Atypical Optic Neuritis -Red Flags

Red Flags in Optic Red Flags in Optic Neuritis Neuritis

Raed Bbehbehani , MD, ABORaed Bbehbehani , MD, ABO

PearlsPearls

• History : Pain ( 92 % mild) and vision loss.History : Pain ( 92 % mild) and vision loss.

• Diagnosis : Pupil + Color vision.Diagnosis : Pupil + Color vision.

• MS PrognosisMS Prognosis

• Neuro-imaging : MRI brain/orbit ( T1 fat Neuro-imaging : MRI brain/orbit ( T1 fat suppressed views of the orbit with Gad).suppressed views of the orbit with Gad).

Optic neuritisOptic neuritis

• Young, femaleYoung, female

• Pain ( dull-aching , periocular headache , Pain ( dull-aching , periocular headache , worse with EOM)worse with EOM)

• Visual acuity can be normal.Visual acuity can be normal.

• RAPD RAPD

• Visual field defectVisual field defect

RAPD

• In the absence of contralateral optic nerve damage.

• Swinging Flash Test.

• Neural Density Filter (0.3-1.2 log)

Signs

•Dyschromatopsia• Hardy Rand Ritter

• Ishihara pseudo=isochomatic plates

• Fans-worth Munsell 100-hue Test

Signs

• Utohff’s phenomenon : visual blurring with heat or exhaustions .

• Vision comes back with cool down (5 min - 24 hours)

• Also seen in Compressive , Toxic , LHON , Inflammatory optic neuritis.

Signs

• Contrast Sensiitivty

• Pelli Robson

• Sloan Low Contrast acuity

Visual Field Defact

• In ONTT : Central field > peripheral

• Focal defect (42%) : Arcuate , Altitudinal , Nasal

OCT in ON

Acute RNFL thickeningLate RNFL loss

Disc Appearance

•Normal – ⅔•Oedematous - ½ •Temporal pallor – 10% , suggestive of preceding attack•Disc Oedema is without Hemorrages / lipids/ cotton wool

MRI in MS

•Brain lesions : > 3mm, oval, in peri-ventricular white matter, radially oriented towards the ventricular spaces on a unenhanced MRI• In Optic neuritis always get – •Optic nerve – STIR signals (fat suppression)•Gadolinium enhancements•Single white matter lesion in AMON – high risk for M.S (ONTT study)

MRI in optic neuritisMRI in optic neuritis

MRI brainMRI brain

The predictive value of MRI to The predictive value of MRI to develop MS (10 year ONTT develop MS (10 year ONTT

Data)Data)

• 22% if normal initial MRI.22% if normal initial MRI.

• 56% if >= 1 baseline lesion (3mm diameter).56% if >= 1 baseline lesion (3mm diameter).

• Risk does not increase appreciably with Risk does not increase appreciably with increasing lesions.increasing lesions.

ONTT 15 years

Should I order Blood work Should I order Blood work up ? up ?

• Optic neuritis treatment trial (ONTT).Optic neuritis treatment trial (ONTT).

• ANA < 1:320 in 13% , >1:320 in 3 %.ANA < 1:320 in 13% , >1:320 in 3 %.

• Only 1 out of 457 was eventually diagnosed with Only 1 out of 457 was eventually diagnosed with collagen vascular disease !collagen vascular disease !

• FTA-ABS positive in 6 patients but none had FTA-ABS positive in 6 patients but none had syphilis.syphilis.

• CXR normal in all patients.CXR normal in all patients.

• No lab studies required for typical optic neuritis.No lab studies required for typical optic neuritis.

ONTT 10 year DataONTT 10 year Data• No cases of CDMS if normal MRI and any of :No cases of CDMS if normal MRI and any of :

1)1) Severe disc edema (n=22)Severe disc edema (n=22)

2)2) Painless (n=18)Painless (n=18)

3)3) Disc hemorrhages (n= 16)Disc hemorrhages (n= 16)

4)4) Retinal exudates (n=8)Retinal exudates (n=8)

5)5) NLP visual acuity (n=6)NLP visual acuity (n=6)

• Low risk for CDMS (5%) if :Low risk for CDMS (5%) if :

- Male- Male

- Disc edema- Disc edema

- normal MRI- normal MRI

Course of optic Course of optic neuritisneuritis

• Vision recovery starts within 2 weeks.Vision recovery starts within 2 weeks.

• ONTT : at 3 months, visual acuity was ONTT : at 3 months, visual acuity was >=20/40 in 93 %.>=20/40 in 93 %.

• 35 % recurrence in the affected or fellow eye 35 % recurrence in the affected or fellow eye ( 10 year ONTT)( 10 year ONTT)

• Recurrence twice more common in MS Recurrence twice more common in MS patients than non-MS patients.patients than non-MS patients.

Mimickers of Typical Optic Mimickers of Typical Optic NeuritisNeuritis

• Ischemic (AION, PION).Ischemic (AION, PION).

• Neuromyelitis Optica (NMO)Neuromyelitis Optica (NMO)

• Compressive.Compressive.

• Infectious/ para-infectious.Infectious/ para-infectious.

• Inflammatory and infiltrative.Inflammatory and infiltrative.

• Leber’s optic neuropathy.Leber’s optic neuropathy.

• Auto-immune.Auto-immune.

• Paraneoplastic.Paraneoplastic.

Atypical optic neuritisAtypical optic neuritis“Red Flags”“Red Flags”

• Age <12 years or >50 yearsAge <12 years or >50 years

• Severe loss of vision (NLP) , Bilateral onset in an adult, no Severe loss of vision (NLP) , Bilateral onset in an adult, no improvement after 6 weeks , progressive course.improvement after 6 weeks , progressive course.

• No pain.No pain.

• Ocular findings : severe disc edema , marked hemorrhages, Ocular findings : severe disc edema , marked hemorrhages, uveitis, exudate, retinitis, phelbitisuveitis, exudate, retinitis, phelbitis

• Recurrences within a short interval or during steroid taper.Recurrences within a short interval or during steroid taper.

• Pre-existing diagnosis of a systemic disease ( Cancer, CT Pre-existing diagnosis of a systemic disease ( Cancer, CT disease, Vasculitis, immunosuppression)disease, Vasculitis, immunosuppression)

• Systemic Symptoms : Arm or leg weakness, bowel or Systemic Symptoms : Arm or leg weakness, bowel or bladder Sx, Arththralgia ,skin rash, feverbladder Sx, Arththralgia ,skin rash, fever

Non-Arteritic Anterior Non-Arteritic Anterior Ischemic Optic Neuropathy Ischemic Optic Neuropathy

(NAION)(NAION)

Non-Arteritic Anterior Non-Arteritic Anterior Ischemic Optic Nuropathy Ischemic Optic Nuropathy

(NAION)(NAION)• Age> 40.Age> 40.

• Unilateral visual acuity/field loss.Unilateral visual acuity/field loss.

• Disc edema ( initially pallid ) , can be sectoral or Disc edema ( initially pallid ) , can be sectoral or diffuse.diffuse.

• Small cup/disc ratio (anamolous disc).Small cup/disc ratio (anamolous disc).

• Vascular risk factors (diabetes,hypertension, Vascular risk factors (diabetes,hypertension, smoking, hypercholesterolemia).smoking, hypercholesterolemia).

• Usually remains static but can improve in 42.7 % or Usually remains static but can improve in 42.7 % or progress over several weeks in 25 %.progress over several weeks in 25 %.

NAIONNAION

Hemorrhage

Anamolousdisc

NAIONNAION

Narrowed arterioles

Segmental pallor

Neuromyelitis Optica• Inflammatory optic neuritis

• Median age : 35-44 years ; children : 4.4 years

• Less common than demyelinating (Asia , African , West Indies 50% of demyelination)

• Diagnostic Criteria

• Optic neuritis

• Transverse Myelitis

• At least 2 of 3

• LETM ( 3 contiguous veterbal segments)

• NMO IgG (70% sensitive , 100% specific)

• Brain lesions not compatible with MS

NMO• NMO disease spectrum ( seropositive optic

neuritis without TM or vice versa)

• Optic neuritis tend to be more severe

• Less visual recovery

• More than 50% of NMO will develop ON in 5 years of Dx

• ON and TM can simultaneous or separated.

When to Suspect

• Severe vision loss

• poor visual recovery

• Severe RNFL loss by OCT

• MRI posterior ON , chiasmal or posterior visual pathway involvement

• CSF - pleocytosis (PMN + eosinophils)

Auto-immune Optic Auto-immune Optic NueropathyNueropathy

• ANA + , anticardiolipin antibody + (89 % IgM). ANA + , anticardiolipin antibody + (89 % IgM).

• Does not meet criteria of collagen vascular Does not meet criteria of collagen vascular disease.disease.

• Skin biopsy 92% abnormal ( 67% Skin biopsy 92% abnormal ( 67% immunofloresence)immunofloresence)

• Multiple recurrences.Multiple recurrences.

• Treatment : Corticosteroids +- Treatment : Corticosteroids +- immunosuppressants.immunosuppressants.

Neuro-retinitisNeuro-retinitis• Cat scratch (Bartonella henselae).Cat scratch (Bartonella henselae).

• TBTB

• SyphilisSyphilis

• SarcoidosisSarcoidosis

• EBV / CMV / HSV / HZV / MumpsEBV / CMV / HSV / HZV / Mumps

• LymeLyme

• ToxoplasmosisToxoplasmosis

Neuro-retinitisNeuro-retinitis

http://medstat.med.utah.edu/NOVEL

Syphilis

• Optic neuritis, uveitis.

• Immunocompromised or HIV.

• Can occur at any stage of disease.

• Positive serum and CSF-VDRL.

• Suspect if reactive CSF and negative serum and CSF VDRL.

Sarcoid Optic Sarcoid Optic NeuropathyNeuropathy

• CXR and ACE are positive in 70 %.CXR and ACE are positive in 70 %.

• MRI and Galium scan are positive in 80%-90%.MRI and Galium scan are positive in 80%-90%.

• Evolving role of PET scan for occult lesions for Evolving role of PET scan for occult lesions for biopsy.biopsy.

• CSF : high protein and lymphocytosis (non-CSF : high protein and lymphocytosis (non-specific)specific)

• Responds to steroids.Responds to steroids.

SarcoidosisSarcoidosis

http://medstat.med.utah.edu/NOVEL

Neuro-sarcoidosisNeuro-sarcoidosis

Leber’s Heriditary Optic Neuropathy

• Mitochondrial optic neuropathy (Maternal Inheritance)

• Males (85% , females 15%) , age 10-80 years.

• Sequential vision loss.

• Acute or chronic presentation.

LHON• Fundus

• Swollen RNFL with circumperipapillary telangectiasia

• Atrophy

LHON

• Rule out cardiac conduction defects (EKG).

• Diagnosis is by mitochondrial genetic testing (m.11778G>A, m.3460G>A or m.14484T>C)

• Treatment : Co-enzyme 10 , Idebenone

Suggested Blood Work up for Atypical Optic Neuritis

Test Disease

CBC with Differntial, ESR, CRPInfections,

Inflammatory

Serum CSF-VDRL, FTA-Abs Syphilis

ACE Sarcoid

ANA, Anti-DNA SLE

NMO IgG NMO

C-ACNA, anti-pretinase 3

PPD TB

Bartoenlla Hensellae Serology Cat Scratch

LHON genetic testing LHON

Additional Work up

• Tissue biopsy of lesions of conjunctiva , ocular adnexa , sinus mucosa and sometimes optic nerve sheath.

• Radiologic studies : must include MRI of the brain and orbit with fat-suppression and gadolinium enhancement of the optic nerve sheath.

• PET/CT imaging, galluim scan.

CaseCase

• VA : 20/30 both eyes.VA : 20/30 both eyes.

• Color : full both eyes.Color : full both eyes.

• Pupils : small right RAPD.Pupils : small right RAPD.

• Inferior visual field defect right eye.Inferior visual field defect right eye.

CaseCase

CaseCase• ANA, C-ANCA, P-ANCA, Lyme titers, FTA-ABS and ACE levels ANA, C-ANCA, P-ANCA, Lyme titers, FTA-ABS and ACE levels

normal. normal.

• Chest x-ray normal.Chest x-ray normal.

• VA decreased to 20/80 right eye and color vision to 2/6 over VA decreased to 20/80 right eye and color vision to 2/6 over 3 months despite oral steroids.3 months despite oral steroids.

• LP: normal CSF.LP: normal CSF.

• Vitreous cells seen.Vitreous cells seen.

• CT of chest and abdomen: normal.CT of chest and abdomen: normal.

• PET scan: normal.PET scan: normal.

12/03

3/04

MRI

Optic Nerve Optic Nerve Sheath BiopsySheath Biopsy

Positive CD20 and CD45

SummarySummary• RAPD and dyschromatopsia are the hallmarks of RAPD and dyschromatopsia are the hallmarks of

optic neuropathy.optic neuropathy.

• Typical optic neuritis is a clinical diagnosis.Typical optic neuritis is a clinical diagnosis.

• Low risk of MS if normal MRI, disc edema and Low risk of MS if normal MRI, disc edema and male.male.

• Suspect atypical optic neuritis (bilateral, painless, Suspect atypical optic neuritis (bilateral, painless, uveitis, no improvement after 6/52, severe disc uveitis, no improvement after 6/52, severe disc edema and hemorrhages).edema and hemorrhages).

• Atypical optic neuritis should be investigated Atypical optic neuritis should be investigated more intensively (serology, LP, biopsy).more intensively (serology, LP, biopsy).