• Neuro-Ophthalmology

    Establishing the diagnosis

    Idiopathic intracranial hypertension (IIH) is defined as elevated intracranial pressure without clinical, radiologic, or laboratory evidence of a secondary cause. The most frequently cited incidence data for IIH in the general population of the United States is from a study by Durcan, et al,1 who reported the annual incidence as 1 in 100,000 individuals. When restricting the inclusion criteria to women aged 20–44 years who are 20% or more above their ideal bodyweight, the annual incidence in the US increases to 15–19 cases per 100,000.1 Although it has historically been described as a condition affecting obese females of childbearing age, IIH can occur in all age groups, both genders, and both obese and non-obese individuals, and is becoming more recognized in the pediatric population. 

    Nomenclature

    There has been much discussion and debate about the appropriate nomenclature to describe this condition. Historically, the condition has been referred to by terms such as meningitis serosa,2 otitic hydrocephalus,3 hypertensive meningeal hydrops,4 pseudotumor cerebri,5 benign intracranial hypertension,6 idiopathic intracranial hypertension,7 and, most recently, pseudotumor cerebri syndrome.8 With so many names, confusion and misunderstanding can occur. The more descriptive term intracranial hypertension, which is then further classified as either “idiopathic” or “secondary,” is used in this discussion. The term “idiopathic” is reserved for those cases in which known secondary causes have been excluded. The term “secondary” is used for those cases in which an underlying cause is identified. These terms are simple, descriptive, and understood by all clinicians. It is important to recognize that little is known about the pathophysiology of idiopathic intracranial hypertension (IIH). What is currently termed “idiopathic” may be termed “secondary” as the disease process becomes better understood. 

    Epidemiology 

    Demographics 

    More information is becoming available on the demographics of pediatric IIH. Current data suggests that intracranial hypertension in prepubertal children is more likely to be secondary than idiopathic in nature. Additionally, the associations with obesity and female gender do not hold true in this population.9,10 Studies also suggest that IIH is infrequent in children less than 10 years of age9 and extremely rare in infants less than 3 years old. 

    Associated Conditions

    There are myriad secondary causes of intracranial hypertension. Systemic conditions, drugs, endocrine abnormalities, and infections etiologies have all been identified as secondary causes of intracranial hypertension. The exact mechanism by which these conditions result in secondary intracranial hypertension (SIH) is not entirely understood in all cases. 

    Evaluation to establish diagnosis

    Diagnostic Criteria

    Dandy first presented diagnostic criteria for IIH without brain tumor in 1937.11 In adults, a modified set of criteria is now utilized.12 As previously mentioned, the pediatric patient with IIH is much different than the typical adult counterpart. Pediatricians and pediatric subspecialists familiar with the adult criteria frequently struggle to apply them in the pediatric population. The challenge of diagnosing IIH in the pediatric population was recently addressed by Friedman, et al.13 They proposed a modified set of criteria that includes specific recommendations for determining whether the patient’s cerebrospinal fluid (CSF) opening pressure is elevated, which is one of the most difficult issues in the pediatric population (Table 1). This proposed set of criteria is comprehensive and addresses an increasingly frequent issue of diagnosing IIH in children without papilledema. Clinicians should be cautioned against empirically dismissing the diagnosis of IIH in pediatric patients without papilledema. The diagnostic category “probable” IIH proposed by Friedman, et al. is suggested in these patients. 

    Table 1. Diagnostic criteria for pseudotumor cerebri syndrome13

    1. Required for diagnosis of pseudotumor cerebri syndrome
    1. Papilledema
    2. Normal neurologic examination except for cranial nerve abnormalities
    3. Neuroimaging: Normal brain parenchyma without evidence of hydrocephalus, mass, or structural lesion and no abnormal meningeal enhancement on MRI, with and without gadolinium, for typical patients (female and obese), and MRI, with and without gadolinium, and magnetic resonance venography for others; if MRI is unavailable or contraindicated, contrast-enhanced CT may be used
    4. Elevated lumbar puncture opening pressure (≥250 mm CSF in adults and ≥280 mm CSF in children [250 mm CSF if the child is not sedated and not obese]) in a properly performed lumbar puncture

    2. Diagnosis of pseudotumor cerebri syndrome without papilledema

    In the absence of papilledema, a diagnosis of pseudotumor cerebri syndrome can be made if B–E from above are satisfied, and in addition the patient has a unilateral or bilateral abducens nerve palsy.

    In the absence of papilledema or sixth nerve palsy, a diagnosis of pseudotumor cerebri syndrome can be suggested but not made if B–E from above are satisfied, and in addition at least 3 of the following neuroimaging criteria are satisfied:

    1. Empty sella
    2. Flattening of the posterior aspect of the globe
    3. Distention of the perioptic subarachnoid space with or without a tortuous optic nerve
    4. iv. Transverse venous sinus stenosis

    A diagnosis of pseudotumor cerebri syndrome is definite if the patient fulfills criteria A–E.

    The diagnosis is considered probable if criteria A–D are met but the measured CSF pressure is lower than specified for a definite diagnosis.

    Adapted from Friedman DI, et al, Neurology 2013.

    Clinical Presentation

    The clinical presentation of pediatric IIH includes many of the same symptoms and objective findings as IIH in the adult patient. Headache is by far the most common symptom of IIH and occurs in over 90% of cases.14 Other symptoms include neck, shoulder, or arm pain; nausea; vomiting; pulsatile tinnitus; diplopia; blurred vision; and transient obscurations of vision.15,16 Infrequently, patients may present with no suggestive symptoms at all and are only diagnosed after papilledema is identified on routine eye examination and prompts further workup.

    Evaluation

    A thorough history is imperative when assessing a child with IIH. Both the parent and child should be involved when the history is obtained, because the child’s input can be a source of valuable information. The history should be focused on clarifying the patient’s symptoms and identifying potential secondary causes. Demographic information should include the child’s age, gender, and weight. Specific questioning should address stage of puberty, recent illnesses, medication use, recent weight gain, headache, nausea, vomiting, neck and back pain, systemic illnesses, and other neurologic complaints.

    The clinical exam should focus on identifying features of IIH. Neurologic and ophthalmologic assessments are indicated. The neurologic exam should be directed at identifying any focal neurologic deficits. The ophthalmic exam should include assessing visual acuity, color vision, visual fields, extraocular movements, and a careful anatomic evaluation. Papilledema is the most important clinical finding, as it is associated with vision loss, the most feared consequence of IIH.

    Differential diagnosis

    Workup

    If intracranial hypertension is suspected, the subsequent workup should be done emergently. Initial neuroimaging, usually with computed tomography (CT) scan, should be performed, and, if the result is unremarkable, a lumbar puncture (LP) with measurement of the opening pressure should be done. Further workup should be directed at ruling out secondary causes and should be guided by the history and exam findings. The workup of any individual patient is unique. The following is therefore offered as a guide and should not be considered a comprehensive assessment approach.

    The LP can be difficult to obtain in an awake child. In many cases, this test must be performed under sedation. The preferred positioning is the lateral decubitus position. Measuring the opening pressure should be done routinely. Cerebrospinal fluid (CSF) should be removed and sent for appropriate diagnostic testing. In general, a basic cell count and cultures are done, with the addition of other tests as directed by the clinical history and exam findings. Interpreting lumbar puncture opening pressure (LPOP) results in the pediatric population is difficult due to the lack of any large-scale normative data. However, there is growing evidence in the literature that can guide the clinician in interpreting these results. Current evidence suggests that the upper limit of normal for LPOP in children between 1 and 18 years of age is 280 mm H20.17-19 Neonates have a lower threshold set at 76 mm H2O.20 However, these studies have small sample sizes, and guidelines based on age alone are problematic. One of the problems this creates is dealing with the ends of the spectrum, such as the 18-year-old patient whose LPOP is considered normal at 270 mm H2O but would be abnormal if she were 19 years old. An LPOP greater than 280 mm H2O is clearly abnormal with or without papilledema. An LPOP of 250 mm H20 may be considered abnormal if papilledema is present in conjunction with other clinical signs, and symptoms are consistent with IIH.

    Neuroimaging is required before a diagnosis of IIH can be made. In some cases, the initial workup for IIH is done emergently due to acute onset of symptoms. In this setting, a CT scan is usually done prior to an LP to rule out intracranial pathology. A normal CT scan of the brain is never adequate in making the diagnosis of IIH. Magnetic resonance imaging (MRI) of the brain, with and without gadolinium, and magnetic resonance venography (MRV) are the studies of choice to rule out known secondary causes.21

    When an initial workup suggests possible IIH, urgent neurologic and ophthalmologic evaluations are mandatory. Other testing to rule out secondary causes should be guided by the history and physical findings. 

    Patient management: treatment and follow-up

    Identifying and directing treatment

    The best approach to managing IIH is with a multidisciplinary team that at minimum includes a neurologist and an ophthalmologist. Specialists in hematology, healthy weight and nutrition, and endocrinology can be called upon as needed. A good working relationship among these specialists is essential. For simplicity, designating one specialist to manage all aspects of pharmacologic treatment will prevent confusion to the patient, parents, and other members of the medical team. The neurologist is a good choice for this management task. The ophthalmologist works closely with the neurologist to guide treatment based on the ophthalmic findings, and the neurologist manages the medications and monitors for systemic side effects and other issues. 

    Randomized clinical trials are lacking in the pediatric population, and the treatment for IIH is largely based on evidence obtained in the adult population. Lowering intracranial pressure (ICP) is the mainstay of treatment, with a purpose of preserving vision and controlling symptoms. However, identifying and directing treatment at the underlying cause cannot be overemphasized. In general, medical management is utilized first, and surgical treatment is reserved for cases in which medical therapy fails to control ICP or if visual function is threatened. Weight loss should not be neglected in patients who are overweight. One case series showed that a weight reduction of 6% can result in reversal of papilledema.22 Fortunately, most cases of pediatric IIH respond well to treatment. However, a small percentage will have some degree of permanent visual loss. 

    Emergent treatment

    Initial treatment is aimed at lowering intracranial pressure and preserving visual function. In cases were visual function is threatened due to severe papilledema, emergent neurosurgical CSF diversion may be required. However, medical management should not be delayed. A short course of high-dose oral or intravenous (IV) steroids can be used in addition to either oral or IV acetazolamide. The patient should be monitored clinically for signs of deterioration in visual function. Optic nerve sheath fenestration (ONSF) is typically reserved for cases in which acute elevation of ICP would threaten visual function and, in recurrent cases, to protect the optic nerve from further injury. The ONSF should not be used as a long-term means of lowering ICP or as a treatment for headaches.   

    Pharmacologic treatment

    Carbonic anhydrase inhibitors have been shown to decrease ICP and treat papilledema.22 Acetazolamide is the most commonly used carbonic anhydrase inhibitor. Furosemide is usually reserved for cases in which acetazolamide is not tolerated due to its minimal effect on lowering ICP. Topiramate is an antiepileptic drug with the secondary effect of inhibiting carbonic anhydrase. It has been used as an alternative to acetazolamide and has the added benefit of suppressing appetite, which makes it a good choice for patients who are obese. The role of corticosteroids has not been proven; however a short course of high-dose corticosteroids can be utilized for acute cases of elevated ICP and for papilledema associated with acute vision loss. 

    Surgery

    The two surgical approaches used in the management of IIH are CSF shunting procedures and optic nerve sheath fenestration. De Wecker introduced ONSF, which is used to treat papilledema that is unresponsive to medical management, in 1873.23 The majority of patients have resolution of papilledema and stabilization of vision with this procedure.24,25 From a vascular perspective, the optic nerve head is a delicate area described as a watershed. CSF pressure at the optic nerve head is thought to cause papilledema. ONSF likely works by inducing a circumferential scar to form between the optic nerve sheath and the optic nerve, directly behind the globe. This effectively redirects the pressure head of CSF from the optic nerve head and moves it posteriorly to an area that is more resilient. This theory is supported by the fact that ICP remains elevated after ONSF and that the fenestration itself scars down and does not remain open over time.26-30 This simple explanation does not entirely explain the mechanism by which ONSF works, and there are reports of patients who have had unilateral ONSF that resulted in a resolution of papilledema in the fellow eye and improvement in headache.24,25,31,32 

    There are several CSF shunting options, but the two most frequently utilized approaches are lumboperitoneal shunt and ventriculoperitoneal shunt. Lumboperitoneal shunting has been found to be a highly effective approach for treating papilledema and alleviating symptoms.26 Serial lumbar puncture continues to be used to treat IIH. In some cases, LPs are performed weekly or biweekly. This can be a poor treatment option, because it has no long-term benefit, is painful for the child, worsens anxiety, is difficult in obese patients, and may require frequent sedation. For these reasons, LP should be reserved for initial diagnostic purposes and subsequently only when needed to monitor CSF pressure in response to treatment.             

    Summary

    The diagnosis of IIH in a pediatric patient is becoming more common. Understanding of this condition, its diagnosis, and its treatment have largely been based on data obtained in the adult population. There is now a growing body of evidence demonstrating that pediatric IIH is quite different from the adult disease. An increased understanding of how this disease affects children has led to more specific diagnostic and treatment guidelines that will aid the clinician in treating these patients. 

    References

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