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


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)


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


20/20 OU


Next step?

• Neuroimaging or LP first?

• What kind of imaging?


Next step?

• Neuroimaging or LP first? Neuroimaging BEFORE LP

• What kind of imaging?


Next step?

• Neuroimaging or LP first? Neuroimaging BEFORE LP

• What kind of imaging? MRI/MRV


Sagittal T1 MRI MRV


Case #1

• Lumbar puncture

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

– Normal CSF constituents

• Diagnosis:

– Idiopathic intracranial hypertension (IIH)

or pseudotumor cerebri


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


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



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



• 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


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


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


• 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


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


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

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

cms.DisplayScheduledContent?id=12


Already 24 articles and 4 editorials/letters from the IIHTT


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?


Venous stenting for IIH

Preliminary data for venous sinus stenting is promising


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


Case #2

• 44 yo female with headaches, pulse

synchronous tinnitus, and transient visual

obscurations


20/20 OU


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


54yo female presents with bilateral papilledema and headaches

20/20 OU

MRI/MRV brain

are normal


Lumbar puncture

• Opening pressure: 320 mm H2O

• 12 white cells (32% neutrophils, 66%

lymphocytes)

• Glucose 104mg/dl

• Protein >300mg/dl (nl <35)

• Cytology negative


Imaging of the spinal cord


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


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

BP 220/120: Malignant hypertension

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


Malignant hypertension


• 8 year old girl referred for bilateral disc edema.

Optic disc drusen(pseudopapilledema)


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


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


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?


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

Treated with acetazolamide. 3 month f/u


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


• 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)


78 yo male referred for disc edema in the right eye

Vitreopapillary traction can cause pseudopapilledema


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

20/20 OU. MRI/MRV were normal.

Incipient NAION in the left eye


4 months later. 20/20 OU

Incipient NAION in the right eye


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


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


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


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.


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

39.5% referred for IIH did not have the diagnosis


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


Pseudopapilledema Papilledema

Ultrasound

MRI optic

nerve sheath

MRI sella

Patterson et al.


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.


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


The Rat Intraventricular Cannula model

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

Baseline OCT Increased ICP


Brain MR elastography:

Measuring stiffness of the brain

Compact 3 Tesla MRI


Inversion

0 40 80Shear Stiffness (kPa)

Elastogram

2.5cm

Driver

Conventional

MR Image

-10

Wave Images

MRE Acquisition

0 +10Displacement (mm)

Brain MR elastographyTechnique


Anatomic Elastogram

8

0

Stiffn

ess (k

Pa)

Wave Image


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


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



Zwart et al., 2019


Lower Body Negative Pressure Box

Potential treatment for space travel?

Non-metal version compatible with MRI


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


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!


Questions & Discussion

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

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