Unlocking the Mysteries of Idiopathic Intracranial Hypertension

Abstracts & Commentary

Sources: King JO, et al. Manometry combined with cervical puncture in idiopathic intracranial hypertension. Neurology. 2002;58:26-30; Higgins JN, et al. Venous sinus stenting for refractory benign intracranial hypertension. Lancet. 2002;359:228-230.

Idiopathic intracranial hypertension (IIH) typically occurs in young obese women and involves a constellation of headache, papilledema, raised intracranial pressure, and normal CNS imaging. IIH, more classically termed pseudotumor cerebri, is also known as benign intracranial hypertension (BIH). This variability in nomenclature in part reflects an overall lack of understanding of the pathophysiology of this disorder. Initial theories postulated an imbalance between excess CSF production and inadequate or impaired CSF resorption. With the advent of imaging techniques such as MR venography (MRV) showing venous sinus thrombosis in some previously idiopathic cases, some have argued that venous hypertension is the unifying cause in all cases of IIH. This hemodynamic explanation is particularly compelling for individuals who are pathologically obese and develop IIH as abdominal or intrathoracic venous pressures are transmitted to the CNS. Such theories are less applicable to patients who are slim or who have no evidence of right-sided heart failure.

Using venous manometric catheters passed intracranially into the tranverse sinus (TVS), torcula, and superior sagittal sinus (SSS), several investigators have demonstrated elevated central venous pressures in patients with IIH. Measured pressures have reached as high as 40 mm Hg, 8-fold greater than normal levels. These may occur due to obstruction in the TVS or in some cases, more uniformly throughout the SSS, torcula, and TVS. At the same time, CSF opening pressures are elevated, perhaps reflecting transmitted pressure from the venous system. CSF volumes may increase as the function of arachnoid granulations is impaired by an inappropriate pressure gradient into the venous outflow system.

The data presented by King and colleagues significantly debunk these "venous" theories. They suggest that elevated venous pressure may exacerbate CSF hypertension, but that it initially occurs only as an epiphenomenon of a primary increase in intracranial pressure (ICP). King et al’s data indicate that when ICP is reduced by CSF drainage, venous pressures drop. King et al studied 21 patients, the majority of whom were postulated to have TVS stenosis, with manometric data showing a significant pressure drop between the proximal and distal TVS. King et al treated a subset of 11 patients with C1-2 puncture and drainage of 20-25 mL of CSF. Somewhat surprisingly, this drainage produced a pressure drop in the proximal transverse sinus by as much as 41 mm Hg, with the most dramatic venous pressure decreases occurring in those patients with the highest initial venous pressures prior to C1-2 puncture. A minority of patients had less striking results, such as Patient 4 whose TVS pressure was only 9 mm Hg prior to CSF drainage, dropping to 5 mm Hg after therapy.

In previous work, King et al demonstrated a pressure drop across the transverse sinus, and postulated that this was due to incomplete recanalization of a thrombosed vein. As noted by King et al, these new data suggest that such a pressure drop may rather be caused by a reversible compression of the transverse sinus in the setting of high ICP. The easily distensible walls of the TVS collapse under pressure, but flow is re-established when ICP is reduced with CSF drainage. King suggests that there may be an asymptomatic phase of the illness during which ICP rises and the TVS remains patent. Once the TVS collapses, the SSS pressure rises rapidly, further impeding CSF absorption and producing a rapid rise in ICP with the acute onset of symptoms. The TVS is thus not the initial culprit in IIH but rather acts as a secondary and multiplicative phenomenon.

In a contrasting report, Higgins and colleagues present a case in which venous sinus stenting dramatically improved a patient with IIH. An obese 30-year-old woman presented with a 2-year history of headache, bilateral papilledema, and normal brain MRI as well as MRV. Therapies such as weight loss and acetazolamide were unhelpful. CSF opening pressure was 35 cm H20. Venography revealed bilateral stenotic lesions in the TVS with pressures of 27 mm Hg at the torcula and 9 mm Hg at the jugular (gradient = 18 mm Hg). A self-expanding stent was deployed across the stenosis in the right TVS, with the torcula-jugular gradient dropping to 3 mm Hg and immediate improvement of headache.

On the basis of this case, Higgins et al argue that CSF diversion procedures (such as serial LPs, VP shunting, or optic nerve sheath fenestration) often fail to treat IIH, because they do not address the fundamental problem: TVS stenosis. Higgins et al suggest that the TVS pathology was not thrombosis (as previously postulated by King) but rather an idiopathic narrowing of the TVS bilaterally.

Commentary

These 2 reports, published almost simultaneously, provide a fascinating juxtaposition. King et al’s work indicates that indeed it is CSF pressure rather than venous disease that may be the true pathophysiology in IIH. Conversely, Higgins et al treated the narrowed TVS, and produced dramatic improvement.

Where do these data leave us in our understanding of this mysterious disorder and how should these findings effect clinical strategies? Most importantly, if increased CSF pressure is the initiating event in IIH, what is the cause of this? How do the arachnoid granulations function and what specific pathology might they develop? With its strong gender predilection, what hormonal influences affect IIH and how does obesity factor in?

Therapeutically, given that IIH is likely a multifactorial process, a combination approach is prudent. Patients failing acetazolamide or other diuretic therapy should be considered for shunt procedures. Venous sinus stenting may be performed in selected cases. Although this may not be treating the primary problem, it may nevertheless be effective. It is possible that ICP-induced TVS compression maintains or even significantly accelerates a process set in motion by excess CSF. —Alan Z. Segal.

Segal, MD, Assistant Professor, Department of Neurology, Weill-Cornell Medical College, Attending Neurologist, New York Presbyterian Hospital, is Assistant Editor of Neurology Alert.