Chronic Relapsing Inflammatory Optic Neuropathy Research Articles

Neuromyelitis Optica Spectrum Disorder (NMOSD) or Chronic-Relapsing Inflammatory Optic Neuropathy (CRION)?: A Challenge in Diagnosis and Treatment

Abstract
 Introduction : Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory, immune-mediated central nervous system disease targeting the AQP4-water channel membrane protein of the optic nerve and the spinal cord. This case report aims to present a case of seroconverting NMOSD which was initially diagnosed as chronic relapsing inflammatory optic neuropathy (CRION).
 Case Illustration : 15-year-old female with recurrent, steroid-dependent optic neuritis of the LE. During the first attack, brain MRI showed optic nerve inflammation with normal brain findings. Initial test for AQP4-IgG, MOG-Ab and ANA profile were negative. The diagnosis of CRION was made. Treatment with corticosteroid and immunosuppressant agent was maintained for one year. After treatment cessation, however, LE optic neuritis recurred with bilateral lower limb weakness. Spinal MRI showed signs of longitudinal extensive transverse myelitis. Re-testing for AQP4-IgG showed positive result. Diagnosis of NMOSD was made, and the patient was treated with high-dose intravenous corticosteroid followed by oral dose, and immunosuppressant. Final visual acuity of the LE was 1.0, with minimal residual visual field defect and good motor function.
 Discussion : During the initial attack, the patient did not meet the 2015 NMOSD international consensus diagnostic criteria. The AQP4-IgG was negative and no other corresponding signs and symptoms. The criteria was met one year after: optic neuritis, LETM and positive seroconversion of AQP4-IgG.
 Conclusion : Diagnosing NMOSD is at times challenging especially during initial attack. Retesting of the AQP4- IgG is at times necessary in seronegative patients, especially in children showing ADEM-like event with optic neuritis and LETM to achieve diagnosis and proper treatment strategy.

Optic neuritis in Turkish children and adolescents: A multicenter retrospective study

BackgroundVarious etiologies may underlie optic neuritis, including autoantibody-mediated disorders described in the last decade. We re-examined demographic, clinical, laboratory features and prognostic factors in pediatric patients with autoimmune optic neuritis according to current knowledge. MethodsCases of pediatric ON from 27 centers in Türkiye diagnosed between 2009 and 2022 were included for retrospective evaluation. ResultsThe study included 279 patients, 174 females and 105 males, with a female-to-male ratio of 1.65. The average age at onset was 12.8 ± 3.4 years, and mean follow-up, 2.1 years (range: 1–12.1 years). Patients <10 years old were grouped as "prepubertal" and those ≥10 years old as "others”. The diagnoses made at the end of follow-up were multiple sclerosis associated optic neuritis (n = 90, 32.3 %), single isolated optic neuritis (n = 86, 31 %), clinically isolated syndrome (n = 41, 14.7 %), myelin oligodendrocyte glycoprotein antibody associated optic neuritis (n = 22, 7.9 %), and relapsing isolated optic neuritis (n = 18, 6.5 %). Predominant diagnoses were myelin oligodendrocyte glycoprotein antibody associated optic neuritis and acute disseminated encephalomyelitis associated optic neuritis in the prepubertal group and multiple sclerosis associated optic neuritis in the older group. Recurrences were observed in 67 (24 %) patients, including 28 with multiple sclerosis associated optic neuritis, 18 with relapsing isolated optic neuritis, 11 with myelin oligodendrocyte glycoprotein antibody associated optic neuritis, 8 with aquaporin-4 antibody related optic neuritis, and 2 with chronic relapsing inflammatory optic neuropathy. Recurrences were more common among female patients. Findings supporting the diagnosis of multiple sclerosis included age of onset ≥ 10 years (OR=1.24, p = 0.027), the presence of cranial MRI lesions (OR=26.92, p<0.001), and oligoclonal bands (OR=9.7, p = 0.001). Treatment in the acute phase consisted of intravenous pulse methylprednisolone (n = 46, 16.5 %), pulse methylprednisolone with an oral taper (n = 212, 76 %), and combinations of pulse methylprednisolone, plasmapheresis, or intravenous immunoglobulin (n = 21, 7.5 %). Outcome at 12 months was satisfactory, with 247 out of 279 patients (88.5 %) demonstrating complete recovery. Thirty-two patients exhibited incomplete recovery and further combination treatments were applied. Specifically, patients with relapsing isolated optic neuritis and aquaporin-4 antibody related optic neuritis displayed a less favorable prognosis. ConclusionOur results suggest optic neuritis is frequently bilateral in prepubertal and unilateral in peri‑ or postpubertal patients. Age of onset 10 or older, presence of oligoclonal bands, and brain MRI findings reliably predict the development of multiple sclerosis. The risk of developing multiple sclerosis increases mostly during the second and third years of follow-up. Relapsing isolated optic neuritis remains a separate group where the pathogenesis and outcome remain unclear. Investigation of predisposing and diagnostic biomarkers and long follow-up could help to define this group.

Сhronic relapsing inflammatory optic neuropathy: diagnostic strategies and treatment (literature review)

The article presents a review and analysis of scientific works on the problem of chronic relapsing inflammatory optic neuropathy, its diagnostic criteria and treatment methods. Chronic relapsing inflammatory optic neuropathy, first described in 2003, is an autoimmune inflammatory disease of the optic nerve of unknown etiology, accompanied by frequent painful episodes of optic neuritis, with a clear response to steroid therapy and relapses after its withdrawal. An analysis of foreign works published in the E-Library, CrossRef, PubMed, Web of Science, Scopus databases was carried out in order to systematize data on the etiology, pathogenesis, clinical manifestations, diagnostic criteria, differential diagnosis and treatment of this pathological condition. It has been established that chronic recurrent inflammatory optic neuropathy is a rare, recurrent, corticosteroid-dependent optic neuropathy in which there is no other neurological deficit, no etiological factor is identified and it is a diagnosis of exclusion. It is important to identify such patients because the appointment of appropriate immunosuppressive therapy causes remission of the disease.

Clinical spectrum of neuro‐ophthalmological manifestations associated in MOG antibodies in children

AbstractIntroduction: The discovery of the role of MOG antibodies over the last decade has tremendously modified our comprehension of inflammatory disorders of the central nervous system (CNS), especially in children.Objective: To describe the clinical spectrum of neuro‐ophthalmological manifestations associated in MOG antibodies in children.Methods: Literature review using Pubmed and Google Scholar and chosen clinical case series.Results: Three long known clinical entities affecting the optic nerve in children have been recently proven to be largely associated with MOG antibodies: optic neuritis in the context of acute disseminated encephalomyelitis (ADEM); monophasic optic neuritis; chronic relapsing inflammatory optic neuropathy (CRION). ADEM is a child's specificity. CRION often starts during late childhood. These entities can occur after one another in a same child.Conclusions: The absence of overlap between multiple sclerosis, aquaporine 4 antibodies (associated with neuromyelitis optica only) and MOG antibodies, allows for a new, clearer delineation of inflammatory disorders of the CNS in children, closer to the precise classical clinical descriptions than to the semi‐recent criteria‐based “spectra”.

Paediatric optic neuritis: experience from a tertiary referral centre in Malaysia

Background: Optic neuritis typically presents with acute or subacute onset of mild or profound blurring of vision. There are very limited reports regarding optic neuritis in the paediatric population compared to adults from the South Asian region. We report a series of 7 cases of paediatric optic neuritis.&#x0D; Methods: All optic neuritis cases aged less than 12 years old in 2016 were studied retrospectively.&#x0D; Results: Out of 44 patients with optic neuritis, 7 of them were of paediatric age. The mean age was 9.9 years. All patients had sudden onset profound vision loss (range 3/60 to hand movement). Four patients had bilateral involvement, all had reduced colour vision. Three had underlying acute disseminated encephalomyelitis. All were treated with high-dose intravenous corticosteroids. Five patients made full recovery, one patient had partial recovery, and one patient had no visual recovery. Interestingly, none of them had multiple sclerosis (MS) or neuromyelitis optica (NMO) at the time of diagnosis.&#x0D; Conclusion: Prognosis is generally good for isolated cases of paediatric optic neuritis. Outcome of cases secondary to ADEM depends on the degree and extent of demyelination. A diagnosis of chronic relapsing inflammatory optic neuropathy can be considered in recurrent cases that are steroid responsive. None of our cases had underlying MS or NMO during the study period.

Treatment and Relapse Prevention of Typical and Atypical Optic Neuritis

Optic neuritis (ON) is an inflammatory condition involving the optic nerve. Several important typical and atypical ON variants are now recognized. Typical ON has a more favorable prognosis; it can be idiopathic or represent an early manifestation of demyelinating diseases, mostly multiple sclerosis (MS). The atypical spectrum includes entities such as antibody-driven ON associated with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD), chronic/relapsing inflammatory optic neuropathy (CRION), and sarcoidosis-associated ON. Appropriate and timely diagnosis is essential to rapidly decide on the appropriate treatment, maximize visual recovery, and minimize recurrences. This review paper aims at presenting the currently available state-of-the-art treatment strategies for typical and atypical ON, both in the acute phase and in the long-term. Moreover, emerging therapeutic approaches and novel steps in the direction of achieving remyelination are discussed.

Optical Coherence Tomography in Chronic Relapsing Inflammatory Optic Neuropathy, Neuromyelitis Optica and Multiple Sclerosis: A Comparative Study.

Purpose: To examine the optical coherence tomography (OCT) features of the retina in patients with chronic relapsing inflammatory optic neuropathy (CRION) and compare them with those of neuromyelitis optica spectrum disorder (NMOSD), relapsing-remitting multiple sclerosis (RRMS) with and without optic neuritis (ON), and healthy controls (HC). Methods: In this retrospective cross-sectional study, we used spectral domain OCT to evaluate the retinal structure of 14 participants with CRION, 22 with NMOSD, 40 with RRMS with unilateral ON, and 20 HC. The peripapillary retinal nerve fiber layer (pRNFL), total macular volume (TMV), and papillomacular bundle (PMB) were measured, and intra-retinal segmentation was performed to obtain the retinal nerve fiber (RNFL), ganglion cell (GCL), inner plexiform (IPL), inner nuclear (INL), outer plexiform (OPL) and outer nuclear (ONL) layer volumes. Results: The global pRNFL [39.33(±1.8) µm] and all its quadrants are significantly thinner in CRION compared with all other groups (p < 0.05). CRION patients have decreased volumes of TMV, RNFL, GCL, and IPL compared with all other groups (p < 0.05). Conclusion: Severe thinning in pRNFL and thinning in intra-retinal segments of IPL, GCL, RNFL, and TMV could be helpful in differentiating CRION from NMOSD and RRMS.

Disease course of Chronic Relapsing Inflammatory Optic Neuropathy (CRION) in a single care center.

Chronic relapsing inflammatory optic neuropathy (CRION) is a recurrent, idiopathic optic neuritis and is considered as a rare disease. To describe the clinical course during long-term follow-up of patients with a diagnosis of CRION. From a cohort of 1,735 patients with demyelinating disorders, we selected patients aged over 16 years with CRION according to current criteria. Demographic and clinical data, including initial presentation, symptoms, number of relapses, time delay in diagnosis, diagnostic methods, and treatment were obtained from clinical files. Infections, autoimmune diseases, and multiple sclerosis, among other conditions, were ruled out in all patients. We analyzed 30 patients with CRION: 24 women and six men, with mean age of 42.8±10.2 years, median disease course of 7.9 years (5.29-13.1), and median number of attacks of 2 (IQR 2-4). The initial manifestation was ocular pain in 97% and bilateral and sequential affection in 87%. Visual acuity was recovered in 50%, did not improve in 33%, and recovered incompletely in 17%. Antibodies against aquaporin-4 (AQP4-Abs) were negative in 73.3%. Magnetic resonance imaging of the brain was normal in 76.7%. None of the patients evolved to another demyelinating disease over time. Initial treatment was methylprednisolone in 100%, and plasmapheresis in 20%. Currently, all patients are on maintenance treatment with mycophenolate mofetil or rituximab with a decrease in relapsing rate. Diagnosis of CRION is challenging and should be kept in mind. Prompt diagnosis, adequate treatment and close follow-up are essential to prevent disabling sequelae in these patients.

A Case of Chronic Relapsing Inflammatory Optic Neuropathy

Chronic relapsing inflammatory optic neuropathy (CRION) is a recently described form of recurrent isolated subacute optic neuropathy, with accumulating evidence that it is a nosological distinct entity. The condition is highly responsive to systemic steroid treatment and prone to relapse on steroid withdrawal. Diagnosis and management of this condition is often challenging. This 33-year-old lady with family history of multiple sclerosis (MS), with uniocular visual loss of her right eye since 2 years old without apparent cause, presented with reduction of vision and loss of colour vision in the left eye, associated with painful eye movement. There was internuclear ophthalmoplegia but slit lamp examination were unremarkable. She had no other related sensory or motor symptoms. Magnetic resonance imaging (MRI) did not reveal any features of MS. Aquaporin-4 antibody, anti-MOG and gene testing for Leber’s hereditary optic neuropathy were all negative. Metabolic, infective, and other autoimmune causes were also excluded. Visual evoked potential studies of left eye showed a mild reduction in amplitude with no prolongation of latency. Her multiple optic neuritis recurrences were treated with intravenous steroids followed by tapering regime of oral prednisolone with good effect. Knowledge of this rare condition as part of the differential diagnoses of possible aetiologies of optic neuropathy is important among Ophthalmologists, as prompt diagnosis and steroid treatment helped reduce the associated risk of blindness. Multiple relapses after initial successful treatment of inflammatory optic neuropathy should raise the suspicion of CRION.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S19

Chronic Relapsing Inflammatory Optic Neuropathy (CRION).

Purpose of review This review highlights the epidemiology, clinical and radiologic characteristics of chronic relapsing inflammatory optic neuropathy (CRION) and treatment modalities. Recent findings Summary CRION is an inflammatory optic neuropathy that is characterized by a chronic and relapsing course, that is characterized by pain associated with subacute vision loss. It is favorably responsive but highly dependent on corticosteroids with frequent relapses in the setting of steroid tapering. Additional diagnostic biomarkers and further studies are required to better diagnose and treat this rare but potentially debilitating condition.

Effect of botulinum toxin type A on the cervical sympathetic trunk in chronic relapsing inflammatory optic neuropathy

Effect of botulinum toxin type A on the cervical sympathetic trunk in chronic relapsing inflammatory optic neuropathy

Variation in Evolving Optic Neuritis.

The typical natural history of optic neuritis is subjected to important exceptions. Recognition of these exceptions has led to valuable insights regarding specific etiologies of optic neuritis. Exceptions to the natural history of recovering optic neuritis are well-defined (e.g., chronic relapsing inflammatory optic neuropathy), but exceptions to the natural history of evolving optic neuritis are less so. Medical records of patients illustrating an atypical course of evolving optic neuritis were reviewed in a retrospective manner. Each patient was treated by at least one of the authors. Four patients were identified who illustrated an atypical natural history of incipient optic neuritis. Diagnoses included idiopathic optic neuritis, seropositive neuromyelitis optica spectrum disease, anti-myelin oligodendrocyte glycoprotein antibody disease, and multiple sclerosis in 1 patient each. Features of interest included an atypical temporal relationship between development of pain and onset of clinical optic neuropathy, an unusually protracted duration of pain, and an unusually long duration of worsening optic neuropathy before stabilization. This case series illustrates the substantial clinical heterogeneity which may be observed in the evolution of optic neuritis. The temporal relationship between development of pain and onset of clinical optic neuropathy, the duration of pain, and duration of worsening optic neuropathy before stabilization are all subjected to significant variability. Although most patients with optic neuritis present with painful vision loss which progresses over 1 week or less, careful attention to the exceptions described herein may facilitate earlier recognition of diagnostically challenging cases.

Crohn-related Chronic Relapsing Inflammatory Optic Neuropathy.

Crohn-related Chronic Relapsing Inflammatory Optic Neuropathy.

Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis: Diagnosis and Treatment

Optic neuritis (ON) is a frequent manifestation of aquaporin-4 (AQP4) antibody-mediated neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disorders, MOGAD). The past few years have seen major advances in the diagnosis and treatment of these two relatively new entities: international diagnostic criteria for NMOSD and MOG-EM have been proposed, improved antibody assays developed, and consensus recommendations on the indications and methodology of serological testing published. Very recently, the results of four phase III trials assessing new treatment options for NMOSD have been presented. With eculizumab, a monoclonal antibody inhibiting complement factor C5, for the first time a relapse-preventing long-term treatment for NMOSD - which has so far mostly been treated off-label with rituximab, azathioprine, and other immunosuppressants - has been approved. Data from recent retrospective studies evaluating treatment responses in MOG-ON suggest that rituximab and other immunosuppressants are effective also in this entity. By contrast, many drugs approved for the treatment of multiple sclerosis (MS) have been found to be either ineffective or to cause disease exacerbation (e.g., interferon-β). Recent studies have shown that not only NMOSD-ON but also MOG-ON usually follows a relapsing course. If left untreated, both disorders can result in severe visual deficiency or blindness, though MOG-ON seems to have a better prognosis overall. Acute attacks are treated with high-dose intravenous methylprednisolone and, in many cases, plasma exchange (PEX) or immunoadsorption (IA). Early use of PEX/IA may prevent persisting visual loss and improve the long-term outcome. Especially MOG-ON has been found to be frequently associated with flare-ups, if steroids are not tapered, and to underlie many cases of "chronic relapsing inflammatory optic neuropathy" (CRION). Both NMOSD-ON and MOG-ON are often associated with simultaneous or consecutive attacks of myelitis and brainstem encephalitis; in contrast to earlier assumptions, supratentorial MRI brain lesions are a common finding and do not preclude the diagnosis. In this article, we review the current knowledge on the clinical presentation, epidemiology, diagnosis, and treatment of these two rare yet important differential diagnoses of both MS-associated ON und idiopathic autoimmune ON.

Хронічна рецидивуюча запальна оптична нейропатія: огляд двох клінічних випадків

Aim. To study the features of the clinical course, diagnosis and treatment of chronic relapsing inflammatory optic neuropathy based on clinical cases. Materials and Methods. Clinical cases of chronic relapsing inflammatory optic neuropathy in two men are presented. The patients underwent neurological and ophthalmological examination, laboratory blood tests, testing of cerebrospinal fluid, magnetic resonance imaging of the brain and spinal cord, perimetry, ophtalmoscopy, optical coherence tomography, ultrasound examination of internal organs and of the branches of the aortic arch, and chest radiography. Results and Discussion. Two cases of chronic relapsing inflammatory optic neuropathy were described in two men aged 44 and 22 years. Episodes of recurrent optic neuritis, both unilateral and bilateral, were observed in patients; their vision improved after corticosteroid therapy. No etiological factors or comorbidities capable of causing the condition were identified. The older patient had 8 attacks of recurrent optic neuritis, with complete recovery of vision after therapy in seven cases, and partial recovery after the last relapse . The 22-year-old patient endured 5 episodes without complete recovery of vision after treatment. Based on the diagnostic criteria of chronic recurrent inflammatory optic neuropathy, this diagnosis was suspected in the patients. Conclusions. Chronic relapsing inflammatory optic neuropathy is a rare pathology whose clinical manifestations must meet diagnostic criteria. Patients with recurrent optic neuritis are to be well examined, in order to make a correct diagnosis and prescribe adequate therapy. Clinical manifestations of chronic relapsing inflammatory optic neuropathy tend to regress and stabilize against a background of immunosuppressive therapy. Keywords: chronic relapsing inflammatory optic neuropathy, clinical cases

A review of chronic relapsing inflammatory optic neuropathy

Chronic relapsing inflammatory optic neuropathy (CRION), initially described in 2003, is a form of recurrent optic neuritis (ON) that has relatively good response/dependency to steroid treatment. In demyelinating ON, patients present with periorbital ache and pain elicited by eye movement, which usually begins insidiously and worsens, in synchrony with or preceding a reduction in vision, which deteriorates over days. The etiology of CRION is unknown. However, the excellent response to corticosteroids and the need for immunosuppressive therapy to prevent relapse suggests an immunomediated origin.

Optic neuritis: Differential diagnosis and management

Optic neuritis is one of the commonest conditions presenting acutely to both Ophthalmic and Neurological services worldwide. In the past 20 years understanding of the management of optic neuritis has departed from an emphasis on those cases associated with multiple sclerosis (emanating from Europe and North America) where there remains no treatment that influences the outcome. We now recognise four additional categories phenotypically and serologically: 1) A post-infectious monophasic disorder 2) An autoimmune, episodic relapsing condition associated with neuromyelitis optica (NMO) and the Aquaporin 4 antibody 3) An autoimmune episodic relapsing condition associated with the myelin oligodendrocyte (MOG) antibody which may show features of NMO and 4) A corticosteroid dependent condition requiring long term immune suppression known as chronic relapsing inflammatory optic neuropathy (CRION), some of which cases are found to have the MOG antibody. In this presentation I will discuss the approach from the point of view of a clinician faced with a patient presenting with his/her first ever episode of optic neuritis. How are the decisions to be made regarding diagnosis and treatment to prevent irreversible visual loss in this and any future attacks, where "time is vision"?

Do Myelin Oligodendrocyte Glycoprotein Antibodies Represent a Distinct Syndrome?

Do Myelin Oligodendrocyte Glycoprotein Antibodies Represent a Distinct Syndrome?

Aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in immune-mediated optic neuritis at long-term follow-up

ObjectivesTo re-evaluate serum samples from our 2007 cohort of patients with single-episode isolated ON (SION), recurrent isolated ON (RION), chronic relapsing inflammatory optic neuropathy (CRION), multiple sclerosis-associated ON (MSON) and...

Chronic relapsing inflammatory optic neuropathy: a literature review

Chronic relapsing inflammatory optic neuropathy (CRION) is an inflammatory disease characterized by painful recurrent episodes of optic neuritis with clear response to steroids and relapses with treatment withdrawal. To performed a systematic review of the literature about CRION, since 2003 to present in medical database. We excluded pediatric or animal research articles. Search terms: CRION, chronic relapsing inflammatory optic neuropathy, recurrent optic neuritis, steroid dependent optic neuritis, and immunosuppression dependent optic neuritis. CRION is a relapsing optic neuritis of unknown aetiology. The strong response to corticosteroids to avoid recurrence suggests that it might be an immune-mediated disease. CRION typically presents as a subacute and recurrent optic neuropathy with severe visual loss. The principal differential diagnoses are the demyelinating (multiple sclerosis, neuromyelitis optica spectrum disorders and anti-MOG), systemic (mostly sarcoidosis) and infectious diseases. CRION has a dramatic and dependent corticoids response; to avoid adverse events, we use immunosuppressive treatment in long-term. CRION is a rare, recurrent and cortico-dependent disease of optic nerve. An early diagnosis and accuracy treatment will improve the prognosis.