Summary
Many patients with medically refractory epilepsy now undergo successful surgery based on noninvasive diagnostic information, but intracranial electroencephalography (IEEG) continues to be ...used as increasingly complex cases are considered surgical candidates. The indications for IEEG and the modalities employed vary across epilepsy surgical centers; each modality has its advantages and limitations. IEEG can be performed in the same intraoperative setting, that is, intraoperative electrocorticography, or through an independent implantation procedure with chronic extraoperative recordings; the latter are not only resource intensive but also carry risk. A lack of understanding of IEEG limitations predisposes to data misinterpretation that can lead to denying surgery when indicated or, worse yet, incorrect resection with adverse outcomes. Given the lack of class 1 or 2 evidence on IEEG, a consensus‐based expert recommendation on the diagnostic utility of IEEG is presented, with emphasis on the application of various modalities in specific substrates or locations, taking into account their relative efficacy, safety, ease, and incremental cost‐benefit. These recommendations aim to curtail outlying indications that risk the over‐ or underutilization of IEEG, while retaining substantial flexibility in keeping with most standard practices at epilepsy centers and addressing some of the needs of resource‐poor regions around the world.
In the context of focal and drug-resistant epilepsy, surgical resection of the epileptogenic zone may be the only therapeutic option for reducing or suppressing seizures. In many such patients, ...intracranial stereo-EEG recordings remain the gold standard for the epilepsy surgery work-up. Assessing the extent of the epileptogenic zone and its organisation is a crucial objective, and requires advanced methods of signal processing. Over the last ten years, considerable efforts have been made to develop signal analysis techniques for characterising the connectivity between spatially distributed regions.
The aim of this study was to evaluate the changes in dynamic connectivity pattern under inter-ictal, pre-ictal and ictal conditions using signals derived from stereo-EEG recordings of 10 patients with Taylor-type focal cortical dysplasia. A causal linear multivariate method – partial directed coherence – and indices derived from graph theory were used to characterise the synchronisation property of the lesional zone (corresponding to the epileptogenic zone in our patients) and to distinguish it from other regions involved in ictal activity or not.
The results show that a significantly different connectivity pattern (mainly in the gamma band) distinguishes the epileptogenic zone from other cortical regions not only during the ictal event, but also during the inter- and pre-ictal periods. This indicates that the lesional nodes play a leading role in generating and propagating ictal EEG activity by acting as the hubs of the epileptic network originating and sustaining seizures. Our findings also indicate that the cortical regions beyond the dysplasia involved in the ictal activity essentially act as “secondary” generators of synchronous activity. The leading role of the lesional zone may account for the good post-surgical outcome of patients with type II focal cortical dysplasia as resecting the dysplasia removes the epileptogenic zone responsible for seizure organisation. Furthermore, our findings strongly suggest that advanced signal processing techniques aimed at studying synchronisation and characterising brain networks could substantially improve the pre-surgical evaluation of patients with focal epilepsy, even in cases without an associated anatomically detectable lesion.
►Type-II focal cortical dysplasia is a model of drug-resistant epilepsy. ►PDC and graph indexes are appropriate tools to localise the epileptogenic zone. ►The lesional nodes play a leading role in the epileptogenic network. ►An abnormal connectivity characterises the inter-ictal activity of the lesional leads. ►Cortical regions outside dysplasia act as secondary sources of synchronous activity.
Cerebrovascular dysfunction and inflammation occur in epilepsy. Here we asked whether pericytes, a pivotal cellular component of brain capillaries, undergo pathological modifications during ...experimental epileptogenesis and in human epilepsy. We evaluated whether pro-inflammatory cytokines, present in the brain during seizures, contribute to pericyte morphological modifications.
In vivo, unilateral intra-hippocampal kainic acid (KA) injections were performed in NG2DsRed/C57BL6 mice to induce status epilepticus (SE), epileptogenesis, and spontaneous recurrent seizures (SRS). NG2DsRed mice were used to visualize pericytes during seizure progression. The effect triggered by recombinant IL-1β, TNFα, or IL-6 on pericytes was evaluated in NG2DsRed hippocampal slices and in human-derived cell culture. Human brain specimens obtained from temporal lobe epilepsy (TLE) with or without sclerosis (HS) and focal cortical dysplasia (FCD-IIb) were evaluated for pericyte-microglial cerebrovascular assembly.
A disarray of NG2DsRed+ pericyte soma and ramifications was found 72 h post-SE and 1 week post-SE (epileptogenesis) in the hippocampus. Pericyte modifications topographically overlapped with IBA1+ microglia clustering around the capillaries with cases of pericytes lodged within the microglial cells. Microglial clustering around the NG2DsRed pericytes lingered at SRS. Pericyte proliferation (Ki67+) occurred 72 h post-SE and during epileptogenesis and returned towards control levels at SRS. Human epileptic brain tissues showed pericyte-microglia assemblies with IBA1/HLA microglial cells outlining the capillary wall in TLE-HS and FCD-IIb specimens. Inflammatory mediators contributed to pericyte modifications, in particular IL-1β elicited pericyte morphological changes and pericyte-microglia clustering in NG2DsRed hippocampal slices. Modifications also occurred when pro-inflammatory cytokines were added to an in vitro culture of pericytes.
These results indicate the occurrence of pericytosis during seizures and introduce a pericyte-microglial mediated mechanism of blood-brain barrier dysfunction in epilepsy.
•Pericyte-microglia pathology is a mechanism of BBB damage in epilepsy.•Pericyte-microglia clusters form at the hippocampal capillaries post-SE and during epileptogenesis.•Pericytosis is provoked by pro-inflammatory cytokines.•Human TLE-HS and FCD type IIb display perivascular microglia aggregates in the lesional areas.
Summary
Objective
To report the presurgical workup, surgical procedures, and outcomes in a series of pediatric patients with drug‐resistant epilepsy involving the perisylvian/insular regions.
Methods
...We retrospectively assessed 16 pediatric patients affected by drug‐resistant focal epilepsy involving perisylvian/insular regions, who consecutively underwent tailored resective surgery. All patients underwent a detailed presurgical workup, which included the analysis of the anatomoelectroclinical correlations with scalp electroencephalography (EEG) and/or with stereo‐electroencephalography (SEEG), brain magnetic resonance imaging (MRI), and comprehensive cognitive and neuropsychological evaluations. After surgery, all patients underwent serial clinical and laboratory evaluations.
Results
Focal motor seizures restricted to perioral area, associated with symptoms related to the surrounding areas (as auditory hallucinations, unpleasant paresthesia, fear, and epigastric sensation), characterized the ictal semiology in 75% of patients. In 50%, autonomic manifestations were present and in 56% subjective manifestations were reported. The 50% of the patients underwent SEEG with insular sampling to better define the epileptogenic zone. In all patients, the insular cortex was always part of the epileptogenic zone, and tailored resections also involved, with variable degree, the frontal, parietal, and temporal opercula. Preoperatively, the neuropsychological assessment revealed impairments in specific cognitive functions and mild or moderate cognitive compromise in 88% of the patients. Postoperatively, one patient had permanent slight hemiparesis. At the most recent follow‐up (median 39 months), seizure outcome was satisfactory in 69% of patients: seven patients were completely seizure‐free (Engel class Ia), two were free of disabling seizure (class Ic), and two had rare disabling seizures (class II). The cognitive functioning remained unchanged in 62%, and improved in 38%.
Significance
The assessment of perisylvian/insular epilepsy in children is particularly challenging. However, tailored resections based on a careful presurgical evaluation, including SEEG recording, may lead to a good seizure control and to a better overall outcome.
Radiofrequency thermocoagulation (RF-TC) of presumed epileptogenic lesions and/or structures has gained new popularity as a treatment option for drug-resistant focal epilepsy, mainly in patients with ...mesial temporal lobe epilepsy. The role of this minimally invasive procedure in more complex cases of drug-resistant epilepsy, which may require intracranial electroencephalographic evaluation, has not been fully assessed. This retrospective study reports on a case series of patients with particularly complex focal epilepsy who underwent stereoelectroencephalography (SEEG) evaluation with stereotactically implanted multicontact intracerebral electrodes for the detailed identification of the epileptogenic zone (EZ) and who received RF-TC in their supposed EZ (according to SEEG findings).
Eighty-nine patients (49 male and 40 female; age range 2-49 years) who underwent SEEG evaluation and subsequent RF-TC of the presumed EZ at the authors' institution between January 2008 and December 2013 were selected. Brain MRI revealed structural abnormalities in 43 cases and no lesions in 46 cases. After SEEG, 67 patients were judged suitable for resective surgery (Group 1), whereas surgery was excluded for 22 patients (Group 2). Thermocoagulation was performed in each of these patients by using the previously implanted multicontact recording electrodes and delivering RF-generated currents to adjacent electrode contacts.
The mean number of TC sites per patient was 10.6 ± 7.2 (range 1-33). Sustained seizure freedom occurred after TC in 16 patients (18.0%) (13 in Group 1 and 3 in Group 2). A sustained worthwhile improvement was reported by 9 additional patients (10.1%) (3 in Group 1 and 6 in Group 2). As a whole, 25 patients (28.1%) exhibited a persistent significant improvement in their seizures. More favorable results were observed in patients with nodular heterotopy (p = 0.0001389), those with a lesion found on MRI (not significant), and those with hippocampal sclerosis (not significant). Other variables significantly correlated to seizure freedom were the patient's age (p = 0.02885) and number of intralesional TC sites (p = 0.0271). The patients in Group 1 who did not benefit at all (21 patients) or who experienced only a transient benefit (30 patients) from TC underwent microsurgical resection of their EZ. Thermocoagulation was followed by severe permanent neurological deficits in 2 patients (an unexpected complex neuropsychological syndrome in one patient and an expected and anticipated permanent motor deficit in the other).
This study provides evidence that SEEG-guided TC in the EZ may be a treatment option for particularly complex drug-resistant focal epilepsy that requires invasive evaluation. A small subset of patients who achieve seizure freedom or worthwhile improvement may avoid open surgery or take advantage of an otherwise unexpected treatment if resection is not an option. Patients with epileptogenic nodular heterotopy are probably ideal candidates for this treatment.
Summary
Objective
Long‐term recording with intracerebral electrodes is commonly utilized to identify brain areas responsible for seizure generation (epileptogenic zone) and to tailor therapeutic ...surgical resections in patients with focal drug‐resistant epilepsy. This invasive diagnostic procedure generates a wealth of data that contribute to understanding human epilepsy. We analyze intracerebral signals to identify and classify focal ictal patterns.
Methods
We retrospectively analyzed stereo‐electroencephalographic (EEG) data in a cohort of patients either cryptogenic (magnetic resonance imaging negative) or presenting with noncongruent anatomoelectroclinical data. A computer‐assisted method based on EEG signal analysis in frequency and space domains was applied to 467 seizures recorded in 105 patients submitted to stereo‐EEG presurgical monitoring.
Results
Two main focal seizure patterns were identified. P‐type seizures, typical of neocortex, were observed in 73 patients (69.5%), lasted 22 ± 13 seconds (mean +SD), and were characterized by a sharp‐onset/sharp‐offset transient superimposed on low‐voltage fast activity (126 ± 19 Hz). L‐type seizures were observed in 43 patients (40.9%) and consistently involved mesial temporal structures; they lasted longer (93 ± 48 second), started with 116 ± 21 Hz low‐voltage fast activity superimposed on a slow potential shift, and terminated with large‐amplitude, periodic bursting activity. In 23 patients (21.9%), the L‐type seizure was preceded by a P seizure. Spasmlike and unclassifiable EEG seizures were observed in 11.4% of cases.
Significance
The proposed computer‐assisted approach revealed signal information concealed to visual inspection that contributes to identifying two principal seizure patterns typical of the neocortex and of mesial temporal networks.
Summary
Objective
Periventricular nodular heterotopias (PNHs) are malformations of cortical development related to neuronal migration disorders, frequently associated with drug‐resistant epilepsy ...(DRE). Stereo‐electroencephalography (SEEG) is considered a very effective step of the presurgical evaluation, providing the recognition of the epileptogenic zone (EZ). At the same time, via the intracerebral electrodes it is possible to perform radiofrequency thermocoagulation (SEEG‐guided RF‐TC) with the aim of ablating and/or disrupting the EZ. The purpose of this study was to evaluate both the relationships between PNH and the EZ, and the efficacy of SEEG‐guided RF‐TC.
Methods
Twenty patients with DRE related to PNHs were studied. Inclusion criteria were the following: (1) patients with epilepsy and PNHs (unilateral or bilateral, single or multiple nodules) diagnosed on brain magnetic resonance imaging (MRI); (2) SEEG recordings available as part of the presurgical investigations, with at least one intracerebral electrode inside the heterotopia; (3) complete surgical workup with SEEG‐guided RF‐TC and/or with traditional neurosurgery, with a follow‐up of at least 12 months.
Results
Complex and heterogenic epileptic networks were found in these patients. SEEG‐guided RF‐TC both into the nodules and/or the cortex was efficacious in the 76% of patients. Single or multiple, unilateral or bilateral PNHs are the most suitable for this procedure, whereas patients with PNHs associated with complex cortical malformations obtained excellent outcome only with traditional resective surgery.
Significance
Each patient had a specific epileptogenic network, independent from the number, size, or location of nodules and from the cortical malformation associated with. SEEG‐guided RF‐TC appears as a new and very effective diagnostic and therapeutic approach for DRE related to PNHs.
Summary
Objectives
Sleep‐related hypermotor epilepsy (SHE), formerly nocturnal frontal lobe epilepsy, is characterized by abrupt and typically sleep‐related seizures with motor patterns of variable ...complexity and duration. They seizures arise more frequently in the frontal lobe than in the extrafrontal regions but identifying the seizure onset‐zone (SOZ) may be challenging. In this study, we aimed to describe the clinical features of both frontal and extrafrontal SHE, focusing on ictal semiologic patterns in order to increase diagnostic accuracy.
Methods
We retrospectively analyzed the clinical features of patients with drug‐resistant SHE seen in our center for epilepsy surgery. Patients were divided into frontal and extrafrontal SHE (temporal, operculoinsular, and posterior SHE). We classified seizure semiology according to four semiology patterns (SPs): elementary motor signs (SP1), unnatural hypermotor movements (SP2), integrated hypermotor movements (SP3), and gestural behaviors with high emotional content (SP4). Early nonmotor manifestations were also assessed.
Results
Our case series consisted of 91 frontal SHE and 44 extrafrontal SHE cases. Frontal and extrafrontal SHE shared many features such as young age at onset, high seizure‐frequency rate, high rate of scalp electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities, similar histopathologic substrates, and good postsurgical outcome. Within the frontal lobe, SPs were organized in a posteroanterior gradient (SP1‐4) with respect to the SOZ. In temporal SHE, SP1 was rare and SP3‐4 frequent, whereas in operculoinsular and posterior SHE, SP4 was absent. Nonmotor manifestations were frequent (70%) and some could provide valuable localizing information.
Significance
Our study shows that the presence of certain SP and nonmotor manifestations may provide helpful information to localize seizure onset in patients with SHE.
Summary Background Half of patients who have resective brain surgery for drug-resistant epilepsy have recurrent postoperative seizures. Although several single predictors of seizure outcome have been ...identified, no validated method incorporates a patient's complex clinical characteristics into an instrument to predict an individual's post-surgery seizure outcome. Methods We developed nomograms to predict complete freedom from seizures and Engel score of 1 (eventual freedom from seizures allowing for some initial postoperative seizures, or seizures occurring only with physiological stress such as drug withdrawal) at 2 years and 5 years after surgery on the basis of sex, seizure frequency, secondary seizure generalisation, type of surgery, pathological cause, age at epilepsy onset, age at surgery, epilepsy duration at time of surgery, and surgical side. We designed the models from a development cohort of patients who had resective surgery at the Cleveland Clinic (Cleveland, OH, USA) between 1996 and 2011. We then tested the nomograms in an external validation cohort operated on over a similar period in four epilepsy surgery centres, in Brazil, France, Italy, and the USA. We assessed performance of the nomogram by calculating concordance statistics and assessing the calibration of predicted freedom from seizures with the reported freedom from seizures and Engel score of 1. Findings The development cohort included 846 patients and the validation cohort included 604 patients. Variables included in the nomograms were sex, seizure frequency, secondary seizure generalisation, type of surgery, and pathological cause. In the development cohort, the baseline risk of complete freedom from seizures was 0·57 at 2 years and 0·40 at 5 years. The baseline risk of Engel score of 1 was 0·69 at 2 years and 0·62 at 5 years. In the validation cohort, the models had a concordance statistic of 0·60 for complete freedom from seizures and 0·61 for Engel score of 1. Calibration curves showed adequate calibration (judged by eye) of predicted and reported freedom from seizures, throughout the range of seizure outcomes. Interpretation If validated in prospective cohorts, these nomograms could be used to predict seizure outcomes in patients who have been judged eligible for epilepsy surgery. Funding Cleveland Clinic Epilepsy Center.
The aim was to compare the outcomes of subdural electrode (SDE) implantations versus stereotactic electroencephalography (SEEG), the 2 predominant methods of intracranial electroencephalography ...(iEEG) performed in difficult-to-localize drug-resistant focal epilepsy.
The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005 and 2019 with ≥1 year of follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints were: (1) likelihood of resection after iEEG; (2) seizure freedom at last follow-up; and (3) complications (composite of postoperative infection, symptomatic intracranial hemorrhage, or permanent neurological deficit).
Ten study sites from 7 countries and 3 continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE and 942 SEEG), of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio OR = 1.4, 95% confidence interval CI 1.05, 1.84) and higher odds of complications (OR = 2.24, 95% CI 1.34, 3.74; unadjusted: 9.6% after SDE vs 3.3% after SEEG). Odds of seizure freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared with SDE (unadjusted: 55% seizure free after SEEG-guided resections vs 41% after SDE).
In comparison to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy but have more surgical complications and lower probability of seizure freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. ANN NEUROL 2021;90:927-939.
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