Pseudotumor cerebri (PTC) is a neurologic disorder that typically manifests with ocular signs and symptoms. Although PTC is a relatively rare condition, we have consistently seen one or two cases annually throughout our careers.
Typically, patients with PTC are overweight women between the ages of 20 and 45.1,2 More than 90% report headache as their chief complaint. Other symptoms may include dizziness, tinnitus, nausea and vomiting.3 Visual symptoms are present in up to 70% of patients and include transient visual obscurations, blurriness and intermittent horizontal diplopia.3 Papilledema is almost always seen in these patients.3 Radiographic imaging is typically unremarkable; however lumbar puncture reveals elevated cerebrospinal fluid pressure in excess of 200mm H2O (or 250mm in the obese patient).3
While the precise mechanism of PTC is not known, many consider the condition to be a result of poor cerebrospinal fluid absorption by the meninges surrounding the brain and spinal cord. Possible causative or contributory agents include: drugs (e.g., naladixic acid, tetracycline, minocycline, corticosteroids, vitamin A, oral contraceptives), endocrinologic abnormalities, anemias, blood dyscrasias, and chronic respiratory insufficiency (e.g., obstructive sleep apnea).4
Another interesting theory of the mechanism of PTC: Increased intra-abdominal pressure (the result of obesity) with subsequent elevation of intrathoracic pressure. This presumably results in diminished venous drainage from the brain.5 Though current theories are not without merit, there is still little consensus as to the exact etiology of PTC.
Diagnosis and Management
Detecting PTC is relatively straightforward. It is a diagnosis of exclusion, made in cases of papilledema that result from raised intracranial pressure and that lack evidence of other intracranial abnormalities. Effective management of PTC, on the other hand, presents a significant challenge. Controversy surrounds the use of drugs for this condition, primarily because of the propensity toward adverse effects.
In most cases of PTC, systemic medications are initiated soon after the diagnosis is established. Historically, the drug of choice for initial management is Diamox (acetazolamide, Wyeth). Diamox is a carbonic anhydrase inhibitor (CAI) and serves to diminish production of cerebrospinal fluid by as much as 50%.6 The typical dosage is between one and three grams per day in three to four divided doses.
Unfortunately, acetazolamide has some negative side effects, including taste alteration, nausea, fatigue, diarrhea and tingling of the extremities. Because of the taste and GI side effects, patients may lose their desire to eat. While these side effects are unpleasant, they often have the beneficial effect of helping PTC patients lose weight.
Historically, patients who are allergic to sulfa medications have been advised to avoid acetazolamide because of potential cross-reactivity, though more recent studies question this practice.7 More serious complications from this medication may include the development of renal stones, metabolic acidosis and aplastic anemia, though such events only occur rarely and with very high doses of this medication.
In general, younger patients tend to tolerate acetazolamide better than older patients. Also, Diamox Sequels seem to be better tolerated because of their time-release formulation.
Other medications that are used for PTC may include:
Other diuretics. When acetazolamide is contraindicated or poorly tolerated, other diuretics may be utilized. Hygroton (chlorthalidone, Aventis) and other thiazide diuretics have been used effectively in numerous cases.8 Loop diuretics, such as Lasix (furosemide, Aventis), have likewise been used with success in treating PTC.9 Both chlorthalidone and furosemide are capable of reducing intracranial pressure without the significant side effects associated with acetazolamide.
Corticosteroids. The efficacy of corticosteroids was first reported in 1961, and since then other studies have documented a prompt and beneficial response to steroids in patients with PTC.10,11 However, the use of corticosteroids in these patients remains controversial.
While a short-term course of oral or intravenous dexamethasone may help to initially lower intracranial pressure, there are numerous long-term side effects to consider. Of particular note is weight gain, which can further exacerbate PTC.
Potential ocular complications, such as cataract and ocular hypertension, are undesirable in patients who are already visually compromised. Also, papilledema may recur with rapid tapering of the dose. For these reasons, most neuro-ophthalmologists have abandoned the use of corticosteroids to treat patients who have PTC.12
Migraine therapy. This may help manage the severe and sometimes incapacitating headaches associated with PTC. Studies have shown that common migraine medications, such as Elavil (amitriptyline, AstraZeneca), Inderal (propranolol, Wyeth), Ergomar (ergotamine tartrate, Harvest Pharmaceuticals) and Imitrex (sumatriptan, GlaxoSmithKline) may help control headache symptoms to a large degree in some patients.13
Topamax (topiramate, Ortho-McNeil Neurologics). This drug is classified as a neuroleptic medication and is specifically indicated for migraine prophylaxis and epilepsy. However, this drug is commonly used off-label to treat a variety of other conditions, both neurological and otherwise. These include bipolar disorder, diabetic neuropathy, alcohol abuse, obesity, post-traumatic stress disorder and autism.
Two reports suggest that Topamax may help manage PTC because of the drugs multiple mechanisms of action, including headache relief and mild inhibition of carbonic anhydrase.14,15 Weight loss is also common with this drug, and most experts consider this a welcome side effect in patients with PTC.16
However, Topamax has recently been implicated in the development of angle-closure glaucoma secondary to choroidal expansion. So, patients who use this medication must be closely monitored for this condition.17,18
Pseudotumor cerebri is an uncommon but potentially serious neurologic condition. Virtually every optometrist will encounter a patient who has PTC at some time during his or her career. Prompt diagnosis and treatment is the key to preventing devastating vision loss. A working knowledge of the available therapeutic options helps you to better manage and communicate with your patient and her primary-care physician.
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