Pseudotumor Cerebri in a Pregnant Patient

Standard treatment may not be appropriate in certain conditions.

By Kasie J. Mix, OD, MS

Elevated cerebrospinal fluid levels may lead to permanent vision loss. They require urgent medical management. In this case, traditional medical therapy is questioned because the patient is pregnant.

— Ahmad M. Fahmy, OD, FAAO, Dipl ABO

 

A 25-year-old white woman presented urgently to our clinic. She reported a chief concern of sudden onset “shadowing” and blurring of her vision with new onset of debilitating headaches for the past week. The patient reported that the shadowing was only present with both eyes open, and it resolved when she closed either eye. Vision in both eyes seemed more blurred even when either eye was closed. The images were not quite doubled, she reported, but were side-by-side shadows, and these had continued to worsen with each passing day. Her vision was equally shadowed at both distance and near, she reported, and she noticed that she could not see her face in the mirror on the morning of her visit, and it appeared “grayed out” for a short period of time. Additionally, the patient said she was in a motor vehicle accident 1 month ago, during which the car’s airbag deployed. Afterward, her eyes were tender to the touch, but this resolved after a few weeks.

The patient was 18 weeks pregnant (second trimester) upon initial presentation to our clinic. She reported a long history of migraine headaches but never to the extent experienced recently (periorbital and hemicranial). She was taking acetaminophen as needed for her migraines, as she was no longer taking sumatriptan (unknown dosage) because of her pregnancy. She had self-discontinued her prenatal vitamins, but this has not helped relieve her symptoms.

The patient’s last comprehensive eye examination was within the past year, and she reported seeing her obstetrician/gynecologist regularly for prenatal appointments. Personal ocular history was unremarkable, with both eyes emmetropic. She reported no history of ocular trauma or surgical intervention. Her medical history included chronic migraine headaches, and, as noted previously, she was 18 weeks pregnant. The patient reported no allergies to medications, and recently she was taking only acetaminophen as needed and the now-discontinued prenatal vitamins. Personal use of tobacco and cigarettes was denied.

The patient’s family ocular history was unremarkable. There was a positive family history of a brain aneurysm (mother, age 40). The patient’s review of systems was positive for binocular horizontal diplopia and headaches.

INITIAL PERTINENT FINDINGS

The patient reported that her visual acuity was mildly decreased in both eyes. All entrance skills measurements, anterior segment examination, and Goldman applanation tonometry were within normal limits for both eyes. The posterior examination of both eyes revealed a very full, swollen optic nerve appearance with indistinct and elevated optic disc margins. The patient’s confrontation visual fields, color vision, and stereopsis of both eyes were normal. Peripheral fundus examination was normal for both eyes. The patient had a body mass index (BMI) score of 30.66 kg/m2 (height 66 in, weight 190 lbs). Blood pressure measurement was within normal limits (122 mm Hg/76 mm Hg).

Figure 1. Optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) performed at initial presentation revealed elevation of the optic nerve tissue of both eyes consistent with papilledema.

Optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) revealed elevation of the optic nerve tissue of both eyes consistent with papilledema (Figure 1).

Initial diagnoses included papilledema OU, diplopia OU, emmetropia OU, and a family history of brain aneurysm.

INITIAL REFERRAL

Due to concern for a space-occupying lesion, it was strongly recommended that the patient immediately undergo magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the brain and orbits. A same-day appointment was made at the patient’s local emergency department. The patient had the confounding factors of being 18 weeks pregnant and having a BMI of 30.66 kg/m2. The patient also had a positive family history of a brain aneurysm at a young age, which increased the necessity for immediate referral.

DIFFERENTIAL DIAGNOSES

There are many etiologies to be considered when a patient presents with papilledema. These include idiopathic, inflammatory, infectious, infiltrative, and other medical etiologies.

• pseudotumor cerebri (idiopathic intracranial hypertension)

• intraorbital neoplasms

• medications

• obstruction to venous drainage

• infections

• medical disorders

• pseudopapilledema

The most common differential for papilledema in young to middle-aged overweight women is pseudotumor cerebri.1 Pseudotumor cerebri is a diagnosis of exclusion that can only be made once other secondary etiologies such as a mass, hydrocephalus, or intracranial venous sinus thrombosis are ruled out.2 MRI imaging can rule out other etiologies of increased cerebrospinal fluid (CSF) pressure and will essentially reveal a normal brain and orbits.3 Certain characteristics may be seen, such as an empty sella tursica or flattening of the posterior aspect of the globe, but pseudotumor cerebri is always also associated with elevated intracranial pressure (ICP).2

The most important differential to rule out as a cause of papilledema is an intraorbital neoplasm causing an elevation in ICP.4 In this event, a space-occupying lesion would be found with MRI or computed tomography (CT) imaging. A variety of medications are known to cause optic disc edema and elevated ICP, including tetracyclines, high levels of vitamin A, oral contraceptives, cyclosporine, and anabolic steroids.2

CSF levels may increase as a result of venous drainage obstruction, which may be associated with an intracranial venous sinus thrombosis or compression via an intracranial mass (meningioma).3 Certain infections, such as HIV and Lyme disease, may also lead to increased ICP. Many medical disorders may lead to increased ICP, such as Addison disease, hypoparathyroidism, obstructive sleep apnea, systemic lupus erythematous, and severe iron deficiency anemia.

Optic nerve head drusen or congenital anomalous discs may also mimic an appearance of pseudopapilledema, in which case additional testing with B-scan ultrasonography or fundus fluorescein angiography may be necessary.2

To reach the proper diagnosis, a thorough case history is necessary, and discontinuing the causative agent (if applicable) may resolve the papilledema. However, due to the potentially vision threatening and even fatal nature of etiologies associated with elevated ICP, referral for MRI, MRA, and magnetic resonance venography (MRV) imaging is absolutely necessary. As stated above, pseudotumor cerebri is a diagnosis of exclusion.

NEUROIMAGING RESULTS AND SECONDARY REFERRAL

The patient underwent MRI and MRA of the brain and orbits to determine the cause of the papilledema of both eyes. These imaging results were normal: no mass or bleed of the brain or orbits were found.

Although the MRI and MRA were normal, more testing was necessary to rule out other possible etiologies such as elevated ICP. It was recommended that the patient see a local neurologist for a next available appointment for review of the imaging and for any additional imaging necessary for precise diagnosis. The neurologist, whom the patient saw the next day, elected to first rule out an intracranial venous sinus thrombosis before proceeding with a lumbar puncture. An MRV was ordered, and results were normal.

Because no mass was found on MRI, and both MRA and MRV were normal, a fluoroscopically guided lumbar puncture was performed. Local lidocaine anesthesia was used to collect a sample of 15 mL of CSF. The opening pressure was found to be elevated at 38 cm of water. The CSF specimen was sent to a laboratory to be analyzed for the following: cell count with differential, protein, oligoclonal bands, immunoglobulin G (IgG) index rate, IgG symphysis rate, and cytology for malignant cells. Serum was also collected and analyzed for oligoclonal bands and immunoglobulin synthesis rate. The CSF and serum laboratory results were of normal composition. The patient was to follow up with the neurologist in 5 to 10 days after the lumbar puncture.

FINAL DIAGNOSIS

The results were finalized by the neurologist, and a diagnostic report was issued with a final diagnosis of pseudotumor cerebri. No causative factor was found aside from the patient’s risk factor of being a young pregnant woman with an above-average BMI.

DISCUSSION

Pseudotumor cerebri is a disease process that occurs as a result of increased ICP secondary to an unidentifiable etiology. The mechanism responsible for the increased ICP is not known, aside from some sort of abnormal absorption of CSF.4 Pseudotumor cerebri tends to occur most commonly in middle-aged overweight women of child-bearing years.4

Arguably, the largest risk factor associated with pseudotumor cerebri is obesity.2 Studies have shown that pseudotumor cerebri patients with a BMI greater than 40 kg/m2 carry a higher risk of severe visual loss.5 Interestingly, it was found that, although individuals with a BMI greater than 40 kg/m2 are more likely to have permanent vision loss, these individuals were actually less likely to complain of visual symptoms upon presentation to a physician.6

Pregnancy has also been found to be associated with pseudotumor cerebri, and the rate of pseudotumor cerebri occurring during pregnancy is the same as the rate within the normal population.4 Because of weight gain and hormone changes during pregnancy, the symptoms associated with pseudotumor cerebri may become exacerbated.

Although there is no clearly identifiable etiology in almost 90% of patients with pseudotumor cerebri, there is indeed a clear etiology, such as occurrence secondary to intracranial venous stenosis, in 10% patients.3 In addition, increased ICP associated with pseudotumor cerebri may cause permanent vision loss. Because of this, some believe that previous terms such as idiopathic or benign intracranial hypertension should no longer be used.

Classically, patients with pseudotumor cerebri present with complaints of headaches and visual changes associated with clinically significant optic disc edema.3 Headaches are the most commonly associated symptom, and they tend to be worst in the morning.4 They may be acute headaches, or they may present in a manner that is more chronic than typical; this is important to recognize, as the patient in this case had a long history of migraine headaches.2

Vision is typically affected as well, with presentations including visual blur, diplopia, and transient visual obscurations. Horizontal diplopia associated with pseudotumor cerebri may occur as a result of an abducens cranial nerve palsy.2 This is due to the elevated CSF compressing the sixth cranial nerve and thus inhibiting the function of the extraocular lateral rectus muscle. Other symptoms may be noted, such as pulsatile tinnitus, a subjective whooshing sound heard in rhythm with each heartbeat.2 Some patients may present with no symptoms whatsoever, and papilledema may be noted upon examination.4

MRI is performed as a means to diagnose pseudotumor cerebri by exclusion: that is, by determining that the elevated CSF is not associated with a secondary cause. The first and most important consideration is to rule out any underlying systemic cause of papilledema, such as an intracranial tumor.4 In the case of pseudotumor cerebri diagnosis, MRI results will reveal normal brain parenchyma without the presence of a mass or hydrocephalus.2

It is important to note that pseudotumor cerebri may be associated with the following findings on MRI imaging: an empty sella tursica; decreased pituitary gland height; flattening of the globe; enlarged optic nerve sheath; and increased tortuosity, protrusion, or enhancement of the optic nerve.3 If an MRI is not available, or the patient is unable to undergo an MRI, a CT scan of the head and CT venogram may be performed.2

Lumbar puncture is the next step in diagnosis of pseudotumor cerebri, and it is performed only after neuroimaging scans are found to be normal. Normal CSF opening pressure is 10 cm to 20 cm of water, whereas elevated CSF opening pressure is 25 cm of water or greater.4 Lumbar puncture is done with the patient lying in a lateral decubitus position, and the procedure is typically done under fluoroscopic or ultrasonic guidance if the physician believes the procedure will be challenging.2 Pseudotumor cerebri diagnosis is supported by an elevated ICP of at least 25 cm of water, as well as by CSF of normal composition.4 Lumbar puncture results in a short-term lowering effect on CSF pressure, and it is very effective in alleviating headaches associated with increased ICP. Therefore, lumbar puncture may be repeated if necessary, but it is not required to be repeated for follow-up care of pseudotumor cerebri.

Ocular coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) is a useful tool to assist in the diagnosis and monitoring of pseudotumor cerebri. OCT of the RNFL will differentiate between optic nerve head edema an optic disc drusen. Papilledema associated with pseudotumor cerebri presents differently on RNFL OCT than does pseudopapilledema associated with optic disc drusen. The calcium deposits (drusen) typically will display an elevation of the optic nerve head associated with an internal optic nerve contour that has a lumpy-bumpy appearance, as well as a rapid decrease in thickness of the subretinal hyporeflective space.7 Conversely, swelling (edema) typically will display an elevation of the optic nerve head with an internal contour that has a smooth appearance, as well as a “lazy V” pattern in the subretinal hyporeflective space.

Humphrey visual field testing is useful not only for diagnosing pseudotumor cerebri but also for quantifying the severity of optic nerve involvement.4 Visual field testing is the most reliable means to establish a baseline assessment of optic nerve function at initial diagnosis of pseudotumor cerebri and also to monitor for progression or resolution of visual field loss over time. Papilledema associated with pseudotumor cerebri may cause enlarged blind spots results on visual field testing, but it may also mimic defects seen in glaucoma.4 Upon successful rapid treatment of pseudotumor cerebri, visual field defects should resolve. However, if permanent optic nerve damage has occurred, visual field defects will persist.

MANAGEMENT

Many treatment options are available for pseudotumor cerebri. The priorities for treatment include reducing morbidity of symptoms, decreasing the chance of permanent vision loss, and treating the underlying etiology2.

Oral carbonic anhydrase inhibitors, such as acetazolamide, are the first line of treatment to significantly reduce ICP in a timely manner.4 Maximum dose is typically 2,000 mg by mouth daily.2 Acetazolamide has many side effects, including diuresis, metallic taste, numbness and tingling of extremities, fatigue, loss of appetite, and gastrointestinal upset.4 They may be sufficiently disturbing to make the patient self-discontinue the medication.

It has been suggested that pseudotumor cerebri should be treated the same way in pregnant patients as in those who are not pregnant, with the exception of drug contraindications.4 On the other hand, it has been found that there are risks of acetazolamide associated with pregnancy, including toxicity to the fetus and risks to the mother during delivery.2 Fetal risks are greatest during the first trimester (weeks 1-12) and lesser during the second and third trimesters. Complications in the form of vision loss during prolonged labor are also increased when a patient is treated with acetazolamide. However, the increased ICP during vaginal delivery typically does not result in a high risk of visual compromise.4

Because untreated pseudotumor cerebri can cause permanent vision loss, it is important to weigh the risks versus the benefits of treating versus monitoring increased ICP in a pregnant woman. Therefore, acetazolamide may be considered as a treatment option in pregnant patients if necessary, principally after completion of the first trimester.2 It is also thought that acetazolamide is safe during breastfeeding postpartum, as only 0.06% of the dose is delivered to the infant.

Other oral agents have been used to treat pseudotumor cerebri. Second-line diuretics such as furosemide have been shown to be effective, but less so than acetazolamide.4 The effect of another carbonic anhydrase inhibitor, topiramate, on lowering ICP in pseudotumor cerebri is being evaluated. Oral corticosteroids may be given for a short period in patients who present with severe symptoms associated with pseudotumor cerebri, including obvious acute optic disc edema, markedly elevated ICP, and severe headaches. The side effects of oral corticosteroids are problematic in these patients, as they cause retention of fluid and weight gain. Stopping oral corticosteroids may also cause a rebound increase in ICP and thus papilledema. Therefore, most physicians do not use oral corticosteroids for treatment of pseudotumor cerebri.

Surgical intervention may be needed in severe cases of pseudotumor cerebri in which other treatments have not been effective and vision loss or symptoms progress. Use of lumbar peritoneal shunts may be necessary as a short term solution in reducing ICP to alleviate debilitating headaches.2 Optic nerve sheath fenestration surgery may also be performed, specifically when visual complaints are substantial and progressive.4 In fenestration, multiple linear incisions are made in the optic nerve sheath, creating new routes of drainage for CSF. Repeat lumbar punctures may also assist in alleviating headaches, but they are not necessary.4

Each of these surgical options requires general anesthesia. Pregnant patients are at increased risk of complications associated with general anesthesia, such as aspiration problems, airway difficulty, and surgical awareness.

Weight loss is arguably the most effective long-term solution in those with pseudotumor cerebri. Weight loss has been found to decrease symptoms associated with the condition.4 In fact, reduction of weight by 15% has been shown to reduce papilledema, headaches, and ICP at significant levels.2 The issue at hand, however, is maintaining weight loss over the long term via an effective diet plan short of bariatric surgery.

Another factor to consider in pregnant patients is that weight gain is a normal and expected side effect of pregnancy. As weight is gained during pregnancy, the risk of developing pseudotumor cerebri is increased.4 The Institute of Medicine has recommended that women with a BMI of 30 kg/m2 or greater who become pregnant should gain only 5 to 9 kg during pregnancy.2 Therefore, implementation of exercise and diet programs is an important consideration for obese patients, especially during pregnancy.

Prognosis of pseudotumor cerebri is excellent if proper diagnosis and implementation of treatment are made in a timely manner. Pseudotumor cerebri can be a self-limiting condition, but it may persist for several years if not treated, and it may also recur at any time.4 Typically, the most debilitating aspect of pseudotumor cerebri is the symptoms associated with increased ICP, principally headaches. When headaches persist despite treatment in pregnant patients, there is an associated 19% risk of permanent vision loss. In general, vision loss associated with pseudotumor cerebri has been estimated to occur in much less than 25% of patients.2

FINAL TREATMENT AND FOLLOW-UP

Following a thorough discussion of our patient’s debilitating symptoms and the available treatment options with her neurologist, taking into consideration the fact that she was now 20 weeks pregnant (second trimester), it was recommended that the patient begin oral acetazolamide at a dose of 250 mg twice daily.

She returned after 10 to 14 days for follow-up, at which time her symptoms had declined significantly. Within 1 week thereafter, the patient reported that her symptoms had returned and that her vision was again beginning to decline. She reported constant horizontal diplopia and headaches and the feeling that her vision fluctuated from day to day. The patient followed up with her neurologist, who noted that Snellen visual acuity was unchanged and there was still no lateral rectus palsy.

Due to her debilitating symptoms, it was decided to repeat the lumbar puncture. Opening pressure was within normal limits at 16 cm of water, and CSF was of normal composition. An increase in the dosage of acetazolamide to 500 mg twice daily was recommended, and she was asked to return in another 10 to 14 days.

Figure 2. Repeat RNFL OCT and baseline Humphrey visual field (VF) performed at 4-week follow-up visit. Elevation of the optic nerve tissue of both eyes, consistent with papilledema, was relatively stable from the initial scan (A). A reliable VF test of the right eye, resulting in nonspecific diffuse depression (B). A reliable VF test of the left eye, with a few scattered nonspecific defects (C). No enlargement of the patient’s blind spot was noted 3 weeks after initial presentation of papilledema.

Due to persistence of her symptoms, the patient followed up with a provider at our clinic for a progress check 4 weeks after her initial visit. She was now 22 weeks pregnant and was taking 500 mg acetazolamide twice daily. Uncorrected visual acuity was 20/20 OU. A repeat RNFL OCT (Figure 2A) showed relatively stable swelling of both optic nerves. Baseline Humphrey visual field testing (Figure 2B and 2C), which was less reliable in the right than the left eye, was essentially normal, with more nonspecific defects in the right than the left eye. The patient was advised to consider patching one eye if diplopia was bothersome while the optic nerve swelling continued to resolve over time.

The patient noted a continual improvement of her visual acuity, with a slower improvement of her diplopia and heachaches, compared with her initial presentation. However, she had become frustrated as a result of the ongoing double vision and headaches. Her diplopia seemed to be worse both at night and in bright sunlight, and she was still having transient visual obscurations.

She saw a neuro-ophthalmologist for a second opinion 5 weeks after initial presentation, at which time she was 23 weeks pregnant. A thorough neurological examination was essentially normal. Uncorrected visual acuity was 20/20 in the right and 20/15 in the left eye. No strabismus, color vision defect, or Humphrey visual field defect was noted. Her diplopia did not change in primary, secondary, or tertiary gazes. The only abnormal finding was the presence of mild optic nerve head edema on RNFL OCT.

The final assessment was pseudotumor cerebri, which has been responsive to treatment, and persistent complaints of a subjective visual disturbance. The patient was advised to continue the dosage of 500 mg acetazolamide twice daily and attend follow-up in 3 months for repeat Humphrey visual field and RNFL OCT of both eyes.

CONCLUSION

Although pseudotumor cerebri is the most common etiology for bilateral optic disc edema in middle-aged overweight women of childbearing years, there are numerous other etiologies for papilledema, including some that are potentially fatal. Obtaining a thorough case history is extremely important, and immediate referral for additional testing is crucial.

The diagnosis of pseudotumor cerebri is a diagnosis of exclusion. It can be made only with normal imaging results on tests including MRI, MRA, and MRV and with increased ICP with CSF of normal composition on lumbar puncture.5 Because additional imaging and management are necessary, taking into consideration any additional confounding factors such as pregnancy is absolutely essential, as certain medications and surgical interventions may be harmful to the fetus or the mother.

Due to persistent symptoms of headache and diplopia, our patient ultimately required repeat lumbar punctures and increased oral acetazolamide dosage during her second trimester, which carries risks to the pregnancy. In such cases, a conversion between the patient and any involved physician, weighing the risks and benefits of pregnancy complications versus permanent vision loss, is necessary.

Although pseudotumor cerebri has excellent prognosis, it may result in permanent vision loss if not treated in a timely manner and may recur at any time. Symptoms may persist for an extended period regardless of a normal ICP as the optic nerve edema resolves. Therefore, frequent follow-up and repeat subjective (Humphrey visual field) and objective (RNFL OCT and dilated fundus examination) evaluations are necessary to monitor progression or improvement of visual symptoms.

As a general rule, referral of any and all optic disc edema for neuroimaging including MRI, MRA, and MRV is absolutely essential for the proper diagnosis and long-term care of any patient presenting with papilledema. n

1. Goal A, Desai PK. Idiopathic intracranial hypertension. Radiopaedia. http://radiopaedia.org/articles/idiopathic-intracranial-hypertension-1. Accessed July 5, 2016.

2. Mollan SP, Markey KA, Benzimra JD, et al. A practical approach to, diagnosis, assessment and management of idiopathic intracranial hypertension. Pract Neurol. 2014;14(6):380-390.

3. Degnan AJ, Levy LM. Pseudotumor cerebi: brief review of clinic syndrome and imaging findings. Am J Neuroradiol. 2011;32:1986-1993.

4. Worrell J, Lane S. Impact of pseudotumor cerebri (idiopathic intracranial hypertension) in pregnancy: a case report. AANA J. 2007;75(3):199-204.

5. Weiner G. Case studies of optic disc edema. Eyenet Magazine. October 2015:43-48.

6. Szewka AJ, Bruce BB, Newman NJ and Biousse V. Idiopathic intracranial hypertension: relation between obesity and visual outcomes. J Neuroophthalmol. 2013;33(1):4-8.

7. Johnson LN, Diehl ML, Hamm CW, et al. Differentiating optic disc edema from optic nerve head drusen on optical coherence tomography. Arch Ophthalmol. 2009;127(1):45-49.

Section Editor Ahmad M. Fahmy, OD, FAAO, Dipl ABO
• Director of optometric services, Minnesota Eye Consultants, Minneapolis, Minnesota
• (612) 813-3600; amfahmy@mneye.com
• Financial interest: none acknowledged

Kasie J. Mix, OD, MS
• Optometry resident 2015-16, emphasis in cornea and refractive eye care
• Minnesota Eye Consultants, Minneapolis, Minnesota
• (612) 813-3600; kasiemix@gmail.com
• Financial interest: none acknowledged