confessions of a pseudotumor...

CONFESSIONS OF A PSEUDOTUMOR CEREBRIST

Jean B Kassem, M.D.Neuro-Ophthalmology, Orbital Surgery, Oculoplastics

Bellingham Eye PhysiciansBellingham, WA

Goals✦ Understand Intracranial Hypertension and its

Effects on Vision✦ History Taking✦ Role of Office Procedures✦ Role of Imaging✦ Treatment

Overview✦ Terminology✦ Differential for Optic Disc Edema/Elevated Intracanial

Pressure✦ Diagnostic Criteria for Idiopathic Intracranial Hypertension

✦ Office Procedures✦ Imaging✦ Lumbar Puncture

✦ Treatment - IIH✦ Medical✦ Surgical

TERMINOLOGY

• Papilledema• Optic disc edema• Papillitis• Pseudopapilledema• Optic neuropathy

TERMINOLOGY• Papilledema

• Due to elevated cerebrospinal fluid (CSF) pressure• Optic disc edema

• Generic term for optic disc swelling• Papillitis

• Inflammation of optic disc• Pseudopapilledema

• Drusen• Optic neuropathy

• Generic term for optic nerve damage

TERMINOLOGY• Papilledema

• Due to elevated cerebrospinal fluid (CSF) pressure• Optic disc edema

• Generic term for optic disc swelling• Papillitis

• Inflammation of optic disc• Pseudopapilledema

• Drusen• Optic neuropathy

• Generic term for optic nerve damage

TERMINOLOGY

• Pseudotumor Cerebri• Idiopathic Intracranial Hypertension• Hydrocephalus

TERMINOLOGY

• Idiopathic Intracranial Hypertension• primary intracranial hypertension with no cause found• (Modified Dandy Criteria)

• Pseudotumor Cerebri• older, now generic term for intracranial hypertension• I use this for the secondary forms

• Hydrocephalus• infantile form, geriatric form (normotensive), obstructive

form

CSF HOMEOSTASIS

CSF HOMEOSTASIS

CSF HOMEOSTASIS

OPTIC DISC EDEMA

• WHAT NOW?

OFFICE TESTING

• Is it edema?• Is there vision loss (optic neuropathy)?

OUTSIDE TESTING

• What is the cause of the elevated intracranial pressure?

• How high is the opening pressure?

OFFICE

Is it edema?• History• Sensorimotor Exam• Funduscopy• IVFA/Autofluorescence• OCT

OFFICE

Is it edema?• History

• signs and symptoms of elevated intracranial pressure• Sensorimotor Exam• Funduscopy• IVFA/Autofluorescence• OCT

HEADACHE

• most frequent symptom• generally holocranial or retrobulbar• relatively constant “aching’ or “throbbing”• variable intensity, often worse supine• may be associated with nausea or lightheadedness

TRANSIENT VISUAL OBSCURATIONS

• unilateral or bilateral blurring, dimming or loss of vision

• lasting 2 or 3 seconds• secondary to optic disc swelling• often with positional changes, head turn or eye

movements

DIPLOPIA

• Horizontal, Binocular• 6th Nerve Palsy

OFFICE

Is it edema?• History• Sensorimotor Exam• Funduscopy• IVFA/Autofluorescence• OCT

OFFICE

Is it edema?• History• Sensorimotor Exam• Funduscopy• IVFA/Autofluorescence• OCT

Copyright © 2012 American Medical Association. All rights reserved.

Diagnosis and Grading of Papilledema in Patients With Raised Intracranial Pressure Using Optical Coherence Tomography vs Clinical Expert Assessment Using a Clinical Staging ScaleArch Ophthalmol. 2010;128(6):705-711. doi:10.1001/archophthalmol.2010.94

OFFICE

Is it edema?• History• Sensorimotor Exam• Funduscopy• IVFA/Autofluorescence• OCT

OFFICE

Is it edema?• History• Sensorimotor Exam• Funduscopy• IVFA/Autofluorescence• OCT

CZMI

OSODHigh Definition Images: HD 5 Line RasterSignal Strength:

Exam Time:Exam Date:

Technician:Gender:DOB:ID:

Name:

10/10

7:58 AM11/23/2015

Operator, CirrusFemale11/30/1982CZMI1355173933

Denton, Loralei

Serial Number: 5000-2742

Length:Spacing:Scan Angle: 6 mm0.25 mm0°

Doctor's SignatureSW Ver: 7.6.0.118Copyright 2015Carl Zeiss Meditec, IncAll Rights Reserved

Page 1 of 1

Comments

CZMI

OSODHigh Definition Images: HD 5 Line RasterSignal Strength:

Exam Time:Exam Date:

Technician:Gender:DOB:ID:

Name:

8/10

3:42 PM3/11/2016

Operator, CirrusMale2/8/1976CZMI1629835404

Kassem, Jean

Serial Number: 5000-2742

Length:Spacing:Scan Angle: 6 mm0.25 mm0°

Doctor's SignatureSW Ver: 7.6.0.118Copyright 2015Carl Zeiss Meditec, IncAll Rights Reserved

Page 1 of 1

Comments

OPTIC DISC DRUSEN(PSEUDOPAPILLEDEMA)

• 1% of the population• More frequent in caucasians• Bilateral in 75%• May be inherited as an AD trait with incomplete penetrance or

may be spontaneous• Usually not visible at birth• Rarely visible < age 10

• “buried”

OPTIC DISC DRUSEN

• Calcify with age, become more prominent• Often asymptomatic, found incidentally• Often mistaken for papilledema• Optic discs often congenitally anomalous

• Crowded• Loss of physiologic cup• Tri-branching vessels• Situs inversus

VISUAL FIELD LOSS

• Internal compressive optic neuropathy• 70% develop some visual field loss• Gamut of visual field deficits, mimics

glaucoma• Increased risk NA-ION, BRVO, CRVO

OPTIC DISC DRUSEN: TREATMENT

• No proven treatment• Monitor for choroidal neovascularization• Monitor HVF• Consider topical therapy to lower IOP

• Neuroprotective agent-> Brimonidine• Radial optic neurotomy

• Manual removal of drusen with vitrectomy

FLUORESCEIN ANGIOGRAM

• differentiate optic disc drusen from true papilledema

• autofluorescence of disc drusen on initial red-free photographs

• may show late staining with optic disc drusen• true leakage in papilledema

B SCAN ULTRASOUND

PSEUDOPAPILLEDEMA

OFFICE

Is There Vision Loss?

• HVF• Vision• Pupils

OFFICEHVF 30-2 Enlarged BS

OFFICEVisual Field in Papilledema

• Enlarged blind spot and generalized constriction are most common

• nasal step and arcuate scotomas possible• cecocentral scotoma less likely

OFFICE

Is There Vision Loss?

• HVF• Vision• Pupils - ALWAYS CHECK FOR APD

OPTIC DISC EDEMA

• WHAT NOW?————> Diagnostics• Imaging• Intracranial Pressure

DIFFERENTIAL DIAGNOSIS• Intracranial mass lesion with obstructive hydrocephalus• Ischemic (AION)• Hypertensive Urgency• Papillitis (infection, inflammation)

• atypical optic neuritis• meningitis• neuroretinitis

• Infiltrative (leukemia, sarcoid)• Pseudopapilledema• IIH or Secondary Pseudotumor

SECONDARY PSEUDOTUMOR CEREBRI

• venous occlusive disease•dural sinus thrombosis

• infiltrative disease•meningeal carcinomatosis•sarcoidosis

• systemic disease•Systemic lupus erythematosis•Behcet’s disease•Acromegaly

• infectious disease• post streptococcal• post viral

• medications• nalidixic acid• fluoroquinolones• tetracycline• doxycycline• minocycline• Acutane• growth hormone• hypervitaminosis A• lithium carbonate• prolonged steroid use

MODIFIED DANDY CRITERIAIIH

• SIGNS AND SYMPTOMS OF ELEVATED INTRACRANIAL PRESSURE

• ABSENCE OF LOCALIZING FINDINGS ON NEUROLOGIC EXAM• NORMAL NEURO IMAGING, EXCEPT EMPTY SELLA AND CSF

SPACE AROUND NERVES (MRI AND MRV)• NORMAL CSF COMPOSITION• AWAKE AND ALERT WITH NO OTHE RCAUSE FOR ELEV CSF• CSF PRESSURE >25CM H20 OR >20 IF:

• PULSATILE TINNITUS• FRISEN GRADE 2 PAPILLEDEMA• B SCAN NEGATIVE FOR DRUSEN• PARTIALLY EMPTY SELLA WITH CSF SPACE NEXT TO

GLOBE ON MRI

IMAGING• MRI Brain• MRV Brain - Dural Sinus Thrombosis

RADIOLOGIC IMAGING STUDIES

• normal to small sized ventricles• no evidence of a mass lesion• empty sella in up to 70%• clear differentiation between the optic

nerve and sheath• enlarged, elongated subarachnoid space• flattening of posterior aspect of the globe• MRI better to rule out infiltrative dz, VST

•opening pressure >20 cm H2O•falsely high reading: position, valsalva•falsely low reading: multiple puncture•R/O infection, inflammation•radiologic guidance if poor landmarks

LUMPAR PUNCTURE• BLIND (BEDSIDE)• FLUOROSCOPIC GUIDED (X Ray)• CT GUIDED

Methods

10 IIH patients underwent 11 ultrasound guided lumbar punctures with a low frequency curvilinear probe (Model M-Turbo, Manufactured by SonoSite, Bothell, WA) between July and October 2013.

SonoSite Model M-Turbo

LUMPAR PUNCTURE

Methods

• 4" 24 gauge Pencan pencil-point needle or a 4.75”

• 6", 24 or 22 gauge Sprotte pencil-point needle

L4L5 S1

ResultsLeft Parasagittal Ultrasound View, Lumbar Region

Results

• In 10/11 procedures, only one attempt at puncture• OP was obtained, as was sufficient CSF for multiple studies• No subject had a post-puncture headache• 2 post-procedure complications

• serous drainage at puncture site (1) - resolved spont.• paresthesia (1) - resolved after a dose of dexamethasone

• They loved it

EPIDEMIOLOGY: IIH

• F:M ratio of 8:1 in the adult population• peak incidence 3rd decade (infancy to old age)• incidence in general population 1:100,000• women 20-44, >10% over IBW 13:100,000• women 20-44, >20% over IBW 19.3:100,000• men 20-44, >20% over IBW 1.5:100,000

IIH in Men

Bruce et al. J Neuro Sci 290;2010, 86–89

• Men with IIH have more symptoms associated with • testosterone deficiency • OSA

• OSA -- cause vs. chance association

PERMANENT VISUAL LOSS

• compressive optic nerve damage• optic disc infarction• choroidal folds• subretinal hemorrhage

VISUAL FIELD LOSS

• Enlarged blind spot and generalized constriction are most common

• nasal step and arcuate scotomas possible• cecocentral scotoma less likely

OBSERVED SIGNS

• papilledema• may be unilateral• sine papilledema

• relative afferent pupillary defect• cranial nerve VI palsy

MANAGEMENT

• suspect exogenous agents should be discontinued

• LP done initially for dx may be therapeutic• weight loss is the most effective treatment

• may get off Rx and avoid surgery• consider dietician

CARBONIC ANHYDRASE INHIBITORS

• Neptazane 50 mg bid to qid• Diamox 250 mg bid to 500 mg qid• common adverse effects

• tingling and numbness in fingers/toes• metallic taste• K+ wasting

• relative contraindication 1st 4 months pregnancy

• sulfa based - can be used if allergy is abs• aplastic anemia is a rare idiosyncratic rxn

ALTERNATIVE DRUGS• Lasix 20 mg qd to 40 mg qid• corticosteroids generally not indicated

• may be useful if inflammatory mechanism (I.e., SLE)• further weight gain and fluid retention• rebound on withdrawal• iv solumedrol may be useful acutely

• Octreotide• Topamax• Beta blockers ?

SURGICAL MEASURES - CSF SHUNTSVentriculoperitoneal Lumboperitoneal

LUMBOPERITONEAL SHUNT

• more likely to reduce ICP, relieve H/A than ONSF

• Contraindicated (relative) in Chiari Malformation

• average replacement every 2-3 shunt years• migration, closure, infection• over or under-filtration

VENTRICULOPERITONEAL SHUNT

• more likely to reduce ICP, relieve H/A• average replacement every 4 shunt years• migration, closure, infection• over or under-filtration

NEUROSURGEON DECIDES WHICH TYPE TO USE

OPTIC NERVE SHEATH FENESTRATION

• window or multiple longitudinal slits made in the anterior dural covering of the optic nerve

• immediate decompression of optic nerve tip• less likely to maintain lower ICP, relieve H/A• neuroprotective

OPTIC NERVE SHEATH FENESTRATION: MEDIAL APPROACH

OPTIC NERVE SHEATH FENESTRATION: MEDIAL APPROACH

Visual Outcomes following Optic Nerve Sheath Fenestration via the Medial Transconjunctival Approach

Steven E Katz, MD1 et al

• 207 eyes of 104 patients from 2005 - 2014• Outcomes: MD on HVF and Papilledema Grade• Followed for 6 months• Edema resolved completely in 76% in 1 week, 71% at 6 months• MD +1.59 at 1 week, +1.30 at 6 months

Conclusion: Safe and effective treatment for disc edema

CASE PRESENTATION• 22 y.o. obese wf presents with severe

holocranial progressive H/A and loss of peripheral vision over 6 months

• hx IIH s/p R ONSF 18 months prior• left relative afferent pupillary defect• generalized visual field constriction L>R• on diamox 500 mg sequels p.o. qid• LP with opening pressure 32 cm H2O

PRESENTING VISUAL FIELDS

1 WEEK AFTER LEFT ONSF

1WEEK AFTER RIGHT ONSF

PATIENT MONITORING• papilledema

• may not resolve completely with tx• may not recur with ICP• optic nerve appearance alone is not adequate to assess

for recurrent elevation of ICP!• subjective symptoms and visual field progression may

be more reliable

• visual fields• patient education and participation are

essential

IIH ACCORDING TO JEAN

• Initial OP < 35 cm H2O• Initial OP 36-45 cm H2O• Initial OP > 46 cm H2O• Low threshold for ONSF• Profound papilledema and ONSF

IDIOPATHIC INTRACRANIAL HYPERTENSION TREATMENT TRIAL (IIHTT)

IIHTT

The IIHTT is a prospective clinical treatment trial on idiopathic intracranial hypertension that includes a genetic association study in search of single polymorphisms (SNPs) to identify metabolic and hormonal factors that differentiate between obese women who have IIH and obese women who do not - the first NORDIC multicenter study.

IIHTT: SPECIFIC AIM ONE

IIH patients with Mild Visual Loss (-2 to -5 dB baseline PMD) will be recrutied to participate in this randomized, double-masked, placebo-controlled trial to determine the additional benefit of acetazolamide (up to 4 gm a day) added to a low sodium, weight reduction diet. Hypothesis: Acetazolamide + diet is superior to diet alone in restoring vision or preventing visual loss in IIH patients with mild visual loss.

IIHTT: SPECIFIC AIM TWO (a) To identify proteomic and genetic risk factors for IIH by screening a large cohort of IIH patients and controls, (b) To determine the serum and CSF levels of potential mediators of IIH suggested by the genetic analysis, and (c) To conduct an association study in search of single nucleotide polymorphisms (SNPs) that confer risk for developing IIH. A cohort of 154 IIH patients and 154 controls matched on body-mass index, ethnicity and gender will be genotyped at SNPs contained within genes encoding molecules likely to be involved in the etiology of IIH using the SNPlex genotyping system. Specifically, genes associated with obesity will be profiled. (d) To test the hypotheses IIH is associated with abnormal metabolism of leptin or vitamin A or both, leptin levels, vitamin A and related factors will be measured at baseline and six months.

IIHTT: RESULTS

IIHTT: RESULTS

IIH: TAKE HOME POINTS

• History - Signs of Elevated ICP• Check for APD!• HVF 30-2• OCT 5 line raster may be helpful• If scheduling LP - OPENING PRESSURE• Vision loss is preventable/treatable

IT’S NOT ALWAYS PSEUDOTUMOR….

MANY OTHER CAUSES FOR BILATERAL DISC EDEMA

PSEUDO PSEUDOTUMOR (TUMOR)

HYPERTENSIVE CRISIS

• Hypertensive crisis• Generally bilateral• Blurred vision• Headache• Dizziness• encephalopathy

IINFECTION

• Meningitis• Stiff neck• Headache• Fever• Skin rash• Obtundation

• Considerations HIV+• Cryptococcus• Tertiary syphylis

• May be associated with raised ICP

INFECTION/INFLAMMATION• Neuroretinitis• Infectious/immune-mediated• Ddx

• Cat scratch disease• Post-viral: HSV, hepatitis B, mumps• Spirochetes: syphylis, Lyme, leptospirosis• Possible: toxoplasmosis, toxocariasis, histoplasmosis• Tuberculosis• Leber’s idiopathic stellate neuroretinitis

• Treatment• Antibiotics: doxycycline, erythromycin, azithromycin, ciprofloxacin,

rifampin• Corticosteroids

INFILTRATIVE: SARCOID• Uveitis• Papillitis• Infiltrative, compressive optic neuropathy• Systemic manifestations: lungs, skin• 5/100,000 caucasians• 40/100,000 African Americans• ACE, lysozyme serum• CSF ACE• MRI brain with gad• Tissue diagnosis

INFILTRATIVE: LEUKEMIA

• Papillitis• Uveitis• Hyphema

INFILTRATIVE: LARGE CELL LYMPHOMA

• Refractory uveitis• Papillitis• Choroidal infiltrates• Usually known CNS involvement• Vitrectomy with cell cytology can be

diagnostic

THANK YOU!

jeankassem@gmail.com