Can histologically normal epileptogenic zone share common electrophysiological phenotypes with focal cortical dysplasia? SEEG-based study in MRI-negative epileptic patients.

OBJECTIVE: We aimed to assess stereoelectroencephalography (SEEG) seizure-onset and interictal patterns associated with MRI-negative epilepsy and investigate their possible links with histology, extent of the epileptogenic zone (EZ) and surgical outcome. METHODS: We retrospectively analysed a cohort of 59 consecutive MRI-negative surgical candidates, who underwent SEEG recordings followed by cortectomy between 2000 and 2016. RESULTS: Most of the eight distinct seizure-onset patterns could be encountered both in confirmed focal cortical dysplasia (FCD) and in histologically non-specific or normal cases. We found strong correlation (p = 0.008) between seizure-onset pattern and histology for: (1) slow-wave/DC-shift prior to low voltage fast activity (LVFA), associated with normal/non-specific histology, and (2) bursts of polyspikes prior to LVFA, exclusively observed in FCD. Three interictal patterns were identified: periodic slow-wave/gamma burst, sub-continuous rhythmic spiking and irregular spikes. Both "periodic" patterns were more frequent in but not specific to FCD. Surgical outcome depended on the EZ complete removal, regardless electrophysiological features. CONCLUSIONS: Histologically normal and FCD-associated epileptogenic zones share distinct interictal and ictal electrophysiological phenotypes, with common patterns between FCD subtypes and between dysplastic and apparently normal brain. SIGNIFICANCE: Some specific seizure-onset patterns seem to be predictive of the underlying histology and may help to detect an MRI-invisible FCD.

Is there a place for surgical treatment of nonpharmacoresistant epilepsy?

Epilepsy surgery has been shown to be the best possible treatment in well-defined and difficult-to-treat epilepsy syndromes, such as mesial temporal lobe epilepsy with unilateral hippocampal sclerosis, even early in the course of the disease if pharmacoresistance is proven. This review addresses the question if epilepsy surgery may be justified today even in nonpharmacoresistant cases. There are two possible groups of patients: first, there are epilepsy syndromes with a benign spontaneous course or with a potentially good treatment prognosis under appropriate antiepileptic drug (AED) treatment. Second, there are epilepsies with potentially worse AED treatment prognosis in which appropriate AED treatment has not yet been applied because of the short course of the disease, tolerability problems that prevented usually effective dosing, or adherence issues. In group one, the good spontaneous prognosis or the usually satisfying course under AED treatment in line with the commonly generalized underlying epileptogenesis does not suggest that epilepsy surgery is a realistic alternative, not even in cases with distinct focal clinical and/or electroencephalography (EEG) patterns like in Rolandic epilepsy with centrotemporal spikes. In the second group, the recent International League Against Epilepsy (ILAE) definition should allow assessment of individual pharmacoresistance early after the onset of the disease in order to avoid any delay. Concerns about a potential disease-specific or drug-specific cognitive decline that could be avoided in early surgery are speculative, a matter of controversial discussion, and certainly not relevant, if pharmacoresistance is consequently addressed in time according to the ILAE recommendations. One should also not forget that even in typically pharmacoresistant epilepsy syndromes that are suitable for surgical procedures, satisfying courses do exist that would not require early or any epilepsy surgery. Therefore, in almost any instance, epilepsy surgery as initial treatment or immediately after a first AED is still not recommended although, especially in cases with nonadherence to AEDs, it may be occasionally considered in order to outweigh the risks of ongoing seizures and epilepsy if surgery is not performed.

Current use of imaging and electromagnetic source localization procedures in epilepsy surgery centers across Europe.

OBJECTIVE: In 2014 the European Union-funded E-PILEPSY project was launched to improve awareness of, and accessibility to, epilepsy surgery across Europe. We aimed to investigate the current use of neuroimaging, electromagnetic source localization, and imaging postprocessing procedures in participating centers. METHODS: A survey on the clinical use of imaging, electromagnetic source localization, and postprocessing methods in epilepsy surgery candidates was distributed among the 25 centers of the consortium. A descriptive analysis was performed, and results were compared to existing guidelines and recommendations. RESULTS: Response rate was 96%. Standard epilepsy magnetic resonance imaging (MRI) protocols are acquired at 3 Tesla by 15 centers and at 1.5 Tesla by 9 centers. Three centers perform 3T MRI only if indicated. Twenty-six different MRI sequences were reported. Six centers follow all guideline-recommended MRI sequences with the proposed slice orientation and slice thickness or voxel size. Additional sequences are used by 22 centers. MRI postprocessing methods are used in 16 centers. Interictal positron emission tomography (PET) is available in 22 centers; all using 18F-fluorodeoxyglucose (FDG). Seventeen centers perform PET postprocessing. Single-photon emission computed tomography (SPECT) is used by 19 centers, of which 15 perform postprocessing. Four centers perform neither PET nor SPECT in children. Seven centers apply magnetoencephalography (MEG) source localization, and nine apply electroencephalography (EEG) source localization. Fourteen combinations of inverse methods and volume conduction models are used. SIGNIFICANCE: We report a large variation in the presurgical diagnostic workup among epilepsy surgery centers across Europe. This diversity underscores the need for high-quality systematic reviews, evidence-based recommendations, and harmonization of available diagnostic presurgical methods.

Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesiotemporal lobe epilepsy and unilateral hippocampal sclerosis: post-operative facial emotion recognition abilities.

Surgical treatment of mesial temporal lobe epilepsy (mTLE) patients involves the removal either of the left or the right hippocampus. Since the mesial temporal lobe is responsible for emotion recognition abilities, we aimed to assess facial emotion recognition (FER) in two homogeneous patient cohorts that differed only in the administered surgery design since anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH) were performed independently of the underlying electroclinical conditions. The patient selection for the two respective surgical procedures was carried out retrospectively between 2000 and 2009 by two independent epilepsy centres, the Kork Epilepsy Centre, Germany and the University Hospital of Strasbourg, France. All included patients had presented with unilateral hippocampus sclerosis (HS) without associated dysplasia or white matter blurring and had become seizure-free postoperatively. Psychometric evaluation was carried out with the Ekman 60 Faces Test and screened for depression and psychosomatic symptoms with the SCL-90 R and the BDI. Thirty healthy volunteers participated as control subjects. Sixty patients were included, 27 had undergone SAH and 33 ATL. Patients and controls obtained comparable scores in FER for surprise, happiness, anger and sadness. Concerning fear and disgust the patient group scored significantly worse. Left-sided operations led to the the most pronounced impairment. The ATL group scored significantly worse for recognition of fear compared with SAH patients. Inversely, after SAH scores for disgust were significantly lower than after ATL, independently of the side of resection. Unilateral temporal damage impairs FER. Different neurosurgical procedures may affect FER differently.

Hypothalamic hamartoma: is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis.

Gelastic seizures associated with hypothalamic hamartomas (HHs) are a clinicoradiologic syndrome presenting with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, electroencephalography (EEG) abnormalities, precocious puberty, behavioral disturbances, and progressive cognitive deterioration. Surgery in adults provides seizure freedom in only one third of patients. The poor results of epilepsy surgery could be explained by an extrahypothalamic epileptogenic zone. The existence of an independent, secondary epileptogenic area with persistent seizures after resection of the presumably primary lesion supports the concept of a "hypothalamic plus" epilepsy. "Hypothalamic plus" epilepsy could be related to either an extrahypothalamic structural lesion (visible on magnetic resonance imaging [MRI] or on neuropathology) or if the former is absent, to a functional alteration with enhanced epileptogenic properties due to a process termed secondary epileptogenesis. We report two patients with gelastic seizures with HH (gelastic seizures isolated or associated with dyscognitive seizures of temporal origin). Both patients underwent two-step surgery: first an endoscopic resection of the HH, followed at a later time by temporal lobectomy. Both patients became seizure-free only after the temporal lobectomy. In both cases, neuropathology failed to demonstrate a significant structural lesion in the temporal lobe. To our knowledge, for the first time, these two cases suggest the existence of independent secondary epileptogenesis in humans.

Quality control of elective surgery for drug-resistant epilepsy in a German reference centre--a long-term outcome study.

PURPOSE: Resective epilepsy surgery is the recommended treatment for a well-defined group of patients with drug-resistant epilepsy. Long-term outcome studies are an appropriate quality control to assess the value of elective surgical procedures ethically and economically. This paper reports the long-term post-surgical follow-up of adult patients of the Kork Epilepsy Centre. METHOD: Data collection was performed by means of a questionnaire to obtain updated information about postsurgical outcome, frequency and postsurgical seizure semiology in case of relapse, postsurgical use of antiepileptic drugs, social issues and satisfaction rates. We classified seizure outcome according to the ILAE surgery outcome scale (OC 1-OC 6). RESULTS: Outcome data of 340 adult patients were obtained. Mean post-operative follow-up was 6.7 years (range 1.0-21.6 years). Seizure remission was 67% if comprising patients with postoperative auras only (OC 1+OC 2). Sixty-two per cent of patients were completely seizure free. The majority of patients (78%) underwent temporal lobe resections. Sixty-four per cent of these and 52% of the patients with extra-temporal resections became completely seizure-free (OC 1). Only 34% of the patients with negative MRI achieved complete seizure-freedom. CONCLUSION: In line with others our huge cohort sample that covers decades of experience with epilepsy surgery revealed satisfying long-term outcome results. Best results were obtained in lesional temporal lobe epilepsy, least favourable results in MRI-negative epilepsy.

Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesial temporal lobe epilepsy and unilateral hippocampal sclerosis.

Several studies have demonstrated the positive effect of resective epilepsy surgery in drug-resistant temporal lobe epilepsy (TLE). However, it is still a matter of debate whether selective amygdalohippocampectomy (SAH) or standard temporal lobectomy (STL) are the most effective approaches concerning seizure outcome, quality of life and memory. In each of the two centers participating in this study either SAH or STL was the neurosurgical standard procedure irrespective of contextual aspects. Thus, with this postoperative assessment of resected patients we sought to avoid any selection bias that usually impaired comparative trials of both surgical approaches. We finally identified and studied 95 adult patients who had undergone either SAH (n=46) or STL (n=49) between 1999 and 2009 and fulfilled the inclusion criteria, namely drug-resistant unilateral mesial TLE with hippocampal sclerosis without any further structural lesions. We assessed the postoperative seizure outcome according to the ILAE criteria and postoperative quality of life by means of standardized questionnaires. Finally, we compared postoperative neuropsychological performance in 60 completely seizure-free patients (n=27 after SAH, n=33 after STL) prior to, one year after surgery and at a long-term follow-up with a mean of seven years. 78.2% of SAH and 85.7% of STL were seizure-free at the last observation. Quality of life had improved in 95.6% of the SAH patients and 89.8% of the STL patients. These differences were not statistically significant. Left-sided TLE patients had a significantly worse verbal memory outcome irrespective of the surgical method. However, SAH patients had a significantly better outcome concerning visual encoding, verbal and visual short-term memory and visual working memory. In this study, seizure outcome and quality of life did not differ depending on the surgical approach. However, a more selective resection led to better neuropsychological performances.

Hyperkinetic seizures in patients with temporal lobe epilepsy: clinical features and outcome after temporal lobe resection.

PURPOSE: Temporal lobe epilepsy (TLE) is usually associated with automatisms. Hyperkinetic seizures are supposed to be unusual. Because we witnessed several patients with TLE and ictal hyperkinetic symptoms, we retrospectively assessed the number, clinical findings, and seizure outcome in such patients who had undergone temporal lobe resection. METHODS: We reviewed medical history, video-electroencephalography (EEG) recording and neuroimaging of adult patients who underwent epilepsy surgery for TLE at the Kork Epilepsy Center over the last 20 years with a minimum postoperative follow-up of 12 months. KEY FINDINGS: Among 294 patients who were resected exclusively in the temporal region, we identified 17 (6%) who presented with hyperkinetic semiology such as violent vocalization, complex movements of the proximal segments of the limbs, rotation of the trunk, pelvic thrusting, or early tonic or dystonic posturing. Most of the patients had a preceding aura. Ictal EEG activity was located in the corresponding temporal region, usually with a wide distribution over temporal electrodes with fast spread to unilateral frontal electrodes and to the contralateral side. Neuroimaging revealed extended lesions in the temporal lobe involving mesial and neocortical structures. Most of the patients underwent classical anterior temporal lobe resection including amygdalo-hippocampectomy. Fourteen patients (82%) became completely seizure-free (Engel class Ia). Histopathology showed mainly focal cortical dysplasia plus hippocampal sclerosis. SIGNIFICANCE: Hyperkinetic seizure semiology may occasionally occur in patients with TLE and is, therefore, no contradiction to the hypothesis of TLE if scalp EEG patterns and neuroimaging findings correspond. The postoperative seizure outcome is favorable in such patients and not different from outcome data in classical TLE.