Pediatric intracranial hypertension: A review of presenting symptoms, quality of life, and secondary causes

Abstract

Our understanding of primary (idiopathic) intracranial hypertension has evolved in recent years. There have been efforts to rename the disorder as pseudotumor cerebri syndrome or primary intracranial hypertension. Some studies have suggested a higher threshold opening pressure to define intracranial hypertension. The reported annual incidence varies from 0.6 to 0.9 per 100 000 children around the world. Patients are typically divided into prepubertal and pubertal groups, with pubertal patients having the same risk factors as adults. Prepubertal patients do not share these risk factors. They are more likely to be asymptomatic, have equal gender distributions, and are less likely to be obese. Headache is the most common presenting complaint, followed by vision changes and nausea/vomiting. A newer concept of fulminant intracranial hypertension has emerged, defined as acute onset with rapid progression of visual deficits or papilledema. Quick insertion of a temporary lumbar drain as a bridge while medical management reaches effectiveness improves visual outcomes and helps avoid permanent shunt placement. Headache is typically the first symptom to resolve with treatment, and papilledema resolves in five to six months. Recurrence rates in children and adolescents range from 28.5% to 36.4%, with higher rates after puberty.

Introduction

Primary intracranial hypertension (idiopathic intracranial hypertension, pseudotumor cerebri) was first described by Quincke in 1897 as “meningitis serosa.” ¹ The same clinical syndrome became known as pseudotumor cerebri beginning in 1904 and as idiopathic intracranial hypertension in the 1980s. ² , ³ Both terms are still frequently used, though confusion between them warrants discussion. Some prefer the broader designation of “pseudotumor cerebri syndrome” (PTCS), which includes the designation of idiopathic if no cause is found. ⁴ , ⁵ We prefer the terms “primary intracranial hypertension” (PIH) and “secondary intracranial hypertension” (SIH) and use these henceforth. ⁶ , ⁷ PIH is diagnosed in cases without a clear causative condition, though a patient may have risk factors including obesity, female gender, and post‐pubertal status. SIH is diagnosed when intracranial hypertension (IH) is the direct result of other conditions, such as medications or cerebral sinus venous thrombosis.

The threshold opening pressure that defines intracranial hypertension has also changed, most recently through a proposed higher cutoff of 28 cm H₂O. ⁵ , ⁸ , ⁹ Avery et al. did find small correlations with higher opening pressures in deeply sedated and obese patients, suggesting 25 cm H₂O as the cutoff for those not meeting these criteria. ⁸ The cutoff of 28 cm H₂O has been incorporated into the PTCS criteria, but there remains debate as their study population included individuals with demyelinating disorders in the normal cohort. ⁵ , ⁸ Pediatric studies have shown higher opening pressures among patients with demyelinating conditions. ⁹ , ¹⁰ , ¹¹ Lee et al. found those with demyelinating disease had a higher mean opening pressure compared with the entire cohort (21.5 cm H₂O vs. 20.3 cm H₂O). ⁹ Narula et al. reexamined their initial cohort used to suggest the cutoff of 28 cm H₂O and documented that 28% of patients with demyelination had elevated opening pressures using this cutoff. ¹⁰ Morgan‐Followell and Aylward compared a series of patients with demyelinating disease to those with PIH and found no statistical difference in opening pressure between the two groups. ¹¹ As expected, PIH patients had a statistically significant higher body mass index (BMI), and the demyelinating group had a higher mean cerebrospinal fluid (CSF) white blood cell count. Due to these concerns, some practitioners still use the older accepted cutoffs of 18 cm H₂O for patients under 8 years of age and 25 cm H₂O for patients 8 years and older. ¹² , ¹³ , ¹⁴

As there is nuance in the definition of IH, there is variation in the epidemiologic profile as well. The reported annual incidence in the United States is 0.63 or 0.32 per 100 000 children for PIH and SIH, respectively. ¹⁵ Ghaffari‐Rafi et al. queried a pediatric inpatient admissions directory and found a median incidence of 0.89 over a 17‐year period. ¹⁶ Internationally the annual incidence in Nova Scotia and Prince Edward Island is 0.6–0.9. ¹⁷ , ¹⁸ In Germany the incidence is estimated to be 0.47, though this is based on a country‐wide survey and appears to include both PIH and “potentially causal” cases. ¹⁹ In the United Kingdom and Ireland the annual incidence is 0.71, though narrowing the sample to obese 12–15‐year‐old males and females increases the respective incidences to 4.18 and 10.7. ²⁰

We describe recent changes in our understanding of the clinical presentation, diagnostic approaches, treatment options, and outcomes in PIH. We review selected aspects of SIH. We then summarize the social and mental health impacts and quality‐of‐life implications for children with IH.

Clinical Presentation

PIH is divided into prepubertal and pubertal groups because pubertal patients have the same risk factors as adults (e.g., female gender, obesity), whereas prepubertal patients do not. The female‐to‐male ratio ranges from 0.8:1 to 13:6 depending on pubertal status, and the rate of comorbid obesity ranges from 12%–75% (Table 1). ¹⁷ , ²¹ , ²² , ²³ , ²⁴ , ²⁵ , ²⁶ Yamamoto et al. reported a significant increase in both the female‐to‐male ratio from 0.8:1 to 4.1:1 as well as BMI in the pubertal group. ²³ Masri et al. found a male‐predominant ratio of 1:2.1 before age 12 and an equal distribution after age 12; obesity was relatively uncommon in this cohort, affecting only 12% of patients. ²⁴ Ballcer et al. and Bursztyn et al. both found a correlation with obesity and increased risk of PIH among patients older than 11 and 12 years, respectively. ¹⁷ , ²⁷

Table 1.

Distribution of risk factors based on puberty.

	Dessardo 21	Tibussek 22	Yamamoto 23	Masri 24	Aylward 25
Female‐to‐male ratio
Prepubertal	3:4	1:1.5	0.8:1		1:1.04
Pubertal	1:2	2:1	4.1:1		6:1
No delineation	13:6			1:2.1	2.6:1
Obesity
Prepubertal	44%	16%
Pubertal	50%	19%
No delineation	48%		33.1%	12%

Most patients with IH are symptomatic, although the rate of asymptomatic presentation ranges from 13.3%–33%. ²³ , ²⁴ , ²⁶ , ²⁸ , ²⁹ , ³⁰ Asymptomatic children are typically younger, male, and less likely to be obese. Gondi and colleagues documented an average age of diagnosis of 10 years in asymptomatic patients compared with 12.5 years in symptomatic patients. ²⁸ Headache is by far the most common complaint, experienced by 56%–97% of the symptomatic patients. ²¹ , ²² , ²³ , ²⁴ , ²⁵ , ²⁶ , ³¹ , ³² Vision changes and nausea/vomiting are the next most common symptom at 28%–49.1% ²³ , ²⁴ , ³¹ and 13.3%–41.8%. ²¹ , ²³ , ²⁴ , ²⁵ , ²⁶ , ³¹

Papilledema is absent in up to 17.8% in most studies. ²¹ , ²² , ²³ , ²⁵ , ²⁶ , ³¹ , ³² Masri et al. reported an outlier rate of 34% without papilledema. ²⁴

Pulsatile tinnitus is an often overlooked symptom but can help differentiate IH‐related headaches from migraine. Only two articles reported the frequency of tinnitus, with rates of 10% and 45.8%. ²¹ , ²⁵ Palsies of cranial nerves VI, III, and VII were reported in 3.8%–18.75%, ²² , ²⁴ , ²⁵ , ³¹ 1.5%–6.25%, ²⁴ , ²⁵ , ³¹ and 1%–6.25% ²⁵ , ³¹ of patients, respectively.

As the most commonly associated symptom, headaches have been studied as a patient‐centered metric in association with IH. Sager et al. reported headache worsening while leaning forward or limiting activity as the only symptom correlated with PIH. ³³ Lee et al. had pediatric patients who presented with a chief complaint of headache draw representations of their headaches and compared depictions of migraine to those of PIH. ³⁴ They were asked to draw how they felt while experiencing a headache and the location, quality of the pain, and symptoms that appeared before a headache. This was done prior to the physician entering the room and reviewing patient charts for a diagnosis of migraine and PIH. Patients in both groups drew representations of pounding and pressure‐like pain, photophobia, dizziness, and lying flat. Severe pain was drawn as hammers, bombs, anvils, and vise grips. Drawings between the two were similar with the exception that 28.6% of PIH patients drew diplopia (crossed eyes, double images) compared with only 0.6% of migraineurs.

Global cognitive dysfunction among IH patients has recently received more attention. Comorbid issues with cognition have been reported in adults, including changes in processing speed and reaction time. ³⁵ , ³⁶ , ³⁷ Mahajnah et al. examined pediatric PIH patients three months after diagnosis and found that they had significantly lower scores in verbal memory, executive function, global cognitive, attention, and information processing speed. Verbal memory was the most affected domain. ³⁸

Diagnosis

The evaluation of IH includes ophthalmologic assessment and neuroimaging. Fundoscopy is aimed at detecting and quantifying optic disc edema using the Frisén scale, where grade 1 represents the mildest form of edema and grade 5 the most severe (Figure 1). ³⁹ In the presence of optic disc edema, optical coherence tomography is indicated to measure and benchmark peripapillary retinal nerve fiber layer thickness, which can later aid in assessment of treatment response. ⁴⁰ , ⁴¹ , ⁴² , ⁴³ Afferent visual function should also be quantified using at least central visual acuity, color acuity, confrontation perimetry, and if age‐appropriate, automated static perimetry (e.g., Humphrey visual field) or manual kinetic perimetry (e.g., Goldmann visual field). Efferent function should also be measured, as diplopia and acquired esotropia in the pattern of false‐localizing abducens palsy can be a common presenting symptom. ⁴⁴

Figure 1.

Fulminant intracranial hypertension. (A) Presentation, grade 4 papilledema. Arrows: peripapillary hemorrhages. Arrowheads: cotton‐wool spots. (B) Four days later, temporary lumbar drain in place, improved grade 3 papilledema with fading peripapillary hemorrhages and cotton‐wool spots. (C) One week later (11 days after presentation), drain removed, grade 1 papilledema, resolved cotton‐wool spots, and nearly resolved hemorrhages. (D) Eighteen days post‐presentation, resolved edema, emerging post‐papilledema pallor.

Neuroimaging should include magnetic resonance imaging (MRI) with and without contrast, including orbital views and magnetic resonance venography, to identify potential causes of increased intracranial pressure. Findings supporting IH include empty or partially empty sella, optic nerve sheath dilation, posterior globe flattening, optic nerve head protrusion, tortuous optic nerves, distal transverse sinus stenosis (TSS), optic nerve head enhancement, and slit ventricles (Figure 2). ⁴⁵ , ⁴⁶ , ⁴⁷ Hirfanoglu et al. proposed a new imaging finding termed the “target sign” denoting dilated optic nerve sheaths on T2‐coronal slices. ⁴⁸ The target sign was reported in 63.6% of their cohort and was seen with increased optic nerve sheath diameters in cross‐section. Although one or more radiologic findings increase the probability of having IH, lack of these findings does not lower the likelihood. ⁴⁵ , ⁴⁶ This has raised many questions regarding the newer PTCS criteria and replacement of clinical criteria with radiographic requirements in the absence of optic edema and cranial nerve (CN) palsies. Kohli et al. reviewed imaging findings of patients undergoing lumbar puncture (LP) for the evaluation of suspected IH. ⁴⁹ They documented evidence of empty/partially empty sella, posterior globe flattening, optic nerve sheath dilation, and TSS. The presence of three or more of these findings had a sensitivity of 62% and a specificity of 95% for IH. The presence of any two findings from empty/partially empty sella, flattening of the posterior globe, or TSS had similar sensitivity and specificity. TSS in isolation had a slightly higher sensitivity of 74% and a specificity of 100%.

Figure 2.

Imaging findings in intracranial hypertension. (A) Sagittal view with empty sella (filled arrow). (B) Axial view with dilated optic nerves (open arrows). (C) Coronal view with “target sign” (asterisks). (D) Venous imaging with narrowed transverse venous sinuses (arrow heads).

Gilbert et al. documented that PIH patients had larger dilated optic nerve sheaths and higher rates of optic nerve head protrusion, posterior globe flattening, empty sella, and venous sinus abnormalities compared with controls. ⁵⁰ The optic nerve sheath diameter of 5.2 mm or greater was an independent predictor of PIH, with 87% sensitivity and 67% specificity. Hartmann et al. found prepubertal patients had lower rates of posterior globe flattening, dilated optic nerve sheaths, tortuous optic nerves, empty/partially empty sella, and TSS compared with adolescents and adults. ⁵¹

Inger et al. applied the PTCS criteria retrospectively to patients previously diagnosed with IH. ⁵² They divided patients into three groups based on PTCS criteria. Group 1 contained 39 patients meeting diagnostic criteria for definite IH. Eight had abnormalities consistent with IH; however, none had TSS or more than two findings. Group 2 contained 10 patients with papilledema and opening pressure less than 28 cm H₂O, meeting criteria for probable IH. One patient had a single radiographic finding. Group 3 contained nine patients with opening pressures greater than 28 cm H₂O and no papilledema or cranial nerve VI (CNVI) palsy, thus not meeting diagnostic criteria for IH. Four had imaging findings, including dilated optic nerve sheaths, tortuous optic nerves, or posterior globe flattening; none had more than two findings.

These studies showed that although imaging findings can be present in IH, their absence (especially the required three of four imaging findings per Friedman et al.) does not exclude the diagnosis. Practitioners then should consider clinical symptomatology to aid the diagnosis.

The final component needed for diagnosis is the LP to both confirm the elevated pressure and rule out secondary causes such as infection. The gold standard for positioning during measurement of the pressure is left lateral decubitus with legs and head extended. Practitioners often allow the pressure to normalize, but the clinical benefit of this practice is unclear. Johnston et al. found the time to return to initial pressure averaged only 82 min. ⁵³ The authors also question the utility of removing large volumes of CSF due to increased risk of developing a post‐LP headache, so our practice is to lower the pressure by less than 10 cm H₂O as patients still report a transient improvement in headache. McLaren et al. documented a linear relationship with CSF change in pressure related to volume removed in pediatric patients. ⁵⁴ When reducing pressure by less than 15 cm H₂O, removal of 0.91 mL of CSF resulted in a 1 cm H₂O decrease in pressure.

The CSF pressure is the most relevant information obtained during LP for a suspected diagnosis of IH, but examination of CSF composition is relevant to help rule out secondary causes such as meningitis. We start with routine CSF cell count, protein, and glucose and expand the diagnostic search based on the results or clinical suspicion. Margeta et al. compared PIH patients with controls who had normal opening pressure on LP. ⁵⁵ The majority of pubertal patients were obese females, which was not true of the prepubertal or control patients. The interesting finding was that CSF protein was significantly lower in prepubertal groups than in pubertal and control groups (17.3, 23.4, and 23.5 mg/dL, respectively). CSF protein increased in all PIH patients with repeat LP following treatment.

Treatment

A multidisciplinary team is needed to treat patients with IH. A neurologist and ophthalmologist are key team members. A neurosurgeon, dietitian, psychologist, and hematologist should be available. In PIH with comorbid obesity, weight loss is a cornerstone of management. The adult literature indicates that 6% of total body weight can result in resolution of papilledema. ⁵⁶ In addition to weight loss, three oral medications are typically used in the treatment of IH: acetazolamide, furosemide, and topiramate.

Acetazolamide is often the first‐line treatment. It acts by reducing CSF production from carbonic anhydrase inhibition. ⁵⁷ Pediatric doses of 25–100 mg/kg/day (up to 2 g/day) divided twice a day (bid) have been used. ²⁶ Adolescent dosing is usually 1–2 g divided bid. Doses above 2 g often result in more side effects with limited additional improvement. Side effects include metallic taste to food (especially carbonated beverages), paresthesias, transient anorexia, and metabolic acidosis. In an adult trial, hypokalemia was only documented with simultaneous valsartan and hydrochlorthiazide use. ⁵⁸ The study authors recommended against routine monitoring for metabolic acidosis or hypokalemia, although due to transient transaminitis and elevated lipase in some patients, monitoring during the titration phase should be considered. Aplastic anemia did not occur, and the authors did not recommend periodic monitoring. Topiramate has a mode of action and side effects similar to acetazolamide. Dosing of 100–150 mg per day has shown benefit in adults. ⁵⁹

Furosemide is often a second‐line therapy and likely works via diuretic effect. ⁶⁰ The usual dose is 1–2 mg/kg/day divided bid. ²⁶ It is second line due to the diuretic effect and need for serial bloodwork. Serum electrolytes should be monitored and potassium supplemented if needed. Studies have reported a synergistic effect when added to acetazolamide. ⁶¹

There is a newer concept of fulminant intracranial hypertension (FIH) that is defined as acute onset of IH with rapid progression of visual deficits or papilledema. Patients can present with FIH or quickly progress following IH diagnosis. Newer reports involving FIH have focused on use of a temporary lumbar drain (TLD) as a bridge while medical management reaches full effectiveness to avoid permanent shunt placement. Jiramongkolchai et al. reported two obese teens with FIH managed with a TLD. ⁶² One patient presented eight weeks after symptom onset and two weeks after diagnosis with worsening visual fields and acuity to point of light perception on right and 20/80 on left, with a right relative afferent pupillary defect. She was started on intravenous methylprednisolone, acetazolamide was increased, and TLD was placed. By 18 months, her vision was 20/200 on the right and 20/50 on the left, with severe optic atrophy bilaterally. The second patient presented with vision loss two weeks after starting acetazolamide. Visual acuity was 20/400 on right and finger counting on left, with bilateral visual field constriction, left relative afferent pupillary defect, and CNVI palsy. Intravenous methylprednisolone was started, acetazolamide increased, and TLD placed. At two months visual acuity was 20/400 on the left and 20/70 on the right with optic disc atrophy. Left optic nerve sheath fenestration was performed, with final visual acuity 20/60 on right and 20/80 on left.

Ploof et al. reported nine patients who were aggressively treated for FIH. ⁶³ At presentation, all patients had headache, vision changes, and papilledema with two being considered legally blind. The average time from IH diagnosis to FIH diagnosis was 14.6 days. Acetazolamide was given to all patients; additional treatment included furosemide (67%) and steroids (78%). Four received TLD, three received shunt without TLD, and two received TLD followed by optic nerve sheath fenestration and shunt. The time from FIH diagnosis to any neurosurgical intervention averaged 4.9 days. All patients were able to be weaned off medication and had resolution of papilledema and cranial nerve palsies. All had final visual acuity of 20/25 or better except a single patient who had 20/40 acuity in the worse eye.

Dotan treated 13 children with median grade 4 edema and five with CNVI palsies with a TLD. ⁶⁴ All had 20/20 visual acuity but did have constricted visual fields. All were started on medical management of acetazolamide, and six also received intravenous methylprednisolone, with average time to TLD insertion of 9.5 days. Ten patients had the TLD for five days, with the remaining three patients tolerating three days before CSF leakage necessitated removal. All patients had resolution of headache and CNVI palsy; none had evidence of optic atrophy, and all had improvement in visual field deficits from presentation. Three did eventually require surgical interventions with either shunt or stent placement or bariatric surgery due to recurrences.

These reports suggest that earlier intervention with TLD can avoid the need for permanent CSF diversion and improves visual field and acuity outcomes (Figure 1). Additionally, intravenous corticosteroids were used for some patients. Steroids were the first treatment used for IH but due to added side effects are now typically reserved for fulminant cases. Optimal dosing has not been established, but most practitioners follow optic neuritis dose recommendations of intravenous methylprednisolone 20 mg/kg (maximum 1 g) daily for five days. This regimen is followed by an oral taper to avoid rebound IH; we typically use a two‐week course.

There are two main surgical interventions considered in pediatric IH: optic nerve sheath fenestration (ONSF) and CSF shunting. Inger et al. examined a series of patients to determine characteristics that may predict the need for surgical interventions. ⁶⁵ Only 9.8% (14/143) of their cohort required surgery, with elevated BMI and opening pressure over 52 cm H₂O increasing the need for interventions. ONSF is used to address papilledema, and the mechanism of improvement is not clear. Initially, it was believed to remove pressure from the optic nerve head; however, in patients who underwent unilateral fenestration, edema resolved in the contralateral eye. ⁶⁶ , ⁶⁷ Surgery does carry risks of ischemic optic neuropathy, transient blindness, pupillary mydriasis, and retrobulbar hemorrhage. Postoperative ischemia is a major concern during the acute presentation with severe papilledema. CSF shunting is primarily used to treat headache but is also used in the acute presentation where ONSF would be risky. Ventricular versus lumbar to peritoneal shunting is often surgeon preference.

Venous sinus stenting (VSS) has been studied in adults with varied success. ⁶⁸ , ⁶⁹ Lee et al. reported 14 patients, 10–17 years of age, who received stenting for an average of five years after diagnosis. ⁷⁰ Sixty percent of patients on medication were able to reduce dosing, 80% had improvement in papilledema, 85.7% reported improved headaches, and 100% had resolution of tinnitus. Four patients required further CSF shunting and/or stenting. Schwarz et al. had eight patients undergo VSS for medication intolerance, failure of medical management, and rapid vision loss. ⁷¹ Half had papilledema, all complained of severe headaches, five reported subjective visual complaints, and three had pulsatile tinnitus and CNVI palsy. All but one patient reported improvement in headaches, of whom six had resolution of headache, tinnitus, and papilledema. Two‐thirds of patients taking acetazolamide were weaned off; the remaining patients received a lower dose or transitioned to topiramate. Five patients with post‐stent LP had an average opening pressure reduction of 28.3 cm H₂O. Two did require repeat stenting, one at 24 months with stenosis proximal to the stent and other after having no symptom relief after the first procedure and demonstration of new stenosis proximal to the stent. Although patients did report improvements following VSS, similar to adult studies, re‐stenting was required in some patients.

Prognosis

Headache is typically the first symptom to resolve with treatment. Papilledema requires five to six months to resolve, largely depending on severity. ²¹ , ²³ Yamamoto et al. reported time to headache improvement of one week in 52.2% of patients after diagnosis, one month in 57%, and three months in 69%. ²³ Those with acute headaches were more likely to report improvement. At one month, patients treated with acetazolamide were more likely to report improvement compared with those receiving topiramate or no treatment, though this trend did not continue at three months. Papilledema severity was not associated with headache improvement. Papilledema resolution took a median of four months, with prepubertal patients typically taking longer. Treatment choice (acetazolamide versus topiramate) did not affect time to resolution of papilledema.

Hilely et al. found a pediatric PIH recurrence rate of 36.4%, which differed widely between the prepubertal group (2.5%) and the pubertal group (50%). ⁷² They found no statistical difference in time to recurrence between groups but did find an earlier time to recurrence in prepubertal patients at 1.3 years compared with 3.8 years. Longer duration of treatment did appear to reduce recurrence rates. Alex et al. found 28.5% of PIH and SIH patients had at least one recurrence, with a median time to first recurrence of 4.7 months. ⁷³ They included patient noncompliance in this recurrence rate. Papilledema at diagnosis carried 4.56 times the risk of recurrence, and those weaned off medication due to side effects (including self‐discontinuation) had 3.91 times higher risk. Headache appeared to be protective, with 60% lower risk of recurrence. The cumulative recurrence risk increased over the first six months following medication wean and leveled off at 12–18 months.

There is a paucity of data on long‐term headache frequency, and data are limited to adult studies. It is not uncommon for patients to develop a newer headache that is different from their presenting IH headache. Older patients are often able to differentiate between their previous IH headaches and the newer ones. An adult study found this trend in two‐thirds of patients, with 30% meeting criteria for tension headache and 20% meeting criteria for migraine without aura. ⁷⁴ Yri et al. found that 43% of their cohort reported continued daily headaches one year from diagnosis. Half of these had no history of headaches before diagnosis. ⁷⁵ We have found that headaches do improve with treatment and are often infrequent, though providers should be aware that chronic headaches may follow resolution of IH.

Secondary Intracranial Hypertension

Potential causes of SIH should always be considered with any new diagnosis as they may warrant additional evaluation or modifications to the current treatment. Many case reports have documented a possible association between medications and SIH, though most are single cases. Minocycline, doxycycline, growth hormone (GH), lithium carbonate, and rapid corticosteroid withdrawal are the most commonly accepted causes of SIH. ⁷⁶ , ⁷⁷ , ⁷⁸ , ⁷⁹ , ⁸⁰ , ⁸¹ , ⁸² , ⁸³ , ⁸⁴ There are three accepted presentation periods associated with minocycline use: early (first two months), delayed (after two months), and indeterminate. ⁷⁷ Hyper‐ and hypovitaminosis A can also result in SIH. ⁸⁵ , ⁸⁶ , ⁸⁷ Hypervitaminosis can result from excessive dietary intake or use of all‐trans retinoic acid in conjunction with chemotherapy. It can also result from the use of elexacaftor/tezacaftor/ivacaftor, a newer combination treatment for cystic fibrosis. ⁸⁸ , ⁸⁹

SIH associated with GH use typically occurs within the first 12 weeks of treatment. ⁷⁹ Martin‐Begue et al. prospectively studied patients started on GH for development of IH symptoms. ⁹⁰ The average age was 9 years, 53% were male, and none had optic disc edema prior to treatment. At follow‐up after starting GH, 1.7% developed asymptomatic optic edema, and all were being treated for GH deficiency. None of the patients who reported new headaches had evidence of optic disc edema. Optic disc edema resolved with discontinuation of GH without the need for medical treatment. Four patients were able to resume GH at a lower dose and titrated doses without recurrence.

Oral contraceptives have long been considered a cause of SIH. The first report of this association was in 1981. ⁹¹ Most reports thereafter were limited to single cases or small groups of patients who were receiving a variety of preparations, including medroxyprogesterone acetate injections, drospirenone and ethinyl estradiol (Yasmin 28), etonogestrel (Implanon, Nexplanon), levonorgestrel, and combination contraceptives. ⁹² , ⁹³ , ⁹⁴ , ⁹⁵ , ⁹⁶ , ⁹⁷ , ⁹⁸ , ⁹⁹ , ¹⁰⁰ Some patients failed to receive venous imaging, and many who did had venous thromboses. More recent studies have largely refuted the link with oral contraceptives. Multiple studies using various registries and insurance databases failed to confirm a link with oral contraceptives. ¹⁰¹ , ¹⁰² , ¹⁰³ , ¹⁰⁴ Tan et al. performed a meta‐analysis of articles that reported medication‐associated IH. ¹⁰⁵ They found few verifiable cases for contraceptives and were only able to suggest a potentially stronger association with progestin‐only preparations compared with combined products. The estrogen to progesterone ratios of many oral contraceptives have changed considerably over the years, so it is difficult to determine whether there ever was an association between oral contraceptive use and IH. Currently, one guideline from the United Kingdom supports this paucity of data for an association and suggests referral to providers experienced in IH management for these patients. ¹⁰⁶ We typically approve continuation or restarting of oral contraceptives with careful follow‐up, and we have not seen patients worsen as a result.

Most practitioners consider cerebral sinus venous thrombosis as the common nonmedication cause for SIH. Table 2 lists other medical causes for SIH. Dsouza et al. examined patients with PIH and SIH for differences in presentation and found that 41.2% of patients with thrombosis had no risk factors for thrombosis development. Nausea and vomiting were the only statistically significant symptoms in those with thrombosis. The nonspecific nature of this finding supports the importance of venous imaging in all newly diagnosed patients. The authors recommended dedicated imaging of indwelling catheters to rule out catheter‐associated thrombosis. ¹⁰⁷

Table 2.

Causes of secondary intracranial hypertension.

Cerebral venous thrombosis

Brain tumor

Intracranial hemorrhage

Meningitis/encephalitis

Demyelinating disease/multiple sclerosis

Refeeding syndrome

Hypoparathyroidism (early in correction)

Hydrocephalus

Craniofacial syndrome

Chiari malformation

Traumatic brain injury

Lyme disease

Cryopyrin‐associated periodic fever syndrome

Leukemia

Lymphoma

Social Determinants, Mental Health, and Quality of Life in IH

In addition to the typical urgent concerns of acute IH, there is a compounding burden of disease for those with more chronic courses of IH. Sleep disturbance, depression, and overall lower quality of life have been observed in pediatric IH. Tokatly Latzer et al. found higher rates of severe/extremely severe depression, anxiety, and stress in PIH than in controls. ¹⁰⁸ Patients with PIH and female gender were more likely to have disordered eating behaviors. Subscale scores for dieting, bulimia, and food preoccupation were higher in the PIH cohort, yet there was no difference with oral control subscales. Those with disordered eating behaviors were typically older, overweight/obese, had weight gain prior to diagnosis, weight loss since diagnosis, longer time since diagnosis, and had recurrence. The presence of disordered eating was not related to medications or having received surgical interventions.

Wesley et al. examined the psychological aspects of IH patients via self‐report and parent proxy questionnaires. ¹⁰⁹ The cohorts included patients at various stages of treatment. Parent proxy and child reports were similar, with reports of higher pain levels correlating with higher BMI. Parents reported higher levels of pain interference than children did, and parent ratings of depression symptoms, BMI, and age affected reports of pain interference. Quality of life was similar to that of other headache populations but lower in patients with other chronic illnesses and healthy patients.

Kornbluh et al. found poorer total sleep disturbance score and subscale scores of sleep onset delay, parasomnias, and sleep‐disordered breathing compared with sibling controls. ¹¹⁰ There was no difference in scores based on PIH versus SIH, BMI, pubertal status, current headaches, or treatment modality. Tokatly Latzer et al. found a significantly higher prevalence of sleep disturbances as well as independent subscales of sleep‐related breathing, daytime sleepiness, sleep/wake disruptions, and sleep‐related depressive tendencies in adolescents with current PIH. ¹¹¹

Ghaffari‐Rafi et al. queried a national payor directory of inpatient admissions for social determinants of developing PIH from 1997 to 2016. ¹⁶ They examined income status between 2003 and 2016 and found a median incidence of 1.56 per 100 000 in the lowest‐income patients compared with 1.21 in middle‐ and high‐income patients. From 2007 to 2016 rural patients had an annual incidence of 1.46, urban 1.44, and suburban 1.30. Between 1997 and 2016, incidence among Black, White, Hispanic, and Asian/Pacific Islander were 2.05, 1.04, 0.67, and 0.16, respectively, with all increasing over time except Asian/Pacific Islander, which decreased. Although geared toward the adult population, this article does support rural, lower socioeconomic, and minority communities as higher‐risk populations.

Author Contributions

Hersh Varma and Shawn C. Aylward:  Conceptualization; data curation; methodology; writing—original draft; writing—review & editing.

Conflict of Interest Statement

Shawn C. Aylward receives honoraria as associate editor of Pediatric Neurology. Hersh Varma declares no conflicts of interest.