1. Idiopathic Intracranial Hypertension (IIH) A review of imaging manifestations and interventional treatment J. Agraval 1, B McGuinness 1, S Brew 1, A Hope 1, M Moriarty 1, 1 Auckland City Hospital, Auckland, New Zealand

2. Definition Raised intracranial pressure in the absence of an identifiable aetiology

3. Theories of aeitology 1,2 1.CSF homeostasis: Inadequate CSF resorption or increased production 2.Venogenic a.Venous sinus thrombus b.Extrinsic venous compression c.Vasculitis 3.Venous outflow obstruction i.e. Venous sinus stenosis Controversial regarding whether this is a causal factor or an effect

4. Cause or effect? Increased intracranial pressure  Intracranial hypertension Compression of the collapsible transverse sinus Venous outflow obstruction Venous hypertension Decreases CSF reabsorption

5. Epidemiology Thought to be rare (1 case per 100,000 5 ) but increasingly diagnosed due rising prevalence of obesity Female predominance 8:1 5 “Classic patient”= Overweight woman of reproductive age Incidence in 20-44y/o overweight women 19 per 100,000 5 Increased estrogen and leptin is also present in overweight patients with IIH Obesity = substantial risk factor. Theories 1,3, Increased BMI  Increased intrathoracic and intrabadominal pressure  elevated central venous pressure Prothrombotic state in obesity Increased leptin and estrogen levels in patients with IIH

6. IIH in Men – epidemiology 6 Older age group often >40 years Symptom profiles Less likely to report headache More common to report visual disturbance Worse visual outcomes: acuity and visual fields Increased risk of severe visual loss No differences in BMI Smaller case series describe men less likely to be overweight but BMI not reported

7. Diagnosis 4 Symptoms and signs related to raised intracranial pressure CSF opening pressure >25cmH 2 0 Normal CSF composition No evidence for underlying structural cause MRI with MR venography ideal

8. Typical Presentation 1 Headaches most common >90% Pressure-like unrelenting Associated retro-orbital pain Visual loss – most commonly transient Tunnel vision Related to transient ischemia of the optic nerve from the increased CSF pressure in optic nerve sheath Papilledema – often seen in routine or symptomatic visual testing

9. Typical Imaging findings -Empty sella: downward herniation of an arachnocele through the diaphragma sella -Posterior scleral flattening with enlarged and tortuous optic nerve sheaths -Distal transverse venous sinus stenoses

10. MR venography Should be routine in suspected cases to evaluate for either thrombus or stenosis 1,12 Stenosis can be seen in up to 90% of IIH patients 12 Stenosis can be seen in up to 90% of IIH patients 12 TOF or PC MRV is usually inadequate and contrast enhanced MRV should be performed It is the authors personal experience that where contrast MRV is not available, 3D gradient post contrast T1 reformatted in sagittal and coronal planes often enables accurate diagnosis of venous stenoses CT venography is also a suitable test

11. Typical Imaging Findings 23 year old female with headache, intermittent pulsatile tinnitus and visual disturbance CSF distension of optic nerve sheaths with posterior scleral indentation on axial T2. Marked concavity to the superior surface of the pituitary on coronal T2 and sagittal T1. Fluid distension of the oculomotor cisterns has also been suggested as a sign of IIH (red arrows).

12. Venous Stenoses 37 year old male with IIH and typical distal transverse sinus stenoses on contrast MRV 18 year old female with IIH and in addition to typical distal transverse sinus stenoses has a stenosis of the distal superior sagittal sinus which is a less common but recognised site of stenosis in this condition

13. Other Presentations 1,4 Pulsatile tinnitis Unilateral “whooshing sound” Exacerbated by positional change Relieved by jugular compression Diplopia due to cranial nerve VI palsy Skull base CSF leaks – sphenoid via lateral sphenoid cephalocele or mastoid via tegmun typani erosion

14. Lateral sphenoid cephalocele and Spontaneous Skull Base CSF leaks Lateral sphenoid cephaloceles and other skull base CSF leaks have clinical manifestations and similar imaging findings to IIH 9,10,11 Retrospective review 11 shows high recurrence rate of leak post surgical repair in “spontaneous” cephaloceles and leaks, this is improved if the IIH is also managed Arachnoid pits (arachnoid granulations outside the dural venous sinuses) are commonly seen in these cases

15. Lateral sphenoid cephalocele Multiple arachnoid pits within the middle cranial fossae (yellow arrows), small surgically proven cephalocele into lateral recess of sphenoid sinus (red arrow) with mild edema or gliosis in the adjacent temporal lobe (green arrow) Distal transverse sinus stenoses and empty sella appearance suggest background IIH 61 year old female presents with recurrent bacterial meningitis and left nasal CSF leak

16. Other Skull Base Leaks and Meningoceles 58 year old male with longstanding headaches & bilateral mastoid CSF leaks. Surgically repaired with subsequent diagnosis of IIH requiring ventricular shunt T2 coronalBilateral tegmen dehiscence, mastoid effusions and adjacent left temporal lobe edema 63 year old female with headaches. Other sequences showed empty sella and bilateral transverse sinuse stenoses. Bilateral CSF enlargement of Meckel’s cave particularly on the left

17. Natural history Historically thought of as a “benign” condition hence previous name “Benign intracranial hypertension” 1 Severe visual deficits can occur in 25% without treatment 7 Lower quality of life scores, greater incidence of depression and anxiety 8

18. Goals of management Cessation of symptoms, in particular restoration of visual acuity and resolution of papilledema

19. Treatment (1,3,4) : conservative Weight loss Carbonic anhydrase inhibitors  decrease the rate of CSF production Acetozolamide Topiromate (partial antagonist) Simple analgesics to relieve headache symptoms Therapeutic lumbar puncture: effects often short lived

20. Treatment: surgical/endovascular Reserved for patients with ongoing visual loss despite conservative management OR those with rapid symptom onset 3 Options: CSF shunting – ventriculoperitoneal or lumboperitoneal Optic nerve sheath fenestration (ONSF) Venous sinus stenting

21. Dural venous sinus stenting 3,4 Retrograde transvenous manometry is performed with patient awake as general anaesthesia can give false negative results threshold for treatment if a gradient >8mm-10mmHg Only one side needs stenting – usually dominant side Premedication with dual antiplatelet medication required. The authors continue this for 3 months following stenting then switch to aspirin alone.

22. Stenting - Technical Issues Stent trackability – carotid stents are typically used and navigation around the distal sigmoid and jugular bulb is often challenging. A long sheath is essential may need to be tracked intracranially to get stent into position Post stenting manometry may show transference of stenosis to another site Trigeminal nerve periorbital referred pain post-stenting is common and may last 2-3 days

23. Stent During Deployment Sheath has been advanced to distal sigmoid sinus to enable the stent to track into position Guidewire tip is in distal superior sagittal sinus with “J” tip to prevent engagement of cortical veins

24. Stenting Efficacy and Outcome No prospective or randomized controlled trials Retrospective cases series (largest 52 patients) suggest stenting is effective in improving symptoms and preserving vision 3,4 Serious complications are uncommon but include intracranial (usually subdural) hemorrhage Re-stenosis adjacent to the stent requiring further stenting occurs in approximately 10% 3 Concerns exist about longterm stent patency although delayed in-stent stenosis has not been described.

25. Case: Adjacent Sinus Stenosis 57 year old male with severe IIH presenting as headache and diplopia due to bilateral VI nerve palsies Cerebral angiogram shows severe stenosis of the distal superior sagittal sinus and dominant distal right transverse sinus. Right image shows tip and 3cm marker of microcatheter used to perform manometry (red arrows)

26. Case: Adjacent sinus stenosis Initial pressure gradient was across the transverse sinus stenosis but after 1 st stent was deployed (red arrows) repeat manometry showed transference of pressure gradient to the superior sagittal sinus stenosis and a 2 nd stent was deployed (green arrows) with restoration of normal calibre at both sites 57 year old male with severe IIH presenting as headache and diplopia due to bilateral VI nerve palsies

27. Case: Adjacent sinus stenosis 57 year old male with severe IIH presenting as headache and diplopia due to bilateral VI nerve palsies Represents 6 months later with recurrence of symptoms and papilloedema. Manometry showed new severe stenosis of mid superior sagittal sinus which was then stented. At 2 years of follow up he remains symptom free with normal vision and no papilloedema

28. Optic Coherence Tomography (OCT) 14,15 Can be used as an objective assessment of retinal thickness and papilledema to assess response to treatment Analogous to ultrasound but uses light instead of sound to yield cross sectional images Provides images on the micron scale Can image the retinal nerve fiber layer (RNFL) Measure swelling at the optic Functions as a type of “optic biopsy”

29. OCT Pre and Post Stenting Pre-stentingPost-stenting Retinal fibre layer thickness (solid line = right eye, dotted line = left eye) is well above the normal range prior to stenting. Near normalization is seen following stenting (right image – small part of left eye is above normal range)

30. Summary Posterior scleral indentation, empty sella and distal transverse venous sinus stenoses are typical imaging features of IIH IIH patients can also present with skull base CSF leaks Venous stenoses can also occur in the distal superior sagittal sinus Stenting of the dural venous sinuses is an alternative to shunting for those patients that fail medical treatment Recurrent stenosis adjacent to stented segments may occur requiring additional stent deployment.

31. References 1.Degnan AJ, Levy LM. Pseudotumour cerebri: Brief Review of Clinical Syndrome and imaging findings. AJNR Am J Neuroradiol 2011;32 :1986-1993 2.Walker RW. Idiopathic intracranial hypertension: any light on the mechanism of the pressure? J Neurol Neurosurg Psychiatry 2001;71:1–7 3.Ahmed RM, Wilkinson M, Parker GD, et al. Transverse sinus stenting for idiopathic intracranial hypertension: a review of 52 patients and of model predictions. AJNR Am J Neuroradiol 2011;32:1408e14 4.Fields JD et al. Dural venous sinus angioplasty and stenging for the treatment of Idiopathic Intracranial hypertension. J NeuroIntervent Surg 2013;5:62-68 5.Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol 1988;45:875e7. 6.Bruce BB, Kedar S et al. Idiopathic intracranial hypertension in Men. Neurology 2009; 72(4):304-9 7.Radhakrishnan K, Ahlskog JE, Cross SA, et al. Idiopathic intracranial hypertension (pseudotumor cerebri): descriptive epidemiology in Rochester, Minn, 1976 to 1990. Arch Neurol 1993;50:78–80 8.Daniels AB, Liu GT, Volpe NJ, et al. Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol 2007;143:635–41

32. References 9.F. Settecase, H.R. Harnsberger, M.A. Michel, P. Chapman, and C.M. Glastonbury. Spontaneous Lateral Sphenoid Cephaloceles: Anatomic Factors Contributing to Pathogenesis and Proposed Classification. AJNR Am J Neuroradiol 2014;35(4):784-89 10.Silver RI, Moonis G. Radiographic signs of elevated intracranial pressure in idiopathic cerebrospinal fluid leaks: a possible presentation of idiopathic intracranial hypertension. Am J Rhinol 2007;21(3):257-61 11.Woodworth BA, Prince A. Spontaneous CSF leaks: a paradigm for definitive repair and management of intracranial hypertension. Otolaryngol Head Neck Surg. 2008 Jun;138(6):715-20. 12.Farb RI, Vanek I, Scott JN, et al. Idiopathic intracranial hypertension: theprevalence and morphology of sinovenous stenosis. Neurology 2003;60:1418–24 13.Fujimoto JG, Pitris C et al. Optical Coherence Tomography: An Emerging Technology for Biomedical Imaging and Optical Biopsy. Neoplasia. 2000 Jan; 2(1-2): 9–25. 14.Mollan SP, Markey KA. A practical approach to, diagnosis, assessment and management of idiopathic intracranial hypertension. Pract Neurol 2014;0:1 – 11