Major ReviewPediatric Idiopathic Intracranial Hypertension
Introduction
Idiopathic intracranial hypertension (IIH) is a condition defined by elevated intracranial pressure but no clinical, laboratory, or radiographic evidence of responsible infection, vascular abnormality, space occupying lesion, or hydrocephalus.57 Simmons Lessell's review of IIH in children,107 published in Survey of Ophthalmology in 1992, provided a general overview, protocol for diagnosis, and review of conditions associated with this disorder in the pediatric age group. Since then, however, further delineation of the demographics of children with IIH, recognition of additional cases with reversible cranial nerve palsies, new etiologies and associations, and updated management strategies have been described in the literature. In light of these developments, we consider it important to provide an updated review. We plan to focus specifically on advances since 1992, with the goal of supplementing ophthalmologists' current fund of knowledge regarding pediatric IIH and its diagnosis and management. Finally, our review has prompted us to propose criteria for the diagnosis of pediatric IIH.
Because IIH is the preferred term, a brief nosological discussion is warranted. A multitude of terms, including “serous meningitis,” “otitic hydrocephalus,” “angioneurotic hydrocephalus,” “meningeal hypertension,” “hypertensive meningeal hydrops,” “pseudotumor cerebri,” and “benign intracranial hypertension” have been used to describe the syndrome.9 Initially, “pseudotumor cerebri” was preferred because the patient's presenting symptoms were consistent with those of a cerebral mass. Later, because the mechanism of the disease seemed to rely on increased intracranial pressure, “intracranial hypertension” was favored in the name. Although initially favored, the adjective “benign” was deemed unsuitable because permanent vision loss, a known complication, could hardly be associated with a benign disease process. For these reasons, idiopathic intracranial hypertension (IIH) became the most favored term.146, 158 We should point out, however, that we do not believe that the disease is truly idiopathic. Although the exact mechanism remains elusive, there are several hypotheses regarding the possible etiologies. As a result, we shall use prudently the name “idiopathic intracranial hypertension,” recognizing that in years to come, this term too may become outdated.
IIH's definition has evolved, and currently the modified Dandy criteria must be met as a prerequisite for adult diagnosis.168, 191 With advances in neuroimaging and recognition of secondary causes, the criteria have been updated to include: 1) general signs and symptoms of generalized ICP or papilledema, 2) elevated cerebrospinal fluid pressure (greater than 250 mm H20), measured in a lateral decubitus position, with normal composition, 3) no evidence of hydrocephalus, mass, structural, or vascular lesion on MRI or contrast-enhanced CT for typical patients, and MRI and MR venography for all others, and 4) no other identified cause of intracranial hypertension.57 However, no specific diagnostic criteria for pediatric IIH currently exist. We believe that as our understanding of pediatric IIH and its demographics and clinical manifestations has evolved, the current criteria warrant revision as they may inappropriately exclude some cases and inappropriately include others.
The pathogenesis of IIH is still not completely understood. Although brain edema, increased cerebral blood volume, and increased cerebrospinal fluid secretion have been postulated to be associated with the condition,82, 170 most attention has been focused on increased venous sinus pressure and decreased cerebrospinal fluid absorption. Decreased absorption at the level of the arachnoid villi has been demonstrated by radioisotope cisternography, although it is unclear whether it is secondary to compression of the arachnoid villi or by elevated intracranial pressure itself.113 Karahalios et al have suggested that elevated intracranial venous pressure is a universal mechanism of all IIH, both adult and pediatric.86 Elevated venous pressure may increase resistance to CSF absorption, subsequently causing the cerebrospinal pressure to increase as well. Others have refuted this theory by suggesting that because venous sinus stenoses reverse with correction of elevated pressure, elevated venous pressure could be an effect, rather than a cause, of intracranial pressure.11, 73, 124 In another study, the authors argued that reduced venous sinus pulsatility may be a marker for IIH secondarily to raised venous pressure.12 Unfortunately most of the studies regarding pathogenesis of IIH have studied adults; similar studies in children have not been done.
A hereditary basis has been suggested for IIH in several reports.60, 61, 87, 160 The cases include homozygous female twins,60 heterozygous female twins,61 siblings,87 mother–daughter pairs,87 mother–son pairs,160 and cousins.87 Unfortunately, genetic linkage analyses are lacking, and the genetic mechanism by which the disorder might be transmitted is far from clear.
Section snippets
Demographics and Epidemiology
Idiopathic intracranial hypertension can occur at any age in childhood, although IIH in infants is uncommon125 and in neonates is exceedingly rare.
The incidence of idiopathic intracranial hypertension in the overall population is 1 out of 100,000.64 However, recent studies have elucidated demographic trends in pediatric IIH.
Presenting Symptoms
The course of pediatric IIH varies, and a child may present hours to several years after symptoms begin. While headache, nausea, and vomiting are known classic symptoms, patients may complain of blurry vision, diplopia, and stiff neck as well.7, 142 Other reported symptoms include increasing head size, photophobia, anorexia, retro-orbital pain, lightheadedness, myalgia, head tilt,7, 142 as well as preferring a knee–chest position.176 Patients with IIH have normal levels of consciousness and
Etiologies/Associated Conditions
Although secondary causes for IIH are less commonly identified in adults (most of whom are obese), 53.2–77.7% of pediatric cases have been associated with identifiable conditions,164, 202 the most common of which include endocrine abnormalities, drugs, and infections. Previously recorded associated causes of idiopathic intracranial hypertension in children include viral infection, hypoparathyroidism, menarche, corticosteroid withdrawal, thyroid treatment, nalidixic acid, tetracyclines, vitamin
History
Age and sex should be noted. Patients and their parents should be asked whether the child 1) had any recent weight gain, 2) took any medications which predispose to IIH such as tetracycline, chronic steroids which were then tapered, minocycline, or synthetic growth hormone, or 3) has any underlying medical conditions associated with IIH such as Addison disease or systemic lupus erythematosus. Development of secondary sexual characteristics should also be recorded. The child should be asked
Optic Nerve Imaging and Related Techniques
Ultrasonography is used frequently in our practice to help distinguish papilledema from pseudopapilledema, in particular when optic disk drusen are suspected. Some authors have suggested optical coherence tomography (OCT), by demonstrating increased retinal nerve fiber layer thickness in papilledema, can be used to make this distinction.141 However, ultrasonography can be performed rapidly, even in young, only mildly cooperative children, whereas OCT requires the patient to hold very still
Neuroimaging
Normal neuroimaging studies are mandatory before diagnosing pediatric IIH. Computed tomographic (CT) scanning was previously considered adequate to exclude ventriculomegaly or mass lesions. However, because there are conditions such as gliomatosis cerebri and cerebral venous thrombosis that can mimic pediatric IIH and may be missed by CT, it now considered suboptimal, and MRI/MRV of the brain with and without gadolinium are the studies of choice in this setting.157
Lumbar Puncture
After normal neuroimaging, a spinal tap is mandatory to measure the CSF opening pressure and to exclude meningitis. However, the parameters for spinal fluid opening pressures in younger children may be different than they are in adolescents and adults, and there are more variables. Normal values for CSF opening pressure and cell composition are well established in adults, but determination of normal CSF pressure and composition in children is challenging because of practical reasons and from
Treatment
Despite limited understanding about the cause and pathophysiology of the disease, advances in treatment have been made in the last decade. Unfortunately, there are still no randomized, controlled, double blind prospective studies of treatment of IIH in children, and therefore, treatment is empirically dictated by the level of vision loss and severity of headache. Toxic, metabolic, and nutritional causes must be promptly addressed, and weight loss must be encouraged in children who are
Outcome
As mentioned earlier, at presentation, visual acuity loss is reported in 6–20% of pediatric cases,7, 29, 142, 158, 202 and visual field loss occurs in up to 91% of cases.7, 29, 92, 158 With prompt diagnosis and medical management, most children with mild-to-moderate disk swelling and visual field defects have complete resolution of disk swelling and visual abnormalities.7 According to one author,29 pediatric IIH responds relatively rapidly to treatment, with resolution of papilledema in an
Conclusion/Diagnostic Criteria for Pediatric IIH
Our understanding of pediatric IIH has been refined since Dr. Lessell's review in 1992. Recent studies' use of rigorous methodologies and standard definitions has elucidated distinct demographic trends. Specifically, the incidence of IIH seems to be increasing among adolescent children, and within older children its clinical picture is similar to that of adult IIH. Within younger age groups there are more boys and nonobese children who may develop IIH. Although the pathogenesis of the disease
Method of Literature Search
To draft this review, a thorough Medline search of all English articles between 1992 and 2006 was conducted. Search terms included: pediatric pseudotumor cerebri, pediatric idiopathic intracranial hypertension (IIH), pediatric neoplasms, pediatric pseudotumor cerebri diagnosis, pseudotumor cerebri AND drug therapy, IIH AND drug therapy, pseudotumor cerebri AND headache, IIH AND headache, pseudotumor cerebri AND acetazolamide, IIH AND acetazolamide, pseudotumor cerebri AND corticosteroids, IIH
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The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. The authors would like to thank Drs. Laura Balcer, James Corbett, Deborah Friedman, Simmons Lessell, and Michael Wall for their extremely helpful suggestions and comments, and to Drs. Friedman and Lessell for critically reviewing the manuscript.