Curr Treat Options Neurol (2018) 20:24

DOI 10.1007/s11940-018-0512-7

Neurologic Ophthalmology and Otology (RK Shin and DR Gold, Section Editors)

Update on Idiopathic
Intracranial Hypertension
Sivashakthi Kanagalingam, MD1
Prem S. Subramanian, MD, PhD2,3,4,*
Address
1
Department of Surgery, Division of Ophthalmology, Dartmouth-Hitchcock Medi-
cal Center, Lebanon, NH, USA
2
Department of Ophthalmology, School of Medicine, University of Colorado
Anschutz Medical Campus, 1675 Aurora Court, Mailstop F-731, Aurora, CO,
80045, USA
3
Department of Neurology, University of Colorado Anschutz Medical Campus,
Aurora, CO, USA
*,4
Department of Neurosurgery, University of Colorado Anschutz Medical Campus,
Aurora, CO, USA
Email: prem.subramanian@ucdenver.edu

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

This article is part of the Topical Collection on Neurologic Ophthalmology and Otology

Keywords Pseudotumor cerebri I Idiopathic intracranial hypertension I Transverse sinus stenosis I Venous sinus
stenting

Abstract
Purpose of review This review presents a critical appraisal of current therapeutic strategies
for patients with idiopathic intracranial hypertension (IIH). We present the reader with
the most recent evidence to support medical and surgical interventions in patients with
IIH and provide recommendations about treatment initiation and escalation. We also
indicate areas where knowledge gaps exist regarding therapeutic efficacy and superiority
of one intervention over another.
Recent findings A double-masked, randomized prospective study of medical management of
patients with mild IIH (Idiopathic Intracranial Hypertension Treatment Trial—IIHTT) has
established that acetazolamide therapy has additional efficacy when compared to weight
loss alone. Furthermore, management of IIH-related headache, even in patients with
papilledema, may require treatment other than ICP lowering for patients to experience
symptomatic relief. Finally, a number of uncontrolled interventional studies have shown
transverse sinus stenting to be a potentially effective treatment for medically refractory IIH.
Summary Medical therapy with acetazolamide should be considered in addition to structured
weight loss in patients with mild IIH. Surgical treatment for patients with vision-
threatening disease IIH can be performed by either optic nerve sheath fenestration or
cerebrospinal fluid diversion, with venous sinus stenting emerging as an alternate therapy.
Headache relief from ICP lowering therapy is variable and often not sustained.
24 Page 2 of 13 Curr Treat Options Neurol (2018) 20:24

Introduction
Idiopathic intracranial hypertension (IIH) is a syn-
drome characterized by raised intracranial pressure
of unknown etiology in the absence of clinical and
radiological evidence of intracranial pathology and
has defined diagnostic criteria [1]. While the annual
incidence in the general population in North Amer-
ica is approximately 1–2 per 100,000 [2], this rises to
15–19 per 100,000 among obese women between 22
and 44 years of age [3,4]. Weight gain of 5–15% of
one’s total bodyweight is associated with a height-
ened risk of IIH development in susceptible popula-
tions. As the global obesity rates increase, the inci-
dence of IIH is similarly expected to rise as well [5].
The precise mechanism responsible for IIH occur-
rence remains unclear. Prior authors have suggested that
dysfunction of CSF dynamics, such as CSF hypersecre-
tion, decreased CSF absorption, or increased venous
sinus pressure, may play a contributory role in the de-
velopment of IIH [6••, 7]. Potential hormonal and
metabolic causes have also been brought forth and con-
tinue to be explored [8•]. Iatrogenic causes of raised
intracranial pressure, such as vitamin A derivatives, cer-
tain antibiotics (tetracycline, minocycline, doxycycline,
nalidixic acid), and lithium, have been well established
and should be identified early. Discontinuation of the
offending medication usually results in resolution of IIH
symptoms [9–11].
Headaches remain the most common clinical symp-
tom with as many as 90–94% of patients reporting this
at presentation [12, 13]. Transient visual obscurations,
pulse-synchronous tinnitus, and binocular horizontal
diplopia are other reported symptoms. Papilledema
seen in these patients is usually bilateral but may also
be asymmetric [14]. Permanent vision loss from
papilledema continues to be the most serious morbidity
in this group of patients. Severe vision loss can occur in
up to 25% of patients, with blindness reported in 10%
of cases [15–17].
IIH treatment is targeted at symptom (headache)
control and prevention of vision loss. We discuss the
evaluation of IIH and the current available medical and
surgical management options available.

Diagnostic evaluation
A comprehensive eye examination with an ophthalmologist or neuro-
ophthalmologist is important in documenting the severity of any presenting
visual dysfunction and guiding the subsequent management options. Assessment
of visual acuity and color vision, formal visual field testing (either automated
static perimetry or manual kinetic perimetry), and sensorimotor examination
looking for abduction deficits suggestive of unilateral or bilateral sixth nerve palsy
should be performed. Dilated ocular examination with optic nerve and macula
assessment should then be undertaken. Commonly seen visual field defects
include enlargement of the physiological blind spot, nasal step defects, arcuate
defects, and generalized peripheral constriction. Central visual acuity is generally
not affected unless there is significant macular edema secondary to acute optic
nerve edema or if there is advanced visual field loss from chronic untreated IIH.
The degree of vision loss has been found to be directly associated with the severity
of papilledema [18,19]. Additionally, poor presenting visual acuity and optic disc
hemorrhages have been found to be predictors of poor visual outcomes [20, 21].
Optic disc edema has traditionally been clinically graded using the Frisén
criteria, an ordinal scale based on descriptive features (Fig. 1) [22]. While this
standardization has been useful, the scale may often fail to detect small changes in
the degree of optic nerve edema which can be useful when assessing response to
IIH treatment. Recently, optical coherence tomography (OCT) has emerged as a
valuable tool in providing quantitative assessments of papilledema changes [23].
Curr Treat Options Neurol (2018) 20:24 Page 3 of 13 24

Fig. 1. Examples of optic disc swelling by the Frisén grading scheme. a Frisén grade 0 swelling with very mild disc elevation and no
loss of disc margin clarity. b Frisén grade 1 (very early papilledema) with a “C”-shaped halo of edema sparing the temporal disc. c
Early (Frisén grade 2) papilledema with 360° of peripapillary retinal nerve fiber layer swelling and margin obscuration. d Moderate
(Frisén grade 3) papilledema with obscuration of major blood vessels as they leave the disc inferiorly. e Marked (Frisén grade 4)
papilledema with numerous peripapillary hemorrhages. Hemorrhage is not part of the Frisén classification system. f Severe
papilledema (Frisén grade 5) with loss of all normal anatomic landmarks of the optic disc. Lipid in the papillomacular bundle is also
seen. Reprinted with permission from Miller NR, Subramanian PS, Patel VR. Walsh & Hoyt’s Clinical Neuro-Ophthalmology: The
Essentials, 3rd Edition. Baltimore: Wolters Kluwer, 2015.

Initial studies [24, 25] utilizing 2-dimensional peripapillary retinal nerve

fiber layer (RNFL) measurements from time-domain OCT were found to cor-
relate well with the clinical examination and the severity of visual dysfunction.
24 Page 4 of 13 Curr Treat Options Neurol (2018) 20:24

However, these were limited to patients with mild papilledema. In cases of

severe papilledema, the ability to differentiate the RNFL from other layers
became more challenging rendering the thickness calculations unreliable in this
subset of patients. With the availability of the newer spectral-domain (SD) OCT
and the introduction of 3-dimensional algorithms, more accurate volumetric
measurements have been obtained even in cases of severe papilledema [26, 27].
They have been found to correlate well with the papilledema grade at baseline
and moderately at a 6-month follow-up assessment [28]. Imaging of the
macular structures containing the retinal ganglion cell layer (RGCL) and inner
plexiform layer (IPL) has demonstrated little change over time despite changes
in optic nerve edema and intracranial pressure. It is thought that the RGCL–IPL
complex may reflect long-term visual function more accurately and potentially
can serve as a structural biomarker of neuronal tissue loss [27, 29••]. While
more longitudinal studies are needed to completely understand their potential
uses, current OCT modalities and volumetric analyses have proven to be useful
in providing a quantitative mode of assessing the effects of IIH therapy.
Magnetic resonance imaging (MRI) is the study of choice for IIH to exclude
an intracranial mass or obstructive hydrocephalus causing optic disc edema.
Recognized imaging findings of raised ICP, such as empty sella turcica, flatten-
ing of the posterior globes, distention of the optic nerve sheaths, and cerebellar
tonsillar descent, have been documented (Fig. 2a,b) [30, 31]. Addition of
magnetic resonance venography (MRV) to the MRI scan has increasingly be-
come prevalent. The chief role for obtaining an MRV is to rule out a cerebral
venous sinus thrombosis (CVST), which can cause a clinically identical picture
to IIH. MRV also can reliably visualize the transverse venous sinuses, where
focal distal stenoses may be identified (Fig. 2c). Treatment of such a stenosis is
an emerging therapeutic option in IIH patients who fail to improve by other
means [32, 33]. Subsequently, lumbar puncture performed in the lateral
decubitus position, with opening pressure greater than 25 cm H20, and with
normal CSF composition, is deemed diagnostic of IIH [34].

Current treatments
Medical therapy and weight loss
Weight loss remains the most important aspect of IIH management given the
integral associations between obesity and IIH. A reduction of as little as 5–10%
of total body weight has been found to be effective in symptom control and
papilledema improvement [35]. Systematic study of the efficacy of physician-
assisted weight loss with use of medications, such as orlistat, phentermine, and/
or liraglutide, has not been performed, but there is no specific contraindication
to the use of these drugs in patients with IIH. However, weight loss is a long-
term lifestyle modification which may not be achieved in a timely manner to
prevent vision loss from papilledema. In patients with worsening symptoms
and documented visual field defects, medical therapy should be initiated in
conjunction with weight loss efforts.
Medical treatments that include carbonic anhydrase inhibitors, such as
acetazolamide and topiramate, are frequently used in lowering intracra-
nial pressure. The initial dosage of acetazolamide, the preferred medica-
tion of choice, historically varied between 1 and 4 g/day. Use of acet-
azolamide in IIH treatment is supported by prospective data from the
Curr Treat Options Neurol (2018) 20:24 Page 5 of 13 24

Fig. 2. Neuroimaging findings in patients with IIH. a T1-weighted sagittal MRI brain with contrast showing empty sella turcica
(arrow). b Coronal STIR MRI orbits with enlarged optic nerve sheath diameters. c Noncontrast MRV head with focal distal left
transverse sinus stenosis (arrow) and distal right transverse sinus arachnoid granulation (arrowheads).
24 Page 6 of 13 Curr Treat Options Neurol (2018) 20:24

Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) [36••]. For

patients with mild visual field loss (defined in the study as mean devi-
ation from − 2 to − 7 dB on Humphrey visual field testing with the 24-2
SITA standard protocol), it established that acetazolamide in conjunction
with weight loss led to improved visual fields, papilledema grades, and
even quality of life measures when compared to weight loss alone [37,
38]. The visual field improvement difference, although statistically sig-
nificant, was modest at 0.71 dB, and the clinical relevance of this change
is not clear. However, secondary analysis suggested that subjects with
worse than − 5 dB MD and/or more severe papilledema benefitted even
more than average from medical therapy [36••,38]. Subjects in the IIHTT
were given an escalating dose of acetazolamide and took a median dose
of 1250 mg twice daily, with a maximal dose of 2000 mg twice daily.
Side effects associated with acetazolamide include paresthesias,
dysgenusia, fatigue, nausea, diarrhea, hypokalemia, metabolic acidosis,
renal stones, drowsiness, depression, or dizziness. While 92% of patients
in the acetazolamide group experienced at least one medication-related
adverse effect, 44% of the patients were able to tolerate the maximum
dose of 4 g/day. The side effects were reported at low dosages of acet-
azolamide and did not appear to increase significantly with high dosages
[37]. Based on the results of the IIHTT, it has become our practice to
initiate treatment of mild IIH with acetazolamide 1000 mg twice daily,
increasing the dose to 1500 mg within 1 month if there is no improve-
ment in papilledema and/or visual fields. We do not use headache relief
as a gauge of therapeutic success, as there was no significant difference in
headache improvement in the IIHTT between acetazolamide- and
placebo-treated subjects [39•].
Topiramate, a weak carbonic anhydrase inhibitor and migraine prophylaxis
agent, also is used in IIH, especially when the predominant symptoms are
headaches. An open-label study of 40 patients found topiramate to be effective
in treating both headache and mild papilledema [40]. Nonetheless, topiramate
also shares part of the side-effect profile of acetazolamide, and some patients
will report cognitive slowing at higher doses. We find topiramate to be most
useful therapeutically in IIH patients who have mild papilledema (grade II or
less), minimal visual field defects, and prominent headache concerns.
When carbonic anhydrase inhibitors are poorly tolerated, furosemide may
be employed for ICP reduction. Clinical evidence for furosemide alone appears
to be lacking, whereas its use in combination with acetazolamide has been
found to be successful in pediatric IIH patients [41]. Corticosteroids may have a
short-term role in fulminant IIH [42] but should not be used in any patients for
long-term management, as weight gain may ensue and complicate the disease
course. Similarly, lumbar puncture and particularly a lumbar drain can be
useful in temporizing patients with acute symptoms in cases of fulminant IIH
[42]. However, repeated lumbar punctures should no longer be offered as a
long-term management of IIH; this practice is not supported by data, symptom
relief is usually temporary, and frequent spinal procedures carry risk of infec-
tion, post-LP overdrainage and low-pressure headache, and local pain. Anec-
dotally, patients have been known to stop seeking care for their IIH because of
treatment with multiple LPs, which puts them at risk for vision loss from
untreated disease.
Curr Treat Options Neurol (2018) 20:24 Page 7 of 13 24

Surgical management
When IIH patients are deemed to be refractory to medical therapy with pro-
gressive visual loss and intractable headaches, surgical options are usually
employed. CSF diversion procedures [e.g., ventriculoperitoneal (VP) and
lumboperitoneal (LP) shunting] and optic nerve sheath fenestration (ONSF)
are the most commonly offered surgical interventions.
Historically, VP or LP shunts have been favored in patients with papilledema
and significant headaches, whereas ONSF has been preferred in patients with
severe papilledema and vision loss with relatively mild or no headache [43].
Recent studies have found CSF shunting procedures to be effective in im-
proving visual acuity, visual field function, RNFL swelling, and papilledema
grades [44, 45]. Among 15 patients, post-operative Humphrey visual field mean
deviation improvement was 5.63 dB [44]. A large retrospective review [46] of LP
and VP shunts in 53 patients reported improvements in visual acuity at 6 and
12 months post-operatively. However, headache symptoms were not relieved in
77% of these patients. Furthermore, overshunting may occur and cause low-
pressure headaches. The insertion of VP shunts in IIH patients also can be
technically challenging, since they do not have enlarged ventricles. The use of
stereotactic-guided insertion can help overcome these challenges [47–50]. Fur-
thermore, shunting procedures have been associated with shunt migration,
infection, intra-cerebral hemorrhage, and acquired Chiairi malformation.
Shunt failure and revision rates have been reported to be as high as 60% for LP
shunts and 30% for VP shunts [49, 51, 52].
ONSF was first described surgically by deWecker, but Hayreh [53] described
its use for resolution of papilledema in the treatment of vision loss. It has been
suggested that the initial improvement in vision after an ONSF is from the
formation of a fistula. This is then followed by fibrous tissue formation over a
course of months, which acts as a barrier to the transmission of CSF pressure to
the retrolaminar portion of the optic nerve [54]. The optic nerve may be
approached via medial orbitotomy, superomedial lid crease incision, or lateral
orbitotomy [55].
A literature survey comparing published series of ONSF and CSF diversion
suggested superior outcomes after ONSF [56]. In one series, ONSF was associ-
ated with stable or improved visual acuity in as many as 94% of patients and
stable or improved visual fields in 88% [57]. Post-operatively, ONSF patients
demonstrate resolution of papilledema and significantly reduced retinal nerve
fiber later thickness on OCT measurements [58].
A 7-year review of visual outcomes from 33 eyes in 15 patients who
underwent ONSF found that 22.6% improved, 58.1% remained stable, and
19.3% worsened [59]. Four patients underwent CSF diversion procedures (VP
or LP shunts) after failed ONSF. The failure rate with recurrence of visual
symptoms has been reported to be as high as 32% [60].
Authors from a single institution compared outcomes of ONSF and CSF
diversion over a 10-year period and found that preoperative visual acuity and
visual field mean deviation were worse in the ONSF group as was papilledema
severity [61]. Although final visual acuity was equivalent, CSF diversion patients
had a better final mean deviation [61]. A multicenter, NIH-funded prospective
study to compare the efficacy of these two surgical procedures is about to start
patient recruitment at the time of this writing. As we await the results of this
24 Page 8 of 13 Curr Treat Options Neurol (2018) 20:24

study (the senior author is principal investigator and orbital surgeon at one
study site), we will continue to offer patients the option of both procedures
when indicated.
Alsuhaibani et al. reviewed the outcome of 78 patients who underwent
ONSF, 62 of whom had only unilateral surgery [62]. They noted similar
improvement in papilledema grade and stability of visual field defects in both
the operated eye and the contralateral unoperated eye. It has been proposed
that CSF drainage through the fenestration can draw fluid from the contralateral
side via communication through the suprasellar cistern. However, research has
shown that trabeculae within the nerve sheath often hinder free flow of CSF
between the optic nerves and the intracranial space [63], and the mechanism
remains unsettled. Because of possible CSF sequestration and unequal response
to surgery, we recommend that fellow eye ONSF be considered if the operated
eye starts to improve in the immediate (24–72 h) postoperative period while
the fellow eye continues to worsen.
Reported complication rates in ONSF vary from 15.6% up to 40%. Com-
plications ranged from self-limiting cases of diplopia, anisocoria, and disc
hemorrhages to more severe cases of profound vision loss [64, 65].
Developments and refinements in MRV technology have allowed us to
identify anatomic abnormalities of the cerebral venous sinuses in patients
with IIH. In a study of 51 IIH patients, 90% displayed evidence of bilateral
transverse sinus stenosis (TSS) on MRV [66]. In IIH patients, either uni-
lateral or bilateral narrowing has been noted at the distal transverse sinus
or transverse/sigmoid sinus junction. This is a distinct finding from trans-
verse sinus asymmetry, which is attributable to anatomical variability [67,
68]. It is still being debated if the observed venous narrowing is pathogenic
via obstruction of venous outflow and resultant decrease in CSF reabsorp-
tion [69,70] or is simply a consequence of elevated ICP itself. Both case
reports [71] and small case series [72] have demonstrated normalization of
CSF opening pressures after endovascular stenting of transverse sinus ste-
noses through which a hemodynamic pressure gradient was measured
before intervention. However, King et al. showed reversal of venous sinus
abnormalities and elimination of the venous pressure gradient after cervical
puncture and CSF drainage to a manometrically normal ICP [73], and
others have reported similar resolution of venous sinus narrowing after CSF
drainage alone via lumbar puncture or CSF diversion [74–77].
Despite this ongoing controversy, venous sinus stenting has emerged as a
potential treatment option for IIH patients. Higgins et al. in 2002 were the first
to report transverse sinus stenting in an IIH patient with bilateral distal trans-
verse sinus stenoses who had failed medical therapy [78]. Reduction in the
transverse sinus pressure gradient, normalization of CSF pressures, and im-
proved symptoms and clinical signs were noted post-stenting. Since then, a
number of authors from several institutions have published their venous sinus
stenting outcomes reflecting both anatomic and symptomatic resolution of
abnormal findings. Most authors measured the pressure gradient across the
stenotic regions using cerebral venography and manometry, with a gradient of
4–10 mmHg being considered significant and amenable to intervention [72,
79–83]. Unilateral venous sinus stenting was undertaken even in the presence
of bilateral stenosis in most studies, with the apparent dominant side or the side
with the higher pressure gradient being selected.
Curr Treat Options Neurol (2018) 20:24 Page 9 of 13 24

Ahmed et al. reported the largest cohort of 52 IIH patients who underwent TSS
stenting after being deemed refractory to medical management [84]. All patients
had resolution of their papilledema post-stenting, with four patients developing
optic atrophy. Similarly, 77% of patients with preprocedure visual field defects and
69% of patients with visual acuity loss had normalization of their visual function
following stenting. Headaches were reported to resolve in 77% of patients in this
series. Six patients (11.5%) developed recurrent headaches and papilledema and
were found to have re-stenosis of the venous sinus, and subsequently underwent
repeat stenting. A meta-analysis of 19 studies with a total of 207 subjects reported
an overall 81% improvement rate for headaches, 87% for papilledema, and 95%
for pulsatile tinnitus [85]. A separate meta-analysis of eight studies with a total of
136 patients reported resolved or improved papilledema in 97% of patients,
improved visual acuity in 78%, and improved headaches in 83% [86].

Table 1. Treatment options for idiopathic intracranial hypertension

Treatment Strength of Estimated costa Risks/benefits

evidence
Weight loss Prospective case Minimal unless weight loss If food intake is too restricted,
series drugs are used (not nutritional deficiency is possible
required for success) Long-term remission most likely with this
treatment
Risk of IIH recurrence if weight is regained
Acetazolamide Double-masked US retail price: Effective for mild vision loss and may
placebo-controlled $300–400/month with encourage weight loss.
prospective study treatment for Renal calculi and dehydration may occur;
6–12 months rare (approx. 1:1,000,000) incidence of
aplastic anemia
Optic nerve sheath Retrospective case $1350 Immediate improvement of papilledema
fenestration series in most cases
Up to 2% risk of vision loss from surgery
Late failure is frequent
Ventriculoperitoneal Retrospective case $7000 ICP lowering may help acute headache
shunt series and papilledema
Risk of neurological injury and failure is
common as is need for revision surgery
Lifelong infection risk with foreign body in
place
Venous sinus Retrospective case $7000 Rapid resolution of papilledema and
stenting series often headaches
Venous sinus perforation or restenosis can
occur
Weight loss is crucial for long-term success
Bariatric surgery Retrospective case $8000–14,4000 May have greatest long-term success rate
series Weight gain may occur years later
Nutritional deficiency risk if diet is not
adequately supplemented
a
Surgical cost estimates are from Ref. [91]
24 Page 10 of 13 Curr Treat Options Neurol (2018) 20:24

Despite post-procedure anticoagulation therapy, restenosis immediately

proximal to the venous stent has been known to occur, with re-stenting rates
at 12% [84]. Stent placement over a longer segment of the venous system may
reduce such occurrences [87]. Other reported complications include subdural
hemorrhage, subarachnoid hemorrhage, in-stent thrombosis, stent migration,
femoral pseudoaneurysm, retroperitoneal hematoma, hearing loss, urinary tract
infection, and syncope [51,79, 84]. Prospective data collection through a regis-
try and/or clinical trial has been proposed to permit a more robust and unbi-
ased evaluation of the efficacy and safety of venous sinus stenting.
Bariatric surgery has been shown to be successful in achieving long-term
weight loss and is usually reserved for IIH patients that fall in the morbidly
obese category with a BMI of over 40. Fridley et al. reviewed 11 studies of a total
of 62 IIH patients who underwent bariatric surgery, with Roux-en-Y gastric bypass
being the most common bariatric procedure [88]. The majority (56/62, 91%)
reported resolution of their IIH symptoms. Eleven of the 12 patients (92%) who
had undergone preoperative visual field testing and were found to have visual
field defects had resolution of their deficits. Papilledema also improved in 34 of
35 patients post-surgery [88]. However, complications from bariatric surgery are
not minimal and can include pulmonary and venous thromboembolism, anas-
tomotic leak, bowel stricture, bowel perforation, band migration, and erosion
[89]. Long-term risks include nutritional deficiencies and late weight gain.
Conclusion
While the visual prognosis is generally good in IIH patients, the risk of perma-
nent visual loss exists and remains a major cause of morbidity of this disease
process. Early and aggressive management is desired to avoid permanent visual
disability. Weight loss efforts in conjunction with adequate doses of acetazol-
amide should continue to be the first-line therapy for IIH patients. However, it
should be noted that as many as 18–22% of IIH patients do not respond to
conservative regimens [90]. Failure of medical therapy should prompt second-
ary surgical measures, which now comprise optic nerve sheath fenestration, CSF
diversion procedures, venous sinus stenting, and bariatric surgery. These treat-
ment options are summarized in Table 1. Regardless of the modality of treat-
ment, each surgical option is not without significant risks, and this should be
taken into consideration especially in patients with milder disease processes.

Compliance with Ethical Standards

Conflict of Interest
Sivashakthi Kanagalingam declares that she has no potential conflicts of interest.
Prem S. Subramanian is supported in part by a Challenge Grant to the Department of Ophthalmology, University of
Colorado School of Medicine, from Research to Prevent Blindness, Inc.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.
Curr Treat Options Neurol (2018) 20:24
References and Recommended Reading
Papers of particular interest, published recently, have been
highlighted as:
• Of importance
•• Of major importance
1. Friedman DI, Liu GT, Digre KB. Revised diagnostic
criteria for the pseudotumor cerebri syndrome in
adults and children. Neurology. 2013;81:1159–65.
2. Ball AK, Clarke CE. Idiopathic intracranial hyperten-
sion. Lancet Neurol. 2006;5:433–42.
3. Durcan FJ, Corbett JJ, Wall M. The incidence of
pseudotumor cerebri: population studies in Iowa and
Louisiana. Arch Neurol. 1988;45:875–7.
4. Radhakrishnan K, Ahlskog JE, Cross SA, et al. Idio-
pathic intracranial hypertension (pseudotumor
cerebri). Descriptive epidemiology in Rochester, Minn,
1976 to 1990. Arch Neurol. 1993;50:78–80.
5. Kesler A, Stolovic N, Bluednikov Y, et al. The incidence
of idiopathic intracranial hypertension in Israel from
2005 to 2007: results of a nationwide survey. Eur J
Neurol. 2014;21:1055–9.
6.•• Markey KA, Mollan SP, Jensen RH, et al. Understanding
idiopathic intracranial hypertension: mechanisms,
management and future directions. Lancet Neurol.
2016;15:78–91.
An important review by one of the top IIH research teams that
synthesizes much of our understanding of the pathogenesis of
this disease and makes progress toward removing the term
“idiopathic” from the process.
7. Malm J, Kristensen B, Markgren P, et al. CSF hydrody-
namics in idiopathic intracranial hypertension: a long
term study. Neurology. 1992;42:851–8.
8.• Markey K, Uldall M, Botfield H, et al. Idiopathic intra-
cranial hypertension, hormones, and 11β-
hydroxysteroid dehydrogenases. J Pain Res.
2016;19:223–32.
Groundwork for a possible directed IIH therapy.
9. Friedman DI. Medication-induced intracranial hyper-
tension in dermatology. Am J Clin Dermatol.
2005;6:29–37.
10. Kesler A, Goldhammer Y, Hadayer A, et al. The out-
come of pseudotumor cerebri induced by tetracycline
therapy. Acta Neurol Scand. 2004;110:408–11.
11. Biousse B, Bruce B, Newman N. Update of the patho-
physiology and management of idiopathic intracranial
hypertension. J Neurol Neruosurg Psychiatry.
2012;83:488–94.
12. Wall M. The headache profile of intracranial hyperten-
sion. Cephalagia. 2002;10:331–5.
13. Francis CE, Quiros PA. Headache management in idi-
opathic intracranial hypertension. Int Ophthalmol
Clin. 2014;54:103–14.
14. Bidot S, Bruce B, Saindane A, et al. Asymmetric
papilledema in idiopathic intracranial hypertension. J
Neuroophthalmol. 2015;35:31–6.
15. Corbett J, Savino P, Thompson H, et al. Visual loss in
pseudotumour cerebri. Arch Neurol. 1982;39:461–74.
Page 11 of 13 24
16. Rowe F, Sarkies N. Assessment of visual function in
idiopathic intracranial hypertension: a prospective
study. Eye. 1998;12:111–8.
17. Wall M, George D. Idiopathic intracranial hyperten-
sion: a prospective study of 50 patients. Brain.
1991;114:155–80.
18. Wall M, White WN. Asymmetric papilledema in idio-
pathic intracranial hypertension: prospective intraocu-
lar comparison of sensory visual function. Invest
Ophthalmol Vis Sci. 1998;39:134–42.
19. Wall M. The morphology of visual field damage in
idiopathic intracranial hypertension: an anatomic re-
gion analysis. In: Miss RP, Heijl A, editors. Perimetry
update: Kugler Publications; 1991. p. 20–7.
20. Friedman DI. Idiopathic intracranial hypertension.
Curr Pain Headache Rep. 2007;11:62–8.
21. Wall M, Thurtell MJ, NORDIC Idiopathic Intracranial
Hypertension Study Group. Optic disc hemorrhages at
baseline as a risk factor for poor outcome in idiopathic
intracranial hypertension treatment trial. Br J
Ophthalmol. 2017;101:1256–60.
22. Frisen L. Swelling of the optic nerve head: a staging
scheme. J Neurol Neurosurg Psychiatr. 1982;45:13–8.
23. Rizzo HG. Use of optical coherence to evaluate
papilledema and pseudopapilledema. Semin
Ophthalmol. 2010;25:198–205.
24. Karam EZ, Hedges TR. Optical coherence tomography of
the retinal nerve fiber layer in mild papiloedema and
pseudopapilloedema. Br J Ophthalmol. 2005;89:294–8.
25. Bebolleda G, Munoz-Negrete FJ. Follow up of mild
papilledema in idiopathic intracranial hypertension
with optical coherence tomography. Invest
Ophthalmol Vis Sci. 2009;50:5197–200.
26. Wang J, Kardon R, Kupersmith M, et al. Automated
quantification of volumetric optic disc swelling in
papilledema using spectral-domain optical conherence
tomography. Invest Ophthalmol Vis Sci.
2012;53:4069–75.
27. Ahuja S, Anand D, Dutta TK, et al. Retinal nerve fiber
layer thickness analysis in cases of papilledema using
optical coherence tomography—a case control study.
Clin Neurol Neurosurg. 2015;136:95–9.
28. OCT Sub-study Committee for NORDIC Idiopathic
Intracranial Hypertension Study Group, Auinger P,
Durbin M, et al. Baseline OCT measurements in the
idiopathic intracranial hypertension treatment trial,
part II: correlations and relationship to clinical features.
Invest Ophthalmol Vis Sci. 2014;55:8173–9.
29.•• Optical Coherence Tomography Sub-study Commit-
tee, NORDIC Idiopathic Intracranial Hypertension
Study Group. Papilledema outcomes from the Optical
Coherence Tomography Sub-study of the Idiopathic
24 Page 12 of 13
intracranial hypertension treatment trial. Ophthal-
mology. 2015;122:1939–45.
Prospective, systematic demonstration of the utility of OCT in
the long-term surveillance and management of patients with
IIH; uses methods that overcome limitations of prior
techniques.
30. Bidot S, Saindane AM, Peragallo JH, et al. Brain imag-
ing in idiopathic intracranial hypertension. J
Neuroophthalmol. 2015;35:400–11.
31. Brodsky MC, Vaphiades M. Magnectic resonance im-
aging in pseudotumor cerebri. Ophthalmology.
1998;105:1686–93.
32. Farb RI, Vanek I, Scott JN, et al. Idiopathic intracranial
hypertension: the prevalence and morphology of
sinovenous stenosis. Neurology. 2003;60:1418–24.
33. Lee AG, Brazis PW. Magnetic resonance venography in
idiopathic pseudotumor cerebri. J Neuroophthalmol.
2000;20:12–3.
34. Whiteley W, Al-Shahi R, Warlow CP, et al. CSF opening
pressure: reference interval and the effect of the body
mass index. Neurology. 2006;67:1690–1.
35. Wong R, Madill SA, Pandey P, et al. Idiopathic intra-
cranial hypertension: the association between weight
loss and the requirement for systemic treatment. BMC
Ophthalmol. 2017;25:342–4.
36.•• NORDIC Idiopathic Intracranial Hypertension Study
Group Writing Committee, Wall M, MP MD, Kieburtz
JD, et al. Effect of acetazolamide on visual function in
patients with idiopathic intracranial hypertension and
mild visual loss: the idiopathic intracranial treatment
trial. JAMA. 2014;311:1641–51.
Landmark prospective study evaluating the efficacy of acet-
azolamide in the treatment of patients with IIH.
37. ten Hove MW, Friedman DI, Patel AD, et al. Safety and
tolerability of acetazolamide in the Idiopathic Intra-
cranial Hypertension Treatment Trial. J
Neuroophthalmol. 2016;36:13–9.
38. Kattah JC, Pula JH, Mejico LJ, et al. CSF pressure,
papilledema grade, and response to acetazolamide in
the Idiopathic Intracranial Hypertension Treatment
Trial. J Neurol. 2015;262:2271–4.
39.• Friedman DI, Quiros PA, Subramanian PS, et al.
Headache in idiopathic intracranial hypertension:
findings from the Idiopathic Intracranial Hyper-
tension Treatment Trial. Headache. 2017;57:1195–
205.
Demonstrates lack of a relationship between ICP lowering
and headache relief in a large prospectively treated cohort.
40. Celebisoy N, Gokcay F, Sirin H, et al. Treatment of
idiopathic intracranial hypertension: topiramate vs ac-
etazolamide, an open-label study. Acta Neurol Scand.
2007;116:322–7.
41. Schoeman JF. Childhood pseudotumor cerebri:
clinical and intracranial pressure response to acet-
azolamide and furosemide treatment in a case
series. J Child Neurol. 1994;9:130–4.
42. Thiambisetty M, Lavin PJ, Newman NJ, et al. Fulmi-
nant idiopathic intracranial hypertension. Neurology.
2007;68:229–32.
Curr Treat Options Neurol (2018) 20:24
43. Wakerley B, Tan M, Ting E. Idiopathic intracranial hy-
pertension. Cephalalgia. 2015;35:248–61.
44. Rizzo JL, Lam KV, Wall M, et al. Perimetry, retinal nerve
fiber layer thickness and papilledema grades after ce-
rebrospinal fluid shunting in patients with idiopathic
intracranial hypertension. J Neuroophthalmol.
2015;35:22–5.
45. Huang LC, Winter TW, Herro AM, et al.
Ventriculoperitoneal shunt as a treatment of visual loss
in idiopathic intracranial hypertension. J
Neuroophthalmol. 2014;34:223–8.
46. Sinclair AJ, Kuruvath S, Sen D, et al. Is cerebrospinal
fluid shunting in idiopathic intracranial hypertension
worthwhile? A 10-year review. Cephalalgia.
2011;31:1627–33.
47. McGirt MJ, Woodworth G, Thomas G, et al. Cerebro-
spinal fluid shunt placement of pseudotumor cerebri-
associated intractable headache: predictors of treat-
ment response and an analysis of long-term outcomes.
J Neurosurg. 2004;101:627–32.
48. Maher CO, Garrity JA, Meyer FB. Refractory idiopathic
intracranial hypertension treated with stereotactically
planned ventriculopertioneal shunt placement.
Neurosurg Focus. 2001;10:E1.
49. Rosenberg MI, Corbett JJ, Smith C, et al. Cerebrospinal
fluid diversion procedures in pseudotumor cerebri.
Neurology. 1993;43:1071–2.
50. Eggenberger ER, Miller NR, Vitale S. Lumboperitoneal
shunt for the treatment of pseudotumor cerebri. Neu-
rology. 1996;46:1524–30.
51. Lueck CJ, McIlwaine GG. Idiopathic intracranial hy-
pertension. Pract Neurol. 2002;2:262–71.
52. Abubaker K, Ali Z, Raza K, et al. Idiopathic intracranial
hypertension: lumboperitoneal shunts versus
ventriculperitoneal shunts—case series and literature
review. Br J Neurosurg. 2011;25:94–9.
53. Hayreh SS. Pathogenesis of oedema of the optic disc. A
preliminary report. Br J Ophthalmol. 1964;48:522–43.
54. Yazici Z, Yazici B, Tuncel E. Findings of magnetic res-
onance imaging after optic nerve sheath decompres-
sion in patients with idiopathic intracranial hyperten-
sion. Am J Ophthalmol. 2007;144:429–35.
55. Sobel RK, Syed NA, Carter KD, et al. Optic nerve sheath
fenestration: current preferences in surgical approach
and biopsy. Ophthal Plast Reconstr Surg.
2015;31:310–2.
56. Feldon SE. Visual outcomes comparing surgical tech-
niques for management of severe idiopathic intracra-
nial hypertension. Neurosurg Focus. 2007;23:E6.
57. Banta JT, Farris BK. Pseudotumor cerebri and optic
nerve sheath decompression. Ophthalmology.
2000;107:1907–12.
58. Starks V, Gilliland G, Vrcek I, et al. Effect of optic nerve
sheath fenestration for idiopathic intracranial hyper-
tension on retinal nerve fiber layer thickness. Orbit.
2016;35:87–90.
59. Obi EE, Lakhani BK, Burns J, et al. Optic nerve sheath
fenestration for idiopathic intracranial hypertension: a
Curr Treat Options Neurol (2018) 20:24
seven year review of visual outcomes in a tertiary cen-
ter. Clin Neurol Neurosurg. 2015;137:94–101.
60. Spoor TC, McHenry JG. Long-term effectiveness of op-
tic nerve sheath decompression for pseudotumor
cerebri. Arch Ophthalmol. 1993;111:632–5.
61. Fonseca PL, Rigamonti D, Miller NR, et al. Visual out-
comes of surgical intervention for pseudotumor
cerebri: optic nerve sheath fenestration versus cerebro-
spinal fluid diversion. Br J Ophthalmol.
2014;98:1360–3.
62. Alsuhaibani AH, Carter KD, Nerad JA, et al. Effect of
optic nerve sheath decompression for the treatment of
visual failure in chronic raised intracranial pressure.
Ophthalmology. 2011;118:412–4.
63. Killer HE, Subramanian PS. Compartmentalized cere-
brospinal fluid. Int Ophthalmol Clin. 2014;54:95–102.
64. Plotnik JL, Kosmorsky GS. Operative complications of
optic nerve sheath decompression. Ophthalmology.
1993;100:683–90.
65. Chandrasekaran S, McCluskey P, Minassian D, et al.
Visual outcomes for optic nerve sheath fenestration in
pseudotumor cerebri and related conditions. Clin Exp
Ophthalmol. 2006;34:661–5.
66. Riggeal BD, Bruce BB, Saindane AM, et al. Clinical
course of idiopathic intracranial hypertension with
transverse sinus stenosis. Neurology. 2013;80:289–95.
67. Stranding S, Ellis H, Healy JC et al. 2005 Gray’s anat-
omy: the anatomical basis of clinical practice. 39th Ed
Edinburgh: Elsevier Churchill Livingstone.
68. Strydom MA, Briers N, Bosman MC, et al. The ana-
tomical basis of venographic filing defects of the
transverse sinus. Clin Anat. 2010;23:153–9.
69. Roche J, Warner D. Arachnoid granulations in the
transverse and sigmoid sinuses: CT, MR, and MR an-
giographic appearance of a normal anatomic variation.
Am J Neuroradiol. 1996;17:677–83.
70. Leach J, Jones BV, Tomsick T, et al. Normal appearance
of Arachnoid granulations on contrast-enhanced CT
and MR of the brain: differentiation from dural sinus
disease. Am J Neuroradiol. 1996;17:1523–32.
71. Zheng HB, Zhou M, Zhao B, et al. Pseudotumor cerebri
syndrome and giant arachnoid granulation: treatment
with venous sinus stenting. J Vasc Interv Radiolo.
2010;21:927–9.
72. Donnet A, Metellus P, Levrier O, et al. Endovascular
treatment of idiopathic intracranial hypertension:
clinical and radiological outcome of 10 consecutive
patients. Neurology. 2008;70:641–7.
73. King JO, Mitchell PJ, Thomson KR, et al. Manometry
combined with cervical puncture in idiopathic intra-
cranial hypertension. Neurology. 2002;58:26–30.
74. De Simone R, Marano E, Fiorillo C, et al. Sudden re-
opening of collapsed transverse sinuses and longstanding
clinical remission after a single lumbar puncture in a case
of idiopathic intracranial hypertension. Pathogenetic im-
plications. Neurol Sci. 2005;25:342–4.
75. Stienen A, Weinzierl M, Ludolph A, et al. Obstruction
of cerebral venous sinus secondary to idiopathic intra-
cranial hypertension. Eur J Neurol. 2008;15:1416–8.
Page 13 of 13 24
76. Horev A, Hallevy H, Plakht Y, et al. Changes in cerebral
venous sinuses diameter after lumbar puncture in idi-
opathic intracranial hypertension: a prospective MRI
study. J Neuroimaging. 2013;23:375–8.
77. Baryshnik DB, Farb RI. Changes in the appearance of
venous sinuses after treatment of disordered intracra-
nial pressure. Neurology. 2004;62:1445–6.
78. Higgins JN, Owler BK, Cousins C, et al. Venous sinus
stenting for refractory benign intracranial hyperten-
sion. Lancet. 2002;359:228–30.
79. Kumpe DA, Bennett JL, Seinfeld J, et al. Dural sinus
stent placement for idiopathic intracranial hyperten-
sion. J Neurosurg. 2012;116:538–48.
80. Owler BK, Parker G, Halmagyi, et al. Pseudotumour
cerebri syndrome: venous sinus bstruction and its
treatment with stent placement. J Neurosurg.
2003;98:1045–55.
81. Radvany MG, Solomon D, Nijjar S, et al. Visual and
neurological outcomes following endovascular
stenting for pseudotumour cerebri associated with
transverse sinus stenosis. J Neuroophthalmol.
2013;33:117–22.
82. Fields JD, Javedani PP, Falardeau J, et al. Dural venous
sinus angioplasty and stenting for the treatment of
idiopathic intracranial hypertension. J Neurointerv
Surg. 2012;5:62–8.
83. Higgins JNP, Cousins C, Owler BK, et al. Idiopathic
intracranial hypertension: 12 cases treated by venous
sinus stenting. J Neurol Neurosur Psychiartry.
2003;74:1662–6.
84. Teleb MS, Cziep ME, Lazzaro MA, et al. Idiopathic
intracranial hypertension. A systemic analysis. Interv
Neurol. 2013;3:132–43.
85. Satti SR. Meta-analysis of CSF diversion procedures and
dural venous sinus stenting in the setting of medically
refractory IIH. Am J Neuroradiol. 2015;36:1899–904.
86. Albuquerque FC, Dashti SR, Hu YC, et al. Intracranial
venous sinus stenting for benign intracranial hyper-
tension: clinical indications, technique, and prelimi-
nary results. World Neurosurg. 2011;75:648–52.
87. Kumpe DA, Seinfeld J, Huang X, et al. Dural sinus
stenting for idiopathic intracranial hypertension: fac-
tors associated with hemodynamic failure and man-
agement with extended stenting. J Neurointerv Surg.
2017;9:867–74.
88. Fridley J, Foroozan R, Sherman V, et al. Bariatric surgery
for the treatment of idiopathic intracranial hyperten-
sion. J Neurosurg. 2011;114:34–9.
89. Favretti F, Segato G, Ashton D, et al. Laparoscopic
adjustable gastric banding in 1791 consecutive obese
patients: 12 year results. Obes Surg. 2007;17:168–75.
90. Garton HJL. Cerebrospinal fluid diversion procedures.
J Neurol. 2004;24:146–55.
91. Kalyvas AV, Hughes M, Koutsarnakis C, et al. Efficacy,
complications, and cost of surgical interventions for
idiopathic intracranial hypertension: a systematic re-
view of the literature. Acta Neurochir. 2017;159:33–49.