Effects of disease-modifying therapies on remyelination in multiple sclerosis; evaluation via visual evoked potential test.

BACKGROUND: Assessment of the visual pathway, which is frequently affected by MS, provides the opportunity to measure the remyelination of acute and chronic MS lesions in vivo and non-invasively. VEP can be used in this context. Amplitude is a parameter of axonal loss, whereas latency is an in vivo biomarker of myelin repair. This study aimed to evaluate DMT's neuroprotective and pro-remyelinating potential by evaluating VEP latency and amplitude in MS patients. MATERIALS AND METHODS: A total of 74 patients with relapsing MS who had no evidence of optic neuritis were included in the study. Patient data were retrospectively analyzed and recorded. In the VEP test, latency above 118 ms and amplitude below 5.0 µV were considered abnormal. Classified according to DMTs (injectables, teriflunomide, dimethyl fumarate, fingolimod, cladribine, and alemtuzumab). Visual evoked potential tests, clinical features, and cerebrospinal fluid examinations were evaluated by three independent neurologists and one clinical neurophysiologist. RESULTS: The mean age at diagnosis was 29.2 ± 9.01, and the mean age at first VEP was 34.97 ± 10.64. In women, latency was lower, and amplitude was higher. The mean differences in latency and amplitude were, respectively, latency prolonged by 0.7 ms on the right and 0.5 ms on the left, and amplitude increased by 0.6 µV on the right and 0.37 µV on the left. However, these changes were not statistically significant. Latency worsening was more prominent in those with longer disease duration (p = 0.011). Those with amplitude or latency worsening had higher EDSS (p = 0.016 and 0.013, respectively). DMTs did not affect these changes. CONCLUSION: Prolonged latency is associated with a long disease duration. Deterioration in both amplitude and latency is evident in high EDSS. These results may be an indirect consequence of axonal degeneration dominating remyelination. DMTs do not ameliorate impaired remyelination and neurodegeneration but seem to be sufficient for short-term maintenance of the current state.

Study of Visual Evoked Potentials in Schoolchildren: A Promising Aid to Pediatric Ophthalmology.

Background Visual evoked potential (VEP) is a noninvasive investigation conducted to identify abnormalities in the visual system. It is especially suitable for young children who are unable to express visual symptoms or participate in conventional vision tests. This study was undertaken to examine the VEP among schoolchildren to assess the functionality of their optic pathway. Methodology This short-term observational study was performed in the Clinical Neurophysiology Unit of the Physiology Department of a rural medical college. The study population consisted of 60 schoolchildren aged 7-12. Both eyes were examined for transient pattern reversal VEP recordings using a Recorders & Medicare Systems Electromyography-Evoked Potential recorder (RMS EMG-EP MARK-II Pvt. Ltd., Chandigarh, India). Results VEPs were analyzed for latency and amplitude of the main components, namely P100, N70, and N155. The results showed markedly extended P100 latency in 33.33%, i.e., eight out of 24 eyes of standard (std.) III children. Similar latency prolongation was obtained in 36.36% (eight out of 22) eyes of std. IV, 30% (six of 20 eyes) of std. V, 13.63% (three of 22 eyes) of std. VI, and 50% (eight of 16 eyes) in std. VII and VIII children. A markedly reduced P100 amplitude was observed in two of 20 eyes (10%) of std. V, two of 16 eyes (12.5%) in std. VII and VIII children, amounting to a P100 amplitude abnormality in 5% eyes in toto. The interocular differences in all VEP parameters among the subjects were statistically insignificant. Conclusion In schoolchildren in whom normal latencies and amplitudes were obtained, the presence of reproducible VEPs indicated the normal functional status of their visual pathway. On the other hand, in those children where altered VEP findings were found, it hinted toward complementary information that they may have underlying ocular disorders that were yet to be diagnosed. Hence, this study provides insight into the assessment of visual system function, which is primarily difficult in young children.

Relationship between function and structure in the visual cortex in healthy individuals and in patients with severe mental disorders.

Patients with schizophrenia spectrum disorders (SCZspect) and bipolar disorders (BD) show impaired function in the primary visual cortex (V1), indicated by altered visual evoked potential (VEP). While the neural substrate for altered VEP in these patients remains elusive, altered V1 structure may play a role. One previous study found a positive relationship between the amplitude of the P100 component of the VEP and V1 surface area, but not V1 thickness, in a small sample of healthy individuals. Here, we aimed to replicate these findings in a larger healthy control (HC) sample (n = 307) and to examine the same relationship in patients with SCZspect (n = 30) or BD (n = 45). We also compared the mean P100 amplitude, V1 surface area and V1 thickness between controls and patients and found no significant group differences. In HC only, we found a significant positive P100-V1 surface area association, while there were no significant P100-V1 thickness relationships in HC, SCZspect or BD. Together, our results confirm previous findings of a positive P100-V1 surface area association in HC, whereas larger patient samples are needed to further clarify the function-structure relationship in V1 in SCZspect and BD.

Visual Abnormalities Associate With Hippocampus in Mild Cognitive Impairment and Early Alzheimer's Disease.

Background and Objective: Alzheimer's disease (AD) has been shown to affect vision in human patients and animal models. This study was conducted to explore ocular abnormalities in the primary visual pathway and their relationship with hippocampal atrophy in patients with AD and mild cognitive impairment (MCI). The aim of this study was to investigate the potential value of ocular examinations as a biomarker during the AD progression. Methods: Patients with MCI (n = 23) or AD (n = 17) and age-matched cognitively normal controls (NC; n = 19) were enrolled. Pattern visual-evoked potentials (PVEP), flash electroretinogram (FERG) recordings and optical coherence tomography (OCT) were performed for all participants. Hippocampal volumes were measured by 3T magnetic resonance imaging. Cognitive function was assessed by Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Pearson correlation was employed to analyze the potential associations between ocular abnormalities and hippocampal volumes. Hierarchical regression models were conducted to determine associations between cognitive performances and ocular abnormalities as well as hippocampal volumes after adjusting for confounding factors including age, sex, cognitive reserve, and APOE4 status. Results: PVEP amplitude of P100 waveform was significantly decreased in AD patients compared to MCI and normal individuals. In FERG test, delayed latencies of rod response, rod cone response and 3.0 flicker time were found in cognitively impaired groups, indicating dysfunctions of both the rod and cone systems in the disease progression. OCT test revealed reduced macular retinal nerve fiber layer (m-RNFL) thickness in MCI and AD patients, which significantly correlated with brain structure of hippocampus particularly vulnerable during the progression of AD. Interestingly, P100 amplitude showed a significant association with hippocampal volumes even after adjusting confounding factors including age, sex, and cognitive reserve. Hierarchical regression analysis further demonstrated that m-RNFL thickness, as well as hippocampal volumes, significantly associated with ADAS-cog scores. Conclusion: P100 amplitude and m-RNFL thickness showed significant correlations with brain structure involved in AD-related neurodegeneration, and therefore proved to be potential indicators of brain imaging pathologies.

Application of PRVEP Waveform Amplitude Ratio to Evaluate Visual Acuity and Its Forensic Significance.

ABSTRACT: Objective To research the correlation between the visual acuity ratio and pattern reversal visual evoked potential （PRVEP） P100 waveform amplitude ratio of both eyes. Methods Forty-seven volunteers were selected, and the visual chart visual acuity of both eyes was measured. The visual acuity ratio of the eye with poor vision to the eye with better vision was calculated by five grade notation method. The amplitudes of P100 waveforms of both eyes were recorded respectively by using black-and-white checkerboard PRVEP and chosing 1°, 15' stimulating visual angle, and the ratio of amplitudes between the two eyes was also calculated. SPSS 20.0 software was used to analyze the correlation between the visual acuity ratio and the ratio of P100 waveform amplitudes between the two eyes. Return test and linear regression analysis with the binocular ratio of P100 waveform amplitudes as the independent variable （x） and the binocular visual acuity ratio as the dependent variable （y） were made. Results There was a positive correlation between the binocular visual acuity ratio and the ratio of P100 waveform amplitudes under 15' stimulating visual angle （Pearson correlation coefficient was 0.62, P=0.000）. The fitting linear regression equation was y=0.090 x+0.846 （F=20.954, P=0.000）. There was no significant correlation between the binocular ratio of visual acuity and the binocular ratio of P100 waveform amplitudes under 1° stimulating visual angle （P>0.05）. Results of return test showed that there was no statistical significance in the difference between visual acuity estimated by equation and actual detected visual acuity. Conclusion In forensic appraisal of monocular injury, fitting linear regression equation of binocular visual acuity ratio and the binocular ratio of P100 waveform amplitudes under 15' stimulating visual angle, is helpful for visual acuity level estimation of the injured eye to some extent.

Normative values of visual evoked potentials in Northeastern of Iran.

PURPOSE: Visual evoked potentials (VEPs) provide important diagnostic information related to the functional integrity of the visual pathways. The aim of this study was to establish normative values of different components of pattern reversal VEPs on Iranian normal adult subjects. METHODS: Monocular and binocular pattern reversal VEPs were recorded on 59 healthy participants (22.55±3.79 years old) using the Roland RETI system for two check sizes of 15 and 60min of arc. The measured VEP components were the latencies of N75, P100, N135 and amplitude of N75-P100. RESULTS: Repeated measures ANOVA showed that viewing eye condition has a significant impact on the amplitude of N75-P100 (P<0.001, F=13.89). Also, the effect of check size on the latencies of N75, P100, N135, amplitude of N75-P100 (P≤0.010), as well as the intraocular difference of P100 latency and amplitude N75-P100 (P=0.007) was significant. More specifically, the amplitude of N75-P100 in both check sizes significantly differed between gender groups (P<0.023). CONCLUSION: According to the results of this study, VEPs components are affected by the stimulus size, monocular and binocular recording conditions and gender. Therefore, it is necessary to determine the normative values of VEPs in each population, so that the results could be used in clinical studies.

Influence of visual angle on pattern reversal visual evoked potentials.

PURPOSE: The aim of this study was to find whether the visual evoked potential (VEP) latencies and amplitude are altered with different visual angles in healthy adult volunteers or not and to determine the visual angle which is the optimum and most appropriate among a wide range of check sizes for the reliable interpretation of pattern reversal VEPs (PRVEPs). MATERIALS AND METHODS: The present study was conducted on 40 healthy volunteers. The subjects were divided into two groups. One group consisted of 20 individuals (nine males and 11 females) in the age range of 25-57 years and they were exposed to checks subtending a visual angle of 90, 120, and 180 minutes of arc. Another group comprised of 20 individuals (10 males and 10 females) in the age range of 36-60 years and they were subjected to checks subtending a visual angle of 15, 30, and 120 minutes of arc. The stimulus configuration comprised of the transient pattern reversal method in which a black and white checker board is generated (full field) on a VEP Monitor by an Evoked Potential Recorder (RMS EMG. EPMARK II). The statistical analysis was done by One Way Analysis of Variance (ANOVA) using EPI INFO 6. RESULTS: In Group I, the maximum (max.) P100 latency of 98.8 ± 4.7 and the max. P100 amplitude of 10.05 ± 3.1 µV was obtained with checks of 90 minutes. In Group II, the max. P100 latency of 105.19 ± 4.75 msec as well as the max. P100 amplitude of 8.23 ± 3.30 µV was obtained with 15 minutes. The min. P100 latency in both the groups was obtained with checks of 120 minutes while the min. P100 amplitude was obtained with 180 minutes. A statistically significant difference was derived between means of P100 latency for 15 and 30 minutes with reference to its value for 120 minutes and between the mean value of P100 amplitude for 120 minutes and that of 90 and 180 minutes. CONCLUSION: Altering the size of stimulus (visual angle) has an effect on the PRVEP parameters. Our study found that the 120 is the appropriate (and optimal) check size that can be used for accurate interpretation of PRVEPs. This will help in better assessment of the optic nerve function and integrity of anterior visual pathways.