Seizure Outcomes and Reoperation in Surgical Rasmussen Encephalitis Patients.

BACKGROUND: Rasmussen encephalitis (RE) is a rare inflammatory disease affecting one hemisphere, causing progressive neurological deficits and intractable seizures. OBJECTIVE: To report long-term seizure outcomes, reoperations, and functional outcomes in patients with RE who underwent hemispherectomy at our institution. METHODS: Retrospective review was performed for all patients with RE who had surgery between 1998 and 2020. We collected seizure history, postoperative outcomes, and functional data. Imaging was independently reviewed in a blinded fashion by 2 neurosurgeons and a neuroradiologist. RESULTS: We analyzed 30 patients with RE who underwent 35 hemispherectomies (5 reoperations). Using Kaplan-Meier analysis, seizure-freedom rate was 81.5%, 63.6%, and 55.6% at 1, 5, and 10 years after surgery, respectively. Patients with shorter duration of hemiparesis preoperatively were less likely to be seizure-free at follow-up (P = .011) and more likely to undergo reoperation (P = .004). Shorter duration of epilepsy (P = .026) and preoperative bilateral MRI abnormalities (P = .011) were associated with increased risk of reoperation. Complete disconnection of diseased hemisphere on postoperative MRI after the first operation improved seizure-freedom (P = .021) and resulted in fewer reoperations (P = .034), and reoperation resulted in seizure freedom in every case. CONCLUSION: Obtaining complete disconnection is critical for favorable seizure outcomes from hemispherectomy, and neurosurgeons should have a low threshold to reoperate in patients with RE with recurrent seizures. Rapid progression of motor deficits and bilateral MRI abnormalities may indicate a subpopulation of patients with RE with increased risk of needing reoperation. Overall, we believe that hemispherectomy is a curative surgery for the majority of patients with RE, with excellent long-term seizure outcome.

Determinants of seizure outcome after resective surgery following stereoelectroencephalography.

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.

Stereoelectroencephalography-Guided Laser Ablations in Patients With Neocortical Pharmacoresistant Focal Epilepsy: Concept and Operative Technique.

BACKGROUND: Laser ablation surgery has had encouraging results in the treatment of multiple intracranial diseases including primary and metastatic brain tumors, radiation necrosis, and epilepsy. The use of the stereoelectroencephalography (SEEG) method in combination with laser thermocoagulation therapy with the goal of modulating epileptic networks in patients with neocortical nonlesional phamacoresistant epilepsy has not been previously described. OBJECTIVE: To describe the novel methodological and conceptual aspects related to SEEG-guided laser ablations in patients with magnetic resonance imaging (MRI)-negative pharmacoresistant neocortical focal epilepsy. METHODS: Guided by previous SEEG intracranial data, a laser ablation probe was inserted by using a robotic guidance device in a 17-yr-old medically refractory epilepsy patient with difficult to localize seizures and nonlesional MRI. The laser applicator position was confirmed by MRI, targeting the left mesial rostral superior frontal gyrus. The ablation was performed under multiplanar digital imaging views and real-time thermal imaging and treatment estimates in each plane. A postablation MRI (contrasted T1 sequence) confirmed the ablation's location and size. RESULTS: The entire procedure was achieved in approximately 100 min. The actual ablation was performed in less than 3 min. Approximately, additional 30 min preoperatively were used for positioning and robot registration. Precise placement of laser application (in comparison with preplanned trajectories) was achieved using the robotic guidance and confirmed by the intraoperative magnetic resonance images. No complications were reported. The patient has been seizure-free since surgery. The follow-up period is 20 mo. Two additional patients, treated with similar methodology, are also described. CONCLUSION: The preliminary experience with the described method shows the feasibility of a unique combination of the SEEG methodology with laser thermocoagulation in patients with neocortical MRI-negative pharmacoresistant focal epilepsy.

A fingerprint of the epileptogenic zone in human epilepsies.

Defining a bio-electrical marker for the brain area responsible for initiating a seizure remains an unsolved problem. Fast gamma activity has been identified as the most specific marker for seizure onset, but conflicting results have been reported. In this study, we describe an alternative marker, based on an objective description of interictal to ictal transition, with the aim of identifying a time-frequency pattern or 'fingerprint' that can differentiate the epileptogenic zone from areas of propagation. Seventeen patients who underwent stereoelectroencephalography were included in the study. Each had seizure onset characterized by sustained gamma activity and were seizure-free after tailored resection or laser ablation. We postulated that the epileptogenic zone was always located inside the resection region based on seizure freedom following surgery. To characterize the ictal frequency pattern, we applied the Morlet wavelet transform to data from each pair of adjacent intracerebral electrode contacts. Based on a visual assessment of the time-frequency plots, we hypothesized that a specific time-frequency pattern in the epileptogenic zone should include a combination of (i) sharp transients or spikes; preceding (ii) multiband fast activity concurrent; with (iii) suppression of lower frequencies. To test this hypothesis, we developed software that automatically extracted each of these features from the time-frequency data. We then used a support vector machine to classify each contact-pair as being within epileptogenic zone or not, based on these features. Our machine learning system identified this pattern in 15 of 17 patients. The total number of identified contacts across all patients was 64, with 58 localized inside the resected area. Subsequent quantitative analysis showed strong correlation between maximum frequency of fast activity and suppression inside the resection but not outside. We did not observe significant discrimination power using only the maximum frequency or the timing of fast activity to differentiate contacts either between resected and non-resected regions or between contacts identified as epileptogenic versus non-epileptogenic. Instead of identifying a single frequency or a single timing trait, we observed the more complex pattern described above that distinguishes the epileptogenic zone. This pattern encompasses interictal to ictal transition and may extend until seizure end. Its time-frequency characteristics can be explained in light of recent models emphasizing the role of fast inhibitory interneurons acting on pyramidal cells as a prominent mechanism in seizure triggering. The pattern clearly differentiates the epileptogenic zone from areas of propagation and, as such, represents an epileptogenic zone 'fingerprint'.awx306media15687076823001.

Interictal ripples nested in epileptiform discharge help to identify the epileptogenic zone in neocortical epilepsy.

OBJECTIVE: This study aimed to identify the subtype of interictal ripples that help delineate the epileptogenic zone in neocortical epilepsy. METHODS: Totally 25 patients with focal neocortical epilepsy who had invasive electroencephalography (EEG) evaluation and subsequent surgery were included. They were followed up for at least 2years. Interictal ripples (80-250Hz) and fast ripples (250-500Hz) during slow-wave sleep were identified. Neocortical ripples were defined as type I ripples when they were superimposed on epileptiform discharges, and as type II ripples when they occurred independently. Resection ratio was calculated to present the extent to which the cortical area showing an interictal event or the seizure onset zone (SOZ) was completely removed. RESULTS: Fast ripples and types I and II ripples were found in 8, 19, and 21 patients, respectively. Only the higher resection ratio of interictal fast or type I ripples was correlated to the Engel 1a surgical outcome. CONCLUSIONS: Type I ripples could assist in localizing the epileptogenic zone in neocortical epilepsy. SIGNIFICANCE: Type I and fast ripples both may be pathological high-frequency oscillations.

Stereoelectroencephalography: Interpretation.

Intracranial EEG has been in use for more than 50 years in the presurgical evaluation of patients with medically intractable focal epilepsy. The stereoelectroencephalography (SEEG) method has expanded very significantly over the last 5 years, in parallel with the increase in the number of complex cases (i.e., MRI-negative) being referred with medically intractable focal epilepsy to major epilepsy surgery centers. Some centers with extensive experience in subdural electrodes are indeed changing or have changed to SEEG as the principal exploration technique, which suggests that SEEG might offer specific benefits through its approach to accurately localizing the epileptogenic zone. However, interpretation of SEEG, which is a key step to its usefulness, may vary from one center to another. This may be due to different conceptual bases and the available expertise in each center. This heterogeneity in use of SEEG should be taken into account as it could contribute to erroneous conclusions and thus unfavorable outcome of epilepsy surgery. At present, there is a lack of guidelines for optimal SEEG use, although development of these is in progress. It remains challenging to translate SEEG interpretation into a practical approach to delineating surgical strategy. Identification of clear biomarkers will help in the definition of the epileptogenic zone and subsequent cortical resection. In addition, SEEG seems to be a unique tool for the in vivo investigation of human cerebral networks distributed over several lobes or sublobar structures, allowing a better understanding of their functioning.

A decrease of ripples precedes seizure onset in mesial temporal lobe epilepsy.

High-frequency oscillations (HFOs) are promising biomarkers for epileptic foci; however, their characteristic changes during the preictal period remain unclear. Here, the preictal HFOs were recorded and detected by an automated HFOs detection method in the mouse pilocarpine model as well as in patients with mesial temporal lobe epilepsy (mTLE) and neocortical epilepsy. A total of sixteen low-voltage fast (LVF) and fifty-three hypersynchronous-onset (HYP) seizures were recorded in ten mice. The rate of ripples (80-250Hz) decreased during 1min before the onset of LVF and HYP seizures, which was primarily due to the reduction of type II (independent of epileptiform discharges) rather than type I ripples (superimposed on epileptiform activities). The ripple rate decreased until 30s before HYP seizure, whereas it increased with a peak at 40s during the 1min preictal period of LVF seizures. Furthermore, the "ripple reduction" phenomenon was also observed in all twelve seizures from nine patients with mTLE but not in neocortical epilepsy. These results indicate that ripples may potentially be helpful for understanding the mechanisms of ictogenesis in mTLE, and the different modes of ripple changes during the minute before LVF and HYP seizures might also be beneficial for the diagnosis of seizure types.

Ripple classification helps to localize the seizure-onset zone in neocortical epilepsy.

PURPOSE: Fast ripples are reported to be highly localizing to the epileptogenic or seizure-onset zone (SOZ) but may not be readily found in neocortical epilepsy, whereas ripples are insufficiently localizing. Herein we classified interictal neocortical ripples by associated characteristics to identify a subtype that may help to localize the SOZ in neocortical epilepsy. We hypothesize that ripples associated with an interictal epileptiform discharge (IED) are more pathologic, since the IED is not a normal physiologic event. METHODS: We studied 35 patients with epilepsy with neocortical epilepsy who underwent invasive electroencephalography (EEG) evaluation by stereotactic EEG (SEEG) or subdural grid electrodes. Interictal fast ripples and ripples were visually marked during slow-wave sleep lasting 10-30 min. Neocortical ripples were classified as type I when superimposed on epileptiform discharges such as paroxysmal fast, spike, or sharp wave, and as type II when independent of epileptiform discharges. KEY FINDINGS: In 21 patients with a defined SOZ, neocortical fast ripples were detected in the SOZ of only four patients. Type I ripples were detected in 14 cases almost exclusively in the SOZ or primary propagation area (PP) and marked the SOZ with higher specificity than interictal spikes. In contrast, type II ripples were not correlated with the SOZ. In 14 patients with two or more presumed SOZs or nonlocalizable onset pattern, type I but not type II ripples also occurred in the SOZs. We found the areas with only type II ripples outside of the SOZ (type II-O ripples) in SEEG that localized to the primary motor cortex and primary visual cortex. SIGNIFICANCE: Neocortical fast ripples and type I ripples are specific markers of the SOZ, whereas type II ripples are not. Type I ripples are found more readily than fast ripples in human neocortical epilepsy. Type II-O ripples may represent spontaneous physiologic ripples in the human neocortex.

Long-term seizure outcome after resective surgery in patients evaluated with intracranial electrodes.

PURPOSE: Despite advances in "noninvasive" localization techniques, many patients with medically intractable epilepsy require the placement of subdural (subdural grid electrode, SDE) and/or depth electrodes for the identification and definition of extent of the epileptic region. This study investigates the trends in longitudinal seizure outcome and its predictors in this group. METHODS: We reviewed the medical records, and electroencephalography (EEG) data of 414 consecutive patients who underwent intracranial electrode placement (SDE and/or depth electrodes) at Cleveland Clinic Epilepsy Center between 1998 and 2008. A favorable outcome was defined as complete seizure freedom, discounting any auras or seizures that occurred within the first postoperative week. Survival curves were constructed, and Cox proportional hazard modeling was used to identify outcome predictors. KEY FINDINGS: The estimated probability of complete seizure freedom was 61% (95% confidence interval [CI] 58-64%) at one postoperative year, 47% (95% CI 44-50%) at 3 years, 42% (95% CI 39-45%) at 5 years, and 33% (95% CI 28-38%) at 10 years. Half of all seizure recurrences occurred within the first two postoperative months. Subsequently, the rate of seizure freedom declined by 4-5% every 2-3 years. After multivariate analysis, two independent predictors of seizure recurrence were identified: (1) prior resective surgery (p ≤ 0.002), mostly in patients with temporal lobe resections, and (2) sublobar or multilobar resection (p ≤ 0.02), mostly in patients following frontal lobe resections. SIGNIFICANCE: Favorable seizure outcomes are possible in the complex epilepsy population requiring invasive EEG studies. We propose that mislocalization of the epileptogenic zone or its incomplete resection account for early postoperative recurrences, whereas epileptogenesis may lead to later relapses.