Chronic relapsing inflammatory optic neuropathy: Difference between revisions
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'''Chronic relapsing inflammatory optic neuropathy''' ('''CRION''') is a form of recurrent [[optic neuritis]] that is steroid responsive.<ref name= " |
'''Chronic relapsing inflammatory optic neuropathy''' ('''CRION''') is a form of recurrent [[optic neuritis]] that is steroid responsive.<ref name= "Kidd_2003">{{cite journal | vauthors = Kidd D, Burton B, Plant GT, Graham EM | title = Chronic relapsing inflammatory optic neuropathy (CRION) | journal = Brain : a Journal of Neurology | volume = 126 | issue = Pt 2 | pages = 276–84 | date = February 2003 | pmid = 12538397 | doi = 10.1093/brain/awg045 }}</ref> Patients typically present with pain associated with visual loss.<ref name= "Kidd_2003"/> CRION is a diagnosis of exclusion, and other demyelinating, autoimmune, and systemic causes should be ruled out.<ref name = "Petzold_2014">{{cite journal | vauthors = Petzold A, Plant GT | title = Chronic relapsing inflammatory optic neuropathy: a systematic review of 122 cases reported | journal = Journal of Neurology | volume = 261 | issue = 1 | pages = 17–26 | date = January 2014 | pmid = 23700317 | doi = 10.1007/s00415-013-6957-4 | url = }}</ref> Early recognition is crucial given risks for severe visual loss and because it is treatable with immunosuppressive treatment such as steroids<ref name= "Petzold_2014"/> or [[B-cell depleting therapy]].<ref name="Lee_2019">{{cite journal | vauthors = Lee HJ, Kim B, Waters P, Woodhall M, Irani S, Ahn S, Kim SJ, Kim SM | display-authors = 6 | title = Chronic relapsing inflammatory optic neuropathy (CRION): a manifestation of myelin oligodendrocyte glycoprotein antibodies | journal = Journal of Neuroinflammation | volume = 15 | issue = 1 | pages = 302 | date = October 2018 | pmid = 30382857 | pmc = 6208174 | doi = 10.1186/s12974-018-1335-x }}</ref> Relapse that occurs after reducing or stopping steroids is a characteristic feature.<ref name= "Petzold_2014"/> |
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==Signs and symptoms== |
==Signs and symptoms== |
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Pain, visual loss, relapse, and steroid response are typical of CRION.<ref name= " |
Pain, visual loss, relapse, and steroid response are typical of CRION.<ref name= "Kidd_2003"/><ref name= "Petzold_2014"/> Ocular pain is typical, although there are some cases with no reported pain.<ref name= "Petzold_2014"/> Bilateral severe visual loss (simultaneous or sequential) usually occurs, but there are reports of unilateral visual loss.<ref name= "Petzold_2014"/> Patients can have an associated [[relative afferent pupillary defect]].<ref>{{cite journal | vauthors = Kaut O, Klockgether T | title = 51-year-old female with steroid-responsive optic neuropathy: a new case of chronic relapsing inflammatory optic neuropathy (CRION) | journal = Journal of Neurology | volume = 255 | issue = 9 | pages = 1419–20 | date = September 2008 | pmid = 18575925 | doi = 10.1007/s00415-008-0919-2 }}</ref> CRION is associated with at least one relapse, and up to 18 relapses have been reported in an individual.<ref>{{cite journal | vauthors = Saini M, Khurana D | title = Chronic relapsing inflammatory optic neuropathy | journal = Annals of Indian Academy of Neurology | volume = 13 | issue = 1 | pages = 61–3 | date = January 2010 | pmid = 20436750 | pmc = 2859591 | doi = 10.4103/0972-2327.61280 }}</ref> Intervals between episodes can range from days to over a decade.<ref name= "Kidd_2003"/> Symptoms will improve with corticosteroids, and recurrence characteristically occurs after reducing or stopping steroids.<ref name= "Petzold_2014"/> |
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==Pathogenesis== |
==Pathogenesis== |
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In 2013, the etiology was unknown.<ref name= " |
In 2013, the etiology was unknown.<ref name= "Kidd_2003"/> Given that CRION is responsive to immunosuppressive treatment, it was presumed be immune-mediated,<ref name= "Petzold_2014"/> but this was uncertain as at the time there were no known associated autoimmune antibodies.<ref name= "Petzold_2014"/><ref>{{cite journal | vauthors = Petzold A, Plant GT | title = Diagnosis and classification of autoimmune optic neuropathy | journal = Autoimmunity Reviews | volume = 13 | issue = 4-5 | pages = 539–45 | date = 2014 | pmid = 24424177 | doi = 10.1016/j.autrev.2014.01.009 | url = }}</ref> |
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In 2015, some research pointed to CRION belonging to the [[antiMOG associated encephalomyelitis]] spectrum.<ref> |
In 2015, some research pointed to CRION belonging to the [[antiMOG associated encephalomyelitis]] spectrum.<ref>{{cite journal | vauthors = Chalmoukou K, Alexopoulos H, Akrivou S, Stathopoulos P, Reindl M, Dalakas MC | title = Anti-MOG antibodies are frequently associated with steroid-sensitive recurrent optic neuritis | journal = Neurology(R) Neuroimmunology & Neuroinflammation | volume = 2 | issue = 4 | pages = e131 | date = August 2015 | pmid = 26185777 | pmc = 4496630 | doi = 10.1212/NXI.0000000000000131 }}</ref> |
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As of 2019, the correlation between CRION and [[antiMOG associated encephalomyelitis]] is so high that now CRION is considered the most common phenotype related to myelin oligodendrocyte glycoprotein antibodies (MOG-IgG)<ref> |
As of 2019, the correlation between CRION and [[antiMOG associated encephalomyelitis]] is so high that now CRION is considered the most common phenotype related to myelin oligodendrocyte glycoprotein antibodies (MOG-IgG).<ref>{{cite journal | vauthors = Cantó LN, Boscá SC, Vicente CA, Gil-Perontín S, Pérez-Miralles F, Villalba JC, Nuñez LC, Casanova Estruch B | title = Brain Atrophy in Relapsing Optic Neuritis Is Associated With Crion Phenotype | journal = Frontiers in Neurology | volume = 10 | issue = | pages = 1157 | date = 2019 | pmid = 31736862 | pmc = 6838209 | doi = 10.3389/fneur.2019.01157 }}</ref> |
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</ref> |
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As of 2021, some reports point out a second kind of CRION due to anti-[[phospholipid]] antibodies (anti-PL)<ref>{{cite journal | |
As of 2021, some reports point out a second kind of CRION due to anti-[[phospholipid]] antibodies (anti-PL)<ref>{{cite journal | vauthors = Navarro CE, Arango GJ, Cubides MF | title = Chronic relapsing inflammatory optic neuropathy in a patient with triple antiphospholipid antibody positivity | journal = Neurological Sciences | volume = 42 | issue = 8 | pages = 3439–3443 | date = August 2021 | pmid = 33880676 | doi = 10.1007/s10072-021-05263-6 }}</ref> |
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==Diagnosis== |
==Diagnosis== |
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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<ref name=" |
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.<ref name="Lee_2019" /> Diagnosis requires exclusion of other neurological, ophthalmological, and systemic conditions.<ref name= "Petzold_2014"/> 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).<ref name= "Petzold_2014"/> Corticosteroid responsive optic neuritis not associated with demyelinating disease should also be ruled out, including [[sarcoidosis]], [[systemic lupus erythematosus]], or other systemic autoimmune disease.<ref>{{cite journal | vauthors = Myers TD, Smith JR, Wertheim MS, Egan RA, Shults WT, Rosenbaum JT | title = Use of corticosteroid sparing systemic immunosuppression for treatment of corticosteroid dependent optic neuritis not associated with demyelinating disease | journal = The British Journal of Ophthalmology | volume = 88 | issue = 5 | pages = 673–80 | date = May 2004 | pmid = 15090422 | pmc = 1772147 | doi = 10.1136/bjo.2003.028472 }}</ref> Hereditary causes such as [[Leber’s hereditary optic neuropathy]] are also part of the differential diagnosis.<ref>Lee MD, Song BJ, Odel JG, Sadun AA. Bilateral vision loss responsive to corticosteroids. Survey of Ophthalmology. Nov-Dec 2013;58(6):634-639</ref> |
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In 2014, there were no diagnostic biomarkers or imaging features typical of CRION.<ref name= " |
In 2014, there were no diagnostic biomarkers or imaging features typical of CRION.<ref name= "Petzold_2014"/> [[Anti-nuclear antibody|ANA]], [[B12 Deficiency|B12]], [[Folate Deficiency|folate]], [[thyroid function tests]], anti-[[aquaporin 4]] antibodies (NMO-IgG), and [[Glial fibrillary acidic protein|GFAP]] can facilitate ruling out of other diseases.<ref name= "Petzold_2014"/> Most patients are seronegative for NMO-IgG and GFAP, biomarkers for [[neuromyelitis optica]].<ref name= "Petzold_2014"/> ANA, indicative of [[autoimmune optic neuropathy]], is also generally negative.<ref name= "Petzold_2014"/> CSF can also be evaluated for oligoclonal bands typical of [[multiple sclerosis]], which will not be present in CRION.<ref name= "Kidd_2003"/> Chest X-ray or CT should be ordered if granulomatous optic neuropathy caused by [[sarcoidosis]] is suspected.<ref name= "Petzold_2014"/> |
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MRI imaging can capture optic nerve inflammation, but this finding is not present in all patients,<ref name= " |
MRI imaging can capture optic nerve inflammation, but this finding is not present in all patients,<ref name= "Kidd_2003"/><ref name= "Petzold_2014"/><ref>{{cite journal | vauthors = Sharma A, Khurana D, Kesav P | title = MRI findings in chronic relapsing inflammatory optic neuropathy | journal = BMJ Case Reports | volume = 2013 | issue = | pages = | date = February 2013 | pmid = 23417378 | pmc = 3604485 | doi = 10.1136/bcr-2012-008100 }}</ref> Diffusion tensor imaging has been shown to detect widespread white matter abnormalities in CRION patients with normal MRI findings.<ref>{{cite journal | vauthors = Colpak AI, Kurne AT, Oguz KK, Has AC, Dolgun A, Kansu T | title = White matter involvement beyond the optic nerves in CRION as assessed by diffusion tensor imaging | journal = The International Journal of Neuroscience | volume = 125 | issue = 1 | pages = 10–7 | date = January 2015 | pmid = 24588222 | doi = 10.3109/00207454.2014.896912 }}</ref> |
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Five diagnostic criteria had been proposed in 2014:<ref name= " |
Five diagnostic criteria had been proposed in 2014:<ref name= "Petzold_2014"/> |
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* History of optic neuritis with one relapse |
* History of optic neuritis with one relapse |
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* Objectively measured visual loss |
* Objectively measured visual loss |
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==Treatment== |
==Treatment== |
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Treatment consists of three phases of [[immunotherapy]]: |
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.<ref name= " |
*1. Acute phase: IV steroids (methylprednisolone 1 mg/kg) for 3–5 days or [[plasmapheresis]] are given to restore visual function.<ref name= "Petzold_2014"/> |
||
*2. Intermediate phase: Oral steroids (typically prednisone 1 mg/kg) with taper are given to stabilize vision.<ref name= " |
*2. Intermediate phase: Oral steroids (typically prednisone 1 mg/kg) with taper are given to stabilize vision.<ref name= "Petzold_2014"/> |
||
*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]]<ref name=" |
*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]]<ref name="Lee_2019" />, [[azathioprine]], [[methotrexate]], [[cyclophosphamide]], [[mycophenolate]], [[IVIG]], [[plasma exchange]], [[cyclosporine]], and [[infliximab]] have been used.<ref name= "Petzold_2014"/> |
||
Visual acuity is dramatically worse with CRION than other forms of optic neuritis.<ref name= " |
Visual acuity is dramatically worse with CRION than other forms of optic neuritis.<ref name= "Petzold_2014"/> Treatment with corticosteroids induces prompt relief of pain and improved vision.<ref name= "Kidd_2003"/> At times, patients obtain complete restoration of vision, although exact success rates are unknown.<ref name= "Kidd_2003"/> |
||
==Prognosis== |
==Prognosis== |
||
Recurrence is essentially inevitable in patients without treatment and patients ultimately will require lifelong immunosuppression to prevent relapse.<ref name= " |
Recurrence is essentially inevitable in patients without treatment and patients ultimately will require lifelong immunosuppression to prevent relapse.<ref name= "Petzold_2014"/><ref>{{cite journal | vauthors = Malik A, Ahmed M, Golnik K | title = Treatment options for atypical optic neuritis | journal = Indian Journal of Ophthalmology | volume = 62 | issue = 10 | pages = 982–4 | date = October 2014 | pmid = 25449930 | pmc = 4278124 | doi = 10.4103/0301-4738.145986 }}</ref> |
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==Epidemiology== |
==Epidemiology== |
||
CRION was first described in 2003.<ref name= " |
CRION was first described in 2003.<ref name= "Kidd_2003"/> The disease is rare, with only 122 cases published from 2003 to 2013.<ref name= "Petzold_2014"/> There is female predominance with 59 females (48%), 25 males (20%), and no gender designation for the rest of the 122 reported cases (32%).<ref name= "Petzold_2014"/> Age ranges from 14 to 69 years of age, and the mean age is 35.6.<ref name= "Petzold_2014"/> The disease is noted to occur worldwide and across many ethnicities, with reported cases in all continents except Africa and Australia.<ref name= "Petzold_2014"/> |
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==See also== |
== See also == |
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* [[Optic neuritis]] |
* [[Optic neuritis]] |
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* [[Optic neuropathy]] |
* [[Optic neuropathy]] |
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==References== |
== References == |
||
{{reflist}} |
{{reflist}} |
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Revision as of 03:39, 29 September 2022
| Chronic relapsing inflammatory optic neuropathy | |
|---|---|
| Other names | Chronic relapsing inflammatory optic neuritis |
| Specialty | Ophthalmology |
Chronic relapsing inflammatory optic neuropathy (CRION) 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] or B-cell depleting therapy.[3] Relapse that occurs after reducing or stopping steroids is a characteristic feature.[2]
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.[4] CRION is associated with at least one relapse, and up to 18 relapses have been reported in an individual.[5] Intervals 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]
Pathogenesis
In 2013, the etiology was unknown.[1] Given that CRION is responsive to immunosuppressive treatment, it was presumed be immune-mediated,[2] but this was uncertain as at the time there were no known associated autoimmune antibodies.[2][6]
In 2015, some research pointed to CRION belonging to the antiMOG associated encephalomyelitis spectrum.[7]
As of 2019, the correlation between CRION and antiMOG associated encephalomyelitis is so high that now CRION is considered the most common phenotype related to myelin oligodendrocyte glycoprotein antibodies (MOG-IgG).[8]
As of 2021, some reports point out a second kind of CRION due to anti-phospholipid antibodies (anti-PL)[9]
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.[3] Diagnosis requires exclusion of other neurological, ophthalmological, and systemic conditions.[2] 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).[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.[10] Hereditary causes such as Leber’s hereditary optic neuropathy are also part of the differential diagnosis.[11]
In 2014, there were no 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][12] Diffusion tensor imaging has been shown to detect widespread white matter abnormalities in CRION patients with normal MRI findings.[13]
Five diagnostic criteria had been proposed in 2014:[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
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]
- 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. B-cell depleting therapy[3], 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]
Prognosis
Recurrence is essentially inevitable in patients without treatment and patients ultimately will require lifelong immunosuppression to prevent relapse.[2][14]
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]
See also
References
- ^ a b c d e f g h i j 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.
- ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa 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.
- ^ a b c 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.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ 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.
- ^ 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.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ 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.
- ^ 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(R) Neuroimmunology & Neuroinflammation. 2 (4): e131. doi:10.1212/NXI.0000000000000131. PMC 4496630. PMID 26185777.
- ^ Cantó LN, Boscá SC, Vicente CA, Gil-Perontín S, Pérez-Miralles F, Villalba JC, Nuñez LC, Casanova Estruch B (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.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ 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.
- ^ 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.
- ^ Lee MD, Song BJ, Odel JG, Sadun AA. Bilateral vision loss responsive to corticosteroids. Survey of Ophthalmology. Nov-Dec 2013;58(6):634-639
- ^ Sharma A, Khurana D, Kesav P (February 2013). "MRI findings in chronic relapsing inflammatory optic neuropathy". BMJ Case Reports. 2013. doi:10.1136/bcr-2012-008100. PMC 3604485. PMID 23417378.
- ^ 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.
- ^ 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.
{{cite journal}}: CS1 maint: unflagged free DOI (link)