Etiology and Causative Agents

Elevated dural venous pressures leading to disturbances in CSF absorption at the level of the arachnoid granulations is a widely proposed pathophysiology for IIH.⁷ Secondary intracranial hypertension as a cause of PTCS has been reported to occur following cerebral venous thrombosis in thrombophilic states, such as systemic lupus erythematosus (SLE),⁸ protein C and protein S deficiencies,^9,10 malignancies, oral contraceptive use,¹¹ pregnancy, polycystic ovary disease,⁹ and from infections including meningitis and mastoiditis. Jugular valve insufficiency has also been found in association with PTCS/IIH.¹² Thrombophlebitis due to an indwelling central venous catheter has also been reported to cause PTCS.¹³ Other associations with PTCS include metabolic and endocrine disturbances/conditions such as Addison disease, hyperthyroidism, hypothyroidism, menarche, and pregnancy. A variety of drugs have been implicated in the development of PTCS, most commonly tetracycline, vitamin A, and lithium carbonate (Table 95-1).

Table 95-1 Causes of Pseudotumor Cerebri Syndrome

Diagnosis

Patients who present with headaches with features suggestive of elevated ICP should undergo a funduscopic examination to assess the optic discs for papilledema. Magnetic resonance imaging (MRI) or computed tomographic (CT) scanning should be performed in all patients with papilledema to evaluate for intracranial masses and to assess ventricular size. Patients with increased ICP may not only have normal or small-sized ventricles,¹⁴ but those with long-standing increased ICP may have an empty appearance of the sella turcica (26.7% sensitive, 94.6% specific), and patients with severe papilledema may show flattening of the posterior aspect of the eye (43.3% sensitive, 100% specific) (Fig. 95-1).¹⁵ The diagnosis of IIH thus should be suspected when no intracranial lesion is found and the ventricles are not dilated. In addition, MR or CT venography should be performed to determine if venous sinus stenosis or thrombosis is present, even if the patient appears to have a physical appearance typical of IIH. Neurologic examination in patients with PTCS/IIH usually reveals no focal deficits except for occasional unilateral or bilateral sixth nerve pareses.

FIGURE 95-1 Thirty-seven-year-old patient with pseudotumor cerebri presenting with headache, papilledema, and a pulsatile tinnitus. A, CT venography, 3D reconstruction prior to stent placement, left posterior oblique projection. Bilateral transverse sinus stenoses initially suspected by MR venography are confirmed by this study performed after lumbar puncture. The arrow points at the left transverse sinus lesion that will be targeted during the endovascular procedure. B, Digital subtraction angiography, injection of the left transverse sinus proximal to the site of stenosis, right anterior oblique projection. The pressure gradient across the lesions was measured at 30 mm Hg. C, Same projection as B, unsubtracted image obtained after stent placement. Measurements performed after treatment showed no residual pressure gradient. D, CT venography, 3D reconstruction, left posterior oblique projection, obtained 6 months after stent placement. The study shows full patency of the stented segment. Clinically, the papilledema had completely resolved. Both the pulsatile tinnitus and the headache had disappeared immediately after treatment. The CSF opening pressure was measured at 42 cm of water before treatment and 20 cm of water after stenting. 3D, three-dimensional; CSF, cerebrospinal fluid; CT, computed tomography; MR, magnetic resonance.

A lumbar puncture to measure opening pressure and to assess CSF content is required to establish the diagnosis of PTCS/IIH. It is important however, that no patient undergoes lumbar puncture until an MRI or CT scan of the brain is performed to exclude an intracranial mass. CSF opening pressures greater than 250 mm H₂O and normal CSF composition and cytology are required for diagnosis. Lumbar opening pressures should be always be measured with patients lying in the lateral decubitus position with legs extended and relaxed. Patients lying prone during the insertion of the LP needle should be repositioned to the lateral decubitus position before opening pressures are measured to prevent falsely high measurements that result from an increase in abdominal pressure when patients lie prone.^1,3 This precaution should be observed especially when a lumbar drain is placed under fluoroscopic guidance during which patients are typically positioned prone. Similarly, patients whose lumbar puncture is performed with the patient sitting upright should be repositioned to the lateral decubitus position, as measurements of ICP in the sitting position are different from those in the lateral decubitus position, because of the relative positions of the heart and head.

Frequently, a single measurement of opening pressure and the presence of other clinical features fulfilling the criteria described above are sufficient to diagnose a patient with PTCS or IIH; however, patients with atypical presentations, such as chronic persistent headaches without papilledema and normal opening pressures, but in whom there is a high suspicion of IIH (obese patients or those with other conditions associated with IIH), require a 24- to 48-hour continuous recording of ICP, as intermittent elevations of ICP, mostly during sleep, can occur.^16,17

In addition to neuroimaging and lumbar puncture, patients with suspected or proven PTCS should be evaluated for endocrine/metabolic disturbances, sleep apnea, and potential drug toxicities. When present, treatment of these entities may result in normalization of ICP and resolution of papilledema without surgery.