Idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, is a syndrome of raised intracranial pressure without an identifiable etiology such as hydrocephalus or occupying lesion. IIH typically presents with headaches, visual disturbances and are found to have papilledema on clinical examination. Normal cerebrospinal fluid (CSF) composition is essential in diagnostic criteria.1 The most important risk factors for the development of IIH include obesity, female gender, and recent weight gain.2 Many theories such as CSF overproduction, impaired CSF absorption, cerebral edema, endocrine disorders and alterations of cerebral blood volume or pressure have been proposed to explain IIH. However, it is still unclear its origin and pathological mechanisms.
Obstruction or impairment of intracranial venous drainage has been considered as an important mechanism.3 Over 90% of patients with IIH have stenotic transverse sinus (TS),4 and these stenotic lesions could cause sinovenous hypertension which has been confirmed by invasive monitoring in typical cases.3,5 It still debates on whether stenotic venous sinus contributes to raised intracranial pressure or is simply a consequence of intracranial hypertension.6 Stent placement to stenotic TS can normalize the CSF pressure and relieve the symptoms.7 We presented the clinical manifestations and outcome of a refractory IIH case treated with stent placement.
A 45-year-old female presented with non-specific headache, vomiting, and visual disturbance for 6 months that had increased in severity during the past 2 weeks. She was irritable and refused to communicate with others. Signs of meningeal irritation were presented.
Ophthalmological examination revealed uni-lateral VI cranial nerve palsy and bilateral swollen optic discs with tortuous blood vessels. Other neurological examination results were unremarkable. Comprehensive laboratory evaluations were all normal, including CSF composition. Lumbar puncture demonstrated a CSF opening pressure of 36 cmH2O.
She was treated with mannitol, acetazolamide, topiramate, and loop diuretics after initially manifested with headache but with poor effect. Magnetic resonance (MR) revealed that there was no significant lesion in the brain, and the morphological characteristics of the ventricular system were normal (Figure 1A). The magnetic resonance venography (MRV) demonstrated that the left TS was totally occluded and there was a distinct stenosis in the right TS (Figure 1B).
Aspirin (300 mg, P.O., q.d) and clopidogrel (75 mg, P.O., q.d) was suggested 3 days before endovascular procedure. The procedure was performed under general anesthesia with systemic anticoagulation by using intravenous heparin administered to maintain an activated clotting time. A high-flow microcatheter was navigated into the lateral sinuses with the support of a microwire. Manometry was obtained by a pressure transducer attached to the microcatheter referenced to zero at the level of midaxillary line. Venous phase of angiography confirmed that the left TS was occluded, while there was a distinct stenosis near the corner of the right TS and sigmoid sinus with a marked pressure gradient. The proximal pressure was 46 mmHg and the distal pressure was 13 mmHg (Figure 1C). A 4.5 mm diameter × 20 mm long (Wingspan, Inc, USA) stent was implanted to the distinct stenosis of the right TS and the sinus returned to its normal caliber immediately after the procedure (Figure 1D). The proximal pressure decreased to 18 mmHg, while the distal became 14 mmHg.
After this procedure, the patient's headache was markedly reduced apart from mild left-sided discomfort over the region of the stent. Intravenous heparin therapy was continued for 48 hours. Her vision remained stable and CSF opening pressure decreased to 24 cmH2O. The patient was discharged home with instructions to maintain her aspirin therapy regimen (100 mg, P.O., q.d) and arrangements for close ophthalmological follow-up were made. One month after initial procedure, the lumbar puncture was performed and CSF opening pressure decreased to 14 cmH2O. A year later, the symptoms and signs were disappeared.
With the new criteria of IIH, the radiological investigation of presumed cases is directed to rule out known causes of increased intracranial pressure.1 Computed tomography (CT) or magnetic resonance imaging (MRI) will exclude hydrocephalus or a mass occupying lesion. Patients with the characteristic clinical features could be considered as IIH once these examinations are found to be normal. Although most IIH patients improve with conservative therapy, an estimated 18%-22% of patients are considered refractory with visual impairment and headaches persisting or progressing despite maximally tolerated treatment with acetazolamide, topiramate, and loop diuretics, surgical therapies for IIH should be considered.8 The mainstay procedures include lumboperitoneal shunt, ventriculoperitoneal shunt and optic nerve sheath fenestration. These traditional surgical procedures are not universally effective. Nearly one-third of the failure rates have been reported and complications are not rare.8–10
Venous sinus stenting for IIH was first introduced by Higgins et al7 in 2002, which based on the theory that sinovenous hypertension is the final common pathway in the etiology of IIH.3 It is reported that more than 90% of IIH patients have TS stenoses.4 And high pressure in the sinovenous was observed by cerebral venography and manometry.3,5 The focal stenotic lesions of the venous sinuses caused partial obstruction to cranial venous outflow and then contributed to intracranial hypertension.
To date, more than 40 IIH cases treated with sinovenous stent placement have been reported.11 After stent placement, not all patients' symptoms resolved or improved, there are 7 of 40 (17.5%) patients reported their headaches still existed.11 The most common adverse effect was transient headache ipsilateral to the stent, including our case. Two cases had new stenoses developed proximal to the stent.6,12 One of them was treated with a ventriculoperitoneal shunt due to persistent symptoms.12
An important problem still needs to resolve. It is lack of generally accepted peri-operative anti-coagulative regimen. There are no detailed illustrations of pre-operative and intra-operative anti-coagulation therapy in reported papers. Moreover, the post-operative therapies were also totally different. Higgins et al13 suggested low dose aspirin for 8 weeks, while Arac et al14 recommended clopidogrel 75 mg/d (the duration was unknown). Bussiere et al11 only suggested antiplate therapy for 3 months (the kind of chemicals, dose and durations are all unknown). In our opinion, aspirin (300 mg, P.O., q.d) and clopidogrel (75 mg, P.O., q.d) was suggested 3 days before endovascular procedure. And systemic anticoagulation by using intravenous heparin administered to maintain an activated clotting time during procedure. The patient was discharged home with instructions to maintain her aspirin therapy regimen (100 mg, P.O, q.d) lifelong.
It still lacks of guidelines on the exact dosage and duration of anticoagulation therapy during the procedure and antiplatelet therapy after the procedure. The proper peri-operative anti-coagulative therapy ought to be evaluated in a prospective, randomized and controlled trial.
There is no doubt that stent placement requires further evaluation. But in strictly selected cases, it avoids traditional surgery and the results seem encouraging. Before it is applied more widely, a larger randomized controlled study is needed.
1. Friedman DI, Jacobson DM. Diagnostic criteria for idiopathic intracranial hypertension. Neurology 2002; 59: 1492-1495.
2. Ko MW, Chang SC, Ridha MA, Ney JJ, Ali TF, Friedman DI, et al. Weight gain and recurrence in idiopathic intracranial hypertension: a case-control study. Neurology 2011; 76: 1564-1567.
3. Karahalios DG, Rekate HL, Khayata MH, Apostolides PJ. Elevated intracranial venous pressure as a universal mechanism in pseudotumor cerebri of varying etiologies. Neurology 1996; 46: 198-202.
4. Farb RI, Vanek I, Scott JN, Mikulis DJ, Willinsky RA, Tomlinson G, et al. Idiopathic intracranial hypertension: the prevalence and morphology of sinovenous stenosis. Neurology 2003; 60: 1418-1424.
5. King JO, Mitchell PJ, Thomson KR, Tress BM. Cerebral venography and manometry in idiopathic intracranial hypertension. Neurology 1995; 45: 2224-2228.
6. Rohr A, Dorner L, Stingele R, Buhl R, Alfke K, Jansen O. Reversibility of venous sinus obstruction in idiopathic intracranial hypertension. AJNR Am J Neuroradiol 2007; 28: 656-659.
7. Higgins JN, Owler BK, Cousins C, Pickard JD. Venous sinus stenting for refractory benign intracranial hypertension. Lancet 2002; 359: 228-230.
8. Garton HJ. Cerebrospinal fluid diversion procedures. J Neuroophthalmol 2004; 24: 146-155.
9. Feldon SE. Visual outcomes comparing surgical techniques for management of severe idiopathic intracranial hypertension. Neurosurg Focus 2007; 23: E6.
10. Brazis PW. Clinical review: the surgical treatment of idiopathic pseudotumour cerebri (idiopathic intracranial hypertension). Cephalalgia 2008; 28: 1361-1373.
11. Bussiere M, Falero R, Nicolle D, Proulx A, Patel V, Pelz D. Unilateral transverse sinus stenting of patients with idiopathic intracranial hypertension. AJNR Am J Neuroradiol 2010; 31: 645-650.
12. Owler BK, Parker G, Halmagyi GM, Dunne VG, Grinnell V, McDowell D, et al. Pseudotumor cerebri syndrome: venous sinus obstruction and its treatment with stent placement. J Neurosurg 2003; 98: 1045-1055.
13. Higgins JN, Cousins C, Owler BK, Sarkies N, Pickard JD. Idiopathic intracranial hypertension: 12 cases treated by venous sinus stenting. J Neurol Neurosurg Psychiatry 2003; 74: 1662-1666.
14. Arac A, Lee M, Steinberg GK, Marcellus M, Marks MP. Efficacy of endovascular stenting in dural venous sinus stenosis for the treatment of idiopathic intracranial hypertension. Neurosurg Focus 2009; 27: E4.