For the last 30 years, MS disease diagnosis, disease activity monitoring, clinical and MRI findings have all been considered . As is well-known, evoked potentials that are easily applied in electrophysiology laboratories are useful for performing quantitative functional measurements of the well-defined central nervous system pathways. Although the role of evoked potentials in MS disease diagnosis and evaluation is limited, because the disease affects the optic nerve, somatosensorial, and pyramidal systems, the use of visual-somatosensorial and motor evoked potentials, which show pathologies in these systems, is particularly useful for detecting subclinical pathologies and clinical changes . VEP has a significant role in determining the degree of demyelination along the optic nerve, a functional region of the central nervous system , and SEP is important in detecting pathologies along the main lemniscal route .
Various prospective and retrospective studies have found that quantitative stimulated potential scores derived from visual, somatosensorial, and motor-stimulated potential values are far more sensitive than clinical evaluation and can be used as a biomarker to monitor disease progression [8, 14, 15]. Evoked potentials can be used during presentation of the disease to verify missed and undetectable recurrence in patients with uncertain or transient symptoms . Previous studies have generally only correlated with EDSS values in terms of disease progression.
Women have a threefold higher prevalence ratio of MS disease than men . In our study, there is a female predominance among our patients, which is consistent with current literature. Male MS patients were more likely than women to have two-sided abnormalities detected in VEP and posterior tibial SEP studies, but this relationship was not statistically significant (p values 0.571 and 0.231 respectively.) Previous studies have yielded conflicting results regarding the effect of gender on the prognosis of MS disease. Tremlett et al. conducted a major geographically based study in a large MS population (2,837 patients) and found that men initially showed a statistically significant faster progression than women (p-values < 0.0005), but when patients were 58–60 years old, this difference was eliminated, and it was later found that both sexes had similar sequencing. So, while being male was a significant risk factor for progression in the early period, they discovered that this was not associated with a poor prognosis in the long term . In our study (similar to Tremlett’s,) 26 out of 181 female patients and 23 out of 78 male patients progressed. We have also detected two-sided pathologies of evoked potential at the beginning of the disease, in men more often than in women. In our study, the disease beginning at a young age was a good prognostic factor  and a late start was reported as a bad prognostic factor . There was no statistically significant relationship between the initial age of the disease and the initial VEP pathologies, but the age of the disease was statistically higher in patients with two-sided posterior tibial SEP pathologies than those found to be normal.
The VEP examination was recommended for MS patients to evaluate the degree of optic nerve demyelination, a functional central nervous system region, to predict the degree of improvement after an ON attack, and to assess the assuring results of events in clinical and subclinical demyelination on the afferent visual path . In our study, patients with an ON attack began with the VEP study, and while the VEP study was statistically significantly unilaterally defective, the tibial SEP examination was statistically significant and normal. As is known, the most common symptom of origin is isolated ON, and while it may remain a single isolated attack, new attacks may develop long after the initial attack.
In a previous study, 84 patients with clinically definite MS were assessed using the EDSS and functional system scoring at the beginning and end of the study. After 11.7 months of monitoring, all evoked potentials (VEP, lower extremity SEP, lower and upper extremity MEP; p-values 0.03, 0.002, and < 0.001 respectively) were found to be statistically significant with patient’s EDSS scores and the calculated global evoked potentials score . In our study, evoked potentials were grouped in a simple manner rather than the complex scores mentioned in other studies, and the current EDSS scores calculated for patients with two-sided pathology detected in VEP and posterior tibial SEP were statistically higher. Our patient follow-up time is longer than this study’s.
Some previous studies that found a relationship between patient clinics and evoked potentials had conflicting or even negative results [22–25], but in other studies, a very strong relationship was found [26–27]. The disparities in these studies’ findings may be due to the use of quantitative different evoked potential measurements, the inclusion of different types of MS patients, and differences in patient monitoring times in the studies. The scores used in practice and in the clinic to assess the evoked potentials in studies are difficult and time-consuming to achieve and use [21, 28–29]. Unlike previous studies, we used a classification (two-sided normal, one-sided abnormal, and two-sided abnormal) to assess the potential that was evoked in our study, which we believe can be used more easily and practically in the clinic.
In our study, we observed that the progression of MS patients with two-sided pathology was statistically significant in basal VEP and tibial SEPs. The course of MS patients with bilateral pathology in basal VEP and tibial SEP was statistically significantly progressive. VEP examination was observed PPMS 1.6 times and SPMS 2.3 times more often in patients with bilateral abnormalities than in two-sided normal patients, while posterior tibial SEP examination was detected PPMS 2.3 times and SPMS 6.5 times more often in patients with bilateral abnormalities than in two-sided normal patients. In progressive MS, lesions may be equally common in gray and white matter and both cortical and deep gray matter have a common neuroaxonal loss. New developments have shown that cortical demyelination is common, particularly in SPMS . As a result of our findings, it was hypothesized that SEP examination pathologies obtained through somatosensory cortical stimulation, especially at the beginning of the disease, may predict progression to SPMS, particularly in MS patients. It is known that the thalamus, which plays an important role in the transmission of motor and sensory signals to the cerebral cortex, is also critically important in MS. Some studies indicate that thalamic pathologies may reflect the net accumulation of damage associated with MS in the central nervous system .
We found that the first SEP examinations of MS patients with low-density lipoprotein cholesterol (LDL) values and high-density lipoprotein cholesterol (HDL) values were statistically significantly bilaterally pathological. A recent study has shown that a high level of circulating LDL and total cholesterol harms clinical and MRI results. In the study, they argued that cholesterol values in MS patients can be used as a biomarker to predict disease activity or treatment outcomes . The relationship between cholesterol levels and MS disease is still unclear. In MS patients, vascular complications caused by hypercholesterolemia may cause disease progression. More longitudinal studies are needed to explain the relationship between cholesterol levels and cholesterol-related biomarkers in MS patients and demyelination, remyelination, and axonal degeneration seen in MS patients. According to the results of our study, bilateral SEP pathologies are more common in MS patients with a high LDL value and a low HDL value, and therefore they may have a poor prognosis in the following period.
In the first CSF examination, we found that MS patients with a high IgG index had a statistically significant double-sided abnormality of the tibial SEP values. One of the most well-known biological characteristics of MS disease is an increase in intrathecal immunoglobulin synthesis. According to immunopathological studies, this humoral immune response, which is important in disease pathogenesis, is thought to have caused irreversible central damage . This attitude is not only a major factor in disease activity but also in the progression of a clinically isolated syndrome in MS . In a very new and important study of 18 centers, it was found that the intrathecal IgG synthesis had statistically worsened the EDSS intensity after four years . This study found that OCB positivity has no meaningful relationship with EDSS violence.
In our study, it was thought that the presence of the OCB did not make a prognostic difference because most patients with CSF examination were positive for OCB (113 out of 148 patients were OCB positive). According to the above-mentioned multi-center study, the OCB positivity ratio among patients is high, and band positivity is not a meaningful parameter that can indicate disease progression. Another retrospective study of 40 patients with definitive MS found no statistically significant relationship between OCB positivity and VEP and SEP parameters .
The lesions of spinal and infratentorial demyelination were statistically significantly more frequent in our study when compared to the current brain and spinal MRI lesion localization of patients with normal initial VEP and SEP studies and patients with pathological evoked potentials. In other studies, the number of lesions, as well as the presence of spinal  and infratentorial lesions, were found to be an important prognostic factor in predicting the risk of transition from clinically isolated syndrome to clinically definite MS .
Restless legs syndrome (RLS) is a sleep-related sensory-motor disorder characterized by an irresistible urge to move the legs, accompanied by unpleasant sensations in the lower extremities. Many studies have found that RLS is more common in MS patients than in non-MS people of similar age. Previous research has found that EDSS values of MS patients with RLS are higher than those without RLS . The underlying mechanism of RLS is now thought to be complex cortico-spinal excitability. A high-frequency somatosensory evoked potentials (HF-SEP) examination revealed functional impairment in the thalamocortical projections and sensorial cortex, especially in severe cases of RLS, according to a recent study . In our study, SEP examinations of MS patients with RLS may therefore be found to be significantly pathological. In one study that conducted VEP examinations of patients with RLS, it was reported that RLS is part of the neuro-degenerative process and pathologies can be detected in VEP examinations due to the disease’s incomplete demyelination . According to the results of our work, which may result in our patients' RLS MS basal evoked potential of the above-mentioned possible reasons for the more pathological resides, and EDSS scores were in the later stages. It can be said that MS with RLS can predict poor prognosis compared to patients without RLS. Unfortunately, more research on the relationship between the presence of RLS and the prognosis of MS is required.