Idiopathic intracranial hypertension
The prevalence and morphology of sinovenous stenosis

We congratulate Farb et al. on their discovery, introduction, and use of the auto-triggered elliptic-centric-ordered three- dimensional gadolinium-enhanced MR venogram (ATECO MRV) to diagnose idiopathic intracranial hypertension (IIH) with unprecedented sensitivity and specificity. [1] The similarities between IIH and cerebral venous thrombosis (CVT) and their established pathophysiological tie to cranial venous outflow obstruction are clear and may change the way we diagnose and treat these conditions. CVT and IIH overlap in risk factor profiles and in their relation to hyperestrogenemic exacerbation. It was recently found that both have a high incidence of hypercoagulable states and systemic inflammatory disease is recognized. [2,3,4] CVT has long been considered to mimic or masquerade as IIH and is frequently underdiagnosed. [2,5] The increased incidence of CVT has allowed the detection of increasingly smaller venous flow abnormalities or thrombus and has paralleled the advent of the conventional CT and MRI scanners.[3] It appears that the ATECO MRV has jumped the barrier and found consistent flow abnormality without radiologically confirmed thrombus in patients with IIH. Although it is unclear if cranial venous outflow obstruction is the primary or a secondary process in IIH, the question is raised, "Is it time to approach these two conditions as a spectrum of the same disease process?"

Bousser et al. have established heparin anticoagulation as the gold standard of treatment for CVT.[2] Heparin is now advocated in CVT patients regardless of clinical or neuroimaging patterns and the abolishment of new randomized placebo controlled trials has been proposed. The dramatic clinical improvement, even in the setting of hemorrhagic stroke, and the tendency of patients to improve following treatment with heparin support these claims. The possible prognosis of death from CVT initially justified anticoagulation as an experimental treatment, which has proven its success.[5] Now, procedural morbidity and mortality from repeated lumbar puncture in IIH and the current 25-30% incidence of blindness can no longer be ignored.[5] We recently performed a comprehensive literature review and found few, if any, descriptions of heparin anticoagulation being used as treatment for IIH. When obvious secondary causes for IIH cannot be determined, hypercoagulability and microthrombosis appear to be a possible mechanism of disease. Given the dramatic improvement seen in patients with CVT and the lack of a consistently effective treatment for IIH—Isn't it time to consider trials of anticoagulation as a treatment strategy for a select group of patients?

References

1. Farb RI, Vanek I, Scott JN, et al. Idiopathic intracranial hypertension, the presence and morphology of sinovenous stenosis. Neurology. 2003;60:1418-24.

2. Bousser MG. Cerebral venous thrombosis: diagnosis and management. J Neurol. 2000;247(4):252-8.

3. Johnston I, Kollar C, Dunkley S, Assaad N, Parker G. Cranial venous outflow obstruction in the pseudotumour syndrome: incidence, nature and relevance. J Clin Neurosci 2002;9(3):273-8.

4. Sussman J, Leach M, Greaves M, Malia R, Davies-Jones GA. Potentially prothrombotic abnormalities of coagulation in benign intracranial hypertension. Neurol Neurosurg Psychiatry 1997 Mar;62(3):229-33.

5. Biousse V, Ameri A, Bousser MG. Isolated intracranial hypertension as the only sign of cerebral venous thrombosis. Neurology. 1999;53:1537-1542.

It is unclear what is shown in neuroradiological examinations at the junction between transverse and sigmoid sinus. As reported by Farb et al [1], digital subtraction angiography requires expert advice and particular technical skills to avoid misinterpretation of filling defects. On 2D TOF MRA, the most currently used technique for cerebral venography, the junction between TS and SS is a favorite location for turbulence artefacts [2]. Moreover, anatomy is variable. Pacchioni granulations are frequently found and a single transverse sinus may be hypoplastic [2]. Different techniques were proposed to improve visualization of dural sinuses, such as CT-angiography [3] phase-contrast MR techniques, and ATECO sequence proposed by Farb et al. [1].

However, this location may be critical in idiopathic intracranial hypertension (IIH). In a relevant percentage of patients, elevated intravascular tension in the superior sagittal sinus and torcular drop to normal values at the TS-SS junction. [4] In a different series, pressure does not drop but remains elevated in all venous systems. [5] The elevated cardiac filling pressure may cause the elevated intracranial pressure. It is unclear if the drop in pressure is due to a stenosis or simply to the critical location of the TS and SS. It is between the supratentorial compartment (where venous pressure is equivalent to the intracranial pressure), and infratentorial and extracranial compartments, (where the venous pressure grossly corresponds to the central venous pressure).

Due to improved neuroimaging facilities, an increasing number of patients with "pseudotumor cerebri" are actually shown to have cerebral venous thrombosis [5] Or, as MR devices and sequences improve, more subtle stenotic venous anomalies, different from typical venous thrombosis, emerge [1]. Many of these patients would have been misdiagnosed in the past as "pseudotumor cerebri" and not cerebral venous thrombosis, with possible invasive treatment such as ventricular drainage. Anticoagulative treatment, highly effective on venous thrombosis, may be a possible treatment in all patients with pseudotumour cerebri. Low dose, low molecular weight heparin may "ex juvantibus" allow diagnosis and treatment of the patient with IIH and cerebral venous thrombosis. It is less dangerous than stenting intracranial sinuses.

References

1. Farb RI, Vanek I, Scott JN, Mikulis DJ, Willinsky RA, Tomlinson G, TerBrugge KG. Idiopathic intracranial hypertension: The prevalence and morphology of sinovenous stenosis. Neurology 2003 May 13;60(9):1418-1424.

2. Ayanzen RH, Bird CR, Keller PJ, McCully FJ, Theobald MR, Heiserman JE. Cerebral MR venography: normal anatomy and potential diagnostic pitfalls. AJNR Am J Neuroradiol. 2000 Jan;21(1):74-78.

3. Ozsvath RR, Casey SO, Lustrin ES, Alberico RA, Hassankhani A, Patel M. Cerebral venography: comparison of CT and MR projection venography. AJR Am J Roentgenol. 1997 Dec;169(6):1699-1707.

4. King JO, Mitchell PJ, Thomson KR, Tress BM. Cerebral venography and manometry in idiopathic intracranial hypertension. Neurology 1995; 45: 2224–2228

5. Sugerman HJ, DeMaria EJ, Felton WL 3rd, Nakatsuka M, Sismanis A. Increased intra-abdominal pressure and cardiac filling pressures in obesity-associated pseudotumor cerebri. Neurology 1997 Aug;49(2):507-511.

1) Why is there a pressure gradient across these narrowed segments as demonstrated by King and confirmed by our unpublished data? Is it due to a supratentorial /infratentorial pressure gradient as queried by Dr. Bergui? If so, would that not lead to signs of transtentorial herniation?

2) Given that the dural sinuses expand and contract depending on the ICP, why is the TS-SS junction the most susceptible region for this narrowing?

3) If this is indeed a secondary finding what role if any does it have in exacerbating the elevated ICP?

4) Will opening the sinus with an intravascular stent actually benefit these patients even though we lack understanding of the primary disease?

This also leads to the fundamental question of etiology. Sinovenous thrombosis (SVT) can clinically masquerade as IIH and is the most important diagnosis to exclude in these patients. The idea that IIH is simply the sequelae of SVT is intriguing but unsupported. In our recent trial [2], we identified all patients who presented with acute SVT and excluded them from the IIH cohort. Some authors imply that discriminating IIH from acute SVT at MRI is occasionally difficult [3]. In our experience, ATECO MRV has trivialized the diagnosis of acute SVT and does not resemble what we have found for IIH at MR imaging. What about chronic SVT? Is IIH simply a long-term chronic sequelae of macroscopic SVT? If IIH was a sequelae of previous or repeated SVT we would expect these patients not only to be more thrombogenic, for which there is some evidence [4], but we would also expect more occurrences of SVT, DVT,CVA or PE. Our series only turned up one "thrombogenic patient" (who had a PE diagnosed subsequent to the diagnosis of IIH). Nonetheless, perhaps the microenvironment of the arachnoid granulation is different. Micro-thrombosis of the arachnoid granulations may cause elevated intracranial pressure similar to other causes of extraventricular hydrocephalus (EVOH). But why then are the ventricles not enlarged as in EVOH? Does it make a difference which side of the membrane is plugged? As suggested by Drs. Bergui and Williams, a randomized trial of anticoagulant treatment of IIH may be informative. Others would argue that a trial of transverse sinus stenting is justified, if not for cure than perhaps for palliation.

References

1. Corbett JJ, Digre K. Idiopathic intracranial hypertension: An answer to, "the chicken or the egg?" Neurology 2002; 58:5-6.

2. Farb RI, Vanek I, Scott J, et al. Idiopathic Intracranial Hypertension: the prevalence and morphology of sinovenous stenosis. Neurology 2003; 60:1418-1424.

3. Johnston I, Kollar C, Dunkley S, Assaad N, Parker G. Cranial venous outflow obstruction in the pseudotumour syndrome: incidence, nature and relevance. Journal of Clinical Neuroscience. 2002; 9:273-8.

4. Sussman J, Leach M, Greaves M, Malia R, Davies-Jones GA. Potentially prothrombotic abnormalities of coagulation in benign intracranial hypertension. Journal of Neurology, Neurosurgery & Psychiatry. 1997; 62:229-33.