From the Department of Ophthalmology, Nationwide Children’s Hospital, Columbus, Ohio.
Presented as a poster at the annual meeting of the American Association for Pediatric Ophthalmology & Strabismus, April 14–18, 2010, Orlando, Florida.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to David L. Rogers, MD, Nationwide Children’s Hospital, 555 S. 18th St. Suite 4C, Columbus, OH 43205. E-mail: firstname.lastname@example.org
Increased intracranial pressure is suspected in all cases of bilateral optic nerve edema. It can occur primarily with unknown etiology or secondary to any number of causes. True idiopathic cases are defined as elevated intracranial pressure without clinical, laboratory, or radiographic evidence of an underlying infectious etiology, vascular abnormality, space-occupying lesion, or hydrocephalus.1 Elevated intracranial pressure is reported to be rare in patients with cystinosis.2,3 We describe our series of patients with cystinosis and underscore the importance of searching for signs and symptoms of increased intracranial pressure in all patients with cystinosis. We believe that all ophthalmologists who treat children and young adults with cystinosis should be aware of this vision-threatening association and propose that it may occur more often than previously reported.
A retrospective review of all patients with cystinosis at Nationwide Children’s Hospital between July 2007 and July 2009 was performed. Each patient underwent a complete eye examination including a dilated fundus examination. Visual fields were attempted in each case, but not every patient was able to complete the test due to both age and severe photophobia. A B-scan ultrasound of the optic nerve sheath was performed to measure the optic nerve sheath diameter 3 mm posterior to the lamina cribrosa. A measurement greater than 5.0 mm was considered wide. Patients with a wide optic nerve sheath diameter were referred for lumbar puncture with measurement of opening pressure. A diagnosis of increased intracranial pressure was only made after lumbar puncture with opening pressure was performed. The study was approved by the Institutional Review Board and was conducted in accordance with the Health Insurance Portability and Accountability Act guidelines.
A total of 6 patients were identified with cystinosis; ages ranged from 7 to 22 years. There were three males and three females. Three patients had secondary increased intracranial pressure, two females and one male. Their ages ranged from 19 to 22 years.
The optic nerve evaluation of these three patients showed one patient with marked optic nerve atrophy, one patient with a normal-appearing optic nerve without edema, and one patient with papilledema. Two of these patients had a B-scan ultrasound of the optic nerve sheath diameter prior to diagnosis and both were wide, measuring greater than 5 mm. The patient with optic nerve atrophy did not have a B-scan performed.
All three patients were referred for neuroimaging and lumbar puncture with measurement of opening pressure. The patient with optic atrophy was referred for further work-up based on uncontrolled headache and optic atrophy. Subsequent neuroimaging was unremarkable and a lumbar puncture revealed an elevated opening pressure in all cases. Treatment was initiated with oral acetazolamide. All patients’ conditions were uncontrolled medically and ultimately required surgical intervention. All three patients had optic nerve sheath fenestration. One patient also required a ventriculo-peritoneal shunt placed to control headaches and persistently elevated intracranial pressure. All patients with secondary increased intracranial pressure were post-renal transplant.
We find a high rate of secondary increased intracranial pressure in patients with cystinosis. In our series, 50% of patients with cystinosis were found to have elevated intracranial pressure. By chance alone, only 1 in 10 billion patients should have both cystinosis and increased intracranial pressure.2 Two recent reports have suggested a potential correlation between increased intracranial pressure and cystinosis. The first such report was published in the pediatric literature.3 There is only one publication of a single case report in the ophthalmology literature.2
These patients have many risk factors known to cause secondary increased intracranial pressure, such as renal transplant status and growth hormone replacement. Another proposed factor is cystine crystal deposition in the meninges and arachnoid granulations that may obstruct cerebrospinal fluid outflow.4 The amount of damage to the central nervous system likely accumulates with time, placing all patients with cystinosis at risk for secondary increased intracranial pressure. In all of these cases, the precise etiology of the increased intracranial pressure is difficult to pinpoint because each patient has multiple potential causes. However, what is clear is that an alarming percentage of patients with cystinosis develop intracranial hypertension.
Dogulu et al. concluded that patients with cystinosis and increased intracranial pressure do not always demonstrate classic optic nerve pathology.3 We found this to be true in our series because one patient presented with optic nerve atrophy and another without edema. The patient with optic nerve atrophy may represent the end stage of long-standing edema and may have had edema in the past; however, this was her first evaluation in more than 6 years. The physician needs to be aware that these patients can present with atypical findings. In addition, these patients do not always exhibit classic symptoms when increased intracranial pressure is present. For example, headache is a common feature in cystinosis and can be overlooked as a symptom of intracranial hypertension.
We recommend routine eye examinations in all patients with cystinosis. We suggest this evaluation include reviewing the classic symptoms of increased intracranial pressure by inquiring about transient obscurations of vision, headache, nausea and vomiting, and pulsatile tinnitus. The examination should include assessment of visual acuity, color vision, pupils, visual fields, and a direct examination of the optic nerve. Any abnormality should prompt a work-up for increased intracranial pressure.
The absence of optic nerve edema does not rule out intracranial hypertension. Increased intracranial pressure can only be ruled out by lumbar puncture with measurement of opening pressure. In the pediatric population, obtaining a lumbar puncture can be traumatic. Because the direct examination of the optic nerve cannot be relied on in these patients, we suggest screening every patient for increased intracranial pressure by measuring the optic nerve sheath diameter using B-scan ultrasound, a technique that has been reported and used by numerous authors.5–14 This information can be used as an additional tool to guide the clinician in ordering lumbar punctures and help ensure they are not overused in the pediatric population.
We find the incidence of increased intracranial pressure to be unusually high in our population of patients with cystinosis. We emphasize the need to routinely monitor patients with cystinosis for increased intracranial pressure and advise using ultrasonography to measure optic nerve sheath diameter to evaluate these patients who are known to have both atypical optic nerve findings and atypical presenting symptoms.
- Friedman DI, Jacobson DM. Diagnostic criteria for idiopathic intracranial hypertension. Neurology. 2002;59:1492–1495.
- Parnes A, Wassner SJ, Weinstein JM. A case of intracranial hypertension and papilledema associated with nephropathic cystinosis and ocular involvement. Binocul Vis Strabismus Q. 2008;23:37–40.
- Dogulu C, Tsilou E, Rubin B, et al. Idiopathic intracranial hypertension in cystinosis. J Pediatr. 2004;145:673–678. doi:10.1016/j.jpeds.2004.06.080 [CrossRef]
- Ehrich JH, Stoeppler L, Offner G, Brodehl J. Evidence for cerebral involvement in nephropathic cystinosis. Neuropadiatrie. 1979;10:128–137. doi:10.1055/s-0028-1085319 [CrossRef]
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- Geeraerts T, Launey Y, Martin L, et al. Ultrasonography of the optic nerve sheath may be useful for detecting raised intracranial pressure after severe brain injury. Intensive Care Med. 2007;33:1704–1711. doi:10.1007/s00134-007-0797-6 [CrossRef]
- Watanabe A, Kinouchi H, Horikoshi T, Uchida M, Ishigame K. Effect of intracranial pressure on the diameter of the optic nerve sheath. J Neurosurg. 2008;109:255–258. doi:10.3171/JNS/2008/109/8/0255 [CrossRef]