/1/18/43316
| Introduction|| |
Papilledema is a well-recognized sign of raised intracranial pressure (ICP). Its presence mandates a detailed diagnostic evaluation to determine underlying etiology and facilitate appropriate management. Central visual acuity is usually preserved in papilledema in the early stages, with impaired visual acuity usually reflecting serious macular involvement or advanced optic nerve damage, possibly irreversible. Pseudotumor cerebri (PTC) is a rare but important differential diagnosis in children presenting with papilledema, and differs in certain characteristics from adults.
| Materials and Methods|| |
Two children with papilledema and visual complaints were referred to the pediatric ophthalmology unit for ophthalmic evaluation. Both patients underwent a detailed ophthalmic and neurological work-up. Our institutional review board did not require a Research Ethics Board review for case reports.
| Results|| |
An 8-year-old girl presented with a 2-week history of fever, upper respiratory tract infection, headache, vomiting, visual impairment in both eyes (OU), and a squint in the left eye (OS). Antibiotic therapy had been commenced at a peripheral hospital, which resulted in partial resolution of symptoms. Past ocular and medical history was noncontributory. Physical examination revealed a tired looking, conscious and oriented girl. A detailed neurological examination was unremarkable. Ophthalmic examination revealed a best-corrected visual acuity of 20/100 in the right eye (OD) and 20/60 OS. Color vision tested with Ishihara chart was normal OU. Orthoptic evaluation showed intermittent esotropia, with full ocular motility. Anterior segments and pupillary size and reactions were normal. Fundus examination revealed severe papilledema with macular star OU [Figure 1a].
Enlarged blind spots were found on Goldman perimetry. Optical Coherence Tomography (OCT) showed retinal thickening and subretinal fluid in the macular area OU [Figure 1b]. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) of the brain were normal. Pattern visual evoked potentials (VEP) showed normal responses OU. Lumbar puncture revealed an elevated opening pressure of > 50 cm H 2 O. The CSF chemistry was normal and culture was negative. Complete blood count, electrolytes, autoantibody profile, viral serology and hormonal assays were tested and reported as normal. A diagnosis of primary PTC was made, and treatment commenced with oral acetazolamide 250 mg twice daily and intravenous methylprednisolone 500 mg. Five days later, examination showed reduced disc swelling and improved visual acuity. The patient was discharged on tapering doses of oral prednisolone. At the one-month follow-up visit, visual acuity was found to have improved markedly to 20/25 OD and 20/40 OS. Fundoscopy showed resolved disc edema with, pigment disturbance and residual exudates in the macula [Figure 1c].
A 9-year-old boy was referred to us with a history of sudden visual loss OU of one-week duration, along with severe headache and vomiting. There was no history of similar problems in the past. His medical history was significant for chronic renal failure and systemic hypertension, for which he had undergone renal transplantation one year back. His current medications included cyclosporine A (CsA), oral prednisolone, and antihypertensive medications. At the time of presentation and also during the episode of severe headache, his blood pressure was recorded as normal. No localizing signs were detected on neurologic examination. Ophthalmic examination showed a best-corrected visual acuity of finger counting OU. Color vision testing with Ishihara chart was abnormal OU. Orthoptic evaluation showed no squint in primary position and significantly restricted motility in all gazes with relative sparing of adduction and depression OD. Pupils were 5mm in diameter OU, and sluggishly reacting to light. No relative afferent pupillary defect was noted. Anterior segment examination was unremarkable. Fundoscopy revealed severe disc edema, tortuous and dilated blood vessels, and extensive retinal thickening, dot hemorrhages and exudation in the posterior pole [Figure 2a]. Neuroimaging was normal. A lumbar puncture revealed high opening pressure of > 40 cm H 2 O. PTC secondary to CsA was diagnosed, treatment with oral acetazolamide 250 mg twice daily was commenced, and CsA discontinued. Three days later, patient showed improvement in vision and extraocular movements. Follow-up examination one month later showed considerable reduction in symptoms. Best-corrected visual acuity was 20/200 OD and 20/60 OS. Color vision remained abnormal. Ocular movements were full. Pupillary responses were sluggish with a 1+ relative afferent defect OD. Fundoscopy revealed optic disc pallor, macular scarring and pigment disturbance [Figure 2c]. Generalized constriction of the visual fields was noted on Goldman perimetry. OCT showed residual macular thickening and subretinal fluid in the macular region. The patient remains on oral acetazolamide 250 mg bid and is under follow-up.
| Discussion|| |
PTC is diagnosed when an increased opening CSF pressure > 20 cm H 2 O is seen in a patient with symptoms and signs of raised ICP, without localizing signs (except for abducens nerve paresis), with normal CSF contents and, absence of deformity, displacement or obstruction of the ventricular system on neuroimaging (modified Dandy criteria). ,, Patients typically present with symptoms such as headache, nausea, vomiting, blurring of vision and diplopia.
PTC is a relatively rare disease in children. In contrast to adults, where there is a strong female predominance and association with obesity, PTC in prepubertal children affects boys and girls almost equally, and obesity does not seem to be a common association. , Beside papilledema, strabismus is the most common presenting feature.  Other presenting features in children include neck pain and stiffness, nausea, vomiting, and photophobia. Infants and very young children may present with irritability and sleep disturbance.  Some children have no obvious symptoms with papilledema found on routine eye examination.  An apparent lack of symptoms therefore may not rule out chronic increased ICP, especially in young children. 
PTC has been classified into primary (idiopathic intracranial hypertension) and secondary forms, with the role of associated diseases and medications being stronger in children than in adults.  The various causes of secondary PTC are summarized in [Table 1].
A hallmark physical finding in patients with PTC is papilledema. Papilledema is usually bilateral, graded according to severity from grade 0-5,  and may evolve over several days.  The raised ICP in the optic nerve sheath produces axoplasmic stasis in the optic disc with resultant disc swelling, venous congestion and exudation. Papilledema must be differentiated from other simulating conditions like optic disc drusen, congenital disc anomalies, myelinated nerve fibers, and hypermetropia. Thickening and grayness of the peripapillary nerve fiber layer (NFL), telangiectatic disc vessels, and obscuration of branch vessels at the disc margins are particularly of great help in identifying true papilledema.
Pediatric series have shown visual failure at presentation in PTC to range between 16-62%.  Transient visual obscurations, attributed to ischemia, last seconds to minutes, and have been reported in 68% of patients.  Occasionally, the sudden loss of central vision may be attributable to an episode of ischemia in an edematous optic nerve.  The severity of papilledema, particularly if pallor and cotton-wool spots (retinal NFL infarcts) at the disc are present, has been reported to have a positive correlation with the risk of visual loss.  Macular changes such as choroidal folds, hemorrhages, exudates, edema, retinal pigment epithelial disturbance, and subretinal fluid have been reported in 44% of eyes with papilledema  and usually affect visual acuity. In general, these accompany long-standing disc swelling. Macular exudation occurs secondary to leakage of proteins and lipids from disc capillaries. These exudates coalesce in the outer plexiform layer of the retina,  forming a "star-shaped figure" between the fovea and the disc (macular fan). Extension of peripapillary fluid into the macula results in macular edema, with the degree of macular thickening directly correlating with the degree of visual loss.  Macular changes in papilledema usually resolve with normalization of ICP and patients may expect improvement in visual acuity with clearing of the exudates, hemorrhage or fluid. However, when the changes are extensive, they can leave residual changes (scarring, pigment disturbance) and cause persistent visual loss after resolution of disc swelling. Chorioretinal striae and pigment mottling do not significantly decrease visual acuity.  Chronic papilledema might lead to progressive and permanent loss of nerve fibers due to secondary optic atrophy.
Visual loss of both field and acuity is thus a serious potential complication of papilledema, and requires careful monitoring and management. Perimetry, is an excellent indicator of optic nerve integrity. , The commonest visual field defect in PTC is enlargement of the blind spot, (prevalence 33-93%) and is attributed to reduced sensitivity of the peripapillary NFL due to accumulation of subretinal fluid in this region. , OCT has been shown to be a sensitive tool to detect and follow patients with PTC and visual loss due to macular changes.  The VEP is a useful tool to detect optic nerve compromise, particularly in non-verbal patients.  VEP (checkerboard pattern reversal stimulation) delays are seen in the presence of macular disease, even without evidence of optic neuropathy, though not to the extent as in the case of optic nerve disease. 
The differential diagnosis of disc swelling with macular exudation (macular star) includes optic disc edema with macular star (ODEMS) among others [Table 2] and must be kept in mind.
Medical therapy is usually successful in treating PTC. Resolution at times may also be achieved without treatment other than a diagnostic lumbar puncture. Acetazolamide is the drug of choice for initial treatment. Children tend to tolerate these medications well and can generally use it for prolonged periods without difficulty. Steroids and frusemide are used as second-line agents for short periods. Intravenous high-dose steroids have been reported to be safe and effective in treating acute, severe visual loss associated with florid papilledema of PTC in adults.  Follow up through serial lumbar punctures and periodic ophthalmic examinations serve to determine response to therapy. Surgical intervention is generally reserved for patients intolerant to medical therapy due to side effects of medications, or patients unresponsive to medical management with symptoms (headache, visual deterioration) persisting despite adequate medical therapy. Some authors advocate surgical intervention in children if they are found to have decreased visual acuity or visual fields at presentation due to difficulty in monitoring visual parameters,  or when papilledema is severe with extensive macular exudation. 
Both patients reported in this paper presented with severe visual impairment at presentation. Resolution of papilledema was achieved with use of acetazolamide. Patient 1 additionally received intravenous methylprednisolone followed by an oral taper and responded better than patient 2, who improved with acetazolamide and cessation of CsA but developed secondary optic atrophy. Further, both patients had residual changes in the macula which contributed to the lack of complete visual recovery. Despite the presentation of headache and acute loss of vision in both patients, we believe that PTC and papilledema might have been long-standing. Patient 2 had multiple risk factors for PTC, including chronic renal disease,  and long-standing therapy with steroids and cyclosporine. ,, We believe CsA could be the causative factor for PTC in this patient due to the rapid resolution of symptoms and signs within few days of stopping CsA, although it is also possible that the severity of PTC lessened during this period due to the concurrent administration of acetazolamide.
10-28% of patients who receive CsA experience some type of neurotoxic adverse event.  Apart from PTC, blurring of vision might be consequent to central serous choroidoretinopathy, serous retinal detachment, ischemic retinal microvasculopathy or cortical blindness.  Patients on long-term CsA therapy should undergo periodic screening due to their predisposition to develop ophthalmic complications.
To summarize, PTC may have different manifestations in young children, when compared to older patients, and may be associated with ophthalmic complications. Visual acuity may be compromised acutely due to several factors. Patients with PTC and severe visual loss at presentation mandate an aggressive management approach. Use of intravenous steroids must be considered along with a high dose of acetazolamide. Physicians who are following patients on systemic CsA need to be alert to the neuro-ophthalmic complications of the drug.
| Acknowledgements|| |
We gratefully acknowledge the contributions of colleagues and para-medical staff who participated in patient care. We also thank our patients and their families for their willingness and co-operation.
| References|| |
|1.||Dandy WE. Intracranial pressure without brain tumor: diagnosis and treatment. Ann Surg 1937;106:492-513. [PUBMED] [FULLTEXT]|
|2.||Lessell SS. Pediatric Pseudotumor Cerebri (Pseudotumor Cerebri). Surv Ophthalmol 1992;37:155-66. |
|3.||Wall M. Idiopathic intracranial hypertension. Neurol Clin 1991;9:73-95. [PUBMED] |
|4.||Cinciripini GS, Donahue S, Borchert MS. Pseudotumor cerebri in prepubertal pediatric patients: Characteristics, treatment and outcome. Am J Ophthalmol 1999;127:178-82. [PUBMED] [FULLTEXT]|
|5.||Al-Futaisi A, Abdwani R, Fathallah M, Al-Zakwani I, Javad H, Al-Zuhaibi S, et al. Pseudotumor cerebri in Omani children. J Pediatr Neurol 2008;6:35-8. |
|6.||Kesler A, Fattal-Valevski A. Pseudotumor Cerebri in pediatric population. J Child Neurol 2002;17:745-8. [PUBMED] |
|7.||Weig SG. Asymptomatic Pseudotumor Cerebri in young children. J Child Neurol 2002;17:239-41. [PUBMED] |
|8.||Distelmyer F, Sengler U, Messing-Juenger M, Assmann B, Mayatepek E, Rosenbaum T. Pseudotumor Cerebri as an important differential diagnosis of papilledema in children. Brain Dev 2006;28:190-5. |
|9.||Scott IU, Siatkowski RM, Eneyni M, Brodsky MC, Lam BL. Idiopathic intracranial hypertension in children and adolescents. Am J Ophthalmol 1997;124:253-5. [PUBMED] |
|10.||Frisen L. Swelling of the optic nerve head: A staging scheme. J Neurol Neurosurg Psychiatry 1982;45:13-8. |
|11.||Schirmer CM, Hedges TR 3rd. Mechanisms of visual loss in papilledema. Neurosurg Focus 2007;23:E5. |
|12.||Lim M, Kurian M, Penn A, Calver D, Lin JP. Visual failure without headache in Pseudotumor Cerebri. Arch Dis Child 2005;90:206-10. [PUBMED] [FULLTEXT]|
|13.||Giuseffi V, Wall M, Siegel PZ, Rojas PB. Symptoms and disease associations in Pseudotumor Cerebri (Pseudotumor Cerebri): A case-control study. Neurology 1991;41:239-44. [PUBMED] |
|14.||Talks SJ, Mossa F, Elston JS. The contribution of macular changes to visual loss in benign intracranial hypertension. Eye 1998;12:806-8. [PUBMED] |
|15.||Hayreh SS. Subretinal fluid in optic disc edema. Arch Ophthalmol 2002;120:673-4. [PUBMED] [FULLTEXT]|
|16.||Carter SR, Seiff SR. Macular changes in Pseudotumor Cerebri before and after optic nerve sheath fenestration. Ophthalmology 1995;102:937-41. [PUBMED] |
|17.||Corbett JJ, Jacobson DM, Mauer RC, Thompson HS. Enlargement of the blind spot caused by papilledema. Am J Ophthalmol 1988;105:261-5. [PUBMED] |
|18.||Hedges TR 3rd, Legge RH, Peli E, Yardley CJ. Retinal nerve fiber layer changes and visual field loss in Pseudotumor Cerebri. Ophthalmology 1995;102:1242-7. [PUBMED] |
|19.||Corbett JJ, Savino PJ, Thompson HS, Kansu T, Schatz NJ, Orr LS, et al. Visual loss in Pseudotumor Cerebri: Follow-up of 75 cases from 5-41 years and a profile of 14 patients with permanent, severe visual loss. Arch Neurol 1982;39:461-74. [PUBMED] |
|20.||Hoye VJ 3rd, Berrocal AM, Hedges TR 3rd, Amaro-Quireza ML. Optical coherence tomography demonstrates subretinal macular edema from papilledema. Arch Ophthalmol 2001;119:1287-90. [PUBMED] |
|21.||Sorensen PS, Trojaborg W, Gjerris F, Krogsaa B. Visual evoked potentials in pseudotumor cerebri. Arch Neurol 1985;42:150-3. |
|22.||Negishi C, Takasoh M, Fujimoto N, Tsuyama Y, Adachi-Usami E. Visual evoked potentials in relation to visual acuity in macular disease. Acta Ophthalmol Scand 2001;79:271-6. [PUBMED] [FULLTEXT]|
|23.||Liu GT, Glaser JS, Schatz NJ. High-dose Methylprednisolone and Acetazolamide for Visual loss in Pseudotumor Cerebri. Am J Ophthalmol 1994;118:88-96. [PUBMED] |
|24.||Thuente DD, Buckley EG. Pediatric optic nerve sheath decompression. Ophthalmology 2005;112:724-7. [PUBMED] [FULLTEXT]|
|25.||Friedman DI, Jacobson DM. Pseudotumor cerebri. J Neuro Ophthalmol 2004;24:138-45. |
|26.||Belson A, Alcorn DM, Yorgin PD, Fisher PG, Sarwal M. Visual loss caused by Pseudotumor Cerebri in an infant on peritoneal dialysis. Pediatr Nephrol 2001;16:216-8. [PUBMED] [FULLTEXT]|
|27.||Avery R, Jabs DA, Wingard JR, Vogelsang G, Saral R, Santos G. Optic disc edema after bone marrow transplantation: Possible role of cyclosporine toxicity. Ophthalmology 1991;98:1294-301. [PUBMED] |
|28.||Rodriguez E, Delucchi A, Cano F. Neurotoxicidal por ciclosporina A en transplante renal en ninos. Rev Med Chile 1992;120:300-3. |
|29.||Somech Raz, Doyle J. Pseudotumor Cerebri after allogenic bone marrow transplant associated with cyclosporine A use for graft-versus-host disease prophylaxis. J Pediatr Hematol Oncol 2007;29:66-8. |
|30.||Lanzetta P, Monaco P. Major ocular complications after organ transplantation. Indian J Ophthalmol 2004;52:95-7. [PUBMED] |
[Figure 1a], [Figure 1b], [Figure 1c], [Figure 2a], [Figure 2c]
[Table 1], [Table 2]