Acute Phase Of Optic Neuritis Research Articles

Serum Vitamin D Levels and Status in Thai Optic Neuritis Subjects: A Case-Control Study.

ObjectiveTo measure serum total vitamin D or 25-hydroxyvitamin D [25(OH)D] levels and status in immune-based optic neuritis (ON) including neuromyelitis optica spectrum disorder (NMOSD)-ON, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)-ON, autoimmune-ON, and idiopathic-ON and compare them with age- and sex-matched healthy controls. The secondary objective was to analyze the association between serum 25(OH)D levels and ON attack severity (nadir best-corrected visual acuity; nadir BCVA).Materials and MethodsThis was a single-center, case–control study. We enrolled 59 subjects (19 NMOSD-ON, 6 MOGAD-ON, 11 autoimmune-ON, 23 idiopathic-ON) diagnosed with acute immune-based ON (any ON attacks) over 11 years. Electronic medical records were reviewed and demographic data (age at sampling, sex, aquaporin-4 immunoglobulin (AQP4-IgG); myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG); other biomarkers of autoimmune disorders), ON attack severity (nadir BCVA), and serum 25(OH)D levels in the acute phase of ON were collected. Serum 25(OH)D levels of 236 age- and sex-matched healthy controls were assessed.ResultsMean serum 25(OH)D levels were significantly lower in each group of immune-based ON compared with healthy controls (p < 0.001 for each ON group). However, mean serum 25(OH)D levels were not significantly different between four ON groups (NMOSD-ON, 20.18±5.90 ng/mL; MOGAD-ON, 23.07±4.94 ng/mL; autoimmune-ON, 21.14±5.29 ng/mL; idiopathic-ON, 19.56 ±5.12 ng/mL; p = 0.525). All immune-based ON subjects had vitamin D insufficiency or vitamin D deficiency. The prevalences of vitamin D insufficiency and vitamin D deficiency were significantly higher than in healthy controls in each ON group (both p < 0.05 in each ON group). No associations were observed between serum 25(OH)D levels and ON attack severity (nadir BCVA).ConclusionsThai immune-based ON subjects had lower serum 25(OH)D levels and higher prevalence of vitamin D insufficiency and vitamin D deficiency compared with age- and sex-matched healthy controls. Serum 25(OH)D levels were not associated with ON attack severity (nadir BCVA). We highly recommend that serum 25(OH)D levels be screened in all subjects with acute immune-based ON.

MRI of acute optic neuritis (ON) at the first episode: Can we predict the visual outcome and the development of multiple sclerosis (MS)?

Our aim was to assess MRI findings in the acute phase of ON and their correlation with visual acuity at presentation, visual outcome (VO) and MS development, to analyze a possible correlation between lesions number and diagnosis, and to assess correlation between orbits MRI and OCT. We retrospectively studied 37 patients, who presented to our Emergency Department with an ON first episode from January 2015 to January 2017. Patients underwent immediately a complete neuro-ophthalmological evaluation, blood test, CSF analysis. MRI of brain, orbits, cervical spine was executed within 7days from ON onset. Brain MRI was classified as: normal, non-specific, suspected demyelination, lesions with dissemination in space and time. Optic nerves findings were localized in three sites (intra-orbital, canalicular and chiasmal) and classified as: normal, STIR- alteration, altered contrast enhancement. Patients underwent neuro-ophthalmological follow-up and MRI at 6months to assess VO (complete recovery, partial recovery, deficit persistence). Another follow-up at 1year was performed to identify MS or clinically isolated syndrome (CIS). 64.8% patients received a diagnosis of MS; 35% of CIS. Lesions of the optic nerve were found in 65.8%. We observed statistically significant correlation between brain MRI pattern and diagnosis and between lesions number and diagnosis. We observed a statistically significant correlation between orbital MRI pattern and optical coherence tomography (OCT) results. MRI brain findings correlate with development of MS. MRI brain features and lesions number can predict the risk of MS conversion.

Chloride imbalance between serum and CSF in the acute phase of neuromyelitis optica

We collected serum-cerebrospinal fluid (CSF)-paired samples during the acute phase of clinical episodes in MS and NMO patients, together with paired samples from non-MS/NMO patients, to compare the quotients of proteins and electrolytes among them. In NMO, the quotient of chloride was significantly higher in the acute phase of optic neuritis and brain lesions, but it was significantly lower in the acute phase of myelitis. Such findings were not observed in MS or in non-MS/NMO cases. With the coexistence of serum anti-AQP4-Ab, chloride imbalance between serum and CSF could be associated with the clinical episodes in NMO.

Differences in pupillary light reflex between optic neuritis and ischemic optic neuropathy.

ObjectivesTo determine the differences in pupillary light reflex (PLR) between the acute and chronic phases of optic neuritis (ON) and nonarteritic anterior ischemic optic neuropathy (NAION).MethodsThe study included 30 patients with ON and 22 patients with NAION whose PLR were measured by a dynamic pupillometer (PLR-200; NeurOptics Inc., Irvine, USA). Age-matched controls included 58 healthy individuals with normal vision and optic nerve function. Pupil diameters, latency, constriction ratio, constriction velocity and dilation velocity were noted. The differences in PLR measurements were compared among the acute and chronic phases of ON and NAION, and in age-matched controls. Regression analysis determined factors associated with PLR measurements, including visual acuity, color vision defect, visual field defects and retinal nerve fiber layer thickness measurements on optical coherence tomography.ResultsPupillary constriction velocity, constriction ratio and latency were all significantly decreased in the acute phase of ON and NAION. ON showed significantly delayed constriction latency compared to NAION (P = 0.047). Pupillary constriction velocity, constriction ratio and latency were recovered in the chronic phase of ON (P = 0.038, 0.018, and 0.045), however, these parameters were not recovered in NAION (P = 0.693, 0.173 and 0.994).ConclusionsPupillary constriction velocity, constriction ratio, and latency were significantly decreased in the acute phase of ON and NAION compared to normal controls. ON showed delayed constriction latency compared to NAION. Decreased PLR were recovered in the chronic phase of ON, but not in NAION.

Functional plasticity of the visual system in multiple sclerosis.

OPINION article Front. Neurol., 08 April 2015Sec. Multiple Sclerosis and Neuroimmunology Volume 6 - 2015 | https://doi.org/10.3389/fneur.2015.00079

Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis

Post-mortem ganglion cell dropout has been observed in multiple sclerosis; however, longitudinal in vivo assessment of retinal neuronal layers following acute optic neuritis remains largely unexplored. Peripapillary retinal nerve fibre layer thickness, measured by optical coherence tomography, has been proposed as an outcome measure in studies of neuroprotective agents in multiple sclerosis, yet potential swelling during the acute stages of optic neuritis may confound baseline measurements. The objective of this study was to ascertain whether patients with multiple sclerosis or neuromyelitis optica develop retinal neuronal layer pathology following acute optic neuritis, and to systematically characterize such changes in vivo over time. Spectral domain optical coherence tomography imaging, including automated retinal layer segmentation, was performed serially in 20 participants during the acute phase of optic neuritis, and again 3 and 6 months later. Imaging was performed cross-sectionally in 98 multiple sclerosis participants, 22 neuromyelitis optica participants and 72 healthy controls. Neuronal thinning was observed in the ganglion cell layer of eyes affected by acute optic neuritis 3 and 6 months after onset (P < 0.001). Baseline ganglion cell layer thicknesses did not demonstrate swelling when compared with contralateral unaffected eyes, whereas peripapillary retinal nerve fibre layer oedema was observed in affected eyes (P = 0.008) and subsequently thinned over the course of this study. Ganglion cell layer thickness was lower in both participants with multiple sclerosis and participants with neuromyelitis optica, with and without a history of optic neuritis, when compared with healthy controls (P < 0.001) and correlated with visual function. Of all patient groups investigated, those with neuromyelitis optica and a history of optic neuritis exhibited the greatest reduction in ganglion cell layer thickness. Results from our in vivo longitudinal study demonstrate retinal neuronal layer thinning following acute optic neuritis, corroborating the hypothesis that axonal injury may cause neuronal pathology in multiple sclerosis. Further, these data provide evidence of subclinical disease activity, in both participants with multiple sclerosis and with neuromyelitis optica without a history of optic neuritis, a disease in which subclinical disease activity has not been widely appreciated. No pathology was seen in the inner or outer nuclear layers of eyes with optic neuritis, suggesting that retrograde degeneration after optic neuritis may not extend into the deeper retinal layers. The subsequent thinning of the ganglion cell layer following acute optic neuritis, in the absence of evidence of baseline swelling, suggests the potential utility of quantitative optical coherence tomography retinal layer segmentation to monitor neuroprotective effects of novel agents in therapeutic trials.

RNFL thickness in MS-associated acute optic neuritis using SD-OCT: critical interpretation and limitations

Axonal loss is considered a key prognostic factor in diagnosing and monitoring the progress of multiple sclerosis (MS). The purpose of our research was to determine whether the measurement of retinal nerve fibre layer thickness (RNFLT) as measured with high-resolution spectral-domain optical coherence tomography (SD-OCT) differs between optic nerve injury following acute optic neuritis (ON) or following unregistered subclinical axonal damage in patients with MS. High-resolution SD-OCT measurements of RNFLT were initially carried out in the acute phase of ON and again after 3 months, in 25 patients with clinical definite MS and 25 sex- and age-matched healthy controls, all at the University Eye Hospital, Vienna. Conventional OCT-based RNFLT analysis correctly identified all three patients with initial RNFL swelling. However, only two of three acute ON eyes with a history of ON were registered with RNFLT decrease in seven peripapillary sectors (PPs). The remaining have only been revealed using RNFLT symmetry comparison. Two of 22 (9%) first-episode ON eyes were labelled as pathologic. The number and metric RNFL values of pathologically labelled PPs remained unchanged after 3 months. Our age- and sex-match-based measurement model, with patients with MS being plotted individually and towards the fellow eye, identified all acute ON eyes (with a history of prior ON) with RNFLT reduction in 11 PPs. A global RNFL loss was registered in 36.4% (eight of 22 eyes). However, in 72%, or 16 of 22 ON eyes presenting with first episode of acute ON, a segmental RNFL loss was initially registered in 39 PPs upon baseline examination. The number of PPs with identified axonal decrease increased to a total of 48 PPs within the observational period. Spectral-domain optical coherence tomography imaging of identical scanning locations, combined with an optimized scan centring around the optic disc, offers the technological potential of detecting prior, subtle, clinically unregistered optic nerve injury within MS individuals. Significant discrepancy in RNFLT to the potential ON eye may be achieved by comparing OCT metrics with the fellow eye and a sufficient number of age and sex-matched controls.

Nerve Fiber Layer and Macular Thinning Measured with Different Imaging Methods during the Course of Acute Optic Neuritis

To compare retinal nerve fiber layer thickness (RNFLT) and inner macula thickness changes measured with Fourier-domain optical coherence tomography (FD-OCT) and scanning laser polarimetry during the course of acute optic neuritis (ON). Nine eyes of 7 consecutive patients with multiple sclerosis (MS) were prospectively imaged from the onset of ON for 6 to 12 months. Nine healthy eyes were imaged for 12 to 19 months. Retinal nerve fiber layer thickness measured with FD-OCT initially increased in all eyes with diffuse optic disc edema. Inner macula thickness and polarimetric RNFLT decreased already in the acute phase, in all eyes. All parameters stabilized at 2 to 5 months. The relative structural loss was different with the different methods. Poor image quality with polarimetry occurred in 2 eyes in the acute phase of ON. In the control eyes all parameters were stable. Change of RNFLT and macular thickness during the course of acute ON in MS strongly depends on the method used for the measurement. Inner macula thickness, measured with FD-OCT, was especially useful for the follow-up, since it was not influenced by initial disc edema and had consistently high image quality.

Retinal nerve fiber layer thickness is associated with lesion length in acute optic neuritis

Acute optic neuritis occurs with and without papillitis. The presence of papillitis has previously been thought to imply an anterior location of the neuritis, but imaging studies seeking to test this hypothesis have been inconclusive. This prospective observational cohort study included 41 patients with unilateral optic neuritis and 19 healthy volunteers. All patients were evaluated and examined within 28 days of onset of symptoms. The peripapillary retinal nerve fiber layer thickness (RNFLT), an objective quantitative measure of optic nerve head edema, was measured by optical coherence tomography and the length and location of the inflammatory optic nerve lesion were evaluated using MRI. Ophthalmoscopically, 34% of the patients had papillitis. The retinal nerve fiber layer in affected eyes (mean 123.1 microm) was higher during the acute phase than that of fellow eyes (mean 98.1 microm, p < 0.0001) and higher than that in healthy control eyes (mean 97.1 microm, p < 0.0001). The RNFLT was related to the length of the optic nerve lesion (p = 0.0002), but not to the location of the optic nerve lesions (p = 0.72). In this study of the acute phase of optic neuritis, the degree of optic nerve head edema depended upon the extent of the optic nerve lesion, but not on its location. This suggests that factors other than inflammation, such as compromised venous drainage, vascular leakage, impaired axonal transport, and other mechanisms, are involved in the development of optic nerve head edema in optic neuritis.

Colour Doppler imaging evaluation of blood flow parameters in the ophthalmic artery in acute and chronic phases of optic neuritis in multiple sclerosis

Optic neuritis (ON) is a common manifestation of multiple sclerosis (MS). It is caused by the immune-mediated inflammation of the optic nerve. Some vascular factors that may influence blood flow in the ophthalmic artery (OA) have also been suggested as factors in the pathogenesis of ON. The purpose of our study was to evaluate blood flow velocities and resistance (RI) and pulsatile (PI) indices in the OA in both orbits in patients in the acute and chronic phases of unilateral ON and to compare these with equivalent findings in healthy control subjects. Orbital colour Doppler imaging (CDI) was performed in 40 consecutive MS patients during acute unilateral ON prior to corticosteroid treatment. Optic neuritis was diagnosed on the basis of clinical presentation and facultative assessment of visual evoked potentials (VEPs). The peak systolic (PSV) and end-diastolic (EDV) velocities and RI and PI were measured in the OA in both eyes. We compared results from affected and unaffected orbits using the paired t-test. The same measurements were performed in 114 MS patients with a history of acute unilateral ON that occurred > 1 year prior to ultrasound examination. We also measured the same parameters in the middle cerebral arteries (MCAs) on both sides in all subjects in both groups. The same measurements were obtained in healthy controls. The PSV (p < 0.0001), RI (p < 0.0001) and PI (p < 0.0001) in the OA in the eye affected with acute ON were significantly higher than in the unaffected eye. There was no difference in EDV in the OA between affected and unaffected eyes (p > 0.05) in the group with acute ON. We did not observe any significant differences between eyes in either blood flow velocities or the RI or PI (p > 0.05) in the group in the chronic phase of ON or in the control group. All the parameters in the MCAs on both sides were normal in both the acute and chronic groups, as well as in the control group. Pathophysiological changes during acute unilateral ON influence orbital haemodynamics, as is indicated by increased PSV, RI and PI in the OA in eyes affected with ON. However, these changes do not persist over longer periods.

Flupirtine as Neuroprotective Add-On Therapy in Autoimmune Optic Neuritis

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system that results in persistent impairment in young adults. During chronic progressive disease stages, there is a strong correlation between neurodegeneration and disability. Current therapies fail to prevent progression of neurological impairment during these disease stages. Flupirtine, a drug approved for oral use in patients suffering from chronic pain, was used in a rat model of autoimmune optic neuritis and significantly increased the survival of retinal ganglion cells, the neurons that form the axons of the optic nerve. When flupirtine was combined with interferon-beta, an established immunomodulatory therapy for MS, visual functions of the animals were improved during the acute phase of optic neuritis. Furthermore, flupirtine protected retinal ganglion cells from degeneration in a noninflammatory animal model of optic nerve transection. Although flupirtine was shown previously to increase neuronal survival by Bcl-2 up-regulation, this mechanism does not appear to play a role in flupirtine-mediated protection of retinal ganglion cells either in vitro or in vivo. Instead, we showed through patch-clamp investigations that the activation of inwardly rectifying potassium channels is involved in flupirtine-mediated neuroprotection. Considering the few side effects reported in patients who receive long-term flupirtine treatment for chronic pain, our results indicate that this drug is an interesting candidate for further evaluation of its neuroprotective potential in MS.

A double-blind, randomized trial of IV immunoglobulin treatment in acute optic neuritis

Previous studies have suggested that intravenous immunoglobulin (IVIG) may be helpful in the treatment of acute and chronic optic neuritis, although this remained debated. The objective of this study was to evaluate the effect of IVIG in the acute phase of optic neuritis (ON) could improve visual outcome and reduce MRI disease activity 6 months after onset of ON. Sixty-eight patients with ON were randomized within 4 weeks from onset of visual loss. Thirty-four patients were randomized to IVIG 0.4 g/kg body wt, and 34 patients were randomized to placebo.

A double-blind, randomized trial of IV immunoglobulin treatment in acute optic neuritis

To investigate if IV immunoglobulin (IVIG) treatment in the acute phase of optic neuritis (ON) could improve visual outcome and reduce MRI disease activity 6 months after onset of ON. Sixty-eight patients with ON were randomized within 4 weeks from onset of symptoms. Thirty-four patients were randomized to IVIG 0.4 g/kg body wt, and 34 patients were randomized to placebo. Infusions were given at days 0, 1, 2, 30, and 60. Contrast sensitivity, visual acuity, and color vision were measured at baseline and after 1 week, 1 month, and 6 months. Pattern reversal visual evoked potential studies and gadolinium-enhanced MRI were performed at baseline and after 1 and 6 months. Clinical relapses during follow-up were recorded. There was no difference in the primary outcome, contrast sensitivity after 6 months, between patients randomized to treatment with IVIG or placebo. In addition, there was no significant difference in the secondary outcome measures, improvement in the visual function measures and MRI, at any time during follow-up. At baseline, a significantly higher number of patients in the IVIG group had one or more enhancing lesions on MRI and IVIG-treated patients had a significantly higher number of enhancing lesions on MRI than patients treated with placebo. No difference was found in number of patients with one or more enhancing lesions or number of enhancing lesions in subsequent scans between treatment groups. Number of relapses was equal in the two treatment groups during follow-up. There was no effect of IV immunoglobulin (IVIG) on long-term visual function following acute optic neuritis, nor was there an effect of IVIG treatment in reducing latency on visual evoked potentials and thus preserving function of axons of the optic nerve.

MRI, VEP, SEP and biothesiometry suggest monosymptomatic acute optic neuritis to be a first manifestation of multiple sclerosis

A cohort of 50 consecutive patients with acute monosymptomatic optic neuritis (ON) from a defined catchment area joined a prospective study. The aim of this study was to compare the sensitivity of magnetic resonance imaging (MRI), electrophysiological methods (VEP and SEP) and biothesiometry to detect abnormalities in other parts of the CNS than the optic nerves during the acute phase of ON. For each method, a scoring system is proposed. This investigation also hoped to achieve a better understanding of the natural history of ON. MRI proved to be the most sensitive tool (63% abnormal) in confirming a second site of involvement, followed by VEP in the clinically unaffected fellow eye (42%), biothesiometry (32%) and SEP (17%). The combination of all these methods, except for MRI (and VEP in eyes with acute ON), revealed abnormalities in 63% of the patients. When the neurophysiological methods were combined with MRI, 79% of the patients had abnormal findings suggesting additional lesions in the CNS. Hence, MRI and neurophysiological examinations supplement each other and together provide evidence that monosymptomatic ON is usually a first manifestation of MS. The development of definite MS at 1-20 months of follow up in 7 patients (all with abnormal MRI initially) supports this view.

The pattern evoked responses (VER) in optic neuritis.

Five patients presenting clinically accepted signs of optic neuritis served as subjects for a study on EP's (evoked potentials); the patients were tested during the acute phase, the chronic phase and at a stage when no impairment was clinically observed. At the acute phase of optic neuritis the VER was massively altered; in the chronic phase delayed latencies depending upon the impairment of visual acuity and visual fields could be recorded. At the recovery stage, while visual acuity and visual field showed no deficit, not only delayed latencies but also reduction in the amplitude at all stimulation frequencies were recorded.