History Of Optic Neuritis Research Articles

Transbulbar B-mode sonography in multiple sclerosis without optic neuritis; clinical relevance

ObjectiveTrans bulbar B-mode sonography (TBS) is a recently proposed method but there is little known about its diagnostic accuracy in patients with multiple sclerosis without acute optic neuritis. Therefore we assessed the correlation between OND, ONSD and OND/ONSD ratio with clinical/para clinical parameters. MethodsIn a comparative study, we intended to examine possible differences in optic nerve diameter (OND) and optic nerve sheath diameter (ONSD) between 60 patients with multiple sclerosis (MS) and 60 individuals as matched healthy controls. ResultsThe OND, ONSD and OND/ONSD ratio in both eyes showed significantly lower amounts in patients compared to healthy controls (p < 0.05). There were no correlations, between either OND or ONSD and factors including gender, age, P100 amplitude, disease duration, history of optic neuritis and number of T2 lesions in MRI (P ≥ 0.05). Expanded disability status scale (EDSS) and p100 Latency were correlated with both OND and ONSD values (P < 0.05). ConclusionsTBS showed significantly lower amounts of OND, ONSD and OND/ONSD ratio in MS patients without current attack compared to their healthy controls indicating a subclinical axonal loss over time. It is suggested that TBS could be an applicable tool for early detection of optic nerve damages along with clinical and para-clinical findings.

Visual Function and Disability Are Associated with Increased Retinal Volumetric Vessel Density in Patients with Multiple Sclerosis

The goal of this study was to determine the volumetric vessel density (VVD) in the intraretinal layers and its relationship with visual function and disability in patients with multiple sclerosis (MS). Cross-sectional study. A total of 80 patients with relapsing-remitting MS and 99 age- and sex-matched healthy controls (HC) were recruited. The retinal microvascular network in the macular area was imaged using optical coherence tomography angiography in 123 eyes without a history of optic neuritis (ON) (MSNON) and 36 eyes with a history of ON (MSON). The VVD was calculated as the vessel densities in the retinal vascular network (RVN), superficial vascular plexus (SVP), or deep vascular plexus (DVP) of an annulus (0.6-2.5mm in diameter), divided by the corresponding tissue volume of the intraretinal layers respectively. The VVD of RVN and DVP in MSNON were significantly higher than in HC (P < .05). The VVD of RVN, SVP, and DVP in MSON were significantly higher than in MSNON and HC (P < .05). The VVD in both RVN and SVP were positively related to EDSS and disease duration, but negatively related to low-contrast letter acuity (P < .05). The VVD measurements were also negatively and strongly related to the corresponding tissue volumes (P < .05). This is the first study to reveal increased retinal VVD in patients with relapsing-remitting MS. The measurements of VVD in the RVN and SVP were related to disability and visual function, which may be developed as image markers for tracking disease progression.

Inner Retinal Layer Disease: Multiple Sclerosis.

Objectives:This study was an analysis of the retinal layer thickness in multiple sclerosis (MS) patients using spectral-domain optical coherence tomography (SD-OCT).Methods:A total of 42 patients diagnosed in the neurology clinic with MS according to the McDonald Criteria and 21 healthy individuals were included in the study and 4 groups were created. The first group comprised 21 eyes of 21 MS patients without eye involvement, the second group was made up of 21 eyes of 21 MS patients with a history of optic neuritis, the third group included the other eye of patients in the second group without a history of optic neuritis, and the fourth group was a control group of 21 eyes of 21 healthy individuals. SD-OCT was used to visualize and measure the retinal layers and the thickness was analyzed using the device software.Results:The mean age of the patient groups was 35.39±7.52 years, while it was 32.86±2.60 years in the control group. The mean duration of the disease was 9.81±6.65 years with a mean of 4.84±2.38 attacks. The ganglion cell layer (GCL) and the inner plexiform layer (IPL) of all of the patients were thinner compared with the control group in the parafoveal and perifoveal areas. All regions of the retinal nerve fiber layer (RNFL) of patients in the second group were thinner than those of the control group. The RNFL, GCL, and IPL in the central, parafoveal and perifoveal macular rings in group 3 were thinner than the group 1 measurements; however, this difference was not statistically significant. Although the RNFL, GCL, and IPL layer thicknesses were lower in group 2 than group 3, only the difference in the parafoveal GCL thickness was statistically significant.Conclusion:This study demonstrated that MS affects retinal layer thickness, and particularly the inner retinal layers.

Detailed Evaluation of Macular Ganglion Cell Complex in Patients with Multiple Sclerosis.

Introduction:Retinal nerve fiber layer thickness has been used for monitoring of disease activity in patients with multiple sclerosis (MS). Macular ganglion cell complex (GCC) layer of retina also can be measured by OCT and has been suggested as a potential biomarker in MS. In this study we investigated the macular GCC and its role as a potential biomarker in patients with Multiple Sclerosis (MS).Methods:A prospective cohort-study, subjects consisted of Relapsing-Remitting MS patients (n=62) and healthy controls (n=60). Eyes of MS patients were divided into two subgroups according to the history of the optic neuritis (ON). Standard peripapillary-RNFL and macular scan protocol, and retinal auto-segmentation of spectral-domain OCT were performed. Macular RNFL (mRNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL), and GCC (the sum of these former three layers) were recorded. The macula was divided into nine sectors using the ETDRS grid (4×9=36 variables).Results:In total, 50 eyes of 36 patients had previous ON attacks. 35/36 GCC parameters were thinner in MS patients and subgroups compared to the control group (p<0.05). When the eyes with and without a history of optic neuritis were compared, 25 of 36 parameters were thinner in those with ON. There were strong correlations between visual acuity-GCC parameters and EDSS scores in patients with a history of optic neuritis. However, no such relationship was found in those without an ON story.Conclusion:Ganglion cell complex gets thinner in patients with MS with a decreasing order of GCL, IPL, and mRNFL. The examination of GCC in detail could be a beneficial biomarker for MS.

Wavelet Features of the Thickness Map of Retinal Ganglion Cell-Inner Plexiform Layer Best Discriminate Prior Optic Neuritis in Patients With Multiple Sclerosis

The goal of this study was to analyze wavelet features of topographic thickness maps of the retinal ganglion cell-inner plexiform layer (GCIPL) and evaluate their discrimination ability in patients with multiple sclerosis (MS) and a history of optic neuritis (ON). Twenty-nine patients with relapsing-remitting MS and a history of ON were recruited together with 63 age- and sex-matched controls (HC). There were 33 eyes with a history of ON (MSON), 25 non-ON fellow eyes (MSFE) and 63 HC eyes. Ultrahigh-resolution optical coherence tomography was used to image the macula of each participant, and the volumetric dataset was segmented to yield a topographic thickness map of the GCIPL. The thickness map was analyzed using discrete wavelet transform to extract useful features, which were further analyzed with three machine learning methods, including logistic regression (LR), logistic regression regularized with the elastic net penalty (LR-EN), and support vector machine (SVM), for classification between groups. LR-EN with nested leave-one-out cross-validation resulted in 94% (83%) sensitivity and 100% (97%) specificity in discriminating MSON (MSFE) eyes from HC eyes in the training data and 88% (64%) sensitivity and 94% (94%) specificity in discriminating MSON (MSFE) eyes from HC eyes in the validation data, which were similar to or better than those resulting from LR and SVM. LR-EN improved the sensitivity and specificity of discriminating prior ON and MSFE eyes in patients with MS from HC eyes compared with traditional thickness analysis. It may be promising in facilitating the diagnosis of subclinical ON in patients with MS.

Evaluation of retinal nerve fiber layer thickness and optic nerve functions in fellow eye of neuromyelitis optica with unilateral optic neuritis.

Purpose:Peripapillary retinal nerve fibre layer (RNFL) thickness might be useful in monitoring ongoing subclinical structural damage especially in eyes with no history of optic neuritis (ON) in neuromyelitis optica (NMO).Objective:To evaluate the peripapillary RNFL thickness and optic nerve functions in fellow eye of NMO with unilateral optic neuritis.Materials and Methods:A comparative cross-sectional study was conducted in 2 tertiary hospitals from August 2017 to May 2019. RNFL thickness and optic nerve functions were evaluated. Statistical analysis was performed using Statistical Package for Social Science version 24.Results:A total of 26 NMO patients and 26 controls were involved in this study. The median age (IQR) of NMO patients was 32.5 (12) years old. The RNFL thickness was significantly reduced in NMO patients with non-ON eyes as compared to control group. Best corrected visual acuity between the 2 groups were comparable (0.20 vs 0.00, p=0.071). Contrast sensitivity was also reduced in NMO patients (non-ON eyes) at all 5 spatial frequencies. In NMO group, 34.6% have normal colour vision. The mean deviation (MD) of Humphrey visual field (HVF) was higher in NMO group (p<0.001). There was a moderate correlation between RNFL thickness and contrast sensitivity. Weak correlation was found between the RNFL thickness with visual acuity and mean deviation of visual field test.Conclusion:Our study showed that the fellow eye of NMO patients with unilateral ON revealed a significant reduction in RNFL thickness and all the optic nerve functions have subtle early changes that signify a subclinical retinal damage.

Axonal damage in the optic radiation assessed by white matter tract integrity metrics is associated with retinal thinning in multiple sclerosis

IntroductionWhite matter damage in the visual pathway is common in multiple sclerosis (MS) and is associated with retinal thinning, although the underlying mechanism of association remains unclear. The goal of this work was to evaluate the presence and extent of white matter tract integrity (WMTI) alterations in the optic radiation (OR) in people with MS and to investigate the association between WMTI metrics and retinal thinning in the eyes of MS patients without a history of optic neuritis (ON) as measured by optical coherence tomography (OCT). We hypothesized that WMTI metrics would reflect axonal damage that occurs in the OR in MS, and that axonal alterations revealed by WMTI would be associated with retinal thinning. MethodsTwenty-nine MS patients without previous ON in at least one eye and twenty-nine age-matched healthy controls (HC) were scanned on a dedicated high-gradient 3-Tesla MRI scanner with 300 mT/m maximum gradient strength using a multi-shell diffusion MRI protocol (b = 800, 1500, 2400 s/mm2). The patients were divided into two subgroups according to history without ON (N = 18) or with ON in one eye (N = 11). Diffusion tensor imaging (DTI) metrics and WMTI metrics derived from diffusion kurtosis imaging were assessed in normal-appearing white matter (NAWM) of the OR and in focal lesions. Retinal thickness in the eyes of MS patients was measured by OCT. Student’s t-test was used to assess group differences between MRI metrics. Linear regression was used to study the relationship between OCT metrics, including retinal nerve fiber layer (RNFL) and combined ganglion cell and inner plexiform layer thickness (GCL/IPL), visual acuity measures and DTI and WMTI metrics. ResultsOR NAWM in MS showed significantly decreased axonal water fraction (AWF) compared to HC (0.36 vs 0.39, p < 0.001), with similar trends observed in AWF of lesions compared to NAWM (0.27 vs 0.36, p < 0.001). Fractional anisotropy (FA) was lower in OR NAWM of MS patients compared to HC (0.49 vs 0.52, p < 0.001). In patients without ON, AWF was the only diffusion MRI metric that was significantly associated with average RNFL (r = 0.68, p = 0.005), adjusting for age, sex and disease duration and correcting for multiple comparisons. Of all the DTI and WMTI metrics, AWF was the strongest and most significant predictor of average RNFL thickness in MS patients without ON. There was no significant correlation between visual acuity scores and DTI or WMTI metrics after correction for multiple comparisons. ConclusionAxonal damage may be the substrate of previously observed DTI alterations in the OR, as supported by the significant reduction in AWF within both NAWM and lesions of the OR in MS. Our results support the concept that axonal damage is widespread throughout the visual pathway in MS and may be mediated through trans-synaptic degeneration.

Empirical Mode Decomposition-Based Filter Applied to Multifocal Electroretinograms in Multiple Sclerosis Diagnosis.

As multiple sclerosis (MS) usually affects the visual pathway, visual electrophysiological tests can be used to diagnose it. The objective of this paper is to research methods for processing multifocal electroretinogram (mfERG) recordings to improve the capacity to diagnose MS. MfERG recordings from 15 early-stage MS patients without a history of optic neuritis and from 6 control subjects were examined. A normative database was built from the control subject signals. The mfERG recordings were filtered using empirical mode decomposition (EMD). The correlation with the signals in a normative database was used as the classification feature. Using EMD-based filtering and performance correlation, the mean area under the curve (AUC) value was 0.90. The greatest discriminant capacity was obtained in ring 4 and in the inferior nasal quadrant (AUC values of 0.96 and 0.94, respectively). Our results suggest that the combination of filtering mfERG recordings using EMD and calculating the correlation with a normative database would make mfERG waveform analysis applicable to assessment of multiple sclerosis in early-stage patients.

Correlation between disease duration and retinal sensitivity and structure in patients with neuromyelitis optica spectrum disorder with no history of optic neuritis

AbstractPurposeTo determine whether there is a significant correlation between the disease duration and the sensitivity and structure of the retina in patients with neuromyelitis optica spectrum disorder (NMOSD) with no history of optic neuritis (ON).MethodsFifteen eyes of 15 patients with NMOSD (2 men, 13 women; mean age 50.2 ± 11.2 years) who had no history of ON were studied. The retinal sensitivity of the central 10º was determined by macular integrity assessment (MAIA), a microperimetric method, and the retinal structure by spectral‐domain optical coherence tomography (SD‐OCT). For MAIA, the retina was stimulated with a scanning laser ophthalmoscope at 37 loci covering 10° of the central retina. For the retinal structures, the mean thickness of the ganglion cell complex (GCC) thickness and outer nuclear layer (ONL) thickness were measured in the SD‐OCT images. The correlations between the disease duration and the sensitivity and the GCC thickness or the ONL thickness were determined by the Spearman’s rank‐correlation coefficients.ResultsThe mean best‐corrected visual acuity(BCVA) was 0.05 ± 0.03 logMAR units. The mean disease duration was 42.4 ± 37.4 months with a range of 1 to 103 months. The mean retinal sensitivity of the central 10º was 27.6 ± 1.78 dB. The mean GCC thickness was 95.0 ± 8.99 μm, and the mean ONL thickness was 53.8 ± 5.43 μm. There was a significant correlation between the disease duration and the sensitivity of the central 10º (r = 0.48, p = 0.034; Spearman’s rank‐correlation coefficients) and the ONL thickness (r = 0.60, p = 0.016; Spearman’s rank‐correlation coefficients). However, there was not a significant correlation between disease duration and GCC thickness (p &gt; 0.05; Spearman’s rank‐correlation coefficients).ConclusionsThese results indicate that the visual function is impaired even before the development of the ON in patients with NMOSD. We recommend that microperimetry and OCT be used in eyes with NMOSD because subclinical optic neuritis may be present.

Retinal oximetry as a biomarker in multiple sclerosis

AbstractPurposeStructural and physiological abnormalities have been reported in the retina in patients with multiple sclerosis (MS). Retinal oximetry has recently detected changes in retinal oxygen metabolism in Alzheimer’s disease, mild cognitive impairment and in a small cohort of MS patients with history of optic neuritis. Our goal was to determine whether oxygen saturation in retinal blood vessels of newly diagnosed MS patients is different from that of a healthy population.MethodsOxygen saturation of hemoglobin was measured in retinal blood vessels, using imaging with spectrophotometric non‐invasive retinal oximeter. Six newly diagnosed MS patients were measured and compared to six healthy individuals that were age‐ and gender‐matched with the MS patients.ResultsVenular oxygen saturation was increased in patients with MS compared to healthy individuals (mean: 61.9% versus 56.3%). Retinal venular diameter (138.2 µm versus 160.2 µm: mean) and retinal arteriolar diameter were smaller in MS patients (111.8 µm versus 131.3 µm: mean) when compared to healthy individuals. No big difference could be measured in the oxygen saturation in arterioles when patients with MS (mean: 91.2%) and healthy individuals (mean: 92.3%) were compared.ConclusionIncreased venular oxygen saturation and smaller retinal venular and arteriolar diameter in patients with MS may indicate reduced oxygen uptake in the retina. This may be due to less oxygen demand following axonal loss and may be a useful objective biomarker for MS. Further studies are needed to confirm and expand these findings.

Functional and structural changes in the visual pathway in multiple sclerosis.

IntroductionMultiple sclerosis (MS) is a heterogeneous disease with an unpredictable course. Visual pathway is a target of the disease and may reflect mechanisms that lead to disability. Structural and functional changes in the visual pathway may be studied by noninvasive techniques such as optical coherence tomography (OCT), visual evoked potentials (VEP), or B‐mode transorbital sonography (TOS).ObjectivesThe aim is to assess changes in the visual pathway in eyes of MS patients with and without a history of optic neuritis over a 3‐year period and to explore their relationship with disability.Materials and MethodsIn total, 112 eyes from 56 patients with relapsing MS were recruited: 29 with, and 83 without a history of ON (hON and nhON, respectively). Several parameters were measured by OCT, VEP, and TOS. Baseline measurements were also compared to 29 healthy controls. At 36 months, measurements were repeated in all eyes.ResultsAt baseline, all tests showed significant differences in optic nerve structure and function in both patient cohorts in all the parameters studied, suggestive of more impairment of the visual pathway among the hON cohort. OCT showed significant differences between healthy controls and the nhON cohort. At 36 months, the nhON cohort showed significant changes by OCT, VEP, and TOS suggestive of further visual pathway impairment. OCT measurements also correlated with baseline EDSS among the nhON cohort.ConclusionsOCT is the most suitable technique and outperforms VEP and TOS to detect subclinical damage in the visual pathway. It discriminated MS patients from healthy controls and showed a progressive decline in optic nerve thickness over time among these patients.

Diagnostic ability of multifocal electroretinogram in early multiple sclerosis using a new signal analysis method.

PurposeTo determine if a novel analysis method will increase the diagnostic value of the multifocal electroretinogram (mfERG) in diagnosing early-stage multiple sclerosis (MS).MethodsWe studied the mfERG signals of OD (Oculus Dexter) eyes of fifteen patients diagnosed with early-stage MS (in all cases < 12 months) and without a history of optic neuritis (ON) (F:M = 11:4), and those of six controls (F:M = 3:3). We obtained values of amplitude and latency of N1 and P1 waves, and a method to assess normalized root-mean-square error (FNRMSE) between model signals and mfERG recordings was used. Responses of each eye were analysed at a global level, and by rings, quadrants and hemispheres. AUC (area under the ROC curve) is used as discriminant factor.ResultsThe standard method of analysis obtains further discrimination between controls and MS in ring R3 (AUC = 0.82), analysing N1 waves amplitudes. In all of the retina analysis regions, FNRMSE value shows a greater discriminating power than the standard method. The highest AUC value (AUC = 0.91) was in the superior temporal quadrant.ConclusionBy analysing mfERG recordings and contrasting them with those of healthy controls it is possible to detect early-stage MS in patients without a previous history of ON.

Brain Atrophy in Relapsing Optic Neuritis Is Associated With Crion Phenotype.

Background and objective: Chronic relapsing inflammatory optic neuritis (CRION) is one of the more common phenotypes related to myelin oligodendrocyte glycoprotein antibodies (MOG-Abs). The absence of specific biomarkers makes distinguishing between CRION and relapsing inflammatory ON (RION) difficult. A recent work has suggested a widespread affectation of the central nervous system in CRION patients. In order to search for a potential CRION marker we have measured brain atrophy in a cohort of patients, stratified by phenotypes: CRION, RION, multiple sclerosis with a history of optic neuritis (MS-ON), and MOG-Abs status.Methods: A cross-sectional study was conducted in 31 patients (seven CRION, 11 RION, and 13 MS-ON). All patients were tested for MOG and aquaporin-4 antibodies (AQ4-Abs). Clinical data were collected. Brain atrophy was calculated by measuring the brain parenchyma fraction (BPF) with Neuroquant® software.Results: Four of seven CRION patients and one of 11 RION patients were positive for MOG-Abs (p = 0.046) and no MS-ON patients tested positive to MOG-Abs. All patients were negative to AQ4-Abs. The BPF was lower in patients with CRION than patients with RION (70.6 vs. 75.3%, p = 0.019) and similar to that in MS-ON patients.Conclusions: Brain atrophy in idiopathic inflammatory relapsing ON is present in patients with the CRION phenotype. Data from this study reflect that the optic nerve is a main target involved in these patients but not the only one. Our results should be further investigated in comprehensive and prospective studies.

Corneal Refractive Surgery in Patients with History of Optic Neuritis.

PurposeThe purpose of this study was to evaluate the risk of recurrence of optic neuritis after corneal refractive surgery in patients with a history of optic neuritis and to examine the safety and efficacy of the procedure in this population.MethodsThis was a retrospective chart review of patients with a history of optic neuritis who underwent laser-assisted in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) at a single tertiary center from June 1996 to December 2014. Fifteen eyes of 14 patients were included in this study. Visual acuity before and after the surgery was recorded. Patients were followed-up for over five years postoperatively for the recurrence of optic neuritis.ResultsThe average LogMAR best corrected visual acuity (BCVA) preoperatively was 0.12 0.19 (–0.10 to 0.60) and postoperatively was 0.06 0.10 (–0.10 to 0.30). No eyes lost lines of BCVA. The average LogMAR uncorrected distance visual acuity (UDVA) after surgery was 0.12 0.13 (0.00 to 0.48). Twenty-eight percent of patients reached a UDVA of 20/20 or better after refractive surgery. Optic neuritis recurred in 3/15 (20%) eyes and 3/14 patients (21%).ConclusionWhile corneal refractive procedures appear safe in patients with a history of optic neuritis, our data suggest that their efficacy may be reduced.

Focal Thickness Reduction of the Ganglion Cell-Inner Plexiform Layer Best Discriminates Prior Optic Neuritis in Patients With Multiple Sclerosis.

PurposeThe goal was to visualize topographic thickness maps of the intraretinal layers and evaluate their discrimination abilities and relationships with clinical manifestations in patients with multiple sclerosis (MS) and a history of optic neuritis (ON).MethodsThirty patients with relapsing-remitting MS (34 eyes with a history of ON [MSON] and 26 non-ON fellow eyes [MSFE]) were recruited together with 63 age- and sex-matched controls (HC). Ultrahigh resolution optical coherence tomography was used to image the macula and the volumetric data set was segmented to yield six intraretinal layers. Topographic thickness maps were aligned and averaged for the visualization. The thickness maps were partitioned using the Early Treatment Diabetic Retinopathy Study (ETDRS) and related to Sloan low-contrast letter acuity (LCLA), Expanded Disability Status Scale (EDSS), and disease duration.ResultsFocal thickness reduction occurred in the macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL), with the most profound reduction occurring in MSON eyes (P < 0.05). A horseshoe-like thickness reduction pattern (U Zone) in the GCIPL appeared in MSON. The thickness of the U Zone had better discrimination power than the ETDRS partitions (area under the curve = 0.97) and differentiated 96% of MSON from HC. The thickness of the U Zone was positively correlated to 2.5% LCLA (r = 0.38, P < 0.05) and 1.25% LCLA (r = 0.57, P < 0.05).ConclusionsThe horseshoe-like thickness reduction of the GCIPL appeared to be an ON-specific focal thickness alteration with the highest discrimination power of prior ON.

Retinal versus optic nerve predictors of early disability in ambulatory patients with multiple sclerosis, a comparative study

Multiple sclerosis (MS) is a common cause of neurological disabilities in adults and commonly affects the visual pathway. To assess and compare the sensitivity of Visual Evoked Potentials (VEP) and Optical Coherence Tomography (OCT) as early correlates of early disability in ambulatory patients with MS.METHODS: Forty-Four patients with MS with Expanded Disability Status Scale (EDSS) of ≤ 4.5 (ambulatory patients) and 14 healthy controls participated in this study. Patients were classified into 3 groups according EDSS. Patients with EDSS of 0-1.5 formed the “No disability”, patients with EDSS of 2-3 formed the “Minimal to mild disability”, and finally patients with EDSS of 3.5-4.5 formed the “Moderate to significant disability” groups. N75/P100 amplitude, P100 latency, Retinal Nerve Fiber Layer (RNFL) thickness, and Ganglion Cell Layer Complex (GCLC) thickness were measured. Patients showed significantly lower N75/P100 amplitude, higher P100 latency, lower RNFL, and GCLC thicknesses compared to controls. However, there were non-significant changes in P100 latency, N75/P100 amplitude, and GCLC thickness among the 3 groups for both patients with and without history of Optic Neuritis (ON). On contrary, RNFL thickness was significantly different between the three groups for both patients with and without ON. Factorial ANOVA revealed non-significant disability x History of ON interaction. Compared to VEP parameters, RNFL thickness was a sensitive correlate with the degree of early disability in fully ambulatory patients with MS with or without history of ON.

Evaluating optic nerve diameter as a possible biomarker for disability in patients with multiple sclerosis.

Background and purposeThe development of new biomarkers for multiple sclerosis (MS) is of paramount importance to improve our ability to predict disease progression and disability. The aim of this study was to evaluate the potential role of the optic nerve diameter (OND) measured by ultrasonography as a biomarker of early disability in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsForty-nine RRMS patients, 23 with a history of optic neuritis (MS-ON) and 26 without a history of optic neuritis (MS N-ON), and 50 age- and sex-matched healthy control subjects were included in the study. The OND and optic nerve sheath diameter (ONSD) were measured by transorbital sonography (TOS), and the retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) thicknesses were measured by optical coherence tomography (OCT) using the Optovue RTVue™ system (Optovue, Inc., Fremont, CA, USA).ResultsThere was no significant difference between the patient (whether ON or N-ON eyes) and control groups in either the OND (p=0.979) or the ONSD (p=0.911). However, patients with an expanded disability status scale (EDSS) score >2 had a significantly lower OND and RNFL thicknesses (p=0.014, p=0.010 respectively) than patients with an EDSS score ≤2. Statistical logistic regression revealed that OND was an independent predictor of EDSS>2 (p=0.044, OR =0.000, 95% CI=0.000–0.589).ConclusionThe OND, as measured by ultrasonography, could be potentially used as a biomarker for the detection of early disability in RRMS patients.

Sleep disturbance and cognitive decline in multiple sclerosis patients with isolated optic neuritis as the first demyelinating event.

Multiple sclerosis (MS) patients whose first demyelinating event is optic neuritis have been claimed to display a milder disease course and reduced physical disability. Our aim was to investigate the impact of the clinical features of the first clinical episode on cognitive disability and sleep dysfunction in MS. A total of 26 (10 with optic neuritis as the first clinical event) MS patients were recruited. A comprehensive sleep study was performed, and a panel of tests were administered to examine cognitive and motor performance. Serum levels of sleep-related mediators orexin-A and melatonin were measured by enzyme-linked immunosorbent assay. Subjective sleep quality was evaluated by Pittsburgh sleep quality test, and daytime excessive sleepiness was tested by Epworth sleepiness scale. MS patients with the first clinical episode of optic neuritis and patients with at least one optic neuritis attack exhibited increased daytime sleepiness, higher sleep efficiency and NREM duration and lower total wake time. Patients with a history of optic neuritis obtained more favorable scores in neuropsychological tests measuring executive functions and complex attention as compared to those who had never experienced optic neuritis. Melatonin and orexin-A levels were lower in patients with optic neuritis onset. The higher no. of optic neuritis attacks was associated with reduced wake time and higher symbol digit modalities test scores. Having a history of optic neuritis is associated with improved sleep quality and executive functions but increased daytime sleepiness. Reduction of orexin-A and melatonin levels might be one of the underlying mechanisms.

Objective quantification of vitreous haze on optical coherence tomography scans: no evidence for relationship between uveitis and inflammation in multiple sclerosis.

Background and purposeThe occurrence of intermediate uveitis, which is characterized by the presence of vitreous haze (VH), in patients with multiple sclerosis (MS) may be a sign of coexistent inflammatory central nervous system (CNS) disease activity. Using an automated algorithm to quantify VH on optical coherence tomography (OCT) scans, the aim was to investigate whether VH in MS patients is associated with signs of inflammatory CNS disease activity.MethodsVitreous haze was quantified on OCT macular volume scans of 290 MS patients and 85 healthy controls (HCs). The relationship between VH and clinical, retinal OCT and magnetic resonance imaging parameters of inflammatory disease activity was investigated using generalized estimating equations.ResultsMean VH scores did not differ between patients and HCs (P = 0.629). Six patients (2.1%) showed values higher than the highest of the controls by HCs. VH scores did not differ between the different disease types or between eyes with and without a history of optic neuritis (P = 0.132). VH was not associated with inner nuclear layer volume on OCT (P = 0.233), cerebral T2 lesion load on magnetic resonance imaging (P = 0.416) or the development of new relapses (P = 0.205).ConclusionIn this study, OCT‐based automated VH estimation did not detect increased vitreous inflammation in MS patients compared to HCs and did not find an association with CNS inflammatory burden.

P.079 4H leukodystrophy: a case series of siblings with an unusually mild phenotype

Background: 4H leukodystrophy is a genetic disorder typically characterized by hypomyelination, hypodontia and hypogonatotropic hypogonadism. Previously reported patients had considerable cognitive and motor deficits. We present a pair of siblings with a less severe phenotype. Methods: Patient data was obtained from medical records from the Children’s Hospital of Eastern Ontario. Results: The first patient was diagnosed with 4H leukodystrophy at the age of 21 years after genetic testing revealed a POLR3B mutation with a homozygous V523E variant. She has hypomyelination on MRI and a history of optic neuritis, as well as intermittent sensory and motor symptoms in the context of a diagnosis of multiple sclerosis. She has no clinical manifestations of 4H leukodystrophy. The patient is now 26 years old and has only mild neurological deficits. Her younger brother was diagnosed with 4H leukodystrophy at the age of 18 years and found to have the same genetic mutation as his sister. He has a history of seizures and mild learning disabilities. He is now 23 years old with no typical symptoms of 4H leukodystrophy. Conclusions: 4H leukodystrophy is usually associated with a severe, disabling phenotype and a poor prognosis. Our patients illustrate that a much milder phenotype exists.