1. Intruduction

A seizure is a burst of uncontrolled electrical activity between brain cells that causes temporary abnormalities in muscle tone or behaviors, sensations, or states of awareness. Anti-seizure drugs are usually used to control seizures in these patients. Like any other drug anti-seizure drugs have certain side effects. The visual system among human organs may be affected by these drugs. Electrophysiological tests of the visual system mainly electrooculogram (EOG), electroretinogram (ERG), and visual evoked potential (VEP) are valuable tools for this purpose. These techniques are used for different pathological conditions of the visual system. Sanaie S et al 2014 worked on the effect of toxoplasmosis on the visual system, mainly the retina of patients suffering from toxoplasmosis. They used the EOG technique for this purpose. The result of their work was a significant difference between the Arden Index (AI) of case and control groups which shows the pathological changes of the retina mainly retinal pigment epithelium of toxoplasmosis patients. [1]

Recently Sarzaeim F and her colleagues published an article on the effect of hand-arm vibration on the retina of road drilling machine laborers. The authors stated that hand-arm vibration produced by road drilling machines can affect retina of the workers which can be measured by ERG [2]. In another work done by the same authors, flash VEP was measured in 10 patients following head trauma. The result was pathological changes of VEP which indicates visual pathway disturbances produced by head trauma and could be diagnosed by VEP [3]. There are quite enough related works in this connection that shows the usefulness of these techniques [4 - 12]. Electroophthalmological techniques can be used to study the side effects of different drugs on the visual system of human beings too. Allahdady F. et al 2016 worked on the toxic effect of hydroxychloroquine on the retina of arthritis rheumatoid patients using the EOG test. They concluded that EOG can be considered a suitable technique to evaluate the retinal damages caused by hydroxychloroquine in related patients [13]. Naser M. and her research team 2017 reported visual disturbances in a patient with amiodarone treatment following refractive surgery. The patient's chief complaint was seeing colored rings around the light. VEP recording in the patient showed prolongation in latency of VEP, P100 peak and reduction of the amplitude of the peak, which is proof of the toxic effect of amiodarone on the visual pathway measured by VEP.

Shushtarian S.M. and his colleagues worked on the probable toxic effect of sodium valproate (SV) on the human retina using ERG. For this purpose, 25 patients who had used SV for more than 3 years were chosen. Flash ERG was measured in these patients. The result of this work was a reduction in amplitude of ERG b wave which is an indication of pathological changes in the human retina due to SV treatment [15]. There is a large number of related other works in this connection [16 - 18]. Considering the extensive survey of the literature, the authors planned research on the probable toxic effect of anti-seizure drugs on human visual pathway using VEP by two types of stimulation techniques i.e. flash and pattern reversal checkerboard.

2. Patients and Methods

In this case-control research work, 20 patients (40 eyes) suffering from seizures were selected as a case group. The patients were in the age range of 15 - 30 years. The case group was under anti-seizure drugs either monotherapy or polypharmacy for a different period longer than one year to control the illness. The patients were tested for visual acuity and brain magnetic resonance imaging (MRI). The case group had sufficient visual acuity to distinguish the fixation point on the monitor and normal MRI. Visual evoked potential test with two types of routine stimulation techniques i.e. flash and pattern reversal checkerboard was examined, the in the patient group. Latency (msec) and amplitude (µv) of VEP, P100 peak was measured for the total patient group using the Mangoni machine. In summary three electrodes were used to connect the machine to patients. Active, reference, and ground electrodes were attached to the occipital, vertex, and forehead of the patient respectively. The same procedure was repeated for 20 (10 male and 10 female) age and sex-matched healthy (visual) subjects as a control group. The results obtained in two groups were compared for probable differences between the two groups.

3. Results

Table 1 shows the demographical findings in the case control groups and there is no statistically significant difference between the two groups regarding age (P = 0.84) and sex whereas the difference between BCVA is significant (P < 0.001).

Table 1: demographic findings in the case and control groups

Table 2 shows the measurements of mean latency and amplitude of VEP, P100 peak in case and control groups using two types of flash and pattern reversal checkerboard stimulations. As it is clear in the table, the differences in latency and amplitude of VEP, P100 peak is significant as far as the two types of stimulation techniques are concerned (P < 0.001).

Table 2: measurement of mean latency and amplitude in case of flash and pattern reversal checkerboard.

4. Discussion

Visual evoked potential with two types of stimulation techniques i.e., flash and pattern reversal checker board were recorded in patients taking anti-seizure medicine for their treatment. There was a delay in latency and fall of the amplitude of VEP, P100 peak in most of the patients compared with the same parameter of a healthy population. Moreover, the VEP pattern obtained in some patients was not reliable in the case of pattern reversal stimulation therefore, flash type of VEP was also performed in the total population i.e., case & control groups. The following discussion is an attempt to explain the findings of the present research work. Regarding the first finding i.e., significant changes in VEP, parameters i.e. latency & amplitude of VEP, P100 peak in patient group, the reason is nothing but visual pathway disturbances in case group either due to diseases itself or side effects of the anti-seizure drug which reflect itself in latency of VEP, P100 peak. It is to mention that latency of VEP, P100 peak originated from visual pathway [19]. To support the above results, Galler AM. et al 2005 measured VEP in epilepsy patients using anti-epileptic drugs and they commented that visual disruption in patients diagnosed may be attributed to either the disease itself or to anti-epileptic drugs prescribed to control the seizures [20].

Dziadkowiak E. et al 2019 worked on 81 patients with newly diagnosed epilepsy of unknown etiology before initiation of treatment VEP test was performed in the total patient group using two types of stimulation techniques i.e., flash and pattern reversal checkerboard. The result of their work showed that VEP parameters obtained with pattern stimulation did not differ significantly between the patients and control groups, whereas in the case of flash stimulation they could find a significant delay in latency of VEP P100 peak [21] which once again support the results of present work. Regarding the side effects of anti-epileptic drugs on VEP, there exist a number of research works [22, 23]. One of the aspects of the present work was a recording of VEP in patients under anti-seizure treatment using two types of stimulation techniques i.e., flash and pattern reversal checkerboard. The reason for this attempt was the drowsiness and fatigue in a few patients which is the side effect of some anti-seizure drugs [24] and therefore lack of fixation and concentration on the monitor fixation point necessary to record VEP using pattern reversal checkerboard. In fact, the selection of stimulation technique plays a vital role in recording VEP in some cases including epilepsy. Shushtarian S.M. and his colleagues reported severe headaches initiated by flash stimulation during visual evoked potential recording in a patient with monocular optic neuritis and a history of migraine headache [25]. Selection of VEP with different stimulation techniques for better diagnosis of seizure epilepsy and other diseases is reported by different research workers [21, 26 - 28] which are proof of the advantage of recent work.

5. Conclusion

Patients suffering from seizures, may have visual disruption which is either due to the disease itself or anti-seizure drugs necessary to treat the seizure. The visual evoked potential is a suitable technique for this purpose, however, two types of stimulation techniques for recording VEP are to be taken into consideration.

Conflict of interest

The authors have no conflict of interest with the subject matter of the present manuscript.

References

1. Sanaie S, Nematian J & Shoushtarian SMM. Study of electrooculogram (EOG) abnormalities in patient with ocular toxoplasmosis. Medical Science Journal of Islamic Azad Univesity-Tehran Medical Branch 24 (2014): 33-36.‏
2. Sarzaeim F, Ojani F, Hojati TS, Shojaei A & Shushtarian SMM. Effect of Hand-Arm Vibration on Retina of Road Drilling Machine Laborers Measured by Electroretinography. Journal of Ophthalmology and Research 5 (2022): 81-85.‏
3. Sarzaeim F, Hashemzehi M, Shushtarian SMM, Shojaei A & Naghib J. Flash Visual Evoked Potential as a Suitable Technique to Evaluate the Extent of Injury to Visual Pathway Following Head Trauma. Journal of Ophthalmology and Research5 (2022): 20-3.‏
4. Shushtarian SM, Kalantari AS, Tajik F & Adhami-Moghadam F. Effect of occupational vibration on visual pathway measured by visual evoked potentials. Journal of Ophthalmic and Optometric Sciences1 (2017): 7-11.‏
5. Keramti S, Ojani F, Shushtarian SMM, Shojaei A & Mohammad-Rabei H. Early Diagnosis of Pathological Changes in Visual System of Prolactinoma Patients Using Visual Evoked Potential. Journal of Ophthalmology and Research4 (2021): 289-93.‏
6. Ojani F, Shushtarian SMM, Shojaei A & Naghib J. Visual Evoked Potential Findings of Bardet-Biedl Syndrome. Journal of Ophthalmology and Research 4 (2021): 254-257.‏
7. Shushtarian SM, Adhami-Moghadam F, Naser M, Khazaii R, Sobhani S, Shabani S, et al. Electroretinographic Changes in Multiple Sclerosis Patients with Abnormal Visual Evoked Potentials. Journal of Ophthalmic and Optometric Sciences1 (2017).‏
8. Shushtarian SM, Mirdehghan MS & Valiollahi P. Retinal damages in turner workers of a factory exposed to intraocular foreign bodies. Indian Journal of Occupational and Environmental Medicine12 (2008): 136.‏
9. Sarzaeim F, Hashemzehi M, Shushtarian SMM & Shojaei A. Visual Evoked Potential Findings in Road Drilling Machine laborers. Journal of Ophthalmology and Research5 (2022): 43-47.‏
10. Keramti S, Javanshir S, Tajik F, Shushtarian SMM, Shojaei A & Abolhasani A. Retinal Screening of Prolactinoma Patients using Flash Electroretinography. Journal of Ophthalmology and Research4 (2021): 321-326.‏
11. Shushtarian SMM, Naghib SJ, Adhami-Moghadam F & Shojaei A. Diplopia and Blurry Vision Following Refractive Eye Surgery: a Comorbidity Case Report. Journal of Ophthalmic and Optometric Sciences4 (2020): 40-42.‏
12. Masoud Shoushtarian SM, Mirdehghan Farashah MS, Valiollahi P, Tajik A, Adhamimoghaddam F & Malekzadeh S. Electroretinogram in amblyopic and non-amblyopic children. The Indian Journal of Pediatrics 77 (2010): 577-578.‏
13. Allahdady F, Aghazadeh Amiri M, Shushtarian M, Tabatabaee SM, Sahraei F, Shojaei Baghini A & Sheibani K. Comparison of visual evoked potential and electro-oculogram tests in early detection of hydroxychloroquine retinal toxicity. Journal of Ophthalmic and Optometric Sciences. Volume1 (2016).‏
14. Naser M, Shushtarian SMM, Shojaei A & Adlami-Moghdam F. Visual Disturbance in a Patient with Amiodarone Treatment Following Refractive Surgery. Journal of Ophthalmic and Optometric Sciences. Volume1 (2017).‏
15. Shushtarian SMM & Hayti Z. Probable Toxic Effect of Sodium Valproate on Retine Using Electroretinogram. Journal of Ophthalmic and Optometric Sciences3 (2019): 24-28.‏
16. Naser M & Shushtarian SM. Study the effect of depakine on retina of epileptic patients using electroretinogram. International journal of scientific research3 (2014): 392-393.‏
17. Tajik F & Shushtarian SMM. Electrooculographic and Electroretinographic Changes among Patients Undergoing Treatment with Amiodarone. Journal of Ophthalmic and Optometric Sciences2 (2018): 7-11.‏
18. Naser M & Shushtarian SMM. Need for Visual Pathway Examination of the Patient Prior to Bone Marrow Transplantation. Journal of Ophthalmology and Research3 (2020): 75-78.‏
19. Hajibeygi R, Shushtarian SMM & Abolghasemi S. Visual Evoked Potential Findings of Sjogren's Syndrome. Journal of Ophthalmic and Optometric Sciences4 (2020): 13-17.‏
20. Geller AM, Hudnell HK, Vaughn BV, Messenheimer JA & Boyes WK. Epilepsy and medication effects on the pattern visual evoked potential. Documenta ophthalmologica110 (2005): 121-131.‏
21. Dziadkowiak E & Podemski R. Impact of hyperventilation and sleep deprivation upon visual evoked potentials in patients with epilepsy. Neurology India67 (2019): 1027.‏
22. Gross-Tsur V, Banin E, Shahar E, Shalev RS & Lahat E. Visual impairment in children with epilepsy treated with vigabatrin. Annals of neurology48 (2000): 60-64.‏
23. Drake Jr ME, Pakalnis A, Padamadan H, Hietter SA & Brown M. Effect of anti-epileptic drug monotherapy and polypharmacy on visual and auditory evoked potentials. Electromyography and clinical neurophysiology29 (1989): 55-58.‏
24. Guerrini R, Zaccara G, La Marca G & Rosati A. Safety and tolerability of antiepileptic drug treatment in children with epilepsy. Drug safety35 (2012): 519-533.‏
25. Shushtarian SMM, Adhami-Moghadam F, Naser M & Shojaei A. Severe Headache Initiated by Flash Stimulation during Visual Evoked Potential Recording in a Patient with Monocular Optic Neuritis and History of Migraine Headache. Journal of Ophthalmic and Optometric Sciences. Volume1 (2017).‏
26. Shushtarian SM. Role of Myelin in Synchronization and Rhythmicity of Visual Impulses. In 4th European Conference of the International Federation for Medical and Biological Engineering(2009): 160-162.
27. Shushtarian SMM. Suitable Stimulation Technique to Record Visual Evoked Potential in Migraine Patients. Journal of Ophthalmic and Optometric Sciences4 (2020): 41-45.‏
28. Naser M, Shushtarian SM, Abdolhoseinpour H & Davari T. Selection of suitable visual stimulator for recording of Visual Evoked Potential in photophobia patients. Indian journal of applied research49 (2014): 112-17.