Atif B.D. Collins, MD
James A. McHale, MD
Steven E. Katz, MD
DESCRIPTION 
Pseudotumor cerebri (PTC) is a condition that mainly affects obese women and is associated with significant morbidity due to increased intracranial pressure (ICP). Headaches, transient visual obscurations (TVOs), and progressive visual loss are the most common presenting symptoms. The elevated ICP is transmitted through the optic nerve sheaths to the optic discs, causing papilledema, which is generally considered a medical emergency. CT scan demonstrates no evidence of a mass lesion, while lumbar puncture reveals an elevated opening cerebrospinal fluid (CSF) pressure. This unchecked process can lead to irreversible blindness.
EPIDEMIOLOGY
Incidence/Prevalence
- Obese women of childbearing age are most commonly affected (1)[B].
- Female/male ratio of 8:1 in the adult population.
- Incidence in general population 0.9:100,000
- In women age 20–44, >20% over ideal body weight 19.3:100,000
- No known association with race.
- Peak incidence is in the third decade, but can occur from infancy to old age.
RISK FACTORS
Pregnancy Considerations
No evidence of an increased risk of PTC onset or exacerbation during pregnancy.
Genetics
No known genetic syndrome.
GENERAL PREVENTION
Maintain ideal body weight.
PATHOPHYSIOLOGY
- Increased resistance to CSF egress at the arachnoid villi or through extracerebral lymphatics
- Brain edema and increased brain water content
- Increased venous pressure and cerebral blood volume
ETIOLOGY
The majority of cases are idiopathic; but resistance to CSF egress may be secondary to venous occlusive disease, sarcoidosis, meningeal carcinomatosis, systemic lupus, Behcet's disease, meningitis, and acromegaly. A variety of medications, including nalidixic acid, fluoroquinolones, tetracycline, doxycycline, minocycline, Accutane, growth hormone and hypervitaminosis A are well known secondary causes. An association with strep throat is common in the pediatric population.
COMMONLY ASSOCIATED CONDITIONS
[Outline]
HISTORY
- Headache (most frequent symptom)
- Generally holocranial or retrobulbar
- Relatively constant, “aching” or “throbbing” quality, variable intensity
- May be associated with nausea or light-headedness
- TVOs
- Unilateral or bilateral blurring, dimming, or loss of vision lasting for 2–3 seconds
- Secondary to optic disc swelling
- Visual loss (optic disc related)
- May be due to compressive optic nerve damage, optic disc infarction, choroidal folds, and subretinal hemorrhage
- Visual field loss
- Diplopia
- Pulsatile tinnitus
PHYSICAL EXAM
- Relative afferent pupillary defect with asymmetric optic nerve involvement.
- Bilateral optic disc swelling secondary to increased ICP (i.e., papilledema) is generally noted; however, asymmetric, unilateral or no optic disc edema may occur.
- Cranial nerve VI palsy, which may be unilateral or bilateral.
DIAGNOSTIC TESTS AND INTERPRETATION
Lab
Initial Lab Tests
Blood work is generally unnecessary in the typical idiopathic PTC patient. In an atypical patient (e.g., thin male) or in a patient with uncharacteristic symptoms or signs (e.g., arthralgias, malar rash, tetanic muscle spasms, cranial nerve III palsy), other laboratory tests may prove diagnostic for secondary forms of PTC: VDRL, antinuclear antibody, anti-dsDNA, serum Ca2+, ACE, lysozyme, growth hormone or IgF-1.
Follow-Up & Special Considerations
Basic metabolic panel to follow electrolytes and kidney function after initiating treatment with diuretics.
Imaging
Initial Approach
CT and MRI are the main imaging techniques used in PTC. Normal- to small-sized ventricles are seen with no evidence of mass lesion. Up to 70% of PTC patients have evidence of an empty sella. Clear differentiation between the optic nerve and sheath, with an enlarged, elongated subarachnoid space, and flattening of the posterior aspect of the globe may also be seen. MRI is better than CT to rule out infiltrative diseases and venous sinus thrombosis. Stenosis of the venous sinuses, often noted on MRI, generally resolves with lowering of the ICP; it appears to be secondary to raised ICP rather than causative (2)[C].
Follow-Up & Special Considerations
Shunt series for patients with recurrent symptoms and signs of raised ICP to evaluate shunt placement and integrity.
Diagnostic Procedures/Other
- Lumbar puncture (LP) is necessary to obtain the opening pressure (OP) and to rule out infection or inflammation. OP >20 cm H2O are considered elevated. Falsely low OP may occur when the LP requires multiple attempts with reinsertion and redirection of the needle. Falsely high OP may occur with patient positioning or Valsalva. LP under radiologic guidance should be considered in obese patients, especially when normal landmarks cannot be palpated. CSF analysis should include cell counts, differential, cytology, protein and glucose levels, Gram stain, and routine cultures and sensitivities. These are all within normal limits in idiopathic PTC.
- Visual acuity testing, pupillary responses, slit lamp and dilated funduscopic evaluation, and visual fields are necessary to assess baseline visual function. Stereoscopic optic disc photographs taken on initial evaluation can be used to monitor disease progression. Fluorescein angiography of the fundus may help to differentiate optic disc drusen (i.e., pseudopapilledema) from true papilledema. Disc drusen may autofluoresce on initial red-free photographs along with late staining, but no true leakage.
- Visual field loss
- Enlarged blind spot and generalized constriction are most common.
- Nasal step, arcuate defects, and cecocentral scotomas may also be encountered.
Pathological Findings
Unknown.
DIFFERENTIAL DIAGNOSIS
The diagnosis of idiopathic PTC is largely one of exclusion. Therefore, it is necessary to rule out other causes of papilledema and increased ICP as well as secondary PTC. Focal neurologic signs other than cranial nerve VI palsy should suggest a diagnosis other than PTC.
- Intracranial mass lesion with obstructive hydrocephalus
- Pseudopapilledema (i.e., optic disc drusen)
- Meningitis (i.e., bacterial, viral, neurosyphilis)
- Venous sinus thrombosis
- Medication related (e.g., tetracycline, growth hormone therapy)
- Systemic disease (e.g., systemic lupus erythematosus, Behcet's disease, acromegaly)
[Outline]
MEDICATION
First Line
Carbonic anhydrase inhibitors (CAIs): Neptazane 50 mg b.i.d. to q.i.d. and acetazolamide 250 mg b.i.d. to 500 mg q.i.d. are generally well tolerated.
- Contraindications
- CAIs are not contraindicated in patients reporting a sulfa allergy to antibiotics as they have a different sulfa moiety. There is a relative contraindication during the first trimester of pregnancy (class C).
- Precautions
- Common adverse effects: Tingling and numbness in the fingers and toes, fatigue, nausea, metallic taste, and K+ wasting. Aplastic anemia is a rare idiosyncratic reaction.
Second Line
- Furosemide: 20 mg b.i.d. to 40 mg q.i.d. is also effective; however, it is important to monitor serum potassium.
- Corticosteroids may be useful in patients with an underlying inflammatory condition such as systemic lupus.
- Octreotide, a somatostatin analog has been found in a small case series to lower ICP, relieve headache, reduce papilledema, and improve vision in PTC patients, although the mechanism of action is unknown (3)[B].
ADDITIONAL TREATMENT
General Measures
Suspect exogenous agents should be discontinued.
Issues for Referral
- Intractable headache, blurred vision, TVOs
- Papilledema, visual field loss, CN VI palsy
Additional Therapies
Analgesics may be used for symptomatic relief of headache.
COMPLEMENTARY AND ALTERNATIVE THERAPIES
Weight loss may reduce the need for medications or surgery, and may require consultation with a dietician.
SURGERY/OTHER PROCEDURES
Surgery may be necessary to control intractable headaches and to preserve visual function. The main options for PTC are neurosurgical shunting and optic nerve sheath fenestration (ONSF). Lumboperitoneal shunting may be preferable in patients with small ventricles, whereas ventriculoperitoneal shunting is a better option in patients with Chiari malformation. In a retrospective study of 30 PTC patients who underwent LP shunting, headache improved in 82%, papilledema resolved in 96%, and visual acuity or field improved in 68% (4)[B]. The mean follow-up duration was 34.9 months and the mean shunt revision rate was 4.2 per patient. In ONSF, a window is made in the anterior dural covering of the optic nerve. ONSF is useful to decompress the optic nerve in cases with papilledema. It is less likely to relieve high ICP in the long run; however, it does reduce the risk of visual loss with recurrent elevation of ICP. Gastric bypass surgery may be indicated to improve weight loss in morbidly obese patients.
IN-PATIENT CONSIDERATIONS
Initial Stabilization
- Intravenous acetazolamide or furosemide for rapid decompression of optic disc
- Potential use of high dose methylprednisolone to reduce optic disc edema
- Papilledema should be reduced with restoration of blood flow in the optic nerve head prior to consideration of ONSF; performing ONSF on an ischemic optic disc was associated with an increased risk of visual loss (5)[A]
- Electrolytes, BUN, creatinine monitored daily
Admission Criteria
Hospital admission may be indicated for (a) expedited brain MRI, fluoroscopically-guided lumbar puncture and initiation of medical therapy, or (b) urgent surgical intervention to preserve vision.
IV Fluids
May be indicated with or without intravenous caffeine for low tension headache after lumbar puncture.
Discharge Criteria
Stabilization with definitive outpatient plan.
[Outline]
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
Papilledema may not resolve completely with appropriate treatment and may not recur significantly with elevated ICP once it becomes chronic in nature. Optic disc appearance alone is not adequate to assess for recurrent elevation in ICP; subjective symptoms and visual field progression may be more reliable.
DIET
Low sodium diet with a goal toward maintaining ideal body weight.
PATIENT EDUCATION
Patients should be educated about the signs and symptoms of PTC as well as the importance of weight loss and regular follow-up.
PROGNOSIS
Once the condition is controlled on medication for 6 months, attempts to wean off the medication should be made periodically, especially when weight loss has been achieved. Systemic hypertension is a risk factor for greater visual loss.
COMPLICATIONS
- Permanent, irreversible vision loss
- Intractable headache with lost productivity
[Outline]
Obese females of childbearing age with chronic headache (with or without papilledema) should receive a thorough eye exam, an MRI brain with gadolinium, and a lumbar puncture.
