Longitudinal VEP Analysis Reveals Divergent Markers of Inflammation and Neurodegeneration in Multiple Sclerosis

Longitudinal VEP Analysis Reveals Divergent Markers of Inflammation and Neurodegeneration in Multiple Sclerosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Longitudinal VEP Analysis Reveals Divergent Markers of Inflammation and Neurodegeneration in Multiple Sclerosis Abdulkadir TUNÇ, Meral Seferoğlu, Sami Ömerhoca, Semanur AKSU, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6572073/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Visual evoked potentials (VEPs) are valuable tools for assessing optic pathway integrity in multiple sclerosis (MS), yet the longitudinal implications of P100 latency and amplitude changes remain unclear. The aim of this study was to explore the clinical and prognostic value of serial VEP assessments in MS, focusing on differences between latency and amplitude changes. Methods We retrospectively analyzed 83 MS patients from three centers who underwent ≥ 2 pattern-reversal VEPs at least one year apart. Patients with recent optic neuritis were excluded. Clinical, radiological, and CSF findings were compared between those with and without significant VEP changes. Disability progression was evaluated using EDSS. Results During follow-up, 43.4% developed new P100 latency prolongation, associated with higher relapse rates, RRMS phenotype, and more favorable baseline MRI/CSF profiles. In contrast, 56.6% showed significant P100 amplitude reduction, linked to greater EDSS worsening (p < 0.05). Latency changes were not associated with disability progression. Amplitude decline—especially in the left eye—correlated modestly but significantly with EDSS change (r = − 0.225, p = 0.041). Conclusions Serial VEPs provide distinct insights into MS pathology. While latency prolongation reflects inflammatory activity, amplitude decline may signal silent neurodegeneration and functional decline. Longitudinal VEP monitoring may improve early detection of progression and guide individualized care. Trial Registration Not applicable Multiple Sclerosis Visual Evoked Potentials Neurodegeneration Disease Progression Prognosis Figures Figure 1 Figure 2 Background Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that frequently involves the visual pathways. Optic neuritis (ON) is a common manifestation of MS, occurring in up to 50–70% of patients at some point during the disease course [ 1 , 2 ]. Even in the absence of overt ON, subclinical demyelination of the optic nerve and visual pathways is often present in MS, contributing to subtle visual dysfunction that may go unrecognized [ 3 – 5 ]. Because the visual system can be readily evaluated with both structural and functional measures, it has emerged as a useful model for studying MS-related neuroinflammation and neurodegeneration in vivo [ 4 , 6 ]. In particular, damage in the anterior visual pathway provides insight into broader MS pathology, given that retinal axons and optic nerve myelin are frequently targets of the disease from its earliest stages [ 7 ]. Visual evoked potentials (VEPs) are a well-established, noninvasive neurophysiological tool for assessing the integrity of the visual pathways [ 8 ]. In MS, conventional full-field pattern-reversal VEPs have long been used to detect optic nerve lesions that may be clinically silent, thereby providing evidence of dissemination in space even when patients have no visual symptoms [ 9 , 10 ]. The P100 component of the pattern-reversal VEP – a positive waveform peaking around 100 ms – is of particular clinical relevance. A delayed P100 latency in MS is highly sensitive for optic nerve demyelination or incomplete remyelination, and can be observed even in eyes without a history of acute ON [ 8 , 11 ]. Thus, VEPs serve as an objective means to uncover subclinical visual pathway involvement in MS, complementing other diagnostic modalities such as MRI. In addition to their diagnostic utility, VEPs are increasingly recognized for their potential use in monitoring disease and as outcome measures in clinical trials aimed at neuroprotection or repair [ 7 , 9 ]. Cross-sectional studies have demonstrated that VEP latency prolongation correlates with greater MRI lesion load and even with brain atrophy, suggesting that slower visual conduction may reflect a broader impact of MS on central nervous system integrity [ 4 , 12 ]. VEP abnormalities have also been associated with clinical disability: for example, patients with prolonged P100 latencies or reduced amplitudes tend to have higher Expanded Disability Status Scale (EDSS) scores and worse functional outcomes [ 3 , 13 ]. Longitudinal assessment of VEPs could offer a means to track subclinical disease progression in MS, but to date only a few studies have addressed this in detail [ 3 , 6 , 7 ]. Earlier investigations provided hints that serial evoked potential testing might predict future outcomes – for example, Fuhr et al. [ 14 ] observed that VEP and motor EP changes over time paralleled clinical evolution in MS, and Kallmann et al. [ 15 ] reported that patients with abnormal baseline EPs developed greater disability on follow-up. Despite these examples, no consensus has been reached on how to incorporate serial VEP monitoring into routine practice, largely because robust longitudinal data linking VEP change to definitive clinical or radiological outcomes are still limited. In particular, the question remains whether progressive latency prolongation or amplitude loss on VEP truly anticipates upcoming disability or MRI changes, or if these measures simply mirror damage that has already occurred. In this context, the current study was designed to investigate the clinical and prognostic value of serial conventional VEP assessments in MS. We conducted a retrospective cohort analysis in MS patients (encompassing both RRMS and SPMS phenotypes) who underwent repeat pattern-reversal VEP testing, with the aim of determining whether longitudinal changes in P100 latency and amplitude are associated with disease activity and progression. Ultimately, the goal was to evaluate the potential prognostic utility of VEP monitoring over time – that is, whether changes in VEP latency or amplitude can serve as early warning signals of clinical deterioration or imaging changes – thereby informing individualized monitoring strategies and improving long-term management of MS. Methods Study Design and Participants This multicenter retrospective cohort study was conducted using patient data from three different MS centers in Turkey. Patients diagnosed with relapsing or progressive MS according to the revised 2017 McDonald criteria [ 16 ] were included. Ethical approval was granted by the Sakarya University Faculty of Medicine Ethics Committee (approval number: 150, 19/11/24). The study complied fully with the Declaration of Helsinki, and informed consent was obtained from all participants. Initially, patient records from 2980 individuals were screened, and ultimately, 83 patients met all inclusion criteria. Eligible patients were aged 18–65 years, had undergone at least two VEP tests at least one year apart, and had complete clinical and radiological records available. Exclusion criteria included significant comorbidities affecting visual function or neurological disability (e.g., diabetes mellitus, Graves' disease, uveitis), baseline EDSS scores > 5.5, incomplete records, and use of non-standard immunosuppressive treatments or multiple disease-modifying therapies (DMTs) within six months prior to or between the two VEP assessments. Additionally, patients who experienced an MS relapse or suspected optic neuritis within three months before VEP testing or who experienced optic neuritis between two VEP assessments were excluded (Fig. 1 ). Data Collection Clinical data collected retrospectively included demographic variables (age, sex), disease duration, clinical phenotype (RRMS or SPMS), EDSS scores, annualized relapse rate (ARR), and types and durations of DMTs. Radiological data included MRI findings at baseline: lesion presence and distribution (brainstem, spinal cord, upper cervical cord segments C1–C4), total T2 lesion count, and gadolinium-enhancing lesions. Cerebrospinal fluid (CSF) analyses included oligoclonal band (OCB) status and IgG index values. Visual Evoked Potentials (VEPs) VEP tests were performed routinely, not due to clinical suspicion of relapse or optic neuritis, using a Key-point Classic EMG device (Alpine Biomed, Skovlunde, Denmark). Testing adhered strictly to the International Society for Clinical Electrophysiology of Vision (ISCEV) guidelines. Pattern-reversal stimulation utilized a checkerboard stimulus (8 × 8 size, high contrast) under optimal conditions, including standardized room temperature (22–24°C), dim lighting, and appropriate patient positioning and fixation. Silver-silver chloride cup electrodes were placed according to the international 10–20 EEG system, with the active electrode over the occipital cortex (Oz), reference electrode at the frontal area (Fz), and ground electrode at the vertex (Cz). Monocular full-field stimulation was performed. P100 latency and N75–P100 peak-to-peak amplitude were measured bilaterally. Published literature defined abnormal findings as P100 latency > 118 ms and amplitude < 5 µV [ 17 ]. Significant latency prolongation was defined as an increase exceeding 1 ms between consecutive tests or crossing the threshold (118 ms), whereas amplitude reduction was defined as a decrease exceeding 0.3 µV or falling below 5 µV [ 17 ]. Disability progression was monitored using annual EDSS evaluations, with clinical worsening defined as any confirmed EDSS increase from baseline. Relapse frequency and ARR were documented. Annual MRI scans assessed new lesion formation and gadolinium enhancement. Associations between VEP parameter changes (latency and amplitude) and disability progression were evaluated using correlation analyses. Statistical Analysis All statistical analyses were performed using IBM SPSS Statistics for MacOS, version 30.0 (IBM Corp., Armonk, NY, USA). Categorical variables were summarized as frequencies and percentages, while continuous variables were reported as medians with minimum and maximum values. The Kolmogorov–Smirnov test was used to assess the normality of continuous data. Group comparisons for continuous variables were conducted using the Mann–Whitney U test, while categorical variables were analyzed using Pearson’s chi-square test or Fisher’s exact test, as appropriate. Associations between changes in VEP parameters and disability progression (EDSS change) were evaluated using Spearman’s rank correlation analysis. Logistic regression analysis was applied to identify independent predictors of P100 latency prolongation. A two-tailed p-value < 0.05 was considered statistically significant for all tests. Results Demographic and Baseline Characteristics A total of 83 MS patients were included (79.5% female) with a median age of 36 years (range 18–60). The majority (90.4%) had RRMS, while 9.6% had SPMS. The median disease duration was 6 years at baseline. Baseline disability was mild with a median EDSS of 1.5 (range 0–6). The median interval between the initial and follow-up VEP assessments was 2.0 years, during which the median ARR was 0.3 relapses per year. At the first visit, median P100 latencies were approximately 115 ms and P100 amplitudes around 9–10 µV (e.g., right eye P100: 116 ms latency, 9.0 µV amplitude). In initial MRI scans, brainstem lesions were present in 32.5% of patients and spinal cord lesions in 57.8% (Table 1). Longitudinal Changes in VEP Parameters and Their Clinical Correlates During follow-up, 36 patients (43.4%) exhibited a significant prolongation of P100 latency in at least one eye (Table 2). Patients who developed latency prolongation had a significantly higher ARR during the follow-up period (median 0.9 vs 0.0, p < 0.001). All patients in this group had RRMS, compared to 83% in the non-prolongation group; no cases of SPMS were observed among them ( p 0.05), patients with latency prolongation had significantly better baseline visual acuity in the right eye (median 0.9 vs 0.8, p = 0.015). Patients who developed latency prolongation demonstrated significantly fewer brainstem lesions (19.4% vs 42.6%, p = 0.047) and spinal cord lesions (38.9% vs 72.3%, p = 0.005) on initial MRI. They also had a lower prevalence of upper cervical cord (C1–C4) lesions (22.2% vs 46.8%, p = 0.038) and gadolinium-enhancing lesions at diagnosis (19.4% vs 53.2%, p = 0.004). In line with these imaging findings, the median CSF IgG index was significantly lower in the latency-prolongation group (0.7 vs 0.9, p = 0.035) (Table 2). Over half of the cohort (47 patients, 56.6%) demonstrated a significant reduction in P100 amplitude during follow-up (Table 3). Notably, baseline P100 latency was shorter in patients who later experienced amplitude loss; for instance, the initial right-eye latency was 112 ms compared to 119.5 ms in the group without amplitude reduction ( p = 0.028). Despite comparable baseline EDSS scores, patients with amplitude reduction accumulated more disability over the study period. Their EDSS scores were significantly higher both at the time of the second VEP assessment (median 1.5 vs 1.0, p = 0.017) and at the final follow-up evaluation (median 1.5 vs 1.0, p = 0.028) (Table 3) (Figure 2). Overall, 23 patients (27.7%) exhibited a significant VEP change during follow-up, defined as either a new P100 latency prolongation or amplitude reduction (Table 4). Compared to patients without VEP changes, those in the VEP-change group had significantly shorter (i.e., more normal) baseline P100 latencies—for example, the initial right-eye latency was 106 ms versus 118.5 ms in the no-change group ( p = 0.002). They also demonstrated better baseline visual acuity in the affected eye (right-eye visual acuity: 1.0 vs 0.8, p = 0.046). The VEP-change group had a significantly higher ARR ( p = 0.014). However, no significant differences in EDSS were observed between the groups at baseline or at the second evaluation (median EDSS ~1.5 in both, p > 0.5) (Table 4). Correlation analyses were conducted to examine the relationship between VEP changes and disability progression. Most associations were weak and not statistically significant. Specifically, changes in P100 latency were not correlated with changes in EDSS ( p > 0.15). However, a modest but significant inverse correlation was found between the change in left-eye P100 amplitude and EDSS change (Spearman’s r = –0.225, p = 0.041), suggesting that greater amplitude loss was associated with slight disability worsening (Table 5). Baseline VEP Abnormalities and Clinical Associations To explore the prognostic relevance of initial VEP status, patients were stratified by baseline P100 latency (normal ≤118 ms vs prolonged >118 ms) and amplitude (normal vs reduced). Prolonged latency at baseline was observed in 26 patients (31.3%) and was associated with a higher frequency of spinal cord lesions on initial MRI (76.9% vs 49.1%, p = 0.032). However, no significant differences were noted in ARR, EDSS scores, or other clinical parameters. In contrast, patients with reduced baseline P100 amplitude had a higher ARR during the follow-up period (median 1.0 vs 0.0, p = 0.044) and more frequently presented with visual symptoms at disease onset (55.6% vs 26.2%, p = 0.029). They were also slightly older (median 40.5 vs 36 years, p = 0.045) and had fewer gadolinium-enhancing lesions on initial MRI (11.1% vs 46.2%, p = 0.015). Despite these associations, no significant differences in EDSS progression were observed between groups with normal and abnormal baseline VEP values (Table 6). Discussion In this retrospective cohort study, we longitudinally evaluated conventional VEP metrics in 83 patients with relapsing or progressive MS. Nearly half of the patients (43.4%) developed a significant P100 latency prolongation during follow-up, which was significantly associated with higher relapse activity and an exclusive RRMS phenotype. Interestingly, this group also exhibited fewer brainstem, spinal cord, and gadolinium-enhancing lesions on baseline MRI, along with a lower CSF IgG index. In parallel, 56.6% of patients experienced a reduction in P100 amplitude over time, and this subgroup showed greater disability accumulation despite similar baseline EDSS scores. Notably, EDSS progression was not correlated with latency changes but showed a modest yet significant association with declining P100 amplitude, particularly in the left eye. While abnormal VEP findings were also identified at baseline—prolonged latencies correlating with spinal cord involvement, and reduced amplitudes with older age and higher relapse risk—these initial abnormalities were not predictive of subsequent disability. The two principal VEP metrics – P100 latency and amplitude – reflect distinct pathophysiological aspects of MS. A prolonged P100 latency indicates slowed axonal conduction caused by demyelination along the visual pathways [ 8 , 11 ], whereas a reduced P100 amplitude signifies axonal loss or persistent conduction block, reflecting irreversible damage [ 9 , 18 ]. For instance, in acute optic neuritis, both latency delay and amplitude attenuation are commonly observed; latency may partially recover with remyelination, but amplitude loss often persists in cases of axonal degeneration [ 11 , 18 ]. These complementary parameters offer a unique window into subclinical demyelination and neurodegeneration. Notably, patients in the progressive phase of MS often exhibit more pronounced abnormalities in both measures, consistent with cumulative axonal loss [ 7 , 10 ]. Our findings support this dual-pathway interpretation. Latency prolongation was strongly associated with relapse activity but not with subsequent disability accumulation, highlighting its sensitivity for inflammatory demyelination rather than neurodegenerative burden. In contrast, amplitude reductions were closely associated with progressive disability, aligning with the concept that axonal loss is the primary driver of irreversible functional decline in MS [ 13 , 18 ]. This dichotomy was further supported by the observation that latency prolongation emerged in patients with favorable baseline characteristics—including fewer spinal cord lesions, lower IgG index, and absence of SPMS—suggesting that focal optic pathway demyelination can evolve independently of global disease burden [ 4 , 19 ]. Conversely, amplitude decline revealed ongoing neurodegeneration, particularly in clinically stable individuals, supporting its role as a marker of “silent progression” or PIRA (progression independent of relapse activity) [ 20 , 21 ]. These results are in line with prior reports that emphasized the prognostic value of VEP abnormalities in predicting future clinical outcomes. Miletic-Drakulic et al. [ 13 ] demonstrated that preserved VEP responses were predictive of achieving NEDA-3 over 10 years, whereas significant unilateral delays were linked to less favorable disease trajectories. Similarly, Vecchio et al. [ 3 ] showed that prolonged latency in non-neuritic eyes at diagnosis forecasted subsequent disability and lesion accrual. Although in our study baseline VEP abnormalities were not independently predictive of disability progression, longitudinal changes—particularly amplitude decline—were more strongly correlated with EDSS worsening. This reinforces the added value of serial monitoring over single-point assessments. Importantly, several classical studies, such as those by Fuhr et al. [ 14 ] and Kallmann et al. [ 15 ], have shown that early evoked potential abnormalities across multiple modalities can predict long-term outcomes. However, their designs typically relied on baseline testing alone. Our findings suggest that monitoring dynamic changes in VEP parameters over time may offer a more nuanced assessment of disease trajectory, particularly in patients who appear clinically stable. This approach is also supported by more recent work highlighting that VEP metrics correlate with MRI parameters such as lesion volume and brain atrophy, and may outperform standard clinical measures in detecting diffuse or subclinical pathology [ 6 , 12 ]. While our findings underscore the utility of VEP monitoring in MS, certain limitations must be acknowledged. The retrospective design and relatively short follow-up period may have limited the ability to detect longer-term associations. In addition, the lack of optical coherence tomography (OCT) data—despite its strong correlation with VEP metrics and visual outcomes—prevented integrated structure-function analysis [ 22 , 23 ]. Although patients with recent optic neuritis were excluded, the possibility of subclinical episodes or partial remyelination cannot be entirely ruled out. Conclusions Taken together, our data support the implementation of serial VEP assessments in MS care—not only to document optic pathway involvement but also to detect early signs of neurodegenerative progression. Specifically, while latency prolongation may serve as an early marker of demyelination in the context of inflammatory activity, amplitude decline appears more directly linked to accumulating disability and may reflect irreversible axonal loss. These findings advocate for the integration of longitudinal VEP metrics into multimodal monitoring strategies, potentially improving risk stratification and treatment optimization in MS patients. Abbreviations ARR Annualized Relapse Rate CSF Cerebrospinal Fluid DMT Disease-Modifying Therapy EDSS Expanded Disability Status Scale Gd+ Gadolinium-Enhancing Lesion IMT Immunomodulatory Treatment ISCEV International Society for Clinical Electrophysiology of Vision MS Multiple Sclerosis MRI Magnetic Resonance Imaging OCB Oligoclonal Bands OCT Optical Coherence Tomography ON Optic Neuritis PIRA Progression Independent of Relapse Activity RRMS Relapsing–Remitting Multiple Sclerosis SPMS Secondary Progressive Multiple Sclerosis VEP Visual Evoked Potential Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of Sakarya University Faculty of Medicine (Approval No: 150, 19/11/24). Written informed consent was obtained from all participants. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Funding The authors received no financial support for the research, authorship, and/or publication of this article. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Authors’ contributions AT and MS conceptualized the study, supervised data collection, and interpreted the data. SO and EC contributed to data collection, statistical analysis, and figure preparation. SA and HK participated in literature review, data analysis, and manuscript editing. SÖ and NKİ supported patient selection, helped prepare tables and figures, and contributed to result interpretation. AT drafted the manuscript. All authors reviewed and approved the final manuscript. Acknowledgements We thank all participating patients and technical staff at the three centers involved. 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Distribution of Demographic and Clinical Characteristics of the Patients (n = 83) Variable Total Age, years 36 (18–60) Sex, n (%) Female 66 (79.5) Male 17 (20.5) Baseline VEP latency (ms) Right eye 116 (95–162) Left eye 114 (96–168) Baseline VEP amplitude (µV) Right eye 9.0 (0.2–20.5) Left eye 9.5 (1.8–20.5) Follow-up VEP latency (ms) Right eye 113 (97–163) Left eye 112 (98–148) Follow-up VEP amplitude (µV) Right eye 9.1 (2.6–21.0) Left eye 9.5 (1.2–21.0) VEP abnormality, n (%) Baseline right eye 9 (10.8) Baseline left eye 9 (10.8) Follow-up right eye 3 (3.6) Follow-up left eye 8 (9.6) Visual acuity Right eye 1.0 (0.1–1.0) Left eye 1.0 (0.1–1.0) Interval between VEPs, years 2.0 (1–6) MS disease duration, years 6.0 (1.3–25.2) Clinical phenotype, n (%) RRMS 75 (90.4) SPMS 8 (9.6) Immunomodulatory treatment during VEP interval, n (%) No treatment 5 (6.0) Interferon 9 (10.8) Glatiramer acetate 10 (12.0) Teriflunomide 16 (19.3) Dimethyl fumarate 19 (22.9) Fingolimod 11 (13.3) Natalizumab 5 (6.0) Cladribine 1 (1.2) Ocrelizumab 7 (8.4) Baseline MRI findings, n (%) Brainstem lesion 27 (32.5) Spinal cord lesion 48 (57.8) Upper cervical cord lesion (C1–C4) 30 (36.1) T2 lesion count <9 37 (44.6) T2 lesion count ≥9 46 (55.4) Gadolinium-enhancing lesion 32 (38.6) Number of Gd+ lesions 1.0 (1–5) CSF findings Oligoclonal bands (n = 72), n (%) Negative 16 (22.2) Positive 56 (77.8) IgG index 0.8 (0.4–2.2) Initial MS symptom, n (%) Visual 27 (32.5) Paresthesia 22 (26.5) Pyramidal 11 (13.3) Cerebellar 6 (7.2) Brainstem 8 (9.6) Other 9 (10.8) Symptom improvement within 6 months after first steroid pulse, n (%) Complete 51 (62.2) Partial 29 (35.4) None 2 (2.4) EDSS scores At baseline VEP 1.5 (0–6.0) At follow-up VEP 1.5 (0–6.5) Current EDSS 1.5 (0–6.5) ARR 0.3 (0–3.0) Abbreviations: MS, multiple sclerosis; VEP, visual evoked potential; RRMS, relapsing–remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; EDSS, Expanded Disability Status Scale; MRI, magnetic resonance imaging; Gd+, gadolinium-enhancing; CSF, cerebrospinal fluid; OCB, oligoclonal bands; ARR, annualized relapse rate. Table 2. Demographic and Clinical Characteristics According to P100 Latency Prolongation Status Variable No Latency Prolongation (n = 47) Latency Prolongation (n = 36) p-value Age, years 36 (23–60) 36 (18–58) 0.993 Sex, n (%) 0.632 Female 36 (76.6) 30 (83.3) Male 11 (23.4) 6 (16.7) Right-eye visual acuity 0.8 (0.1–1.0) 0.9 (0.1–1.0) 0.015 Left-eye visual acuity 1.0 (0.1–1.0) 1.0 (0.5–1.0) 0.188 Interval between VEPs, years 2.0 (1–6) 2.4 (1–4.5) 0.732 MS disease duration, years 7.0 (1.3–25.2) 5.0 (1.6–14.2) 0.062 Clinical phenotype, n (%) 0.009 RRMS 39 (83.0) 36 (100.0) SPMS 8 (17.0) 0 (0.0) IMT use between VEPs, n (%) 0.280 No treatment 3 (6.4) 2 (5.6) Interferon 4 (8.5) 5 (13.9) Glatiramer acetate 4 (8.5) 6 (16.7) Teriflunomide 8 (17.0) 8 (22.2) Dimethyl fumarate 9 (19.1) 10 (27.8) Fingolimod 10 (21.3) 1 (2.8) Natalizumab 4 (8.5) 1 (2.8) Cladribine 1 (2.1) 0 (0.0) Ocrelizumab 4 (8.5) 3 (8.3) Baseline MRI findings, n (%) Brainstem lesion 20 (42.6) 7 (19.4) 0.047 Spinal cord lesion 34 (72.3) 14 (38.9) 0.005 Upper cervical cord lesion (C1–C4) 22 (46.8) 8 (22.2) 0.038 T2 lesion count ≥9 28 (59.6) 18 (50.0) 0.518 Gadolinium-enhancing lesion 25 (53.2) 7 (19.4) 0.004 Gd+ lesion count 1 (1–5) 2 (1–3) 0.532 CSF findings OCB positivity (n = 72), n (%) 32/39 (82.1) 24/33 (72.7) 0.507 IgG index 0.9 (0.5–2.2) 0.7 (0.4–1.4) 0.035 Initial MS symptom, n (%) 0.088 Visual 19 (40.4) 8 (22.2) Paresthesia 8 (17.0) 14 (38.9) Pyramidal 4 (8.5) 7 (19.4) Cerebellar 4 (8.5) 2 (5.6) Brainstem 5 (10.6) 3 (8.3) Other 7 (14.9) 2 (5.6) Improvement after first pulse steroid, n (%) 0.461 Complete 29 (61.7) 22 (62.9) Partial 16 (34.0) 13 (37.1) None 2 (4.3) 0 (0.0) EDSS scores At first VEP 1.5 (0–6.0) 1.5 (1.0–3.5) 0.521 At second VEP 1.5 (0–6.5) 1.5 (1.0–3.5) 0.422 At last follow-up 1.5 (0–6.5) 1.5 (1.0–3.5) 0.648 ARR 0.0 (0–2.0) 0.9 (0–3.0) <0.001 Statistical comparisons were conducted using Mann–Whitney U test for continuous variables and Fisher’s exact test or Pearson’s chi-square test for categorical variables, as appropriate. A p-value < 0.05 was considered statistically significant. Abbreviations: RRMS, relapsing–remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; IMT, immunomodulatory treatment; VEP, visual evoked potential; MRI, magnetic resonance imaging; Gd+, gadolinium-enhancing; OCB, oligoclonal bands; EDSS, Expanded Disability Status Scale; ARR, annualized relapse rate. Table 3. Demographic and Clinical Characteristics According to P100 Amplitude Reduction Status Variable No Amplitude Reduction (n = 36) Amplitude Reduction (n = 47) p-value Age, years 37 (23–58) 36 (18–60) 0.639 Sex, n (%) 0.304 Female 31 (86.1) 35 (74.5) Male 5 (13.9) 12 (25.5) Baseline VEP latency (ms) Right eye 119.5 (96.6–162) 112 (95–151) 0.028 Left eye 115.5 (100–163) 113 (96–168) 0.184 Follow-up VEP latency (ms) Right eye 112.5 (99–163) 113 (97–142) 0.398 Left eye 110.5 (101–146) 113 (98–148) 0.523 Visual acuity Right eye 1.0 (0.2–1.0) 1.0 (0.1–1.0) 0.581 Left eye 1.0 (0.5–1.0) 1.0 (0.1–1.0) 0.840 Interval between VEPs, years 2.0 (1–5) 2.2 (1–6) 0.191 MS disease duration, years 5.3 (1.5–25.2) 6.0 (1.3–20.0) 0.266 Clinical phenotype, n (%) 0.456 RRMS 34 (94.4) 41 (87.2) SPMS 2 (5.6) 6 (12.8) IMT use between VEPs, n (%) 0.317 No treatment 2 (5.6) 3 (6.4) Interferon 2 (5.6) 7 (14.9) Glatiramer acetate 2 (5.6) 8 (17.0) Teriflunomide 9 (25.0) 7 (14.9) Dimethyl fumarate 8 (22.2) 11 (23.4) Fingolimod 7 (19.4) 4 (8.5) Natalizumab 3 (8.3) 2 (4.3) Cladribine 1 (2.8) 0 (0.0) Ocrelizumab 2 (5.6) 5 (10.6) Baseline MRI findings, n (%) Brainstem lesion 12 (33.3) 15 (31.9) 1.000 Spinal cord lesion 20 (55.6) 28 (59.6) 0.886 Upper cervical cord lesion (C1–C4) 10 (27.8) 20 (42.6) 0.247 T2 lesion count ≥9 21 (58.3) 25 (53.2) 0.807 Gadolinium-enhancing lesion 15 (41.7) 17 (36.2) 0.778 Gd+ lesion count 1 (1–3) 2 (1–5) 0.278 CSF findings OCB positivity (n = 31 vs 41), n (%) 25 (80.6) 31 (75.6) 0.824 IgG index 0.8 (0.5–2.2) 0.8 (0.4–2.1) 0.722 Initial MS symptom, n (%) 0.568 Visual 13 (36.1) 14 (29.8) Paresthesia 7 (19.4) 15 (31.9) Pyramidal 4 (11.1) 7 (14.9) Cerebellar 3 (8.3) 3 (6.4) Brainstem 3 (8.3) 5 (10.6) Other 6 (16.7) 3 (6.4) Improvement after first steroid, n (%) 0.720 Complete 24 (66.7) 27 (58.7) Partial 11 (30.6) 18 (39.1) None 1 (2.8) 1 (2.2) EDSS scores At baseline VEP 1.0 (0–4.5) 1.5 (1–6.0) 0.118 At follow-up VEP 1.0 (0–5.0) 1.5 (1–6.5) 0.017 At last follow-up 1.0 (0–5.0) 1.5 (0–6.5) 0.028 ARR 0.0 (0–2.0) 0.3 (0–3.0) 0.849 Continuous variables were analyzed using the Mann–Whitney U test, while categorical variables were compared using Fisher’s exact test or Pearson’s chi-square test. Statistical significance was defined as p < 0.05. Abbreviations: RRMS, relapsing–remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; IMT, immunomodulatory treatment; VEP, visual evoked potential; MRI, magnetic resonance imaging; Gd+, gadolinium-enhancing; OCB, oligoclonal bands; EDSS, Expanded Disability Status Scale; ARR, annualized relapse rate. Table 4. Demographic and Clinical Characteristics According to the Presence of Any VEP Change (P100 Latency Prolongation or Amplitude Reduction) Variable No VEP Change (n = 60) VEP Change (n = 23) p-value Age, years 38 (23–60) 35 (18–51) 0.339 Sex, n (%) 1.000 Female 48 (80.0) 18 (78.3) Male 12 (20.0) 5 (21.7) Right-eye visual acuity 0.8 (0.1–1.0) 1.0 (0.1–1.0) 0.046 Left-eye visual acuity 1.0 (0.1–1.0) 1.0 (0.6–1.0) 0.094 Interval between VEPs, years 2.0 (1–6) 2.2 (1–4) 0.735 MS disease duration, years 6.5 (1.3–25.2) 4.8 (2–14.2) 0.191 Clinical phenotype, n (%) 0.099 RRMS 52 (86.7) 23 (100.0) SPMS 8 (13.3) 0 (0.0) IMT use between VEPs, n (%) 0.116 No treatment 4 (6.7) 1 (4.3) Interferon 5 (8.3) 4 (17.4) Glatiramer acetate 4 (6.7) 6 (26.1) Teriflunomide 13 (21.7) 3 (13.0) Dimethyl fumarate 12 (20.0) 7 (30.4) Fingolimod 10 (16.7) 1 (4.3) Natalizumab 5 (8.3) 0 (0.0) Cladribine 1 (1.7) 0 (0.0) Ocrelizumab 6 (10.0) 1 (4.3) Baseline MRI findings, n (%) Brainstem lesion 22 (36.7) 5 (21.7) 0.300 Spinal cord lesion 38 (63.3) 10 (43.5) 0.164 Upper cervical cord lesion (C1–C4) 24 (40.0) 6 (26.1) 0.355 T2 lesion count ≥9 35 (58.3) 11 (47.8) 0.538 Gadolinium-enhancing lesion 26 (43.3) 6 (26.1) 0.233 Gd+ lesion count 1 (1–5) 1.5 (1–3) 0.689 CSF findings OCB positivity (n = 51 vs 21), n (%) 40 (78.4) 16 (76.2) 1.000 IgG index 0.8 (0.5–2.2) 0.7 (0.4–1.4) 0.208 Initial MS symptom, n (%) 0.107 Visual 23 (38.3) 4 (17.4) Paresthesia 12 (20.0) 10 (43.5) Pyramidal 6 (10.0) 5 (21.7) Cerebellar 5 (8.3) 1 (4.3) Brainstem 6 (10.0) 2 (8.7) Other 8 (13.3) 1 (4.3) Improvement after first steroid, n (%) 0.687 Complete 37 (61.7) 14 (63.6) Partial 21 (35.0) 8 (36.4) None 2 (3.3) 0 (0.0) EDSS scores At baseline VEP 1.5 (0–6.0) 1.5 (1–3.5) 0.734 At follow-up VEP 1.5 (0–6.5) 1.5 (1–3.5) 0.850 Current EDSS 1.5 (0–6.5) 1.5 (1–3.5) 0.651 ARR 0.0 (0–2.0) 0.7 (0–3.0) 0.014 Abbreviations: RRMS, relapsing–remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; IMT, immunomodulatory treatment; VEP, visual evoked potential; MRI, magnetic resonance imaging; Gd+, gadolinium-enhancing; OCB, oligoclonal bands; EDSS, Expanded Disability Status Scale; ARR, annualized relapse rate. Statistical comparisons were performed using the Mann–Whitney U test for continuous variables and Fisher’s exact test or Pearson’s chi-square test for categorical variables, as appropriate. Statistical significance was defined as p < 0.05. Table 5. Correlation Between Changes in VEP Parameters and Changes in Disability (EDSS) VEP Parameter Change Change in EDSS (2nd VEP – 1st VEP) Change in EDSS (Current – 2nd VEP) Right-eye P100 latency r = –0.150, p = 0.175 r = 0.009, p = 0.936 Left-eye P100 latency r = –0.157, p = 0.157 r = –0.140, p = 0.208 Right-eye P100 amplitude r = –0.140, p = 0.208 r = 0.019, p = 0.864 Left-eye P100 amplitude r = –0.225, p = 0.041 r = 0.019, p = 0.866 Abbreviations: VEP, visual evoked potential; EDSS, Expanded Disability Status Scale. Spearman correlation analysis was used to assess the relationship between changes in VEP parameters and disability progression. A p-value < 0.05 was considered statistically significant. Table 6. Comparison of Clinical and Radiological Features Based on Baseline VEP Latency and Amplitude Status Variable P100 Latency ≤118 ms (n = 57) P100 Latency >118 ms (n = 26) p Normal Amplitude (n = 65) Reduced Amplitude (n = 18) p Age, years 36 (18–60) 37 (23–55) 0.666 36 (18–60) 40.5 (23–58) 0.045 Sex, female (%) 45 (78.9) 21 (80.8) 1.000 53 (81.5) 13 (72.2) 0.509 Right-eye visual acuity 1.0 (0.1–1.0) 1.0 (0.1–1.0) 0.036 1.0 (0.1–1.0) 1.0 (0.2–1.0) 0.791 Left-eye visual acuity 1.0 (0.2–1.0) 1.0 (0.1–1.0) 0.027 1.0 (0.1–1.0) 1.0 (0.5–1.0) 0.713 Interval between VEPs, years 2.0 (1–5) 2.1 (1–6) 0.527 2.1 (1–6) 1.8 (1–5) 0.257 MS disease duration, years 5.2 (1.3–15.0) 6.0 (3.0–25.2) 0.182 5.2 (1.3–20.0) 6.9 (1.9–25.2) 0.289 RRMS, n (%) 53 (93.0) 22 (84.6) 0.251 57 (87.7) 18 (100.0) 0.191 Spinal cord lesion, n (%) 28 (49.1) 20 (76.9) 0.032 36 (55.4) 12 (66.7) 0.556 Gd+ lesion, n (%) 25 (43.9) 7 (26.9) 0.220 30 (46.2) 2 (11.1) 0.015 OCB positive, n (%) 38 (74.5) 18 (85.7) 0.365 47 (82.5) 9 (60.0) 0.084 IgG index 0.8 (0.4–2.2) 0.8 (0.5–1.4) 0.702 0.8 (0.4–2.2) 0.7 (0.5–1.1) 0.169 Visual symptom onset, n (%) 18 (31.6) 9 (34.6) 0.819 17 (26.2) 10 (55.6) 0.029 EDSS at baseline VEP 1.5 (0–6.0) 1.5 (0–5.5) 0.231 1.5 (0–6.0) 1.0 (1–3.0) 0.254 EDSS at 2nd VEP 1.5 (0–6.5) 1.5 (0–6.0) 0.366 1.5 (0–6.5) 1.3 (1.0–2.5) 0.099 Current EDSS 1.5 (0–6.5) 1.5 (0–6.5) 0.303 1.5 (0–6.5) 1.0 (1.0–6.5) 0.213 ARR between VEPs 0.3 (0–2.0) 0.2 (0–3.0) 0.566 0.0 (0–3.0) 1.0 (0–2.0) 0.044 Abbreviations: VEP, visual evoked potential; RRMS, relapsing–remitting multiple sclerosis; Gd+, gadolinium-enhancing lesion; OCB, oligoclonal bands; EDSS, Expanded Disability Status Scale; ARR, annualized relapse rate. Statistical comparisons were performed using the Mann–Whitney U test for continuous variables and Fisher’s exact or Pearson’s chi-square test for categorical variables. A p-value < 0.05 was considered statistically significant. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6572073","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":462892078,"identity":"d1e8895e-a1ae-414c-bf66-b5bfd08954cb","order_by":0,"name":"Abdulkadir TUNÇ","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABKUlEQVRIiWNgGAWjYDACCQYDhgcHGBjbIFwbBgYemNQBPFoSwFqYQdw0FC2MDfi0NEC0HCashX928zaJhDN2sn3S549JF9Sct+fvOfzsM08NgxzfjQT2xxVYLLlzrEwi4UaycRtfMpv0jGO3E2ecbTOezXOMwVjyRgJj4xks1tzIMZNI+MCc2MbDzCbN23A7geE8gzEzDxtD4gaQFiwuk4doqYdpOWcvf579MzPPP4Z6XFoMwFpuHIZpOcC44WyPMTNvG0OCAQ4thneOFVsknDluDNRibM1zLDlx45kzxYxz+yQMZ5552DgTixa5280bb3w4Vi07v4fx4W2eGjt7uTPpmxnefLOR5zuefOAjtlDGCph4gPHFgCMmsQPGH8SrHQWjYBSMguEPAP7ya+OrHDphAAAAAElFTkSuQmCC","orcid":"","institution":"Sakarya University","correspondingAuthor":true,"prefix":"","firstName":"Abdulkadir","middleName":"","lastName":"TUNÇ","suffix":""},{"id":462892079,"identity":"12b0d702-a101-4b83-ade7-83ac4dde3cdf","order_by":1,"name":"Meral Seferoğlu","email":"","orcid":"","institution":"Bursa Yüksek İhtisas Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Meral","middleName":"","lastName":"Seferoğlu","suffix":""},{"id":462892080,"identity":"ca1c9ad5-4e8f-4e8a-97fe-422acd1a824c","order_by":2,"name":"Sami Ömerhoca","email":"","orcid":"","institution":"Bağcılar Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sami","middleName":"","lastName":"Ömerhoca","suffix":""},{"id":462892081,"identity":"f5b14fe6-0dcb-4bf6-8a24-1a5a3160fb41","order_by":3,"name":"Semanur AKSU","email":"","orcid":"","institution":"Sakarya University","correspondingAuthor":false,"prefix":"","firstName":"Semanur","middleName":"","lastName":"AKSU","suffix":""},{"id":462892082,"identity":"fa3a9820-727a-4c8c-b951-588f16d18f57","order_by":4,"name":"Ertuğrul Çınar","email":"","orcid":"","institution":"Bağcılar Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ertuğrul","middleName":"","lastName":"Çınar","suffix":""},{"id":462892083,"identity":"a35e9ff3-031e-4c28-a788-561364de5d10","order_by":5,"name":"Hakan Kılıçaslan","email":"","orcid":"","institution":"Bursa Yüksek İhtisas Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hakan","middleName":"","lastName":"Kılıçaslan","suffix":""},{"id":462892084,"identity":"733d2d7b-11a0-4dfa-b4c1-97bd84e6086c","order_by":6,"name":"Samet Öncel","email":"","orcid":"","institution":"Sakarya Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Samet","middleName":"","lastName":"Öncel","suffix":""},{"id":462892085,"identity":"a41d3378-19c6-4b3e-a89c-02bf3a193755","order_by":7,"name":"Nilüfer Kale İçen","email":"","orcid":"","institution":"Bağcılar Training and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nilüfer","middleName":"Kale","lastName":"İçen","suffix":""}],"badges":[],"createdAt":"2025-05-01 13:08:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6572073/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6572073/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83766762,"identity":"0527448c-8d67-4c0e-b43e-f6449b217610","added_by":"auto","created_at":"2025-06-02 11:21:01","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":33841,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient Selection Flowchart\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFlowchart illustrating the selection process for patients included in the study. From a total of 2980 patients with MS followed across three centers, 920 underwent VEP testing at diagnosis. Following exclusions based on availability of serial VEPs and clinical eligibility criteria, 83 patients with at least two VEP assessments spaced ≥1 year apart and complete clinical/imaging data were included in the final analysis.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6572073/v1/fd0a3b8d87ec7ba365fabe35.jpg"},{"id":83766761,"identity":"afce1250-aeb2-4ae9-8bc8-d5e1759a0069","added_by":"auto","created_at":"2025-06-02 11:21:01","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":17912,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAssociation Between Amplitude Reduction and Disability Progression.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEDSS scores were consistently higher in patients with VEP amplitude reduction, with error bars estimated from observed min–max distributions. Visual differences are supported by statistically significant p-values at follow-up and last evaluation.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6572073/v1/75ae6faa3d1996c6b3e43834.jpg"},{"id":90965589,"identity":"3df20722-00b5-4855-9fe6-76c576932e3f","added_by":"auto","created_at":"2025-09-10 06:24:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2452877,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6572073/v1/4f24d391-a53d-4bf4-8173-3fc563e875fb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Longitudinal VEP Analysis Reveals Divergent Markers of Inflammation and Neurodegeneration in Multiple Sclerosis","fulltext":[{"header":"Background","content":"\u003cp\u003eMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that frequently involves the visual pathways. Optic neuritis (ON) is a common manifestation of MS, occurring in up to 50\u0026ndash;70% of patients at some point during the disease course [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Even in the absence of overt ON, subclinical demyelination of the optic nerve and visual pathways is often present in MS, contributing to subtle visual dysfunction that may go unrecognized [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Because the visual system can be readily evaluated with both structural and functional measures, it has emerged as a useful model for studying MS-related neuroinflammation and neurodegeneration in vivo [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In particular, damage in the anterior visual pathway provides insight into broader MS pathology, given that retinal axons and optic nerve myelin are frequently targets of the disease from its earliest stages [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVisual evoked potentials (VEPs) are a well-established, noninvasive neurophysiological tool for assessing the integrity of the visual pathways [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In MS, conventional full-field pattern-reversal VEPs have long been used to detect optic nerve lesions that may be clinically silent, thereby providing evidence of dissemination in space even when patients have no visual symptoms [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The P100 component of the pattern-reversal VEP \u0026ndash; a positive waveform peaking around 100 ms \u0026ndash; is of particular clinical relevance. A delayed P100 latency in MS is highly sensitive for optic nerve demyelination or incomplete remyelination, and can be observed even in eyes without a history of acute ON [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Thus, VEPs serve as an objective means to uncover subclinical visual pathway involvement in MS, complementing other diagnostic modalities such as MRI. In addition to their diagnostic utility, VEPs are increasingly recognized for their potential use in monitoring disease and as outcome measures in clinical trials aimed at neuroprotection or repair [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Cross-sectional studies have demonstrated that VEP latency prolongation correlates with greater MRI lesion load and even with brain atrophy, suggesting that slower visual conduction may reflect a broader impact of MS on central nervous system integrity [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. VEP abnormalities have also been associated with clinical disability: for example, patients with prolonged P100 latencies or reduced amplitudes tend to have higher Expanded Disability Status Scale (EDSS) scores and worse functional outcomes [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Longitudinal assessment of VEPs could offer a means to track subclinical disease progression in MS, but to date only a few studies have addressed this in detail [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Earlier investigations provided hints that serial evoked potential testing might predict future outcomes \u0026ndash; for example, Fuhr et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] observed that VEP and motor EP changes over time paralleled clinical evolution in MS, and Kallmann et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] reported that patients with abnormal baseline EPs developed greater disability on follow-up. Despite these examples, no consensus has been reached on how to incorporate serial VEP monitoring into routine practice, largely because robust longitudinal data linking VEP change to definitive clinical or radiological outcomes are still limited. In particular, the question remains whether progressive latency prolongation or amplitude loss on VEP truly anticipates upcoming disability or MRI changes, or if these measures simply mirror damage that has already occurred.\u003c/p\u003e \u003cp\u003eIn this context, the current study was designed to investigate the clinical and prognostic value of serial conventional VEP assessments in MS. We conducted a retrospective cohort analysis in MS patients (encompassing both RRMS and SPMS phenotypes) who underwent repeat pattern-reversal VEP testing, with the aim of determining whether longitudinal changes in P100 latency and amplitude are associated with disease activity and progression. Ultimately, the goal was to evaluate the potential prognostic utility of VEP monitoring over time \u0026ndash; that is, whether changes in VEP latency or amplitude can serve as early warning signals of clinical deterioration or imaging changes \u0026ndash; thereby informing individualized monitoring strategies and improving long-term management of MS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Participants\u003c/h2\u003e \u003cp\u003eThis multicenter retrospective cohort study was conducted using patient data from three different MS centers in Turkey. Patients diagnosed with relapsing or progressive MS according to the revised 2017 McDonald criteria [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] were included. Ethical approval was granted by the Sakarya University Faculty of Medicine Ethics Committee (approval number: 150, 19/11/24). The study complied fully with the Declaration of Helsinki, and informed consent was obtained from all participants. Initially, patient records from 2980 individuals were screened, and ultimately, 83 patients met all inclusion criteria. Eligible patients were aged 18\u0026ndash;65 years, had undergone at least two VEP tests at least one year apart, and had complete clinical and radiological records available. Exclusion criteria included significant comorbidities affecting visual function or neurological disability (e.g., diabetes mellitus, Graves' disease, uveitis), baseline EDSS scores\u0026thinsp;\u0026gt;\u0026thinsp;5.5, incomplete records, and use of non-standard immunosuppressive treatments or multiple disease-modifying therapies (DMTs) within six months prior to or between the two VEP assessments. Additionally, patients who experienced an MS relapse or suspected optic neuritis within three months before VEP testing or who experienced optic neuritis between two VEP assessments were excluded (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eClinical data collected retrospectively included demographic variables (age, sex), disease duration, clinical phenotype (RRMS or SPMS), EDSS scores, annualized relapse rate (ARR), and types and durations of DMTs. Radiological data included MRI findings at baseline: lesion presence and distribution (brainstem, spinal cord, upper cervical cord segments C1\u0026ndash;C4), total T2 lesion count, and gadolinium-enhancing lesions. Cerebrospinal fluid (CSF) analyses included oligoclonal band (OCB) status and IgG index values.\u003c/p\u003e\n\u003ch3\u003eVisual Evoked Potentials (VEPs)\u003c/h3\u003e\n\u003cp\u003eVEP tests were performed routinely, not due to clinical suspicion of relapse or optic neuritis, using a Key-point Classic EMG device (Alpine Biomed, Skovlunde, Denmark). Testing adhered strictly to the International Society for Clinical Electrophysiology of Vision (ISCEV) guidelines. Pattern-reversal stimulation utilized a checkerboard stimulus (8 \u0026times; 8 size, high contrast) under optimal conditions, including standardized room temperature (22\u0026ndash;24\u0026deg;C), dim lighting, and appropriate patient positioning and fixation. Silver-silver chloride cup electrodes were placed according to the international 10\u0026ndash;20 EEG system, with the active electrode over the occipital cortex (Oz), reference electrode at the frontal area (Fz), and ground electrode at the vertex (Cz). Monocular full-field stimulation was performed. P100 latency and N75\u0026ndash;P100 peak-to-peak amplitude were measured bilaterally. Published literature defined abnormal findings as P100 latency\u0026thinsp;\u0026gt;\u0026thinsp;118 ms and amplitude\u0026thinsp;\u0026lt;\u0026thinsp;5 \u0026micro;V [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Significant latency prolongation was defined as an increase exceeding 1 ms between consecutive tests or crossing the threshold (118 ms), whereas amplitude reduction was defined as a decrease exceeding 0.3 \u0026micro;V or falling below 5 \u0026micro;V [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDisability progression was monitored using annual EDSS evaluations, with clinical worsening defined as any confirmed EDSS increase from baseline. Relapse frequency and ARR were documented. Annual MRI scans assessed new lesion formation and gadolinium enhancement. Associations between VEP parameter changes (latency and amplitude) and disability progression were evaluated using correlation analyses.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using IBM SPSS Statistics for MacOS, version 30.0 (IBM Corp., Armonk, NY, USA). Categorical variables were summarized as frequencies and percentages, while continuous variables were reported as medians with minimum and maximum values. The Kolmogorov\u0026ndash;Smirnov test was used to assess the normality of continuous data. Group comparisons for continuous variables were conducted using the Mann\u0026ndash;Whitney U test, while categorical variables were analyzed using Pearson\u0026rsquo;s chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. Associations between changes in VEP parameters and disability progression (EDSS change) were evaluated using Spearman\u0026rsquo;s rank correlation analysis. Logistic regression analysis was applied to identify independent predictors of P100 latency prolongation. A two-tailed p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant for all tests.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eDemographic and Baseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 83 MS patients were included (79.5% female) with a median age of 36 years (range 18\u0026ndash;60). The majority (90.4%) had RRMS, while 9.6% had SPMS. The median disease duration was 6 years at baseline. Baseline disability was mild with a median EDSS of 1.5 (range 0\u0026ndash;6). The median interval between the initial and follow-up VEP assessments was 2.0 years, during which the median ARR was 0.3 relapses per year. At the first visit, median P100 latencies were approximately 115 ms and P100 amplitudes around 9\u0026ndash;10 \u0026micro;V (e.g., right eye P100: 116 ms latency, 9.0 \u0026micro;V amplitude). In initial MRI scans, brainstem lesions were present in 32.5% of patients and spinal cord lesions in 57.8% (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLongitudinal Changes in VEP Parameters and Their Clinical Correlates\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring follow-up, 36 patients (43.4%) exhibited a significant prolongation of P100 latency in at least one eye (Table 2). Patients who developed latency prolongation had a significantly higher ARR during the follow-up period (median 0.9 vs 0.0,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001). All patients in this group had RRMS, compared to 83% in the non-prolongation group; no cases of SPMS were observed among them (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01). Although disease duration and baseline EDSS scores were similar between groups (\u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05), patients with latency prolongation had significantly better baseline visual acuity in the right eye (median 0.9 vs 0.8,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.015). Patients who developed latency prolongation demonstrated significantly fewer brainstem lesions (19.4% vs 42.6%,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.047) and spinal cord lesions (38.9% vs 72.3%,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.005) on initial MRI. They also had a lower prevalence of upper cervical cord (C1\u0026ndash;C4) lesions (22.2% vs 46.8%,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.038) and gadolinium-enhancing lesions at diagnosis (19.4% vs 53.2%,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.004). In line with these imaging findings, the median CSF IgG index was significantly lower in the latency-prolongation group (0.7 vs 0.9,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.035) (Table 2).\u003c/p\u003e\n\u003cp\u003eOver half of the cohort (47 patients, 56.6%) demonstrated a significant reduction in P100 amplitude during follow-up (Table 3). Notably, baseline P100 latency was shorter in patients who later experienced amplitude loss; for instance, the initial right-eye latency was 112 ms compared to 119.5 ms in the group without amplitude reduction (\u003cem\u003ep\u003c/em\u003e = 0.028). Despite comparable baseline EDSS scores, patients with amplitude reduction accumulated more disability over the study period. Their EDSS scores were significantly higher both at the time of the second VEP assessment (median 1.5 vs 1.0,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.017) and at the final follow-up evaluation (median 1.5 vs 1.0,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.028) (Table 3) (Figure 2).\u003c/p\u003e\n\u003cp\u003eOverall, 23 patients (27.7%) exhibited a significant VEP change during follow-up, defined as either a new P100 latency prolongation or amplitude reduction (Table 4). Compared to patients without VEP changes, those in the VEP-change group had significantly shorter (i.e., more normal) baseline P100 latencies\u0026mdash;for example, the initial right-eye latency was 106 ms versus 118.5 ms in the no-change group (\u003cem\u003ep\u003c/em\u003e = 0.002). They also demonstrated better baseline visual acuity in the affected eye (right-eye visual acuity: 1.0 vs 0.8,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.046). The VEP-change group had a significantly higher ARR (\u003cem\u003ep\u003c/em\u003e = 0.014). However, no significant differences in EDSS were observed between the groups at baseline or at the second evaluation (median EDSS ~1.5 in both,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e \u0026gt; 0.5) (Table 4).\u003c/p\u003e\n\u003cp\u003eCorrelation analyses were conducted to examine the relationship between VEP changes and disability progression. Most associations were weak and not statistically significant. Specifically, changes in P100 latency were not correlated with changes in EDSS (\u003cem\u003ep\u003c/em\u003e \u0026gt; 0.15). However, a modest but significant inverse correlation was found between the change in left-eye P100 amplitude and EDSS change (Spearman\u0026rsquo;s\u0026nbsp;\u003cem\u003er\u003c/em\u003e = \u0026ndash;0.225,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.041), suggesting that greater amplitude loss was associated with slight disability worsening (Table 5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline VEP Abnormalities and Clinical Associations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo explore the prognostic relevance of initial VEP status, patients were stratified by baseline P100 latency (normal \u0026le;118 ms vs prolonged \u0026gt;118 ms) and amplitude (normal vs reduced). Prolonged latency at baseline was observed in 26 patients (31.3%) and was associated with a higher frequency of spinal cord lesions on initial MRI (76.9% vs 49.1%,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.032). However, no significant differences were noted in ARR, EDSS scores, or other clinical parameters. In contrast, patients with reduced baseline P100 amplitude had a higher ARR during the follow-up period (median 1.0 vs 0.0,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.044) and more frequently presented with visual symptoms at disease onset (55.6% vs 26.2%,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.029). They were also slightly older (median 40.5 vs 36 years,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.045) and had fewer gadolinium-enhancing lesions on initial MRI (11.1% vs 46.2%,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e = 0.015). Despite these associations, no significant differences in EDSS progression were observed between groups with normal and abnormal baseline VEP values (Table 6).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective cohort study, we longitudinally evaluated conventional VEP metrics in 83 patients with relapsing or progressive MS. Nearly half of the patients (43.4%) developed a significant P100 latency prolongation during follow-up, which was significantly associated with higher relapse activity and an exclusive RRMS phenotype. Interestingly, this group also exhibited fewer brainstem, spinal cord, and gadolinium-enhancing lesions on baseline MRI, along with a lower CSF IgG index. In parallel, 56.6% of patients experienced a reduction in P100 amplitude over time, and this subgroup showed greater disability accumulation despite similar baseline EDSS scores. Notably, EDSS progression was not correlated with latency changes but showed a modest yet significant association with declining P100 amplitude, particularly in the left eye. While abnormal VEP findings were also identified at baseline\u0026mdash;prolonged latencies correlating with spinal cord involvement, and reduced amplitudes with older age and higher relapse risk\u0026mdash;these initial abnormalities were not predictive of subsequent disability.\u003c/p\u003e \u003cp\u003eThe two principal VEP metrics \u0026ndash; P100 latency and amplitude \u0026ndash; reflect distinct pathophysiological aspects of MS. A prolonged P100 latency indicates slowed axonal conduction caused by demyelination along the visual pathways [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], whereas a reduced P100 amplitude signifies axonal loss or persistent conduction block, reflecting irreversible damage [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. For instance, in acute optic neuritis, both latency delay and amplitude attenuation are commonly observed; latency may partially recover with remyelination, but amplitude loss often persists in cases of axonal degeneration [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These complementary parameters offer a unique window into subclinical demyelination and neurodegeneration. Notably, patients in the progressive phase of MS often exhibit more pronounced abnormalities in both measures, consistent with cumulative axonal loss [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Our findings support this dual-pathway interpretation. Latency prolongation was strongly associated with relapse activity but not with subsequent disability accumulation, highlighting its sensitivity for inflammatory demyelination rather than neurodegenerative burden. In contrast, amplitude reductions were closely associated with progressive disability, aligning with the concept that axonal loss is the primary driver of irreversible functional decline in MS [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This dichotomy was further supported by the observation that latency prolongation emerged in patients with favorable baseline characteristics\u0026mdash;including fewer spinal cord lesions, lower IgG index, and absence of SPMS\u0026mdash;suggesting that focal optic pathway demyelination can evolve independently of global disease burden [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Conversely, amplitude decline revealed ongoing neurodegeneration, particularly in clinically stable individuals, supporting its role as a marker of \u0026ldquo;silent progression\u0026rdquo; or PIRA (progression independent of relapse activity) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThese results are in line with prior reports that emphasized the prognostic value of VEP abnormalities in predicting future clinical outcomes. Miletic-Drakulic et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] demonstrated that preserved VEP responses were predictive of achieving NEDA-3 over 10 years, whereas significant unilateral delays were linked to less favorable disease trajectories. Similarly, Vecchio et al. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] showed that prolonged latency in non-neuritic eyes at diagnosis forecasted subsequent disability and lesion accrual. Although in our study baseline VEP abnormalities were not independently predictive of disability progression, longitudinal changes\u0026mdash;particularly amplitude decline\u0026mdash;were more strongly correlated with EDSS worsening. This reinforces the added value of serial monitoring over single-point assessments.\u003c/p\u003e \u003cp\u003eImportantly, several classical studies, such as those by Fuhr et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and Kallmann et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], have shown that early evoked potential abnormalities across multiple modalities can predict long-term outcomes. However, their designs typically relied on baseline testing alone. Our findings suggest that monitoring dynamic changes in VEP parameters over time may offer a more nuanced assessment of disease trajectory, particularly in patients who appear clinically stable. This approach is also supported by more recent work highlighting that VEP metrics correlate with MRI parameters such as lesion volume and brain atrophy, and may outperform standard clinical measures in detecting diffuse or subclinical pathology [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile our findings underscore the utility of VEP monitoring in MS, certain limitations must be acknowledged. The retrospective design and relatively short follow-up period may have limited the ability to detect longer-term associations. In addition, the lack of optical coherence tomography (OCT) data\u0026mdash;despite its strong correlation with VEP metrics and visual outcomes\u0026mdash;prevented integrated structure-function analysis [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Although patients with recent optic neuritis were excluded, the possibility of subclinical episodes or partial remyelination cannot be entirely ruled out.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003e Taken together, our data support the implementation of serial VEP assessments in MS care\u0026mdash;not only to document optic pathway involvement but also to detect early signs of neurodegenerative progression. Specifically, while latency prolongation may serve as an early marker of demyelination in the context of inflammatory activity, amplitude decline appears more directly linked to accumulating disability and may reflect irreversible axonal loss. These findings advocate for the integration of longitudinal VEP metrics into multimodal monitoring strategies, potentially improving risk stratification and treatment optimization in MS patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eARR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAnnualized Relapse Rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCSF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCerebrospinal Fluid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDMT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDisease-Modifying Therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEDSS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eExpanded Disability Status Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGd+\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGadolinium-Enhancing Lesion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIMT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eImmunomodulatory Treatment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eISCEV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Society for Clinical Electrophysiology of Vision\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMultiple Sclerosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagnetic Resonance Imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOCB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOligoclonal Bands\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOptical Coherence Tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eON\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOptic Neuritis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePIRA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProgression Independent of Relapse Activity\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRRMS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRelapsing\u0026ndash;Remitting Multiple Sclerosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSPMS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSecondary Progressive Multiple Sclerosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVEP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVisual Evoked Potential\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Sakarya University Faculty of Medicine (Approval No: 150, 19/11/24). Written informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAT and MS conceptualized the study, supervised data collection, and interpreted the data. SO and EC contributed to data collection, statistical analysis, and figure preparation. SA and HK participated in literature review, data analysis, and manuscript editing. SÖ and NKİ supported patient selection, helped prepare tables and figures, and contributed to result interpretation.\u003cbr\u003e\u0026nbsp;AT drafted the manuscript. All authors reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eWe thank all participating patients and technical staff at the three centers involved.\u003c/em\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHojjati SM, Zarghami A, Hojjati SA, Baes M. Optic neuritis, the most common initial presenting manifestation of multiple sclerosis in northern Iran. 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Distribution of Demographic and Clinical Characteristics of the Patients (n = 83)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eAge, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e36 (18\u0026ndash;60)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eSex, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Female\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e66 (79.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Male\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e17 (20.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline VEP latency (ms)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Right eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e116 (95\u0026ndash;162)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Left eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e114 (96\u0026ndash;168)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline VEP amplitude (\u0026micro;V)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Right eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9.0 (0.2\u0026ndash;20.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Left eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9.5 (1.8\u0026ndash;20.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-up VEP latency (ms)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Right eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e113 (97\u0026ndash;163)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Left eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e112 (98\u0026ndash;148)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-up VEP amplitude (\u0026micro;V)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Right eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9.1 (2.6\u0026ndash;21.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Left eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9.5 (1.2\u0026ndash;21.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eVEP abnormality, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Baseline right eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9 (10.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Baseline left eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9 (10.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Follow-up right eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e3 (3.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Follow-up left eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (9.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eVisual acuity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Right eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Left eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eInterval between VEPs, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2.0 (1\u0026ndash;6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eMS disease duration, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6.0 (1.3\u0026ndash;25.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eClinical phenotype, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;RRMS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e75 (90.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;SPMS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (9.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eImmunomodulatory treatment during VEP interval, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;No treatment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (6.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Interferon\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9 (10.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Glatiramer acetate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e10 (12.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Teriflunomide\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e16 (19.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Dimethyl fumarate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e19 (22.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Fingolimod\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e11 (13.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Natalizumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (6.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Cladribine\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (1.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Ocrelizumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7 (8.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline MRI findings, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Brainstem lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e27 (32.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Spinal cord lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e48 (57.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Upper cervical cord lesion (C1\u0026ndash;C4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e30 (36.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;T2 lesion count \u0026lt;9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e37 (44.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;T2 lesion count \u0026ge;9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e46 (55.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Gadolinium-enhancing lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e32 (38.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Number of Gd+ lesions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (1\u0026ndash;5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eCSF findings\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Oligoclonal bands (n = 72), n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;\u0026emsp;Negative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e16 (22.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;\u0026emsp;Positive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e56 (77.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;IgG index\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.8 (0.4\u0026ndash;2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eInitial MS symptom, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Visual\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e27 (32.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Paresthesia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e22 (26.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Pyramidal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e11 (13.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Cerebellar\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6 (7.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Brainstem\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (9.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Other\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9 (10.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eSymptom improvement within 6 months after first steroid pulse, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Complete\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e51 (62.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Partial\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e29 (35.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;None\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (2.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eEDSS scores\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;At baseline VEP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;At follow-up VEP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Current EDSS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eARR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.3 (0\u0026ndash;3.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e MS, multiple sclerosis; VEP, visual evoked potential; RRMS, relapsing\u0026ndash;remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; EDSS, Expanded Disability Status Scale; MRI, magnetic resonance imaging; Gd+, gadolinium-enhancing; CSF, cerebrospinal fluid; OCB, oligoclonal bands; ARR, annualized relapse rate.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Demographic and Clinical Characteristics According to P100 Latency Prolongation Status\u003c/strong\u003e\u003c/p\u003e\n\u003ctable\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eNo Latency Prolongation (n = 47)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eLatency Prolongation (n = 36)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eAge, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e36 (23\u0026ndash;60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e36 (18\u0026ndash;58)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.993\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eSex, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.632\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Female\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e36 (76.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e30 (83.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Male\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e11 (23.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6 (16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eRight-eye visual acuity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.8 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.9 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.015\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eLeft-eye visual acuity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.5\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.188\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eInterval between VEPs, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2.0 (1\u0026ndash;6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2.4 (1\u0026ndash;4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.732\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eMS disease duration, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7.0 (1.3\u0026ndash;25.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5.0 (1.6\u0026ndash;14.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.062\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eClinical phenotype, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.009\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;RRMS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e39 (83.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e36 (100.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;SPMS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (17.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eIMT use between VEPs, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.280\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;No treatment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e3 (6.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (5.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Interferon\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4 (8.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (13.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Glatiramer acetate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4 (8.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6 (16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Teriflunomide\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (17.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (22.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Dimethyl fumarate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9 (19.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e10 (27.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Fingolimod\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e10 (21.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (2.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Natalizumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4 (8.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (2.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Cladribine\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (2.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Ocrelizumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4 (8.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e3 (8.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline MRI findings, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Brainstem lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e20 (42.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7 (19.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.047\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Spinal cord lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e34 (72.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e14 (38.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Upper cervical cord lesion (C1\u0026ndash;C4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e22 (46.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (22.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.038\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;T2 lesion count \u0026ge;9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e28 (59.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e18 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.518\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Gadolinium-enhancing lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e25 (53.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7 (19.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.004\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Gd+ lesion count\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (1\u0026ndash;5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (1\u0026ndash;3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.532\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eCSF findings\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;OCB positivity (n = 72), n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e32/39 (82.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e24/33 (72.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.507\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;IgG index\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.9 (0.5\u0026ndash;2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.7 (0.4\u0026ndash;1.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.035\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eInitial MS symptom, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.088\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Visual\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e19 (40.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (22.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Paresthesia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (17.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e14 (38.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Pyramidal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4 (8.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7 (19.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Cerebellar\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4 (8.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (5.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Brainstem\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (10.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e3 (8.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Other\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7 (14.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (5.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eImprovement after first pulse steroid, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.461\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Complete\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e29 (61.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e22 (62.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Partial\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e16 (34.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e13 (37.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;None\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eEDSS scores\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;At first VEP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (1.0\u0026ndash;3.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.521\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;At second VEP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (1.0\u0026ndash;3.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.422\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;At last follow-up\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (1.0\u0026ndash;3.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.648\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eARR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.0 (0\u0026ndash;2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.9 (0\u0026ndash;3.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eStatistical comparisons were conducted using Mann\u0026ndash;Whitney U test for continuous variables and Fisher\u0026rsquo;s exact test or Pearson\u0026rsquo;s chi-square test for categorical variables, as appropriate. A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e RRMS, relapsing\u0026ndash;remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; IMT, immunomodulatory treatment; VEP, visual evoked potential; MRI, magnetic resonance imaging; Gd+, gadolinium-enhancing; OCB, oligoclonal bands; EDSS, Expanded Disability Status Scale; ARR, annualized relapse rate.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Demographic and Clinical Characteristics According to P100 Amplitude Reduction Status\u003c/strong\u003e\u003c/p\u003e\n\u003ctable\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eNo Amplitude Reduction (n = 36)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eAmplitude Reduction (n = 47)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eAge, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e37 (23\u0026ndash;58)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e36 (18\u0026ndash;60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.639\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eSex, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.304\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Female\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e31 (86.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e35 (74.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Male\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (13.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e12 (25.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline VEP latency (ms)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Right eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e119.5 (96.6\u0026ndash;162)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e112 (95\u0026ndash;151)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.028\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Left eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e115.5 (100\u0026ndash;163)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e113 (96\u0026ndash;168)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.184\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-up VEP latency (ms)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Right eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e112.5 (99\u0026ndash;163)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e113 (97\u0026ndash;142)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.398\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Left eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e110.5 (101\u0026ndash;146)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e113 (98\u0026ndash;148)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.523\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eVisual acuity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Right eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.2\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.581\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Left eye\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.5\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.840\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eInterval between VEPs, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2.0 (1\u0026ndash;5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2.2 (1\u0026ndash;6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.191\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eMS disease duration, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5.3 (1.5\u0026ndash;25.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6.0 (1.3\u0026ndash;20.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.266\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eClinical phenotype, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.456\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;RRMS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e34 (94.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e41 (87.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;SPMS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (5.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6 (12.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eIMT use between VEPs, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.317\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;No treatment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (5.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e3 (6.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Interferon\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (5.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7 (14.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Glatiramer acetate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (5.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (17.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Teriflunomide\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9 (25.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7 (14.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Dimethyl fumarate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (22.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e11 (23.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Fingolimod\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7 (19.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4 (8.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Natalizumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e3 (8.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Cladribine\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (2.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Ocrelizumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (5.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (10.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline MRI findings, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Brainstem lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e12 (33.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e15 (31.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Spinal cord lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e20 (55.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e28 (59.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.886\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Upper cervical cord lesion (C1\u0026ndash;C4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e10 (27.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e20 (42.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.247\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;T2 lesion count \u0026ge;9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e21 (58.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e25 (53.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.807\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Gadolinium-enhancing lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e15 (41.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e17 (36.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.778\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Gd+ lesion count\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (1\u0026ndash;3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (1\u0026ndash;5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.278\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eCSF findings\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;OCB positivity (n = 31 vs 41), n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e25 (80.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e31 (75.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.824\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;IgG index\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.8 (0.5\u0026ndash;2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.8 (0.4\u0026ndash;2.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.722\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eInitial MS symptom, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.568\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Visual\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e13 (36.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e14 (29.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Paresthesia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7 (19.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e15 (31.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Pyramidal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4 (11.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7 (14.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Cerebellar\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e3 (8.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e3 (6.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Brainstem\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e3 (8.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (10.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Other\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6 (16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e3 (6.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eImprovement after first steroid, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.720\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Complete\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e24 (66.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e27 (58.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Partial\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e11 (30.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e18 (39.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;None\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (2.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eEDSS scores\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;At baseline VEP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0\u0026ndash;4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (1\u0026ndash;6.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.118\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;At follow-up VEP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0\u0026ndash;5.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (1\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.017\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;At last follow-up\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0\u0026ndash;5.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.028\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eARR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.0 (0\u0026ndash;2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.3 (0\u0026ndash;3.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.849\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eContinuous variables were analyzed using the Mann\u0026ndash;Whitney U test, while categorical variables were compared using Fisher\u0026rsquo;s exact test or Pearson\u0026rsquo;s chi-square test. Statistical significance was defined as p \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e RRMS, relapsing\u0026ndash;remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; IMT, immunomodulatory treatment; VEP, visual evoked potential; MRI, magnetic resonance imaging; Gd+, gadolinium-enhancing; OCB, oligoclonal bands; EDSS, Expanded Disability Status Scale; ARR, annualized relapse rate.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Demographic and Clinical Characteristics According to the Presence of Any VEP Change (P100 Latency Prolongation or Amplitude Reduction)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eNo VEP Change (n = 60)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eVEP Change (n = 23)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eAge, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e38 (23\u0026ndash;60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e35 (18\u0026ndash;51)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.339\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eSex, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Female\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e48 (80.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e18 (78.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Male\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e12 (20.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (21.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eRight-eye visual acuity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.8 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.046\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eLeft-eye visual acuity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.6\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.094\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eInterval between VEPs, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2.0 (1\u0026ndash;6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2.2 (1\u0026ndash;4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.735\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eMS disease duration, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6.5 (1.3\u0026ndash;25.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4.8 (2\u0026ndash;14.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.191\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eClinical phenotype, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.099\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;RRMS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e52 (86.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e23 (100.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;SPMS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (13.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eIMT use between VEPs, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.116\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;No treatment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4 (6.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Interferon\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (8.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4 (17.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Glatiramer acetate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4 (6.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6 (26.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Teriflunomide\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e13 (21.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e3 (13.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Dimethyl fumarate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e12 (20.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7 (30.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Fingolimod\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e10 (16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Natalizumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (8.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Cladribine\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (1.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Ocrelizumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6 (10.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline MRI findings, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Brainstem lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e22 (36.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (21.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.300\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Spinal cord lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e38 (63.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e10 (43.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.164\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Upper cervical cord lesion (C1\u0026ndash;C4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e24 (40.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6 (26.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.355\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;T2 lesion count \u0026ge;9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e35 (58.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e11 (47.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.538\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Gadolinium-enhancing lesion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e26 (43.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6 (26.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.233\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Gd+ lesion count\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (1\u0026ndash;5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (1\u0026ndash;3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.689\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eCSF findings\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;OCB positivity (n = 51 vs 21), n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e40 (78.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e16 (76.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;IgG index\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.8 (0.5\u0026ndash;2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.7 (0.4\u0026ndash;1.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.208\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eInitial MS symptom, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.107\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Visual\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e23 (38.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e4 (17.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Paresthesia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e12 (20.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e10 (43.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Pyramidal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6 (10.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (21.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Cerebellar\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5 (8.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Brainstem\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6 (10.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (8.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Other\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (13.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1 (4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eImprovement after first steroid, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.687\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Complete\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e37 (61.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e14 (63.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Partial\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e21 (35.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e8 (36.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;None\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (3.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eEDSS scores\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;At baseline VEP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (1\u0026ndash;3.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.734\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;At follow-up VEP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (1\u0026ndash;3.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.850\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026emsp;Current EDSS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (1\u0026ndash;3.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.651\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eARR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.0 (0\u0026ndash;2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.7 (0\u0026ndash;3.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.014\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e RRMS, relapsing\u0026ndash;remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; IMT, immunomodulatory treatment; VEP, visual evoked potential; MRI, magnetic resonance imaging; Gd+, gadolinium-enhancing; OCB, oligoclonal bands; EDSS, Expanded Disability Status Scale; ARR, annualized relapse rate.\u003c/p\u003e\n\u003cp\u003eStatistical comparisons were performed using the Mann\u0026ndash;Whitney U test for continuous variables and Fisher\u0026rsquo;s exact test or Pearson\u0026rsquo;s chi-square test for categorical variables, as appropriate. Statistical significance was defined as\u0026nbsp;\u003cem\u003ep\u003c/em\u003e\u0026nbsp;\u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5. Correlation Between Changes in VEP Parameters and Changes in Disability (EDSS)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eVEP Parameter Change\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eChange in EDSS (2nd VEP \u0026ndash; 1st VEP)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eChange in EDSS (Current \u0026ndash; 2nd VEP)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eRight-eye P100 latency\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003er\u003c/em\u003e\u0026nbsp;= \u0026ndash;0.150,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e\u0026nbsp;= 0.175\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003er\u003c/em\u003e\u0026nbsp;= 0.009,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e\u0026nbsp;= 0.936\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eLeft-eye P100 latency\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003er\u003c/em\u003e\u0026nbsp;= \u0026ndash;0.157,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e\u0026nbsp;= 0.157\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003er\u003c/em\u003e\u0026nbsp;= \u0026ndash;0.140,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e\u0026nbsp;= 0.208\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eRight-eye P100 amplitude\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003er\u003c/em\u003e\u0026nbsp;= \u0026ndash;0.140,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e\u0026nbsp;= 0.208\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003er\u003c/em\u003e\u0026nbsp;= 0.019,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e\u0026nbsp;= 0.864\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eLeft-eye P100 amplitude\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003er\u003c/em\u003e\u0026nbsp;= \u0026ndash;0.225,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e\u0026nbsp;= 0.041\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cem\u003er\u003c/em\u003e\u0026nbsp;= 0.019,\u0026nbsp;\u003cem\u003ep\u003c/em\u003e\u0026nbsp;= 0.866\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e VEP, visual evoked potential; EDSS, Expanded Disability Status Scale.\u003c/p\u003e\n\u003cp\u003eSpearman correlation analysis was used to assess the relationship between changes in VEP parameters and disability progression. A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6. Comparison of Clinical and Radiological Features Based on Baseline VEP Latency and Amplitude Status\u003c/strong\u003e\u003c/p\u003e\n\u003ctable\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eP100 Latency \u0026le;118 ms (n = 57)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eP100 Latency \u0026gt;118 ms (n = 26)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eNormal Amplitude (n = 65)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eReduced Amplitude (n = 18)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eAge, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e36 (18\u0026ndash;60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e37 (23\u0026ndash;55)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.666\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e36 (18\u0026ndash;60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e40.5 (23\u0026ndash;58)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.045\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eSex, female (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e45 (78.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e21 (80.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e53 (81.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e13 (72.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.509\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eRight-eye visual acuity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.036\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.2\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.791\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eLeft-eye visual acuity\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.2\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.027\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.1\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0.5\u0026ndash;1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.713\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eInterval between VEPs, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2.0 (1\u0026ndash;5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2.1 (1\u0026ndash;6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.527\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2.1 (1\u0026ndash;6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.8 (1\u0026ndash;5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.257\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eMS disease duration, years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5.2 (1.3\u0026ndash;15.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6.0 (3.0\u0026ndash;25.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.182\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e5.2 (1.3\u0026ndash;20.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e6.9 (1.9\u0026ndash;25.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.289\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eRRMS, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e53 (93.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e22 (84.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.251\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e57 (87.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e18 (100.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.191\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eSpinal cord lesion, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e28 (49.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e20 (76.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.032\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e36 (55.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e12 (66.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.556\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eGd+ lesion, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e25 (43.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e7 (26.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.220\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e30 (46.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e2 (11.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.015\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eOCB positive, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e38 (74.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e18 (85.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.365\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e47 (82.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9 (60.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.084\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eIgG index\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.8 (0.4\u0026ndash;2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.8 (0.5\u0026ndash;1.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.702\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.8 (0.4\u0026ndash;2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.7 (0.5\u0026ndash;1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.169\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eVisual symptom onset, n (%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e18 (31.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e9 (34.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.819\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e17 (26.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e10 (55.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.029\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eEDSS at baseline VEP\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;5.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.231\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (1\u0026ndash;3.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.254\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eEDSS at 2nd VEP\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.366\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.3 (1.0\u0026ndash;2.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.099\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eCurrent EDSS\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.303\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.5 (0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (1.0\u0026ndash;6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.213\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003e\u003cstrong\u003eARR between VEPs\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.3 (0\u0026ndash;2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.2 (0\u0026ndash;3.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.566\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.0 (0\u0026ndash;3.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e1.0 (0\u0026ndash;2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.044\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e VEP, visual evoked potential; RRMS, relapsing\u0026ndash;remitting multiple sclerosis; Gd+, gadolinium-enhancing lesion; OCB, oligoclonal bands; EDSS, Expanded Disability Status Scale; ARR, annualized relapse rate.\u003c/p\u003e\n\u003cp\u003eStatistical comparisons were performed using the Mann\u0026ndash;Whitney U test for continuous variables and Fisher\u0026rsquo;s exact or Pearson\u0026rsquo;s chi-square test for categorical variables. A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Multiple Sclerosis, Visual Evoked Potentials, Neurodegeneration, Disease Progression, Prognosis","lastPublishedDoi":"10.21203/rs.3.rs-6572073/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6572073/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eVisual evoked potentials (VEPs) are valuable tools for assessing optic pathway integrity in multiple sclerosis (MS), yet the longitudinal implications of P100 latency and amplitude changes remain unclear. The aim of this study was to explore the clinical and prognostic value of serial VEP assessments in MS, focusing on differences between latency and amplitude changes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed 83 MS patients from three centers who underwent\u0026thinsp;\u0026ge;\u0026thinsp;2 pattern-reversal VEPs at least one year apart. Patients with recent optic neuritis were excluded. Clinical, radiological, and CSF findings were compared between those with and without significant VEP changes. Disability progression was evaluated using EDSS.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eDuring follow-up, 43.4% developed new P100 latency prolongation, associated with higher relapse rates, RRMS phenotype, and more favorable baseline MRI/CSF profiles. In contrast, 56.6% showed significant P100 amplitude reduction, linked to greater EDSS worsening (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Latency changes were not associated with disability progression. Amplitude decline\u0026mdash;especially in the left eye\u0026mdash;correlated modestly but significantly with EDSS change (r = \u0026minus;\u0026thinsp;0.225, p\u0026thinsp;=\u0026thinsp;0.041).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eSerial VEPs provide distinct insights into MS pathology. While latency prolongation reflects inflammatory activity, amplitude decline may signal silent neurodegeneration and functional decline. Longitudinal VEP monitoring may improve early detection of progression and guide individualized care.\u003c/p\u003e\u003ch2\u003eTrial Registration\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e","manuscriptTitle":"Longitudinal VEP Analysis Reveals Divergent Markers of Inflammation and Neurodegeneration in Multiple Sclerosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-02 11:20:57","doi":"10.21203/rs.3.rs-6572073/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e41bba96-6589-489a-84d1-6ae06ae5bae6","owner":[],"postedDate":"June 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-10T06:23:52+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-02 11:20:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6572073","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6572073","identity":"rs-6572073","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}