papilledema and intracranial hypertension–papilledema (disc edema from raised icp) • idiopathic...

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Papilledema and Intracranial Hypertension

John J. Chen, MD, PhDNeuro-Ophthalmology

Nebraska Academy of Eye Physicians and Surgeons Fall Scientific Meeting September 20, 2019

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DISCLOSUREJohn J. Chen, M.D., Ph.D.

Relevant Financial Relationship(s)

None

Off Label Usage

MR elastography

Presentation Learning Objectives

• Discuss the most common causes of papilledema and workup

Presentation Learning Objectives

• Describe the diagnosis and treatment of idiopathic intracranial hypertension

• Describe common mimickers of papilledema (pseudopapilledema)

• Discuss tools for detecting and following papilledema (including recent/future studies)

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Case #1: Classic case of idiopathic intracranial hypertension

• 23 yo female presented with headaches

– Also c/o hearing her heart beat in her ears (pulse

synchronous tinnitus)

– Also episodes of vision blacking out a couple of

seconds at a time (transient visual obscurations)

– Gained 30lb over the past 6 months, BMI 35

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20/20 OU

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Next step?

• Neuroimaging or LP first?

• What kind of imaging?

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Next step?

• Neuroimaging or LP first? Neuroimaging BEFORE LP

• What kind of imaging?

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Next step?

• Neuroimaging or LP first? Neuroimaging BEFORE LP

• What kind of imaging? MRI/MRV

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Sagittal T1 MRI MRV

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Case #1

• Lumbar puncture

– opening pressure of 390mm H20 (normal is <250)

– Normal CSF constituents

• Diagnosis:

– Idiopathic intracranial hypertension (IIH)

or pseudotumor cerebri

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Idiopathic intracranial hypertension (IIH)

• Signs and symptoms of increased intracranial

pressure

• No localizing neurologic findings (Cranial nerve

VI palsies are allowed)

• Normal neuroimaging (with the exception of

indirect signs of raised ICP)

• Opening pressure of lumbar puncture of

greater than 250 mm water, with normal CSF

• No other cause of increased intracranial

pressure present

• DIAGNOSIS OF EXCLUSION

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Symptoms

Pulse synchronous tinnitus

Transient visual obscurations

Headaches

Horizontal diplopia (6th nerve palsies)

Associated with:

Vitamin A toxicity, retinoic acid, ATRA, tetracyclines, lithium, withdrawal

from steroids, possibly sleep apnea

Obesity

>90% have BMI >30

>50% have BMI >40

Female sex

♀:♂ ≈ 10:1

Child-bearing age

• Incidence 3.3/100K in all women

• 6.8/100K in women 15-44 years old

• 22.0/100K in obese women 15-44 years old

Idiopathic intracranial hypertension (IIH)

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Incidence has more than

doubled over the past 20 yrs.

Now 2.4 per 100,000

22 per 100,000 in obese

young adult females

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Idiopathic intracranial hypertension (IIH)

• Neuroimaging needed to r/o tumor,

hydrocephalus, meningeal lesion, cerebral

venous sinus thrombosis

– Indirect signs of raised ICP

• Empty sella, flattened globe, enlarged optic nerve sheaths,

narrowing of the transverse sinus

• LP to rule out infectious, inflammatory, or

neoplastic process

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IIH treatment

• Permanent vision loss in up to 40% of patients

• Treatment

– Serial follow-up with visual fields is important

– Weight loss

– Acetazolamide or topiramate

– Optic nerve sheath fenestration or VP shunt for

vision threatening disease

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IIH treatment trial (IIHTT)

• VF mean deviation

-2 to -7 db

• Randomized to

acetazolamide or

placebo

– 500 mg bid titrated

to 4000 mg/day

– All pts diets

w/personal weight

coaches

IIHTT Conclusions

0 1 2 3 4 5 6

-2.0

-1.5

-1.0

-0.5

0.0

Month

M

ean

Cha

nge

in F

rise

n G

rade

(Wor

st E

ye)

0 1 2 3 4 5 6

-2.0

-1.5

-1.0

-0.5

0.0

Month

M

ean

Cha

nge

in F

rise

n G

rade

(Wor

st E

ye)

Acetazolamide + diet

Placebo + diet

Acetazolamide + diet

Placebo + diet

Change in Papilledema

Grade in Worse EyeJAMA. 2014;311(16):1641-1651

Change in PMD in Worse Eye

Acetazolamide improved

visual field function

Acetazolamide improved

papilledema grade

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• Acetazolamide well tolerated up to 4 grams/day (44% of patients)

• Side effects common: paresthesias, dysgeusia, vomiting/diarrhea, nausea, fatigue

• Serial lab monitoring, potassium supplementation not required

J. Neuro- Ophthalmology . 2016;36:13–19

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M Wall, et al. Neurology 2015;85:799–805

• 7 patients

• 6 in placebo arm

• Higher grade papilledema (grade 3-5)

• Decreased acuity

• Male gender

• >30 transient visual obscurations per month

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Headache. 2017;57(8):1303-10

https://www.nordicclinicaltrials.com/wicket/bookmarkable/org.slr.nordic.webapp.

cms.DisplayScheduledContent?id=12

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Already 24 articles and 4 editorials/letters from the IIHTT

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Surgery for IIH

• Surgery for IIH in 3 main scenarios:

– 1. Fulminant IIH with vision threatening disease

– 2. Extended period of max medical therapy and

weight loss with persistent disc edema

– 3. Significant papilledema with functional overlay

• Role of venous sinus stenting?

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Venous stenting for IIH

Preliminary data for venous sinus stenting is promising

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Terminology of disc edema

• Disc edema: disc swelling from any cause

– Includes papilledema, NAION, optic neuritis

• Papilledema: disc edema from raised

intracranial pressure

– Usually intact vision with full fields other than

enlarged blind spots

• Pseudopapilledema: anomalous nerves or

optic nerve drusen that mimic the appearance

of disc edema

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Case #2

• 44 yo female with headaches, pulse

synchronous tinnitus, and transient visual

obscurations

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20/20 OU

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Cerebral venous sinus thrombosis

• MRV or CTV is important in the setting of

papilledema to r/o venous sinus thrombosis

• Cerebral venous sinus thrombosis can cause

stroke

• Treatment with anticoagulation

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54yo female presents with bilateral papilledema and headaches

20/20 OU

MRI/MRV brain

are normal

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Lumbar puncture

• Opening pressure: 320 mm H2O

• 12 white cells (32% neutrophils, 66%

lymphocytes)

• Glucose 104mg/dl

• Protein >300mg/dl (nl <35)

• Cytology negative

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Imaging of the spinal cord

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Melanocytic

meningeal neoplasm

Imaging of the spinal cord

Dissemination of tumor cells

Elevated CSF protein and protein degradation products

=> CSF obstruction (decreased CSF absorption)

IIH is a diagnosis of exclusion that

requires MRI/MRV and lumbar puncture

Courtesy of

Valerie Biousse

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24yo female with headaches. 20/20 OU. Full fields

BP 220/120: Malignant hypertension

Must check blood pressure. IIH is a diagnosis of exclusion!

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Malignant hypertension

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• 8 year old girl referred for bilateral disc edema.

Optic disc drusen(pseudopapilledema)

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Example of prominent calcified drusen in an older patient

36 yo female referred

for disc edema

OCT shows a small disc area and normal/thin RNFL thickness: pseudopapilledema

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Differentiating pseudopapilledema from papilledema

True disc edema: Paton’s lines, choroidal folds, hyperemia, hemorrhages, loss of

spontaneous venous pulsations, obscuration of vessels, leakage on fluorescein

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18 yo female with headaches x 6 months, no other sx of raised ICP.

Ultrasound negative for drusen.

Imaging unremarkable, LP with an opening pressure of 22 cm H20

True disc edema or anomalous nerves?

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Mild IIH confirmed by improvement in the disc edema in response to acetazolamide

Treated with acetazolamide. 3 month f/u

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23 yo female c/o headaches. Denies changes in vision. 20/20 OU

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• MRI/MRV showed no abnormalities.

• LP showed an opening pressure of 320mmH20

– Confirms IIH

• Asymmetric papilledema in IIH

– 10% of IIH has asymmetric papilledema (interocular

difference of ≥2 grades)

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78 yo male referred for disc edema in the right eye

Vitreopapillary traction can cause pseudopapilledema

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51 yo male with diabetes, HTN, HLD, sleep apnea.

20/20 OU. MRI/MRV were normal.

Incipient NAION in the left eye

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4 months later. 20/20 OU

Incipient NAION in the right eye

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Incipient NAION vs. diabetic papillitis

• Likely the same disease process

• Disc edema with preserved vision

• Mild, reversible ischemia

• Can progress to ischemic optic neuropathy

with permanent vision loss in 25% of cases

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Swollen optic nerve with preserved vision

– Papilledema (disc edema from raised ICP)

• Idiopathic intracranial hypertension (need MRI/MRV and LP)

• Intracranial hypertension

– Tumor, meningitis, venous sinus thrombosis, obstructive

hydrocephalus, etc

– Malignant hypertension

– Incipient NAION or diabetic papillitis

– Optic perineuritis (ex. syphilis)

– Pseudopapilledema

• Optic disc drusen

• Small little red disc or anomalous optic nerve

• Myelinated nerve fiber

• Vitreopapillary traction

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Idiopathic intracranial hypertension without papilledema?

If you can have unilateral papilledema, you can likely have IIH without papilledema

Unilateral papilledema from IIH

However, you cannot make a definite diagnosis of IIH without papilledema

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Idiopathic intracranial hypertension without papilledema?

Friedman, Liu, Digre 2013

Without papilledema or

6th nerve palsy, the

diagnosis can only be

suggested.

3 indirect signs of raised

ICP are required to make

that suggestion.

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Fisayo A, Bruce BB, Newman NJ, Biousse V. Neurology. 2015 Dec 30

39.5% referred for IIH did not have the diagnosis

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Current methods of measuring intracranial pressure

• Lumbar puncture

– Invasive and variable

– Valsalva can cause a 5 fold increase in opening

pressure

• Direct intracranial pressure monitoring

– Gold standard: intraventricular catheter

– Invasive and requires hospitalization

• Noninvasive ICP measurements

– MRI, ultrasound, OCT, tympanic membrane

displacement

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Pseudopapilledema Papilledema

Ultrasound

MRI optic

nerve sheath

MRI sella

Patterson et al.

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Selected Parameters Sensitivity Specificity

US ONSD 79.2 82.4

MRI ONSD 91.7 70.0

Pituitary/sella ratio 91.7 73.3

US ONSD & MRI pit/sella 70.8 100

MRI ONSD & MRI pit/sella 83.3 94.1

MRI ONSD or MRI pit/sella 100 64.7

US ONSD or MRI ONSD or MRI pit/sella 100 47.1

US ONSD & MRI ONSD & MRI pit/sella 66.7 100

(MRI ONSD or US ONSD) & MRI pit/sella 87.5 94.1

Sensitivity/Specificity Calculations

Ultrasound alone is fairly sensitive/specific

MRI alone has slightly better sensitivity/specificity

Combining ultrasound and MRI slightly increased sensitivity

Patterson et al.

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23 yo with bilateral grade IV papilledema

from idiopathic intracranial hypertension

Patient underwent LP

Bruch’s membrane returns

to a more neutral position

OCT shows an upturned

Bruch’s membrane

Position of Bruch’s membrane on OCT correlates with intracranial pressure

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The Rat Intraventricular Cannula model

ICP can be raised and lowered chronically. (model created by Dr. Fautch and Chowdhury)

Baseline OCT Increased ICP

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Brain MR elastography:

Measuring stiffness of the brain

Compact 3 Tesla MRI

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Inversion

0 40 80Shear Stiffness (kPa)

Elastogram

2.5cm

Driver

Conventional

MR Image

-10

Wave Images

MRE Acquisition

0 +10Displacement (mm)

Brain MR elastographyTechnique

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Anatomic Elastogram

8

0

Stiffn

ess (k

Pa)

Wave Image

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MR elastography to measure brain stiffness

Arvin Arania, Hoon-Ki Mina,b, Nikoo Fattahia, Nicholas M Wetjena, Joshua D Trzaskoa, Armando Manducac, Clifford

Jacka, Kendall H. Leeb, Richard L Ehmana, John Huston IIIa (manuscript submitted)

• Increasing ICP in a pig model resulted in stiffer brain

• We are currently enrolling patients in a clinical trial to evaluate

raised ICP using MR elastography with the compact 3 Tesla MRI

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The Final Frontier: Space Flight-associated Neuro-ocular Syndrome (SANS)

N o (C P G 0 ) Y e s (C P G 1 -4 )

G G

AA/AG

O p h th a lm ic Is s u e s

MT

RR

A6

6G

• Many astronauts with papilledema were found to have specific

polymorphisms

• We have a grant with NASA to evaluate patients with IIH and

polycystic ovarian syndrome for these mutations

MTRR polymorphism

Astronaut Papilledema and One Carbon Metabolism

The Final Frontier: Space Flight-associated Neuro-ocular Syndrome (SANS)

The Final Frontier: Space Flight-associated Neuro-ocular Syndrome (SANS)

Zwart et al., 2019

The Final Frontier: Space Flight-associated Neuro-ocular Syndrome (SANS)

Zwart et al., 2019

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Lower Body Negative Pressure Box

Potential treatment for space travel?

Non-metal version compatible with MRI

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Summary

• IIH is a disease that affects young adult females,

often triggered by weight gain

– Must rule out other causes of raised ICP with

MRI/MRV + LP

– The incidence is rising with the increase in obesity

• Papilledema = disc edema from raised ICP

– Ddx includes Pseudopapilledema, malignant

hypertension, and others

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Summary

• IIH is a disease that affects young adult females,

often triggered by weight gain

– Must rule out other causes of raised ICP with

MRI/MRV + LP

– The incidence is rising with the increase in obesity

• Papilledema = disc edema from raised ICP

– Ddx includes Pseudopapilledema, malignant

hypertension, and others: including Astronauts!

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Questions & Discussion