Prognostic value of scalp EEG ictal patterns in epilepsy surgery of hippocampal sclerosis.

BACKGROUND: Temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) is a surgically treatable epileptic syndrome. While the core of pre-surgical evaluations rely on video-EEG, recent studies question the necessity of recorded seizures denying a possible role of ictal EEG in surgical decision. This study aims to retrospectively assess the prognostic value of EEG ictal patterns in TLE-HS, in order to identify which patients need further investigations before offering surgery. METHODS: We included TLE-HS patients who underwent surgery with at least one captured seizure during non-invasive pre-surgical video-EEG recordings. They were classified in "mesial" and "lateral/mixed", according to the ictal EEG patterns, defined by the frequency of the discharge (mesial ≥ 5 Hz, lateral < 5 Hz). Seizure outcome was assessed by Engel's Class. Statistical analyses were performed to evaluate associations between EEG patterns and post-surgical outcomes. RESULTS: Sixty-nine exhibited a mesial pattern, forty- two displayed lateral/mixed patterns. Mesial pattern group had a significantly higher rate of postsurgical seizure freedom (82.7% vs. 28.6%). Gender, age of onset, age at surgery, duration of epilepsy, seizure frequency, and lateralization did not influence the outcome. Mesial pattern significantly correlated with favorable outcomes (p < 0.001), suggesting its potential predictive value. CONCLUSION: This retrospective study proposes ictal EEG patterns as possible predictors of postoperative prognosis in TLE-HS. A mesial pattern correlates with better outcomes, indicating a potentially more circumscribed epileptogenic zone. Patients with lateral/mixed patterns may benefit from additional investigations to delineate the epileptogenic zone. Further studies are warranted to validate and extend these findings.

Sleep macrostructure and cyclic alternating pattern in patients who underwent surgery for hippocampal sclerosis: A prospective controlled polysomnographic study.

INTRODUCTION: Temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS) is one of the most common drug-resistant epilepsy. Surgery is currently accepted as an effective and safe therapeutic approach compared to antiseizure medications (ASMs). The study aims to evaluate the effect of surgical treatment of TLE-HS on sleep profile and architecture by subjective and objective evaluation of sleep in basal condition after one month and one year. METHODS: Thirteen patients with TLE-HS were recruited to undergo overnight polysomnography and a subjective evaluation of nocturnal sleep utilizing the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence through the Epworth Sleepiness Scale (ESS) in basal condition (T0), one month (T1) and one year after surgery (T2), respectively. Thirteen healthy controls (HC) matched for age, sex and BMI were recruited. Scoring and analysis of sleep macrostructure and cyclic alternating pattern (CAP) parameters were performed. RESULTS: The comparison between patients in basal condition (T0) and HC showed a significant lower sleep efficiency (p = 0.003) and REM percentage (p < 0.001). Regarding CAP, patients at T0 showed higher total CAP rate (p < 0.001), CAP rate in N2 (p < 0.001), higher A3 (%) (p = 0.001), higher mean duration of A1 (p = 0.002), A3 index (p < 0.001), cycle in sequences (p < 0.001), lower B duration (p < 0.001), cycle mean duration (p < 0.001) than HC. Surgery did not induce significant changes in nocturnal macrostructural polysomnographic variables in T1 and T2. Lower CAP rate (T1 vs T0 and T2 vs T0 p < 0.001), CAP rate in N3 (T1 vs T0 and T2 vs T0 p < 0.001), A3 (%) (T1 vs T0 and T2 vs T0 p < 0.001); lower phase A2 index (T1 vs T0 p < 0.001) and A3 index (T1 vs T0 p < 0.001), lower phase A1 index (T2 vs T0 p < 0.001) and cycle in sequences (T2 vs T0 p = 0.002) higher B mean duration (T2 vs T0 p = 0.002). No significant differences were found between T1 and T2 in CAP parameters. CONCLUSION: We found a significant NREM sleep instability in patients with TLE-HS compared with HC. In addition, anterior temporal lobectomy (ATL) induced a significant improvement in sleep continuity as evaluated by cyclic alternating pattern already one month later and this effect persisted after one year. ALT seems to restore a more resilient sleeping brain.

Bilateral epileptogenesis in temporal lobe epilepsy due to unilateral hippocampal sclerosis: A case series.

INTRODUCTION: Bitemporal epilepsy (biTLE), a potential cause of failure in TLE surgery, is rarely associated with unilateral HS and could be suggested by not lateralizing ictal scalp EEG/interictal PET-FDG findings. We evaluated the proportion of biTLE in a population of drug-resistant TLE-HS subjects who underwent intracranial investigation for lateralizing purpose. METHODS: We retrospectively included all consecutive refractory TLE-HS patients and not lateralizing ictal scalp EEG/interictal PET-FDG findings, investigated by intracranial bilateral longitudinal hippocampal electrodes. Demographic characteristics, electroclinical findings and seizure outcome were evaluated. RESULTS: We identified 14 subjects (7 males; mean age 39.5 years; mean age at disease onset 14.4 years), 7 of them had biTLE diagnosed after intracranial investigations. In the remaining 7 with unilateral epileptogenesis (uniTLE) anterior temporal lobectomy was performed (6/7 were in Engel class I). Preoperative neuropsychological assessment differentiated biTLE from uniTLE, as it was normal in six uniTLE patients but only in one with biTLE (p < 0.05). CONCLUSIONS: Not lateralizing ictal scalp EEG and functional imaging findings in TLEHS should alert about the possibility of a true biTLE also in presence of unilateral findings at MRI. Intracranial investigations with bilateral longitudinal hippocampal electrodes can localize the EZ with a good risk-benefit profile. Consistently with the warning on memory functions in TLE patients explored by using longitudinal hippocampal electrodes, further studies are needed to better define the optimal investigation strategy.

Focal Cortical Dysplasia IIIa in Hippocampal Sclerosis-Associated Epilepsy: Anatomo-Electro-Clinical Profile and Surgical Results From a Multicentric Retrospective Study.

BACKGROUND: Hippocampal sclerosis (HS) may be associated with focal cortical dysplasia IIIa (FCD IIIa) in patients undergoing surgery for temporal lobe epilepsy (TLE). OBJECTIVE: To investigate whether the anatomo-electro-clinical profile and surgical outcome in patients with HS-related TLE are affected by coexisting FCD IIIa. METHODS: A total of 220 patients, operated in 5 centers, with at least 24 mo follow-up (FU), were retrospectively studied. Preliminary univariate and subsequent multivariate analyses were performed to investigate possible associations between several potential presurgical, surgical, and postsurgical predictors and different variables (Engel's class I and Engel's class Ia, co-occurrence of FCD IIIa). RESULTS: At last available postoperative control (FU: range 24-95 mo, median 47 mo), 182 (82.7%) patients were classified as Engel's class I and 142 (64.5%) as Engel's class Ia. At multivariate analysis, extension of neocortical resection and postoperative electroencephalogram were significantly associated with Engel's class I, whereas length of FU had a significant impact on class Ia in the whole cohort and in isolated HS (iHS) patients, but not in the FCD IIIa group. No differences emerged in the anatomo-electro-clinical profile and surgical results between patients with FCD IIIa and with iHS. CONCLUSION: Coexistence of FCD IIIa did not confer a distinct anatomo-electro-clinical profile to patients with HS-related epilepsy. Postoperative seizure outcome was similar in FCD IIIa and iHS cases. These findings indicate limited clinical relevance of FCD IIIa in HS-related epilepsy and might be useful for refining future FCD classifications. Further studies are needed to clarify the correlation of class Ia outcome with the duration of FU.

A European questionnaire survey on epilepsy monitoring units' current practice for postoperative psychogenic nonepileptic seizures' detection.

BACKGROUND: In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures' outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs could provide to retrospectively detect cases with postoperative PNES and to assess the feasibility of a subsequent postoperative PNES research project for cases with postoperative PNES. METHODS: We developed and distributed a questionnaire survey to 57 EMUs. Questions addressed the number of patients undergoing epilepsy surgery, the performance of systematic preoperative and postoperative psychiatric evaluation, the recording of sexual or other abuse, the follow-up period of patients undergoing epilepsy surgery, the performance of video-electroencephalogram (EEG) and postoperative psychiatric assessment in suspected postoperative cases with PNES, the existence of electronic databases to allow extraction of cases with postoperative PNES, the data that these bases could provide, and EMUs' interest to participate in a retrospective postoperative PNES project. RESULTS: Twenty EMUs completed the questionnaire sheet. The number of patients operated every year/per center is 26.7 ( ±â€¯19.1), and systematic preoperative and postoperative psychiatric evaluation is performed in 75% and 50% of the EMUs accordingly. Sexual or other abuse is systematically recorded in one-third of the centers, and the mean follow-up period after epilepsy surgery is 10.5 ±â€¯7.5 years. In suspected postoperative PNES, video-EEG is performed in 85% and psychiatric assessment in 95% of the centers. An electronic database to allow extraction of patients with PNES after epilepsy surgery is used in 75% of the EMUs, and all EMUs that sent the sheet completed expressed their interest to participate in a retrospective postoperative PNES project. CONCLUSION: Postoperative PNES is an underestimated and not well-studied entity. This is a European survey to assess the type of data that the EMUs surgical cohorts could provide to retrospectively detect postoperative PNES. In cases with suspected PNES, most EMUs perform video-EEG and psychiatric assessment, and most EMUs use an electronic database to allow extraction of patients developing PNES.

Long-term seizure outcome in frontal lobe epilepsy surgery.

PURPOSE: The purpose of this study was to report long-term seizure outcome in patients who underwent frontal lobe epilepsy (FLE) surgery. METHOD: This retrospective study included 44 consecutive subjects who underwent resective surgery for intractable FLE at IRCCS NEUROMED (period 2001-2014), followed up for at least 2 years (mean: 8.7 years). All patients underwent noninvasive presurgical evaluation and/or invasive electroencephalography (EEG) monitoring when nonconcordant data were obtained or epileptogenic zone was hypothesized to be close to the eloquent cortex. Electroclinical, neuroimaging, surgical data, and histology were compared to seizure outcome. RESULTS: Mean epilepsy duration was 19 years; mean age at surgery was 31.6 years. Preoperative magnetic resonance imaging (MRI) showed a frontal lesion in 86.4 % of cases. Scalp video-electroencephalography (VEEG) monitoring detected a focal ictal onset in 90% of cases. Twenty-seven patients (61.4%) underwent invasive recordings. Resections involved dorsolateral (47.7%), medial (9%), orbital (13.6%), and rolandic (13.6%) region. Lobectomy within functional boundaries was performed in the remaining 7 cases (16%). Transient and permanent neurological deficits were observed in 2 and 3 cases, respectively. Histology revealed focal cortical dysplasia (45.5%), World Health Organization (WHO) I-II grade tumors (15.9%), gliosis (22.7%), vascular malformations (4.5%), Rasmussen encephalitis (6.8%), and normal tissue (4.5%). At last observation 68.1% of patients were in Engel's class I, 11.4% in class II, 9% in class III, and 11.4% in class IV. A favorable outcome was associated with focal ictal scalp EEG onset (p = 0.0357). CONCLUSION: Surgery is a safe treatment option in drug-resistant FLE with a satisfying long-term outcome. These data highlight the importance of an appropriate selection of potential surgical candidates.

Possible autoantibody-negative limbic encephalitis after anterior temporal lobectomy for hippocampal sclerosis.

PURPOSE: Amnestic syndromes are acknowledged to be associated to bilateral hippocampal damage. MATERIALS AND METHODS: We briefly report the case of a young man who underwent anterior left temporal lobectomy for a medically refractory temporal lobe epilepsy due to hippocampal sclerosis with an excellent seizure and neuropsychological outcome. Approximately 10 years later, he presented with a subacute severe global amnesia and neuroimaging findings of a damage involving the contralateral mesial temporal lobe structures. RESULTS: A diagnosis of a possible autoimmune encephalitis was made. CONCLUSIONS: Due to its peculiarities (compared with other cases of bilateral temporal lesions, the damage occurred on two distinct occasions), this case might contribute to shed light on the issue of the possible contralateral reorganization of memory processes subserved by the mesial temporal lobe structures chronically involved in epileptogenesis.

Severe and rapidly-progressive Lafora disease associated with NHLRC1 mutation: a case report.

Lafora disease (LD), also known as progressive myoclonic epilepsy-2 (EPM2), is a rare, fatal autosomal recessive disorder typically starting during adolescence in otherwise neurologically normal individuals. It is clinically characterized by insidious of progressive neurological features including seizures, action myoclonus, visual hallucination, ataxia and dementia. Mutations in the laforin (EPM2A) gene on chromosome 6q24 or in the malin gene (NHLRC1) on chromosome 6p22 are responsible of LD phenotype. Diagnostic workup includes genetic analysis as well as axillary skin biopsy with evidence of typical periodic acid-Schiff (PAS)-positive polyglucosan inclusion bodies (Lafora bodies) in the apocrine glands and/or in the eccrine duct. Usually, genotype-phenotype correlations do not reveal substantial differences between patients carrying EPM2A and NHLRC1 mutations, but a few specific NHLRC1 mutations appear to correlate with a late onset and slow progressing LD. We report a case of LD due to compound heterozygote NHLRC1 mutation in an adolescent presenting with severe and atypical electro-clinical features, mimicking an autoimmune encephalopathy, and a rapidly progressive clinical course.

Temporal pole abnormalities detected by 3 T MRI in temporal lobe epilepsy due to hippocampal sclerosis: No influence on seizure outcome after surgery.

PURPOSE: To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) detected by using 3 Tesla MRI in the preoperative workup in patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS) who underwent surgery. METHODS: We studied 78 consecutive patients with TLE-HS who underwent surgery and were followed up for at least 2 years. Based on findings of pre-surgical 3 Tesla MRI, patients were subdivided in subgroups according to the presence of TB or TA. Subgroups were compared on demographic, clinical, neuropsychological data and seizure outcome. RESULTS: TB was found in 39 (50%) patients, while TA was found in 32 (41%) patients, always ipsilateral to HS, with a considerable degree of overlap (69%) between TB and TA (p=0.01). Patients with temporopolar abnormalities did not significantly differ from those without TB or TA with regard to sex, age, age of epilepsy onset, duration of epilepsy, history of febrile convulsions or birth complications, side of surgery, seizure frequency at surgery, presence of GTCSs, and, in particular, seizure outcome. On the other hand, TB patients show a less frequent family history of epilepsy (p<.05) while age at epilepsy onset showed a trend to be lower in the TB group (p=.09). Patients with temporopolar atrophy did not significantly differ from those without TA on any variable, except for age at epilepsy onset, which was significantly lower for the TA group (p<.05). History of birth complications and longer duration of epilepsy also showed a trend to be associated with TA (p=.08). Multivariate analysis corroborated the association between temporopolar abnormalities and absence of family history of epilepsy and history of birth complications. CONCLUSIONS: High-field 3 T MRI in the preoperative workup for epilepsy surgery confirms that temporopolar abnormalities are frequent findings in TLE-HS patients and may be helpful to lateralize the epileptogenic zone. Their presence did not influence seizure outcome.

Deep brain stimulation for intractabile epilepsy.

INTRODUCTION: Deep brain stimulation (DBS) is currently considered a promising neuromodulation therapy for refractory epilepsy not suitable for resective surgery. Several anatomical targets and different stimulation approaches have been proposed in order to obtain satisfactory seizures reduction. As expected, according with different patterns of neural pathways involvement, the efficacy of each anatomical target stimulation in reducing seizure frequency varies among the different epileptic syndromes. EVIDENCE ACQUISITION: We reviewed the current literature on this topic to provide an overview of the clinical efficacy of the main stimulation targets (anterior nucleus of the thalamus [ANT], hippocampus formation [HF] and centromedian nucleus of the thalamus [CMT]) related to the different epileptic syndromes. We also summarized the available data concerning side effects, neuropsychological outcome, quality of life and future perspective of DBS in intractable epilepsy. EVIDENCE SYNTHESIS: Encouraging results were reported for each target stimulation. However, only in ANT and responsive neurostimulation (RNS) the efficacy and safety were tested on large series of patients and achieving class I evidence level. CONSLUSIONS: We concluded that responsive stimulation could be more appropriate in focal epilepsy, while ANT stimulation could be properly performed also in multifocal seizures with predominant limbic involvement. Despite the small samples size, HF stimulation reduces seizure frequency in (bi) temporal lobe epilepsy, as well as CMT stimulation is able to reduce, seizure frequency, in generalized epilepsy.

Temporal pole abnormalities in temporal lobe epilepsy with hippocampal sclerosis: Clinical significance and seizure outcome after surgery.

PURPOSE: To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) with a long post-surgical follow-up. METHODS: We studied 60 consecutive patients with TLE-HS and 1.5 preoperative MRI scans who underwent surgery and were followed up for at least 5 years (mean follow-up 7.3 years). Based on findings of pre-surgical MRI, patients were classified according to the presence of TB or TA. Groups were compared on demographic, clinical, neuropsychological data, and seizure outcome. RESULTS: TB was found in 37 (62%) patients, while TA was found in 35 (58%) patients, always ipsilateral to HS, with a high degree of overlap (83%) between TB and TA (p<0.001). Patients with TB did not differ from those without TB with regard to history of febrile convulsions, GTCSs, age of epilepsy onset, side of surgery, seizure frequency, seizure outcome, and neuropsychological outcome. On the other hand, they were significantly older, had a longer duration of epilepsy, and displayed lower preoperative scores on several neuropsychological tests. Similar findings were observed for TA. Multivariate analysis corroborated the association between temporopolar abnormalities and age at onset, age at surgery (for TB only), and lower preoperative scores on some neuropsychological tests. CONCLUSIONS: Temporopolar abnormalities are frequent in patients with TLE-HS. Our data support the hypothesis that TB and TA are caused by seizure-related damages. These abnormalities did not influence seizure outcome, even after a long-term post-surgical follow-up.

Epilepsy surgery in adult-onset Rasmussen's encephalitis: case series and review of the literature.

Rasmussen's encephalitis (RE) is a rare immune-mediated condition characterized by drug-resistant focal epilepsy, progressive neurological, and cognitive deficits associated to unilateral hemispheric atrophy. The onset is typically reported in childhood, although adult cases (A-RE) have been described. While surgical strategies in childhood RE are well defined, little is known about usefulness of epilepsy surgery in A-RE patients. We describe clinical features, surgical approach, and outcome of five A-RE patients who underwent epilepsy surgery, and we review the literature with regard to surgical A-RE cases. We retrospectively studied five A-RE patients aged 21-38 years (mean age 22.8 years) who were followed after surgery for a period ranging from to 1 to 6 years. Demographic, electroclinical, and neuroimaging data were systematically reviewed. Four out of five subjects underwent invasive EEG monitoring to define epileptogenic zone. Epilepsy outcome was defined according to Engel's classification. Surgery consisted of frontal corticectomy in three patients, temporal lobectomy in one, combined temporal lobectomy plus insular, and frontobasal corticectomy in the remaining case. No permanent neurological deficits were observed after surgery. At the last follow-up observation, one patient was seizure-free, two subjects experienced rare disabling seizures, another had moderate seizure reduction, and one had no clinical improvement. Our experience, although limited to few cases, suggests that resective surgery in A-RE may play a role in the context of multidisciplinary therapeutical approach of this severe condition. Since the lack of specific data about surgical options, this topic seems to deserve further investigations and more targeted studies.

Acute postoperative seizures and long-term seizure outcome after surgery for hippocampal sclerosis.

PURPOSE: To assess the incidence and the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS). METHODS: We studied 139 consecutive patients with TLE-HS who underwent epilepsy surgery and were followed up for at least 5 years (mean duration of follow-up 9.1 years, range 5-15). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class Ia at the last contact were classified as having a favorable outcome. RESULTS: Seizure outcome was favorable in 99 patients (71%). Six patients (4%) experienced APOS and in all cases their clinical manifestations were similar to the habitual preoperative seizures. All patients with APOS had unfavorable long-term outcome, as compared with 35 (26%) of 133 in whom APOS did not occur (p<0.001). CONCLUSIONS: Our study suggests that APOS, despite being relatively uncommon in patients undergoing resective surgery for TLE-HS, are associated with a worse long-term seizure outcome. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicenter studies.

Serial postoperative awake and sleep EEG and long-term seizure outcome after anterior temporal lobectomy for hippocampal sclerosis.

OBJECTIVE: To test if postoperative prolonged awake and sleep EEG monitoring predict long-term seizure outcome in patients operated for drug-resistant temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS). METHODS: This longitudinal study includes 107 patients with MTLE-HS who underwent anterior temporal lobectomy (ATL), were followed for at least 5 years (mean 8.3, range 5-12), had postoperative EEG after 2 months and at least one prolonged video-EEG monitoring during both wakefulness and sleep after 12 and 24 months. At each follow-up visit, the presence of interictal epileptiform discharges (IED) was determined, and seizure outcome was evaluated. RESULTS: Sixty-six patients (62%) remained free from auras and seizures throughout the follow-up period. Twenty-six (24%), 22 (21%), and 16 (16%) patients had IED at the 2-month, 12-month, and 24-month follow-up, respectively. The presence of IED at each time point was found to be associated with seizure or aura recurrence. Sleep recording contributed to the identification of patients with IED, as half of patients with IED displayed anomalies in sleep EEG only. In multivariate analysis, the presence of IED 2 months after surgery was found to be associated with seizure or aura recurrence independent of pre-operative factors consistently reported as outcome predictors in the literature. CONCLUSIONS: The presence of IED in serial postoperative EEG including sleep recording may predict long-term seizure outcome after ATL for TLE-HS. Serial postoperative EEGs may contribute to outcome prediction and help making decision about medication withdrawal in patients operated for TLE-HS.

Prognostic significance of acute postoperative seizures in extra-temporal lobe epilepsy surgery.

OBJECTIVE: This study aims to assess the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant extra-temporal lobe (ET) epilepsy. METHODS: We studied 77 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 years, range 2-14). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class I at the last contact were classified as having a favourable outcome. RESULTS: Seizure outcome was favourable in 47 patients (61%). The occurrence of APOS and incompleteness of resection were found to be independently associated with unfavourable outcome in a multiple regression model including all preoperative factors identified as outcome predictors in univariate analysis. Duration of illness was the only independent preoperative predictor of APOS. CONCLUSIONS: Our study suggests that APOS may predict long-term outcome in patients undergoing resective surgery for ET epilepsy. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicentre studies. SIGNIFICANCE: Caution may be required in the clinical management of patients experiencing APOS.