Current Pain and Headache Reports (2018) 22: 14

https://doi.org/10.1007/s11916-018-0665-9

CHILDHOOD AND ADOLESCENT HEADACHE (S EVERS, SECTION EDITOR)

Pediatric Intracranial Hypertension: a Current Literature Review

Shawn C. Aylward 1 & Amanda L. Way 2

Published online: 13 February 2018

# Springer Science+Business Media, LLC, part of Springer Nature 2018

Abstract
Purpose of Review The purpose of this review is to provide an update on pediatric intracranial hypertension.
Recent Findings The annual pediatric incidence is estimated at 0.63 per 100,000 in the USA and 0.71 per 100,000 in Britain. The
Idiopathic Intracranial Hypertension Treatment Trial found improvement in visual fields, optical coherence tomography, Frisen
grade, and quality of life with acetazolamide compared to placebo in adult patients, and these findings have been translated to the
pediatric population.
Summary Pediatric intracranial hypertension is a disorder that if left untreated can lead to poor quality of life and morbidity.
There are no current treatment studies in pediatrics, but adult data suggests acetazolamide remains an acceptable first-line
medication.

Keywords Pseudotumor cerebri . Intracranial hypertension . Pediatric . Papilledema . Headache

Introduction
Primary intracranial hypertension (PIH) has gone by multiple
names since its original designation as “meningitis serosa” by
Quincke in 1897 [1]. “Pseudotumor cerebri” was coined by
Nonne in 1904 due to a similar presentation as patients who
had an intracranial mass [2]. In 1955, Foley suggested “benign
intracranial hypertension” which remained in vogue until a
series of case reports describing permanent visual defects
forced it to be renamed “idiopathic intracranial hypertension”
[3–5].
Today, pseudotumor cerebri and idiopathic intracranial hy-
pertension remain the two common terms amongst both
This article is part of the Topical Collection on Childhood and Adolescent
Headache
practitioners and the lay public. There have been attempts to
clarify the terminology surrounding the ambiguity in these
two names. Some have attempted to use a broader designation
of “pseudotumor cerebri syndrome” which still includes the
designation of idiopathic when a cause is not found [6, 7•].
The authors prefer the use of the terms PIH and secondary
intracranial hypertension (SIH) [8•]. When a clear precipitant
resulting in increased intracranial pressure is not found, indi-
viduals are labeled as primary. They can have risk factors such
as female gender, post-pubertal status, obesity, or polycystic
ovarian syndrome, but these conditions do not directly result
in increased pressure. SIH is then reserved for patients whose
intracranial hypertension results from another cause, such as
cerebral sinus venous thrombosis or oral fluoroquinolone use
(see Table 1) [9].

* Shawn C. Aylward Diagnostic Criteria

Shawn.Aylward@nationwidechildrens.org
The original criteria for adult PIH appeared following a series
Amanda L. Way of 22 patients reported by Dandy in 1937 [10]. The main
Amanda.Way@nationwidechildrens.org
limitation of these criteria is that the pneumoencephalogram
1
Department of Neurology, Nationwide Children’s Hospital, The
was the only imaging modality available at that time. A mod-
Ohio State University College of Medicine, 700 Children’s Drive, ification to the criteria occurred in 1985 into what is now
Columbus, OH 43205, USA referred to as the modified Dandy criteria [11]. These criteria
2
Department of Ophthalmology, Nationwide Children’s Hospital, stipulated that patients have (1) signs and symptoms of raised
Columbus, OH, USA intracranial pressure (headache, nausea, vomiting, transient
14 Page 2 of 9 Curr Pain Headache Rep (2018) 22: 14

Table 1 Common causes of secondary intracranial hypertension does not reduce the likelihood [12, 13]. Two recent studies
Medical conditions have applied these newer criteria to previously confirmed pa-
Cerebral venous thrombosis tients. Inger et al. found only 62% met the definitive criteria
Hydrocephalus
for PIH, 20% met probable, and 18% did not meet the criteria
Pregnancy/eclampsia
at all [14•]. Moreover, none, including those in the definite
Adrenal insufficiency (often on steroids)
group, displayed the required number of radiographic findings
to support a diagnosis of PIH. Gerstl et al. found a similar rate
Hypoparathyroidism (early in correction)
when they applied these criteria to their cohort [15•].
Behcet’s disease
Although these newer criteria do not imply withholding treat-
Crohn’s disease
ment if the patient does not meet definite or probable criteria,
Refeeding syndrome
it does raise concern that these stricter criteria may result in
Craniofacial syndromes
missed or untreated patients, and thus increased morbidity.
Chiari malformation
Another area that is debated is the normative pediatric CSF
Traumatic brain injury
opening pressure values. In adults, these values are well
Intracranial tumor
established and must be above 25 cm H20 to be considered
Intracranial hemorrhage
elevated. Previous studies have determined normal values of
Meningitis/encephalitis
less than 18 cm H20 for children under 8 years of age and less
Lyme disease
than 25 cm H20 for children 8 years or above (mirroring adult
Demyelinating disease/multiple sclerosis
normals) [16–18]. Avery et al. examined the opening pres-
Leukemia
sures of patients 1–18 years of age that received a lumbar
Lymphoma puncture as part of their routine work-up [19]. They found
Vitamin A (excess or deficiency) the 90th percentile was 28 cm H20 and suggested this should
Vitamin D (deficiency) be the cutoff for an elevated opening pressure in a sedated
Medications patient and 25 cm H20 if unsedated or not obese. They did
Minocycline/tetracycline/doxycycline not find a correlation of opening pressure with age or BMI.
Fluoroquinolone Lee et al. examined 44 sedated patients and found the mean
Growth hormone opening pressure was 20.3 cm H20 [20]. The main weakness
Oral contraceptives (likely secondary due to venous thrombosis) in both studies is that patients with white matter and demye-
Corticosteroids (especially withdrawal) linating disorders were also included as normal patients. Lee
Cyclosporine A et al. analyzed these patients separately and noted a higher
Cytarabine mean opening pressure compared to their total cohort. Avery
Lithium carbonate et al. did not conduct a separate analysis to determine if these
Nalidixic acid patients had a higher mean pressure. There have been other
Retinoic acid publications documenting elevated opening pressure in these
disorders in both adult and pediatric patients, so their inclusion
may have resulted in the elevation of the mean opening pres-
visual obscurations, or papilledema), (2) absence of localizing sure [21–23]. One study found elevated opening pressure in
neurologic signs (with exception of unilateral or bilateral 28% of pediatric patients with demyelinating disorders using
abducens nerve palsy), (3) CSF opening pressure of greater the 28 cm H20 cutoff previously proposed by Avery et al.
than 25 cm H20 with normal composition, and (4) normal to [22]. Morgan-Followell and Aylward compared a cohort of
small ventricles as demonstrated by computed tomography patients with demyelinating disorders to age- and sex-
(CT) study (magnetic resonance imaging (MRI) is the modal- matched PIH patients [23]. They found no statistical differ-
ity of choice today). ence in opening pressure between the two groups. The only
Recent revisions to the criteria for PIH still include the parameters that reached significance were white blood cell
basic concepts but have changed some requirements [7•]. count, the demyelinating group had a higher average, and
These newer criteria remove the clinical symptomology seen BMI, the PIH group was higher.
with intracranial hypertension. They divide patients into cate- The International Classification of Headache Disorders
gories of definite or probable based on the number of criteria (ICHD-3) revision includes intracranial hypertension disor-
met. It does include criteria for PIH without papilledema but ders in the subheading of headache related to non-vascular
requires a set of imaging findings be met in place of intracranial disorders [24]. The guidelines require the head-
papilledema. Studies have shown that the presence of one or aches be temporally associated to the development or discov-
more radiographic findings increases the probability of having ery of the patient’s intracranial hypertension, relieved by im-
intracranial hypertension; however, the lack of these findings proving the intracranial pressure, or worsen with an increase
Curr Pain Headache Rep (2018) 22: 14
in pressure. The guidelines also allow for the inclusion of
intracranial hypertension without papilledema without requir-
ing patients meet imaging requirements as suggested by
Friedman et al.
Positioning and changes in arterial carbon dioxide (CO2) at
the time of pressure measurement have been shown to in-
crease CSF opening pressure in pediatric patients [25, 26].
Comparing readings in both the flexed and extended position
does result in a statistically significant difference [25]. The
authors claim this change is of little clinical significance; how-
ever, some patients had a change of over 5 cm H20. The end-
tidal CO2 should be kept near normal in sedated patients as an
increase of 1 kPa results in an increase of 3.5–12 cm H20 in
the opening pressure [26].
Epidemiology
PIH is thought of by most practitioners to be a rare condition.
The adult annual incidence in the USA is estimated at 0.9–
1.07 per 100,000 [27••]. The annual pediatric incidence is
estimated to be 0.63 per 100,000 [28]. In Germany, the annual
pediatric incidence is estimated at 0.47 per 100,000, and in
Croatia, 1.2 per 100,000 [29, 30]. In Britain, they found an
annual incidence of 0.71 per 100,000 in children aged 1–
16 years [31]. Pediatric PIH is often divided into pre-
pubertal or pubertal groups. Pubertal patients are thought to
have the same risk factors and female-to-male ratio as adults,
whereas pre-pubertal children have a female-to-male ratio of
nearly 1:1 [30, 32]. Obesity has not been found to correlate
with an increased risk of PIH until around the time of puberty
[33]. In Britain, there was a noticeable difference in frequency
of obese females around age 7 with a 2:1 female-to-male ratio
[31].
Familial case reports are occasionally seen, with twin case
reports even more rare [34–36]. Polemikos et al. reported ho-
mozygous twins that presented 3 years apart [36]. Both sisters
were morbidly obese which may have played a role in the
development of their PIH.
Signs and Symptoms
The symptomatology of intracranial hypertension tends to be
less evident in younger patients. Incidental discovery of optic
disc edema on routine ophthalmologic examination is relative-
ly common. Up to 18% of patients have symptoms suggestive
of intracranial hypertension, without papilledema, and are
found to have elevated opening pressure [29, 30, 32, 37••].
Optic nerve edema is typically bilateral, though rare cases of
unilateral edema have been reported. Optic edema grades
should be relatively symmetric between eyes. The Idiopathic
Intracranial Hypertension Treatment Trial (IIHTT) found
Page 3 of 9 14
optic edema severity was the same between eyes in 58.2%
of patients, and within one grade in 92.8% [38].
The most common symptom at the time of presentation is
headache, seen in 85.5–96.5% of pediatric PIH patients [30,
39, 40]. Review of symptomatology in the IIHTT found 84%
reported headache at diagnosis [38]. They found migraine in
52% of patients, tension-type headache was the next most
common, and 37% met the criteria for medication overuse
headache. Participants localized pain as frontal (68%), gener-
alized (36%), occipital (39%), unilateral (30%), ocular (47%),
and neck (47%). Twenty-three percent of patients had a daily
headache with overall median frequency of 12 headache days
per month. Pain quality was described as pressure-like in 47%
and throbbing in 42%. Patients reported associated symptoms
of photophobia (70%), phonophobia (52%), and worsening
pain with routine physical activity (50%).
Other symptoms include nausea and vomiting (12.7–52%)
and diplopia (16–42.3%) in pediatric patients [30, 40]. Adult
patients also report nausea (47%), vomiting (17%), diplopia
(22%), and dizziness (53%) [38].
Transient visual obscurations (TVOs) are episodes of bin-
ocular or monocular blurry vision often precipitated by posi-
tion changes that last less than 30 s. Sixty-eight percent of
patients in the IIHTT reported this symptom [38]. Often un-
reported until directly asked, 10% of pediatric patients expe-
rience a pulsatile tinnitus, described as a whooshing sound
[30]. Fifty-two percent of adults reported this symptom in
the IIHTT. Patients note resolution with lowered intracranial
pressure, whether via lumbar puncture or medication. It is the
authors’ observation that return of tinnitus following medica-
tion wean can precede other symptoms or even papilledema.
Spontaneous CSF rhinorrhea and otorrhea have both been
reported as the first signs of PIH [41, 42]. Patients usually
have rhinorrhea or otorrhea, headache (due to intracranial hy-
potension), and rarely bacterial meningitis. Only after the leak
is repaired or spontaneously resolves do the symptoms of PIH
appear.
Evidence of olfactory dysfunction was recently found in
adult PIH patients [43, 44]. On direct questioning, five PIH
patients endorsed a reduced sense of smell, and direct testing
found hyposmia in 41% of PIH patients. This was in compar-
ison to only 6% of age- and sex-matched controls. The highest
rates of dysfunction were in acute presentations along with a
decreased odor detection threshold [43]. A similar impairment
in olfactory detection and mild reduction in smell identifica-
tion was seen by Bershad et al. [44].
Cognitive decline is a frequent report with PIH, but
studies have only been performed in adult patients [45,
46, 47••]. The most common areas affected were process-
ing speed and reaction time. Working memory was not
affected in all but one, small retrospective study [45].
Yuri et al. found normalization of attention scores and
visuospatial memory tests at repeat testing, regardless of
14 Page 4 of 9
whether there was normalization or continued elevation
(albeit improvement) of opening pressure [46].
Diagnosis
The ophthalmologic exam plays an important role in the di-
agnosis of elevated intracranial pressure. Pertinent examina-
tion pieces include visual acuity, pupillary function,
extraocular motility, color vision evaluation, and optic nerve
appearance via fundoscopy. Patients may present with unilat-
eral or bilateral abducens palsy.
Raised intracranial pressure may cause swelling of the
intralaminar portion of the optic nerve, leading to optic nerve
edema. A dilated fundus examination allows for characteriza-
tion of the nerve appearance, and the presence and degree of
optic nerve edema help guide diagnosis and monitoring. The
Frisen grading scale is a previously validated system which
grades the degree of disc edema, on a scale of 0 to 5 with 0
representing no disc edema to 5, severe edema with loss of the
vessel architecture on the disc head [48••].
True optic nerve swelling may be associated with blurred
disc margins, vessel obscuration on the disc head or edge, and
peripapillary hemorrhage or exudates. In comparison, optic
disc drusen may solely present with an irregular disc margin
in an asymptomatic child [49]. Optic disc drusen are typically
deeper during childhood and become more superficial in later
childhood and through adulthood.
Differentiation of these two conditions may be aided with the
use of orbital B-scan ultrasonography, which may demonstrate
enlarged optic nerve sheath diameter with elevated intracranial
pressure [50, 51] or show hyper-echogenic calcifications on the
disc head on low gain [52]. B-scan ultrasonography is less sen-
sitive in children as compared to adults, and this is thought to be
due to drusen that are not as calcified or superficial.
Additionally, an increase in optic nerve sheath diameter of great-
er than 4.5 mm in children has demonstrated some potential in
predicting elevated intracranial pressure [51].
In children with buried drusen, fundus autofluorescence
may also serve as an adjunct to B-scan ultrasound, though it
is also less reliable in identifying deeper drusen [53]. In older
children, formal perimetry also identifies peripheral or central
visual deficits. Younger children may be unable to cooperate
with automated perimetry and manual perimetry such as a
Goldmann visual field may be more helpful.
Optical coherence tomography of the retinal nerve fiber
layer (OCT RNFL) has shown promise with detection and
monitoring in pediatric intracranial hypertension [54–56]. In
particular, thickness of the retinal nerve fiber layer (RNFL)
may correlate with the degree of papilledema [57].
Fluorescein angiography is also a useful modality to differ-
entiate between disc edema due to elevated intracranial pres-
sure, optic nerve drusen, or in cases where both conditions
Curr Pain Headache Rep (2018) 22: 14
may co-exist [58]. In patients with true swelling, angiography
demonstrates progressive hyperfluorescence consistent with
disc leakage. In comparison, optic nerve drusen demonstrate
hypofluorescence or only faint nodular hyperfluorescence
consistent with late staining. Chang et al. performed a pro-
spective observational study of 19 children to compare com-
mon imaging modalities to differentiate between optic disc
edema and optic nerve drusen [49]. They found that fluores-
cein angiography was found to have the highest accuracy as
compared to fundus photography, B-scan ultrasound, OCT
RNFL, and fundus autofluorescence. Practitioners should re-
member that the lack of optic nerve edema does not preclude
elevated intracranial pressure.
Neuroimaging should include MRI and MRV to rule out
secondary causes. The different sets of criteria for diagnosis all
state neuroimaging should be normal; however, subtle findings
suggestive of increased intracranial pressure can occur. These
include partial or empty sella turcica, optic nerve sheath dilation,
posterior globe flattening, anterior protrusion of the optic nerve
head, vertical tortuosity of the optic nerve, distal transverse sinus
stenosis, optic nerve head enhancement, and slit-like ventricles
[12, 13, 59]. Hartmann et al. compared the MRIs of children
with PIH to those of adults [60]. They found all of the imaging
findings seen in adults except for meningoceles in their cohort.
Bilateral transverse venous narrowing is felt to be a result and
not cause of the intracranial hypertension as resolution is often
noted following treatment [61].
The final piece for diagnosis is the opening pressure on lum-
bar puncture (LP). Convention dictates it should be measured
with the patient in the lateral decubitus position with the legs
and head extended. The tendency is to withdraw a large CSF
volume resulting in a near normal closing pressure. The authors’
experience found that a substantial drop in intracranial pressure
from baseline only increases the risk of developing a post-LP
headache. The exact pathophysiology in the development of a
post-LP headache is not clear, but theories suggest that the de-
crease in intracranial pressure results in a caudal movement of the
brain itself and resulting traction on the brain support structures
and cranial nerves. This results in dural stretching and stretching
of pain-sensing intracranial structures. With previous work by
Johnston and Paterson in adult patients showing an average of
82 min before returning to the pre-LP pressure [62], the authors
began limiting the change from the initial pressure to less than
10 cm H20 and have seen fewer post-LP headaches and a similar
amount of patients reporting transient headache relief. A recent
study found the intracranial pressure change was 1 cm H20 for
roughly 0.91 mL of CSF removed [63]. The authors anecdotally
find this is a good estimation.
Needle type also appears to play a role in the development
of a post-lumbar puncture headache. Hatfield et al. found the
Whitacre needle produced a rate of 4.2% post-LP headaches
requiring blood patches whereas the same gauge Quincke cut-
ting needle produced 15.1% [64]. Lower puncture sites (i.e.,
Curr Pain Headache Rep (2018) 22: 14
L5-S1 vs L3-L4) showed a higher rate of post-LP headaches.
The more experienced the person performing the LP, the lower
the rates were as well. Other studies have also looked at the
rates of post-LP headache with use of traditional cutting ver-
sus non-cutting needles and found lower rates with use of the
non-cutting needle [65, 66]. An interesting study looked at
needle type, length, and gauge in terms of opening pressure
accuracy and time to obtain the opening pressure measure-
ment with a patient simulator [67]. They found it took a longer
time to obtain a measurement (defined as time to three identi-
cal measurements spaced at 10 sec intervals) when comparing
increasing gauge, length, and Quincke to pencil-point needles.
The opening pressure measurements do not vary statistically
by gauge, needle type, or length.
CSF protein has a negative linear relationship with the open-
ing pressure and no correlation with BMI, age, or gender [68].
Treatment
To date, there have been no intervention studies in pediatrics.
The most recent treatment trial in adults was the IIHTT. They
identified patients aged 18–60 years with mild vision loss,
papilledema, and diagnosis of PIH. These patients were ran-
domized to either acetazolamide or placebo treatment, with
both groups also receiving weight loss interventions [38].
Acetazolamide dosing was up to 4 g/day, and weight loss
aim was 6% of initial diagnosis weight.
The group receiving acetazolamide had significant im-
provements in visual fields (areas around the physiologic
blind spot and nasal fields), OCT, Frisen grade, and quality
of life compared to placebo at 6 months. Aplastic anemia or
clinically significant hypokalemia was not seen, and the au-
thors suggest routine monitoring is not necessary.
Unfortunately, despite doses up to 4 g/day, there was no ben-
efit in headache severity shown. This study did not include
pediatric patients, and we find most patients report improve-
ment in headache on acetazolamide.
Topiramate is a weak carbonic anhydrase inhibitor similar
to acetazolamide. Celebisoy et al. compared 40 adult patients
on open-label treatment of acetazolamide or topiramate.
Monitoring visual field grades, they saw a statistically signif-
icant improvement in both groups [69].
One of the vital components of treatment involves weight
loss. Many patients report recent weight gain in the 6–
12 months prior to diagnosis. There are no pediatric studies
in this area, but adult studies have shown a reduction in symp-
toms, papilledema, and recurrence rates in patients who lost
weight [70, 71]. A loss of at least 6% of total body weight has
been shown to result in papilledema resolution [72].
Surgical intervention is performed if a patient has worsen-
ing vision loss, intractable headaches despite maximal medi-
cal management, or in selected cases, if a patient is intolerant
Page 5 of 9 14
to medical therapy. Surgical management includes optic nerve
sheath fenestration or cerebrospinal fluid diversion. Lumbar
drains may also be considered as a temporizing agent prior to
surgical treatment.
Optic nerve fenestration is typically preferred as a treat-
ment for patients with significant visual impairment. A large
study including 158 eyes of 86 IIH patients undergoing nerve
sheath fenestration demonstrated stable to improved vision in
148 eyes [73].
Interestingly, unilateral optic nerve sheath fenestration may
improve papilledema in contralateral unoperated eyes.
Although reduction in papilledema was greatest in the operat-
ed eye, improvement in disc edema was present at 3, 6, and
12 months post-operatively [74]. Risks associated with the
procedure include vascular complications causing an ischemic
retinopathy or optic neuropathy, pupillary mydriasis, motility
disorder, or retrobulbar hemorrhage [75].
CSF shunting can be considered and is generally more
effective when the main symptom is pain, though it is also
used for protection of vision in the acute presentation. It was
previously believed that ventricular diversion is superior to
lumbar. Abubaker et al. compared 25 patients shunted for their
intracranial hypertension. Classification of shunt failure was
return of initial symptoms (or failure of resolution) with radio-
graphic verification of shunt placement and normal opening
pressure. The need for revision was defined as radiographic
evidence of shunt disturbance, blockage, or increased opening
pressure. Failure rates for LP and VP shunts were similar at 11
and 14%, respectively, with revision rates of 60 and 30%,
respectively [76]. Liu et al. found shunt series and CT scans
do not aid in increased rates of changes in management. Shunt
series only detected issues 3.9% of the time [77, 78]. CT scans
discovered new issues only 4% of the time; most common was
evidence of overdrainage.
Sinus venous stenosis stenting is used in adults with PIH
[79–81]. Headache resolution or reduction is seen in 58.4–
84.6% and resolution of papilledema in 62.5–100%. The most
frequent side effect is a transient headache or partial hearing
loss on the treated side. Venous guidewire perforation, intracra-
nial hemorrhage, and temporary unsteadiness are rarely seen.
Compared to shunting for hydrocephalus, the costs of
transverse sinus stenting for PIH were similar [82].
Increased costs were associated with problems or complica-
tions which lead to a high shunt revision rate. Greater than
90% of stent patients required only one procedure.
Outcome
Unfortunately, a patient’s sense of quality of life is heavily tied
to pain and permanent vision loss, the two major complica-
tions associated with intracranial hypertension [83, 84].
Headache is reported as the first symptom to resolve in the
14 Page 6 of 9
first weeks of treatment, with papilledema resolving in 4.2–
5 months [30, 85]. Grade 3 to 5 papilledema was a strong
predictor permanent vision deficits in pediatric patients, with
50% of eyes having a degree of permanent visual loss [86].
The IIHTT found the degree of visual compromise at the time
of diagnosis has been the best prognostic factor for visual
outcome following resolution in adults [87].
PIH recurrence is reported around 18–20% [32, 85]. Ko
et al. found in a series of adult patients that weight gain after
resolution resulted in recurrence of papilledema [70]. A pa-
tient’s initial BMI was not linked to recurrence as the average
BMI in patients without recurrence was higher than those with
recurrence.
Conclusions
In summary, PIH and SIH are both seen in pediatrics with an
estimated annual PIH incidence of 0.63 per 100,000 in the
USA. This condition does have the potential to impact patient
quality of life and results in significant morbidities of pain and
permanent vision loss. Recent publications have attempted to
clarify the nomenclature and criteria for this condition. The
authors suggest practitioners avoid absolute application of the
newer criteria as this may result in missed cases. The IIHTT
demonstrated acetazolamide is an effective first-line treatment
option.
Compliance with Ethical Standards
Conflict of Interest Shawn C. Aylward and Amanda L. Way declare no
conflict of interest.
Human and Animal Rights and Informed Consent All reported studies/
experiments with human or animal subjects performed by the authors
have been previously published and complied with all applicable ethical
standards (including the Helsinki declaration and its amendments,
institutional/national research committee standards, and international/na-
tional/institutional guidelines).
References
Papers of particular interest, published recently, have been
highlighted as:
• Of importance
•• Of major importance
1. Quincke H. Uber Meningitis serosa and verwandte Zustande. Dtsch
Z Nervenheilkd. 1897;9:149–68. (Atricle in German).
2. Nonne M. Ueber Falle vom Symptomkomplex “tumor cerebri” mit
Ausgang in Heilung. Dtsch Z Nervenheilkd. 1904;27(3–4):169–
216. https://doi.org/10.1007/BF01667111.
3. Corbett JJ, Savino PJ, Thompson HS, Kansu T, Schatz NJ, Orr LS,
et al. Visual loss in pseudotumor cerebri. Follow-up of 57 patients
from five to 41 years and a profile of 14 patients with permanent
Curr Pain Headache Rep (2018) 22: 14
severe visual loss. Arch Neurol. 1982;39(8):461–74. https://doi.
org/10.1001/archneur.1982.00510200003001.
4. Wall M, Hart WM Jr, Burde RM. Visual field defects in idiopathic
intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol.
1983;96(5):654–69. https://doi.org/10.1016/S0002-9394(14)
73425-7.
5. Foley J. Benign forms of intracranial hypertension; toxic and otitic
hydrocephalus. Brain. 1955;78(1):1–41. https://doi.org/10.1093/
brain/78.1.1.
6. Friedman DI. The pseudotumor cerebri syndrome. Neurol Clin.
2014;32(2):363–96. https://doi.org/10.1016/j.ncl.2014.01.001.
7.• Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the
pseudotumor cerebri syndrome in adults and children. Neurology.
2013;81(13):1159–65. Most recent adult and pediatric revision
attempt. https://doi.org/10.1212/WNL.0b013e3182a55f17.
8.• Aylward SC. Pediatric idiopathic intracranial hypertension: a need
for clarification. Pediatr Neurol. 2013;49(5):303–4. Pediatric in-
tracranial hypertension criteria. https://doi.org/10.1016/j.
pediatrneurol.2013.05.019.
9. Sodhi M, Sheldon CA, Carleton B, Etminan M. Oral
fluoroquinolones and risk of secondary pseudotumor cerebri syn-
drome: nested case-control study. Neurology. 2017;89(8):792–5.
https://doi.org/10.1212/WNL.0000000000004247.
10. Dandy WE. Intracranial pressure without brain tumor: diagnosis
and treatment. Ann Surg. 1937;106(4):492–513. https://doi.org/
10.1097/00000658-193710000-00002.
11. Smith JL. Whence pseudotumor cerebri? J Clin Neuroophthalmol.
1985;5(1):55–6.
12. Maralani PJ, Hassanlou M, Torres C, Chakraborty S, Kingstone M,
Patel V, et al. Accuracy of brain imaging in the diagnosis of idio-
pathic intracranial hypertension. Clin Radiol. 2012;67(7):656–63.
https://doi.org/10.1016/j.crad.2011.12.002.
13. Gorkem SB, Doganay S, Canpolat M, Koc G, Dogan MS, Per H,
et al. MR imaging findings in children with pseudotumor cerebri
and comparison with healthy controls. Child’s Nerv Syst.
2015;31(3):373–80. https://doi.org/10.1007/s00381-014-2579-0.
14.• Inger HE, Rogers DL, McGregor ML, Aylward SC, Reem RE.
Diagnostic criteria in pediatric intracranial hypertension. J
AAPOS: the official publication of the American Association for
Pediatric Ophthalmology and Strabismus / American Association
for Pediatric Ophthalmology and Strabismus. 2017;21(6):492-5 e2.
https://doi.org/10.1016/j.jaapos.2017.08.003 Application of past
patients with modern proposed criteria.
15.• Gerstl L, Schoppe N, Albers L, Ertl-Wagner B, Alperin N, Ehrt O,
et al. Pediatric idiopathic intracranial hypertension—is the fixed
threshold value of elevated LP opening pressure set too high? Eur
J Paediatr Neurol. 2017;21(6):833–41. Application of past pa-
tients with modern proposed criteria. https://doi.org/10.1016/j.
ejpn.2017.08.002.
16. Tschudy MM, Arcara KM, Johns Hopkins Hospital. Children’s
Medical and Surgical Center. The Harriet Lane handbook: a manual
for pediatric house officers. 19th ed. Philadelphia: Mosby Elsevier;
2012. xvi, 1132 p., 10 p. of plates p
17. Swaiman KF. Swaiman’s pediatric neurology: principles and prac-
tice. 5th ed. Elsevier Saunders: Edinburgh; 2012.
18. Rangwala LM, Liu GT. Pediatric idiopathic intracranial hyperten-
sion. Surv Ophthalmol. 2007;52(6):597–617. https://doi.org/10.
1016/j.survophthal.2007.08.018.
19. Avery RA, Shah SS, Licht DJ, Seiden JA, Huh JW, Boswinkel J,
et al. Reference range for cerebrospinal fluid opening pressure in
children. N Engl J Med. 2010;363(9):891–3. https://doi.org/10.
1056/NEJMc1004957.
20. Lee MW, Vedanarayanan VV. Cerebrospinal fluid opening pressure
in children: experience in a controlled setting. Pediatr Neurol.
2011;45(4):238–40. https://doi.org/10.1016/j.pediatrneurol.2011.
07.002.
Curr Pain Headache Rep (2018) 22: 14
21. Williams BJ, Skinner HJ, Maria BL. Increased intracranial pressure
in a case of pediatric multiple sclerosis. J Child Neurol. 2008;23(6):
699–702. https://doi.org/10.1177/0883073807313040.
22. Narula S, Liu GT, Avery RA, Banwell B, Waldman AT. Elevated
cerebrospinal fluid opening pressure in a pediatric demyelinating
disease cohort. Pediatr Neurol. 2015;52(4):446–9. https://doi.org/
10.1016/j.pediatrneurol.2015.01.002.
23. Morgan-Followell B, Aylward SC. Comparison of cerebrospinal
fluid opening pressure in children with demyelinating disease to
children with primary intracranial hypertension. J Child Neurol.
2017;32(4):366–70. https://doi.org/10.1177/0883073816681936.
24. 7.1.1 Headache attributed to idiopathic intracranial hypertension
(IIH). https://www.ichd-3.org/7-headache-attributed-to-non-
vascular-intracranial-disorder/7-1-headache-attributed-to-
increased-cerebrospinal-fluid-pressure/7-1-1-headache-attributed-
to-idiopathic-intracranial-hypertension-iih/.
25. Avery RA, Mistry RD, Shah SS, Boswinkel J, Huh JW, Ruppe MD,
et al. Patient position during lumbar puncture has no meaningful
effect on cerebrospinal fluid opening pressure in children. J Child
N e u r o l . 2 0 1 0 ; 2 5 ( 5 ) : 6 1 6 – 9 . h t t p s : / / d o i . o r g / 1 0 . 11 7 7 /
0883073809359198.
26. Lim MJ, Lin JP. The effects of carbon dioxide on measuring cere-
bral spinal fluid pressure. Child's Nerv Syst. 2009;25(7):783–4.
https://doi.org/10.1007/s00381-009-0902-y.
27.•• Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor
cerebri. Population studies in Iowa and Louisiana. Arch Neurol.
1988;45(8):875–7. First report of pediatric incidence in the
United States. https://doi.org/10.1001/archneur.1988.
00520320065016.
28. Gillson N, Jones C, Reem RE, Rogers DL, Zumberge N, Aylward
SC. Incidence and demographics of pediatric intracranial hyperten-
sion. Pediatr Neurol. 2017;73:42–7. https://doi.org/10.1016/j.
pediatrneurol.2017.04.021.
29. Tibussek D, Distelmaier F, von Kries R, Mayatepek E.
Pseudotumor cerebri in childhood and adolescence—results of a
Germany-wide ESPED-survey. Klin Padiatr. 2013;225(2):81–5.
https://doi.org/10.1055/s-0033-1333757.
30. Dessardo NS, Dessardo S, Sasso A, Sarunic AV, Dezulovic MS.
Pediatric idiopathic intracranial hypertension: clinical and demo-
graphic features. Coll Antropol. 2010;34(Suppl 2):217–21.
31. Matthews YY, Dean F, Lim MJ, McLachlan K, Rigby AS, Solanki
GA, et al. Pseudotumor cerebri syndrome in childhood: incidence,
clinical profile and risk factors in a national prospective population-
based cohort study. Arch Dis Child. 2017;102(8):715–21. https://
doi.org/10.1136/archdischild-2016-312238.
32. Tibussek D, Schneider DT, Vandemeulebroecke N, Turowski B,
Messing-Juenger M, Willems PH, et al. Clinical spectrum of the
pseudotumor cerebri complex in children. Child’s Nerv Syst.
2010;26(3):313–21. https://doi.org/10.1007/s00381-009-1018-0.
33. Bursztyn LL, Sharan S, Walsh L, LaRoche GR, Robitaille J, De
Becker I. Has rising pediatric obesity increased the incidence of
idiopathic intracranial hypertension in children? Can J
Ophthalmol. 2014;49(1):87–91. https://doi.org/10.1016/j.jcjo.
2013.09.015.
34. Beri S, Chandratre S, Chow G. Familial idiopathic intracranial hy-
pertension with variable phenotype. Eur J Paediatr Neurol.
2011;15(1):81–3. https://doi.org/10.1016/j.ejpn.2010.02.005.
35. Corbett JJ. The first Jacobson Lecture. Familial idiopathic intracra-
nial hypertension. J Neuroophthalmol. 2008;28(4):337–47. https://
doi.org/10.1097/WNO.0b013e31818f12a2.
36. Polemikos M, Heissler HE, Hermann EJ, Krauss JK. Idiopathic
intracranial hypertension in monozygotic female twins: intracranial
pressure dynamics and treatment outcome. World Neurosurg.
2017;101:814 e11–4. https://doi.org/10.1016/j.wneu.2017.03.004.
37.•• Aylward SC, Aronowitz C, Roach ES. Intracranial hypertension
without papilledema in children. J Child Neurol. 2016;31(2):177–
Page 7 of 9 14
83. IIHTT outcomes in the first large-scale adult trial. https://
doi.org/10.1177/0883073815587029.
38. Smith SV, Friedman DI. The idiopathic intracranial hypertension
treatment trial: a review of the outcomes. Headache. 2017;57(8):
1303–10. https://doi.org/10.1111/head.13144.
39. Aylward SC, Aronowitz C, Reem R, Rogers D, Roach ES.
Intracranial hypertension without headache in children. J Child
N e u r o l . 2 0 1 5 ; 3 0 ( 6 ) : 7 0 3 – 6 . h t t p s : / / d o i . o rg / 1 0 . 11 7 7 /
0883073814540522.
40. Aylward SC, Waslo CS, Au JN, Tanne E. Manifestations of pediat-
ric intracranial hypertension from the intracranial hypertension reg-
istry. Pediatr Neurol. 2016;61:76–82. https://doi.org/10.1016/j.
pediatrneurol.2016.04.007.
41. Brainard L, Chen DA, Aziz KM, Hillman TA. Association of be-
nign intracranial hypertension and spontaneous encephalocele with
cerebrospinal fluid leak. Otol Neurotol. 2012;33(9):1621–4. https://
doi.org/10.1097/MAO.0b013e318271c312.
42. Rosenfeld E, Dotan G, Kimchi TJ, Kesler A. Spontaneous cerebro-
spinal fluid otorrhea and rhinorrhea in idiopathic intracranial hyper-
tension patients. J Neuroophthalmol. 2013;33(2):113–6. https://doi.
org/10.1097/WNO.0b013e18274b870.
43. Kunte H, Schmidt F, Kronenberg G, Hoffmann J, Schmidt C,
Harms L, et al. Olfactory dysfunction in patients with idiopathic
intracranial hypertension. Neurology. 2013;81(4):379–82. https://
doi.org/10.1212/WNL.0b013e31829c5c9d.
44. Bershad EM, Urfy MZ, Calvillo E, Tang R, Cajavilca C, Lee AG,
et al. Marked olfactory impairment in idiopathic intracranial hyper-
tension. J Neurol Neurosurg Psychiatry. 2014;85(9):959–64.
https://doi.org/10.1136/jnnp-2013-307232.
45. Kharkar S, Hernandez R, Batra S, Metellus P, Hillis A, Williams
MA, et al. Cognitive impairment in patients with pseudotumor
cerebri syndrome. Behav Neurol. 2011;24(2):143–8. https://doi.
org/10.1155/2011/630475.
46. Yri HM, Fagerlund B, Forchhammer HB, Jensen RH. Cognitive
function in idiopathic intracranial hypertension: a prospective case-
control study. BMJ Open. 2014;4(4):e004376. https://doi.org/10.
1136/bmjopen-2013-004376.
47.•• Zur D, Naftaliev E, Kesler A. Evidence of multidomain mild cog-
nitive impairment in idiopathic intracranial hypertension. J
Neuroophthalmol. 2015;35(1):26–30. Papilledema grading scale.
https://doi.org/10.1097/WNO.0000000000000199.
48.•• Frisen L. Swelling of the optic nerve head: a staging scheme. J
Neurol Neurosurg Psychiatry. 1982;45(1):13–8. Comparison of
pediatric imaging in papilledema vs pseudopapilledema.
https://doi.org/10.1136/jnnp.45.1.13.
49. Chang MY, Velez FG, Demer JL, Bonelli L, Quiros PA, Arnold AC,
et al. Accuracy of diagnostic imaging modalities for classifying
pediatric eyes as papilledema versus pseudopapilledema.
Ophthalmology. 2017;124(12):1839–48. https://doi.org/10.1016/j.
ophtha.2017.06.016.
50. Atta HR. Imaging of the optic nerve with standardised echography.
Eye (Lond). 1988;2(Pt 4):358–66. https://doi.org/10.1038/eye.
1988.66.
51. Irazuzta JE, Brown ME, Akhtar J. Bedside optic nerve sheath di-
ameter assessment in the identification of increased intracranial
pressure in suspected idiopathic intracranial hypertension. Pediatr
Neurol. 2016;54:35–8. https://doi.org/10.1016/j.pediatrneurol.
2015.08.009.
52. Carter SB, Pistilli M, Livingston KG, Gold DR, Volpe NJ, Shindler
KS, et al. The role of orbital ultrasonography in distinguishing
papilledema from pseudopapilledema. Eye (Lond). 2014;28(12):
1425–30. https://doi.org/10.1038/eye.2014.210.
53. Kurz-Levin MM, Landau KA. Comparison of imaging techniques
for diagnosing drusen of the optic nerve head. Arch Ophthalmol.
1999;117(8):1045–9. https://doi.org/10.1001/archopht.117.8.1045.
14 Page 8 of 9
54. Kulkarni KM, Pasol J, Rosa PR, Lam BL. Differentiating mild
papilledema and buried optic nerve head drusen using spectral do-
main optical coherence tomography. Ophthalmology. 2014;121(4):
959–63. https://doi.org/10.1016/j.ophtha.2013.10.036.
55. El-Dairi MA, Holgado S, O'Donnell T, Buckley EG, Asrani S,
Freedman SF. Optical coherence tomography as a tool for monitor-
ing pediatric pseudotumor cerebri. J AAPOS. 2007;11(6):564–70.
https://doi.org/10.1016/j.jaapos.2007.06.018.
56. Martinez MR, Ophir A. Optical coherence tomography as an ad-
junctive tool for diagnosing papilledema in young patients. J Pediatr
Ophthalmol Strabismus. 2011;48(3):174–81. https://doi.org/10.
3928/01913913-20100719-05.
57. Lee YA, Tomsak RL, Sadikovic Z, Bahl R, Sivaswamy L. Use of
ocular coherence tomography in children with idiopathic intracra-
nial hypertension—a single-center experience. Pediatr Neurol.
2016;58:101–6 e1. https://doi.org/10.1016/j.pediatrneurol.2015.
10.022.
58. Pineles SL, Arnold AC. Fluorescein angiographic identification of
optic disc drusen with and without optic disc edema. J
Neuroophthalmol. 2012;32(1):17–22. https://doi.org/10.1097/
WNO.0b013e31823010b8.
59. Fraser JA, Leung AE. Reversibility of MRI features of
pseudotumor cerebri syndrome. J Can Sci Neurol. 2014;41(4):
530–2. https://doi.org/10.1017/S0317167100018643.
60. Hartmann AJ, Soares BP, Bruce BB, Saindane AM, Newman NJ,
Biousse V, et al. Imaging features of idiopathic intracranial hyper-
tension in children. J Child Neurol. 2017;32(1):120–6. https://doi.
org/10.1177/0883073816671855.
61. Horev A, Hallevy H, Plakht Y, Shorer Z, Wirguin I, Shelef I.
Changes in cerebral venous sinuses diameter after lumbar puncture
in idiopathic intracranial hypertension: a prospective MRI study. J
Neuroimaging. 2013;23(3):375–8. https://doi.org/10.1111/j.1552-
6569.2012.00732.x.
62. Johnston I, Paterson A. Benign intracranial hypertension. II. CSF
pressure and circulation. Brain. 1974;97(2):301–12.
63. McLaren SH, Monuteaux MC, Delaney AC, Landschaft A, Kimia
AA. How much cerebrospinal fluid should we remove prior to
measuring a closing pressure? J Child Neurol. 2017;32(4):356–9.
https://doi.org/10.1177/0883073816681352.
64. Hatfield MK, Handrich SJ, Willis JA, Beres RA, Zaleski GX.
Blood patch rates after lumbar puncture with Whitacre versus
Quincke 22- and 20-gauge spinal needles. AJR Am J Roentgenol.
2008;190(6):1686–9. https://doi.org/10.2214/AJR.07.3351.
65. Engedal TS, Ording H, Vilholm OJ. Changing the needle for lum-
bar punctures: results from a prospective study. Clin Neurol
Neurosurg. 2015;130:74–9. https://doi.org/10.1016/j.clineuro.
2014.12.020.
66. Castrillo A, Tabernero C, Garcia-Olmos LM, Gil C, Gutierrez R,
Zamora MI, et al. Postdural puncture headache: impact of needle
type, a randomized trial. Spine J. 2015;15(7):1571–6. https://doi.
org/10.1016/j.spinee.2015.03.009.
67. Bellamkonda VR, Wright TC, Lohse CM, Keaveny VR, Funk EC,
Olson MD, et al. Effect of spinal needle characteristics on measure-
ment of spinal canal opening pressure. Am J Emerg Med.
2017;35(5):769–72. https://doi.org/10.1016/j.ajem.2017.01.047.
68. Berezovsky DE, Bruce BB, Vasseneix C, Peragallo JH, Newman
NJ, Biousse V. Cerebrospinal fluid total protein in idiopathic intra-
cranial hypertension. J Neurol Sci. 2017;381:226–9. https://doi.org/
10.1016/j.jns.2017.08.3264.
69. Celebisoy N, Gokcay F, Sirin H, Akyurekli O. Treatment of idio-
pathic intracranial hypertension: topiramate vs acetazolamide, an
open-label study. Acta Neurol Scand. 2007;116(5):322–7. https://
doi.org/10.1111/j.1600-0404.2007.00905.x.
70. Ko MW, Chang SC, Ridha MA, Ney JJ, Ali TF, Friedman DI, et al.
Weight gain and recurrence in idiopathic intracranial hypertension:
Curr Pain Headache Rep (2018) 22: 14
a case-control study. Neurology. 2011;76(18):1564–7. https://doi.
org/10.1212/WNL.0b013e3182190f51.
71. Sinclair AJ, Burdon MA, Nightingale PG, Ball AK, Good P,
Matthews TD, et al. Low energy diet and intracranial pressure in
women with idiopathic intracranial hypertension: prospective co-
hort study. BMJ. 2010;341(jul07 2):c2701. https://doi.org/10.1136/
bmj.c2701.
72. Johnson LN, Krohel GB, Madsen RW, March GA Jr. The role of
weight loss and acetazolamide in the treatment of idiopathic intra-
cranial hypertension (pseudotumor cerebri). Ophthalmology.
1998;105(12):2313–7. https://doi.org/10.1016/S0161-6420(98)
91234-9.
73. Banta JT, Farris BK. Pseudotumor cerebri and optic nerve sheath
decompression. Ophthalmology. 2000;107(10):1907–12. https://
doi.org/10.1016/S0161-6420(00)00340-7.
74. Alsuhaibani AH, Carter KD, Nerad JA, Lee AG. Effect of optic
nerve sheath fenestration on papilledema of the operated and the
contralateral nonoperated eyes in idiopathic intracranial hyperten-
sion. Ophthalmology. 2011;118(2):412–4. https://doi.org/10.1016/
j.ophtha.2010.06.025.
75. Plotnik JL, Kosmorsky GS. Operative complications of optic nerve
sheath decompression. Ophthalmology. 1993;100(5):683–90.
https://doi.org/10.1016/S0161-6420(93)31588-5.
76. Abubaker K, Ali Z, Raza K, Bolger C, Rawluk D, O'Brien D.
Idiopathic intracranial hypertension: lumboperitoneal shunts versus
ventriculoperitoneal shunts—case series and literature review. Br J
Neurosurg. 2011;25(1):94–9. https://doi.org/10.3109/02688697.
2010.544781.
77. Liu A, Elder BD, Sankey EW, Goodwin CR, Jusue-Torres I,
Rigamonti D. Are shunt series and shunt patency studies useful in
patients with shunted idiopathic intracranial hypertension in the
emergency department? Clin Neurol Neurosurg. 2015;138:89–93.
https://doi.org/10.1016/j.clineuro.2015.08.008.
78. Liu A, Elder BD, Sankey EW, Goodwin CR, Jusue-Torres I,
Rigamonti D. The utility of computed tomography in shunted pa-
tients with idiopathic intracranial hypertension presenting to the
emergency department. World Neurosurg. 2015;84(6):1852–6.
https://doi.org/10.1016/j.wneu.2015.08.008.
79. Ahmed RM, Wilkinson M, Parker GD, Thurtell MJ, Macdonald J,
McCluskey PJ, et al. Transverse sinus stenting for idiopathic intra-
cranial hypertension: a review of 52 patients and of model predic-
tions. AJNR Am J Neuroradiol. 2011;32(8):1408–14. https://doi.
org/10.3174/ajnr.A2575.
80. Radvany MG, Solomon D, Nijjar S, Subramanian PS, Miller NR,
Rigamonti D, et al. Visual and neurological outcomes following
endovascular stenting for pseudotumor cerebri associated with
transverse sinus stenosis. J Neuroophthalmol. 2013;33(2):117–22.
https://doi.org/10.1097/WNO.0b013e31827f18eb.
81. Kumpe DA, Bennett JL, Seinfeld J, Pelak VS, Chawla A, Tierney
M. Dural sinus stent placement for idiopathic intracranial hyperten-
sion. J Neurosurg. 2012;116(3):538–48. https://doi.org/10.3171/
2011.10.JNS101410.
82. Ahmed RM, Zmudzki F, Parker GD, Owler BK, Halmagyi GM.
Transverse sinus stenting for pseudotumor cerebri: a cost compari-
son with CSF shunting. AJNR Am J Neuroradiol. 2014;35(5):952–
8. https://doi.org/10.3174/ajnr.A3806.
83. Digre KB, Bruce BB, McDermott MP, Galetta KM, Balcer LJ, Wall
M, et al. Quality of life in idiopathic intracranial hypertension at
diagnosis: IIH treatment trial results. Neurology. 2015;84(24):
2449–56. https://doi.org/10.1212/WNL.0000000000001687.
84. Mulla Y, Markey KA, Woolley RL, Patel S, Mollan SP, Sinclair AJ.
Headache determines quality of life in idiopathic intracranial hyper-
tension. J Headache Pain. 2015;16(1):521.
85. Ravid S, Shahar E, Schif A, Yehudian S. Visual outcome and re-
currence rate in children with idiopathic intracranial hypertension. J
Curr Pain Headache Rep (2018) 22: 14
Child Neurol. 2015;30(11):1448–52. https://doi.org/10.1177/
0883073815569306.
86. Gospe SM 3rd, Bhatti MT, El-Dairi MA. Anatomic and visual
function outcomes in paediatric idiopathic intracranial hyperten-
sion. Br J Ophthalmol. 2016;100(4):505–9. https://doi.org/10.
1136/bjophthalmol-2015-307043.
Page 9 of 9 14
87. Agarwal A, Vibha D, Prasad K, Bhatia R, Singh MB, Garg A, et al.
Predictors of poor visual outcome in patients with idiopathic intra-
cranial hypertension (IIH): an ambispective cohort study. Clin
Neurol Neurosurg. 2017;159:13–8. https://doi.org/10.1016/j.
clineuro.2017.05.009.