Neuromyelitis Optica (NMO) (Grand Rounds)

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Original article contributed by: Jesse L. Berry, MD
All contributors: Jesse L. Berry, MD
Assigned editor:
Review: Assigned status Up to Date by Jesse L. Berry, MD on June 8, 2017.


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History

  • Previously healthy 56-year-old female
  • Presents with acute simultaneous bilateral vision loss of one day duration
  • Associated with bilateral eye pain and pain with eye movements

Exam Findings

  • VA: NLP; 20/400
  • Pupils: Sluggishly reactive OU, +2 RAPD OD
  • IOP: 15; 15
  • EOM: Full OU
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Differential Diagnosis - Acute Optic Neuropathy

  • Infectious
    • Syphilis
    • Tuberculosis
    • Lyme
  • Inflammatory
    • Demyelinating optic neuritis (multiple sclerosis)
    • Neuromyelitis optica (NMO)
    • Sarcoidosis
    • Systemic Lupus Erythematosis (SLE)
    • Granulomatosis with Polyangiitis
    • Chronic relapsing inflammatory optic neuropathy (CRION)
    • Autoimmune optic neuritis
  • Compressive/Infiltrative
    • Optic nerve sheath meningioma
    • Glioma
    • Metastasis
    • Leukemia/lymphoma
  • Toxic
    • Methanol
  • Ischemic
    • Giant cell arteritis (GCA)
    • Non-Arteritic anterior ischemic optic neuropathy

Additional Investigations

  • Lab work and a lumbar puncture were performed for various infectious and inflammatory causes of atypical optic neuritis
  • MRI of the cervical and thoracic spine to detect any myelitis given the high suspicion for NMO

Lab Testing Results

  • Infectious
    • RPR and FTA-ABS-ve
    • QuantGold-ve
    • B. henselae-ve
  • Inflammatory
    • Antinuclear antibody (ANA)-ve
    • c-ANCA, pANCA-ve
    • SS-A, SS-B Ab-ve
    • ACE-ve
    • Anti-aquaporin 4-ve
  • Lumbar puncture
    • Glucose, 106mg/ml (mildly elevated)
    • Protein, 22mg/ml (normal)
    • Two nucleated cells (equivocal)
    • No growth on culture
  • MRI C-spine w/wo contrast
    • No intrinsic cord signal abnormality or abnormal post contrast enhancement
  • MRI T-spine w/wo contrast

Diagnosis

  • Neuromyelitis Optica (NMO) spectrum disorder

Pathophysiology

  1. NMO (Devic’s disease) is an autoimmune disease in which auto-antibodies attack myelin. Specifically IgG antibodies against aquaporin 4 protein channels present in the cell membrane of astrocytes has been implicated in the pathophysiology of NMO.
  2. Aquaporin 4 channels are found on astrocytes in the blood brain barrier. Therefore, auto-antibodies in NMO are believed to lead to a breakdown in the blood brain barrier.
  3. A second subset of patients is NMO IgG negative for aquaporin 4. Some of these patients may test positive for another antibody, anti-MOG, which is thought to primarily attack myelin followed by degeneration of axons and astrocytes.

Treatment

  • The patient was treated with five days of IV 1G Solu-Medrol
  • Given the suspicion of an aggressive inflammatory optic neuropathy as the patient presented with acute NLP vision, plasmapheresis was started at the same time as the IV Solu-Medrol. The patient received five doses of plasmapheresis (2on-1off-2on-1off-1on schedule).
  • She was then transitioned to 60mg PO prednisone for two weeks
  • Prednisone was tapered to 40mg PO prednisone for the subsequent two weeks
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Prognosis and Future Directions

  • The prognosis for typical demyelinating optic neuritis is very good, with more than 90 percent of patients having improved visual acuity in the first two weeks. Patients presenting typically have an excellent prognosis (~95 percent have vision at six months better than 20/30).
  • At 15 years, approximately 50 percent of these patients will have developed MS, and 75 percent will have developed MS if they demonstrated at least one typical demyelinating lesion on MRI at presentation.
  • IV steroids may be associated with more rapid improvement in vision, but no change in final visual prognosis or long-term protection in the development of MS.
  • If a patient presents with the following typical features, further workup beyond MRI brain and orbits is not recommended (i.e. Lumbar puncture, extensive serological testing)
    • Ages 18 to 50 years old
    • Pain with eye movements
    • No to minimal intraocular inflammation
    • Unilateral
    • No hemorrhages or exudates in posterior pole
    • Demonstrate improvement in vision several weeks after onset
  • Based on Optic Neuritis Treatment Trial findings, an optic neuritis is considered “atypical” for the classical MS-associated form when any of the above features are absent, precipitating further workup.
  • Neuromyelitis Optica is now defined as:
    • Major criteria (need both):
      • Unilateral or bilateral optic neuritis
      • Transverse Myelitis (TM)
  • Supportive criteria (need two or three):
    • Longitudinally extensive (>=3 vertebral segments) TM
    • MRI brain not consistent with MS pattern
    • Aquaporin-4 antibody positive
  • For NMO-associated optic neuritis, the prognosis is less favorable than typical demyelinating optic neuritis. Approximately 85 percent of patients have relapses of either optic neuritis or transverse myelitis.
  • In patients classified as NMO spectrum disease (i.e. either optic neuritis or transverse myelitis but do not meet the full diagnostic criteria for NMO), prognosis has been shown to vary depending on whether patients are anti-AQP4-Ab positive or anti-MOG-Ab (myelin-oligodendrocyte glycoprotein antibody) positive. Patients who are anti-AQP4 are more likely to have optic neuritis that progresses to significant optic atrophy with worse visual prognosis compared to anti-MOG-Ab. Patients who are anti-MOG-Ab are more likely to present with bilateral optic neuritis, respond better to treatment with steroids and are less likely to have extensive optic atrophy.
  • While azathioprine and rituximab are commonly used immunosuppressive therapies in patients with NMO, there are no randomized controlled trials comparing the effectiveness of various immunosuppressive therapies. Future randomized controlled trials may help guide immunosuppressive treatment in patients with NMO or NMO spectrum disease.

References

  • Palace J, Leite MI, Nairne A and Vincent A. (2010) Interferon Beta treatment in neuromyelitis optica: increase in relapses and aquaporin 4 antibody titers. Arch Neurol. 2010 Aug;67(8):1016-1017.
  • Paty DW, Oger JJ, Kastrukoff LF, et al. MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. Neurology. 1988 Feb;38(2):180-5.
  • Akaishi T, Nakashima I, Sato DK, Takahashi T, Fujihara K. Neuromyelitis Optica Spectrum Disorders. Neuroimaging Clin N Am. 2017 May;27(2):251-265.
  • Voss E, Raab P, Trebst C, Stangel M. Clinical approach to optic neuritis: pitfalls, red flags and differential diagnosis. Ther Adv Neurol Disord. 2011;4(2):123-34.
  • Ikeda K, Kiyota N, Kuroda H, et al. Severe demyelination but no astrocytopathy in clinically definite neuromyelitis optica with anti-myelin-oligodendrocyte glycoprotein antibody. Mult Scler. 2015;21(5):656-9.
  • Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti, CF, Weinshenker BG. (2006) Revised diagnostic criteria for neuromyelitis optica. Neurology 2006 May23;66(10):1485-1489.
  • Sellner J, Boggild M, Clanet M, Hintzen RQ, Illes Z, Montalban X, et al. EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol. 2010 Aug;17(8):1019-32.

Contact

  • Vivek Patel, MD, Associate Professor of Clinical Ophthalmology, Director, Neuro-Ophthalmology Service, vivek.patel@med.usc.edu
  • Nadim Rayess, MD, PGY-2 Ophthalmology resident, nadim.rayess@med.usc.edu