Inflammatory Optic Neuropathy Research Articles

The investigation of acute optic neuritis: a review and proposed protocol.

Optic neuritis is an inflammatory optic neuropathy that affects many patients with multiple sclerosis (MS) at some point during their disease course. Differentiation of acute episodes of MS-associated optic neuritis from other autoimmune and inflammatory optic neuropathies is vital for treatment choice and further patient management, but is not always straightforward. Over the past decade, a number of new imaging, laboratory and electrophysiological techniques have entered the clinical arena. To date, however, no consensus guidelines have been devised to specify how and when these techniques can be most rationally applied for the diagnostic work-up of patients with acute optic neuritis. In this article, we review the literature and attempt to formulate a consensus for the investigation of patients with acute optic neuritis, both in standard care and in research with relevance to clinical treatment trials.

White matter involvement beyond the optic nerves in CRION as assessed by diffusion tensor imaging

Background: Chronic relapsing inflammatory optic neuropathy (CRION) is an inflammatory optic neuropathy, characterized by relapses and remissions in patients with normal brain and spinal magnetic resonance imaging (MRI). Discrepancy from other demyelinating diseases is important, and it is still uncertain whether CRION is restricted to the optic pathways or it affects other brain white matter (WM) structures. Objective: To assess WM structure in patients with CRION by using diffusion tensor imaging (DTI). Methods: DTI was performed in six CRION patients and six age- and sex-matched healthy controls on a 3 T scanner. Tract-based spatial statistics (TBSS) was used for voxelwise statistical analysis of DTI data. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) measures were obtained. Results: TBSS analysis revealed two different patterns of WM alterations in patients with CRION. The optic chiasm and connected structures had significantly higher FA and lower RD, AD and MD in the patients than in the healthy controls. On the other hand, anterior frontal bundles of inferior fronto-occipital tracts, left uncinate fascicule and internal capsule showed decreased FA and increased RD. No correlation was found between the clinical variables and diffusion measures. Conclusion: WM appearing normal on brain MRI shows widespread abnormalities in a cohort of CRION patients as assessed by DTI.

Treatment options for atypical optic neuritis.

Context:Optic neuritis (ON) is defined as inflammation of the optic nerve and can have various etiologies. The most common presentation in the US is demyelinating, or “typical” ON, usually associated with multiple sclerosis. This is in contrast to “atypical” causes of ON, which differ in their clinical presentation, management, and prognosis. These atypical cases are characterized by lack of eye pain, exudates, and hemorrhages on exam, very severe, bilateral or progressive visual loss, or with failure to recover vision.Aims:The aim was to describe the clinical presentations of atypical ON and their treatments.Settings and Design:Review article.Materials and Methods:Literature review.Results:Types of atypical ON identified include neuromyelitis optica, autoimmune optic neuropathy, chronic relapsing inflammatory optic neuropathy, idiopathic recurrent neuroretinitis, and optic neuropathy associated with systemic diseases. Atypical ON usually requires corticosteroid treatment and often will require aggressive immunosuppression.Conclusions:Unlike demyelinating ON, atypical ON requires treatment to preserve vision.

Microcystic Changes in the Retinal Internal Nuclear Layer Associated with Optic Atrophy: A Prospective Study

Purpose. This study aimed at assessing the prevalence of pathologies presenting retinal inner nuclear layer (RINL) microcystic perimacular changes associated with optic nerve atrophy (OA). The charts of patients presenting a significant defect of the Retinal Nerve Fiber Layer (RNFL) were included prospectively in this study. Patients were classified according to the etiology of the RNFL defect. Two hundred and one eyes of 138 patients were enrolled in this analysis. Retinal images obtained showed the typical hyporeflective perifoveal crescent-shaped lesion composed of small round hyporeflective microcysts confined to the RINL in 35.3% of the eyes. Those findings were found in 75% of eyes presenting hereditary OA, 50% of eyes presenting ischemic optic neuritis, 50% of eyes with drusen of the optic nerve (ON), 44.4% of eyes presenting a compressive OA, 32% of eyes presenting inflammatory optic neuropathy from multiple sclerosis, 18.5% of eyes presenting OA from undetermined origin, and 17.6% of eyes having primary open-angle glaucoma. This study demonstrates that microcystic changes in RINL are not specific to a disease but are found in OA of various etiologies. Moreover, their incidence was found to be dependent upon the cause of OA, with the highest incidence occurring in genetic OA.

Neuro-ophthalmology update

This review summarizes the most relevant articles from the field of neuro-ophthalmology published in the Journal of Neurology from January 2012 to July 2013. With the advent of video-oculography, several articles describe new applications for eye movement recordings as a diagnostic tool for a wide range of disorders. In myasthenia gravis, anti-Kv1.4 and anti-Lrp4 have been characterized as promising novel autoantibodies for the diagnosis of hitherto 'seronegative' myasthenia gravis. Several articles address new diagnostic and therapeutic approaches to neuromyelitis optica, which further sharpen its profile as a distinct entity. Additionally, 4-aminopyridine has become a standard therapeutic for patients with cerebellar downbeat nystagmus. Finally, revised diagnostic criteria have been proposed for chronic relapsing inflammatory optic neuropathy based on a careful literature review over the last decade.

Optic Neuritis Is Associated with Inner Nuclear Layer Thickening and Microcystic Macular Edema Independently of Multiple Sclerosis

BackgroundMicrocystic macular edema (MME) and inner nuclear layer thickening (INL) were described in multiple sclerosis (MS) and neuromyelitis optica (NMO) patients using optical coherence tomography (OCT). The cause of these findings is currently unknown and a relation to inflammatory or degenerative processes in the optic nerve is discussed.ObjectiveThe aim of our study was to investigate whether INL thickening and MME are related to optic neuritis (ON) in various neuro-inflammatory disorders causingON: MS, NMO and chronic inflammatory optic neuropathy.MethodsWe retrospectively analyzed data from 216 MS patients, 39 patients with a clinically isolated syndrome, 20 NMO spectrum disorder patients, 9 patients with chronic inflammatory optic neuropathy and 121 healthy subjects. Intra-retinal layer segmentation was performed for the eyes of patients with unilateral ON. Scanning laser ophthalmoscopy (SLO) images were reviewed for characteristic ocular fundus changes.ResultsIntra-retinal layer segmentation showed that eyes with a history of ON displayed MME independent INL thickening compared to contralateral eyes without previous ON. MME was detected in 22 eyes from 15 patients (5.3% of all screened patients), including 7 patients with bilateral edema. Of these, 21 had a prior history of ON (95%). The SLO images of all 22 MME-affected eyes showed crescent-shaped texture changes which were visible in the perifoveal region. A second grader who was blinded to the results of the OCT classified all SLO images for the presence of these characteristic fundus changes. All MME eyes were correctly classified (sensitivity = 100%) with high specificity (95.2%).ConclusionThis study shows that both MME and INL thickening occur in various neuro-inflammatory disorders associated with ON. We also demonstrate that detection and analysis of MME by OCT is not limited to B-scans, but also possible using SLO images.

SIRT1 Promotes RGC Survival and Delays Loss of Function Following Optic Nerve Crush

Activation of SIRT1 deacetylase prevents retinal ganglion cell (RGC) loss in experimental optic neuritis, an inflammatory optic neuropathy. While mechanisms of this effect are not known, evidence suggests it involves reduction of oxidative stress. We hypothesized that SIRT1 reduces RGC loss due to oxidative stress in noninflammatory optic neuropathies, and examined effects following traumatic injury. Optic nerve crush injury was induced in wild-type C57BL/6 mice, mice overexpressing SIRT1, and mice with conditional deletion of SIRT1 in neurons. Wild-type mice were treated daily with vehicle or 250 mg/kg resveratrol, a naturally occurring polyphenol that activates SIRT1. RGC function was assessed by pupillometry and optokinetic responses (OKR), and RGC survival was measured. Superoxide levels were measured to assess oxidative stress. Significant decreases in pupillary light responses, OKR and RGC survival occurred 1 week after optic nerve crush, with progressive worsening at 2 to 4 weeks. Resveratrol treatment and SIRT1 overexpression delayed RGC loss and loss of pupillary light responses following optic nerve crush, although no change in RGC loss occurred in neuronal SIRT1-deficient mice. A significant accumulation of superoxide was detected in wild-type optic nerves following crush, and was reduced in mice overexpressing SIRT1 or treated with resveratrol. SIRT1 delays RGC loss following traumatic injury. Effects are associated with reduced oxidative stress. Results suggest SIRT1-activating drugs may have a specific role in preventing traumatic optic nerve damage, and suggest a broader role for this strategy in treating a variety of optic neuropathies that may include a component of oxidative stress.

Chronic relapsing inflammatory optic neuropathy: a systematic review of 122 cases reported

Chronic relapsing inflammatory optic neuropathy (CRION) is an entity that was described in 2003. Early recognition of patients suffering from CRION is relevant because of the associated risk for blindness if treated inappropriately. It seems timely to have a clinical review on this recently defined entity. A systematic literature review, irrespective of language, retrieved 22 case series and single reports describing 122 patients with CRION between 2003 and 2013. We review the epidemiology, diagnostic workup, differential diagnosis, and treatment (acute, intermediate, and long term) in view of the collective data. These data suggest that CRION is a distinct nosological entity, which is seronegative for anti-aquaporin four auto-antibodies and recognized by and managed through its dependency on immuno-suppression. Revised diagnostic criteria are proposed in light of the data compromising a critical discussion of relevant limitations.

Mimics and Rare Presentations of Pediatric Demyelination

This article reviews the features that should prompt consideration of diseases that mimic acquired demyelinating syndromes and multiple sclerosis using vignettes to highlight unusual clinical and radiologic features. Cases of transverse myelitis, spinal infarction, acute disseminated encephalomyelitis, fever-induced refractory epileptic encephalopathy in school-aged children, small-vessel vasculitis, Griscelli syndrome type 2, cysticercosis, vitamin B12 deficiency, and chronic relapsing inflammatory optic neuropathy are presented.

Radiological evolution and delayed resolution of an optic nerve tuberculoma: Challenges in diagnosis and treatment

Optic nerve tuberculomas are rarely reported and their natural history, prognosis, and duration of required treatment remain unclear. A 40-year-old immunocompetent male presented with complete loss of vision in his right eye, which had evolved over 6 weeks. He had optic atrophy on examination. Initial imaging showed right optic nerve swelling and thickening suggesting an infiltrative inflammatory optic neuropathy (infectious or noninfectious). Serial imaging revealed appearance of ring enhancement with a necrotic centre. Biopsy and culture of the coexistent parietal lobe lesion revealed Mycobacterium tuberculosis. Persistent optic nerve granuloma with evidence of radiological improvement was noted at 18 months follow-up with antituberculous therapy (ATT). Visual recovery could not be achieved. The salient features in this case include the clinical presentation initially mimicking an infiltrative or compressive optic neuropathy, rapidradiological evolution into a tuberculoma, subtle paradoxical radiological worsening after initiation of ATT and persistence of granuloma on follow up scan. The challenges involved in early diagnosis and during the treatment course will be discussed.

Bilateral vision loss responsive to corticosteroids

A 48-year-old woman presented with painless bilateral vision loss that began in the left eye and responded to steroids, followed by vision loss in the right eye one day after completing her steroid taper. Diagnosis was complicated by a positive screening test for Leber hereditary optic neuropathy and a negative workup for demyelinating disease. Steroid-dependent optic neuropathies such as autoimmune optic neuropathy and chronic relapsing inflammatory optic neuropathy were considered in the differential. Seven months after initial presentation, the patient developed a new periventricular white matter lesion, lesions on her cervical and thoracic spinal cord, bilateral leg weakness, and sensory loss consistent with multiple sclerosis.

‘BLINDNESS CURED!’: RESPONSE TO LATE STEROIDS IN CRION

A 50-year-old man presented with a 7 year history of visual loss. He was medically retired as a doctor. His right eye was amblyopic. Initial loss was subacute, bilateral and...

Inflammatory optic neuropathies

AbstractAcute inflammatory optic neuropathy result frequently from a demyelinating disorder, multiple sclerosis being often the underlying pathology. However, the possibility of other causes of inflammatory optic neuropathies should be entertained when the clinical presentation is atypical (for example, massive disc swelling, painless visual loss, bilateral simultaneous optic neuropathy or, relentless progression of visual loss). This presentation will discuss the clinical presentations and differential diagnosis of typical optic neuritis, including Devic’s syndrome (neuromyelitis optica), neuroretinitis, sarcoidosis, acute idiopathic blind spot enlargement, optic perineuritis, Leber’s hereditary optic neuropathy. At the end of the session, participants should be able to recognize the typical and atypical features of optic neuritis.

Chronic Relapsing Inflammatory Optic Neuropathy: A Differential Diagnosis from Multiple Sclerosis (P02.151)

Objective: We report 3 cases of possible CRION (chronic relapsing inflammatory optic neuritis), review the literature and discuss its differential diagnoses. Background Currently there is no population-based data on the natural history, prognosis and treatment plan for CRION (Kidd et al Brain 2003). Optic neuritis (ON) is the initial presentation in 20% of cases of MS. Recurrent ON affecting either eye, excluding cases of ON appearing in systemic disease, occurs in 20 to 36% of all cases with a documented first attack with ON. Relapsing-remitting inflammatory optic neuropathy is rare, often bilateral, and typically steroid responsive. Design/Methods: We reviewed 3327 patients in the MS Clinic in London, Ontario seen in the last decade. specifically searched for clinically isolated syndrome (CIS) and ON cases to be included in this review. Data were collected regarding demographics, past medical history, history of present illness, brain MRI scans and laboratory tests. We used the McDonald 2005 diagnostic criteria for MS and the Kidd et al 2003 definition for CRION. Results: We found 3 cases compatible with the definition CRION. One male and 2 females, caucasian, ages 31 to 46 years old, followed for over 12 months and up to 10 years. Oligoclonal bands in CSF were negative. Brain and spine MRI did not meet diagnostic criteria for MS and did not reveal any other pathology. We ruled out Leber9s hereditary optic neuropathy, Neuromyelitis optica, Vitamin B12 deficiency, Sarcoidosis, Rheumatological or connective tissue diseases, and Multiple Sclerosis. Conclusions: CRION should be considered in the differential diagnosis of MS, however, it is a diagnosis of exclusion, distinguished from demyelinating disease, granulomatous, infectious, and other inflammatory or infiltrative ON. Steroid-sparring agents should be considered in the long term while pulse steroids appear to be the treatment of choice for relapses until further evidence is available. Disclosure: Dr. Di Guglielmo has nothing to disclose. Dr. Kremenchutzky has received personal compensation for activities with MS Society of Canada, the End MS Research and Training Network, the Research Scientific Foundation of the MS Society of Canada, and the Canadian Institute of Health Research, Bayer Pharmaceuticals, Biogen Idec, Serono, Inc., Genzyme Corporation, Novartis, Sanofi-Aventis Pharmaceuticals, and Teva Neuroscience as a speaker, researcher and/or consultant. Dr. Kremenchutzky has received research support from MS Society of Canada, Bayer Pharmaceuticals Corporation, Biogen Idec, Serono, Inc., Teva Neuroscience, Genetech, Inc., and Novartis.

Avaliação da camada de fibras nervosas da retina nas afecções neuroftalmológicas da via óptica anterior

Retinal nerve fiber evaluation is important in the diagnosis and management of several diseases of the anterior visual pathway. In this report we review the clinical findings and the current techonologies avalilable to analyse the retinal nerve fiber layer. We furthermore review the main findings in several disease of the anterior visual pathways including inflammatory, ischemic, toxics, hereditary, compressive and traumatic optic neuropathies as well as lesion of the optic chiasm, optic tract and lateral geniculate body. Retinal nerve fiber [...]

Neuropathie optique unilatérale récidivante liée au VIH

HIV-related optic neuropathy is rare compared to optic neuropathies secondary to opportunistic infections in seropositive patients. We report the case of a 39-year-old HIV-positive woman referred for unilateral visual loss leading to the diagnosis of recurrent, unilateral, inflammatory optic neuropathy directly associated with HIV. Despite initial recovery after steroid treatment, she relapsed twice. Absence of any opportunist infections or toxic causes and presence of a very high viral load due to non-compliance with treatment led to the diagnosis of HIV-related optic neuropathy. Steroids and effective anti-retroviral treatment resulted in definitive and complete recovery. Inflammatory, degenerative and/or vascular mechanisms have been hypothesized to explain the occurrence of these rare HIV-related optic neuropathies. This diagnosis remains a diagnosis of exclusion to be considered in the work-up of seropositive patients with optic neuropathies.

Recurrent subacute visual loss presenting in a 52-year-old Caucasian woman with chronic relapsing inflammatory optic neuropathy: a case report

IntroductionChronic relapsing inflammatory optic neuropathy is a recently described form of recurrent isolated subacute optic neuropathy. The condition is highly responsive to systemic steroid treatment and prone to relapse on steroid withdrawal. A complete work up for demyelination, autoimmune disease and sarcoidosis must be made before considering chronic relapsing inflammatory optic neuropathy.Case presentationWe describe the case of a 52-year-old Caucasian woman who presented with isolated subacute optic neuropathy. There was no evidence of demyelination, autoimmunity or sarcoidosis. There was an abrupt and prompt response to systemic corticosteroids and a relapse of the condition on steroid withdrawal.ConclusionsChronic relapsing inflammatory optic neuropathy requires careful consideration and differentiation from demyelinating optic neuritis and ischemic optic neuropathy since the treatment is different and the outcome without treatment is likely to be poor. The importance of identifying these patients has considerable clinical implications as the condition is highly responsive to steroids.

A case of chronic relapsing inflammatory optic neuropathy (crion)

AbstractPurpose The chronic relapsing inflammatory optic neuropathy (CRION) is a recurrent optic neuropathy not associated with any demyelinating or systemic desease, characterized by the need for prolonged immunosuppressive therapy to prevent relapse.Methods We report the case of a 32 year old man who presented three episodes of optic neuritis in the left eye over a period of 8 months. Each episode remitted quickly with intravenous steroids and resorted after gradual withdrawal thereof. The initial visual acuity in left eye was counting fingers, had relative afferent pupillary defect and diffuse edema of the optic nerve. All systemic examinations were normal (analytics, and serology tests, imaging studies, lupus anticoagulant, ECA and autoimmunity tests).Results After CRION suspected, corticosteroid treatment was decided at a dose of 1mg/kg/day maintained in decreasing doses associated with azathioprine, and response to treatment was favorable, with no new episodes. Actually, visual acuity is 7/10 , there are palidness optic disc and inferior visual field lost in perimetry due to optic neuritis.Conclusion CRION is a recurrent optic neuritis, corticoid dependent, not associated with any neurological deficit or autoimmune disease. Severe visual loss, associated with persistence of pain after onset of visual loss and frequent recurrences should make us suspect this entity.

Preserving and Restoring Optic Nerve Function

Preserving and Restoring Optic Nerve Function

MRI Demonstrates Restricted Diffusion in Distal Optic Nerve in Atypical Optic Neuritis

A 4-year-old healthy girl with acute visual loss in the right eye had ophthalmoscopic evidence of a swollen optic disc combined with central retinal artery and vein occlusion in the affected eye. MRI showed that the intraorbital optic nerve on the affected side was thickened and enhancing. Diffusion-weighted imaging showed restricted diffusion in the distal intraorbital segment of the optic nerve, consistent with infarction attributed to compression or inflammation of the vessels serving the optic nerve and retina. Although such clinical phenomena have been described previously, this is the first patient to demonstrate restricted diffusion in an inflammatory optic neuropathy. The presence of restricted diffusion is helpful in excluding a neoplastic cause of a thickened optic nerve.