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Chronic relapsing inflammatory optic neuropathy (CRION) is a form of recurrent optic neuritis that is steroid responsive and dependent. Patients typically present with pain associated with visual loss. CRION is a clinical diagnosis of exclusion, and other demyelinating, autoimmune, and systemic causes should be ruled out. An accurate antibody test which became available commercially in 2017 has allowed most patients previously diagnosed with CRION to be re-identified as having MOG antibody disease, which is not a diagnosis of exclusion. Early recognition is crucial given risks for severe visual loss and because it is treatable with immunosuppressive treatment such as steroids or B-cell depleting therapy. Relapse that occurs after reducing or stopping steroids is a characteristic feature.

Signs and symptoms

Pain, visual loss, relapse, and steroid response are typical of CRION. Ocular pain is typical, although there are some cases with no reported pain. Bilateral severe visual loss (simultaneous or sequential) usually occurs, but there are reports of unilateral visual loss. Patients can have an associated relative afferent pupillary defect. CRION is associated with at least one relapse, and up to 18 relapses have been reported in an individual. Intervals between episodes can range from days to over a decade. Symptoms will improve with corticosteroids, and recurrence characteristically occurs after reducing or stopping steroids.

Pathogenesis

In 2013, the etiology was unknown. Given that CRION is responsive to immunosuppressive treatment, it was presumed to be immune-mediated, but this was uncertain as at the time there were no known associated autoimmune antibodies.

In 2015, some research pointed to CRION belonging to the MOG antibody-associated encephalomyelitis spectrum.

As of 2019, the correlation between CRION and MOG antibody-associated encephalomyelitis is so high that now CRION is considered the most common phenotype related to myelin oligodendrocyte glycoprotein antibodies (MOG-IgG).

As of 2021, some reports point out a second kind of CRION due to anti-phospholipid antibodies.

Diagnosis

In 2018, of 12 patients in a study who fulfilled the then-current diagnostic criteria for CRION, eleven (92%) were positive for MOG-IgG, and the last patient was borderline. Diagnosis requires exclusion of other neurological, ophthalmological, and systemic conditions. Any cause of optic neuropathy should be ruled out, including demyelinating (MOG antibody disease, multiple sclerosis, and neuromyelitis optica) and systemic disease (diabetic, toxic, nutritional, and infectious causes). Corticosteroid responsive optic neuritis not associated with demyelinating disease should also be ruled out, including sarcoidosis, systemic lupus erythematosus, or other systemic autoimmune disease. Hereditary causes such as Leber's hereditary optic neuropathy are also part of the differential diagnosis.

In 2014, there were no diagnostic biomarkers or imaging features typical of CRION. Antinuclear antibodies (ANA), B₁₂, folate, thyroid function tests, anti-aquaporin-4 antibodies (NMO-IgG), and glial fibrillary acidic protein (GFAP) can facilitate ruling out of other diseases. Most patients are seronegative for NMO-IgG and GFAP, biomarkers for neuromyelitis optica. ANA, indicative of autoimmune optic neuropathy, is also generally negative. CSF can also be evaluated for oligoclonal bands typical of multiple sclerosis, which will not be present in CRION. A chest X-ray or CT scan should be ordered if granulomatous optic neuropathy caused by sarcoidosis is suspected.

Magnetic resonance imaging can capture optic nerve inflammation, but this finding is not present in all patients, Diffusion tensor imaging has been shown to detect widespread white matter abnormalities in CRION patients with normal MRI findings.

Five diagnostic criteria had been proposed in 2014:

• History of optic neuritis with one relapse
• Objectively measured visual loss
• NMO-IgG seronegative
• Contrast enhancement on imaging of acutely inflamed optic nerves
• Response to immunosuppressive treatment and relapse on withdrawal or dose reduction.

CRION has been included as a subtype in a 2022 international consensus classification of optic neuritis.

Treatment

Treatment consists of three phases of immunotherapy:

• 1. Acute phase: IV steroids (methylprednisolone 1 mg/kg) for 3–5 days or plasmapheresis are given to restore visual function.
• 2. Intermediate phase: Oral steroids (typically prednisone 1 mg/kg) with taper are given to stabilize vision.
• 3. Long-term phase: To avoid adverse effects of long-term steroids and to avoid relapse of disease, physicians can transition to a steroid-sparing agent. B-cell depleting therapy, azathioprine, methotrexate, cyclophosphamide, mycophenolate, IVIG, plasma exchange, cyclosporine, and infliximab have been used.

Visual acuity is dramatically worse with CRION than other forms of optic neuritis. Treatment with corticosteroids induces prompt relief of pain and improved vision. At times, patients obtain complete restoration of vision, although exact success rates are unknown.

Prognosis

Recurrence is essentially inevitable in patients without treatment, and patients ultimately will require lifelong immunosuppression to prevent relapse.

Epidemiology

CRION was first described in 2003. The disease is rare, with only 122 cases published from 2003 to 2013. There is female predominance with 59 females (48%), 25 males (20%), and no gender designation for the rest of the 122 reported cases (32%). Age ranges from 14 to 69 years of age, and the mean age is 35.6. The disease is noted to occur worldwide and across many ethnicities, with reported cases in all continents except Africa and Australia.

See also

• Optic neuritis
• Optic neuropathy

References

1. ^ Kidd D, Burton B, Plant GT, Graham EM (February 2003). "Chronic relapsing inflammatory optic neuropathy (CRION)". Brain: A Journal of Neurology. 126 (Pt 2): 276–84. doi:10.1093/brain/awg045. PMID 12538397.
2. ^ Petzold A, Fraser C, Abegg M, Alroughani R (2022). "Diagnosis and Classification of Optic Neuritis". The Lancet Neurology. 21 (12): 1120–1134. doi:10.1016/S1474-4422(22)00200-9. PMID 36179757. S2CID 252564095.
3. ^ Petzold A, Plant GT (January 2014). "Chronic relapsing inflammatory optic neuropathy: a systematic review of 122 cases reported". Journal of Neurology. 261 (1): 17–26. doi:10.1007/s00415-013-6957-4. PMID 23700317. S2CID 31281504.
4. ^ Lee HJ, Kim B, Waters P, Woodhall M, Irani S, Ahn S, et al. (October 2018). "Chronic relapsing inflammatory optic neuropathy (CRION): a manifestation of myelin oligodendrocyte glycoprotein antibodies". Journal of Neuroinflammation. 15 (1): 302. doi:10.1186/s12974-018-1335-x. PMC 6208174. PMID 30382857.
5. Kaut O, Klockgether T (September 2008). "51-year-old female with steroid-responsive optic neuropathy: a new case of chronic relapsing inflammatory optic neuropathy (CRION)". Journal of Neurology. 255 (9): 1419–20. doi:10.1007/s00415-008-0919-2. PMID 18575925. S2CID 31618770.
6. Saini M, Khurana D (January 2010). "Chronic relapsing inflammatory optic neuropathy". Annals of Indian Academy of Neurology. 13 (1): 61–3. doi:10.4103/0972-2327.61280. PMC 2859591. PMID 20436750.
7. Petzold A, Plant GT (2014). "Diagnosis and classification of autoimmune optic neuropathy". Autoimmunity Reviews. 13 (4–5): 539–45. doi:10.1016/j.autrev.2014.01.009. PMID 24424177.
8. Chalmoukou K, Alexopoulos H, Akrivou S, Stathopoulos P, Reindl M, Dalakas MC (August 2015). "Anti-MOG antibodies are frequently associated with steroid-sensitive recurrent optic neuritis". Neurology: Neuroimmunology & Neuroinflammation. 2 (4): e131. doi:10.1212/NXI.0000000000000131. PMC 4496630. PMID 26185777.
9. Cantó LN, Boscá SC, Vicente CA, Gil-Perontín S, Pérez-Miralles F, Villalba JC, et al. (2019). "Brain Atrophy in Relapsing Optic Neuritis Is Associated With Crion Phenotype". Frontiers in Neurology. 10: 1157. doi:10.3389/fneur.2019.01157. PMC 6838209. PMID 31736862.
10. Navarro CE, Arango GJ, Cubides MF (August 2021). "Chronic relapsing inflammatory optic neuropathy in a patient with triple antiphospholipid antibody positivity". Neurological Sciences. 42 (8): 3439–3443. doi:10.1007/s10072-021-05263-6. PMID 33880676. S2CID 233314170.
11. Myers TD, Smith JR, Wertheim MS, Egan RA, Shults WT, Rosenbaum JT (May 2004). "Use of corticosteroid sparing systemic immunosuppression for treatment of corticosteroid dependent optic neuritis not associated with demyelinating disease". The British Journal of Ophthalmology. 88 (5): 673–80. doi:10.1136/bjo.2003.028472. PMC 1772147. PMID 15090422.
12. Lee MD, Song BJ, Odel JG, Sadun AA. Bilateral vision loss responsive to corticosteroids. Survey of Ophthalmology. Nov-Dec 2013;58(6):634-639
13. Sharma A, Khurana D, Kesav P (February 2013). "MRI findings in chronic relapsing inflammatory optic neuropathy". BMJ Case Reports. 2013: bcr2012008100. doi:10.1136/bcr-2012-008100. PMC 3604485. PMID 23417378.
14. Colpak AI, Kurne AT, Oguz KK, Has AC, Dolgun A, Kansu T (January 2015). "White matter involvement beyond the optic nerves in CRION as assessed by diffusion tensor imaging". The International Journal of Neuroscience. 125 (1): 10–7. doi:10.3109/00207454.2014.896912. PMID 24588222. S2CID 207419720.
15. Malik A, Ahmed M, Golnik K (October 2014). "Treatment options for atypical optic neuritis". Indian Journal of Ophthalmology. 62 (10): 982–4. doi:10.4103/0301-4738.145986. PMC 4278124. PMID 25449930.

External links

• Eye diseases
• Steroid-responsive inflammatory conditions