Intracranial EEG in temporal lobe epilepsy.

Intracranial EEG monitoring before epilepsy surgery, while becoming less commonly performed in patients with unilateral mesial temporal lobe epilepsy, is still widely used when bilateral independent temporal lobe seizures are suspected or when extratemporal foci cannot be ruled out by noninvasive means. Additionally, many epilepsy centers are reporting excellent surgical outcome in patients with neocortical temporal lobe epilepsy, when resections are guided by intracranial EEG studies. This article reviews the indications, technical aspects, risks, and interpretation of intracranial EEG in patients with temporal lobe seizures. It also considers intracranial EEG features predictive of surgical outcome.     

Prognostic significance of serial postoperative EEG in extratemporal lobe epilepsy surgery

Objective

To assess the prognostic value of postoperative EEG in patients surgically treated for drug-resistant extra-temporal lobe (ET) epilepsy.

Methods

We studied 63 consecutive patients with ET epilepsy who underwent epilepsy surgery and were followed up for at least 2 years (mean duration of follow-up 6.2 ± 2.3 years, range 2–12). Follow-up evaluations were performed 2, 12, and 24 months after surgery, and included standard EEG (at 2 months) and long-term video-EEG monitoring during both wakefulness and sleep (at 12 and 24 months). Seizure outcome was determined at each follow-up evaluation, and then at yearly intervals. Patients who were in Engel Class I at the last contact were classified as having a good outcome.

Results

Seizure outcome was good in 39 patients (62%). The presence of interictal epileptiform discharges (IED) in postoperative EEG at each time point was found to be associated with poor outcome. The strength of this association was greater for awake plus sleep recording as compared with awake recording alone. In a multiple regression model including all pre- and post-operative factors identified as predictors of outcome in univariate analysis, the presence of early (2 months after surgery) EEG epileptiform abnormalities was found to be independently associated with poor seizure outcome.

Conclusions

Postoperative IED may predict long-term outcome in patients undergoing resective surgery for ET epilepsy.

Significance

The increase in risk of unfavourable outcome associated with EEG epileptiform abnormalities detected as early as two months after surgery may have substantial practical importance. Serial postoperative EEGs including sleep recording may add further predictive power and help making decision about antiepileptic drug discontinuation.     

Objective evaluation of personality and psychopathology in temporal lobe versus extratemporal lobe epilepsy

Previous research has been equivocal on personality trait and psychopathology differences between temporal lobe and other types of epilepsy, as well as between patients with right and left temporal lobe seizure foci. In this study, personality differences between patients with right temporal (n = 23), left temporal (n = 21), and extratemporal (n = 24) epilepsy were investigated using the NEO Personality Inventory—Revised (NEO-PI-R). No statistically significant differences were found on any of the NEO-PI-R domains or facet trait scales. There were also no significant differences between groups on the Minnesota Multiphasic Personality Inventory 2 (MMPI-2), a measure of psychopathology. However, mild elevations were seen in all groups on clinical scales related to physical symptoms, health concern, and depression. These data suggest there are no consistent personality or psychopathology differences, as measured by the NEO-PI-R and the MMPI-2, between patients with left temporal, right temporal, and extratemporal epilepsy whose seizures are localized using video/EEG monitoring.     

Psychopathology in children before and after surgery for extratemporal lobe epilepsy

Aim To establish the rates and types of psychiatric disorder in children before and after surgery for extratemporal epilepsy. Relationships between psychiatric morbidity and demographic/clinical variables were examined. Method A retrospective case note review of 71 children undergoing extratemporal focal resection for drug resistant epilepsy in a specialist epilepsy surgery programme between 1997 and 2008. Psychiatric diagnoses were derived from pre‐ and postoperative assessments according to DSM‐IV criteria. Results Seventy‐one children (38 males, 33 females) were eligible for this study. Mean age (SD) at surgery was 9 (5) years. Frontal resections were performed in 73% of the children, parietal in 17%, and occipital in 10%. Mental health problems were present in 37 of 71 (52%) children pre‐ and/or postoperatively. A similar proportion of children had psychiatric diagnoses pre‐ and postoperatively: 31 of 71 (44%) and 32 of 71 (45%) respectively. Interpretation Psychopathology is common in children with extratemporal epilepsy. In this sample, the impact of surgery on psychiatric symptoms was not predictable: some children were unchanged, others improved, and others acquired new psychiatric diagnoses postoperatively. Given the high rates of psychiatric disorder in this group of patients, detection and treatment of mental health needs may be important.     

Intracranial EEG findings in patients with lesional lateral temporal lobe epilepsy

PURPOSE: Intracranial EEG in patients with lesional lateral temporal lobe epilepsy is rarely reported. Therefore, the number of patients with seizures arising independently from ipsilateral mesial structures or contralateral hemisphere has not been clarified. We analyzed the intracranial EEG of cases with localized lesion in the lateral temporal cortex. METHODS: We studied 15 patients who satisfied the following criteria: (1) MRI depicted a lesion less than 4cm in diameter located lateral to the collateral sulcus and at least 3cm posterior to the temporal pole; (2) intracranial EEG with electrodes placed on bilateral temporal lobes captured at least one complex partial seizure; and (3) postoperative follow-up period of 2 years or longer. The mean age of seizure onset was 16.6 years (range, 11-25) and that at surgery was 26.7 years (range, 16-36). RESULTS: A total of 147 complex partial seizures, 51 simple partial seizures, 16 secondarily generalized seizures, and over 80 subclinical seizures were recorded. On the lesional side, many clinical seizures were recorded from the lateral cortex. Independent of the lateral temporal onset seizures, ictal discharges originating from the mesial temporal structures were recorded in 7 of 15 patients (47%). Moreover, onset of ictal discharges from the contralateral temporal lobe was recorded in 7 of 15 patients (47%). Interictal spikes from ipsilateral mesial structures were recorded in all patients. The presence of ipsilateral mesial onset seizures was not associated with hippocampal neuron losses. CONCLUSION: Intracranial EEG analysis revealed that approximately one-half of the patients with structural lesions in the lateral cortex showed independent epileptogenic areas in ipsilateral mesial structures. Although ictal discharges originating from the contralateral temporal lobe were recorded in a half of these patients, this finding does not constitute a contraindication of resective surgery. Interictal spike is not an indicator of whether mesial structures should be resected.     

Intracranial EEG in predicting surgical outcome in frontal lobe epilepsy

Purpose: Surgery in frontal lobe epilepsy (FLE) has a worse prognosis regarding seizure freedom than anterior lobectomy in temporal lobe epilepsy. The current study aimed to assess whether intracranial interictal and ictal EEG findings in addition to clinical and scalp EEG data help to predict outcome in a series of patients who needed invasive recording for FLE surgery. Methods: Patients with FLE who had resective surgery after chronic intracranial EEG recording were included. Outcome predictors were compared in patients with seizure freedom (group 1) and those with recurrent seizures (group 2) at 19–24 months after surgery. Key Findings: Twenty‐five patients (16 female) were included in this study. Mean age of patients at epilepsy surgery was 32.3 ± 15.6 years (range 12–70); mean duration of epilepsy was 16.9 ± 13.4 years (range 1–48). In each outcome group, magnetic resonance imaging revealed frontal lobe lesions in three patients. Fifteen patients (60%) were seizure‐free (Engel class 1), 10 patients (40%) continued to have seizures (two were class II, three were class III, and five were class IV). Lack of seizure freedom was seen more often in patients with epilepsy surgery on the left frontal lobe (group 1, 13%; group 2, 70%; p = 0.009) and on the dominant (27%; 70%; p = 0.049) hemisphere as well as in patients without aura (29%; 80%; p = 0.036), whereas sex, age at surgery, duration of epilepsy, and presence of an MRI lesion in the frontal lobe or extrafrontal structures were not different between groups. Electroencephalographic characteristics associated with lack of seizure freedom included presence of interictal epileptiform discharges in scalp recordings (31%; 90%; p = 0.01). Detailed analysis of intracranial EEG revealed widespread (>2 cm) (13%; 70%; p = 0.01) in contrast to focal seizure onset as well as shorter latency to onset of seizure spread (5.8 ± 6.1 s; 1.5 ± 2.3 s; p = 0.016) and to ictal involvement of brain structures beyond the frontal lobe (23.5 ± 22.4 s; 5.8 ± 5.4 s; p = 0.025) in patients without seizure freedom. The distribution of ictal onset patterns was similar in both groups, and fast rhythmic activity in the beta to gamma range was found in 57% of seizure‐free patients compared to 70% of patients with recurrent seizures. Analysis of the temporal relation between first clinical alterations and EEG seizure onset did not reveal significant differences between both groups of patients. In multivariate analysis, resection in the left hemisphere (odds ratio [OR] 12.197 95% confidence interval [95% CI] 1.33–111.832; p = 0.027) and onset of seizure spread (odds ratio [OR] 0.733, 95% CI 0.549–0.978, p = 0.035) were independent predictors of ongoing seizures. Significance: Widespread epileptogenicity as indicated by rapid onset of spread of ictal activity likely explains lack of seizure freedom following frontal resective surgery. The negative prognostic effect of surgery on the left hemisphere is less clear. Future study is needed to determine if neuronal network properties in this hemisphere point to intrinsic interhemispheric differences or if neurosurgeons are restrained by proximity to eloquent cortex.     

Potentially misleading extratemporal lobe lesions in patients with temporal lobe epilepsy

From a series of 217 consecutive temporal resections for intractable epilepsy between 1993 and 2000, we identified all patients with large non-neoplastic extratemporal lesions. Only patients with known postsurgical outcomes with follow up for more than two years were included. Fifteen patients were identified. All patients had a history of medically refractory epilepsy with clinical and ictal evidence of mesial temporal seizure onset. Eleven patients had extratemporal lesions ipsilateral to the seizure focus, whereas four patients had the lesions contralateral to the seizure focus. Nine of the 15 patients had evidence of hippocampal atrophy on magnetic resonance imaging (MRI). Following temporal resection, nine of these patients (60%) became seizure free (Engel class 1A), two patients were free of disabling seizures only (Engel class 1B), and two patients had a few early seizures but then became seizure free for at least two years (Engel class 1C). Two patients had significant improvement (Engel class 2). Thus, the finding of large extratemporal lesions on MRI was potentially misleading. When clinical semiology and ictal EEG recordings provide evidence of temporal onset seizures, anterior temporal resection should be considered in patients with extratemporal lesions.     

Ictal magnetoencephalography in temporal and extratemporal lobe epilepsy

PURPOSE: We evaluated visual patterns and source localization of ictal magnetoencephalography (MEG) in patients with intractable temporal lobe epilepsy (TLE) and extratemporal epilepsy (ETE). METHODS: We performed spike and seizure recording simultaneously with EEG and MEG on two patients with TLE and five patients with ETE. Scalp EEG was recorded from 21 channels (10-20 international system), whereas MEG was recorded from two 37-channel sensors. We compared ictal EEG and MEG onset, frequency, and evolution and performed MEG dipole source localization of interictal spikes and early ictal discharges and co-registered dipoles to brain magnetic resonance imaging (MRI). We correlated dipole characteristics with intracranial EEG, surgical resection, and outcome. RESULTS: Ictal MEG lateralized seizure onset in both TLE patients and demonstrated ictal onset, frequency, and evolution in accordance with EEG. Ictal MEG source analysis revealed tangential vertical dipoles in the anterolateral angle in one patient, and anterior dipoles with anteroposterior orientation in the other. Intracranial EEG revealed regional entorhinal seizure onset in the first patient. Both patients became seizure free after temporal lobectomy. In ETE, ictal MEG demonstrated visual patterns similar to ictal EEG and had concordant localization with interictal MEG in all five patients. Two patients underwent surgery. Ictal MEG localization was concordant with intracranial EEG in both cases. One patient had successful outcome after surgery. The second patient did not improve after limited resection and multiple subpial transections. CONCLUSIONS: Ictal MEG can demonstrate ictal onset frequency and evolution and provide useful localizing information before epilepsy surgery.     

Surgical treatment for extratemporal lobe epilepsy]

We analyzed the seizure outcome of 140 patients who underwent resective surgeries of extratemporal lobes including multilobar resection and hemispherectomy. The patients were followed for 2.0 to 16.7 years after surgery (mean, 6.2 years). The overall seizure outcome was Engel's class I in 87 patients (62%), class II in 14 (10%), class III in 13 (9%), and class IV in 26 (19%). The proportion of class I cases was 76% in 71 patients with discrete lesions under 5 cm in diameter on MRI, whereas the proportion was 52% in 46 patients with widespread lesions over 5 cm, and 39% in 23 patients with no MRI-detectable lesion. The seizure-free rates of extratemporal lobe resection was slightly lower compared with temporal lobe resection. Even in patients with extratemporal lobe epilepsies, clinicians should consider the option of surgical intervention from the early stage of disease.     

Systematic approach to dipole localization of interictal EEG spikes in children with extratemporal lobe epilepsies.

OBJECTIVES: To assess the reliability of dipole localization based on residual variances (RV), using equivalent current dipole analysis of interictal EEG spikes in children with extratemporal lobe epilepsy. METHODS: Four pediatric patients with extratemporal lobe epilepsy were studied. Digital EEG was recorded from 19 scalp electrodes. Computer programs for spike detection and clustering analysis were used to select spikes. Dipoles were calculated 5 times for each spike using different initial guesses by the moving dipole model. Standard deviation (SD) of the dipole positions was calculated at each time point in the 5 trials. RESULTS: We analyzed the dipoles at 1097 time points from 4 patients. Among 106 time points with RV < 2%, the SD was < 1 mm in 78 (74%), while in those with SD > 1 mm the dipole positions varied between 2.8 and 52.6 mm. Of dipoles with RV < 1%, 26 of 27 (96%) had an SD < 1 mm; the one dipole with SD > 1 mm varied within 2.5 mm. The dipole localizations with RV < 2% corresponded to the epileptogenic zones identified on intracranial invasive video EEG and intraoperative ECoG. CONCLUSIONS: The systematic approach of equivalent current dipole analysis using spike detection, clustering analysis, and an RV < 2% as a standard is useful for identifying extratemporal epileptic regions.     

Relationship of flumazenil and glucose PET abnormalities to neocortical epilepsy surgery outcome.

BACKGROUND: Cortical areas showing abnormal glucose metabolism and [(11)C]flumazenil (FMZ) binding are commonly seen on PET scans of patients with intractable partial epilepsy, but it is unclear whether these must be totally resected to achieve seizure control. OBJECTIVE: To analyze whether the extent of cortex showing 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) or FMZ PET abnormalities correlates with the outcome of resective epilepsy surgery. METHODS: Cortical FDG and FMZ PET abnormalities in 15 young patients (mean age, 12.2 +/- 7.0 years) with intractable partial epilepsy of neocortical origin were marked as regions with abnormal asymmetry using an objective semiautomated software package. These marked regions were then projected and measured on the brain surface reconstructed from the coregistered high-resolution MRI. Following cortical resection, the size of nonresected cortex with preoperative PET abnormalities was also measured (calculated separately for marked areas in the lobe of seizure onset as defined by long-term video EEG monitoring, and in remote cortical areas). Extent of preoperative PET abnormalities and postoperative nonresected cortex abnormalities on PET were correlated with outcome scores. RESULTS: Large preoperative FMZ PET abnormalities were associated with poor outcome (r = 0.57; p = 0.025). Larger areas of nonresected cortex with preoperative FMZ PET abnormalities in the lobe of seizure onset were also associated with worse outcome in the whole group (r = 0.66; p = 0.007) as well as in patients with extratemporal resection (r = 0.73; p = 0.007), and in those with no lesion on MRI (r = 0.60; p = 0.049). Patients with seizure-free outcome had significantly smaller nonresected cortex with preoperative FMZ PET abnormalities than those who continued to have seizures (p = 0.022). No significant correlations between nonresected FDG PET abnormalities and surgical outcome were found. CONCLUSIONS: Extensive cortical abnormalities on FMZ PET predict poor outcome in neocortical epilepsy surgery. Resection of FMZ abnormalities in the lobe of seizure onset is associated with excellent outcome even in the absence of a structural lesion. In contrast, although FDG PET abnormalities regionalized the epileptogenic area, their size was not related to the extent of epileptogenic tissue to be removed.     

Facing the hidden wall in mesial extratemporal lobe epilepsy

Refractory extratemporal lobe epilepsy (ETLE) tends to have a less favourable surgical outcome in comparison to temporal lobe epilepsy. ETLE poses specific diagnostic and therapeutic challenges, particularly in cases where seizures develop from the midline. This review focuses on the diagnostic challenges and therapeutic strategies in mesial ETLE. The great diversity of interhemispheric functional areas and extensive connectivity to extramesial structures results in very heterogeneous seizure semiology. Specific signs, such as ictal body turning, can suggest a mesial onset. The hidden cortex of the mesial wall furthermore gives rise to specific diagnostic difficulties due to the low localizing value of scalp EEG. Advanced imaging, as well as targeted intracranial studies, can substantially contribute to depict the seizure onset zone since electroclinical findings are difficult to interpret in most cases. Surgical accessibility of the interhemispheric space can be challenging, both for the placement of subdural grids, as well as for resective surgery. When facing the hidden cortex on the mesial wall of the hemispheres, targeted intra‐ or extra‐operative intracranial recordings can lead to satisfactory outcomes in properly selected cases.     

Medial temporal lobe neuronal damage in temporal and extratemporal lesional epilepsy

OBJECTIVE: To assess the extent of medial temporal lobe (TL) abnormalities of the neuronal marker N-acetylaspartate (NAA) in TL and extra-TL lesional partial epilepsy, and to determine whether decreases in NAA are related to lesion location, to lesion pathology, or to the seizures themselves. METHODS: The authors studied 19 patients with intractable partial epilepsy and an isolated structural cerebral lesion (10 TL, 9 extra-TL; 10 cortical dysplasia [CD], 9 non-CD lesions). Proton MRS imaging was used to determine the average relative resonance intensity of NAA for the TL regions of the left and right hemispheres. Values less than two SDs below the mean of normal control subjects were considered abnormal. RESULTS: Fourteen patients (74%) had abnormally low NAA relative to creatine (NAA/Cr) in at least one TL. Three-way analysis of variance (ANOVA; lesion pathology, lesion location, side of NAA/Cr decrease) showed that ipsilateral NAA/Cr was lower than contralateral (p = 0. 04). Three-way ANOVA (lesion location, generalized tonic-clonic seizures, side of NAA/Cr decrease) showed that generalized tonic-clonic seizures were associated with lower TL NAA/Cr (p = 0. 02). Lesion location and pathology showed no main effect on the NAA-to-Cr ratio in either analysis (p > 0.05). Linear regression analyses between seizure duration and NAA/Cr decrease was not significant. CONCLUSION: The authors demonstrated abnormally low TL NAA/Cr in the majority of patients with structural cerebral lesions. This abnormality did not differ with lesion location or pathology. They propose that the altered function of neuronal networks by an isolated structural cerebral lesion results in remote "functional dual pathology."     

Ictal PET in presurgical workup of refractory extratemporal epilepsy

Ictal Pet in presurgical workup of refractory epilepsy is seldom performed and limited due to technical difficulties. In carefully selected patient subset with frequent extratemporal seizures, ictal PET depicts ‘seizure onset zone’ with high spatial resolution even within a widespread pathology. We here depict a four year old with posterior quadrant dysplasia evaluated with ictal PET.Key Words: Epilepsy, Ictal PET, presurgical workup, refractory     

Pre-surgical evaluation and surgical treatment in children with extratemporal epilepsy

Introduction This review summarizes some patterns of pre-surgical evaluation and surgical treatment of extratemporal epilepsy in pediatric patients with medically refractory seizures, whose ictal behavior is variable. The most effective treatment for intractable partial epilepsy is a focal cortical resection with excision of the epileptogenic zone (the area of ictal onset and initial seizure propagation). This might be risky, though, in the case of a widespread lesion, sometimes encroaching one or more lobes, given the risk to the functional cerebral cortex. An anterior temporal lobectomy might prove more effective then in preventing seizures with fewer potential complications. If partial extratemporal epilepsy is associated with pharmaco-resistant seizures, the preoperative evaluation and operative strategy are determined according to the epileptogenic zone and to the relationship between a substrate-directed disorder and eloquent areas. The pediatric treatment of extratemporal epilepsy is aimed at controlling the seizures, avoiding morbidity, and improving the patient’s quality of life through psychosocial integration. Since the immature brain is more plastic than when mature, the recovery of functions after surgery is greater in children than in adults.Recommendation Early surgery is recommended for children with intractable epilepsy, and is now accepted as an important therapeutic modality also for children with chronic epilepsy.Conclusion Technological advances in the last two decades, mainly in neuroimaging, have led many medical centers to consider surgical treatment of epilepsy, accuracy being granted by MRI-based neuronavigation systems—an interface between the lesion seen in the preoperative magnetic resonance imaging (MRI) and the operative field, often invisible to the surgeon.     

The topography and significance of extratemporal hypometabolism in refractory mesial temporal lobe epilepsy examined by FDG‐PET

Purpose: This study aims to map the temporal and extratemporal 18‐fluorodeoxyglucose positron emission tomography (FDG‐PET)–defined hypometabolism in mesial temporal lobe epilepsy (MTLE). We hypothesize that quantitative analysis will reveal extensive extratemporal glucose hypometabolism (EH), that the EH is related to seizure propagation beyond the temporal lobe, hypometabolism restricted to one temporal lobe predicts a good outcome following surgery, and EH predicts a poor outcome. Methods: Sixty‐four patients were studied who had undergone temporal lobectomy for intractable MTLE and had at least 2 years of postoperative follow‐up. Spatial preprocessing and statistical analysis on preoperative interictal FDG‐PET using statistical parametric mapping (SPM 2) identified significant regions of hypometabolism compared to normal controls. The predictors of outcome were determined by univariable and multiple logistic regression analyses. Results: EH was common and widespread, occurring most frequently in the ipsilateral insula and frontal lobe. The extent of EH was not significantly associated with age of onset or the duration of epilepsy. Presence of secondarily generalized tonic‐–clonic seizures (SGTCS) was associated with a larger extent of remote hypometabolism (RH, p < 0.005). Multiple logistic regression analysis identified the extent of RH and the age at surgery as independent predictors of seizure outcome. Discussion: Our results indicate that RH in MTLE is associated with a poorer surgical outcome, especially if seen in the contralateral hemisphere. The extent of RH relates to SGTCS but not to duration of epilepsy.     

Visual versus computer evaluation of thiopental-induced EEG changes in temporal lobe epilepsy

Thiopental-induced EEG beta activity was analyzed both visually and by computer in 33 patients with complex partial epilepsy. Studies were done in 16 patients with depth electrodes in limbic structures and 17 patients with scalp and sphenoidal electrodes. The percentage of drug-induced change in beta activity was quantified by computer using spectral analysis. The statistical significance of asymmetries between homologous sites in the amount of change was determined. The spatial distribution of significant asymmetries was used for localization and compared with the results of independent visual analysis of the thiopental EEG. Concordance between computer and visual evaluation occurred in 10 of 17 scalp/sphenoidal and 10 of 16 depth electrode tests. The accuracy of visual and computer localization was determined by comparing them with locus of itcal EEG onset, interictal spikes, and positron emission tomography. In scalp/sphenoidal studies, computer analysis indicating asymmetry appeared more likely to correlate with independent clinical criteria than visual analysis. In depth studies the reverse appeared to be true. Scalp/sphenoidal tests yielded positive results in 25-30% of patients whereas depth electrode tests were positive in 50-70% of patients. The results indicate that computer analysis of surface thiopental tests is an accurate and useful supplement to visual evaluation of these tests.