An Update on Idiopathic Intracranial Hypertension

Abstract

Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology often encountered in neurologic practice. It produces nonlocalizing symptoms and signs of raised intracranial pressure and, when left untreated, can result in severe irreversible visual loss. It most commonly occurs in obese women of childbearing age, but it can also occur in children, men, nonobese adults, and older adults. Although it is frequently associated with obesity, it can be associated with other conditions, such as obstructive sleep apnea and transverse cerebral venous sinus stenoses. Recent identification of subgroups at high risk for irreversible visual loss, including black patients, men, and patients with fulminant forms of IIH, help guide the optimal management and follow-up. Ongoing studies of venous anatomy and physiology in IIH patients, as well as a recently begun randomized clinical treatment trial, should provide further insight into this common yet poorly understood syndrome.

Full text

e56 VOL. 7 NO. 2/3 2010 REVIEWS IN NEUROLOGICAL DISEASES
MANAGEMENT UPDATE
An Update on Idiopathic
Intracranial Hypertension
Matthew J. Thurtell, MBBS, FRACP,1Beau B. Bruce, MD,1,2
Nancy J. Newman, MD,1,2,3 Valérie Biousse, MD1,2
Departments of 1Ophthalmology, 2Neurology, and 3Neurological Surgery, Emory University,
Atlanta, GA
Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology often
encountered in neurologic practice. It produces nonlocalizing symptoms and signs of
raised intracranial pressure and, when left untreated, can result in severe irreversible
visual loss. It most commonly occurs in obese women of childbearing age, but it can
also occur in children, men, nonobese adults, and older adults. Although it is fre-
quently associated with obesity, it can be associated with other conditions, such as
obstructive sleep apnea and transverse cerebral venous sinus stenoses. Recent identifi-
cation of subgroups at high risk for irreversible visual loss, including black patients,
men, and patients with fulminant forms of IIH, help guide the optimal management
and follow-up. Ongoing studies of venous anatomy and physiology in IIH patients, as
well as a recently begun randomized clinical treatment trial, should provide further
insight into this common yet poorly understood syndrome.
[Rev Neurol Dis. 2010;7(2/3):e56-e68 doi: 10.3909/rind0256]
© 2010 MedReviews®, LLC
Key words: Idiopathic intracranial hypertension • Venous sinus stenosis •
Ventriculoperitoneal shunting • Lumboperitoneal shunting • Optic nerve sheath
fenestration • Venous sinus stenting
Idiopathic intracranial hypertension (IIH) is a syndrome in which there is in-
creased intracranial pressure (ICP) of unknown etiology. Previously known
as pseudotumor cerebri or benign intracranial hypertension, this condition most
frequently occurs in obese women of childbearing age. It is defined by the re-
vised modified Dandy criteria,1including 1) symptoms and signs of raised ICP
(headache, nausea, vomiting, pulsatile tinnitus, transient visual obscurations,
papilledema); 2) no localizing signs, except for sixth nerve palsy; 3) no cause for
raised ICP identified on neuroimaging (brain magnetic resonance imaging
[MRI]); 4) cerebrospinal fluid (CSF) opening pressure of greater than 25 cm H2O,
with normal CSF composition; and 5) no alternate explanation for the raised
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Idiopathic Intracranial Hypertension
VOL. 7 NO. 2/3 2010 REVIEWS IN NEUROLOGICAL DISEASES e57
ICP. Although it is well known that
untreated IIH can result in severe
irreversible visual loss, major contro-
versies remain regarding its patho-
physiology, natural history, and
treatment.
What’s In a Name? “Idiopathic
Intracranial Hypertension”
IIH, by its very name, assumes that
no underlying cause for raised ICP
has been identified. IIH is a diagnosis
of exclusion that can only be made
in patients who satisfy the revised
modified Dandy criteria.1Brain
imaging studies, including a brain
MRI, often with additional specific
venous sequences (eg, computed
tomography [CT] or MR venogra-
phy), and a lumbar puncture are
therefore required in the evaluation
of patients with suspected IIH.
Numerous studies have emphasized
that a head CT is not sufficient to
exclude other causes of raised ICP,
such as cerebral venous thrombosis.2
By definition, IIH includes all
patients with isolated raised ICP that
is not related to an intracranial
process, cerebral venous thrombosis,
or a meningeal process. Somewhat
ironically, patients who develop a
syndrome of raised ICP secondary to
specific medications or who are
found to have a cerebral venous
sinus stenosis (not thrombosis) are
still conventionally classified as
having IIH. Therefore, although not
always ideal, the term idiopathic in-
tracranial hypertension is the preferred
designation for this disorder in the
English literature. The term pseudotu-
mor cerebri should not be used, as it
often includes patients with other
causes of raised ICP and is thus con-
fusing. The term benign intracranial
hypertension erroneously suggests
that this disorder is benign, whereas
up to 31% of patients with IIH irre-
versibly lose vision.3It has been sug-
gested that the terms primary and
secondary intracranial hypertension
might be considered to describe ei-
ther 1) young obese women with iso-
lated raised ICP and no obvious pre-
cipitating factors, or 2) patients with
isolated raised ICP associated with
factors such as endocrine disorders,
anemia, obstructive sleep apnea,
medications, or cerebral venous
sinus stenoses.4,5 At this point, the
preferred term idiopathic intracranial
hypertension emphasizes our general
lack of understanding of the patho-
physiology of this disorder.
Update on the Epidemiology
of IIH
In the United States, the annual inci-
dence of IIH has been reported to be
0.9 per 100,000 in Iowa and 1.07 per
100,000 in Louisiana.6IIH is more
common in women and obese indi-
viduals.6-9 Among women aged 20 to
44 years who are 20% or more above
ideal body weight, the incidence
increases to approximately 19 per
100,000, about 20 times the inci-
dence in the general population and
similar to the incidence of multiple
sclerosis.6,10 Obese women with IIH
might have a preferential accumula-
tion of fat in the lower body relative
to other obese women in the same
age range.11 In a recent multicenter,
case-control study comparing newly
diagnosed women with IIH and
women who were newly diagnosed
with other neuro-ophthalmologic
disorders, it was confirmed that
higher body mass index (BMI) is as-
sociated with a greater risk of IIH.12
Interestingly, this study showed that
even nonobese patients were at
greater risk for IIH if they had a re-
cent moderate weight gain. Thus, it
is likely that the prevalence of IIH in
the developed world will rise in par-
allel with that of obesity.10
Despite a high predilection for
obese young women, IIH can occur
in children, older adults, and in
nonobese persons of either sex.13,14
IIH does occur in childhood, but no
large epidemiologic studies in this
age group have been reported to
date. The disorder is rare in prepu-
bertal children and has distinct
characteristics from the adult form,
including no apparent predilection
for obese girls.13,15 In older teenagers
with IIH, however, the rate of obesity
is similar to that in the adult IIH
population.13-15 In a recent large
series, the prevalence of IIH in men
was approximately 10%,9thereby
confirming that IIH in men is
rare.16-19 Affected men have a similar
BMI when compared with affected
women, but are, on average, about a
decade older than women at the
time of presentation.9Ethnic back-
ground is not thought to affect the
incidence of IIH,8,20 although few
studies have addressed this question.
Familial cases are occasionally en-
countered, but there is little evidence
to support a genetic predisposition.21
Clinical Features of IIH
Headache
IIH typically presents with symp-
toms and signs of raised ICP.
Headache, the most common symp-
tom at presentation,18,22 is less likely
to be reported by men than by
women.9The headache of IIH is typ-
ically holocranial, worse after wak-
ing, and exacerbated by maneuvers
In a recent multicenter, case-control study comparing newly diagnosed
women with IIH and women who were newly diagnosed with other neuro-
ophthalmologic disorders, it was confirmed that higher body mass index
(BMI) is associated with a greater risk of IIH.
2. RIND0256_07-28.qxd 7 /28/10 4:54 PM Page e57

that increase ICP. If it is predomi-
nantly due to raised ICP, it can
improve dramatically following a
lumbar puncture or a CSF diversion
procedure. However, many patients
have a coexisting primary headache
disorder, such as migraine or tension
headache,23 and hence the headache
does not always respond to treat-
ments that decrease ICP.
Papilledema and Visual Loss
Papilledema is the most common
sign at presentation and is indistin-
guishable from papilledema occur-
ring with other causes of raised ICP
(Figure 1). In patients with IIH, the
severity of papilledema does not cor-
relate with age, race, or BMI.24 It is
usually symmetric, but can be asym-
metric, unilateral, or even absent.25-28
Some studies have suggested that, in
patients with asymmetric or absent
papilledema, anatomic compartmen-
talization of the subarachnoid space
around the optic nerve might stop
the CSF pressure gradient from
reaching the retrolaminar portion
of the optic nerve.29,30 Papilledema
can be associated with peripapillary
hemorrhages, exudates, and macular
edema.
Papilledema often produces brief
episodes of monocular or binocular
visual loss, called transient visual
obscurations (TVOs).18,22 TVOs are
often precipitated by postural
changes and Valsalva-like maneu-
vers, with vision rapidly recovering
back to baseline between episodes.
TVOs are thought to occur due to
transient ischemia of the swollen
optic nerve head and, although dra-
matic, are not a sign of impending
permanent visual loss. Rarely, IIH pa-
tients with papilledema can report
gaze-evoked amaurosis, which is
transient visual loss precipitated by
Idiopathic Intracranial Hypertension continued
e58 VOL. 7 NO. 2/3 2010 REVIEWS IN NEUROLOGICAL DISEASES
A
B
C
Right Eye Right EyeLeft Eye Left Eye
30
30
30
30
30
30
Figure 1. Papilledema and subtle visual field changes in an obese young woman with idiopathic intracranial hypertension (IIH). (A) At presentation,
the patient had severe headache, bilateral papilledema (elevated optic nerves, peripapillary hemorrhages, and dilated retinal veins), and enlargement
of the physiologic blind spots on 24-2 Humphrey visual fields. Following a diagnostic lumbar puncture, her headache improved for several days. She
had refused to take acetazolamide, but attempted to lose weight. (B) The patient’s headaches and papilledema worsened, despite one lumbar punc-
ture and attempts at weight loss, but her visual fields remained stable. Because she reported dramatic, but transient, improvement in symptoms fol-
lowing serial lumbar punctures, she was referred for a cerebrospinal fluid shunting procedure. (C) Three months following lumbo-peritoneal shunting,
her symptoms and signs had resolved. The optic nerves remained mildly elevated, with mild gliosis and pallor, but her visual fields were full.
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Idiopathic Intracranial Hypertension
VOL. 7 NO. 2/3 2010 REVIEWS IN NEUROLOGICAL DISEASES e59
movement of the eye into an eccen-
tric gaze position.31
Untreated papilledema can result
in progressive irreversible visual loss
and secondary optic atrophy in up to
31% of patients.16,18,32-34 However,
sustained visual loss is less com-
monly reported than TVOs at the
time of presentation.18 Irreversible
visual loss is more likely to occur in
men,9black patients,8patients with a
fulminant onset of IIH,35 and pa-
tients with coexisting systemic
hypertension16 or anemia.36 In most
IIH patients, papilledema produces
insidious and slowly progressive
visual loss. Enlargement of the phys-
iologic blind spot (Figure 1) is the
earliest visual field defect to occur
and is not of great concern, because
it is simply a refractive scotoma re-
sulting from elevation of the peri-
papillary retina. Other visual field
defects develop with time, including
nasal (especially inferonasal) defects,
arcuate defects, and severe visual field
constriction (Figure 2).18,37 These vi-
sual field defects may not be recog-
nized by patients and may only be
evident on formal perimetry. Central
visual field defects and decreased
visual acuity usually occur in IIH
patients with longstanding severe
papilledema,18,37 but can sometimes
develop rapidly and be present early
in the course of the disease.35 In these
cases, emergent intervention is re-
quired to prevent irreversible visual
loss and optic atrophy (Figure 2).
Central visual loss can also result
from macular edema, macular exu-
dates, or a hyperopic shift resulting
from flattening of the globe or papil-
lomacular choroidal folds,18,38-40 in
which case the prognosis for visual
recovery is relatively good. Rarely,
acute visual loss might result from
anterior ischemic optic neuropa-
thy,41 choroidal infarction,42 or hem-
orrhage from peripapillary choroidal
neovascular membranes,43 particu-
larly in the setting of severe or
chronic papilledema. Not uncom-
monly, nonphysiologic visual field
constriction occurs in patients who
have coexisting organic visual loss
from papilledema,44 sometimes mak-
ing management decisions difficult.
Patients with raised ICP and visual
loss should have obvious pa-
pilledema, unless they have already
developed severe secondary optic
atrophy. In patients with raised ICP
Irreversible visual loss is more likely to occur in men, black patients, pa-
tients with a fulminant onset of IIH, and patients with coexisting systemic
hypertension or anemia.
A
B
Right Eye Left Eye Right EyeLeft Eye
Figure 2. Fulminant onset idiopathic intracranial hypertension, with severe headaches, bilateral papilledema, and visual loss. (A) At the time of presentation, the patient had
severe papilledema, with exudates, decreased visual acuity in both eyes, and severely constricted Goldmann visual fields in both eyes. Her headaches dramatically improved for
a few hours after the diagnostic lumbar puncture. She worsened over the next 24 hours and received a lumbar drain, followed by an urgent cerebrospinal fluid shunting pro-
cedure. (B) Despite shunting, the patient developed secondary optic atrophy in both eyes and had persistent severe visual field loss.
2. RIND0256_07-28.qxd 7 /28/10 4:54 PM Page e59

without papilledema, another cause
for visual loss or nonorganic visual
loss should be considered.27 Visual
loss without papilledema that is di-
rectly due to raised ICP has been re-
ported, but remains exceedingly
rare.28,45
Tinnitus
Pulsatile (pulse-synchronous) tinni-
tus is a common symptom of IIH,18,22
but may not be reported by patients
unless they are specifically asked
about it. It can be unilateral or bilat-
eral, intermittent or continuous.46,47
It is often worse at night and can be
so loud that it is audible to adjacent
people.47 It usually resolves with dig-
ital pressure over the ipsilateral inter-
nal jugular vein, suggesting that it is
venous in origin.48 Indeed, pulsatile
tinnitus probably arises due to turbu-
lent blood flow through transverse
cerebral venous sinus stenoses.
Diplopia and Other Symptoms
Binocular horizontal diplopia occurs
in IIH patients who have unilateral
or bilateral sixth nerve palsies. Verti-
cal diplopia, due to third nerve palsy,
fourth nerve palsy, or skew devia-
tion, has been rarely reported in
patients with high CSF opening pres-
sure and usually improves dramati-
cally once the ICP is lowered.49-53
Other focal neurologic symptoms,
such as facial weakness54 and hearing
loss,46,55 can occur, but are atypical
and should prompt a thorough
search for an alternative diagnosis.
It is also not uncommon to have a
diagnosis of IIH made when pa-
pilledema is detected on a routine
eye examination in an asympto-
matic patient.56
Course of IIH
The course of IIH is somewhat un-
predictable in any given individual.
Most IIH patients do well with obser-
vation and medical management.
However, many have persistent
headaches (that might not be due to
raised ICP), with reduced quality of
life and depression.12,57 When IIH is
associated with an identified trigger-
ing factor, such as anemia or un-
treated obstructive sleep apnea, or a
specific medication, treatment of the
triggering factor or discontinuation
of the offending medication often re-
sults in rapid improvement.36,58,59
The principal morbidity of IIH is
visual loss due to papilledema. Most
patients have visual field defects at
presentation18 and up to 31% will
develop irreversible visual
loss.8,16,18,20,32-34 Thus, all IIH patients
must be monitored during careful
follow-up with formal automated
perimetry, with intervention when-
ever deterioration of visual fields is
documented. Progression of visual
field abnormalities is usually slow
and, in general, reversible if appro-
priately treated. Although the syn-
drome of raised ICP might resolve
within a few months, it has been
suggested that the disorder is often
chronic unless a major intervention
occurs.60 Recurrence is unpre-
dictable, although recent weight
gain has been noted to be a definite
precipitant in many cases.10,12,61
However, there is a small subset of
patients with IIH who have an acute
onset of symptoms and signs of
raised ICP (4 weeks between onset
of initial symptoms and severe visual
loss), with rapid worsening of visual
loss over a few days, who still fit the
criteria for IIH, who have normal
brain MRI and venography results.
In a recent study of 16 such “fulmi-
nant IIH” cases, all were women, all
were obese, and the first CSF open-
ing pressure was, on average, 54 cm
H2O.35 Surgical treatment was re-
quired due to ongoing visual loss in
all patients, but 50% remained
legally blind and the visual fields
remained severely impaired in all
cases. Prompt recognition and early
aggressive treatment of patients
with fulminant IIH is therefore
essential.35,62
No consistent correlations have
been found between visual outcome
and age at diagnosis, BMI, medica-
tion use, CSF opening pressure, dura-
tion or type of symptoms, and
chronicity of papilledema. A signifi-
cant association was found between
visual loss and the occurrence of sys-
temic hypertension in one study,16
but not others. Anemia was associ-
ated with a worse visual outcome in
2 studies.36,63 A recent study showed
that black patients with IIH were
3 times more likely than other pa-
tients to have severe visual loss in at
least one eye and were nearly 5 times
more likely to be blind in both eyes.8
The difference was shown not to be
the result of racial differences in di-
agnosis, treatment, or access to care.
IIH in black patients appears to be a
more aggressive disease and, there-
fore, needs closer follow-up and a
lower threshold for early aggressive
intervention. A second study from
the same patient database showed
that men were more likely to have
worse visual acuity and visual fields
at presentation and follow-up, and
were less likely to report headaches
than women.9The relative risk of
severe visual loss for men compared
with women was at least 2.1. Similar
to black patients, men with IIH
should be followed closely, because
Idiopathic Intracranial Hypertension continued
e60 VOL. 7 NO. 2/3 2010 REVIEWS IN NEUROLOGICAL DISEASES
A recent study showed that black patients with IIH were 3 times more likely
than other patients to have severe visual loss in at least one eye and were
nearly 5 times more likely to be blind in both eyes.
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Idiopathic Intracranial Hypertension
VOL. 7 NO. 2/3 2010 REVIEWS IN NEUROLOGICAL DISEASES e61
they may not reliably experience or
report other symptoms of raised ICP.
Men with IIH may also need more
aggressive treatment. In a recent
study comparing white French and
American IIH patients,20 American
patients had worse visual outcomes,
despite receiving more aggressive
treatment. The differences in out-
come could not be explained by dif-
ferences in known risk factors.20
Brain Imaging in IIH
By definition, brain imaging must
exclude other causes of raised ICP,
such as mass lesions, hydrocephalus,
and cerebral venous thrombosis, to
make the diagnosis of IIH.1However,
imaging abnormalities associated
with raised ICP are commonly ob-
served in patients with IIH. These in-
clude empty sella or flattening of the
pituitary, tight subarachnoid spaces,
flattening of the posterior globe, pro-
trusion of the optic nerve head, en-
hancement of the prelaminar por-
tion of the optic nerve head,
distension of the optic nerve sheath,
and vertical tortuosity of the optic
nerve (Figure 3).64,65 Some patients
with presumed IIH have a type I
Chiari malformation.66 However, the
diagnosis of IIH should be made with
caution in these patients, in whom
the Chiari malformation might be
the cause of raised ICP and might
contraindicate a lumbar puncture.
Imaging of the cerebral venous
system with MR or CT venography
should be routinely obtained to ex-
clude cerebral venous thrombosis in
patients with presumed IIH, espe-
cially in men, nonobese patients,
children, older patients, and those
with an atypical or fulminant pre-
sentation.2,67 Whether dedicated ve-
nous imaging must be systematically
obtained in all IIH patients remains
debated. In most cases, routine brain
MRI is sufficient to exclude cerebral
venous thrombosis.
Numerous studies published in the
past decade have shown that
changes at the level of the transverse
cerebral venous sinuses (not throm-
bosis) are common in typical IIH pa-
tients.68,69 With older time-of-flight
MR venography techniques, these
changes were often dismissed as
flow-related artifacts.70 However,
more recent studies using either di-
rect retrograde cerebral venography,
contrast-enhanced MR venography,
or contrast-enhanced CT venogra-
phy have confirmed the presence of
true stenoses in the transverse ve-
nous sinuses (Figure 4).68,69,71,72 These
stenoses can be bilateral or, in those
with a dominant transverse sinus,
unilateral (Figure 4). Although pa-
tients without IIH rarely have trans-
verse sinus stenoses, the origin and
functional significance of these
stenoses remain uncertain.
Other imaging studies are gener-
ally not required in patients with
suspected IIH. However, in those
with an atypical presentation or
raised CSF protein, cerebral angiogra-
phy (looking for a dural fistula)73 and
spine MRI (to exclude a spinal
tumor)74 should be considered, be-
cause both conditions can occasion-
ally give rise to isolated raised ICP.
Update on Associated
Conditions
Although the pathogenesis of IIH re-
mains unknown, obesity and female
sex are clearly associated with it.9,12
The likely role of sex hormones in
its pathogenesis is highlighted by
the predilection for postpubertal
ABC
Figure 3. Imaging findings in idiopathic intracranial hypertension. (A) Empty sella (*) on sagittal T1-weighted imaging. (B) Dilated optic nerve sheaths (arrowheads) on axial
T2-weighted imaging. (C) Posterior globe flattening (arrowheads) and enhancement of protruding optic nerve heads (arrows) on axial T1-weighted imaging with contrast.
2. RIND0256_07-28.qxd 7 /28/10 4:54 PM Page e61

premenopausal women,6as well as
the absence of a sex preference be-
fore puberty.15,75,76 It has recently
been shown that men with IIH are
more likely than matched control
subjects to have symptoms associ-
ated with testosterone deficiency
and obstructive sleep apnea.77
Many other factors have been
proposed to cause, precipitate, or
worsen IIH, including various med-
ications (eg, tetracycline and its
derivatives, cyclosporine, lithium,
nalidixic acid, nitrofurantoin, oral
contraceptives, levonorgestrel, dana-
zol, and tamoxifen), endocrine ab-
normalities (eg, corticosteroid with-
drawal, anabolic steroids, excessive
growth hormone, and thyroid
disease), vitamin A excess78,79 or
deficiency, and systemic conditions
(eg, pregnancy, menstrual irregulari-
ties, polycystic ovarian syndrome,
anemia, and obstructive sleep
apnea).61,80 With some implicated
medications, test-retest data in single
cases provide compelling evidence
for causation. However, in the few
case-control studies published to
date, no definite association was
found between any of these condi-
tions and IIH patients, as compared
with age- and sex-matched control
subjects.12,22,33,61 Several factors (eg,
pregnancy, oral contraceptives, and
menstrual irregularities) are very
common in young women, and
therefore are expected to be com-
mon in IIH patients. Studies evaluat-
ing the prevalence of obstructive
sleep apnea in IIH are ongoing.
Update on the Pathophysiology
of IIH
The pathophysiologic mechanisms
underlying the raised ICP in IIH re-
main unclear, but must account for
the remarkable predilection for obese
young women. Theories include in-
creased brain water content, excess
CSF production, reduced CSF absorp-
tion, and increased cerebral venous
pressure.10,61,81 Underlying endocrine
dysfunction related to sex hormones
and adipose tissue as an actively
secreting endocrine organ has also
been proposed.82
A great controversy exists regard-
ing the role of cerebral venous hy-
pertension in the etiology of IIH.83
Older studies suggested that in-
creased ICP might be a direct result
of increased intra-abdominal pres-
sure, via elevation of the diaphragm,
raised pleural pressure, decreased
cerebral venous return, and, conse-
quently, sustained cerebral venous
hypertension.84 However, this theory
requires that central rather than
lower body obesity be present to in-
crease intra-abdominal pressure,11
and does not account for the prepon-
derance of women with the disorder.
Even more interesting are the
numerous recent reports discussing
the role of transverse venous sinus
stenoses in the pathophysiology of
IIH.71,83,85-91 Because CSF drains
passively into the venous sinuses, a
stenosis of a dominant transverse
sinus or stenoses of both transverse
sinuses could reduce venous outflow,
resulting in cerebral venous hyper-
tension and impaired CSF resorption
Idiopathic Intracranial Hypertension continued
e62 VOL. 7 NO. 2/3 2010 REVIEWS IN NEUROLOGICAL DISEASES
It has recently been shown that men with IIH are more likely than matched
control subjects to have symptoms associated with testosterone deficiency
and obstructive sleep apnea.
ABC
Figure 4. Transverse cerebral venous sinus stenosis in a patient with idiopathic intracranial hypertension, as seen on contrast-enhanced magnetic resonance venography. There
is a long narrow stenosis of the right transverse venous sinus (arrowheads) and a hypoplastic left transverse venous sinus. (A) Sagittal plane. (B) Coronal plane. (C) Axial plane.
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Idiopathic Intracranial Hypertension
VOL. 7 NO. 2/3 2010 REVIEWS IN NEUROLOGICAL DISEASES e63
(Figure 5). Studies using direct ret-
rograde cerebral venography with
manometry have demonstrated pres-
sure gradients across these stenoses,
with proximal cerebral venous hy-
pertension.71 The origin of these
stenoses has been debated, with
some anatomic studies suggesting
that they might be related to the
presence of trabeculae, septae, or
large arachnoid granulations in the
transverse sinuses.92,93 However, it
has also been suggested that patients
with increased intracranial pressure
may develop transverse sinus
stenoses due to external compres-
sion, because the stenoses can resolve
once CSF pressure is normalized by a
lumbar puncture or a CSF shunting
procedure.85,94-98 Even if these venous
sinus stenoses are due to raised CSF
pressure, it is likely that their pres-
ence will still result in decreased CSF
absorption and, thus, further eleva-
tion of ICP, if there is cerebral venous
hypertension due to a pressure gradi-
ent across them (Figure 5), suggesting
a possible role for venous sinus stent-
ing in the treatment of IIH. Also of
interest is the observation that trans-
verse venous sinus stenoses can occur
in patients without IIH, suggesting
that they may have no functional
significance in some patients.
Treatment
The 2 goals of treatment in IIH are
to alleviate unpleasant symptoms
(eg, headache) and to preserve vi-
sion.10,81 General recommendations
include weight loss (most successful
when under the direction of a nutri-
tionist), evaluation and treatment of
potential contributing factors (in-
cluding medication use, anemia, and
obstructive sleep apnea), and even
conventional headache manage-
ment.
The treatment of raised ICP itself
begins with the diagnostic lumbar
puncture, which is often effective in
transiently improving symptoms
and signs. Occasionally, patients can
have a lasting clinical remission fol-
lowing a single lumbar puncture,97
obviating the need for further med-
ical or surgical treatment. Although
lumbar punctures can be useful as a
temporizing measure in emergency
situations,35 they are poorly tolerated
by many patients, especially when
technically difficult.
Patients with persistent symptoms
and signs can be treated using
medical and surgical approaches, al-
though there have been no random-
ized controlled trials prospectively
assessing and comparing these treat-
ments.99 Because some patients with
papilledema never develop visual
field defects, whereas others develop
rapid visual loss, a combination of
ophthalmologic examination and
quantitative perimetry is required
to guide management decisions. A
suggested treatment algorithm,
based on the severity of symptoms
and signs, is given in Figure 6.100 It is
important to note that patients with
severe symptoms, significant visual
loss, or a fulminant onset of disease
require more aggressive manage-
ment from the outset, to prevent ir-
reversible visual loss.35
Weight Loss
Because obesity and weight gain are
well known to be associated with
IIH,12 weight loss is routinely advised
for obese IIH patients. Only a modest
degree of weight loss (about 5% to
10% of total body weight) is usually
required for improvement in symp-
toms and signs.101-104 A recent study
of 25 obese women with IIH showed
that weight loss effectively reduces
not only headaches and papilledema,
but also ICP in IIH patients (M. Bur-
don, personal communication,
March 2010). However, weight loss
is not an effective short-term treat-
ment and, thus, other treatments
must be initiated in parallel for most
patients. Bariatric surgery can be con-
sidered in morbidly obese IIH
patients in whom attempts at weight
loss have been unsuccessful.105,106
Drug Treatments
Carbonic anhydrase inhibitors, such
as acetazolamide, are the main med-
ical treatment prescribed for IIH, al-
though no trial data are currently
available to confirm their effective-
ness.99 They are thought to exert their
Transverse Venous
Sinus Stenosis
Venous Outflow Obstruction
Venous Hypertension
Decreased CSF Absorption
Increased ICP
Figure 5. Schematic summary of the presumed role of
transverse venous sinus stenosis in idiopathic intracranial
hypertension. CSF, cerebrospinal fluid; ICP, intracranial
pressure.
Although lumbar punctures can be useful as a temporizing measure in emer-
gency situations, they are poorly tolerated by many patients, especially when
technically difficult.
Carbonic anhydrase inhibitors, such as acetazolamide, are the main medical
treatment prescribed for IIH, although no trial data are currently available
to confirm their effectiveness.
2. RIND0256_07-28.qxd 7 /28/10 4:54 PM Page e63

therapeutic effect by decreasing CSF
production, although they also have a
mild diuretic effect. Doses of 1 to 2 g
daily, given in divided doses, can be
effective, although many patients
cannot tolerate high doses due to in-
tolerable side effects, such as pares-
thesias, altered taste sensation, and
lethargy. The preliminary results of
the IIH Pilot Trial from Birmingham,
UK, in which 50 patients were ran-
domized to receive acetazolamide or
no acetazolamide, emphasize the dif-
ficulties of performing such a study
due to side effects (T. Matthews, per-
sonal communication, March 2010).
The findings of another small trial
suggest that acetazolamide can be
safely used in pregnant patients with
IIH.107 A randomized clinical trial of
acetazolamide versus placebo for IIH
has just begun in North America.108
Excessive analgesic use is discour-
aged, given the high likelihood of
rebound headaches; therefore, pro-
phylactic headache treatments are
often required in patients with
prominent headache. Of these, topi-
ramate is the most commonly used,
because it is a weak carbonic anhy-
drase inhibitor, is effective in treat-
ing primary headache disorders
(eg, migraine and chronic daily
Idiopathic Intracranial Hypertension continued
e64 VOL. 7 NO. 2/3 2010 REVIEWS IN NEUROLOGICAL DISEASES
Idiopathic Intracranial Hypertension
Evaluate the severity of IIH
• Diplopia (Vlth nerve palsy)
• Visual function: visual acuity, visual field testing
• Severity/tolerance of headache
Evaluate and correct predisposing factors
Careful follow-up (visual acuity, formal visual fields)
No headache or diplopia
No visual loss
Normal visual fields
Headaches ± diplopia ± tinnitus
No visual loss
Normal visual fields
Headaches ± diplopia ± tinnitus
Visual loss
Visual field defects
Conservative management
• No treatment
• Careful follow-up
Medical management
• ± repeat lumbar puncture
• Acetazolamide*
± Surgical treatment
CSF shunting procedure
CSF shunting procedure >>
Optic nerve sheath fenestration
Surgical treatment
No or mild
Headaches
Headaches
and diplopia
Severe
Optic nerve sheath
fenestration >> CSF
shunting procedure
± Repeat Lumbar puncture
(immediate decrease in ICP)
Mild
Figure 6. Algorithm summarizing our suggested approach to management of idiopathic intracranial hypertension (IIH), including conservative, med-
ical, and surgical treatments. In all patients who are overweight, weight loss is essential; bariatric surgery is sometimes recommended for those with
morbid obesity. CSF, cerebrospinal fluid; ICP, intracranial pressure. *Although there has been no clinical trial evaluating the treatment of IIH, aceta-
zolamine is commonly prescribed (between 1 and 2 g/d) to decrease CSF production. Reprinted with permission from Biousse and Newman.100
2. RIND0256_07-28.qxd 7 /28/10 4:54 PM Page e64

Idiopathic Intracranial Hypertension
VOL. 7 NO. 2/3 2010 REVIEWS IN NEUROLOGICAL DISEASES e65
headache), and often brings about
some weight loss as a side effect. A
randomized open-label study has
shown that topiramate and acetazo-
lamide have similar beneficial effects
at 12 months in IIH patients,109 but
further controlled studies are re-
quired to confirm these findings.
Steroids have been used as a treat-
ment of IIH in the past, but are asso-
ciated with significant long-term
side effects, such as weight gain,
that are undesirable in this patient
population. High-dose intravenous
steroids are still occasionally used
in patients with rapidly progressive
visual loss from fulminant IIH
while a more definitive treatment is
awaited.35,62
A Randomized, Controlled Treatment
Trial for IIH
Beginning in 2009, the National Eye
Institute of the National Institutes of
Health has sponsored the Neuro-
Ophthalmology Research Disease In-
vestigator Consortium (NORDIC) to
proceed with a multicenter, double-
blind, placebo-controlled clinical
trial, called the Idiopathic Intracra-
nial Hypertension Treatment Trial
(IIHTT), comparing the efficacy of
acetazolamide and placebo in the
treatment of IIH patients.108 Patients
must satisfy the modified Dandy cri-
teria for diagnosis of IIH and have
mild to moderate disease (mean de-
viations on automated perimetry
ranging from 2 to 5 dB). Patients
will be randomized to receive either
acetazolamide at increasing doses, as
tolerated, or placebo. All patients
will also be treated with a low-
sodium diet and will participate in a
standardized weight loss program.
Patients will be monitored with au-
tomated perimetry, which is the pri-
mary outcome measure at 6 months.
Secondary outcome measures will in-
clude changes in CSF pressure, pa-
pilledema, and quality of life.
Surgical Procedures
Surgery is required in patients with a
fulminant onset of disease or when
other treatments have failed to pre-
vent progressive visual loss. The
choice of procedure depends on local
resources, as well as the patient’s
symptoms and signs (Figure 6). In
patients with papilledema who have
severe visual loss but minimal or no
headache, optic nerve sheath fenes-
tration (ONSF) is often advised,
whereas in those with visual loss,
papilledema, and headache, a CSF
diversion procedure, such as ven-
triculo- or lumboperitoneal shunt-
ing, is preferred. Aggressive manage-
ment with CSF shunting is usually
required to prevent catastrophic vi-
sual loss in those with acute and
rapidly progressive visual loss.35 In
contrast, CSF shunting should not be
routinely offered for the treatment of
isolated headache, given the high
rate of complications and the fact
that many IIH patients have a coex-
isting primary headache disorder that
does not improve with lowering of
ICP.
CSF shunting produces a rapid re-
duction in ICP, often with a subse-
quent improvement in symptoms
and signs.110-114 Complications are
common, however, and many pa-
tients develop infections, shunt ob-
struction, or migration of the shunt
tubing; therefore, revisions are often
required.111-114 Although ventricu-
loperitoneal shunting is more tech-
nically challenging and often re-
quires a stereotactic approach, as IIH
patients do not have enlarged ventri-
cles, it may be preferred due to its
lower complication rate.115,116
In ONSF, the dural sheath sur-
rounding the retrolaminar portion of
the optic nerve is fenestrated, creat-
ing a fistula between the subarach-
noid space and orbital cavity. Conse-
quently, there is a reduction in
pressure on the optic nerve, leading
to reduced papilledema and im-
proved visual function in that
eye.117-121 Although the papilledema
and visual function on the contralat-
eral side can sometimes improve,
most patients with bilateral pa-
pilledema require sequential bilateral
ONSF.118 The papilledema tends not
to recur, although the mechanism
for this remains uncertain. Although
a fluid collection can be seen adja-
cent to the operated site in the initial
weeks following ONSF, suggesting
a persistent fistula, fibrous tissue
formation is observed after a few
months, suggesting that scarring at
the ONSF site prevents transmission
of the CSF pressure gradient to the
retrolaminar portion of the nerve.122
ONSF is generally ineffective in re-
ducing ICP, so it will not usually be
effective in treating any other symp-
toms and signs of raised ICP.123,124
Furthermore, some patients might
develop transient or permanent
visual loss125-127 or continue to lose
vision following ONSF,128 so poten-
tial risks of the procedure need to be
weighed against benefits.
Modeling studies have suggested
that stenting of transverse venous
sinus stenoses will reduce cerebral ve-
nous pressure, leading to increased
CSF absorption, reduced ICP, and
improved symptoms and signs, even
in cases where the stenoses are sec-
ondary to raised ICP.91 Supporting
this notion are the findings of several
case studies and small series, in which
patients have undergone endovascu-
lar stenting of the stenoses, with
Surgery is required in patients with a fulminant onset of disease or when
other treatments have failed to prevent progressive visual loss.
2. RIND0256_07-28.qxd 7 /28/10 4:54 PM Page e65

subsequent normalization of ICP
and resolution of symptoms and
signs.87,89,129-133 However, venous
sinus stenting can result in serious
complications, such as stent throm-
bosis and subdural hemorrhage,89,131
and patients can develop recurrent
stenoses immediately proximal to the
stent.87,89 Furthermore, prospective
controlled studies are lacking, and the
indications for this treatment remain
poorly defined, and therefore it is cur-
rently not recommended for routine
clinical practice.
Conclusions
Many questions remain unanswered
about IIH. Its association with female
sex and obesity is striking, and the
common finding of transverse ve-
nous sinus stenosis is intriguing. Re-
cent large studies have indicated that
IIH can also occur in men, nonobese
adults, older adults, and prepubertal
children. Identification of subgroups
at high risk for irreversible visual
loss, such as black patients, men, and
patients with fulminant IIH, help
determine management approaches
and follow-up criteria. Ongoing
studies of venous anatomy and
physiology in IIH patients, as well
as a recently begun clinical trial, are
promising and should provide more
insight into this common yet poorly
understood syndrome.
This work was supported in part by a depart-
mental grant (Department of Ophthalmol-
ogy) from Research to Prevent Blindness,
Inc., New York, NY; core grant P30-EY06360
(Department of Ophthalmology) from the
National Institutes of Health/National Eye
Institute; and by grants KL2-RR025009
(BBB) and National Institutes of Health
grant UL1-RR025008 (BBB/VB).
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Main Points
• Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology; it produces nonlocalizing symptoms
and signs of raised intracranial pressure and can result in severe irreversible visual loss when left untreated.
• Despite a high predilection for obese young women, IIH can occur in children, older adults, and in nonobese persons
of either sex.
• Clinical features of IIH include headache, papilledema, visual loss, pulsatile tinnitus, and diplopia, among other
symptoms.
• The 2 main goals of treatment are the reduction of unpleasant symptoms (eg, headache) and the preservation of
vision.
• Treatments for IIH include weight loss, pharmacotherapy with carbonic anhydrase inhibitors, and surgical interven-
tion in those who are unresponsive to other treatment methods, and those with fulminant onset of disease.
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