Chronic relapsing inflammatory optic neuropathy

Chronic relapsing inflammatory optic neuropathy (CRION), sometimes called chronic relapsing inflammatory optic neuritis, is a form of recurrent optic neuritis that is steroid responsive.^[1] Patients typically present with pain associated with visual loss.^[1] CRION is a diagnosis of exclusion, and other demyelinating, autoimmune, and systemic causes should be ruled out.^[2] Early recognition is crucial given risks for severe visual loss and because it is treatable with immunosuppressive treatment such as steroids.^[2] Relapse that occurs after reducing or stopping steroids is a characteristic feature ^[2]

Pathogenesis

The etiology remains unknown.^[1] Given that CRION is responsive to immunosuppressive treatment, it may be immune-mediated.^[2] CRION has been classified as an autoimmune process but this description is not established with certainty and there is no known associated autoimmune antibody ^[2][3]

Some research points to CRION belonging to the antiMOG associated encephalomyelitis spectrum.^[4]

Signs and Symptoms

Pain, visual loss, relapse, and steroid response are typical of CRION.^[1][2] Ocular pain is typical, although there are some cases with no reported pain.^[2] Bilateral severe visual loss (simultaneous or sequential) usually occurs, but there are reports of unilateral visual loss.^[2] Patients can have an associated relative afferent pupillary defect.^[5] CRION is associated with at least one relapse, and up to 18 relapses have been reported in an individual.^[6] Interval between episodes can range from days to over a decade.^[1] Symptoms will improve with corticosteroids, and recurrence characteristically occurs after reducing or stopping steroids.^[2]

Epidemiology

CRION was first described in 2003.^[1] The disease is rare, with only 122 cases published from 2003 to 2013.^[2] There is female predominance with 59 females (48%), 25 males (20%), and no gender designation for the rest of the 122 reported cases (32%).^[2] Age ranges from 14 to 69 years of age, and the mean age is 35.6.^[2] The disease is noted to occur worldwide and across many ethnicities, with reported cases in all continents except Africa and Australia.^[2]

Diagnosis

Diagnosis requires exclusion of other neurological, ophthalmological, and systemic conditions.^[2] Any cause of optic neuropathy should be ruled out, including demyelinating (multiple sclerosis, and neuromyelitis optica) and systemic disease (diabetic, toxic, nutritional, and infectious causes).^[2] Corticosteroid responsive optic neuritis not associated with demyelinating disease should also be ruled out, including sarcoidosis, systemic lupus erythematosus, or other systemic autoimmune disease.^[7] Hereditary causes such as Leber’s hereditary optic neuropathy are also part of the differential diagnosis.^[8]

There are no current diagnostic biomarkers or imaging features typical of CRION.^[2] ANA, B12, folate, thyroid function tests, anti-aquaporin 4 antibodies (NMO-IgG), and GFAP can facilitate ruling out of other diseases.^[2] Most patients are seronegative for NMO-IgG and GFAP, biomarkers for neuromyelitis optica.^[2] ANA, indicative of autoimmune optic neuropathy, is also generally negative.^[2] CSF can also be evaluated for oligoclonal bands typical of multiple sclerosis, which will not be present in CRION.^[1] Chest X-ray or CT should be ordered if granulomatous optic neuropathy caused by sarcoidosis is suspected.^[2]

MRI imaging can capture optic nerve inflammation, but this finding is not present in all patients,^[1][2][9] Diffusion tensor imaging has been shown to detect widespread white matter abnormalities in CRION patients with normal MRI findings ^[10]

Five diagnostic criteria have been proposed:^[2]

• 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

Treatment and Prognosis

Treatment consists of three phases:

• 1. Acute phase: IV steroids (methylprednisolone 1 mg/kg) for 3–5 days or plasmapheresis are given to restore visual function.^[2]
• 2. Intermediate phase: Oral steroids (typically prednisone 1 mg/kg) with taper are given to stabilize vision.^[2]
• 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. Azathioprine, methotrexate, cyclophosphamide, mycophenolate, IVIG, plasma exchange, cyclosporine, and infliximab have been used.^[2]

Visual acuity is dramatically worse with CRION than other forms of optic neuritis.^[2] Treatment with corticosteroids induces prompt relief of pain and improved vision.^[1] At times, patients obtain complete restoration of vision, although exact success rates are unknown.^[1] Recurrence is essentially inevitable in patients without treatment and patients ultimately will require lifelong immunosuppression to prevent relapse.^[2][11]

See also

• Optic neuritis
• Optic neuropathy

References