Predicting Cued and Oddball Visual Search Performance from fMRI, MEG, and DNN Neural Representational Similarity.

Capacity limitations in visual tasks can be observed when the number of task-related objects increases. An influential idea is that such capacity limitations are determined by competition at the neural level: two objects that are encoded by shared neural populations interfere more in behavior (e.g., visual search) than two objects encoded by separate neural populations. However, the neural representational similarity of objects varies across brain regions and across time, raising the questions of where and when competition determines task performance. Furthermore, it is unclear whether the association between neural representational similarity and task performance is common or unique across tasks. Here, we used neural representational similarity derived from fMRI, MEG, and a deep neural network (DNN) to predict performance on two visual search tasks involving the same objects and requiring the same responses but differing in instructions: cued visual search and oddball visual search. Separate groups of human participants (both sexes) viewed the individual objects in neuroimaging experiments to establish the neural representational similarity between those objects. Results showed that performance on both search tasks could be predicted by neural representational similarity throughout the visual system (fMRI), from 80 ms after onset (MEG), and in all DNN layers. Stepwise regression analysis, however, revealed task-specific associations, with unique variability in oddball search performance predicted by early/posterior neural similarity and unique variability in cued search task performance predicted by late/anterior neural similarity. These results reveal that capacity limitations in superficially similar visual search tasks may reflect competition at different stages of visual processing.

Sleep, physical activity, and psychological outcomes in children and adolescents with pediatric onset multiple sclerosis.

BACKGROUND: Sleep, physical activity (PA) and sedentary behavior (SED) have bidirectional associations with mental health in children. The relationships among sleep, PA, SED, with depressive and fatigue symptoms have not been investigated in Pediatric Onset Multiple Sclerosis (POMS) but are needed to inform sleep and PA behavior change interventions. OBJECTIVES: (1) To describe sleep quality including: sleep efficiency, latency, total sleep time, number of awakenings, time in bed, and wake after sleep onset using actigraphy in children and adolescents ages 11 to 18 diagnosed with POMS, and to compare these sleep metrics to those of an age- and sex-matched non-MS group (2) To examine the relationship between time spent in sedentary, light (LIPA), moderate and vigorous PA (MVPA), sleep quality, with depression, fatigue, and quality of life in children and adolescents with POMS and an age and sex matched non-MS group. METHODS: A cross-sectional study recruited children and adolescents with POMS ages 11 to 18 years followed at a tertiary pediatric hospital (Toronto, Canada) and an age and sex matched non-MS group from the general population. Participants were consented prior to initiation of study procedures. Participants wore an Actiwatch monitor and GT3X accelerometer and completed standardized questionnaires validated to capture data on sleep disturbances, depression, fatigue, and quality of life. Objective sleep data were collected using an Actiwatch including sleep efficiency, total sleep time, number of awakenings, wake after sleep onset (WASO), and sleep latency. A GT3X accelerometer was used to collect PA data including time spent in SED, light (LPA), and moderate to vigorous (MVPA) PA. Correlational analyses and tests of difference were used to compare the groups. RESULTS: 25 POMS (21F; 16.6 years ±1.1 yrs., median Expanded Disability Status Scale (EDSS) =1.5, IQR=1) and 25 Non-MS (22 F; 16±1.3 yrs.) took part. POMS had higher BMI (T= -5.1, P<0.001) compared to Non-MS. No differences in sleep efficiency (MS mean = 87%, vs. 88%) sleep time (MS Mean = 7.3 hrs. vs. 7.4 hrs.,), WASO (MS mean=37 mins. vs. 36 mins), latency (MS mean=15 mins vs. 11 mins), SED (MS mean =763 mins. vs. 730 mins) or PA (MS, mean LPA = 68 mins. vs 60 mins; MS mean MVPA = 12.7 mins. vs. 12.4 mins). Within POMS, higher sleep efficiency was associated with more SED (SR= 0.4, p = 0.05), while higher sleep efficiency was associated with less SED in Non-MS (SR = -0.7, p< 0.0). In children with POMS, less sleep time, shorter sleep onset latency and more WASO was associated with more SED (SR range = -0.45 to -0.58, P< 0.01). Higher sleep efficiency was associated with less fatigue. Less WASO was associated with lower depression, lower fatigue (SR = 0.67, p<0.01) and better quality of life (SR= -0.6, p<0.01). Greater LPA was associated with lower sleep onset latency (-0.45, p<0.05). CONCLUSIONS: Children with POMS did not differ in Actiwatch monitored sleep quality metrics. However, within the POMS group sleep quality was associated with better fatigue, depression and QOL. Further, total sleep time, WASO and latency associated with time spent SED and LPA, which independently associate with mental health outcome. Longitudinal work should determine the temporal associations between WASO, sleep latency, sleep time, PA, and mental health outcomes and whether reallocation of specific sleep or PA behaviors (time to sleep, total sleep time, sedentary to MVPA) result in improved depression fatigue, or quality of life in children and adolescents with POMS.

Structural visual metrics associate with moderate to vigorous physical activity in youth with pediatric onset neuroinflammatory disorders.

BACKGROUND: Higher levels of moderate to vigorous physical activity (MVPA) associate with disease activity in pediatric multiple sclerosis (MS). Further, measures of retinal integrity associate with lower brain atrophy, yet the relationship of retinal integrity with MVPA has not been investigated. OBJECTIVE: To determine the relationship between MVPA and retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness in patients with MS, myelin oligodendrocyte glycoprotein-associated disorders (MOGAD), neuromyelitis optica spectrum disorder (NMOSD), and monophasic acquired demyelinating syndromes (monoADS). METHODS: 150 consecutive children ≤18 y.o with neuroinflammatory disorders were included. Outcomes included the Godin Leisure Time Activity Questionnaire (GLTEQ) modeled as both a continuous and categorical variable (any vs no MVPA/Strenuous activity), and RNFL and GCIPL using linear mixed models (JASP 0.14.1). RESULTS: An association was identified between MVPA with RNFL thickness (F (1,133) = 8.40, p = .004) and GCIPL thickness (F(1, 131) = 7.68, p = .006). In the MS cohort, any strenuous physical activity was associated with greater RNFL (F(1,35) = 7.30, p = .011) and GCIPL thickness (F(1,35) = 8.73, p =.006). CONCLUSIONS: Any MVPA participation is associated with higher RNFL and GCIPL thickness across neuroinflammatory disorders.

Reduction of Connexin 43 Attenuates Angiogenic Effects of Human Smooth Muscle Progenitor Cells via Inactivation of Akt and NF-κB Pathway.

OBJECTIVE: Circulating progenitor cells possess vasculogenesis property and participate in repair of vascular injury. Cx (connexin) 43-a transmembrane protein constituting gap junctions-is involved in vascular pathology. However, the role of Cx43 in smooth muscle progenitor cells (SPCs) remained unclear. Approach and Results: Human SPCs cultured from CD34+ peripheral blood mononuclear cells expressed smooth muscle cell markers, such as smooth muscle MHC (myosin heavy chain), nonmuscle MHC, calponin, and CD140B, and Cx43 was the most abundant Cx isoform. To evaluate the role of Cx43 in SPCs, short interference RNA was used to knock down Cx43 expression. Cellular activities of SPCs were reduced by Cx43 downregulation. In addition, Cx43 downregulation attenuated angiogenic potential of SPCs in hind limb ischemia mice. Protein array and ELISA of the supernatant from SPCs showed that IL (interleukin)-6, IL-8, and HGF (hepatocyte growth factor) were reduced by Cx43 downregulation. Simultaneously, Cx43 downregulation reduced the phosphorylation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and Akt (protein kinase B) pathway and reactivation of NF-κB and Akt using betulinic acid, and SC79 could restore the secretion of growth factors and cytokines. Moreover, FAK (focal adhesion kinase)-Src (proto-oncogene tyrosine-protein kinase Src) activation was increased by Cx43 downregulation, and inactivation of Akt-NF-κB could be restored by Src inhibitor (PP2), indicating that Akt-NF-κB inactivated by Cx43 downregulation arose from FAK-Src activation. Finally, the depressed cellular activities and secretion of SPCs after Cx43 downregulation were restored by FAK inhibitor PF-562271 or PP2. CONCLUSIONS: SPCs possess angiogenic potential to repair ischemic tissue mainly through paracrine effects. Gap junction protein Cx43 plays an important role in regulating cellular function and paracrine effects of SPCs through FAK-Src axis.

The computer-based Symbol Digit Modalities Test: establishing age-expected performance in healthy controls and evaluation of pediatric MS patients.

Decreased information processing speed (IPS) is frequently reported in pediatric multiple sclerosis (MS) patients. The computerized version of the Symbol Digit Modalities Test (c-SDMT) measures IPS over eight consecutive trials per session and additionally captures changes in performance within the session. Here, we establish normative c-SDMT performance and test-retest reliability in healthy children (HC) and explore differences in the overall c-SDMT-performance between HC and MS patients. This cross-sectional study included 478 HC (237 female, 49.5%) divided into five age groups (2 years each), and 27 MS patients (22 female, 81.5%) aged 8-18 years. The average time to complete the c-SDMT increased with age (|r| 0.70, 95% CI -0.74, -0.64). Test-retest reliability was high (ICC = 0.91) in HC. The total time to complete the c-SDMT did not differ between children with MS and sex- and age- matched HC (p = 0.23). However, MS patients were less likely to show faster performance across all the successive eight trials compared to HC (p = 0.0001). Healthy children demonstrate faster IPS with increasing age, as well as during successive trials of the c-SDMT. The inability of pediatric MS patients to maintain the increase in processing speed over successive trials suggests a reduced capacity for procedural learning, possibly resulting from cognitive fatigue.

Regression-based norms improve the sensitivity of the National MS Society Consensus Neuropsychological Battery for Pediatric Multiple Sclerosis (NBPMS).

The National Multiple Sclerosis Society Consensus Neuropsychological Battery for Pediatric Multiple Sclerosis (NBPMS) was designed to detect cognitive impairment in children and adolescents with multiple sclerosis. One weakness of the battery is the reliance on published manual-based normative samples varying in size and quality. These primary sources base interpretation on discrete age bands, a practice which may be particularly problematic during periods of rapid development in childhood and adolescence. A further impediment to valid NBPMS interpretation is the lack of control for demographic factors other than age. We endeavored to develop regression-based norms for the NBPMS by gathering a demographically balanced sample of 102 healthy control children and using their performance to derive normalization, controlling for multiple demographic variables (i.e., age, age(2), gender, parent education). The regression-based normative equations were applied to the performance of 51 children with MS. For many of the major test scores, the regression-based norms more readily detected impairment. As in the case of adult MS, these results indicate that regression-based norms offer interpretive benefits over their manual-based counterparts.

No association between conventional brain MR imaging and chronic cerebrospinal venous insufficiency in multiple sclerosis.

BACKGROUND AND PURPOSE: CCSVI has been reported to occur at high frequency in MS. Its significance in relation to MR imaging parameters also needs to be determined, both in patients with MS and HCs. Therefore, this study determined the associations of CCSVI and conventional MR imaging outcomes in patients with MS and in HCs. MATERIALS AND METHODS: T2, T1, and gadolinium lesion number, LV, and brain atrophy were assessed on 3T MR imaging in 301 subjects, of whom 162 had RRMS, 66 had secondary-progressive MS subtype, and 73 were HCs. CCSVI was assessed using extracranial and transcranial Doppler evaluation. The MR imaging measure differences were explored with 27 borderline cases for CCSVI, added to both the negative and positive CCSVI groups to assess sensitivity of the results of these cases. RESULTS: No significant differences between subjects with and without CCSVI were found in any of the individual diagnostic subgroups or MS disease subtypes for lesion burden and atrophy measures, independently of the CCSVI classification criteria used, except for a trend for higher T2 lesion number (irrespective of how borderline cases were classified) and lower brain volume (when borderline cases were included in the positive group) in patients with RRMS with CCSVI. No CCSVI or MR imaging differences were found between 26 HCs with, or 47 without, a familial relationship. CONCLUSIONS: CCSVI is not associated with more severe lesion burden or brain atrophy in patients with MS or in HCs.

Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis.

New therapies are being evaluated by clinical trials and, if efficacious, introduced for the treatment of adult MS. The role of these new and existing agents in the management of pediatric MS has yet to be defined. Pediatric investigation plans are now required by the Food and Drug Administration and European Medicines Agency for approval of new biological agents, providing an important opportunity to gather much-needed data for clinicians caring for children and adolescents with MS. However, challenges include the small number of patients, and the need for efficient yet comprehensive study designs incorporating factors necessary to inform the clinical care of children with MS. The elected Steering committee of the International Pediatric MS Study Group (IPMSSG) conducted a structured review of existing data on the disease-modifying therapies in pediatric MS and developed a consensus statement, which was further modified by the IPMSSG general membership, using an online survey tool. Fifty-one IPMSSG members from 21 countries responded to the survey, and 50 approved the final statement. Consensus recommendations regarding use of existing first- and second-line therapies, as well as a proposed definition for inadequate treatment response, are presented. Recommendations for the use and evaluation of emerging therapies (currently in phase III clinical trials or recently approved for adult MS) are discussed. The IPMSSG endorses the inclusion of pediatric MS patients in trials evaluating appropriate new and emerging therapies. Mechanisms for conducting high-impact, multicenter studies, including long-term follow-up in pediatric MS, are required to ensure that all MS patients, irrespective of age, benefit from advances in MS therapeutics.

Common viruses associated with lower pediatric multiple sclerosis risk.

BACKGROUND: Because common viruses are encountered during childhood, pediatric multiple sclerosis (MS) offers a unique opportunity to investigate the influence of these viruses on disease susceptibility and the interactions between seroprevalence and select HLA genotypes. We studied seroprevalence for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV) type 1 and HLA-DRB1*1501/1503 status as predictors of pediatric MS. METHODS: This was a retrospective analysis of prospectively collected demographic, clinical, and biologic data in subjects up to 18 years of age with early MS, control subjects seen at the same regional referral pediatric MS clinics, and additional healthy pediatric control subjects. RESULTS: Patients with early pediatric MS (n=189) and pediatric control subjects (n=66) were tested. Epstein-Barr nuclear antigen-1 seropositivity was associated with an increased odds of MS (odds ratio [OR] 3.78, 95% confidence interval [CI] 1.52-9.38, p=0.004) in analyses adjusted for age, sex, race, ethnicity, and HLA-DRB1*1501/1503 status. In multivariate analyses including EBV status, a remote infection with CMV (OR 0.27, 95% CI 0.11-0.67, p=0.004) was associated with a lower risk of developing MS. Although a remote infection with HSV-1 was not associated with an increased odds of MS, a strong interaction was found between HSV-1 status and HLA-DRB1 in predicting MS (p<0.001). HSV-1 was associated with an increased risk of MS in those without a DRB1*15 allele (OR 4.11, 95% CI 1.17-14.37, p=0.03), whereas the effect was reversed in those who were DRB1*15-positive (OR 0.07, 95% CI 0.02-0.32, p=0.001). CONCLUSIONS: These findings suggest that some infections with common viruses may in fact lower MS susceptibility. If this is confirmed, the pathways for risk modification remain to be elucidated.

Regression-based pediatric norms for the brief visuospatial memory test: revised and the symbol digit modalities test.

The Brief Visuospatial Memory Test - Revised (BVMTR) and the Symbol Digit Modalities Test (SDMT) oral-only administration are known to be sensitive to cerebral disease in adult samples, but pediatric norms are not available. A demographically balanced sample of healthy control children (N = 92) ages 6-17 was tested with the BVMTR and SDMT. Multiple regression analysis (MRA) was used to develop demographically controlled normative equations. This analysis provided equations that were then used to construct demographically adjusted z-scores for the BVMTR Trial 1, Trial 2, Trial 3, Total Learning, and Delayed Recall indices, as well as the SDMT total correct score. To demonstrate the utility of this approach, a comparison group of children with acute disseminated encephalomyelitis (ADEM) or multiple sclerosis (MS) were also assessed. We find that these visual processing tests discriminate neurological patients from controls. As the tests are validated in adult multiple sclerosis, they are likely to be useful in monitoring pediatric onset multiple sclerosis patients as they transition into adulthood.

Visual-cognitive processing deficits in pediatric multiple sclerosis.

BACKGROUND: Children with multiple sclerosis (MS) can suffer significant cognitive deficits. This study investigates the sensitivity and validity in pediatric MS of two visual processing tests borrowed from the adult literature, the Brief Visuospatial Memory Test-Revised (BVMTR) and the Symbol Digit Modalities Test (SDMT). OBJECTIVE: To test the hypothesis that visual processing is disproportionately impacted in pediatric MS by comparing performance with that of healthy controls on the BVMTR and SDMT. METHODS: We studied 88 participants (43 MS, 45 controls) using a neuropsychological assessment battery including measures of intelligence, language, visual memory, and processing speed. Patients and demographically matched controls were compared to determine which tests are most sensitive in pediatric MS. RESULTS: Statistically significant differences were found between the MS and control groups on BVMTR Total Learning (t (84) = 4.04, p < 0.001, d = 0.87), BVMTR Delayed Recall (t (84) = 4.45, p < 0.001, d = 0.96), and SDMT (t (38) = 2.19, p = 0.035, d = 0.69). No significant differences were found between groups on confrontation naming or general intellectual ability. Validity coefficients exploring correlation between BVMTR, SDMT, and disease characteristics were consistent with the adult literature. CONCLUSIONS: This study found that BVMTR and SDMT may be useful in assessing children and adolescents with MS.

Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis.

Anti-myelin basic protein (MBP) antibodies in pediatric-onset MS and controls were characterized. Serum samples were obtained from 94 children with MS and 106 controls. Paired CSF and serum were obtained from 25 children with MS at time of their initial episode of acute demyelinating syndrome (ADS). Complementary assays were applied across samples to evaluate the presence, and the physical binding properties, of anti-MBP antibodies. While the prevalence and titers of serum anti-MBP antibodies against both immature and mature forms of MBP were similar in children with MS and in controls, binding characteristics and formal Surface Plasmon Resonance (SPR) studies indicated surprisingly high binding affinities of all pediatric anti-MBP antibodies. Serum levels of anti-MBP antibodies correlated significantly with their CSF levels, and their presence in children with MS was associated with significantly increased risk of an acute disseminated encephalomyelitis-like initial clinical presentation. While antibodies to both immature and mature forms of MBP can be present as part of the normal pediatric humoral repertoire, these anti-myelin antibodies are of surprisingly high affinity, can access the CNS during inflammation, and have the capacity to modulate disease expression. Our findings identify an immune mechanism that could contribute to the observed heterogeneity in spectrum of clinical presentations in early-onset MS.

Younger children with MS have a distinct CSF inflammatory profile at disease onset.

BACKGROUND: The clinical and MRI presentation differs between earlier- and later-onset pediatric multiple sclerosis (MS), whereas the effect of age on the CSF inflammatory profile is unknown and may contribute to delayed diagnosis. OBJECTIVES: To compare the CSF cellular and immunoglobulin G (IgG) profiles between earlier- and later-onset pediatric MS. METHODS: We queried the databases of 6 pediatric MS centers for earlier-onset (onset <11 years) and later-onset (> or = 11 and <18 years) patients with MS or clinically isolated syndrome who underwent CSF analysis within the first 3 months of presentation (observational study). We compared CSF white blood cell (WBC) differential count, IgG index, and IgG oligoclonal bands between age groups. RESULTS: We identified 40 earlier-onset (mean age at onset = 7.2 +/- 2.7 years, 60% females) and 67 later-onset pediatric MS patients (15.1 +/- 1.7 years, 63% females). Although WBC count tended to be higher in earlier-onset patients (median = 9/mm(3) [0-343] vs 6 [0-140], p = 0.15), they had a lower proportion of lymphocytes (70% [0-100] vs 93% [0-100] of WBCs, p = 0.0085; difference = +3% per 1-year increase of age, p = 0.0011) and higher proportion of neutrophils than later-onset patients (0.5% [0-75] vs 0% [0-50] of WBCs, p = 0.16; difference = -1% per 1-year increase of age, p = 0.033). In earlier-onset disease, fewer patients had an elevated IgG index than in the later-onset group (35% vs 68% of patients, p = 0.031). CONCLUSION: Age modifies the CSF profile at pediatric multiple sclerosis (MS) onset, which may mislead the diagnosis. Our findings suggest an activation of the innate rather than the adaptive immune system in the earlier stages of MS or an immature immune response.

Magnetic resonance imaging characteristics of children and adults with paediatric-onset multiple sclerosis.

The purpose of this study was to compare the clinical and quantitative magnetic resonance imaging metrics of paediatric-onset multiple sclerosis to adult-onset multiple sclerosis. It was a prospective comparison of clinical and magnetic resonance imaging characteristics of two paediatric onset multiple sclerosis and two adult onset multiple sclerosis groups that were matched for disease duration. The paediatric-onset-C group consisted of children with paediatric-onset multiple sclerosis with mean disease duration of 2.7 years, whereas the paediatric onset-A group consisted of adults with mean disease duration of 20 years. The adult onset multiple sclerosis-1 and adult onset multiple sclerosis-2 groups were matched to the paediatric onset-C and paediatric onset-A groups. The brain magnetic resonance imaging measures included: T(1)-, T(2)- and gadolinium contrast-enhancing volumes and the T(2)-lesion volume relative magnetization transfer ratio, global and tissue specific white and grey matter brain atrophy and normal appearing grey and white matter magnetization transfer ratio. Regression analyses were employed for magnetic resonance imaging measures. The paediatric onset multiple sclerosis-C (n = 17) and adult onset multiple sclerosis-1 (n = 81) groups had mean disease duration values of 2.7 +/- standard deviation 2.0 and 2.6 +/- 1.1 years, respectively. The paediatric onset multiple sclerosis-A group (n = 33) and adult onset multiple sclerosis-2 group (n = 300) had mean disease durations of 20 +/- standard deviation 10.9 and 20 +/- 9.3 years, respectively. In regression analysis, the T(2)- lesion volume of the paediatric onset multiple sclerosis-C and adult onset multiple sclerosis-1 groups were similar but there was a trend toward higher T(1)- lesion volume (P = 0.028) in the paediatric onset group. The brain parenchymal fraction and grey matter fraction in the paediatric-onset multiple sclerosis-C group were higher than those for the adult onset multiple sclerosis-1 group (both P < 0.001). The frequency of progressive multiple sclerosis in the paediatric onset multiple sclerosis-A group (27.3%) trended lower (odds ratio = 0.43, P = 0.042) than that in the adult onset multiple sclerosis-2 group (46.3%). The Expanded Disability Status Scale (median; inter-quartile range) in the paediatric onset multiple sclerosis-A group (2.25; 2.5) trended lower (P = 0.058) compared with the adult onset multiple sclerosis-2 group (3.5; 4.0). There was a trend toward lower magnetization transfer ratio values in T(2)-lesions, normal appearing grey matter and normal appearing white matter and higher grey matter fraction in the paediatric onset multiple sclerosis-A group compared with the adult onset multiple sclerosis-2 group. There was no evidence for differences on T(2)-lesion volume, T(1)-lesion volume, brain parenchymal fraction or white matter fraction. Paediatric-onset multiple sclerosis is characterized by a significant disease burden both early and later in the disease course. Despite this, disability is slower to accrue in paediatric onset multiple sclerosis than adult onset multiple sclerosis.

Retinal nerve fiber thickness in inflammatory demyelinating diseases of childhood onset.

PURPOSE: To evaluate retinal nerve fiber layer thickness (RNFLT) using optical coherence tomography (OCT) in children with acquired demyelinating diseases. METHODS: This is a cross-sectional study of patients seen between 2006-2008 at the Pediatric MS Center of the Jacobs Neurological Institute. Consensus definitions for pediatric demyelinating disease were followed. All children received OCT testing and assessment of visual acuity (VA) using Snellen and low contrast letter acuity (LCLA) charts. RESULTS: Thirty-eight children diagnosed with acquired demyelinating disease, 15 healthy controls, and five children with other neurological disorders (OND) were included. Average RNFLT in healthy controls was 107 +/- 12 microm(n = 30) versus 108 +/- 5 microm (n = 10) in OND controls. In children with multiple sclerosis, average RNFLT +/- SD was 99 +/- 14 microm in unaffected (n = 24) versus 83 +/- 12 micromin eyes affected by optic neuritis ("affected eyes") (n = 10). Average RNFLT in children with acute disseminated encephalomyelitis and transverse myelitis was 102 +/- 15 microm in unaffected (n = 18) versus 67 +/- 17 microm in affected eyes (n = 6). In children with optic neuritis (ON), average RNFLT +/- SD was 97 +/- 13 microm in unaffected (n = 5) versus 89 +/- 12 microm in affected eyes (n = 9). Differences between children with demyelinating disease and controls and between ON and nonON eyes were statistically significant (P < 0.001). Bivariate correlations of RNFLT with LCLA (P = 0.002) and VA (P < 0.001) were significant. CONCLUSIONS: OCT may be a valuable tool for the assessment and monitoring of anterior optic pathway dysfunction in children with demyelinating diseases.