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Autoimmune Diseases of the CNS: Optic Neuritis and Myelitis Michael J. Bradshaw, MD
Rosalind Franklin University of Medicine and Science
Billings Clinic Neurology
Disclosures/Off-Label Use
No financial conflicts of interest
Off-label treatment of neuromyelitis optica spectrum disorders is discussed
Goals
Recognize and understand diagnostic evaluation of two common presentations of autoimmune CNS disease:
Optic Neuritis
Myelitis
Review the neuromyelitis optica spectrum disorders
Case 1
46 year old woman with no medical history reports two days progressive vision loss in the left eye. Her vision started out “cloudy” and has been getting progressively worse. She noticed that while driving, it looked like cars were swerving toward her. She also has mild retro-orbital discomfort.
Optic Neuritis: Typical Symptoms
Subacute, progressive monocular vision loss
Decreased visual acuity
Dyschromatopsia
Variably accompanied by retro-orbital pain
Mayoclinic.org
Optic Neuritis: Unusual Symptoms
Phosphenes: light flashes with eye mvmt
Photisms: light induced by noise, taste or touch
Pulfrich effect: false perception of depth in lateral motion
“What is out of the common is usually
a guide rather than a hindrance.”
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Pulfrich Effect
https://www.youtube.com/watch?v=1mnWI_u_zBg
Watch with dark sunglasses blocking the left eye only and the image will appear three-dimensional due to the Pulfricheffect
Patient’s view
Neurology July 19, 2016, 87:3 338-339.
Localization: surface of the eye to the optic chiasm (on the left)
Baehr M, Frotscher M. Duus’ topical diagnosis in neurology. Thieme.
Mayoclinic.org
Case 1
Physical exam: visual acuity 20/80 OS, 20/20 OD, left eye red desaturation, and a
relative afferent pupillary defect in the left eye. No disc edema.
aapos.org
Optic Nerve Lesion:Physical exam
Decreased visual acuity (especially to low contrast chart)
Color desaturation
Relative afferent pupillary defect
May not have optic disc edema
Lancet Neurol 2014; 13: 83–99.
Relative Afferent Pupillary Defect
https://www.youtube.com/watch?v=soiKbngQxgw
Normal: 1:20 min
Right eye relative afferent pupillary defect: 2:10 min
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DDx
Lancet Neurol 2014; 13: 83–99.
Immune-mediated CIS/MS
NMOSD
ANCA-associated vasculitis
Neurosarcoidosis
Paraneoplastic(e.g. CRMP5)
Infectious Neuroretinitis (viral, toxo,
bartonella)
Syphilis
Lyme disease (rare)
Vascular Nonarteritic ischemic optic
neuropathy
Giant cell arteritis
Retinal hemorrhage
Mass Glioma, meningioma
Toxic/metabolic B12/folate deficiency
Drugs
Genetic (rare) Leber hereditary optic
neuropathy
Kjer-type autosomal dominant optic atrophy
Inflammatory Non-Inflammatory
Case 1: Next step?
Diagnostic Evaluation
Serum:
ANA, SSA/B, ANCAs, ESR/CRP, AQP4/MOG, B12/Folate
CSF: Cell count/diff, glucose, protein, OCBs, IgG index, VDRL (others)
Imaging:
MRI orbits w/wo contrast
AQP4 = Aquaporin-4
MOG = myelin oligodendrocyte glycoprotein Axial T1 Postcontrast
Optic Neuritis:
MRI
MRI orbit w/wocontrast (includes brain)
T2 hyperintensityand contrast enhancement of the affected optic nerve
Coronal T1 Postcontrast
Ann Neurol 2011;69:292-302.
Visual evoked potentials
Diagnosis: Optic Neuritis/RRMS
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Optic Neuritis: Treatment
1 g IV methylprednisolone daily x 3-5 days
Some give an oral prednisone taper
Oral prednisone 1250 mg/day (=25 pills!) x 3-5 days
Oral methylpred (1g; 1:1 oral availability)x 3-5 days
N Engl J Med. 1992 Feb 27;326(9):581-8.
PO Steroids: Non-Inferior to IV in the Short-Term
COPOUSEP trial: 1 g IVMP vs 1 g POMP
JAMA Study: 1g IVMP vs 1.25 g PO prednisone
Both demonstrated non-inferiority in short term
Decrease risk to MS conversion with IV?
Reserve PO route for relapses with special circumstances, rather than initial presentation
JAMA Neurol. 2018 Jun 1;75(6):690-696.
Lancet. 2015 Sep 5;386(9997):974-81.
Optic Neuritis: Prognostication
Long term risk of conversion to clinically definite MS
Additional lesions: ~80%
No lesions, +OCBs: ~23%
No lesions: ~20%
No lesions and no OCBs: ~4%
Arch Neurol. 2008;65:727–32. Brain. 2008;131(Pt 3):808–17. Neurology.
2006;67:968–72. Mult Scler. 2011;17:312–8. Neurology. 2008; 70:1079–83.
Case 2
A three year old girl is brought to the emergency department for vision changes.
Four days ago, she reported “seeing water” on the floor, then over the next few days seemed to have difficulty seeing objects, such as a toy held out to her. Today, she started walking into walls, saying she couldn’t see them.
Physical exam: no central vision in either eye (light perception only), but some preserved peripheral vision. There is no relative afferent pupillary defect. Left Babinski.
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Optic Neuritis: RED FLAG Features
Severe visual deficits
Bilateral optic neuritis
Involvement of the chiasm on MRI
Longitudinally extensive optic neuritis (>1/2 length of the ON)
Concerning for neuromyelitis optica spectrum disorders
Poor recovery from attacks; emergent
treatment indicated
CSF: 0 WBC, normal glucose, normal protein, no oligoclonal bands, elevated IgG index
Treated with emergent IVMP and PLEX- vision fully recovered
Serum AQP4 IgG positive, MOG negative
Diagnosis: AQP4+ neuromyelitis optica spectrum disorder (AKA “Devic’s disease”)
Maintenance therapy with rituximab q3 months
Case 2
Neuromyelitis Optica Spectrum Disorders
Divided into three groups:
Aquaporin 4+
Aquaporin 4-, MOG +
Aquaporin 4-, MOG-
Relapsing myelitis, relapsing optic neuritis, etc.
MOG = myelin oligodendrocyte glycoprotein
AQP4+ NMOSD
Relapsing autoimmune astrocytopathy
AKA Devic’s disease
Episodes resemble demyelinating events
Predominant optic neuritis and myelitis
Once thought to be a
form of MS
Eugène Devic, 1894
NMOSD: Core Clinical Features
Optic neuritis
Bilateral, severe, poor recovery, longer lesions/chiasm
Myelitis
>3 segments, extensive, swelling, central cord
Area postrema syndrome
Intractable hiccups, nausea, vomiting
Brainstem syndrome
Symptomatic narcolepsy/diencephalicsyndrome
Cerebral syndromeContinuum (Minneap Minn) 2016;22(3):864–896. Bradshaw MJ, Kimbrough DK. Practical Neurology 2/2019;76-89.
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AQP4+ NMOSD
AQP4 is a water channel heavily expressed on optic nerves, brainstem, spinal cord
Aquaporin-4 IgG are pathogenic
Fix complement: kills the astrocyte Neuronal death
J Exp Med 2005;202(4):473-477. Neurology. 2013 Oct;81(14):1197-204.
NMOSD Acute Treatment
All disability accumulates during relapses
Relapses should be treated aggressively
IVMP and early plasma exchange
Area postrema syndrome generally responds to steroids alone
NMOSD Maintenance Treatment
Eculizumab (C5 complement inhibitor; FDA approved)
Rituximab (CD20 Ab)
Mycophenolate mofetil, azathioprine
Clinical trials:
Tocilizumab/satralizumab (IL-6R antagonist)
Inebilizumab (CD19 Ab)
Case 427 yoF presents to her PCP after she developed paresthesias in the hands and feet over the course of a few days. Several days later, she noted sensory loss/paresthesias from the nipple line down.
She had an episode of optic neuritis 12 years ago.
Next step?
Case 2: Next steps?
Ascending sensory
pathways
Descending motor
pathways
Fine touch, vibration, proprioception
(ipsilateral)ARM LEG
Motor control
extremities(ispilateral)
Motor control
trunk (bilateral)
Crude touch,
temperature, pinprick(contralateral)
VENTRAL
DORSAL
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Myelopathy
Spinal cord dysfunction from any cause
Compression, immune-mediated,
infectious, spinal cord infarct,
toxic/metabolic
Myelitis is spinal cord dysfunction with evidence of inflammation
MRI or CSF
A Systematic Approach to MyelopathyClinical evidence of spinal cord
dysfunction
MRI spine w/wo contrast Extrinsic compression NSGY
CSF analysis
Cord pathology?
Evidence of Inflammation?
Myelitis
- Immune-mediated- Infectious
- Malignant
Cord inflammation
Myelopathy
- Compressive- Toxic/Metabolic
- Vascular
Cord pathology
No inflammation
Consider myelopathy
- MRI/CSF too early?- Not myelopathy?
No cord pathology
No inflammation
Image the suspected
localization AND more Rostrally
e.g. sx from
T4 down- include C spine MRI
T2 T1-Post T2 T1-Post
Longitudinally extensive transverse myelitis (LETM): Spinal cord lesion > 3 spinal segments suggests against MS
Bradshaw MJ, et al. Neuro Board Rev, 6/2018.
Spinal cord lesion typical of MS: short segment, dorsal cord
T2 T1 Post T1 Post
T2
Baehr M, Frotscher M. Duus’ topical diagnosis in neurology. Thieme.
ArmLegs
Arm
C3
NORMAL T2 T1 post-contrast
Spinal cord lesion typical of NMOSD: Longitudinally extensive, grey matter/ventral cord
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West Nile Myelitis: Grey matter lesion with flaccid paralysis
Baehr M, Frotscher M. Duus’ topical diagnosis in neurology. Thieme.
T2 T1 Post T1 PostNeurosarcoidosis: nodular meningeal enhancement and
LETM (wide range possible)
Case 4
Brain MRI normal; spine with LETM
CSF: 23 (89%lymph, 10%mono), normal glucose, protein, no OCBs
Serum: MOG IgG positive 1:1000
AQP4 IgG neg
MOG + NMOSD
Neuromyelitis optica
spectrum disorder with
IgG antibodies against
MOG
Myelin oligodendrocyte
glycoprotein
Expressed on outer
surface of myelin sheath,
involved in cell
adhesion/microtubule
stability
MOG+ NMOSD
Optic neuritis, myelitis, brainstem encephalitis, ADEM
~25-33% of AQP4 negative NMOSD patients have MOG IgG
Treatment is similar to AQP4+NMOSD, but still being defined
MMF, rituximab, IVIg
Generally carries better prognosis than AQP4+ NMOSD
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Questions?
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