Neuro-ophthalmology: 5 new-ish things (controversies)

Eric Eggenberger DO Neuro-Ophthalmology

Neuro-ophthalmology: 5 new-ish things (controversies)

Neuro-ophthalmology: 5 new things1.Retinal ischemia 2.Ocular myasthenia gravis 3.Vergence/sagging eye 4.Optic neuritis x 3 5.Giant cell arteritis

TMVL DWI %

BRAO DWI %

CRAO DWI %

Hellenius et al Ann Neurol 2012

66 18% DWI+

46 33% DWI+

Lauda et al CV Dis 2015

68 16% DWI+

44 31% DWI+

101 53% DWI+

Golsari et al Stroke 2017

35 12% DWI+

8 12% DWI+

69 76% DWI+

+DWI% AVG 38% 15% 27% 62%

RAO & TMVL: MRI DWI

Acute Retinal Ischemia Management• Stroke referral: 3 days (or 7 days with emboli source)

•ABCD >2-3; clinical, labs

AHA Stroke 2009; Biousse, Nahab, Newman. Ophth 2018

Vascular imagingMRI with DWI

Echo & EKG/monitor

44-♂ Transient Diplopia

5

Binocular? Vertical vs horizontal? Co-morbidities? Associated symptoms?

Episodic Diplopia

Episodic Misalignment

Episodic Malfusion

?Fatigue“Make

everything as simple as

possible, but not simpler”

*Albert Einstein

Everything is worse with fatigue!

Ocular MG Generalization

*50% +Ab *Natural Hx: ~50% generalize !Risk/time: 2 years: 15%, 3 years: 6% generalize

**70% +Ab (MSU + UM cohort) **33/158 (21%) converted to GMG 10 (30%) converted >2years

*Oosterhuis, JNNP 1989;52:1121; Glob. MG. 1999. Bever. Ann Neurol 1983 **Nagia, Lemos, Abusamra, Cornblath, Eggenberger. Opthalmology 2015

OMGRate: Rating Scale for Ocular Myasthenia Gravis

Wong S, Xhepa S, Miranda E, Lee H, Burke A, DelArti L, Cornblath W, Eggenberger E, Barnett C. J Neuro-Ophth, in press

OMGRate-e: Eye Movements

1 point 1 point

1 point

1 point2 points

1 point

1 point

1 point

3 points

3 points

OMGRate-e: Lids

1 point

2 points

Correlation: OMGRATS-e and -q & MG-QOL = 0.65, i.e. good

OMGRATS-questionnaire good indicator of QOL

010

2030

4050

0 20 40 60totalMGQOLscore

Fittedvalues OMGRATSqwithweighteddiplopiascores

020

4060

0 20 40 60totalMGQOLscore

Fittedvalues OMGRATSe&OMGRATSqweighted

• Pupil-sparing • Painless • Variable

MG Conclusion

1. Cogan Lid Twitch 2. Enhancement of Ptosis

70% +Ab 21% (33/158) convert *30% convert >2yrs

13

Binocular Horizontal Diplopia

Alternate Cover Distance

2. Parinaud Dorsal Midbrain Syndrome Convergence retraction “nystagmus”

1.CRN 2.LND 3.Lid 4.SWJ 5.Vergence 6.Vertical 7.Skew

LR-SR Band

100 Pts w/o strabismus LR-SR band: 95% coronal T1WI 70% Coronal CT LR-SR Bowing ⍺ age (50, 9-81 yrs)

Patel et al. AJNR 2014

EOM: Sagging EyeEOM: Sagging Eye

Optic Neuritis

Papillitis 35%

Retrobulbar neuritis

65%

• Evaluation? • OCT • MRI

NMOSD Core Character1.Optic neuritis: 33% <20/200

Wingerchuk et al. Neurology 2015

2. Acute myelitis 3. Area postrema syndrome: hiccups or nausea and vomiting 4. Acute brainstem syndrome 5. Narcolepsy or acute diencephalic syndrome with MRI lesions 6. Symptomatic cerebral syndrome with typical MRI

NMOSD Dx Criteria+Aquaporin-4 IgG1. >1 core clinical characteristic2. Positive AQP4-IgG using best available method (cell-based assay)3. Exclusion of alternative diagnosis

Wingerchuk et al. Neurology 2015

MOG-IgG:October 2017Mayo Labs

Optic Neuritis #3

Antel NEJM 2004

MOG Optic Neuritis: Clinical n=87

MOG Ab-Positive Optic Neuritis. Chen, Flanagan, JIitprapaikulsan, Lopez-Chiriboga, Fryer, Leavitt, Weinshenker, McKeon, Tillema, Lennon, Tobin, Keegan, Luchinetti, Kantarci, McClelland, Lee, Bennett, Pelak, Chen, VanStavern, Adesina, Eggenberger, Acierno, Wingerchuk, Brazis, Sagan, Pittock. AJO 2018

57% female; median age onset 31 (2–79) Yrs

63% Unilateral optic neuritis: Average VA nadir: count fingers Average final VA: 20/30

5 patients (6%) <20/200 in either eye

86% Disc edema and pain

Median attacks 3 (1–8) Followup 2.9 yrs (0.5–24 yrs) Annualized relapse rate 0.8

1 patient diagnosed MS (MOG-IgG index 2.8 (<2.5))


MOG Optic Neuritis: Clinical n=87

0%

12.5%

25%

37.5%

50%

ON + Neuro Recurrent ON CRION Single ON

12%16%

30%41%

MOG Optic Neuritis: CSF

↑WBC 44% (24/50), median 4 (0 - 568)

↑Protein 42%, median 46 (19-181)

0 Oligoclonal bands (0/45)


MOG Optic Neuritis Therapy n=87

Acute: 83% IVMP 9% IVMP + PLEX 3% IVMP + IVIG 3% No Tx 1% IVIG

Chronic: 61% Chronic Tx •MMF •Azathioprine •Rituximab


0/177 AQP4-IgG; but 3/177 MOG-IgG

Initial VA 20/50, 20/50, HM 3/3 Disc edema 3/3 Final VA 20/20 (1 PBO, 2 prednisone)

0/3 MRI lesions; 0/3 MS

Chen, Tobin, Majed, Jitprapaikulsan, Fryer, Leavitt, Flanagan, McKeon, Pittock. JAMA Ophth 2018

AQP4 & MOG in the ONTT n=3

Optic Neuritis x 3• MRI + Labs • AQP-4, MOG-IgG Ab • Disc edema, MRI features

• Acute Tx: IVMP, PLEX • Most AQP4 & MOG are recurrent • AQP-4 poor prognosis untreated • MOG: ideal treatment?

Mayo Fla Photo: Jason Calhoun

78♀ VA Loss OS•20/20, 20/100 •RAPD OS •8 & 0/10 HRREvaluation? Labs? MRI? Doppler? CT?

27

Benjamin, Goodman, AJM 1979; Huston AIM 1978; Machado Arth Rheum 1988

Fever

Anorexia/Wt Loss

Myalgia

J Claudication

Scalp Tender

TA Tender

Headache

0% 23% 45% 68% 90%

GCA Symptoms

GCA Dx: CRP & ESR

Parikh, Miller, Lee, Savino, Vacarezza, Cornblath, Eggenberger, Antonio, Golnik, Kardon, Wall. Ophth 2006

Sens

iitivi

ty76%

99%

1.7%

+ESR +CRP +ESR +CRP

-ESR -CRP

98%

0.8%

15%

N = 119 +TAB

+ESR -CRP

+CRP -ESR

86%

Inflammation Endurance

Malaszewski, Younge, Fritzlen et al. Mod Path 2017;30:788

Time

Gran

ulom

a Va

scul

itis

71%67%

50%

25%

3 Mo 6 Mo 9 Mo 12 Mo

70%75%

44% 44%

N = 40

GCA: Tocilizumab 162mg sc q week

Week 52 remission: Tocilizumab 53 - 56% vs 14 - 18% prednisone

Stone et al. Tocilizumab in GCA. NEJM 2017

Inciting event

Exact pathophysiology

Early remission/prognostic markers

Biopsy vs angiography

GCA Unmet Needs

• Afferent 1.GCA 2.MOG Ab 3.Retinal ischemia

• Efferent 4.Sagging eye 5.Myasthenia

N-O New-ish Things

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Neuro-ophthalmology: 5 new-ish things (controversies)