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Background: Idiopathic Intracranial Hypertension (IIH) is characterized by an elevation of intracranial pressure (ICP no identifiable cause. The aetiology remains largely unknown, however observations made in a number of recent clinical studies are increasing the understanding of the disease and now provide the basis for evidence-based treatment strategies. Methods: The Embase, CDSR, CENTRAL, DARE and MEDLINE databases were searched up to 1st June 2018. We analyzed randomized controlled trials and systematic reviews that investigate IIH. Results: Diagnostic uncertainty, headache morbidity and visual loss are among the highest concerns of clinicians and patients in this disease area. Research in this field is infrequent due to the rarity of the disease and the lack of understanding of the underlying pathology. Conclusions: This European Headache Federation consensus paper provides evidence-based recommendations and practical advice on the investigation and management of IIH.
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C O N S E N S U S A R T I C L E Open Access
European Headache Federation guideline
on idiopathic intracranial hypertension
Jan Hoffmann
1*
, Susan P Mollan
2
, Koen Paemeleire
3
, Christian Lampl
4
, Rigmor H Jensen
5
and Alexandra J Sinclair
6
Abstract
Background: Idiopathic Intracranial Hypertension (IIH) is characterized by an elevation of intracranial pressure (ICP
no identifiable cause. The aetiology remains largely unknown, however observations made in a number of recent
clinical studies are increasing the understanding of the disease and now provide the basis for evidence-based
treatment strategies.
Methods: The Embase, CDSR, CENTRAL, DARE and MEDLINE databases were searched up to 1st June 2018. We
analyzed randomized controlled trials and systematic reviews that investigate IIH.
Results: Diagnostic uncertainty, headache morbidity and visual loss are among the highest concerns of clinicians
and patients in this disease area. Research in this field is infrequent due to the rarity of the disease and the lack of
understanding of the underlying pathology.
Conclusions: This European Headache Federation consensus paper provides evidence-based recommendations
and practical advice on the investigation and management of IIH.
Objective
Idiopathic Intracranial Hypertension (IIH) is character-
ized by an elevation of intracranial pressure (ICP) with
no identifiable cause [1]. Despite the fact that its aeti-
ology remains largely unknown, the observations made
in a significant number of recent clinical studies and the
resulting increase in the understanding of its clinical pic-
ture have led to modifications in its diagnostic classifica-
tion and provide the basis for evidence-based treatment
strategies. This consensus paper is based on the current
literature on diagnosis and treatment of IIH and pro-
vides evidence-based recommendations on its treatment
where randomized-controlled trials are available.
Background
The entire clinical syndrome of IIH is defined in the
diagnostic criteria established by Friedman et al. [2]
(Fig. 1) whereas the associated headache is defined in
the Headache Classification of the International
Headache Society (IHS) [3] (Table 1). The term pseudo-
tumor cerebri, in the past commonly used as a synonym
for IIH, is now used as an umbrella term that describes
the chronic elevation of ICP regardless of its aetiology
and further subdivides in the primary (IIH) and second-
ary forms [2]. The remit of this manuscript will exclu-
sively focus on the diagnostic and therapeutic algorithm
of primary IIH.
IIH is a disorder that mainly affects obese women of
childbearing age. Its prevalence has been estimated
between 0.52 per 100,000 of the general population [4].
However, due to the lack of awareness of the clinical
syndrome as well as its potential similarity to primary
headaches including migraine, it has been suggested that
the disorder may be underdiagnosed [5]. In contrast,
given the strong association between obesity and ele-
vated ICP, it can be expected that the increasing obesity
in the general population will increase the prevalence as
well as the socioeconomic burden of the disease [1,6].
This outlook underlines the importance of clear diagnos-
tic criteria that allow an accurate diagnostic algorithm as
well as recommending effective management strategies.
* Correspondence: jan.hoffmann@kcl.ac.uk
1
Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and
Neuroscience, Wellcome Foundation Building, Denmark Hill Campus, Kings
College London, London SE5 9PJ, UK
Full list of author information is available at the end of the article
The Journal of Headache
and Pain
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
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Clinical symptoms and diagnostic algorithm
Clinical picture
Headache
Headache, present in up to 90% of IIH patients, is com-
monly the primary symptom leading IIH patients to seek
medical advice [7,8]. Headache is also the key factor
driving reduced quality of life in IIH [9]. The features of
IIH-related headache vary substantially and in the con-
text of a limited amount of clinical studies that aim at
characterizing them, the IHS-criteria remain relatively
unspecific in their description. Patients commonly de-
scribe their headache as pressing, explosive with a
frontal, retroorbital localization [3,10]. Frequently the
headache has a migraine phenotype and overuse of anal-
gesic is observed in over a third of IIH patients [11].
Phenotypic similarities may hamper its distinction from
migraine and other headaches [7,8,1217]. In order to
establish the diagnosis of IIH it is required that the caus-
ality between the clinical symptoms and elevated ICP is
demonstrated by a temporal relationship between head-
ache onset and the identification of elevated ICP or an
alleviation after a reduction of ICP. However, one study
reported that over 20% of patients with other headache
disorders also improve after lumbar puncture (LP) [18].
The second edition of the International Headache Clas-
sification (ICHD-2) detailed headache alleviation after
pressure reduction was a required diagnostic criterion of
IIH, however in the recent ICHD-3 criteria this criterion
has been removed as headache duration can vary sub-
stantially with almost two thirds of IIH-patients com-
plaining of persisting chronic headache despite a
normalization of ICP [3,10,18,19]. However, the pre-
cise onset of increased ICP and the related headache are
difficult to establish, so the preliminary version of the
present diagnostic ICHD-3 criteria (ICHD-3 beta) for
IIH-headache have been field tested in a recent study
and more sensitive and specific criteria have been sug-
gested [18].
Ophthalmic features
Bilateral disc swelling, termed papilloedema when it is
caused by raised ICP, is a cardinal feature of IIH and on
examination it can be asymmetrical in 4% of cases [7,20
25]. Examination of the eye can be challenging and in case
of diagnostic uncertainty, papilloedema should be con-
firmed by an experienced ophthalmologist. Exclusion of
pseudopapilloedema is recommended to prevent unneces-
sary investigations and procedures. These include mea-
surements of intraocular pressure, ruling out hypotony,
and critical examination of the optic nerve as small hyper-
metropic discs, titled myopic discs, vitreous traction and
disc drusen can all be mistaken for papilloedema. There is
a high frequency (40%) of diagnostic errors in IIH, with
the main cause being an incorrect ophthalmic examin-
ation [26].
Raised ICP can lead to a number of visual symptoms
including transient visual obscurations, visual blurring
and double vision. All IIH patients with active papilloe-
dema need close ophthalmological monitoring to evalu-
ate the visual function and assess the risk of visual loss
as in some the visual disturbances are progressive and
may lead to prolonged ischemia of the optic nerve head
resulting in complete and irreversible sight loss second-
ary to optic atrophy. The tests of visual function are im-
portant as no correlation between headache frequency
Fig. 1 Diagnostic criteria for IIH (Friedman criteria). Diagnostic criteria for IIH and IIH without papilloedema. Infogram demonstrating the grey
zonein which LP pressure is normal in some individuals but can indicate pathologically raised ICP in some. Measurements in the grey zone
need to be interpreted with caution and patients must fit the other criteria for IIH for a diagnosis to be confirmed
Table 1 Diagnostic criteria for IIH-related headache according to
the International Classification of Headache Disorders (ICHD-3)
A. New headache, or a significant worsening of a pre-existing headache,
fulfilling criterion C
B. Both of the following:
1. idiopathic intracranial hypertension (IIH) has been diagnosed
2. cerebrospinal fluid (CSF) pressure exceeds 250 mm CSF (or 280 mm
CSF in obese children)
C. Either or both of the following:
1. headache has developed or significantly worsened in temporal
relation to the IIH, or led to its discovery
2. headache is accompanied by either or both of the following:
a) pulsatile tinnitus
b) papilloedema
D. Not better accounted for by another ICHD-3 diagnosis
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and the degree of papilloedema has been demonstrated
[27]. Data from a recent randomized-controlled clinical
trial with acetazolamide for the treatment of IIH, the
IIH Treatment Trial (IIHTT), revealed that higher-grade
papilloedema and a significant loss in visual acuity at
presentation are associated with a higher risk of progres-
sion to visual field loss despite adequate treatment [28].
Ophthalmic examination should include: visual acuity,
a pupil examination, formal visual field assessment and
dilated fundal examination to evaluate the papilloedema.
The typical visual field findings are that of an enlarge-
ment of the blind spot, peripheral constriction and or an
inferior nasal step or partial arcuate defect [22,29]
(Fig. 2). To interpret visual fields with confidence a basic
understanding of the plots (Table 2), reliability indices
(Table 3), and global parameters (Table 3) is required.
Visual field testing is a psychophysical test and can be
demanding to interpret in any disease including IIH. Be-
sides physical obstacles, cognitive factors including sub-
ject attention, motivation, fatigue, and response bias can
influence the obtained thresholds. Improvement in reli-
ability has been shown to improve with clear instruc-
tions [30]. Despite clear instructions in the IIHTT,
performance failures were observed at some point in
one fifth of the participants and were likely due to
behavioural factors as the fields returned to baseline
values on re-testing: therefore not deemed to be disease
progression. Retesting is recommended where there is
perimetric worsening, in the presence of unreliable indi-
ces (Table 3)[31].
The role of imaging the optic nerve head is becoming
increasingly important. Qualitative analysis of photo-
graphic images remains useful for clinical records.
Newer techniques such as wide field imaging using the
Optosallow high resolution image capture through an
undilated pupil, with a magnification tool to examine
the optic nerve head (Fig. 3). Optical Coherence Tomog-
raphy (OCT), in particular spectral domain OCT, offers
a non-invasive technique for both qualitative and object-
ive quantification of papilloedema that can support the
detection of papilloedema [3234]. OCT is found to be
a valuable tool for quantification of papilloedema in lon-
gitudinal assessment: Fig. 4demonstrates the clear im-
provement in papilloedema in a newly diagnosed IIH
patient who undertook a low calorie diet for 6 weeks
[35]. However, OCT has limitations. In cases of severe
papilloedema errors occur in the automated software
analysis which can lead to unreliable values, these scans
need manual adjustment to ensure reliable results [36].
However as peripapillary retinal nerve fibre layer (RNFL)
Fig. 2 Typical visual field defects in IIH. Common visual field defects seen in IIH with the Humphrey visual field analyser grey scale. a, Left eye
with a slightly enlarged blind spot; b, right eye with slightly enlarged blind spot; c, Left eye obvious enlarged blind spot; d, right eye with
enlarged blind spot and paracentral scotoma; e, left eye with enlarged blind spot and prominent inferior nasal step; f, Left eye with enlarged
blind spot, dense superior and inferior arcuate scotomas
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thickness resolves, most systems do not allow the distinc-
tion between reduction in oedema and optic atrophy as
both conditions lead to a reduction in RNFL thickness [37].
Software enhancements on certain OCT platforms allow
the determination of ganglion cell layer thickness and this
may prove to be beneficial to correlate with visual loss.
Some OCT platforms have the ability to capture short video
footage which is useful to document location and presence
of spontaneous venous pulsations (Additional file 1). OCT
imaging supports the diagnosis and monitoring of papilloe-
dema as demonstrated in Fig. 5where there is an increase
in the volume at the optic nerve head with recurrence of
symptoms of headache and pulsatile tinnitus for one month
in a patient previously in ocular remission, but does not
mitigate the continued monitoring of all measures of visual
function through clinical examination and formal perimetry.
Other symptoms
IIH can cause other symptoms, as well as headache and
visual disturbances. Recent data however suggests that
other systems may also be affected in IIH, presumably as
the result of increased ICP, although the exact mecha-
nisms leading to these alterations remain largely un-
known. In this context, structural changes in the olfactory
nerve [38], which are associated with an olfactory dysfunc-
tion in up to 80% of IIH patients, have been demonstrated
[39,40]. Nevertheless, despite an easy determination of ol-
factory function by the use of extended SniffinSticks, this
observation is not useful for the diagnosis or follow-up ex-
aminations in IIH as the effects of a variation in ICP may
reflect on olfactory function with a significant delay.
A uni- or bilateral pulsatile tinnitus is commonly ob-
served in IIH [7,8,41]. Its underlying cause is not entirely
elucidated but it is hypothesized that stenoses in the trans-
verse sinus, which are commonly observed in IIH, may in-
duce audible turbulences in blood flow. Nevertheless
further studies are required to confirm this assumption.
Unilateral or bilateral sixth-nerve palsy may occur in IIH
causing horizontal diplopia [42,43]. The reason for this
neurological deficit in the context of IIH has not been fully
investigated. The pathophysiological mechanism has trad-
itionally been thought to be due to compression against the
Table 2 Interpretation of Humphrey visual field plots. In static perimetry the stimulus is stationary but it changes its intensity until
the sensitivity of the eye at the particular point is found. It is measured at preselected locations in the visual field. Most IIH patients
have a threshold test where steps of 4 dB are used until detected then re-tested at every point in 2 dB steps
Term Explanation Notes
Numerical
Display
These are the raw values of the individuals retinal sensitivity at
predetermined points in decibels (dB). Normal values are approximately
30 dB while recorded values of < 0 dB equate to no sensitivity measure.
The HVF analyser uses light between 0 and 50 dB (0 is the brightest
and 50 is the dimmest). Sensitivity is greatest in the central field and
decreases towards the periphery.
Grey scale This is a graphical representation of the numerical display. It allows
for quick assessment of the field as values closer to 0 dB (low sensitivity)
are coded with black and those closer to 50 dB with white
(highest sensitivity).
This parameter should not be used alone, the reliability and global
indices are critical to interpreting this map.
Total
deviation
This demonstrates the difference between measured values and
population age-normal values at specific retinal points. The
numbers indicate the difference compared to the mean. A negative
value indicates less visual sensitivity compared to the mean population.
Both the total deviation and the pattern deviation provide a numerical
total plot (top) and the probability plot which gives a visual
representation of statistical analysis (t test) of this deviation from
the mean; the larger departure from the mean, the darker the
symbol.
Pattern
deviation
This represents focal depressed areas in the points tested when
accounting for overall general reductions of vision caused by media
opacities (e.g. cataracts), uncorrected refractive error, reductions in
sensitivity due to age and pupil miosis.
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petrous ligament or the ridge of the petrous temporal bone,
or stretching along the intracranial course of the nerve.
Cognitive function has been reported to be affected in
IIH. While a number of small uncontrolled studies,
which occasionally focused only on single neuropsycho-
logical domains, suggested a relationship between IIH
and cognitive decline [4446], Yri et al. demonstrated in
an extensive prospective case-control study that IIH is
associated with a global cognitive dysfunction with the
most extensive deficit in reaction time and processing
speed [47]. Interestingly, the results of this study reveal
that despite an improvement of ICP and headache after
3 months of adequate treatment, the cognitive dysfunc-
tion appears to persist raising the question if IIH-related
cognitive decline is the result of more complex mecha-
nisms rather than the direct effect of mechanical com-
pression. These neuropsychological deficits may hamper
significantly a professional reintegration after prolonged
absence from work.
Investigations
Neuroimaging
Brain imaging is an essential part of the diagnostic algo-
rithm and MRI should be considered the gold standard
of care to exclude secondary causes of elevated ICP and
to identify structural alterations associated with IIH.
These include an empty sella turcica (or at least signifi-
cant changes in size, shape and volume of the pituitary
gland) and a flattening of the posterior optic globe. IIH
also leads to an enlargement of the optic nerve sheath
and an increased tortuosity of the optic nerve [12,48
51]. However, the volume of the optic nerve is not af-
fected [12]. In contrast to early imaging studies based on
plain film X-ray imaging that suggested a reduced ven-
tricle size (slit-like ventricles) as indicative for IIH [52],
data based on CT and MR imaging techniques demon-
strates that size and volume of the lateral ventricles are
not altered in IIH [49,53].
Diagnostic brain imaging in IIH should always include
a CT- or MR venography to exclude a venous sinus
thrombosis as even clinically inapparent microthrom-
boses may induce a venous outflow obstruction that in-
creases ICP [54]. Furthermore the venography may
demonstrate the presence of uni- or bilateral transverse
sinus stenoses (TSS) as these are frequently observed in
IIH patients with reported prevalence rates of up to 90%
[51,55,56]. However, if TSS are cause or consequence
of elevated ICP remains controversial. Additionally,
Table 3 Interpretation of Humphrey visual field parameters
Term Explanation Notes Example
Reliability indices:
Fixation
Losses
Fixation is plotted, if the patient moves and
the machine re-tests and patient sees spot
then a fixation loss is recorded.
Fixation losses above 20% may significantly
compromise the reliability of the test.
OD- Right eye;
OS Left eye.
Note the longer the test time the more
tired the patient will be.
False POS
(Positive)
Errors
Patient responds to the normal whirr noise of
the computer when it sounds as if is about to
present a light but does not.
High false positive score occur in a
trigger happypatient. < 33% is an
unacceptable test.
False NEG
(Negative)
Errors
A brighter light is presented in an area in which
the threshold has already been determined and
the patient does not respond to it.
High false negative score occurs in fatigued
or inattentive patients. < 33% is
an unacceptable test.
Global indices:
Glaucoma
Hemifield
Test (GHT)
This assesses clusters of points above and
below the horizontal meridian for any
significant difference.
It describes the field as Within normal
limits,Borderlineor Outside normal limits
242 denotes the test strategy
(24 degrees temporally and 30 degrees
nasally and tests 54 points).
VFI
Mean
deviation
(MD)
A measure of overall field loss
Pattern
standard
deviation
(PSD)
Measure of focal loss or variability within the
field taking into account any generalised
depression.
An increased PSD is more indicative of
glaucomatous field loss than MD.
Probability
values
These indicate the significance of the defect
< 5%, < 2%, < 1% and 0.5%.
The lower the pvalue the greater its clinical
significance and the lesser the likelihood of
the defect occurring by chance.
Reference: Mollan, SP (2018). Investigations and their interpretation. In Denniston AK and Murray PI, 4thed., Oxford handbook of ophthalmology: Oxford University press: Oxford
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asymmetry of the transverse sinus can occur in 50% of
healthy individuals [57].
Despite the value of neuroimaging in the diagnostic
workup of IIH, it does not replace the need for a measure-
ment of lumbar opening pressure as imaging abnormal-
ities show a large interindividual variation and none of the
findings are pathognomonic of IIH hence imaging findings
only serve as supportive evidence for the diagnosis of IIH.
Lumbar puncture
LP is mandatory in the diagnostic algorithm of IIH. In
addition to a normal CSF composition, diagnostic criteria
Fig. 3 Wide-field imaging using. Wide-field imaging with the Optosthrough an undilated pupil in a, normal patient and b, a patient with IIH. a,
normal fundus with blue high magnification box to inspect the optic nerve. Peripapillary atrophy 360
o
around the disc which is normal. Note the
lashes seen inferiorly as artefact on image. b, right optic nerve which has grade 2 Frisen swelling where there is elevation of the optic disc margin
360
o
, loss of the clear optic disc margin as seen in a.c, the high magnification tool allows excellent visualisation of the swelling without degradation
of the image
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require that opening pressure, which should be measured
in the lateral decubitus position with stretched legs and
without sedative medications, should not exceed 25
cmH
2
O in adults and 28 cmH
2
O in children [2,58,59].
Increases of ICP may also occur intermittently, in particu-
lar in IIH patients without papilloedema [60,61]. There-
fore, if IIH is suspected but opening pressure lies within
the normal range during the initial assessment, a second
measurement or even continuous monitoring could be
considered [6163]. Conversely, pressures above 25
cmH
2
O can occur in normality [64], with pressures in the
range 2530 cmH
2
O constituting a grey area that could
be pathological or normal and should be interpreted with
caution [43]. Patients with pressures in this grey zone
should be evaluated cautiously to ensure they meet the
other aspects of the IIH diagnostic criteria [43].
Blood tests
Blood tests should be performed for the exclusion of
secondary causes of elevated ICP or other medical con-
ditions that may clinically present with similar symp-
toms. Blood test should be tailored to the individual
patients presentation. In the absence of typical
phenotypic characteristics of IIH (obese female of child-
bearing age) blood tests to exclude secondary causes of
pseudotumor cerebri are key. Excluding conditions that
increase the likelihood of a sinus vein thrombosis, which
could obstruct venous outflow, may be performed. These
could include analysis of coagulation parameters to iden-
tify hypercoagulable states as well as a search for dis-
eases that are associated with a higher risk of venous
(micro-) thrombosis such as systemic lupus erythemato-
sus and infections of the middle ear or mastoid. Endo-
crine disorders that may mimic IIH symptoms include
Addisons disease, Cushings syndrome, hypoparathyroid-
ism as well as the use of growth hormones and may
need to be excluded. Other medical conditions that may
induce a secondary increase of ICP and should be identi-
fied via serologic examinations include systemic infec-
tions, uraemia, renal failure and anaemia [65] (Table 4).
Treatment
Surgical treatment
Surgical management is essential for IIH patients with rap-
idly declining visual function. The evidence base for choice
Fig. 4 Optical coherence tomography highlighting improvement of papilloedema. OCT is useful for monitoring of changes in papilloedema. a,
Right eye infrared (IR) image of a swollen optic nerve. Note the Patons lines (circumferential lines) between 9 oclock and 11 oclock. b, Right eye
IR image the nerve following a low calorie diet 6 weeks later. Note the tidemark changes of the extent of the previous oedema. c, Right eye cross-sectional
image half way through the optic nerve head. Note the high line indicates the height of the swelling at diagnosis and the green volume
reduction from the first scan to the most recent one (in this case 6 weeks). d, Left eye IR image of a swollen optic nerve. Note the difference between
aand d, indicating asymmetric papilloedema with worse papilloedema in the left eye. e, Left eye IR image the nerve following a low calorie diet
6 weeks later. Note the tidemark changes of the extent of the previous oedema. f, Left eye cross-sectional image half way through the optic nerve
head. Note the high line indicates the height of the swelling at diagnosis and the green volume reduction from the first scan to the most recent one
(in this case 6 weeks)
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Fig. 5 (See legend on next page.)
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of surgical technique is lacking and practice varies inter-
nationally and with surgeon preference. CSF diversion pro-
cedures including ventriculo-peritoneal, lumbo-peritoneal,
and less frequently ventriculo-atrial shunting may be uti-
lised. Ventriculo-peritoneal shunts are preferred due to
lower revision rates compared to lumbo-peritoneal shunts
(1.8 versus 4.3 revisions per patient respectively) [66].
Ventriculo-peritoneal shunts are typically placed using
neuro-navigation and adjustable valves (anti-gravity or
anti-siphon devices) that can reduce the risk of low pres-
sure headaches [66]. However, ventriculo-peritoneal shunt
insertion leads to a temporary driving restriction in some
countries such as the United Kingdom. Lumbo-peritoneal
shunting may be considered but should be avoided in those
with low lying cerebellar tonsils due to the risk of
post-operative cerebellar tonsillar descent. Shunt revision is
common with 51% requiring revision and multiple revisions
required in 30% [67]. Complications can occur including
abdominal pain, shunt obstruction, migration and infection,
low pressure headaches and subdural haematoma [67,68].
An alternative to shunting is optic nerve sheath fenestration
(ONSF) [69] which is more cost effective in some health
care systems than CSF shunting [66]. But, this procedure
also has a 26% revision rate, due to closing over of the fen-
estration, with an ensuring rise in ICP and consequent po-
tential for further visual deterioration [66]. Headache
improvement after ONSF is variable (one third to one-half
have no headache response) [70].
The Neuro-Ophthalmology Research Disease Investi-
gator Consortium (NORDIC) are currently planning a
randomised controlled surgical trial, SIGHT, which will
compare shunting with ONSF and acetazolamide. The
trial will recruit patients with a severe visual loss defined
as a parametric mean deviation between -6 dB and
-27 dB assessed on the Humphrey visual field analyser.
Endovascular stenting
Venography brain imaging in IIH frequently demon-
strates venous sinus stenosis [55,71]. These stenoses
typically regress after CSF drainage which induces re-
duction of ICP, consequently the stenoses are thought to
represent an effect of raised ICP not the underlying
cause [72]. The extent of the stenoses does not correlate
with ICP or predict the risk of visual loss [55]. Some
centres are conducting venous sinus stenting to treat
IIH but utility is debated. Case series have reported im-
provement in symptoms of intracranial hypertension,
however case selection is not randomised which can lead
to selection bias and there are a lack of long term out-
comes [73]. Complications of the procedure are reported
and include a short-lived ipsilateral headache in many,
Table 4 Medical conditions that may induce a secondary elevation
of ICP or produce symptoms that may mimic IIH (adapted from
[2,25,6669])
1. Medical disorders that may induce a sinus vein thrombosis or that may
cause a venous outflow obstruction through other mechanisms:
Thrombophilia and other hypercoagulable conditions
Systemic lupus erythematodes
Infections of the middle ear or mastoid
CNS- infections
Increased right heart pressure with pulmonary hypertension
Chronic obstructive pulmonary disease
Superior vena cava syndrome
Arteriovenous fistulas
Glomus tumour
Tumour process that may compress parts of the venous outflow system
2. Medications
Fluoroquinolones [70]
Tetracycline
Vitamin A and retinoids
Anabolic steroids
Withdrawal of corticosteroids (in particular after prolonged administration)
Administration of growth hormone
Lithium
Nalidixic acid
Oral contraceptives
Levonorgestrel implant system
Amiodarone
Cyclosporine
Cytarabine
3. Other medical conditions
HIV
Syphilis
Borreliosis
Varicella
Addisons disease
Hypoparathyroidism
Obstructive sleep apnoea
Pickwickian syndrome
Uraemia
Severe iron deficiency anaemia
Renal failure
Turner syndrome
Down syndrome
(See figure on previous page.)
Fig. 5 Optical coherence tomography highlighting worsening of papilloedema. OCT is useful for monitoring of changes in papilloedema. a, Right
eye infrared (IR) image of a normal small optic nerve in a patient in IIH with ocular remission. Note the tidemark changes of the extent of the
previous oedema. b, Colour photograph of right optic nerve with swelling and haemorrhage with recurrence of symptoms. c, Right eye IR image
taken at the same time as b. Note the extent of the oedema and the optic nerve is more visible with the OCT image compared to the photo. d,
Right eye cross-sectional image half way through the optic nerve head. Note the high line indicates the height of the swelling at this visit and
the red volume increase is from the last OCT scan to the most recent one. e, Left eye IR image of a normal small optic nerve in a patient in IIH
with ocular remission. Note the tidemark changes of the extent of the previous oedema. f, Colour photograph of left optic nerve with swelling
and cotton wool spot changes with recurrence of symptoms. g, Left eye IR image taken at the same time as f. Note the extent of the oedema
and the optic nerve is more visible with the OCT image compared to the photo. h, Left eye cross-sectional image half way through the optic nerve
head. Note the high line indicates the height of the swelling at this visit and the red volume increase is from the last OCT scan to the most recent one
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Content courtesy of Springer Nature, terms of use apply. Rights reserved.
stent-adjacent stenosis that requires retreatment in a
third, and in rare cases vessel perforation leading to
acute subdural haematoma, stent migration, thrombosis
and death [73]. The comparative efficacy of stenting and
shunting is not established, nor are the long-term effi-
cacy, revision rate and safety data. There may be a role
in some highly selected IIH patients [74].
We do not advocate CSF diversion or shunting tech-
niques to treat isolated headache symptoms due to the
poor outcomes (ongoing headache in 68% at 6 months,
77% at 12 months and 79% at 2 years post-shunting),
high revision rates and risk of complications [67]. There
is insufficient evidence to support venous stenting to ex-
clusively treat headache.
Disease modification through weight loss
There is a clear association between IIH and weight with
over 9095% of patients being obese [4]. Additionally,
IIH is reported in the context of gaining 515% of body
weight [75]. Weight loss is the only established disease
modifying therapy in IIH [76]. Consequently, patients
should be sensitively counselled about the importance of
weight loss. However, the amount of weight loss re-
quired is not well established. Additionally, the optimal
method of weight loss is uncertain. Dietary strategies are
notoriously difficult to achieve and maintain in the long term
[77,78]. The role of bariatric surgery is being increasingly
suggested as a lasting therapy to induce IIH remission.
Bariatric surgery leads to greater weight loss compared
to dietary regimes, with mean reduction in body mass
index (BMI) of 7.0515.34 m/kg
2
at 12 months [79]and
significant sustained long term weight loss [80]. Bariatric
surgery has been found to be cost effective for other obes-
ity related conditions with very low associated mortality
(0.05%0.14%, which is akin to laparoscopic cholecystec-
tomy) [79,81,82]. A systematic review of the IIH cases
treated with bariatric surgery report 100% resolution of
papilloedema and 90% experience headache improvement
[83]. A randomised control trial evaluating bariatric sur-
gery in IIH is underway (IIH Weight Trial) [84].
Symptomatic therapy with therapeutics
Acetazolamide
Therapeutic agents currently used in IIH aim to reduce
ICP through reduction in CSF secretion. There are few
therapeutic options and the recent Cochrane review re-
ported: the two included randomised controlled trials
showed modest benefits for acetazolamide for some out-
comes, there is insufficient evidence to recommend or
reject the efficacy of this intervention, or any other treat-
ments currently available, for treating people with IIH
[85]. The IIHTT is the largest RCT to date and reports
improvement in visual field function in patients with
mild visual loss when treated with acetazolamide [86].
Benefits were most marked in those with the most
marked papilloedema. However high doses of acetazol-
amide were used (greater than 40% of patients were
treated with 4 g of acetazolamide daily) and this may not
be tolerable. Previous studies have demonstrated that
48% of patients discontinue acetazolamide when doses
of just 1500 mg are utilised [87]. Side effects include
paraesthesia, dysgeusia, vomiting and diarrhoea as well
as malaise, fatigue and depression [88,89]. Acetazol-
amide is the only therapeutic that has been evaluated in
RCT and is regarded as the first line therapy for IIH.
However, not all clinicians prescribe acetazolamide for
IIH due to the limitations of the evidence base
highlighted by the 2015 Cochrane review in conjunction
with the potential side effect profile.
In pregnancy the use of acetazolamide is controversial.
Data from case series (n= 50 IIH patients using acet-
azolamide in the first trimester) has not identified an in-
creased risk of foetal malformations although animal
data has highlighted teratogenic effects [90,91].
Alternative therapeutics
A number of alternative therapeutic agents are used in
IIH, however there is little evidence to support their use.
In animal studies, intravenous and intraventricular high
dose furosemide has been shown to reduce CSF secretion
by 2050% [9295]. However, clinically relevant routes of
delivery and dosing have not been studied. A paediatric
case series (n= 8) demonstrated that together acetazol-
amide and furosemide reduced ICP over 6 weeks, however
the absence of a control group limits interpretation [96].
Bumetamide does not reduce CSF secretion in animal
studies, and human studies have not been conducted [92].
Amiloride administered into the carotid artery in ani-
mal models reduces CSF secretion by up to 50% [97,
98]. But these studies have not used clinically relevant
doses or routes of delivery.
Octreotide has been hypothesised to manipulate CSF
secretion as there are somatostatin receptors on the
choroid plexus [99]. A prospective open-label study of
26 patients reported resolution of papilloedema in 92%
of cases however cautious interpretation is needed in the
absence of a control group [100].
Topiramate utility in IIH has been suggested by an
open label study which randomly assigned 40 patients to
acetazolamide or topiramate. They demonstrated treat-
ment equivalence with all patients experiencing im-
provement in visual fields (ICP was not measured) [101].
Topiramate may have additional advantages in IIH as it
can induce weight loss and has efficacy as a migraine
preventive therapy [102105]. Recently reported in vivo
studies demonstrated that both subcutaneous and oral
administration of topiramate significantly lowers ICP in
rodents whilst other drugs tested, including
Hoffmann et al. The Journal of Headache and Pain (2018) 19:93 Page 10 of 15
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
acetazolamide, furosemide, amiloride and octreotide, did
not significantly reduce ICP [106].
Novel therapeutics
Future therapies would ideally control ICP acutely as well
as treat the underlying disease process through weight
loss. There is growing interest in the role of gut neuro
peptides in IIH. The gut peptide glucagon-like peptide-1
(GLP-1) regulates insulin secretion and weight, and cur-
rently GLP-1 mimetic drugs are used extensively to treat
diabetes (without risk of hypoglycaemia) and obesity
[107]. Recent in vitro assays have demonstrated that the
GLP-1 receptor agonist exendin-4 reduces CSF secretion
[108]. Additionally, clinically relevant doses of exendin-4
dramatically reduced ICP in rodents with raised ICP (44%
reduction in ICP within 10 min of dosing with effect
maintained for 24 h [108]. A clinical trial is currently un-
derway exploring the physiological effects of exenatide in
reducing ICP in IIH.
Therapeutic agents inhibiting the actions of 11Beta hy-
droxysteroid dehydrogenase type 1 (11β-HSD1) have
been proposed in IIH. 11β-HSD1 is an enzyme which
converts inactive cortisone to active cortisol and conse-
quently regulates local cortisol availability, a key deter-
minant of fluid secretion [109]. 11β-HSD1 inhibitors
have been shown to reduce intraocular pressure through
reduction of aqueous humour production by the ocular
ciliary body [110]. Akin to this mechanism, 11β-HSD1 is
functionally active in the CSF secreting choroid plexus
epithelial cells [111]. In patients with IIH, reduction in
ICP correlates with reduction in global 11β-HSD1 activ-
ity measures [111]. 11β-HSD1 inhibitors have been de-
veloped to treat obesity and metabolic syndrome. A
phase 2 randomised controlled trial has been conducted
in IIH which assesses a specific 11β-HSD1 inhibitor
(AZ4017), results are awaited [112].
Managing headache
Headache is the predominant morbidity in IIH and sig-
nificantly reduces quality of life [9]. Headaches occur
not only during the active stages of the disease when
ICP is elevated, but frequently continue even after the
ICP has settled [10,67]. In those IIH patients with re-
solved papilloedema (IIH in ocular remission), the on-
going headaches cause significant morbidity. Evidence to
guide headache management is very limited. Principles
of managing headache in IIH could include [113]:
1. In those IIH patients with ongoing raised ICP,
weight loss has been shown to significantly improve
the Headache Impact Test 6 score (HIT-6) as well
as headache severity, frequency and acute analgesic
use [114]. Interestingly acetazolamide does not
improve headache disability scores on the HIT-6 [86].
2. Medication-overuse headaches are a frequent
co-morbidity in IIH (37%) and patients will likely
benefit from withdrawal [11].
3. Headache phenotype should be carefully evaluated
to look for features of co-existing migraine. In those
with IIH in ocular remission and migraine or in
those with migraine-like headache with active IIH,
acute and preventive strategies may be useful
although there are no dedicated studies in this area.
Preventive strategies may have particular benefit for
those patients in whom the ICP is settling (IIH in
ocular remission). Choice of migraine prevention
should consider avoiding drugs that induce weight
gain. Potential choices could include topiramate,
candesartan and onabotulinum toxin A, although
there is no evidence of efficacy of these drugs in the
setting of IIH [113,115].
Therapeutic lumbar puncture
Therapeutic serial LPs are not advocated as a long-term
treatment strategy for IIH. Although LP induces a tran-
sient reduction of CSF pressure the effect is typically
short lived with pressures rising rapidly after the proced-
ure [116]. Therapeutic LP has limited application for
managing headache, as headache improves in 71%, but
the improvement is small (1 point on the verbal rating
score 010) and there is also a 64% chance of a head-
ache exacerbation in the week following LP in IIH pa-
tients [117]. Additionally, IIH patients frequently report
a very negative and emotional experience when they
undergo a LP [118,119]. In the short term, LP may have
a role as a temporising procedure to preserve vision in
patients with fulminant IIH awaiting an imminent CSF
diversion procedure.
Pregnancy
Pregnancy can potentially limit the ability to perform
neuroimaging studies for investigation and restrict thera-
peutic options. Hence the management of those who ei-
ther present in pregnancy for the first time with IIH or
for the majority who become pregnant during the course
of their disease management should be determined on a
case-by-case basis [120122].
Patients should be cautioned about excessive weight gain
during pregnancy that could precipitate a worsening of
their IIH. If there is access to a weight management service,
this is useful so that clear advice regarding weight gain is
appropriate for the gestational age of the foetus [123].
Use of acetazolamide in pregnancy is controversial,
and should be discussed with the individual as perinatal
exposure in rodents has caused teratogenic effects [124,
125]. The postaxial limb deformities, such as polydactyly
or limb deficiency, that have been reported in small ani-
mals were not found in primate studies [126]. The
Hoffmann et al. The Journal of Headache and Pain (2018) 19:93 Page 11 of 15
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
manufacturers do not recommend its use in pregnancy,
but some have reported using it in other conditions and
the risk of malformation was no higher than expected in
the general population however few patients had expos-
ure in the first trimester [127]. In the largest study on
the use of acetazolamide in IIH, 101 pregnant women
(158 pregnancies) took acetazolamide in a daily dose
ranging between 250 and 2000 mg. Over half took acet-
azolamide prior to 13th gestational week, abortion rate
(both spontaneous and induced) was higher in the acet-
azolamide group; the authors therefore recommended
that acetazolamide should be used with caution and jus-
tification in the pregnant IIH patient [91].
Topiramate should not be used in pregnancy, due to
the clear higher rate of foetal abnormalities following its
use [128]. Many other headache treatments are not rec-
ommended in pregnancy; therefore the risk-benefit
should be discussed with the patient.
Few patients present with IIH in pregnancy, and if there
is imminent risk to the vision, serial LPs, optic nerve
sheath fenestration or CSF diversion can be considered
[120,129]. Clear communication with the obstetric and
gynaecological services is key to help reassure healthcare
professionals and the patient. Increased observations dur-
ing pregnancy also serves to reassure. Alterations to birth
plans should not be made on the basis of the historical
diagnosis of IIH and only if there is likely to be precipitous
visual decline in the settling of moderate to severe papilloe-
dema. If there is a potential for a prolonged second stage of
labour assisted deliveries (such as caesarean section or in-
strumental deliveries) should be considered.
Idiopathic intracranial hypertension without Papilloedema
(IIHWOP)
This is a rare form of IIH where there is no evidence of
papilloedema in the setting of raised ICP. Headache is
the principle morbidity in these patients.
The diagnostic criteria for definite IIHWOP are the
same as for IIH, except there is no papilloedema, but
unilateral or bilateral sixth nerve palsies may be present.
A diagnosis of possible IIHWOP can be made without
the presence of unilateral or bilateral sixth nerve palsies,
however in this case at least 3 out of the following 4 fea-
tures on brain imaging need to be present: an empty
sella, flattening of the eye globe, widening of the space
around the optic nerve and/or transverse venous sinus
stenosis [2]. In patients with IIHWOP risk of vision loss
has not been identified and does not seem to develop
over the disease course. The commonest symptoms of
IIHWOP include headache, pulsatile tinnitus, visual phe-
nomena such as visual obscurations, blurred vision,
photopsia and diplopia (due to sixth nerve palsy) [27].
Once a diagnosis of IIHWOP is established, all patients
should be counselled about weight management. As there
is no threat to vision, long term visual monitoring is not re-
quired. Management of headache should be the same as in
IIH. Escalation of managementtosurgerytocontrolele-
vated ICP in IIHWOP should not be routinely considered.
Conclusion
IIH is a challenging disease which crosses many specialties.
At investigation it requires careful exclusion of secondary
causes through history, neuroimaging, LP and ophthalmic
examination. Once a diagnosis is established of typical IIH,
it requires regular visual monitoring, neurological input for
active headache management, and direct conselling regard-
ing weight loss. When there is no immediate threat to vi-
sion, medical treatment with acetazolamide should be
considered. Less commonly required are surgical treat-
ments to preserve vision when fulminant IIH exists. There
is increasing research in this area and as evidence is pub-
lished this document will require timely revision.
Additional file
Additional file 1: This is an infrared 10 s video as taken with the
Heidelberg Engineeringoptical coherence tomography instrument.
There is clear evidence of spontaneous venous pulsation at the optic
nerve head in a normal person. The veins at the optic nerve head cup
move in and out, with colour and shape change. (MOV 4666 kb)
Abbreviations
11β-HSD1: 11Beta hydroxysteroid dehydrogenase type 1; BMI: Body Mass
Index; CSF: Cerebrospinal fluid; CT: Computerised tomography; GLP-1: Gut
peptide glucagon-like peptide-1; ICHD: International Classification of Headache
Disorders; ICP: Intracranial pressure; IHS: International Headache Society;
IIH: Idiopathic intracranial hypertension; IIHTT: Idiopathic Intracranial
Hypertension Treatment Trial; IIHWOP: Idiopathic intracranial hypertension
without papilloedema; LP: Lumbar pincture; MR: Magnetic resonance;
MRI: Magnetic resonance imaging; NORDIC: Neuro-Ophthalmology Research
Disease Investigator Consortium; OCT: Optical coherence tomography;
ONSF: Optic nerve sheath fenestration; RCT: Randomised controlled trial;
RNFL: Retinal nerve fibre layer
Acknowledgements
Not applicable.
Funding
AS is funded by an NIHR Clinician Scientist Fellowship (NIHR-CS-011-028) and
by the Medical Research Council, UK (MR/K015184/1).
Availability of data and materials
Not applicable.
Authorscontributions
JH, SPM and AS performed the literature review and interpretation, conceptualized
and designed the statement and drafted and reviewed the manuscript.
RHJ conceptualized, designed and drafted the manuscript. KP and CL
performed a critical review of the manuscript. KP, CL and RHJ are or were
Members of Council of the European Headache Federation. All authors
read and approved the final manuscript
Ethics approval and consent to partcipate
Not applicable.
Consent for publication
Not applicable.
Hoffmann et al. The Journal of Headache and Pain (2018) 19:93 Page 12 of 15
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Competing interests
JH received honoraria for consulting for and/or serving on advisory boards
for Allergan, Autonomic Technologies Inc. (ATI), Chordate Medical AB, Eli Lilly,
Hormosan Pharma, Novartis and Teva. He received honoraria for speaking from
Allergan, Autonomic Technologies Inc. (ATI), Chordate Medical AB, Novartis
and Teva. These activities are/were unrelated to the submitted work. SPM
reports no conflict of interest. KP reports no conflict of interest. CL reports
no conflict of interest. RHJ has received honoraria for lectures and patient
leaflets from MSD, Berlin-Chemie, Menarini, Autonomic Technologies Inc. (ATI)
and Pfizer; participated in medical advisory boards for ATI and Electrocore and
conducted clinical trials for ATI and Eli Lilly. AJS reports no conflict of interest.
PublishersNote
Springer Nature remains neutral with regard to jurisdictional claims in published
maps and institutional affiliations.
Author details
1
Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and
Neuroscience, Wellcome Foundation Building, Denmark Hill Campus, Kings
College London, London SE5 9PJ, UK.
2
Birmingham Neuro-Ophthalmology,
University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth
Hospital, Birmingham, UK.
3
Department of Neurology, Ghent University
Hospital, Ghent, Belgium.
4
Headache Medical Centre, Seilerstaette Linz,
Ordensklinikum Linz, Barmherzige Schwestern, Linz, Austria.
5
Danish
Headache Center, Department of Neurology, Rigshospitalet-Glostrup,
University of Copenhagen, Glostrup, Denmark.
6
Metabolic Neurology,
Institute of Metabolism and Systems Research, University of Birmingham,
Edgbaston, UK.
Received: 31 July 2018 Accepted: 14 September 2018
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... There are patients with chronic daily headache-like manifestation, frequently associated with analgesic abuse, but almost two-thirds of IIH patients complain of persisting chronic headache despite a normalization of ICP [28]. ...
... Since increased values of ICP may occur intermittently, especially in IIH patients without papilledema, in the presence of suspected intracranial hypertension syndrome with classical clinical presentation and suggestive MRI findings for intracranial hypertension, a second lumbar puncture should be performed if the first lumbar puncture revealed an opening pressure of CSF within the normal range [28]. ...
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In this review, we provide an update on the pathogenesis, diagnosis, and management of adults with idiopathic intracranial hypertension (IIH) and implications of the cerebral venous system, highlighting the progress made during the past decade with regard to mechanisms of the venous outflow pathway and its connection with the cerebral glymphatic and lymphatic network in genesis of IIH. Early diagnosis and treatment are crucial for favorable visual outcomes and to avoid vision loss, but there is also a risk of overdiagnosis and misdiagnosis in many patients with IIH. We also present details about treatment of intracranial hypertension, which is possible in most cases with a combination of weight loss and drug treatments, but also in selected cases with surgical interventions such as optic nerve sheath fenestration, cerebral spinal fluid (CSF) diversion, or dural venous sinus stenting for some patients with cerebral venous sinus stenosis, after careful analysis of mechanisms of intracranial hypertension, patient clinical profile, and method risks.
... This condition can be entirely responsible of difficult-to-treat headache or can contribute to drug resistance or refractoriness in patients who have concomitant migraine. Criteria which increase the likelihood of IIIWP are represented by the presence, at brain magnetic resonance, of empty sella, flattening of the posterior part of the ocular globe, distension of the perioptic subarachnoid space, tortuous optic nerve, transverse sinus stenosis [52]. If this IIIWP is suspected, a lumbar puncture with measurement of cerebrospinal fluid pressure should be performed and patients treated according to available guidelines [52]. ...
... Criteria which increase the likelihood of IIIWP are represented by the presence, at brain magnetic resonance, of empty sella, flattening of the posterior part of the ocular globe, distension of the perioptic subarachnoid space, tortuous optic nerve, transverse sinus stenosis [52]. If this IIIWP is suspected, a lumbar puncture with measurement of cerebrospinal fluid pressure should be performed and patients treated according to available guidelines [52]. ...
... Fulminant IIH is rare to begin with [2], but the situation of fulminant IIH during pregnancy was unique and prompted multidisciplinary discussions and decisions about management. Our overall approach to this challenge was (a) to adhere to principles of IIH management as set out in guidelines [3,4] and of fulminant IIH management as far as they could be determined given its rarity [2] and (b) to adapt measures to her pregnant state. Weight reduction is the cornerstone of IIH treatment but could not be immediately implemented due to the pregnancy and because it would take too long to work given the urgency of the visual loss. ...
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... This was followed by transient visual obscurations (31.25%), tinnitus (12.5%), and diplopia (9.3%). Previous research work of Hoffman et al, 14 has shown association of headache (100%) with IH, which supports findings of the present study. ...
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Objective: To assess the clinical spectrum and various etiological factors of idiopathic intracranial hypertension in Pakistani patients. Study Design: Cross-sectional study. Place and Duration: Neuro-Ophthalmology Clinic, Armed Forces Institute of Ophthalmology, Rawalpindi Pakistan, from Jan 2017 to Jul 2018. Methodology: A total of 64 individuals with intracranial hypertension (IH) were screened. On the basis of inclusion criteria 32 patients were selected for the study. The demographics, clinical features and etiologies were recorded for each patient. Results: High frequency was noted among females, affecting 26 (84.37%) as compared to males who were 6 (18.75%) in number. Half of the patients had body weight lying in range of overweight, 16 (50%), however, only 5 (15.6%) patients fell into the category of obesity. Among clinical features, headache was the most prominent symptom seen in 17 (53.12%) patients and severe disc swelling seen in 19 (59.3%) was the most common sign. Most prevalent systematic association was anemia, 11 (34.3%), and the most prominent etiology was idiopathic intracranial hypertension, being 26 (81.25%). Conclusion: There was high frequency of intracranial hypertension in the females with obesity, pregnancy and in the age group of 20-30 years.
... The decrease in venous congestion and CSF outflow disorders caused by space flight increases ICP to a certain extent, and pressure is transferred to orbit, resulting in dilation of the ONS and optic disc edema. These changes are similar to those occurring in terrestrial IIH [31] . IIH, also known as pseudotumor cerebri, is characterized by headache, yet imaging evaluation reveals no intracranial space-occupying tumors, more than 90% of IIH patients have significant headaches, but only mild or sporadic headaches have occurred among astronauts aboard the ISS [11] . ...
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With the continuing progress in space exploration, a new and perplexing condition related to spaceflight ocular syndrome has emerged in the past four decades. National Aeronautics and Space Administration (NASA) has named this condition “spaceflight-associated neuro-ocular syndrome” (SANS). This article gives an overview of the current research about SANS and traditional Chinese medicine (TCM) by analyzing the existing publications on PubMed and CNKI and reports from NASA about SANS, summarizing the potential pathogenesis of SANS and physical interventions for treating SANS, and discussing the feasibility of treating SANS with TCM. Due to the unique characteristics of the space environment, it is infeasible to conduct large-scale human studies of SANS. SANS may be the result of the interaction of multiple factors, including inflammation and fluid displacement in the optic nerve sheath and cerebrospinal fluid. We should pay attention to SANS. Visual function is not only related to the health of astronauts but also closely related to space operations. TCM has antioxidative stress and antiapoptotic effects and is widely used for optic nerve diseases. TCM has great potential to prevent SANS.
... In reports from Western countries, the importance of weight control has been emphasized for the long-term durability of initially responsive dural sinus stenting. 6 Even bariatric surgery is considered in a refractory situation. However, measures to be taken for Asian patients, who are not overweight or may essentially be underweight, are unclear. ...
... As a rule, for the majority of elderly people, the diagnosis of "essential" or "idiopathic" AHT simply implies nothing more than a compensatory increase in BP due to circulatory disturbances in the brain stem due to compression of the vessels at the level of the cervical spine [40][41][42][43]. Over time the patient develops an osteochondrosis process in the cervical region, and since this is where the vertebral arteries pass through the transverse processes of the vertebrae, their lumen naturally narrows blood flow into the brain stem and into the rhomboid fossa where the vascular center is located. ...
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We found the logical way to prove the existence of the mechanism that maintains the rates of biodegradation and regeneration of cervical spine cartilage. We demonstrate, that after we restore access to arterial blood flow through cervical vertebral arteries to rhomboid fossa it causes the prevalence of regeneration over biodegradation. This is in the frames of consideration of the human body as a dissipative structure. Then the recovery of the body should be considered as a reduction of the relative rates of decay below the regeneration ones. Then the recovery of cervical spine cartilage through redirecting of inner dissipative flow depends on the information about oxygen availability that is provided from oxygen detectors in the rhomboid fossa to the cerebellum. Our proposed approach explains already collected data, which satisfies all the scientific requirements. This allows us to draw conclusions that permit reconsidering the way of dealing with multiple chronic diseases.
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Context Idiopathic intracranial hypertension (IIH) is a disease of raised intracranial pressure (ICP) of unknown aetiology. Reductions in glucocorticoid metabolism are associated with improvements in IIH disease activity. The basal IIH glucocorticoid metabolism yet to be assessed. Objective To determine the basal glucocorticoid phenotype in IIH and assess the effects of weight loss on the IIH glucocorticoid phenotype. Design A retrospective case-control study and a separate exploratory analysis of a prospective randomised intervention study. Methods The case-control study compared female IIH patients to body mass index, age, and sex-matched controls. The randomised intervention study, different IIH patients were randomized to either a community weight management intervention, or bariatric surgery, with patients assessed at baseline and 12 months. Glucocorticoid levels were determined utilising 24-hour urinary steroid profiles alongside the measurement of adipose tissue 11β-HSD1 activity. Results Compared to control subjects, patients with active IIH had increased systemic 11β-hydroxysteroid dehydrogenase (11β-HSD1) and 5α-reductase activity. The intervention study demonstrated that weight loss following bariatric surgery reduced systemic 11β-HSD1 and 5α-reductase activity. Reductions in these were associated with reduced ICP. Subcutaneous adipose tissue explants demonstrated elevated 11β-HSD1 activity compared to samples from matched controls. Conclusion We demonstrate that in IIH, there is a phenotype of elevated systemic and adipose 11β-HSD1 activity in excess to that mediated by obesity. Bariatric surgery to induce weight loss was associated with reductions in 11β-HSD1 activity and decreased ICP. These data reflect new insights into the IIH phenotype and further point towards metabolic dysregulation as a feature of IIH.
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In this article, we aimed to describe some of the currently most challenging problems in neurosurgical management of hydrocephalus and how these can be reasons for inspiration for and development of research. We chose 4 areas of focus: 2 dedicated to improvement of current treatments (shunt implant surgery and endoscopic hydrocephalus surgery) and 2 dedicated to emerging future treatment principles (molecular mechanisms of cerebrospinal fluid secretion and hydrocephalus genetics).
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Idiopathic intracranial hypertension (IIH) is a disorder characterized by elevated intracranial pressure (ICP) that predominantly affects young obese women. IIH is a diagnosis of exclusion. That is, if increased ICP is suspected, magnetic resonance imaging and magnetic resonance venography of the brain are recommended to exclude secondary causes. Imaging findings, such as empty sella, orbital findings, meningocele, and encephalocele, are not diagnostic of ICP, nor does their absence exclude ICP either. Therefore, venous manometry is recommended as the gold standard for evaluation, regardless of previous anatomic imaging results. Venous manometry is an invasive examination that is frequently applied to derive physiologic information concerning the nature of the pressure gradient. However, the pathogenesis of IIH has not been fully elucidated. The presence of venous sinus stenosis in a subset of patients has provided some support for the potential mechanisms underlying this condition. Hence, this review provides an up‐to‐date discussion on the potential pathogenic mechanisms of IIH with a special focus on venous sinus stenosis. 1 2
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Background: Traditional risk factors associated with idiopathic intracranial hypertension (IIH) include obesity, weight gain, and female sex. The incidence of IIH is increasing and yet the underlying trigger and the fueling pathological mechanisms are still poorly understood. Evidence acquisition: Review of ophthalmology, neurology, general surgery, obesity, endocrinology, nutrition, and neurosurgery literature was made. Results: The facts that implicate sex and obesity in IIH and headache are examined. The role of fat distribution in IIH is questioned, and the concept of adipose tissue functioning as an endocrine organ driving IIH is discussed. The impact of androgen metabolism in IIH is reviewed as is the emerging role of glucagon-like-peptide-1 analogues in modulating intracranial pressure. This introduces the concept of developing targeted disease-modifying therapeutic strategies for IIH. Conclusions: This review will discuss the possible role of the adipose/gut/brain metabolism axis in IIH and speculate how this may impact the pathogenesis of IIH and therapeutic opportunities.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Article
Full-text available
Background: Migraine occurs in around 15% of adults and is ranked as the seventh most disabling disease amongst all diseases globally. Despite the available treatments many people suffer prolonged and frequent attacks which have a major impact on their quality of life. Chronic migraine is defined as 15 or more days of headache per month, at least eight of those days being migraine. People with episodic migraine have fewer than 15 headache days per month. Botulinum toxin type A has been licensed in some countries for chronic migraine treatment, due to the results of just two trials. Objectives: To assess the effects of botulinum toxins versus placebo or active treatment for the prevention or reduction in frequency of chronic or episodic migraine in adults. Search methods: We searched CENTRAL, MEDLINE & MEDLINE in Process, Embase, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry (to December 2017). We examined reference lists and carried out citation searches on key publications. We sent correspondence to major manufacturers of botulinum toxin. Selection criteria: Randomised, double-blind, controlled trials of botulinum toxin (any sero-type) injections into the head and neck for prophylaxis of chronic or episodic migraine in adults. Eligible comparators were placebo, alternative prophylactic agent or different dose of botulinum toxin. Data collection and analysis: Two review authors independently selected trials and extracted data. For continuous outcomes we used mean change data when available. For dichotomous data we calculated risk ratios (RRs). We used data from the 12-week post-treatment follow-up time point. We assessed the evidence using GRADE and created two 'Summary of findings' tables. Main results: Description of trialsWe found 90 articles describing 28 trials (4190 participants), which were eligible for inclusion. The longest treatment duration was three rounds of injections with three months between treatments, so we could not analyse long-term effects. For the primary analyses, we pooled data from both chronic and episodic participant populations. Where possible, we also separated data into chronic migraine, episodic migraine and 'mixed group' classification subgroups. Most trials (21 out of 28) were small (fewer than 50 participants per trial arm). The risk of bias for included trials was low or unclear across most domains, with some trials reporting a high risk of bias for incomplete outcome data and selective outcome reporting.Botulinum toxin versus placeboTwenty-three trials compared botulinum toxin with placebo. Botulinum toxin may reduce the number of migraine days per month in the chronic migraine population by 3.1 days (95% confidence interval (CI) -4.7 to -1.4, 4 trials, 1497 participants, low-quality evidence). This was reduced to -2 days (95% CI -2.8 to -1.1, 2 trials, 1384 participants; moderate-quality evidence) when we removed small trials.A single trial of people with episodic migraine (N = 418) showed no difference between groups for this outcome measure (P = 0.49).In the chronic migraine population, botulinum toxin reduces the number of headache days per month by 1.9 days (95% CI -2.7 to -1.0, 2 trials, 1384 participants, high-quality evidence). We did not find evidence of a difference in the number of migraine attacks for both chronic and episodic migraine participants (6 trials, N = 2004, P = 0.30, low-quality evidence). For the population of both chronic and episodic migraine participants a reduction in severity of migraine rated during clinical visits, on a 10 cm visual analogue scale (VAS) of 3.3 cm (95% CI -4.2 to -2.5, very low-quality evidence) in favour of botulinum toxin treatment came from four small trials (N = 209); better reporting of this outcome measure from the additional eight trials that recorded it may have improved our confidence in the pooled estimate. Global assessment and quality-of-life measures were poorly reported and it was not possible to carry out statistical analysis of these outcome measures. Analysis of adverse events showed an increase in the risk ratio with treatment with botulinum toxin over placebo 30% (RR 1.28, 95% CI 1.12 to 1.47, moderate-quality evidence). For every 100 participants 60 experienced an adverse event in the botulinum toxin group compared with 47 in the placebo group.Botulinum toxin versus other prophylactic agentThree trials studied comparisons with alternative oral prophylactic medications. Meta-analyses were not possible for number of migraine days, number of headache days or number of migraine attacks due to insufficient data, but individually trials reported no differences between groups for a variety of efficacy measures in the population of both chronic and episodic migraine participants. The global impression of disease measured using Migraine Disability Assessment (MIDAS) scores were reported from two trials that showed no difference between groups. Compared with oral treatments, botulinum toxin showed no between-group difference in the risk of adverse events (2 trials, N = 114, very low-quality evidence). The relative risk reduction (RRR) for withdrawing from botulinum toxin due to adverse events compared with the alternative prophylactic agent was 72% (P = 0.02, 2 trials, N = 119).Dosing trialsThere were insufficient data available for the comparison of different doses.Quality of the evidenceThe quality of the evidence assessed using GRADE methods was varied but mostly very low; the quality of the evidence for the placebo and active control comparisons was low and very low, respectively for the primary outcome measure. Small trial size, high risk of bias and unexplained heterogeneity were common reasons for downgrading the quality of the evidence. Authors' conclusions: In chronic migraine, botulinum toxin type A may reduce the number of migraine days per month by 2 days compared with placebo treatment. Non-serious adverse events were probably experienced by 60/100 participants in the treated group compared with 47/100 in the placebo group. For people with episodic migraine, we remain uncertain whether or not this treatment is effective because the quality of this limited evidence is very low. Better reporting of outcome measures in published trials would provide a more complete evidence base on which to draw conclusions.
Article
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Background: Headache is disabling and prevalent in idiopathic intracranial hypertension. Therapeutic lumbar punctures may be considered to manage headache. This study evaluated the acute effect of lumbar punctures on headache severity. Additionally, the effect of lumbar puncture pressure on post-lumbar puncture headache was evaluated. Methods: Active idiopathic intracranial hypertension patients were prospectively recruited to a cohort study, lumbar puncture pressure and papilloedema grade were noted. Headache severity was recorded using a numeric rating scale (NRS) 0-10, pre-lumbar puncture and following lumbar puncture at 1, 4 and 6 hours and daily for 7 days. Results: Fifty two patients were recruited (mean lumbar puncture opening pressure 32 (28-37 cmCSF). At any point in the week post-lumbar puncture, headache severity improved in 71% (but a small reduction of -1.1 ± 2.6 numeric rating scale) and exacerbated in 64%, with 30% experiencing a severe exacerbation ≥ 4 numeric rating scale. Therapeutic lumbar punctures are typically considered in idiopathic intracranial hypertension patients with severe headaches (numeric rating scale ≥ 7). In this cohort, the likelihood of improvement was 92% (a modest reduction of headache pain by -3.0 ± 2.8 numeric rating scale, p = 0.012, day 7), while 33% deteriorated. Idiopathic intracranial hypertension patients with mild (numeric rating scale 1-3) or no headache (on the day of lumbar puncture, prior to lumbar puncture) had a high risk of post- lumbar puncture headache exacerbation (81% and 67% respectively). Importantly, there was no relationship between lumbar puncture opening pressure and headache response after lumbar puncture. Conclusion: Following lumbar puncture, the majority of idiopathic intracranial hypertension patients experience some improvement, but the benefit is small and post-lumbar puncture headache exacerbation is common, and in some prolonged and severe. Lumbar puncture pressure does not influence the post-lumbar puncture headache.
Article
Full-text available
Methods: Between September 2015 and October 2017, a specialist interest group including neurology, neurosurgery, neuroradiology, ophthalmology, nursing, primary care doctors and patient representatives met. An initial UK survey of attitudes and practice in IIH was sent to a wide group of physicians and surgeons who investigate and manage IIH regularly. A comprehensive systematic literature review was performed to assemble the foundations of the statements. An international panel along with four national professional bodies, namely the Association of British Neurologists, British Association for the Study of Headache, the Society of British Neurological Surgeons and the Royal College of Ophthalmologists critically reviewed the statements. Results: Over 20 questions were constructed: one based on the diagnostic principles for optimal investigation of papilloedema and 21 for the management of IIH. Three main principles were identified: (1) to treat the underlying disease; (2) to protect the vision; and (3) to minimise the headache morbidity. Statements presented provide insight to uncertainties in IIH where research opportunities exist. Conclusions: In collaboration with many different specialists, professions and patient representatives, we have developed guidance statements for the investigation and management of adult IIH.
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Background: The management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of some of the drugs commonly used to manage idiopathic intracranial hypertension, therefore we propose to evaluate the efficacy of these drugs at lowering intracranial pressure in healthy rats. Methods: We measured intracranial pressure in female rats before and after subcutaneous administration of acetazolamide, topiramate, furosemide, amiloride and octreotide at clinical doses (equivalent to a single human dose) and high doses (equivalent to a human daily dose). In addition, we measured intracranial pressure after oral administration of acetazolamide and topiramate. Results: At clinical and high doses, subcutaneous administration of topiramate lowered intracranial pressure by 32% ( p = 0.0009) and 21% ( p = 0.015) respectively. There was no significant reduction in intracranial pressure noted with acetazolamide, furosemide, amiloride or octreotide at any dose. Oral administration of topiramate significantly lowered intracranial pressure by 22% ( p = 0.018), compared to 5% reduction with acetazolamide ( p = >0.999). Conclusion: Our in vivo studies demonstrated that both subcutaneous and oral administration of topiramate significantly lowers intracranial pressure. Other drugs tested, including acetazolamide, did not significantly reduce intracranial pressure. Future clinical trials evaluating the efficacy and side effects of topiramate in idiopathic intracranial hypertension patients would be of interest.
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Objectives Patients with idiopathic intracranial hypertension (IIH) usually require multiple lumbar punctures (LPs) during the course of their disease, and often report significant morbidity associated with the procedure. The aim of this study was to assess the patient’s experience of diagnostic LP in IIH. Design, methods and participants A cross-sectional study of patients with IIH was conducted using an anonymous online survey, with the questions designed in collaboration with IIH UK (the UK IIH charity). Responses were collated over a 2-month period from April to May 2015. Patients were asked to quantify responses using a Verbal Rating Score (VRS) 0–10 with 0 being the minimum and 10 the maximum score. Results 502 patients responded to the survey, of which 463 were analysed for this study. 40% of patients described severe pain during the LP (VRS ≥8), and the median pain score during the LP was 7 (VRS, IQR 5–7). The majority of patients felt they received insufficient pain relief (85%). Levels of anxiety about future LPs were high (median VRS 7, IQR 4–10), with 47% being extremely anxious (VRS ≥8). LPs performed as an emergency were associated with significantly greater pain scores compared with elective procedures (median 7, IQR 5–7 vs 6, IQR 4–8, p=0.012). 10.7% went on to have an X-ray-guided procedure due to failure of the initial LP, and the body mass index was significantly higher in this group (mean kg/m²40.3 vs 35.5, p=0.001). Higher LP pain scores (VRS) were significantly associated with poorly informed patients (Spearman’s correlation, r=−0.32, p<0.001). Patients felt more informed when the LP was performed by a specialist registrar compared with a junior doctor (median 7 vs 5, p=0.001) or a consultant compared with a junior doctor (median 8 vs 5, p<0.001). Conclusions This study was commissioned by the IIH patient group and is the first to document the patient experience of diagnostic LPs in IIH. It shows that the majority of these patients are experiencing significant morbidity from pain and anxiety. Patient experience of LP may be improved through changing clinical practice to include universal detailed preprocedural information, and where possible, avoiding emergency LPs in favour of LPs booked on an elective day-case unit.
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Background: Optical Coherence Tomography (OCT) imaging is being increasingly used in clinical practice for the monitoring of papilloedema. The aim is to characterise the extent and location of the Retinal Nerve Fibre Layer (RNFL) Thickness automated segmentation error (SegE) by manual refinement, in a cohort of Idiopathic Intracranial Hypertension (IIH) patients with papilloedema and compare this to controls. Methods: Baseline Spectral Domain OCT (SDOCT) scans from patients with IIH, and controls with no retinal or optic nerve pathology, were examined. The internal limiting membrane and RNFL thickness of the most severely affected eye was examined for SegE and re-segmented. Using ImageJ, the total area of the RNFL thickness was calculated pre and post re-segmentation and the percentage change was determined. The distribution of RNFL thickness error was qualitatively assessed. Results: Significantly greater SegE (p = 0.009) was present in RNFL thickness total area, assessed using ImageJ, in IIH patients (n = 46, 5% ± 0-58%) compared to controls (n = 14, 1% ± 0-6%). This was particularly evident in moderate to severe optic disc swelling (n = 23, 10% ± 0-58%, p < 0.001). RNFL thickness was unable to be quantified using SDOCT in patients with severe papilloedema. Conclusions: SegE remain a concern for clinicians using SDOCT to monitor papilloedema in IIH, particularly in the assessment of eyes with moderate to severe oedema. Systematic assessment and manual refinement of SegE is therefore important to ensure the accuracy in longitudinal monitoring of patients.
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Introduction Effective treatments are lacking for idiopathic intracranial hypertension (IIH), a condition characterised by raised intracranial pressure (ICP) and papilloedema, and found primarily in obese women. Weight loss and lowering body mass index (BMI) have been shown to lower ICP and improve symptoms in IIH; however, weight loss is typically not maintained, meaning IIH symptoms return. The Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) will assess whether bariatric surgery is an effective long-term treatment for patients with IIH with a BMI over 35 kg/m2. The National Institute for Health and Care Excellence recommends bariatric surgery in people with a BMI over 35 kg/m2 and a qualifying comorbidity; currently IIH does not qualify as a comorbidity. Methods and analysis IIH:WT is a multicentre, open-label, randomised controlled clinical trial of 64 participants with active IIH and a BMI over 35 kg/m2. Participants will be randomised in a 1:1 ratio to bariatric surgery or a dietary weight loss programme and followed up for 5 years. The primary outcome measure is ICP at 12 months. Secondary outcome measures include ICP at 24 and 60 months, and IIH symptoms, visual function, papilloedema, headache, quality of life and cost-effectiveness at 12, 24 and 60 months. Trial registration number IIH:WT is registered as ISRCTN40152829 and on ClinicalTrials.gov as NCT02124486 and is in the pre-results stage.