Seizure outcomes and predictors in patients with repeat epilepsy surgery

doi:10.21203/rs.3.rs-3902867/v1

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Seizure outcomes and predictors in patients with repeat epilepsy surgery

https://doi.org/10.21203/rs.3.rs-3902867/v1

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(1) Background: One of the most important goals of surgical epilepsy treatment is seizure freedom. Patients who continue to experience seizures after epilepsy surgery could be considered for a repeat surgical treatment. This study aimed to analyze the seizure outcomes of re-peat surgical treatment of epilepsy and evaluate the prognostic factors.

(2) Methods: This single-center cohort study retrospectively collected clinical data from patients undergoing repeat epilepsy surgery at the Aviation General Hospital from 2016 to 2022. Patients who met the inclusion criteria were followed up for at least one year, and seizure outcomes were based on the International League Against Epilepsy (ILAE) seizure outcome classification.

(3) Results: A total of 43 patients were included in this study, with a mean follow-up of 43.95 months. Malformation of cortical development was the most common postoperative pathology finding, occurring in 19 (44.2%) patients, followed by tumors in seven (16.3%) patients. Following repeat epilepsy surgery, 23 (53.5%) patients achieved ILAE Class 1 or 2. Multifactorial analysis showed that lesional magnetic resonance imaging (MRI) was associated with favorable seizure outcomes, and bilateral or multifocal ictal discharge patterns predicted poor seizure outcomes. Repeat epilepsy surgeries resulted in 13 (30.2%) patients with permanent neurological deficits.

(4) Conclusions: Following a detailed assessment, including imaging, electroencephalography (EEG), and invasive evaluation, repeat epilepsy surgery is a safe and effective option for patients who have failed resective epilepsy surgery. Meanwhile, possible neurological permanent deficits should be taken into account when considering repeat surgery.

Biological sciences/Neuroscience

Biological sciences/Neuroscience/Cognitive neuroscience

Biological sciences/Neuroscience/Development of the nervous system

Biological sciences/Neuroscience/Diseases of the nervous system

Epilepsy

Repeat epilepsy surgery

Predictor

Failure

Seizure outcome

Epilepsy surgery is the best treatment option for drug-refractory epilepsy and can help achieve seizure freedom in 40–80% of patients^1–3. Unfortunately, despite progress in the preoperative assessment of epileptic foci localization, a certain percentage of epileptic patients continue to have seizures of varying severity, affecting their lives following epilepsy surgery⁴. There is a presumption that these patients are not suitable candidates for surgery⁵. For these patients, additional medication regimen adjustments or palliative surgery, such as vagus nerve stimulation or deep brain stimulation, are typically options⁶. Previous studies demonstrated that seizure freedom is the most significant predictor of quality of life⁷. In order to control seizures, repeat surgery is also an option for a subset of patients.

There are numerous potential causes for continued seizures after epilepsy surgery; classical explanations include inaccurate localization of the epileptic focus, tumor recurrence, involvement of functional areas by the epileptic focus and preoperative proven multifocal epilepsy only to alleviate the frequency or severity of seizures^5,8,9. Regardless of the reason, the accuracy of seizure focus localization and seizure-free rates after repeat surgery are challenging for neurosurgeons. Moreover, the seizure-free rate following repeat surgery is 23.5–69.7%^9–12. Given the risks associated with repeat surgery and the expense of preoperative evaluation, this is daunting for many patients. In one review report, the repeat surgery rate ranged from 3.8–14%⁶.

Thus, assessing which patients are best candidates for repeat resective surgery is critical. The risk of neurological or surgical complications also rises with each additional operation. However, due to the complexity of repeat surgery for epilepsy, previous research reports did not pay sufficient consideration to the optimal timing of repeat surgery, criteria for suitable candidates, favorable predictors of epilepsy prognosis and safety of repeat surgery. In the present study, we performed a retrospective analysis of epileptic patients who underwent repeat surgery at our epilepsy center to describe clinical characteristics and epilepsy outcomes and to assist clinicians in making decisions when confronted with patients who continue to experience seizures after surgery.

2.1. Patient selection

We retrospectively analyzed the clinical data of 59 patients who underwent repeat epilepsy surgery from January 2016 to June 2022 at the Aviation General Hospital. Patient inclusion criteria included the following: 1) patients responded poorly to antiepileptic drugs; 2) had undergone resective surgical treatment; 3) had undergone repeat surgery at the Aviation General Hospital between January 2016 and June 2022; 4) clinical data such as electroencephalography (EEG), magnetic resonance imaging (MRI), computed tomography (CT), and follow-up data were available; and 5) informed consents were provided by patients' guardians or patients themselves. The exclusion criteria were as follows: 1) no recurrence of seizures after the initial resection surgery; 2) patients underwent repeat surgeries, but palliative procedures such as vagus nerve stimulator implantation or corpus callosotomy were excluded; 3) electrophysiological, neuropathological and other clinical data unavailable for review; and 4) patients were lost to follow-up. This study was approved by the Ethics Committee of Aviation General Hospital.

2.2. Preoperative evaluation

The non-invasive evaluations of all patients included seizure semiology, MRI and long-term video-EEG. MRI scan contained T1-, T2- and fluid-attenuated inversion (FLAIR) routinely to identify patients with lesional or non-lesional epilepsy. Diffusion tensor imaging (DTI) or magnetization-prepared rapid acquisition gradient echo sequences (MPRAGE) were conducted when required. The electrodes were placed ac-cording to 10–20 system with 64-channel long-term VEEG monitoring. Positron emission tomography (PET) scan was performed if necessary. The analysis included imaging before initial surgery as an important indicator. Since we intended to analyze the seizure outcomes and prognostic factors of repeat surgery, detailed demographic characteristics such as age at seizure onset, age at initial or last surgery, seizure frequency, side or lobe of resection, and postoperative pathology were recorded.

A multidisciplinary team of neurologists, electrophysiologists, neurosurgeons and neuroradiologists would discuss the treatment program for each patient. If non-invasive evaluations failed to delineate the extent of the epileptogenic zone, stereotactic intra-cranial depth electrode implantation would be performed. Intracerebral 8-, 10-, 12-, 16- and 18-contact depth electrodes (with an electrode diameter of 0.8 mm) were employed. Patients continued to undergo stereoelectroencephalography (SEEG) monitoring after electrode implantation to detect spontaneous seizures. The location of the seizure onset zone and the extent of resection were determined based on monitoring results. In patients who did not undergo an invasive examination, electrocorticography was used to acquire additional information and guide the margin of resection. Diagnostic pathology was based on the pathologist's view of the postoperative brain specimen and the initial postoperative pathology findings. We compared the patients' records of the initial operation and the evaluation before reoperation to explore the reasons for the failure of the initial surgery. Moreover, the probable explanation could be inadequate resection, involvement of eloquent areas, inaccurate localization of epileptogenic zone and extensive or multifocal epileptogenic zones. The evaluation process and postoperative image of a patient selected for this study are shown in Fig. 1.

2.3. Follow-up and outcomes

All patients who underwent repeat epilepsy surgery were scheduled to be followed up at three and six months, one year and yearly after that. After undergoing reoperations, patients enrolled in this study were followed up for at least one year. Repeat MRI and scalp EEG were compulsory for review. On the basis of medical records, telephone interviews, and objective examination, seizure outcomes and postoperative complications were determined. Acute postoperative seizure (APOS) is defined as a seizure occurring during the first seven days of surgery. It is not considered to be seizure recurrence. For recurrent seizures a week later, patients were asked to record the date and form of seizure and provide feedback. Seizure outcomes were assessed postoperatively using the International League Against Epilepsy (ILAE) classification, with favorable seizure outcomes defined as ILAE Class 1–2 and unfavorable as ILAE Class 3–6.

2.4. Statistical analysis

Descriptive statistics of the variables were computed, including means and standard errors for continuous variables and frequencies and percentages for categorical variables. Unpaired two-sided student t-test for continuous variables and Pearson chi-square or Fisher's exact tests were used for categorical variables. Prognostic factors on repeat epilepsy surgery were measured by univariate and multivariate analyses. Variables with p-value < 0.1 in the univariate analysis were entered into the multivariate analysis. A p-value < 0.05 was considered statistically significant. The statistical analyses were conducted using Statistical Product and Service Solution(SPSS)statistics software version 25.0 (IBM).

3.1. Demographic characteristics

Overall, 43 patients met the enrollment criteria (26 males and 17 females) from January 2016 and June 2022. The mean age at seizure onset was 9.46 (seizures from birth to 52 years old). The mean duration before the initial surgery was 6.41 years (0.5–27 years), and the mean duration between the initial and last surgery was 4.08 years (0.25–20 years). Furthermore, 21 patients (48.8%) were minors at the time of their last surgery. Seven (16.3%) patients had a previous history of encephalitis, five (11.6%) were born with ischemic hypoxia, four (9.3%) had a history of head trauma, and two (4.7%) were diagnosed with cerebral palsy.

3.2. Epilepsy characteristics

Seizures could be preceded by an aura in 18 (58.1%) patients, and 11 (25.6%) patients had previous epileptic sustained status epilepticus (SE). Prior to undergoing repeat surgery, the majority of patients had a high frequency of seizures, with 19 (44.2%) patients having daily seizures. All patients were treated with multiple anti-seizure medication (ASM). The mean number of ASM was 2.84 ± 0.95. Focal seizures were observed in 13 (30.2%) patients, and generalized seizures in 15 (34.9%) patients. The remaining 15 patients (34.9%) had multiple seizure forms, including focal and generalized seizures. Additionally, 25 (58.1%) patients had focal to bilateral tonic-clonic seizures.

3.3. Diagnostics characteristics

In 25 patients (58.1%), when combined with data from previous examinations, MRI scans were able to reveal the presence of clear lesions. All patients underwent scalp EEG monitoring and capture of usual seizures before reoperation. Onset EEG was focal in 18 (41.9%) patients, unilateral in 11 (25.6%) patients and bilateral or multifocal in 14 (32.6%) patients. To further determine the extent of epileptic foci, 32 (74.4%) patients underwent PET and 25 (58.1%) patients underwent deep intracranial electrode implantation. Postoperative histopathology found cortical dysplasia in 19 (44.2%) patients, tumors in seven (16.3%) patients, and no positive findings in five (11.6%) other patients.

3.4. Surgical characteristics

The temporal lobe was involved in the initial surgical site in 17 (39.5%) patients. APOS occurred in 17 (39.5%) patients. Moreover, 29 (67.4%) patients showed reduced seizures postoperatively before repeat surgery. After combining the patients' preoperative examinations and postoperative seizure outcomes, we found that inadequate re-section and multifocal epileptogenic zones were the primary causes of initial surgery failure in 22 (51.2%) and 11 (25.6%) patients, respectively. In addition, six (14.0%) patients had conservative resection of the epileptogenic zone adjacent to the eloquent zone, and four (9.3%) patients had inaccurate localization of the epileptogenic zone. The characteristics of patients are summarized in Table 1.

Table 1

Univariate analysis of prognostic factors influencing seizure outcome. (n = 43)
Characteristics	Favorable outcomes	Unfavorable outcomes	p
Demographic characteristics
Sex			1.000
M, n = 26	14 (53.8%)	12 (46.2%)
F, n = 17	9 (52.9%)	8 (47.1%)
Age at seizure onset	11.13 ± 2.70	7.54 ± 1.51	0.271
Duration before the initial surgery	7.91 ± 1.61	4.69 ± 1.30	0.134
Duration between surgeries	4.61 ± 1.61	3.48 ± 4.93	0.461
Age at last surgery			0.547
≤ 18y, n = 21	10 (47.6%)	11 (52.4%)
>18y, n = 22	13 (59.1%)	9 (40.9%)
Past history			0.365
Normal, n = 25	15 (60.0%)	10 (40.0%)
Abnormal, n = 18	8 (44.4%)	10 (55.6%)
Number of ASM	2.87 ± 0.87	2.80 ± 1.06	0.814
Epilepsy characteristics
Aura			0.365
Yes, n = 18	8 (44.4%)	10 (55.6%)
No, n = 25	15 (60.0%)	10 (40.0%)
History of SE			0.078
Yes, n = 11	3 (27.3%)	8 (72.7%)
No, n = 32	20 (62.5%)	12 (37.5%)
Seizure frequency			0.685
Daily, n = 19	9 (47.4%)	10 (52.6%)
Weekly, n = 13	7 (53.8%)	6 (46.2%)
Monthly, n = 11	7 (63.6%)	4 (36.4%)
Seizure types			0.429
Focal, n = 13	8 (61.5%)	5 (38.5%)
Generalized, n = 15	6 (40.0%)	9 (60.0%)
Both, n = 15	9 (60.0%)	6 (40.0%)
Focal to bilateral tonic-clonic seizures			0.395
No, n = 18	11 (61.1%)	7 (38.9%)
Yes, n = 25	12 (48.0%)	13 (52.0%)
Diagnostics
Lesion on MRI			0.004*
No, n = 18	5 (27.8%)	13 (72.2%)
Yes, n = 25	18 (72.0%)	7 (28.0%)
Invasive monitoring			0.763
No, n = 18	9 (50.0%)	9 (50.0%)
Yes, n = 25	14 (56.0%)	11 (44.0%)
PET			0.295
No, n = 11	4 (36.4%)	7 (63.6%)
Yes, n = 32	19 (59.4%)	13 (40.6%)
EEG			0.002*
Focal, n = 18	15 (83.3%)	3 (16.7%)
Unilateral, n = 11	5 (45.5%)	6 (54.5%)
Bilateral or multifocal, n = 14	3 (21.4%)	11 (78.6%)
Pathology			0.391
CD, n = 19	10 (62.6%)	9 (47.4%)
Tumor, n = 7	5 (71.4%)	2 (28.6%)
Non-special	1 (20.0%)	4 (80.0%)
Others	7 (58.3%)	5 (41.7%)
Surgical characteristics
First resection location			0.233
Temporal, n = 17	11 (64.7%)	6 (35.3%)
Extratemporal, n = 26	12 (46.2%)	14 (53.8%)
Acute postoperative seizure			0.001*
Yes, n = 17	4 (23.5%)	13 (76.5%)
No, n = 26	19 (82.6%)	7 (26.9%)
Seizure reduction			1.000
No, n = 14	7 (50.0%)	7 (50.0%)
Yes, n = 29	16 (55.2%)	13 (44.8%)
Repeat resection location			0.225
Temporal	16 (61.5%)	10 (38.5%)
Extratemporal	7 (41.2%)	10 (58.8%)
Reason for initial failure			0.032*
Inaccurate localization of epileptogenic zone	2 (50.0%)	2 (50.0%)
Extensive / multifocal epileptogenic zone	2 (18.2%)	9 (81.8%)
Involvement of eloquent areas	3 (50.0%)	3 (50.0%)
Inadequate resection	16 (72.7%)	6 (27.3%)
Surgical complication			0.975
No, n = 29	16 (53.3%)	14 (46.7%)
Yes, n = 14	7 (53.8%)	6 (46.2%)
M: male; F: female; ASM: anti-seizure medication; SE: status epilepticus; MRI, magnetic resonance imaging; PET, positron emission tomography; EEG: electroencephalogram; CD: cortical dysplasia.
* p < 0.05.

3.5. Outcomes and predictors

All patients were followed up for at least one year, with a mean follow-up duration of 43.95 ± 19.68 (range from 12–98) months. Ultimately, 23 patients (53.5%) achieved a favorable seizure outcome after repeat surgery. While 13 (30.2%) patients had surgical complications. Potential prognostic factors associated with seizure outcome in the univariate factor analysis were as follows: history of SE (p = 0.078), preoperative baseline MRI findings (p = 0.004), EEG (p = 0.002), APOS (p = 0.001) and reasons of initial failure (p = 0.032). A multivariate analysis was utilized to evaluate the aforementioned five factors, and the results were as follows: lesion on MRI (odds ration (OR) = 0.049, confidence interval (CI): 0.003–0.873, p = 0.040) was associated with favorable seizure outcomes, and bilateral or multifocal ictal discharge patterns (OR = 25.082, CI: 1.726–364.533, p = 0.018) predicted poor seizure outcome. Detailed data is provided in Table 2.

Table 2

Potential prognostic factors associated with seizure outcome in multivariate analysis. (n = 43)
Characteristics	OR	95%CI	p
History of SE	2.217	0.096–51.199	0.619
APOS	3.206	0.256–40.153	0.366
Lesion on MRI	0.049	0.003–0.873	0.040*
Reason for initial failure
Inaccurate localization of epileptogenic zone	Ref.
Extensive / multifocal epileptogenic zone	4.069	0.046-356.914	0.539
Involvement of eloquent areas	10.201	0.043-2394.836	0.404
Inadequate resection	2.003	0.024-165.027	0.758
EEG
Focal	Ref.
Unilateral	13.293	0.704-251.148	0.084
Bilateral or multifocal	25.082	1.726-364.533	0.018*
OR: odds ration; CI, confidence interval; APOS, acute postoperative seizure; SE: status epilepticus; MRI, magnetic resonance imaging; Ref., reference; EEG: electroencephalogram.
* p < 0.05.

Surgical resective surgery is a viable treatment option for patients with drug-resistant epilepsy¹². Prior research indicates that seizure freedom rates after resective surgery can range from 40–80%^1–3. About 80% seizure-free rate can be achieved in patients with temporal lobe epilepsy. However, 30–40% of patients suffer from seizures even after resective epilepsy surgery, which is considered a surgical failure. After initial surgical interventions have failed, epilepsy treatment can become challenging, frustrating patients and clinicians⁸. Moreover, managing patients who have failed initial epilepsy surgery is also difficult. Recurrent seizures in these patients are closely associated with neurologic and neuropsychological deterioration, resulting in a substantial decline in quality of life⁴. However, few scholars or research organizations have paid attention to this population. Patients may require experimental medical treatments, additional surgical intervention, or neuromodulation, including vagus nerve stimulation, deep brain stimulation, and responsive neurostimulation^5,6. Therefore, the data available to assist in selecting candidates for repeat surgery are limited. This study retrospectively analyzed the clinical characteristics of patients who underwent repeat resective surgery at our center to support the surgeon's clinical practice.

A meta-analysis of 782 patients found that 47% of patients who received resective surgery and subsequently underwent repeat resective surgery were seizure-free⁸. In this study, a total of 43 patients met the inclusion criteria. All patients were followed up for at least one year after undergoing repeat resective surgery. Favorable seizure outcome was achieved in 23 patients (53.5%). Furthermore, 38 patients underwent a second surgery, and the remaining five had an additional third surgery; three out of the five patients underwent vagus nerve stimulator implantation before undergoing repeat resective surgery. The seizure freedom rate was consistent with previous studies' findings^12,13.

However, despite the undeniable possibility of seizure freedom after repeat surgery, the situation remains complicated; the optimal time for reassessment and the criteria for suitable candidates for reoperation are still unclear. Previous reports have identified certain prognostic factors for patients undergoing reoperation. This study found that the presence of a lesion on preoperative MRI was an independent predictor of excellent seizure outcome. Thus, a negative MRI strongly correlates with a worse seizure outcome. Moreover, 25 patients (58.1%) displayed lesions on MRI before initial surgery and had postoperative seizure recurrence after resective surgery. Seizure freedom was achieved in 18 patients following repeat surgery. A study by Grote reported similar findings⁹. The conservative approach led to smaller tailored resection limited by eloquent zones¹⁴, which is the structural basis of seizure recurrence. Besides, 16 of the 25 patients had reoperation sites close to the initial surgery site. Although most patients underwent a lesion-tailored resection, insufficient resection was an acceptable explanation for the recurrence of seizures in these individuals. Previous studies have demonstrated that surgical total resection was significantly better than subtotal resection in patients with focal radiological lesions such as cavernous malformation, focal cortical dysplasia (FCD), and tumors¹⁰. Moreover, Ruta et al. considered that the epileptogenic zone extends beyond the obvious lesion on MRI¹⁵. Some patients' postoperative histopathology revealed dual pathology, and studies estimated that the likelihood of this phenomenon ranged from 3–13.5%^16,17. In developmental tumors, the tumor may be combined with FCD, and they are epileptogenic. FCD lesions are subtle and difficult to distinguish from the tumor or surrounding cortical structures. A well-tailored lesionenctomy that excludes adjacent cortical malformations is unlikely to prevent recurrent seizures. Even though 3.0-T MRI is routinely used for pre-surgical evaluation at our center, FCD localization still has some limitations. Future imaging research exploration, such as higher resolution MRI applications for clinical practice, could aid in guiding surgical strategy.

In this study, the distribution of seizure patterns on the preoperative EEG played a crucial role in predicting postoperative outcomes. In the case of preoperative focal or unilateral onset seizures, 15 of 18 patients (83.3%) and five of 11 patients (45.5%) reached favorable seizure outcomes following repeat surgery, respectively. In contrast, 78.6% of patients with bilateral or multifocal seizures had persistent seizures. Schmeiser et al. stated that 64% of patients with bilateral seizure onset experienced postoperative seizure recurrence¹⁸. In addition, they discovered an association between preoperative secondary generalized seizures and bilateral ictal or interictal epileptiform activity. However, our findings were inconsistent. This may be because their study was limited to patients with temporal lobe epilepsy (TLE). Possible reasons for bilateral seizure onset could be the presence of bilateral epileptogenic zones or epileptic foci deep in the brain due to extensive epileptic pathologic networks manifesting bilateral seizure onset. According to an invasive EEG study by Reinhard, the remaining ipsitemporal epileptogenic tissue near the anterior or posterior hippocampal commissures could assume contralateral seizure onset¹⁹.

APOS was a significant risk factor that predicted seizure recurrence after repeat surgery. Bo et al. recently demonstrated a strong association between APOS and seizure recurrence²⁰. This report aimed to identify predictive factors in patients with FCD, where 13 of 120 patients presented with habitual APOS, and only two achieved seizure freedom. In a report on repeat surgery for drug-resistant epilepsy, Sean et al. noted APOS as a predictor of failure in repeat surgery. In the current study, 17 patients suffered from APOS after repeat epilepsy surgery, and 13 experienced seizures. Possible explanations were that APOS reacted to incomplete removal of the epileptogenic tissue, it was incorrectly localized, or it could be due to a complication of the surgery. The univariate analysis also showed a correlation between the history of SE and poor seizure outcomes. This is consistent with a previous study stating that SE is an important prognostic factor²¹. In contrast, subsequent multivariate analysis did not yield comparable outcomes. Also, extratemporal lobe epilepsy, lower frequency of seizures and surgery on the right side were associated with favorable seizure outcomes^15,22,23. In comparison, these traits were not found to be significant in the present study.

Defining the failure of epilepsy surgery is challenging and requires individualized analysis of each patient. There are many variables influencing surgery. We retrospectively analyzed the possible reasons for surgical failure as follows. First, initial surgical failure was attributed to incomplete resection of the epileptogenic zone. In this study, 22 cases were due to incomplete resection, and 16 cases achieved favorable seizure outcomes after reoperation. In the univariate analysis, incomplete resection had a significantly better prognosis than other causes, but it was excluded from the multivariate analysis. The other reason was that the epileptogenic foci were adjacent to eloquent areas and could not be completely resected to avoid postoperative neurologic deficits. Some scholars categorized such causes as the former². However, we did not agree. The former is due to inadequate identification of the epileptogenic zone in preoperative assessment, and the latter is pertaining to difficulties in the operation of surgical technique, which are completely different concepts. Sacino et al. demonstrated that patients with functional limitations preventing a complete initial resection would have better seizure outcomes following reoperation²⁴. Additionally, if a patient's epileptogenic and eloquent zones overlap, an invasive test is required to avoid subsequent resective surgery.

Failure of epilepsy surgery also relates to extensive or multifocal epileptic zones. Multiple epileptogenic foci are common in patients with tuberous sclerosis complex (TSC) due to the presence of multiple tubers^6,25. In this case, resective surgery aimed to reduce seizure; therefore, seizure freedom was not expected. A recent systematic review found that patients with TSC achieved a 90% reduction in seizure frequency following resection²⁶. Other causes include preoperative mislocalization, formation of new epileptogenic foci and diffuse epileptogenic process of genetic or encephalitic origin¹. Ruta et al. considered the presence of a highly epileptogenic substrate reflected by its ability to generate a new epileptogenic focus after surgery¹⁵, which required further research into the mechanisms of seizure recurrence. Based on symptomatology and scalp EEG findings, some patients with extratemporal lobe epilepsy might be misidentified as TLE²⁷. A previous report by Lee found that out of 33 patients initially diagnosed with TLE who underwent invasive monitoring, 11 had extratemporal seizure onset²⁸. Another study found that patients with primary temporal lobectomy were reevaluated, and 50% had insula involvement¹. Jimmy et al. reported that 14 patients failed epilepsy surgery, and nine had insula epilepsy after invasive testing²⁹. Non-invasive tests such as single-photon emission computed tomography (SPECT), PET and magnetoencephalography (MEG) help localize the epileptogenic zone, but the sensitivity and specificity of these techniques are limited. Therefore, the implantation of SEEG to localize the epileptogenic zone is a reasonable option, especially for patients undergoing repeat surgeries because of changes in anatomical structure and reorganization of the epileptic network. In this paper, 25 patients underwent invasive monitoring, and 14 achieved favorable seizure outcomes. It appeared to make no discernible difference as it was applied to increasingly complex cases.

Sometimes, seizure freedom could be achieved with multiple surgeries. In the meantime, planned neurological deficits are acceptable if seizure freedom can be achieved³⁰. The overall complication rate for repeat epilepsy surgery was 30.2% in this study, similar to previous reports³¹. Nevertheless, a wide variation was reported in different literature. A recent review reported postsurgical complications in 13.5% of patients after reoperation⁶. Ramantani et al. exposed that 57% of their patients had some form of adverse event, while no complications were observed in the study by Holmes et al.^4,32. Postoperative complications are mainly categorized into neurological deficits and common surgical complications. Among these, visual field impairment is the most prevalent complication, especially in TLE patients. In the present study, complications were mainly visual field defects, mild hemiparesis and infections. Notably, we only accounted for new complications following repeat surgery to assess the safety of repeat surgery, while initial surgery complications were not included. A higher risk of neurological deficits might be expected when initial surgeries fail due to conservative resection. Persistent seizures associated with quality of life could lead to various progressive neurological issues. A study regarding neuropsychological profiles conducted by Grote demonstrated that repeated losses in the same cognitive domain were rare, and those losses would improve in time due to favorable seizure outcomes^9,33. If a favorable seizure outcome comes with complications, the surgeon must be cautious and discuss the situation with the patient.

Limitation

There were several limitations to this study. This retrospective analysis was single-centered, so methodological limitations could not be avoided. Furthermore, many of the factors associated with surgical failure were not included in the study, such as postoperative medication regimens, and previous studies have shown that levetiracetam application reduced the frequency of seizures. In addition, previous studies found that neurocognitive improvement is strongly associated with good seizure outcomes. Due to the small sample size with pertinent clinical data, we will analyze this further in subsequent studies. Last but not least, patients with repeat surgery need longer follow-up.

Our study found that patients with recurrent seizures after the initial surgery could benefit significantly from repeat surgery; more than half (23 out of 43 patients) achieved seizure freedom. Lesional MRI predicted a favorable seizure outcome and bilateral or multifocal ictal discharge patterns were associated with poor seizure outcomes. Repeat surgery had a significantly higher complication rate than initial surgery to achieve a satisfactory seizure outcome. Therefore, after a detailed preoperative reassessment, a decision to proceed with repeat surgery and postoperative complications should be taken into account when advising the family on the likelihood of seizure outcome.

Author Contributions: Conceptualization, Yue Hu, Guoqiang Chen and Guangming Zhang; Data curation, Yaoling Liu and Yue Hu; Formal analysis, Rui Zhang; Funding acquisition, Guangming Zhang; Methodology, Rui Zhang, Jianwei Chen and Yue Hu; Project administration, Guangming Zhang; Resources, Junjian Zhou and Zhaozhao Zhang; Software, Jianfei Hu; Supervision, Guoqiang Chen and Guangming Zhang; Validation, Guangming Zhang; Visualization, Yue Hu; Writing – original draft, Yue Hu; Writing – review & editing, Rui Zhang and Qiang Liu. All authors have read and agreed to the published version of the manuscript.

Funding: This work was supported by Science and Technology Innovation 2030-Brain Science and Brain-Inspired Intelligence Project (Grant No. 2021ZD0200200).

Institutional Review Board Statement: The study was approved by the Ethics Committee of the Aviation General Hospital (protocol code IA-202130). This study was done in accordance with the principles outlined in the Declaration of Helsinki.

Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.

Data Availability Statement: The data used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Acknowledgments: The authors gratefully thank the staffs of the Aviation General Hospital, Beijing 100012, China.

Conflicts of Interest: The author(s) declare no competing interests.

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No competing interests reported.

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Seizure outcomes and predictors in patients with repeat epilepsy surgery

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Abstract

Figures

1. Introduction

2. Materials and Methods

2.1. Patient selection

2.2. Preoperative evaluation

2.3. Follow-up and outcomes

2.4. Statistical analysis

3. Results

3.1. Demographic characteristics

3.2. Epilepsy characteristics

3.3. Diagnostics characteristics

3.4. Surgical characteristics

3.5. Outcomes and predictors

4. Discussion

5. Conclusions

Declarations

References

Additional Declarations

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