An exploratory study into the influence of laterality and location of hippocampal sclerosis on seizure prognosis and global cortical thinning

AbstractIn mesial temporal lobe epilepsy (mTLE), the correlation between disease duration, seizure laterality, and rostro-caudal location of hippocampal sclerosis has not been examined in the context of seizure severity and global cortical thinning. In this retrospective study, we analyzed structural 3 T MRI from 35 mTLE subjects. Regions of FLAIR hyperintensity (as an indicator of sclerosis)—based on 2D coronal FLAIR sequences—in the hippocampus were manually segmented, independently and in duplicate; degree of segmentation agreement was confirmed using the DICE index. Segmented lesions were used for separate analyses. First, the correlation of cortical thickness with disease duration and seizure focus laterality was explored using linear model regression. Then, the relationship between the rostro-caudal location of the FLAIR hyperintense signal and seizure severity, based on the Cleveland Clinic seizure freedom score (ccSFS), was explored using probabilistic voxel-wise mapping and functional connectivity analysis from normative data. The mean DICE Index was 0.71 (range 0.60–0.81). A significant correlation between duration of epilepsy and decreased mean whole brain cortical thickness was identified, regardless of seizure laterality (p < 0.05). The slope of cortical volume loss over time, however, was greater in subjects with right seizure focus. Based on probabilistic voxel-wise mapping, FLAIR hyperintensity in the posterior hippocampus was significantly associated with lower ccSFS scores (greater seizure severity). Finally, the right hippocampus was found to have greater brain-wide connectivity, compared to the left side, based on normative connectomic data. We have demonstrated a significant correlation between duration of epilepsy and right-sided seizure focus with global cortical thinning, potentially due to greater brain-wide connectivity. Sclerosis along the posterior hippocampus was associated with greater seizure severity, potentially serving as an important biomarker of seizure outcome after surgery.

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Resective Epilepsy Surgery for Tuberous Sclerosis in Children

Neurosurgery ◽

10.1227/neu.0000000000000875 ◽

2015 ◽

Vol 77 (4) ◽

pp. 517-524 ◽

Cited By ~ 43

Author(s):

Aria Fallah ◽

Shaun D. Rodgers ◽

Alexander G. Weil ◽

Sumeet Vadera ◽

Alireza Mansouri ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Epilepsy Surgery ◽

Medical Center ◽

Cleveland Clinic ◽

Intractable Epilepsy ◽

Seizure Outcome ◽

Seizure Freedom ◽

Epileptogenic Zone ◽

Children's Hospital ◽

Children’S Hospital

Abstract BACKGROUND: There are no established variables that predict the success of curative resective epilepsy surgery in children with tuberous sclerosis complex (TSC). OBJECTIVE: We performed a multicenter observational study to identify preoperative factors associated with seizure outcome in children with TSC undergoing resective epilepsy surgery. METHODS: A retrospective chart review was performed in eligible children at New York Medical Center, Miami Children's Hospital, Cleveland Clinic Foundation, BC Children's Hospital, Hospital for Sick Children, and Sainte-Justine Hospital between January 2005 and December 2013. A time-to-event analysis was performed. The “event” was defined as seizures after resective epilepsy surgery. RESULTS: Seventy-four patients (41 male) were included. The median age of the patients at the time of surgery was 120 months (range, 3-216 months). The median time to seizure recurrence was 24.0 ± 12.7 months. Engel Class I outcome was achieved in 48 (65%) and 37 (50%) patients at 1- and 2-year follow-up, respectively. On univariate analyses, younger age at seizure onset (hazard ratio [HR]: 2.03, 95% confidence interval [CI]: 1.03-4.00, P = .04), larger size of predominant tuber (HR: 1.03, 95% CI: 0.99-1.06, P = .12), and resection larger than a tuberectomy (HR: 1.86, 95% CI: 0.92-3.74, P = .084) were associated with a longer duration of seizure freedom. In multivariate analyses, resection larger than a tuberectomy (HR: 2.90, 95% CI: 1.17-7.18, P = .022) was independently associated with a longer duration of seizure freedom. CONCLUSION: In this large consecutive cohort of children with TSC and medically intractable epilepsy, a greater extent of resection (more than just the tuber) is associated with a greater probability of seizure freedom. This suggests that the epileptogenic zone may include the cortex surrounding the presumed offending tuber.

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Seizure Outcome After Ipsitemporal Reoperation in Pharmacoresistant Temporal Lobe Epilepsy Patients With Hippocampal Sclerosis and Nonspecific Pathology

Neurosurgery Open ◽

10.1093/neuopn/okab001 ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Jugoslav Ivanović ◽

Kristin Åshild Alfstad ◽

Pål Bache Marthinsen ◽

Ketil Berg Olsen ◽

Pål Gunnar Larsson ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Surgical Complications ◽

Postoperative Morbidity ◽

Hippocampal Sclerosis ◽

Neurological Impairment ◽

Seizure Outcome ◽

Seizure Freedom ◽

Before And After ◽

Repeated Surgery

ABSTRACT BACKGROUND Treatment of patients with pharmacoresistant temporal lobe epilepsy with hippocampal sclerosis and nonspecific pathology who failed initial resection is challenging, although selected patients may benefit from repeated surgery. OBJECTIVE To determine seizure outcome, postoperative morbidity, and possible predictors of seizure freedom after repeated ipsitemporal resection. METHODS We reviewed the results of comprehensive epilepsy evaluations performed before the initial and repeated resections in 10 patients with hippocampal sclerosis and 13 with nonspecific pathology. We assessed the Engel classification of seizure outcome 2 yr after repeated resection, evaluated postoperative morbidity, and examined the association of epilepsy and surgical characteristics with seizure freedom before and after reoperation. RESULTS After reoperation, in patients with hippocampal sclerosis, seizure freedom (Engel class I) was achieved in 2 (20%), 1 (10%) experienced surgical complications, and 1 (10%) experienced permanent neurological impairment. Following reoperation in patients with nonspecific pathology, seizure freedom was achieved in 1 (8%), 3 (23%) experienced surgical complications, and 4 (31%) experienced permanent neurological impairment. Epilepsy and surgical characteristics before and after reoperation were not associated with seizure freedom. CONCLUSION Patients with hippocampal sclerosis and nonspecific pathology who underwent a comprehensive initial work-up and failed original temporal lobe resection rarely become seizure-free after repeated ipsitemporal reoperation. Reoperations carry a high risk of surgical complications and neurological impairment. Predictors for seizure freedom could not be defined.

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Determinants of seizure outcome after resective surgery following stereoelectroencephalography

Journal of Neurosurgery ◽

10.3171/2021.6.jns204413 ◽

2021 ◽

pp. 1-9

Author(s):

Juan C. Bulacio ◽

James Bena ◽

Piradee Suwanpakdee ◽

Dileep Nair ◽

Ajay Gupta ◽

...

Keyword(s):

Temporal Lobe ◽

Univariate Analysis ◽

Cleveland Clinic ◽

Secondary Outcome ◽

Seizure Outcome ◽

Seizure Freedom ◽

Outcome Predictors ◽

Seizure Recurrence ◽

Resective Surgery

OBJECTIVE The aim of this study was to investigate seizure outcomes after resective epilepsy surgery following stereoelectroencephalography (SEEG), including group characteristics, comparing surgical and nonsurgical groups and assess predictors of time to seizure recurrence. METHODS Clinical and EEG data of 536 consecutive patients who underwent SEEG at Cleveland Clinic Epilepsy Center between 2009 and 2017 were reviewed. The primary outcome was defined as complete seizure freedom since the resective surgery, discounting any auras or seizures that occurred within the 1st postoperative week. In addition, the rate of seizure freedom based on Engel classification was determined in patients with follow-up of ≥ 1 year. Presumably significant outcome variables were first identified using univariate analysis, and Cox proportional hazards modeling was used to identify outcome predictors. RESULTS Of 527 patients satisfying study criteria, 341 underwent resective surgery. Complete and continuous seizure freedom after surgery was achieved in 55.5% of patients at 1 year postoperatively, 44% of patients at 3 years, and 39% of patients at 5 years. As a secondary outcome point, 58% of patients achieved Engel class I seizure outcome for at least 1 year at last follow-up. Among surgical outcome predictors, in multivariate model analysis, the seizure recurrence rate by type of resection (p = 0.039) remained statistically significant, with the lowest risk of recurrence occurring after frontal and temporal lobe resections compared with multilobar and posterior quadrant surgeries. Patients with a history of previous resection (p = 0.006) and bilateral implantations (p = 0.023) were more likely to have seizure recurrence. The absence of an MRI abnormality prior to resective surgery did not significantly affect seizure outcome in this cohort. CONCLUSIONS This large, single-center series shows that resective surgery leads to continuous seizure freedom in a group of patients with complex and severe pharmacoresistant epilepsy after SEEG evaluation. In addition, up to 58% of patients achieved seizure freedom at last follow-up. The authors’ results suggest that SEEG is equally effective in patients with frontal and temporal lobe epilepsy with or without MRI identified lesions.

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Epilepsy Surgery of the Temporal Lobe in Pediatric Population: A Retrospective Analysis

Neurosurgery ◽

10.1227/neu.0b013e318235183d ◽

2011 ◽

Vol 70 (3) ◽

pp. 684-692 ◽

Cited By ~ 25

Author(s):

Miguel Angel Lopez-Gonzalez ◽

Jorge Alvaro Gonzalez-Martinez ◽

Lara Jehi ◽

Prakash Kotagal ◽

Ann Warbel ◽

...

Keyword(s):

Temporal Lobe ◽

Epilepsy Surgery ◽

Pediatric Patients ◽

Hippocampal Sclerosis ◽

Pediatric Population ◽

Cleveland Clinic ◽

Seizure Freedom ◽

Complication Rates ◽

Long Term Outcome

Abstract Background: There is still some reluctance to refer pediatric patients for epilepsy surgery, despite evidence of success in retrospective series. Objective: To describe surgical experience and long-term outcome in pediatric temporal lobe epilepsy (TLE) at a single institution. Methods: Retrospective review of pediatric (<18-years-old) TLE patients who underwent surgery between November 1996 and December 2006 at Cleveland Clinic Epilepsy Center. Cox proportional hazard modeling was used to assess outcome predictors. Results: One hundred thirty pediatric patients met study criteria. Mean time between seizure onset and surgery was 6.3 years. Invasive evaluation was used in 32 patients (24.5%). Hippocampal sclerosis was present in 70 patients (53.8%), either alone or associated in dual pathology. The complication rate was 7%. The seizure-freedom rates at 1, 2, 5, and 12 years were 76%, 72%, 54%, and 41%, respectively (Kaplan-Meier). With the use of the Engel outcome classification, 98 (75.3%) patients were class I, 11 (8.5%) class II, 9 (7%) class III, and 12 (9.2%) were class IV at last follow-up. Only 4 (3.1%) patients underwent reoperations. Antiepileptic drugs (AEDs) were discontinued in 36 patients (28.3%) in a mean period of 18 months (SD ± 17 months; range, 6-102 months). Although left-sided resection, lower number of preoperative AED trials (≤4), and tumor pathology correlated with favorable seizure outcomes, extensive surgical resection remained the only significant outcome predictor after multivariate analysis (P = .007; HR = 0.13 [95% confidence interval 0.007–0.64]). Conclusion: Careful selection of surgical candidates by multidisciplinary evaluations is required. Long-term seizure control is achieved successfully with acceptable low complication rates.

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Normal cerebral cortical thickness in first-degree relatives of temporal lobe epilepsy patients

Neurology ◽

10.1212/wnl.0000000000006834 ◽

2018 ◽

Vol 92 (4) ◽

pp. e351-e358 ◽

Cited By ~ 5

Author(s):

Saud Alhusaini ◽

Magdalena A. Kowalczyk ◽

Clarissa L. Yasuda ◽

Mira K. Semmelroch ◽

Marilise Katsurayama ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Cortical Thickness ◽

Hippocampal Sclerosis ◽

Brain Mri ◽

Intractable Epilepsy ◽

Intracranial Volume ◽

Related Factors ◽

Cortical Thinning ◽

First Degree Relatives

ObjectiveTo examine cerebral cortex thickness in asymptomatic first-degree relatives of patients with mesial temporal lobe epilepsy (MTLE).MethodsWe investigated 127 asymptomatic first-degree relatives of patients with MTLE due to hippocampal sclerosis (HS) (mean age ± SD = 39.4 ± 13 years) and 203 healthy control individuals (mean age ± SD = 36.0 ± 11 years). Participants underwent a comprehensive clinical evaluation and structural brain MRI at 3 study sites. Images were processed simultaneously at each site using a surface-based morphometry method to quantify global brain measures, hippocampal volumes, and cerebral cortical thickness. Differences in brain measures between relatives of patients and controls were examined using generalized models, while controlling for relevant covariates, including age and sex.ResultsNone of the asymptomatic first-degree relatives of MTLE + HS patients showed evidence of HS on qualitative image assessments. Compared to the healthy controls, the asymptomatic relatives of patients displayed no significant differences in intracranial volume, average hemispheric surface area, or hippocampal volume. Similarly, no significant cerebral cortical thinning was identified in the relatives of patients. This was consistent across the 3 cohorts.ConclusionLack of cortical thickness changes in the asymptomatic relatives of patients indicates that the previously characterized MTLE + HS-related cortical thinning is not heritable, and is likely driven by disease-related factors. This finding therefore argues for early and aggressive intervention in patients with medically intractable epilepsy.

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Stereoelectroencephalography: retrospective analysis of 742 procedures in a single centre

Brain ◽

10.1093/brain/awz196 ◽

2019 ◽

Vol 142 (9) ◽

pp. 2688-2704 ◽

Cited By ~ 23

Author(s):

Francesco Cardinale ◽

Michele Rizzi ◽

Elena Vignati ◽

Massimo Cossu ◽

Laura Castana ◽

...

Keyword(s):

Focal Cortical Dysplasia ◽

Hippocampal Sclerosis ◽

Significant Risk ◽

Progressive Increase ◽

Seizure Outcome ◽

Seizure Freedom ◽

Consecutive Series ◽

Epileptogenic Zone ◽

Thermal Coagulation ◽

Resective Surgery

AbstractThis retrospective description of a surgical series is aimed at reporting on indications, methodology, results on seizures, outcome predictors and complications from a 20-year stereoelectroencephalography (SEEG) activity performed at a single epilepsy surgery centre. Prospectively collected data from a consecutive series of 742 SEEG procedures carried out on 713 patients were reviewed and described. Long-term seizure outcome of SEEG-guided resections was defined as a binomial variable: absence (ILAE classes 1–2) or recurrence (ILAE classes 3–6) of disabling seizures. Predictors of seizure outcome were analysed by preliminary uni/bivariate analyses followed by multivariate logistic regression. Furthermore, results on seizures of these subjects were compared with those obtained in 1128 patients operated on after only non-invasive evaluation. Survival analyses were also carried out, limited to patients with a minimum follow-up of 10 years. Resective surgery has been indicated for 570 patients (79.9%). Two-hundred and seventy-nine of 470 patients operated on (59.4%) were free of disabling seizures at least 2 years after resective surgery. Negative magnetic resonance and post-surgical lesion remnant were significant risk factors for seizure recurrence, while type II focal cortical dysplasia, balloon cells, glioneuronal tumours, hippocampal sclerosis, older age at epilepsy onset and periventricular nodular heterotopy were significantly associated with seizure freedom. Twenty-five of 153 patients who underwent radio-frequency thermal coagulation (16.3%) were optimal responders. Thirteen of 742 (1.8%) procedures were complicated by unexpected events, including three (0.4%) major complications and one fatality (0.1%). In conclusion, SEEG is a safe and efficient methodology for invasive definition of the epileptogenic zone in the most challenging patients. Despite the progressive increase of MRI-negative cases, the proportion of seizure-free patients did not decrease throughout the years.

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Long-term seizure outcomes after pediatric temporal lobectomy: does brain MRI lesion matter?

Journal of Neurosurgery Pediatrics ◽

10.3171/2019.4.peds18677 ◽

2019 ◽

Vol 24 (2) ◽

pp. 200-208

Author(s):

Ravindra Arya ◽

Francesco T. Mangano ◽

Paul S. Horn ◽

Sabrina K. Kaul ◽

Serena K. Kaul ◽

...

Keyword(s):

Repeated Measures ◽

Mixed Model ◽

Linear Mixed Model ◽

Hippocampal Sclerosis ◽

Brain Mri ◽

Temporal Lobectomy ◽

Seizure Freedom ◽

Seizure Onset

OBJECTIVEThere is emerging data that adults with temporal lobe epilepsy (TLE) without a discrete lesion on brain MRI have surgical outcomes comparable to those with hippocampal sclerosis (HS). However, pediatric TLE is different from its adult counterpart. In this study, the authors investigated if the presence of a potentially epileptogenic lesion on presurgical brain MRI influences the long-term seizure outcomes after pediatric temporal lobectomy.METHODSChildren who underwent temporal lobectomy between 2007 and 2015 and had at least 1 year of seizure outcomes data were identified. These were classified into lesional and MRI-negative groups based on whether an epilepsy-protocol brain MRI showed a lesion sufficiently specific to guide surgical decisions. These patients were also categorized into pure TLE and temporal plus epilepsies based on the neurophysiological localization of the seizure-onset zone. Seizure outcomes at each follow-up visit were incorporated into a repeated-measures generalized linear mixed model (GLMM) with MRI status as a grouping variable. Clinical variables were incorporated into GLMM as covariates.RESULTSOne hundred nine patients (44 females) were included, aged 5 to 21 years, and were classified as lesional (73%), MRI negative (27%), pure TLE (56%), and temporal plus (44%). After a mean follow-up of 3.2 years (range 1.2–8.8 years), 66% of the patients were seizure free for ≥ 1 year at last follow-up. GLMM analysis revealed that lesional patients were more likely to be seizure free over the long term compared to MRI-negative patients for the overall cohort (OR 2.58, p < 0.0001) and for temporal plus epilepsies (OR 1.85, p = 0.0052). The effect of MRI lesion was not significant for pure TLE (OR 2.64, p = 0.0635). Concordance of ictal electroencephalography (OR 3.46, p < 0.0001), magnetoencephalography (OR 4.26, p < 0.0001), and later age of seizure onset (OR 1.05, p = 0.0091) were associated with a higher likelihood of seizure freedom. The most common histological findings included cortical dysplasia types 1B and 2A, HS (40% with dual pathology), and tuberous sclerosis.CONCLUSIONSA lesion on presurgical brain MRI is an important determinant of long-term seizure freedom after pediatric temporal lobectomy. Pediatric TLE is heterogeneous regarding etiologies and organization of seizure-onset zones with many patients qualifying for temporal plus nosology. The presence of an MRI lesion determined seizure outcomes in patients with temporal plus epilepsies. However, pure TLE had comparable surgical seizure outcomes for lesional and MRI-negative groups.

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Seizure outcome in temporal glioblastoma surgery: lobectomy as a supratotal resection regime outclasses conventional gross-total resection

Journal of Neuro-Oncology ◽

10.1007/s11060-021-03705-x ◽

2021 ◽

Author(s):

Valeri Borger ◽

Motaz Hamed ◽

Inja Ilic ◽

Anna-Laura Potthoff ◽

Attila Racz ◽

...

Keyword(s):

Tumor Resection ◽

Temporal Lobectomy ◽

Secondary Outcome ◽

Seizure Outcome ◽

Seizure Freedom ◽

Secondary Outcome Measure ◽

Total Resection ◽

Class 1 ◽

Postoperative Seizure ◽

The Impact

Abstract Introduction The postoperative seizure freedom represents an important secondary outcome measure in glioblastoma surgery. Recently, supra-total glioblastoma resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma compared to conventional gross-total resections (GTR). However, the impact of ATL on seizure outcome in these patients is unknown. We therefore analyzed ATL and GTR as differing extents of resection in regard of postoperative seizure control in patients with temporal glioblastoma and preoperative symptomatic seizures. Methods Between 2012 and 2018, 33 patients with preoperative seizures underwent GTR or ATL for temporal glioblastoma at the authors’ institution. Seizure outcome was assessed postoperatively and 6 months after tumor resection according to the International League Against Epilepsy (ILAE) classification and stratified into favorable (ILAE class 1) versus unfavorable (ILAE class 2–6). Results Overall, 23 out of 33 patients (70%) with preoperative seizures achieved favorable seizure outcome following resection of temporal located glioblastoma. For the ATL group, postoperative seizure freedom was present in 13 out of 13 patients (100%). In comparison, respective rates for the GTR group were 10 out of 20 patients (50%) (p = 0.002; OR 27; 95% CI 1.4–515.9). Conclusions ATL in terms of a supra-total resection strategy was associated with superior favorable seizure outcome following temporal glioblastoma resection compared to GTR. Regarding above mentioned survival benefit following ATL compared to GTR, ATL as an aggressive supra-total resection regime might constitute the surgical modality of choice for temporal-located glioblastoma.

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The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature

Brain Sciences ◽

10.3390/brainsci11060793 ◽

2021 ◽

Vol 11 (6) ◽

pp. 793

Author(s):

Chiara Pepi ◽

Luca de Palma ◽

Marina Trivisano ◽

Nicola Pietrafusa ◽

Francesca Romana Lepri ◽

...

Keyword(s):

Epilepsy Surgery ◽

Focal Cortical Dysplasia ◽

Hippocampal Sclerosis ◽

Brain Mri ◽

Seizure Freedom ◽

Histopathological Diagnosis ◽

Cortical Malformation ◽

Cognitive Improvement ◽

Cortical Malformations ◽

Nevus Sebaceous

The rare nevus sebaceous (NS) syndrome (NSS) includes cortical malformations and drug-resistant epilepsy. Somatic RAS-pathway genetic variants are pathogenetic in NS, but not yet described within the brain of patients with NSS. We report on a 5-year-old boy with mild psychomotor delay. A brown-yellow linear skin lesion suggestive of NS in the left temporo-occipital area was evident at birth. Epileptic spasms presented at aged six months. EEG showed continuous left temporo-occipital epileptiform abnormalities. Brain MRI revealed a similarly located diffuse cortical malformation with temporal pole volume reduction and a small hippocampus. We performed a left temporo-occipital resection with histopathological diagnosis of focal cortical dysplasia type Ia in the occipital region and hippocampal sclerosis type 1. Three years after surgery, he is seizure-and drug-free (Engel class Ia) and showed cognitive improvement. Genetic examination of brain and skin specimens revealed the c.35G > T (p.Gly12Val) KRAS somatic missense mutation. Literature review suggests epilepsy surgery in patients with NSS is highly efficacious, with 73% probability of seizure freedom. The few histological analyses reported evidenced disorganized cortex, occasionally with cytomegalic neurons. This is the first reported association of a KRAS genetic variant with cortical malformations associated with epilepsy, and suggests a possible genetic substrate for hippocampal sclerosis.

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