Operative Procedures vs. Endovascular Neurosurgery for Untreated Pseudotumor Trial

Screening evaluation: Screening will include standard-of-care IIH evaluation including
general medical and neurological examinations, blood chemistries, complete blood count,
prothrombin time (PT),partial thromboplastin time (PTT), and pregnancy test.
Ophthalmological evaluation will include visual acuity, pellucid marginal degeneration
(PMD), and optical coherence tomography (OCT). Quality of life assessments are Headache
Impact Test-6, Short Form Health Survey-36 and Visual Function Questionnaire-25 +
Neuro-Ophthalmology supplement tests. Participants must have had a recent (within 6 months
of enrollment) magnetic resonance imaging (MRI) of the brain as well as a diagnostic lumbar
puncture (including opening pressure, cerebrospinal fluid (CSF) cell count, CSF glucose and
CSF protein), both of which are also part of the standard of care for diagnosis of IIH.

Eligible patients will undergo outpatient diagnostic venography within one month of initial
IIH evaluation. Under local anesthesia, transfemoral venous access will be obtained and a
guide catheter will be placed in the right jugular bulb. A microcatheter (Excelsior SL-10,
Stryker Neurovascular) will then be advanced into the dural venous sinuses, and venography
will be performed to determine the presence of any dural venous sinus stenosis. Then, blood
pressure will be transduced through the microcatheter at the following anatomic locations:
Anterior superior sagittal sinus, posterior superior sagittal sinus, bilateral transverse
sinuses, bilateral sigmoid sinuses and bilateral jugular bulbs. The venous pressure gradient
will be defined as the difference in pressure measurements between the anatomic locations
proximal and distal to any stenotic venous sinus segment, or between the transverse and
sigmoid sinuses. A pressure gradient of ≥ 8 mmHg is considered sufficient for subsequent
randomization. In patients in which pressure gradient is < 8 mmHg, the patient will not be
randomized.

Subsequent visits: Once a patient has met eligibility criteria and undergone randomization,
treatment will occur within two weeks of the Neuro-Ophthalmology evaluations and within one
month of diagnostic venography. Follow-up visits will occur at two weeks, six months and one
year after the index procedure.

At two-week follow-up (within one week on either side), patients will undergo neurological
and ophthalmological evaluations, OCT, perimetry, and visual acuity testing for safety.
While perimetry at this point will not be used for primary outcome analysis, substantial
worsening in any of the above measures despite treatment will prompt consideration for
treatment failure.

At six-month follow-up, subjects will undergo perimetry for primary outcome analysis,
outpatient diagnostic cerebral venography, and pressure measurements identical to that of
the screening evaluation (including pressure measurements at all predefined anatomical
locations) within four weeks on either side of the six-month target date. Patients will also
complete follow-up quality of life questionnaires (HIT-6, SF-36 and VFQ-25 +
Neuro-Ophthalmology supplement) The one-year follow-up will include queries regarding
interim medical history, headache status, medication usage (specifically details and dose of
those agents used to treat IIH or headache), and the number of IIH-related procedures each
subject has undergone since the index procedure. Follow-up will occur within four weeks on
either side of the one-year target date.

Inclusion Criteria:

- Age ≥ 18 years old.

- Diagnosis of Idiopathic Intracranial Hypertension according to the Modified Dandy
Criteria.

- Moderate to severe visual field loss defined by perimetric mean deviation of at least
-8 dB but better than -30 dB in the worst eye.

- Diagnostic cerebral venography demonstrating a pressure gradient of ≥ 8 mmHg across
at least one segment of the dural venous sinus as measured during transfemoral
cerebral venography

- Signed informed consent obtained from the patient.

Exclusion Criteria:

- CSF pressure <20 cm H2O on lumbar puncture.

- Abnormal CSF analysis such as elevated protein (>60 mg/dL), low glucose (<30 mg/dL),
elevated cell count >5 (unless traumatic lumbar puncture).

- Previous CSF shunt or diversion procedure of any kind, or previous optic nerve sheath
fenestration.

- Uncontrolled second primary headache disorder (e.g. chronic migraine, medication
overuse headache).

- Allergic reaction to radiological iodine contrast agent.

- Significant renal impairment (serum creatinine >1.5 mg/dL or creatinine clearance <60
mL/min).

- Contraindication to general anesthesia.

- Contraindication to aspirin, clopidogrel or other anticoagulants.

- Presence of a cranial vascular abnormality (arteriovenous malformation, dural
arteriovenous fistula, dural venous sinus thrombosis) or other intracranial mass.

- Presence of a hypercoagulable state such as Factor V Leiden, Protein C or S
deficiency or anti-cardiolipin syndrome.

- Inability to provide reliable and reproducible visual field examinations (>15% false-
positive errors and/or failure to maintain fixation for eye monitoring).

- Previous or ongoing eye disease such as glaucoma or retinopathy.

- Pre-existing corrected visual acuity worse than 20/200 in the study eye as measured
by early treatment diabetic retinopathy high-contrast study charts, without meeting
eligible ophthalmological criteria in the contralateral eye.

- Other pre-existing conditions accounting for optic atrophy that could produce
irreversible vision loss in the study eye without meeting eligible ophthalmological
criteria for IIH in the contralateral eye.

- Condition associated with high risk of retinopathy (e.g. type I diabetes).

- Previously (within the last 2 months) or currently exposed to a drug or substance
that may elevate intracranial pressure (e.g. lithium, high-dose vitamin A,
tetracyclines, anabolic steroids, chlordecone, amiodarone, diphenylhydantoin,
nalidixic acid).

- Pregnancy.

- Presence of a physical, mental or social condition that could prevent adequate
follow-up such as terminal illness, homelessness, lack of telephone, drug dependency
or anticipation of a significant move away from a study site within one year of
enrollment.