Prospective observational study: Fast ripple localization delineates the epileptogenic zone

ObjectiveTo investigate spatial correlation between interictal HFOs and neuroimaging abnormalities, and to determine if complete removal of prospectively identified interictal HFOs correlates with post-surgical seizure-freedom.MethodsInterictal fast ripples (FRs: 250–500 Hz) in 19 consecutive children with pharmacoresistant focal epilepsy who underwent extra-operative electrocorticography (ECoG) recording were prospectively analyzed. The interictal FRs were sampled at 2000 Hz and were visually identified during 10 min of slow wave sleep. Interictal FRs, MRI and FDG-PET were delineated on patient-specific reconstructed three-dimensional brain MRI.ResultsInterictal FRs were observed in all patients except one. Thirteen out of 18 patients (72%) exhibited FRs beyond the extent of neuroimaging abnormalities. Fifteen of 19 children underwent resective surgery, and survival analysis with log-rank test demonstrated that complete resection of cortical sites showing interictal FRs correlated with longer post-operative seizure-freedom (p < 0.01). Complete resection of seizure onset zones (SOZ) also correlated with longer post-operative seizure-freedom (p = 0.01), yet complete resection of neuroimaging abnormalities did not (p = 0.43).ConclusionsProspective visual analysis of interictal FRs was feasible, and it seemed to accurately localize epileptogenic zones.SignificanceTopological extent of epileptogenic region may exceed what is discernible by multimodal neuroimaging.     

Depth versus subdural temporal electrodes revisited: Impact on surgical outcome after resective surgery for epilepsy

Objective

To study retrospectively the impact of electrode modality (subdural or depth electrodes) during presurgical assessment on surgical outcome after temporal lobectomy.

Beamforming applied to surface EEG improves ripple visibility

Objective

Surface EEG can show epileptiform ripples in people with focal epilepsy, but identification is impeded by the low signal-to-noise ratio of the electrode recordings. We used beamformer-based virtual electrodes to improve ripple identification.

Interictal high-frequency oscillations (80-500 Hz) are an indicator of seizure onset areas independent of spikes in the human epileptic brain

Purpose: High‐frequency oscillations (HFOs) known as ripples (80–250 Hz) and fast ripples (250–500 Hz) can be recorded from macroelectrodes inserted in patients with intractable focal epilepsy. They are most likely linked to epileptogenesis and have been found in the seizure onset zone (SOZ) of human ictal and interictal recordings. HFOs occur frequently at the time of interictal spikes, but were also found independently. This study analyses the relationship between spikes and HFOs and the occurrence of HFOs in nonspiking channels. Methods: Intracerebral EEGs of 10 patients with intractable focal epilepsy were studied using macroelectrodes. Rates of HFOs within and outside spikes, the overlap between events, event durations, and the percentage of spikes carrying HFOs were calculated and compared according to anatomical localization, spiking activity, and relationship to the SOZ. Results: HFOs were found in all patients, significantly more within mesial temporal lobe structures than in neocortex. HFOs could be seen in spiking as well as nonspiking channels in all structures. Rates and durations of HFOs were significantly higher in the SOZ than outside. It was possible to establish a rate of HFOs to identify the SOZ with better sensitivity and specificity than with the rate of spikes. Discussion: HFOs occurred to a large extent independently of spikes. They are most frequent in mesial temporal structures. They are prominent in the SOZ and provide additional information on epileptogenicity independently of spikes. It was possible to identify the SOZ with a high specificity by looking at only 10 min of HFO activity.     

Analysis of clinical patterns and underlying epileptogenic zones of hypermotor seizures

Background: Hypermotor seizures (HMS) are characterized by complex movements involving the proximal segment of the limbs and trunk. Although they are primarily reported in mesial frontal or orbitofrontal epilepsies, they have also been described in patients with temporal or insular epilepsies, questioning the localizing value of HMS in patients contemplating epilepsy surgery. Furthermore, HMS can include different forms of HM behaviors. Whether these clinical variations may be systematized and may reflect different locations of the epileptogenic zone (EZ) has not been evaluated yet. Methods: We have retrospectively analyzed ictal signs and intracerebral EEG data in 11 patients presenting with HMS who became seizure free following epilepsy surgery with a minimum follow‐up of 24 months. Clinical phenomena were reviewed blinded to seizure onset zone. Results: Two types of HMS could be distinguished in this population: HMS1, observed in six patients, mainly consisted of marked agitation that either included body rocking, kicking, or boxing, associated with a facial expression of fear. HMS2, observed in the five other patients, mainly consisted of mild agitation that included either horizontal movements or rotation of trunk and pelvis while lying on the bed, usually associated with tonic/dystonic posturing. SEEG findings showed that the EZ associated with HMS1 was mainly centered on the ventromesial frontal cortex. Conversely, HMS2 was primarily associated with an EZ localized within the mesial premotor cortex. Conclusions: Although these findings remain to be confirmed by larger studies, they may help optimize the placement of intracerebral electrodes in patients contemplating epilepsy surgery.     

Simultaneous MEG and EEG to detect ripples in people with focal epilepsy

ObjectiveWe studied ripples (80–250 Hz) simultaneously recorded in electroencephalography (EEG) and magnetoencephalography (MEG) to evaluate the differences.MethodsSimultaneous EEG and MEG were recorded in 30 patients with drug resistant focal epilepsy. Ripples were automatically detected and visually checked in virtual channels throughout the cortex. The number and location of ripples in EEG and MEG were compared to each other and to a region of interest (ROI) defined by clinically available information.ResultsEleven patients showed ripples in both MEG and EEG, 11 only in EEG and one only in MEG. Twenty-four percent of the ripples occurred simultaneously in EEG and MEG, 71% only in EEG, and 5% only in MEG. Three patients without spikes in EEG showed EEG ripples. Ripple localization was concordant with the ROI in 80% of patients with MEG ripples, as opposed to 62% full or partial concordance for EEG ripples. With the optimal threshold for localizing the ROI, sensitivity and specificity were more than 80%.ConclusionsRipples in MEG are less frequent but more specific and sensitive for the region of interest than ripples in EEG. Ripples in EEG can exist without spikes in the EEG.SignificanceRipples in MEG and EEG provide complementary information.     

Ictal perfusion patterns associated with single MRI-visible focal dysplastic lesions: implications for the noninvasive delineation of the epileptogenic zone

BACKGROUND: Invasive electroencephalogram (EEG) studies are often considered necessary to localize the epileptogenic zone in partial epilepsies associated with focal dysplastic lesions (FDL). Our aim was to evaluate the relationships between subtraction ictal SPECT coregistered with magnetic resonance imaging (MRI) (SISCOM) hyperperfusion clusters and MRI-visible FDL, and to establish a preliminary algorithm for a noninvasive presurgical evaluation protocol for MRI-visible FDLs in patients with refractory epilepsy. METHODS: Fifteen consecutive patients with refractory partial epilepsy and a single MRI-visible FDL underwent a noninvasive presurgical evaluation including SISCOM. Each hyperperfusion cluster was visually analyzed, automatically quantitated, and its distance form the lesion as outlined on the MRI was measured. In patients who underwent surgery, the volumes of resected brain tissue containing the FDL, the SISCOM hyperperfusion cluster, and surrounding regions were assessed on postoperative MRI and correlated with surgical outcome. RESULTS: Fourteen of the 15 patients (93%) showed SISCOM hyperperfusion overlapping with the FDL. The FDL was detected only after reevaluation of the MRI guided by the ictal SPECT in 7 of the 15 patients (47%). Four distinct hyperperfusion patterns were observed, representing different degrees of seizure propagation. Nine patients have been operated on. Five have been seizure-free since surgery and one since a reoperation. The degree of resection of the MRI-visible FDL was the major determinant of surgical outcome. Full resection of the SISCOM hyperperfusion cluster was not required to render a patient seizure-free. CONCLUSION: Detailed analysis of SISCOM hyperperfusion patterns is a promising tool to detect subtle FDL on MRI and to establish the epileptic nature of these lesions noninvasively. Overlap between the SISCOM hyperperfusion cluster and MRI-visible FDL in a noninvasive presurgical evaluation with concordant data may suffice to proceed to epilepsy surgery aimed at removing the MRI-visible FDL and the part of the hyperperfusion cluster within and immediately surrounding the FDL.     

Surgery for medically intractable epilepsy due to postinfectious etiologies

Medically intractable epilepsy (MIE) resulting from postinfectious etiologies requiring surgery have been uncommonly reported. A series of 28 cases are presented (hospital prevalence 5.7%). The mean duration of epilepsy prior to surgery was 8.2 ± 2.1 years. The mean time of onset of epilepsy after central nervous system infection was 1.4 ± 0.9 years (range 0–19 years). The pathologies included postpyogenic meningitic/encephalitic sequel (8), neurocysticercosis (6), tuberculomas/posttuberculous etiology (4), postpyogenic abscess of otogenic etiology (4), posttraumatic abscess–related gliosis (2), and gliosis of unknown infectious etiology (4) cases. Surgery included mesial temporal (11), lateral temporal (4), frontal (9), parietal (2) resections and hemispherotomy (1). Hippocampal sclerosis was seen in nine cases (4 neurocysticercosis) and this occurred in younger persons as compared to neocortical epilepsies. Good outcome (Engel class I and II) was seen in 23 of 28 cases (Engel class I in 17).     

Safety of Intrahippocampal Depth Electrodes for Presurgical Evaluation of Patients with Intractable Epilepsy

: Purpose: Intracerebral depth electrodes are used in preoperative evaluation of selected patients with intractable epilepsies. In spite of their usefulness, safety of depth electrodes is disputed, and the number of insertions is decreasing. This study examined retrospectively possible deleterious effects such as perioperative complications, induction of epileptogenesis, and neuropsychologic deficits. Methods: Clinical course and neuroradiologic findings of 115 patients with bilaterally inserted longitudinal intrahippocampal depth electrodes (IDEs) were analyzed. Hippocampal resection specimens were examined histopathologically. To detect newly developed epileptogenic areas, EEG recordings, seizure control, and semiology after standardized resection procedures were compared between patients who received IDEs and those who did not. To demonstrate functional deficits caused by IDE insertion into an unaffected hippocampus of the speech-dominant hemisphere, changes of verbal learning and memory performances before and after right amygdalohippocampectomy were compared between patients evaluated with and without IDEs. Results: Five significant complications without any permanent neurologic deficit were noted, and only one was specifically linked to IDE insertion. The tissue damage associated with the insertion was minimal and sharply circumscribed. No differences of seizure outcome after standardized resections were identified between patients with and without IDEs. In postoperative EEG recordings, there was no evidence of new epileptogenic areas. No verbal memory deficit caused by IDE implantation into the hippocampus of the speech-dominant hemisphere was detectable. Conclusions: Results indicate that it is safe to implant these IDEs in selected patients.     

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.     

Survival analysis of the surgical outcome of temporal lobe epilepsy due to hippocampal sclerosis

PURPOSE: Surgical results in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS) are often reported in conjunction with other etiologies of TLE. METHODS: We prospectively collected surgical outcome data for 2 to 11 years for 134 consecutive patients who specifically had MTLE and unilateral HS, according to magnetic resonance imaging (MRI) and confirmed by histopathology. Sixty-five had postoperative neuropsychological testing. Outcome was analyzed by using Engel's classification (a) through Kaplan-Meier estimated survival curves (as a function of the time to seizure recurrence), (b) as percentage of patients in each outcome class on a yearly basis, and (c) at the last updated follow-up. RESULTS: Kaplan-Meier estimates of complete seizure freedom (Engel's class IA) for years 1, 2, 5, and 10 were 85%, 77%, 74%, and 66%, and of Engel's class I were 89%, 86%, 83%, and 81%. Only nine (6.7%) patients had outcome classes III or IV at any point during follow-up. Of the patients tested, 26% of those operated on the left side and 22% of those operated on the right had postoperative decline of >1 SD in verbal or visual memory, respectively. CONCLUSIONS: High rates of seizure freedom can be obtained and remain stable over the years in patients operated on for unilateral MTLE/HS, even in countries with limited resources.     

High-resolution MRI enhances identification of lesions amenable to surgical therapy in children with intractable epilepsy

PURPOSE: Many children with refractory epilepsy can achieve better seizure control with surgical therapy. An abnormality on magnetic resonance imaging (MRI), along with corroborating localization by other modalities, markedly increases chances of successful surgical outcome. We studied the impact of high-resolution MRI on the surgical outcome of intractable epilepsy. METHODS: High-resolution MRI using four-coil phased surface array was obtained as part of the comprehensive presurgical protocol for children with focal onset intractable seizures evaluated by our epilepsy center during the first half of 2002. RESULTS: Thirteen consecutive children, ages 5 to 18 years, entered this prospective study. For four patients with a lesion on a recent MRI examination with a standard head coil, management did not change with high-resolution MRI. Standard MRI in the other nine patients did not identify a lesion. However, high-resolution MRI with the phased-array surface coil found previously undiagnosed focal abnormalities in five of nine patients. These abnormalities included hippocampal dysplasia, hippocampal atrophy, and dual pathology with frontal cortical dysplasia. In four of nine patients, no identifiable lesion was identified on the high-resolution MRI. All patients underwent invasive monitoring. In three of five patients, newly diagnosed lesions correlated with EEG abnormalities, and resection was performed. CONCLUSIONS: In our center, high-resolution MRI identified lesions not detected by standard MRI in more than half the children (56%). Technical advances such as four-coil phased surface array MRI can help identify and better delineate lesions, improving the diagnosis of patients who are candidates for surgical treatment of refractory epilepsy.