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[page 42] [Eye Reports 2011; 1:e13]

Idiopathic intracranial
hypertension: a possible 
association with Imatinib
Anja M. Palmowski-Wolfe,1 Eva Pape,2
Thomas Baumann,3
Margarita G. Todorova1
1University of Basel, Department of
Ophthalmology; 2University Basel,
Department of Neurology, Basel;
3Neurozentrum Bern, Bern, Switzerland

Abstract 

Idiopathic intracranial hypertension (IIH) is
characterized by an increased intracranial pres-
sure in the absence of a tumor and in the
absence of a venous thrombosis. Associated risk
factors include obesity and several medications
such as tetracyclines. We report a 60-year-old
patient who developed IIH under treatment with
imatinib. To our knowledge such a possible con-
nection has not been reported in the literature,
even though intracranial hypertension is now
listed as a rare possible side effect of treatment
with imatinib in the Swiss List of Medications
Arzneimittelkompendium. It remains to be
seen, if further case reports will support this
observation.

Introduction

Imatinib inhibits particular tyrosine kinases
that are expressed excessively in certain carci-
nomatous diseases and also inhibits platelet-
derived growth factor. It was introduced approx-
imately a decade-and-a-half ago to treat chronic
myeloid leukaemia (CML). In this disease a cer-
tain tyrosine kinase, encoded by the BCR-Abl
gene transcript, is expressed and causes uncon-
trolled cell divisions through its excess activity.
This process can be blocked with imatinib
which results in a reduction of the number of
pathologic tumor cells.1 Meanwhile imatinib is
also applied to treat patients with gastrointesti-
nal stromal tumors.1 Imatinib is the only FDA
approved tyrosine kinase inhibitor for the treat-
ment of patients with systemic mastocytosis,
where a majority of patients excessively express
the mast and stem cell growth factor receptor,
SCFR or CD117, encoded by the KIT gene, and
which has tyrosine kinase activity.2 As imatinib
has only been on the market for a relatively
short time, with time, new side effects are being
described.1 We report a possible association
between imatinib and Idiopathic intracranial
hypertension (IIH).

Case Report

A 60-year-old Caucasian female presented
with blurred vision at our department of neu-
rology. Her past medical history was remark-
able for a systemic mastocytosis of more than
35 years, with possible gastrointestinal
involvement, and with bone marrow involve-
ment proven by histology. For the last 3 years,
the mastocytosis was treated with imatinib,
which is marketed by Novartis under the name
of Glivec (imatinib ut imatinib mesilate) in
Europe and under the name of Gleevec (ima-
tinib mesilate) in the US. The patient also had
obesity of more than 30 kg excess body weight
(WHO III) and arterial hypertension.
On examination, her Snellen visual acuity in

decimal equivalents was 0.7 in each eye.
Chronic papilledema was present in both eyes,
and as a consequence, there were already signs
of chronic nerve fibre damage, notably disc atro-
phy (Figure 1). The optical coherence tomogra-
phy demonstrated a superior temporal nerve
fibre layer defect (Figure 2). This nerve fiber
layer defect correlated with a bilateral caudal
nasal visual field defect (Figure 3). Magnetic
resonance imaging revealed enlarged optic
nerve sheaths with increased filling on both
sides and a partial empty sella, which had
already been described 4 years previously
(Figure 4). A thrombosis of the sinus veins was
ruled out with magnetic resonance venography
(Figure 5). On lumbar puncture an increased
intracranial pressure (ICP) of 38.5 cmH2O was
measured. The number of cells in the cere-
brospinal fluid was normal (0.3¥106/L), and
total protein was 349 mg/L.
In order to reduce ICP, the patient was start-

ed on oral acetazolamide 250 mg four times per
day. Weight reduction was recommended and
dietary training was provided, albeit with limit-
ed success. Under the hypothesis that imatinib
might be associated with the increased ICP, the
manufacturer of the imatinib was contacted. A
closer association to imatinib could not be
proven at the time. Nevertheless the patient
was switched to nilotinib (Tasigna, Novartis), a
second-generation tyrosine kinase inhibitor.
Under these measures, the blurred vision went
away and the visual acuity improved to 0.8 in
the right eye and 1.0 in the left eye. Over a time
period of one-and-a-half years, the visual fields
showed no significant changes. When an
attempt was made to discontinue diamox,
blurred vision recommenced but then resolved
again with oral acetazolamide. Acetazolamide
was then switched to topiramate, an anticonvul-
sant that, among other presumed actions,
inhibits the carbonic anhydrase enzyme and
has an anorectic side effect. Under this treat-
ment, the patient became free of symptoms and
lost 3 kg over the course of 2 months.

Discussion

IIH is a disease of unknown etiology. Obesity,
especially of the lower body half, increases the
risk of developing IIH. Medications such as tetra-
cyclines have also been associated with this dis-
ease.3 In rare cases, IIH has been described as a
presenting symptom in CML, a myeloproliferative

Eye Reports 2011; volume 1:e13

Correspondence: Prof. Dr. Anja Palmowski-Wolfe,
Universität Basel, Augenklinik, Mittlere Strasse
91, CH 4031 Basel, Switzerland.
Tel. +41.61.265.8722 - Fax: +41.61.265.8744.
E-mail: palmowskia@uhbs.ch

Key words: idiopathic intracranial hypertension,
glivec, imatinib.

Received for publication: 30 May 2011.
Revision received: 30 September 2011.
Accepted for publication: 30 October 2011.

This work is licensed under a Creative Commons
Attribution NonCommercial 3.0 License (CC BY-
NC 3.0).

©Copyright A.M. Palmowski-Wolfe et al., 2011
Licensee PAGEPress, Italy
Eye Reports 2011; 1:e13
doi:10.4081/eye.2011.e13

Figure 1. Fundus photographs of the right
and left optic nerve heads show the
patient’s chronic papilledema with a
resulting slight disc pallor as a sign of
beginning optic atrophy.

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[Eye Reports 2011; 1:e13] [page 43]

disorder that results in an increase of leucocytes
present in the bone marrow and blood. It has been
postulated, that the very high white blood cell
count in CML reduces the absorption of cere-
brospinal fluid (CSF) into the sinuses, thus lead-
ing to IIH.4,5 Mastocytosis is a rare disease that
also leads to an increased production of cells, in

this instance mast cells and their precursors. 
In our patient, her mastocytosis was well

controlled and, at the time where she devel-
oped IIH, there was no increased number of
cells in her blood. Therefore, an increased
hyperviscosity of the peripheral blood prevent-
ing resorption of CSF into the sinuses seems

an unlikely cause of IIH in our patient. In addi-
tion, we have not found any reports in the
peer-reviewed medical literature (using MED-
LINE) that describe IIH in mastocytosis.
Imatinib is a recent drug which means, that

with time, new side effects are being
described.1 In a search of the peer-reviewed
medical literature (using MEDLINE), we have
not found a reported association of imatinib and
IIH. However, a non peer-reviewed anecdotal
report revealed a possible connection in one
individual who was on imatinib for 10 months
and ended up with pseudo tumor cerebri.6 In
another non peer-reviewed literature document
IIH is claimed as a potential rare side effect of
imatinib, though no clinical case report, refer-
ence, or substantiation is provided.7
The pathomechnism by which imatinib

might cause IIH is not clear. Weight gain from
fluid retention has been reported as a frequent
side effect of imatinib.1 In fact, this fluid reten-

Case Report

Figure 2. The optical coherence tomography reveals superior temporal nerve fibre layer
(NFL) loss. The black line demarcates the patient’s NFL thickness for the right eye (top)
and for the left eye (below). Reduced NFL thickness (marked by the black arrows) is indi-
cated when this line deviates from the green area of normative values in to the red area.

Figure 3. The nerve fibre layer loss seen in Figure 2 correlates well with the visual fields
obtained at that time. These show a nasal, more caudal field loss (black arrows) in the
right eye more than the left eye.

Figure 4. Magnetic resonance imaging
demonstrates enlarged optic nerve sheaths
(red arrows) as well as a partial empty sella
(asterisk).

Figure 5. The sinus veins are shown with
contrast medium (asterisk). With this mag-
netic resonance venography a thrombosis
of the sinus veins could be ruled out.

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[page 44] [Eye Reports 2011; 1:e13]

Case Report

tion can also occur in the brain. In 2002,
Ebnöether, et al. reported 2 patients who devel-
oped cerebral edema under imatinib; in one of
these patients, this cerebral edema occurred 6
months after the treatment was started. The
authors explained the underlying pathomech-
anism as follows: imatinib inhibits platelet
derived growth factor which may result in a
decrease in interstitial fluid pressure and
increase in capillary-to-interstitium transport.8

In addition, imatinib may increase appetite
and lead to weight gain from increased food
intake, as in our patient who had gained 30 kg
when started on imatinib. 
An association between imatinib and IIH

may thus exist either as a direct association or
as an indirect association through induction of
a weight increase. As such an association
could not be ruled out, the patient was
switched to nilotinib. Nilotinib is a second
generation tyrosine kinase inhibitor that has a
target profile similar to imatinib.2 Even though
it is not quite as successful as imatinib in the

treatment of systemic masocytosis,2 to our
knowledge, IIH has so far not been associated
with nilotinib. In the meantime, IIH has been
included in the Swiss medical compendium as
a possible side effect of imatinib. However, the
Swiss medical compendium does not suggest a
pathomechanism and also does not provide
additional reasoning for this listing.

References

1. Mughal TI, Schrieber A. Principal long-term
adverse effects of imatinib in patients with
chronic myeloid leukemia in chronic phase.
Biologics 2010;4:315-23.

2. Ustun C, DeRemer DL, Akin C. Tyrosine
kinase inhibitors in the treatment of sys-
temic mastocytosis Leuk Res 2001;35:
1143-52.

3. Kapoor KG. More Than Meets The Eye?

Redefining Idiopathic Intracranial Hyper-
tension. Int J Neurosci 2010;120:471-82.

4. Abbot L, Mioneau G, Johnston D. An unusu-
al cause of headaches and priapism in a
teenager. Paediatr Child Health 2008;13:
299-301.

5. Falardeau J, Lee A. Chronic myeloid
leukemia mimicking idiopathic intracra-
nial hypertension. Neuro-Ophthalmology
2001;26:229-34.

6. Side Effects with Glivec. CMLSupport
Chronic Myeloid Leukaemia Support
Group. Available from: http://www.cmlsup-
port.org.uk/node/5984

7. Imatinib Side Effects. Drugs.com, Drug
Information online. Available from:
http://www.drugs.com/sfx/imatinib-side-
effects.html

8. Ebnöether M, Stentoft J, Ford J, et al.
Cerebral oedema as a possible complication
of treatment with imatinib. Lancet 2002;
359:1751-52.

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