Keywords
pseudotumor cerebri - idiopathic intracranial hypertension - unilateral papilledema
- iron-deficiency anemia
Palavras-chave
pseudotumor cerebral - hipertensão intracraniana idiopática - papiledema unilateral
- anemia ferropriva
Introduction
Pseudotumor Cerebri (PTC), also known as idiopathic intracranial hypertension (IIH)
or benign intracranial hypertension (BIH), is a medical condition characterized by
increased intracranial pressure (ICP) without evidence of intracranial mass, hydrocephalus,
infection or hypertensive encephalopathy. It usually affects overweight women of childbearing
age, and its pathogenesis is uncertain.[1]
[2]
[3]
[4] Some studies indicate that this is an absorbing problem at the arachnoid level,[4] but there is much controversy in the literature. The diagnosis of PTC is based on
clinical symptoms and signs, normal findings in imaging studies, increased cerebrospinal
fluid (CSF) opening pressure, and exclusion of other probable pathologies.[5]
Case Report
A 44-year-old female patient, who was previously healthy, underwent an abdominoplasty
under epidural anesthesia. The surgery was uneventful, and the patient was discharged
in good general condition ∼ 24 hours after the procedure. About 48 hours after discharge,
the patient sought care with an ophthalmologist due to loss of vision in the right
eye. In addition, she had a sudden headache of strong intensity and holocranial in
nature, which was associated with an emetic episode, diplopia and dizziness. Papilledema
was observed in the ophthalmologist's office, and the patient was referred to our
clinic.
Upon admission, the general physical examination revealed a heart rate of 120 bpm,
and the carotid auscultation revealed bilateral bruits. The body mass index (BMI)
was 28 kg/m2. A neurological examination showed a reduction in visual acuity in the right eye,
maintaining only the perception of movement. In addition, an edema was found in the
ipsilateral papilla. The other aspects of the neurological examination did not suggest
other abnormalities.
Due to the rapid onset of symptoms, the patient underwent magnetic resonance imaging
(MRI) with and without contrast, which revealed only relatively small ventricles ([Fig. 1]). In addition, arterial and venous angio-MRIs were performed, and the results were
considered normal ([Fig. 2]). After the radiological investigation, the patient was admitted for a clinical
investigation.
Fig. 1 Normal magnetic resonance imaging (MRI) scan of the brain. T1-weighted, axial plane.
Fig. 2 Normal three-dimensional gadolinium-enhanced magnetic resonance venogram (MRV), sagittal
view.
The laboratory investigation revealed levels of serum hemoglobin of 5.2 g/dL. In addition,
the hemogram showed microcytosis and hypochromia. The cardiologic evaluation revealed
no abnormalities. A lumbar puncture was performed, and the opening pressure was of
34 cm H2O. The diagnosis of BIH was made, and the treatment for anemia associated with blood
transfusion and iron supplements was initiated. Due to severe vision loss, intravenous
(IV) methylprednidisolone 250 mg was prescribed every 6 hours associated with acetazolamide
1,000 mg twice a day.
The patient presented a dramatic response to the treatment, with complete improvement
of the symptoms, except for the visual deficit, which remained unchanged. She was
discharged 72 hours after admission, with no complaints, maintaining only the visual
deficit. The ophthalmologic evaluation after discharge suggested a probably irreversible
lesion in the right optic nerve.
Discussion
Pseudotumor cerebri is a disorder that affects overweight/obese women of childbearing
age, and it has an annual incidence of 1–2/100,000 inhabitants among the general population.[4]
[6]
[7]
[8] However, it is a disease that can affect men, children, the elderly, and patients
who are not obese.[9]
[10]
[11]
[12]
[13] When it affects younger people, gender and weight appear to have no significance
in the incidence.[14]
[15]
A considerable number of systemic conditions, drugs and vitamin deficiency have been
associated with PTC. One peculiar condition mentioned in the literature is iron-deficiency
anemia, whose prevalence in patients diagnosed with PTC is ∼ 10%.[16]
[17]
[18]
[19] However, the statistically significant association between PTC and the other conditions
is unclear in many cases.
Typically, PTC is a self-limited but recurrent pathology, with a recurrence rate ranging
from 9–43%.[6]
[7] Severe visual deficits develop in 4–12% of the patients, although there is no relation
to the duration of the symptoms, the degree of the papilledema, headache or the number
of recurrences.[20]
Due to the intrinsic mechanisms of the body, it is conclusive that the increase in
intracranial pressure is originated in at least one of the following body components:
CSF, blood, interstitial fluid or cerebral cells. Cerebrospinal fluid production is
relatively constant and independent of its internal pressure, at least to some extent.
Hence, the increase in pressure is not quickly normalized with the reduction in CSF
production, facilitating the development of the condition, once the process is initiated.[21]
[22]
[23] An increase in CSF production has been suggested in PTC,[24] but there is no evidence to support such a theory, or any structural changes in
the choroid plexus, such as hypertrophy. There is some evidence to suggest that CSF
production is normal in PTC.[25]
Most of the focus on PTC pathogenesis studies has been on resistance to the CSF absorption
mechanism. Several studies involving CSF infusion have been published, and all showed
a greater resistance to CSF absorption in PTC.[26]
[27]
[28] Gjerris et al found a lower CSF flow in 12 out of 14 patients with PTC, with 2 normal
values measured after the beginning of the treatment.[27] Janny et al demonstrated resistance to the flow in all 16 patients with PTC studied.[28] Although most studies have focused on the intracranial CSF compartment, new imaging
techniques using dynamic contrast phases suggest that there is an increase in extraventricular
CSF volume and a decrease in jugular venous output in PTC compared with control individuals.[29] Alterations in spinal canal compliance may be a contributory factor.[30] It seems likely that the decrease in absorption is the core of the pathophysiology,
possibly due to a local effect involving the epithelial membrane of the CSF output
routes.
Magnetic resonance venography demonstrates that the majority of PTC patients have
venous sinus stenosis.[31] It is unclear if such stenosis is the cause or consequence of PTC, although cases
of demonstrated resolution of collapsible venous sinus segments after CSF drainage
and pressure normalization have suggested that the latter is true.[32]
[33] Cerebral venous sinus narrowing usually develops at the transverse sinuses or transverse/sigmoid
junction, and may be bilateral or unilateral.[34]
For the cases of venous sinus stenosis, the placement of a stent seems to be a good
therapeutic option. In a study conducted with a large cohort composed of 52 patients
who underwent unilateral cerebral venous sinus stenting, all patients had resolution
of the papilledema; 23 out of 30 patients had resolution of the visual field loss,
and headache only persisted in 3 patients.[34]
Etiology – Association with Iron-deficiency Anemia
Etiology – Association with Iron-deficiency Anemia
Even though the condition is also known as idiopathic intracranial hypertension (IIH),
the nomenclature of pseudotumor cerebri (PTC) syndrome is more inclusive, because
it covers both the idiopathic cause and the secondary etiologies.
Giuseffi et al[17] reported a prospective controlled study adjusted for age and sex that investigated
the associations of diseases and drugs in PTC. They found that iron-deficiency anemia
was not more common in patients with intracranial hypertension than in controls. This
result was similar to the ones published by Ireland et al,[16] who reported that iron-deficiency anemia was more frequently found in the control
group. However, the association between the two conditions seems to be strong, since
PTC symptoms resolve when the patient is treated for iron-deficiency anemia, as it
happened in the case presented here.[17]
[35]
In a study by Mollan et al,[35] 8 patients with PTC and iron-deficiency anemia were reported, and 7 of them had
remission of the symptoms with the treatment for anemia. The patients were treated
with blood transfusion and oral iron replacement, depending on the severity of the
symptoms.
Clinical Features
The most prevalent symptoms in PTC are headache (88%), transient visual obscurations
(70%), pulsatile tinnitus (56%), nausea (32%), diplopia (28%), and visual loss (14%).
The presentation can be acute with recurrences or chronic (26–32%).[8]
[19]
The characteristics of the headache can be variable. Unilateral or bilateral headaches
that are pulsatile and with a retro-ocular location have been reported.[36] Transient visual obscurations occur in two thirds of the patients with papilledema,
and they may be unilateral or bilateral.[8] The frequency ranges from rare episodes to multiple cases per day. However, the
presence of this symptom does not seem to be correlated with the severity of the disease.[17]
[37] It is believed that pulsatile tinnitus represents vascular pulsations transmitted
by the CSF to the venous sinuses at high pressure.[38] When it occurs along with headache, it is highly suggestive of PTC.[17]
[39]
[40]
The principal signs of PTC are papilledema, visual field loss, and abducens nerve
palsy.
Papilledema is generally symmetrical and bilateral, and is one of the hallmark features
of PTC.[41]
[42]
[43] The presence of unilateral papilledema is rare, and the degree of visual field loss
is greater in the eye with the higher grade of papilledema.[42] This uncommon unilateral commitment was present in our patient, and it was associated
with the permanent loss of the visual field.
Abducens nerve palsy may present unilaterally or bilaterally, and it reflects the
effect of the elevated intracranial pressure on this nerve, which has the largest
intracranial pathway.[19]
[44]
In the presence of signs of intracranial hypertension, neuroimaging should be performed
to discard a secondary cause, such as tumor, intracranial hemorrhage or venous sinus
thrombosis. In the absence of altered imaging, lumbar puncture and CSF analysis are
indicated to discard other causes. It is also necessary to request a blood count to
verify the presence of anemia, a condition that may be associated with PTC.[45]
In general, the patients present spontaneous resolution of the symptoms within a year.
Therefore, the interventional treatment is commonly suggested whether the patients
are symptomatic or did not have resolution of the set.[46]
[47]
[48] However, recurrence may occur in those patients who received the medical treatment,
as well as in those who did not need it. In obese patients, weight loss has been associated
with complete resolution of the papilledema.[49]
[50] Weight loss has shown such good results that bariatric surgery has been studied
as an option of treatment for obese patients. Nevertheless, this improvement may be
too slow for cases of highly-threatened vision; thus, in these cases, pharmacological
treatment would be helpful.[50] The interventional treatment is based on fluid and salt restriction combined with
diuretics. Acetazolamide, a carbonic anhydrase inhibitor, has been widely used to
reduce the intracranial pressure with good results; therefore it seems to be a good
drug to be administered as a first choice, even though no randomized clinical trial
data have confirmed its effectiveness. A long-term follow-up study demonstrated that
60% of the patients had recurrent episodes during a period of 6.2 years; however,
none of these episodes occurred during the time the patients were taking acetozalamide.[51] Other drugs, such as furosemide, methazolamide and topiramate, have also been used
to manage the symptoms, but they do not seem to be as effective as acetazolamide when
used alone. Corticosteroids do not seem to be recommended as a routine choice of treatment,
especially because of their relationship to weight gain, but in a critical situation,
they may be useful to relieve the symptoms.[46]
[47]
[49]
[52]
Additionally, as PTC appears to be related to different causes, it is plausible that
the underlying cause is corrected.[48] In our case, we prescribed acetazolamide and corticosteroid ,since the patient presented
a high risk of visual loss. We treated the patient for iron-deficiency anemia with
ferrous sulfate. In the cases that cannot be managed with drugs, ventricle or lumbar-peritoneal
shunts have been shown to be effective choices. However, some patients may develop
chronic daily headaches, and this may be understood as shunt failure.[47]
[49] Furthermore, if the condition cannot be managed only by pharmacological treatment
or with a shunt, an optic nerve sheath fenestration is an option in order to preserve
the visual function.[46]
[47]
Conclusion
Our case highlights an uncommon presentation of PTC with unilateral papilledema and
the still poorly-understood association between iron deficiency and BIH. As reported
in the literature, our case presented a dramatic response to PTC symptoms with the
treatment for iron-deficiency anemia. This response points to a possible association
between these two conditions, but more studies should be conducted to elucidate this
correlation.
