For IIH to be diagnosed, brain scans (such as MRI) must be performed to ensure there is no underlying cause for the increased pressure around the brain
Idiopathic intracranial hypertension (IIH; also known as pseudotumor cerebri [PTC] or benign intracranial hypertension [BIH]) is characterized by signs and symptoms of increased intracranial pressure (ICP) in the absence of a space-occupying lesion.[1]
IIH mainly occurs among obese women of childbearing age.[2] Although its prevalence among the pediatric population is not known, it is not uncommon among the young. In children younger than 6 years, a specific cause of intracranial hypertension can usually be identified. Primary or idiopathic cases of intracranial hypertension are usually seen after age 11 years.
Prepubertal children with PTC have a lower incidence of obesity compared with adults, and there is no sex predilection. Similar to adult patients, children are at risk for the development of permanent visual loss.[3]
Children with IIH usually complain of headaches and may have vomiting, blurred vision, and horizontal diplopia. The headaches are diffuse, worse at night, and often aggravated by sudden movement. Less common complaints include irritability, transitory visual obscurations, dizziness, and tinnitus.
As in adults, treatment is designed to reduce ICP and preserve vision. (See Idiopathic Intracranial Hypertension.)
Although IIH has been recognized for over a century, the need remains for prospectively collected data to promote a better understanding of the etiology, risk factors, evaluative methods, and effective treatments for children with this syndrome.[4]
The precise mechanism of the ICP elevation in IIH is unknown. Factors that may play an important role in the pathogenesis include excessive cerebrospinal fluid (CSF) and extracellular edema, increased venous sinus pressure, and defective CSF absorption. There is some evidence for each of these factors in the literature, and it is likely that more than 1 mechanism is responsible.
The importance of venous sinus pressure is seen in children who develop increased ICP after thrombosis of 1 or more dural sinuses, usually secondary to otitis or mastoiditis. Studies of pediatric IIH patients have shown elevated sagittal sinus pressure, which could lead to resistance to CSF absorption at the arachnoid villi. Through radioisotope cisternography, affected patients have also been found to have a 3- to 5-fold decrease in CSF absorption.
A number of studies of IIH patients have suggested the presence of excessive “brain water” (ie, an edematous brain). Although the finding is somewhat controversial, histologic evidence of vasogenic brain edema has been observed in biopsy specimens from a small number of patients. Increased intracranial blood volume has also been shown in several studies, and excessive white matter water has been reported on magnetic resonance imaging (MRI).
Malm et al used a constant pressure infusion method to study CSF dynamics in 17 patients older than 15 years and found reduced conductance to CSF flow; however, the reduction was insufficient to explain the increase in CSF pressure.[5] No significant difference in the rate of CSF production was noted between IIH patients and control subjects. The investigators also noted that sagittal sinus pressure was elevated in more than half of their patients, which was attributed to increased brain water content causing compression of venous outflow.
Using sophisticated magnetic resonance (MR) venography, Farb et al found a high incidence of transverse and sigmoid sinus stenoses in patients with IIH as compared with control subjects.[6] Other studies indicated that increased ICP can cause a collapse of the walls of the transverse sinus, which suggests that venous sinus stenosis is a secondary phenomenon.
Hormonal influences appear to play some role in the pathogenesis of IIH. In postpubertal patients, the condition is distinctly more common among females. Obesity is a well-recognized risk factor. Childhood obesity is strongly associated with an increased risk of pediatric IIH in adolescents. The current childhood obesity epidemic is likely to lead to increased morbidity from IIH, particularly among extremely obese, white, non-Hispanic, teenage girls. Vigilant screening of these at-risk individuals may lead to earlier detection and opportunity for treatment of IIH.[7, 8, 9, 10]
Studies have suggested associations of IIH with nonspecific infections, minor head injury, withdrawal from corticosteroid therapy, vitamin A,[11] acne treatment, and certain antibiotics (eg, tetracyclines). On rare occasions, severe iron deficiency anemia, endocrinopathies, and CO2 retention have been implicated.
Of the many conditions that have been associated with IIH in children, none has been convincingly shown to be causative, except perhaps for certain medications.[12] The following medications may be associated with IIH:
Refeeding and weight gain in nutritionally deprived children (eg, children with cystic fibrosis) may be associated with IIH. Endocrine abnormalities potentially associated with IIH include adrenal dysfunction and Addison disease, hypothyroidism or hyperthyroidism, hypocalcemia due to vitamin D deficiency or hypoparathyroidism, and panhypopituitarism.
Obstructive sleep apnea has been shown to increase intracranial pressure, and proposed to be a secondary cause of intracranial hypertension.[14]
Epidemiologic studies of IIH in US children are not available. The annual incidence among all adults in the United States appears to be 0.9 per 100,000 population; that among US females, 3.5 per 100,000; and that among obese US females, 13-19 per 100,000. An incidence of 1.7 per 100,000 was reported in Libya.
IIH has a strong predilection exists for postpubertal women. Although IIH is most common among women of childbearing age, it has been reported in early infancy. Typically, a specific cause of intracranial hypertension can be identified among young children. Some studies have suggested that urban African Americans may be at increased risk.
The natural history of IIH in childhood is poorly understood. Some children respond to initial lumbar puncture alone. Visual loss can occur at any point in the disease, and no predictive factors have been reliably associated with this complication. Patient and parental education as to the seriousness of permanent visual loss should be given. Early intervention in rapidly declining visual function is crucial to improve the long-term visual outcome.
The mortality associated with IIH is no higher than that seen in the general population. The only major morbidity is visual loss. The incidence of visual loss among children with IIH is unknown. Among all patients, some degree of permanent visual loss occurs in approximately 10% of cases. In a study by Soiberman et al, pediatric patients with IIH have a favorable visual outcome in terms of both visual acuity and visual field. If there is any recurrence, it is most likely to occur during the first 18 months after diagnosis.[15]
Common signs and symptoms of idiopathic intracranial hypertension (IIH) in the young include headache, vomiting, blurred vision, and diplopia.[16, 17]
Headaches are intermittent, diffuse, and worse at night; they may awaken the child and are often aggravated by sudden movement. Visual disturbances include transient visual obscurations, blurred vision, double vision, and photophobia. Diplopia is almost always horizontal (side by side) and is secondary to paresis of cranial nerve (CN) VI (the abducens nerve). It has been estimated that up to 50% of children with IIH have CN VI dysfunction.
Other symptoms of increased intracranial pressure (ICP) include lethargy, irritability, and vomiting. Nonspecific associated symptoms include neck stiffness, tinnitus, dizziness, clumsiness, and paresthesias.
The possible association of pseudotumor cerebri and signs and symptoms suggestive of varicella infection has previously been mentioned in a few case reports. Ravid S et al have described 3 immunocompetent children with pseudotumor cerebri as the only manifestation of varicella zoster virus reactivation. They have suggested considering varicella zoster virus in children with pseudotumor cerebri, even in the absence of a history of recent varicella infection.[18]
The general medical examination may reveal signs of otitis media or mastoiditis, which raise the possibility of venous sinus thrombosis. The presence of acne vulgaris should prompt an inquiry about the possible use of retinoic acid or tetracyclines. Physical findings of adrenal or thyroid dysfunction may also be present.
The neurologic examination typically yields normal results, with the exception of papilledema and weakness of one or both of the abducens nerves. Obeid M et al reported 10-week-old monozygotic twins with cystic fibrosis, facial palsy, and increased intracranial pressure.[19] Low levels of vitamin A are associated with facial nerve paralysis and are at least partly implicated in the development of increased intracranial pressure in infants with cystic fibrosis. Other CN palsies have been reported on rare occasions.
Ophthalmoscopic (funduscopic) examination reveals optic disk nerve swelling (papilledema). The diagnosis of IIH should not be made in the absence of papilledema unless the patient has optic atrophy. Papilledema is typically bilateral but may be asymmetrical or unilateral.[12] Initially, visual acuity is usually preserved, which helps the clinician to distinguish acute papilledema from optic neuritis.
Visual field testing is useful for both examination and monitoring. Perimetry can be used to evaluate response to therapy.[20] Common field defects include enlargement of the blind spot, loss of the inferonasal portion and generalized constriction. Other defects include a variety of scotomas and altitudinal patterns of visual loss. Visual acuity assessment is helpful. Most patients will have some measurable visual loss that is often asymptomatic, usually occurs gradually, and improves with therapy. Komur et al have described coexisting optic disc drusen and idiopathic intracranial hypertension.[21]
Serial photographs of the fundus may be taken for follow-up. A related article is Anterior Segment and Fundus Photography.
The diagnosis of idiopathic intracranial hypertension (IIH) is made after other causes of increased intracranial pressure (ICP)—such as mass lesions (particularly those involving the midline [eg, medulloblastoma], and causes of recurrent or chronic headache (eg, migraine and hydrocephalus) have been excluded.
Laboratory studies should include evaluation for endocrine abnormalities if such evaluation is indicated by the history or the physical examination findings.
Magnetic resonance imaging (MRI) of the brain with magnetic resonance venography (MRV) is preferred. In children, computed tomography (CT) of the head should be avoided when possible to minimize radiation exposure. The addition of MRV should enable one to exclude thrombosis of a major venous sinus.[20] Stenosis of the transverse sinus is a common finding in IIH but is probably the result of increased ICP. Brain MRI is normal but may show relatively small ventricles. Horev et al demonstrated narrowing of the transverse sinuses in IIH patients.[22] The main finding of their study is the increase in cerebral sinuses diameter after lumbar puncture. This observation should be considered when evaluating cerebral venous sinuses after lumbar puncture. The authors have recommended a larger scale study to validate their findings.
In a study by Gerstl L et al., they suggest that the revised diagnostic criteria for IIH may be too strict, especially in children without papilledema. MRI-based measurement and venous ophthalmodynamometry are promising complementary procedures for monitoring disease progression and response to treatment.[23]
In a study from Shofty et al, pediatric patients with IIH, the optic nerve sheath diameter on MRI is significantly larger than that in healthy controls regardless of age group and sex.[24] This measurement might prove to be an auxiliary tool in the diagnosis of increased ICP in pediatric patients.
Brain imaging should be obtained before a lumbar puncture is performed. Careful measurements of opening and closing pressures should be obtained. Cerebrospinal fluid (CSF) studies yield normal results, except for an elevated opening pressure.
In the emergency department, bedside ultrasonography has been used to identify intracranial hypertension by measuring the diameter of the optic nerve sheath.[25]
Performing lumbar puncture in children can be challenging and difficult; sedation may be required. CSF pressure may be falsely elevated in a crying child. In addition, no consensus exists as to what constitutes the upper limit of normal for different age groups.[12] In their review, Soler et al[26] gave the following values:
An intracranial pressure of 280 mm water has recently been established as the upper limit of normal in children.[3]
Diurnal variations in CSF pressure are seen; therefore, the pressure measured at any given time may not reflect the peaks. CSF pressure may be normal in patients with florid papilledema. If the diagnosis of IIH is suspected, repeat lumbar puncture or prolonged pressure monitoring (ie, with a Camino catheter or lumbar pressure catheter) should be considered.
The diagnosis of IIH requires that the CSF be of normal composition with respect to cell count, protein, and glucose.
The care of patients with pseudotumor cerebri requires a multidisciplinary approach. Neurosurgical interventions are sometimes needed for diagnostic and treatment purposes. Prompt and accurate communication among specialists is necessary to ensure timely treatment and optimal outcomes.[27]
Medical therapy appeared to be successful in treating pediatric pseudotumor cerebri in most patients. However, despite adequate treatment, children can rarely experience loss of visual field and acuity; thus, prompt diagnosis and management are important.[28] Sometimes, the symptoms of idiopathic intracranial hypertension (IIH) resolve with the initial diagnostic lumbar puncture. If this occurs, no further medical treatment is required. When medical treatment is required, most children respond to medications such as steroids, acetazolamide, furosemide, or topiramate.
Surgical treatment such as optic nerve sheath fenestration, sinus stenting, and shunting procedures are indicated for children with severe headaches, visual loss, or both, despite maximal tolerated medical treatment.[3, 29]
The most serious potential complication is permanent visual loss and blindness. Low-salt diet and weight loss may be beneficial. The authors’ experience suggests that weight loss is difficult to achieve in the overweight adolescent.
Consultations with an optometrist, a neuro-ophthalmologist, and/or a pediatric neurologist may be indicated.[27] Neuro-ophthalmology follow-up with frequent assessment of visual fields is indicated.
Although IIH has been recognized for over a century, the need remains for prospectively collected data to promote a better understanding of the etiology, risk factors, evaluative methods, and effective treatments for children with this syndrome.[4]
In a study by Elder et al, data show that transverse sinus stenting, in conjunction with temporary CSF diversion, represents an appropriate treatment option in the acute setting.[30]
Acetazolamide is administered at an initial dosage of 25 mg/kg/day, which is titrated upward until a clinical response is attained (maximum, 100 mg/kg/day). Electrolyte concentrations must be monitored to evaluate for the development of hypokalemia and acidosis. If the patient remains on treatment for more than 6 months, renal ultrasonography should be ordered to look for the presence of renal calculi. If acetazolamide is ineffective, prednisone can be given at a dosage of 2 mg/kg/day for 2 weeks, followed by a 2-week taper.
Topiramate is now being widely used in the treatment of migraine and IIH in adults. Topiramate functions as a carbonic anhydrase (CA) inhibitor and appears to be efficacious in the treatment of both conditions. This medication may prove to be useful in selected children with IIH.
Repeat lumbar puncture may help in some patients, but its invasiveness and the difficulty of performing it in children make it a less than ideal medical therapy. The reduction in pressures is often only transient.
A low-salt diet and weight reduction have been shown to be helpful in adult patients. If the child is obese, weight reduction may be beneficial.
The main indications for surgical intervention to treat IIH are deterioration in vision and incapacitating headaches despite aggressive medical management. There are 2 main surgical approaches to the treatment of pediatric IIH: optic nerve sheath fenestration and CSF diversion (typically, lumboperitoneal shunting).[20] The authors prefer optic nerve fenestration to lumboperitoneal shunting.
Optic nerve sheath fenestration (ONSF) has been shown to improve visual outcome. It yields better results in patients with acutely decompensating vision and papilledema. Lumboperitoneal shunting may relieve headache and reduce ICP in patients with IIH. The long-term visual outcome of patients treated with this procedure is unknown. Complications include infection and shunt obstruction. Low-pressure headaches have also been reported to develop as a result of lumboperitoneal shunting.
There are pros and cons for doing either ONSF or CSF diversion. However, the decision for ONSF versus CSF shunting is somewhat institution- and surgeon-dependent. ONSF is preferred for patients with visual symptoms whereas shunting is reserved for patients with headache.[31]
Medications used in the treatment of idiopathic intracranial hypertension (IIH) include acetazolamide and corticosteroids.
Clinical Context: Acetazolamide is a first-line drug for treatment of IIH.
Carbonic anhydrase (CA) is an enzyme found in many tissues of the body, including the eye. CA inhibitors catalyze a reversible reaction in which carbon dioxide becomes hydrated and CA dehydrated.
Clinical Context: If acetazolamide fails to relieve symptoms of IIH, corticosteroids may be tried. Experience with prednisone in the treatment of pediatric IIH has shown that short-term use (ie, ≤ 1 month) is safe and effective.
Clinical Context: Prednisolone decreases inflammation by suppressing the production of leukotrienes and migration of polymorphonuclear leukocytes and by reducing capillary permeability. Experience has shown that short-term corticosteroid use (ie, ≤1 month) is safe and effective.
Corticosteroids agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body’s immune response to diverse stimuli.
For IIH to be diagnosed, brain scans (such as MRI) must be performed to ensure there is no underlying cause for the increased pressure around the brain
Left optic disc with moderate chronic papilledema in patient with idiopathic intracranial hypertension (pseudotumor cerebri). Paton lines (arc-shaped retinal wrinkles concentric with disc margin) are seen along temporal side of inferior pole of disc.
Right optic disc with postpapilledema optic atrophy in patient with idiopathic intracranial hypertension (pseudotumor cerebri). Diffuse pallor of disc and absence of small arterial vessels on surface are noted, with very little disc elevation. Disc margin at upper and lower poles and nasally is obscured by some residual edema in nerve fiber layer and gliosis that often persists even after all edema has resolved.
Most common early visual field defect in papilledema as optic nerve develops optic atrophy is inferior nasal defect, as shown in left eye field chart (left side of figure). Shaded area indicates defective portion of field. Note sharp line of demarcation between defective lower nasal quadrant and normal upper nasal quadrant along horizontal midline. This is characteristic of early papilledema optic atrophy and is referred to as nasal step or inferonasal step.
