study of cerebral venous sinus thrombosis in children563 found papilledema in only 18%. However, we have seen several cases of hyperacute bilateral visual loss following venous sinus thrombosis, presumably reflecting a greater or more precipitous rise in intracranial pressure in this condition.

Early investigators noted that IIH in children may develop after a symptom-free period of weeks following bacterial or viral infection. They speculated that IIH in such patients might be related to venous thrombosis in the pterygoid plexus, with propagation of the thrombus into the jugular vein (Fig. 3.5).466,540 It may also result from blockage of the arachnoid granulation with inflammatory material in predisposed individuals.

Papilledema, with or without a macular star, may be seen in children with arteriovenous malformations who have no signs of hydrocephalus or recent subarachnoid hemorrhage.183,559 In this setting, papilledema probably results from decreased CSF absorption related to high pressure in the venous sinuses caused by arterial blood shunted directly into the cerebral veins, resulting in increased cerebral venous pressure.324,568 In theory, impairment of cranial venous outflow could elevate intracranial pressure in three ways: (1) an increase in venous intracranial pressure may distend the capacitance component of the intracranial vasculature, leading to an increase in cerebral blood volume; (2) brain edema with or without venous infarction; and (3) impairment of CSF absorption due to reduction or reversal of the normal pressure gradient between the subarachnoid space and the superior sagittal sinus, which drives the bulk flow of CSF across the absorptive channels in the arachnoid villi.272 Postoperative intracranial pressure elevation associated with cerebral edema and/or hemorrhage may also complicate embolization or surgical obliteration of large arteriovenous malformations.14,576

Papilledema may develop in children with meningitis or meningoencephalitis.380 In most cases, elevated intracranial pressure is presumed to result from a secondary IIH mechanism in which abnormal CSF composition impedes the absorption of CSF through cellular or macromolecular obstruction of channels in the arachnoid villi or by involvement of the narrow supracortical subarachnoid space over the cerebral convexities.272 Meningitis can also be associated with an inflammatory optic neuritis, which should be suspected in a child with swollen discs and decreased acuity. It is difficult to distinguish inflammatory disc swelling from papilledema on the basis of clinical findings alone.380 Only when a lumbar puncture is performed and a normal opening pressure with increased protein and cellular contents is found can the diagnosis of inflammatory optic neuritis be surmised.380

An association between Chiari malformations and IIH has recently been recognized. Disturbed CSF move-

ment at the foramen magnum with increased resistance to outflow and venous flow abnormalities resulting in venous hypertension are likely to be contributory risk factors for the development of IIH in this setting.488 When both conditions coexist boney decompression of the posterior fossa can produce resolution of IIH. Other neuro-ophthalmologic symptoms and signs associated with Chiari I malformation often stabilize, improve, or resolve after suboccipital craniotomy.736,856 Conversely, decompressive surgery for Chiari 1 malformation can lead to IIH in children, although these patients tend to be asymptomatic and rarely require treatment.

IIH Secondary to Systemic Disease

Malnutrition

IIH has been recognized in malnourished children and immediately upon renourishment.10 Couch et al108 found this to be the underlying cause in 26% of children with IIH. They noted that nutritionally deprived children often display accelerated growth of the head when they are renourished. Animal models have shown malnutrition to severely impede bone growth. Refeeding presumably permits more rapid growth of the brain than the skull vault, which would explain the development of raised intracranial pressure.108 Couch et al described a transient type of “nutritional IIH” that occurs within days of starting treatment for cystic fibrosis.108 The rapid early onset and rapid resolution in this group suggests that some mechanism other than differential brain growth is occuring.108

Severe Anemia

Papilledema is a rare but well-recognized complication of severe anemia in children as well as adults.551,589 Guiseffi and colleagues216 and Ireland and colleagues259 found similar frequencies of iron deficiency anemia in adults with IIH and controls, suggesting that the purported association of iron deficiency (a common condition) with IIH may be spurious. Nevertheless, some cases of childhood IIH associated with severe iron deficiency anemia have been reported to resolve following iron supplementation.214,258

While papilledema develops in few patients with iron deficiency anemia, this finding may be more common in patients with aplastic anemia. In a review of 120 patients with aplastic anemia, Wang et al561 found unequivocal optic disc swelling in 10 patients and blurred disc margins in another 34 patients. Papilledema in patients with immune hemolytic anemia may also be due to treatment with Danazol, an attenuated androgen derived from

ethisterone. Although it has been suggested that optic disc swelling in such patients could also result from local hypoxia associated with anemia (i.e., an “energy-deficient” optic neuropathy),359 the cause of elevated intracranial pressure in the context of severe anemia is unknown. IIH can also complicate sickle cell disease.236

Addison Disease

Although many purported cases of IIH in Addison disease have been incompletely documented, the association seems to be real.115 Alexandrakis et al7 provided convincing documentation of this association in a 12-year-old boy in whom papilledema resolved following corticosteroid replacement. The findings of weakness, weight loss, hypotension, cutaneous or mucous membrane pigmentation, and abdominal symptoms should suggest this diagnosis. Another case required acetazolamide.97 In both cases, glucocorticoid and mineralocorticoid replacement produced resolution of symptoms

Bone Marrow Transplantation

Bone marrow transplantation is an increasingly successful treatment for aplastic anemia and for a variety of hematologic malignancies when chemotherapy has failed.536 Bone marrow transplantation has produced a marked improvement in long-term survival, especially in the pediatric population.536 When optic disc edema complicates bone marrow transplantation in children, it may be accompanied by vascular telangiectasias, retinal hemorrhages, lipid exudates, cotton wool spots, and macular edema.121,536 Kawase et al288 described these findings in a 4-month-old infant with acute lymphocytic leukemia, whose retinal neovascularization responded to oral prednisolone. Initially attributed to cyclosporin toxicity, the source of the optic disc swelling may be multifactorial, with graft-versus-host disease and total body irradiation also playing contributory roles.

The differential diagnostic considerations of optic disc swelling in this setting must also include an intracranial mass lesion, optic nerve infiltration or metastasis, leptomeningeal carcinomatosis, infection (e.g., cytomegalovirus), and paraneoplastic optic neuropathy.

Renal Transplantation

IIH has been reported in 4.4% of children following renal transplantation.283 This condition must be distinguished from the apoplectic anterior ischemic optic neuropathy that may produce sudden blindness in children on continuous peritoneal dialysis.319

Down Syndrome

Pseudopapilledema is the usual cause of optic disc elevation in children with Down syndrome.9,80,118 In these cases, the asymmetry in optic disc elevation in the two eyes can be quite striking. However, Esmaili and Bradfield148 reported four patients with Down syndrome and IIH. We have seen three similar cases (figure). Since children with Down syndrome may not be able to articulate symptoms of elevated intracranial pressure, papilledema must be carefully ruled out by ophthalmoscopy, and by MR imaging and lumbar puncture when necessary.

Gliomatosis Cerebri

The development of gliomatosis cerebri in a 16-year-old who presented with signs and symptoms of IIH has recently been described.581 Gliomatosis cerebri is an uncommon central nervous system primary neoplasm characterized by proliferation of neoplastic glial cells, usually astrocytes with varying degrees of malignant potential. These cells infiltrate the cerebral cortex but do not destroy its cytoarchitecture.581 Because the clinical presentation is usually neurologically nonfocal, diagnosis is often delayed. Diffuse infiltration produces increased intracranial pressure and headache, nausea, vomiting, and papilledema. In the absence of a localized intracranial mass, these signs may lead to the diagnosis of IIH.581 The diagnosis of gliomatosis cerebri should be considered in a child with IIH in whom progressive, neurologic dysfunction or MR evidence of subtle signal abnormalities develop. The prognosis of gliomatosis cerebri is dismal, with survival ranging from a few weeks to several years after diagnosis. Responsiveness to radiation therapy presumably depends on the grade of the neoplasm. New chemotherapeutic regimens are currently under investigation.581

Systemic Lupus Erythematosis

Systemic lupus erythematosis is sometimes complicated by IIH in children prior to commencement of corticosteroid therapy.343 IIH has also been described in a child as a feature of polyangiitis overlap syndrome.181 It is important to remember that IIH can occasionally be the presenting sign of systemic vasculitis, and to be attuned to associated signs of systemic vasculitis in children with IIH to enable early intervention.

Sleep Apnea

The association of sleep apnea with IIH, which is well recognized­ in adults, has rarely been reported in a child.401a Because sleep apnea produces a potentially curable form