¹Department of Biotechnology & Bioinformatics, University of Hyderabad, Gachibowli, Telangana, India
²Centre for Applied Sciences, Government Degree College (Men)-Srikakulam, Andhra Pradesh, India
³Department of Neurology, Krishna Institute of Medical Sciences, Secunderabad, India
⁴Department of Biotechnology, Dr. B. R. Ambedkar University-Srikakulam, Andhra Pradesh, India
⁵Department of Biotechnology, Andra University, Visakhapatnam, India

^*Corresponding author: Prakash Babu Panithi, Department of Biotechnology & Bioinformatics, University of Hyderabad, Gachibowli, Telangana, India. E-mail Id: prakash@uohyd.ac.in

Article Information: Submission: 14/08/2023; Accepted: 19/09/2023; Published: 22/09/2023

Copyright: © 2023 Madhamanchi P, et al. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HS associated TLE is the common cause of PRE. Surgery is generally used to control seizures for these patients but most often seizure recurrence observed, reasons are not known. The aim of the study is to evaluate the effects of seizure rate and epilepsy duration on the long term post-surgical outcome of AEDs and onset age matched 153 HS associated PR-TLE patients. All the patients invariantly associated with HS. Clinical data recorded during 2011 and 2023 obtained from outpatient at the department of Neurology, Krishna Institute of Medical Sciences, Secunderabad, India. EEG, MRI and FluoroJade stain used to diagnose the TLE-HS in patients. All patients undergone medial temporal lobectomy for HS and assessed for seizure free outcome after first, third and fifth years using Engel’s and ILAE outcome system of classification. Overall 70.8% patients had very good post-surgical outcome (Engel’s-I & II or ILAE-I) in first year, it was reduced to 59.3% in third year and 47.6% in fifth year. The mean seizure rate was 6 per month (range 0.3 – 258 per month). Patients belong to daily and yearly seizure classes had good post-surgical outcome after first year of the surgery (p = 0.43), however mean drop of Engel’s-I or ILAE-I & II outcome after 5th year of the surgery was more in patients with weekly seizures (p = 0.63). Likely the mean epilepsy duration was 13.57 years (range 01 M – 42 years). Patients with less epilepsy duration had good post-surgical outcome than higher duration (p = 0.41). Besides unreliability of Engel’s-I or ILAE-I & II outcome during post-surgical period observed in patients with less epilepsy duration (p = 0.58) and less surgery age (p = 0.32). Through this study we observed that high seizure rate reduced the consistency of the seizure freeness after surgery. On the other side, higher duration of epilepsy and surgery ages lessen the immediate seizure freeness as well as consistency in outcome. However, we did not find any statistical significance (p< 0.05) while analyzing these data. This study suggests the valuation of Histology, Biochemical, and Molecular factors with long-term post-surgical outcome.

Keywords: Seizure Rate; Epilepsy Duration; Hippocampal Sclerosis; Temporal Lobe Epilepsy; Pharmaco Resistant Epilepsy; Engel’s Outcome; ILAE Outcome

AEDs: Antiepileptic drugs;DN-KIMS: Department of Neurology, Krishna Institute of Medical Sciences; EEG: Electro Encephalo Gram;HS: Hippocampal Sclerosis;ILAE: International League Against Epilepsy; MRI: Magnetic Resonance Imaging;PR-TLE: Pharmaco resistant temporal lobe epilepsy;TLE: Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is a form of focal epilepsies that is always recalcitrant to antiepileptic drugs (AEDs) known as pharmaco resistant temporal lobe epilepsy (PR-TLE) [1,2] . Hippocampal sclerosis (HS) is the most common epileptic foci finding in PR-TLE patients where surgery is enormously used to control seizures [3-6]. Despite the seizure freeness allied with epilepsy surgery, sizable number of post-surgical patients remains to have seizures. Also, it has been noticed that decreasing of seizure freeness over the years in patients with seizure free outcome, although AEDs used [7,8] . The motives for surgery failure in PR-TLE patients and lack of seizure free consistency over the post-surgical period are not well acknowledged. One conceivable supposition is that an enduring seizures cause an epileptogenic fuel processes such as synaptic plasticity, cell proliferation, cell death, inflammation and immune responses [7-12], that finally triggers new epileptic foci [13-14]. So it is presumed that higher the seizure rate and longer the epilepsy, the higher the risk of new epileptic foci, consequently lower the chance to be seizure free after epilepsy surgery. Therefore the seizure rate and duration of epilepsy should be an important prophets of outcome in epilepsy surgery. The purpose of our study was to determine whether there is a link to seizure rate and duration with long term outcome.

The study was recorded and conducted as a review at the Department of Neurology, Krishna Institute of Medical Sciences (DN-KIMS), Secunderabad, India. Our internal ethical committee was informed about the study and it has approved. Data from HS associated PR-TLE patients operated at the DN-KIMS were collected. Patients were examined and operated on between 2011 and 2023 were reviewed. A total of 153 PR-TLE patients using 3-4 AEDs with <12 years of onset age were considered for this analysis [Table 1]. Histological studies with fluorojade stain confirmed the association of HS (Neuronal cell death) in the PR-TLE tissue samples [15]. All patients underwent unvarying presurgical examination like neuropsychology, EEG and MRI including quantitative hippocampal volume measurements with T2 relaxation time [16] and Sodium Amytal (WADA) test [17]. Post-surgical MRI studies in patients with no significant seizure free showed that the envisioned structures were resected. Post-surgical upshot data at first, third and fifth year postoperatively were classified by means of Engel’s classification. (Engel’s-I = seizure free with rare auras, Engel’s-II = 1 or 2 seizures per year, Engel’s-III = more than 90% of the seizures reduced, Engel’s- IV = no significant reduction or worse [18]. Patients falling into the various subgroups of Engel’s classes were pooled. The International League against Epilepsy (ILAE) lately advocated a revision of the classification [19]. In this study Engel’s-I = ILAE 1 and 2, Engel’s-II = ILAE 3, Engel’s-III = ILAE 4, Engel’s-IV = ILAE 5. The outcome of the surgery considered into ILAE classification criteria was collected individually. Student t-test was used to identify the significant variances.

EEG, MRI and histological studies confirmed the association of HS to PR-TLE patients [Figure 1]. Overall 70.8%, 59.3% and 47.6% HS allied PR-TLE patients were seizure-free (ILAE-I outcome) in one year, three years and five years after the surgery. The number of patients with different outcome classes after 1st, 3rd and 5th years of surgery were as follows: ILAE-I = 109, 97, 73; ILAE-II = 34, 45, 56; ILAE-III = 10, 11, 24; ILAE-IV-VI = 00, 00, 00. The mean seizure rate was 6 per month (range 0.3 – 258 per month). As per the ILAE outcome chart [19] we noticed that patients be the members of daily (mean seizures 37.6 per month) and yearly (mean seizures 0.7 per

month) seizure classes were good post-surgical outcome after first year of the surgery (p = 0.61). For instance post-surgical ILAE-I outcome in different seizure classes: daily = 84%, 70.8%, 64.5%; weekly = 63%, 44%, 31%; monthly = 66%, 52%, 47%; yearly = 71.8%, 62.5%, 50% after 1st, 3rd and 5th years respectively [Figure 2]. But average falling of seizure freeness after 5th year of surgery was more in patients with weekly seizures (p = 0.63). Mean dropping of ILAE-I outcome in various seizure classes: Daily = 10.5%, weekly = 16.2%, monthly = 7.8% and yearly = 11.5% after 5th year of surgery [Figure 3].

The mean duration of epilepsy was 13.57 years (range 01 M – 42 years). Based on the outcome chart of different epilepsy duration groups it was observed that patients be the members of less epilepsy duration groups (<1 year and 1-12 years) were exhibiting good postsurgical outcome after first year of the surgery (p = 0.41) than more epilepsy duration groups. For instance post-surgical ILAE-I outcome in different epilepsy duration groups after 1st, 3rd and 5th years: <1 year = 83%, 67%, 50%; 1-12 years = 92%, 79%, 71%; 13-22 years = 41%, 23.7%, 19%; 23-32 years = 36%, 26%, 13.6%; 33-42 years = 15%, 11%, 09% respectively [Figure 4]. Interestingly dipping of seizure freeness after 5th year of surgery was more in patients with lowest epilepsy duration. In this study the average falling of ILAE-I outcome in various epilepsy duration groups: <1 year = 16.5%; 1-12 years = 10.5%; 13-22 years = 10.5%; 23-32 years = 11.5%; 33-42 years = 3% after 5th year of surgery (p = 0.58) [Figure 5]. Further, we studied the association of surgery age of patients with different seizure frequency and epilepsy duration groups. We observed a positive correlation of surgery age with different epilepsy duration groups and also dropping of ILAE-I outcome after 5th year of surgery, in illustration the surgery age of 13.4 years = 8%, 20.4 years = 5.5%, 28.3 years = 7.5%, 38.12 years = 16.5% and 40.6 years = 18% reduction in seizure free outcome (p = 0.32). The youngest patient was 7 years old at the time of operation with ILAE-I outcome thereafter the surgery. She had suffered from epilepsy since the age of 4 years (4 years of epilepsy duration) with seizure frequency of 8 per year. Similarly the oldest patient was 50 years old at the time of operation with ILAE-III outcome afterwards the surgery. He had suffered from epilepsy since the age of 24 years (26 years of epilepsy duration) with seizure frequency of 9 per year.

In this study we observed that, the seizure rate and the duration that the patients have had HS linked PR-TLE, have a profound effect on the outcome of their subsequent surgery. We found a trend for a better outcome in patients with daily and yearly seizures as well as shorter duration of epilepsy and surgery age which was not statistically significant. All the PR-TLE patients were homogeneous in terms of onset age, AEDs usage and surgery procedures [1,20-22]. Patient assortment and presurgical investigations were standardized. The upshot of the surgery considered into ILAE classification criteria was collected independently and blindly (i.e. with no submission while collecting the information as to what it was to be analysed for), to reduce information collection bias. Our study was based on the results of most other studies, which tried to link up the seizure rate and duration of epilepsy discretely with post-surgical outcome [23-29] . Due to polemics in prediction of long term outcome [1,30-32], we used one year, three years and five years next to the surgery for outcome prediction. Our study plainly described that the seizure rate and epilepsy duration govern the seizure predisposition later years after the surgery. The main advantage of our study was that no patient was lost throughout the follow-up assessments and all supported well. Patients who grieved from epilepsy with frequent seizures for a long time may have greater risk of depressive and cognitive side effects of epilepsy surgery [33], but some patients can have a tremendous outcome. This result is imperative when determining whether a patient should be offered surgery. Furthermore our data fairly support the existence of an ongoing epileptogenic process, triggered by frequent seizures and duration of epilepsy within certain surgery age. At least in our patient population, a kindling process can be entirely included. Kindling may be related to the seizure rate and duration of epilepsy besides, lack of statistical significance.