The role of SEEG in the presurgical decision-making process in MRI-normal mesial temporal lobe epilepsy.

OBJECTIVES: In patients with mesial temporal lobe epilepsy (mTLE) and normal MRI, anterior temporal lobectomy sparing the hippocampus might be considered because of the risk of post-operative memory deficit. However, it is unclear whether some patients with normal MRI and non-invasive EEG and semiological pattern highly suggestive of mesial temporal seizures demonstrate a seizure onset network sparing the hippocampus, potentially warranting surgery. METHODS: A retrospective study of 17 patients with mTLE epilepsy and normal MRI who underwent SEEG. Only patients whose non-invasive presurgical data suggested an unilateral mesial temporal epileptogenic zone (EZ), as defined by combination of ictal semiology and ictal EEG during scalp video-EEG, were included. SEEG data were analyzed using both visual and quantitative approaches. Two EZ organization were defined: (i) EZ involved the hippocampus at the onset of the ictal discharge (HIP group): (ii) patients in whom a delay>1sec was observed between the seizure onset and the involvement of the hippocampus (nHIP group). Non-invasive clinical and functional imaging data, as well as post-operative outcomes, were compared across groups. RESULTS: Eleven patients were included in HIP group and 6 in the nHIP group. In the nHIP group, the maximal epileptogenicity was in the amygdala in five patients and in the entorhinal cortex in one. The hippocampus normalized interictal spiking activity was not different between groups. None of the patients characteristics collected during the non-invasive presurgical workup was associated with the SEEG-based organization of the EZ. Twelve patients underwent a surgical resection, including temporal cortectomy sparing hippocampus in six. Seizure and neuropsychological post-operative outcomes were similar. CONCLUSION: In patients with MRI-normal mTLE, SEEG should be included in the surgical decision-making process because seizure organization cannot be predicted from non-invasive investigations. When hippocampus is not included in the EZ, temporal resection sparing the hippocampus can be considered.

Predictive factors of postoperative outcome in the elderly after resective epilepsy surgery.

OBJECTIVE: To evaluate the efficiency of resective epilepsy surgery (RES) in patients over 50 years and determine prognostic factors. RESULTS: Over the 147 patients over 50 years (54.9±3.8 years [50-69]) coming from 8 specialized French centres for epilepsy surgery, 72.1%, patients were seizure-free and 91.2% had a good outcome 12 months after RES. Seizure freedom was not associated with the age at surgery or duration of epilepsy. In multivariate analysis, seizure freedom was associated with MRI and neuropathological hippocampal sclerosis (HS) (P=0.009 and P=0.028 respectively), PET hypometabolism (P=0.013), temporal epilepsy (P=0.01). On the contrary, the need for intracranial exploration was associated with a poorer prognosis (P=0.001). Postoperative number of antiepileptic drugs was significantly lower in the seizure-free group (P=0.001). Neurological adverse event rate after surgery was 21.1% and 11.7% of patients had neuropsychological adverse effects overall transient. CONCLUSIONS: RES is effective procedure in the elderly. Even safe it remains at higher risk of complication and population should be carefully selected. Nevertheless, age should not be considered as a limiting factor, especially when good prognostic factors are identified.

Malformations of cortical development: New surgical advances.

Epilepsy related to malformations of cortical development is frequently drug resistant or requires heavy medication, therefore surgery is key in their management. The role of stereotactic surgery has recently changed the diagnosis and treatment of focal cortical dysplasias (FCD), hypothalamic hamartomas (HH) and periventricular nodular heterotopias (PNH). In HH, radiosurgery using Gammaknife® leads to 60 % of seizure control and is associated with excellent neuropsychological results without significant endocrine function impairment. The seizure control rate is even higher (more than 80 %) with monopolar multiple stereotactic thermocoagulations and Laser interstitial Thermal Therapy (LiTT). While the first technique is associated with a 2 % complications rate (but with excellent neuropsychological outcomes), the latest has up to 22 % side effects in some series. All three of these techniques have encouraging results, but controlled studies are still lacking to provide evidence-based new therapeutic algorithms. With regard to the PNH, surgical management has long been limited by the depth of the lesions and their close anatomical relations with the functional brain connectome. Stereotactic approaches required to perform a SEEG, to locate the part of the PNH responsible for the seizure onset, are later followed by a stereotactic lesioning procedure, therefore doubling the bleeding risk. That is why SEEG-guided radiofrequency-thermocoagulation (SEEG guided-RF-TC), which makes it possible to perform these two steps in a single procedure, was considered as a promising option. A recent meta-analysis confirmed this intuition and reported 38 % of seizure-free patients and 81 % of responders with only 0.3 % of complications, making this approach the first treatment line, followed by LiTT. Among the multiple advances in the FCD identification by non-invasive investigations, a new modality of per-operative diagnostic procedure, the three-dimensional electrocorticography may lead to simplify the preoperative investigation and enhance the accuracy of FCD delineation. Evidence is nevertheless still insufficient to validate this promising concept. Conventional surgical resection has also been concerned by significant conceptual advances during the past few years, in particular with the development of the hodotopic approach, initially in oncologic surgery. Associated with a better understanding of neuroplasticity in epilepsy and the setting up of functional mapping during SEEG or during awake surgery, the possibility of surgical resections grew up. A short-term perspective in this field, when surgical resection remains impossible, would be to target crucial nodes of the epileptic network, distinct from the core functional connectome.

Semiology of insular lobe seizures.

After the early attempts of intra-operative electrocorticography and insulectomy in the 1950s, the notion of insular lobe seizures was largely forgotten for decades. It is only since the late 1990s that the recent technique of stereo-electroencephalography (SEEG) enabled preoperative diagnosis of insular origin seizures and thus gave rise to a renewed interest for this ill-defined electroclinical entity. Owing to the multiple functional roles of insula and its extensive connectivity with adjacent as well as distant brain structures, insular lobe seizures present with a combination or series of diverse subjective and objective symptoms. In this review, we summarize current knowledge on the semiology of insular origin seizures. The following two distinct forms of clinical presentation have been recognized: 1) Seizures with predominant insulo-perisylvian symptoms, most notably paraesthesia and cervico-laryngeal discomfort. The former typically involves a large/bilateral cutaneous territory and can be perceived as cold, hot, or painful sensations. The latter ranges from slight dyspnea to strong sensation of strangulation. Other symptoms include epigastric discomfort/nausea, hypersalivation, auditory, vestibular, gustatory, and aphasic symptoms. 2) Nocturnal hyperkinetic seizures with/without tonic elevation of upper limbs, masquerading as fronto-mesial seizures. Patients are usually not fully aware of their symptoms despite preserved contact and organized behavior to others. Ipsilateral eye blinking can be observed. These two patterns often occur in succession or simultaneously. This characteristic combination and progression of ictal symptoms orients us strongly towards an insular origin of seizure, a better understanding of which is a crucial key to further optimize modern SEEG strategy.

Resective surgery in tuberous Sclerosis complex, from Penfield to 2018: A critical review.

Medically treated patients suffering from tuberous sclerosis complex (TSC) have less than 30% chance of achieving a sustained remission. Both the international TSC consensus conference in 2012, and the panel of European experts in 2012 and 2018 have concluded that surgery should be considered for medically refractory TSC patients. However, surgery remains currently underutilized in TSC. Case series, meta-analyses and guidelines all agree that a 50 to 60% chance of long-term seizure freedom can be achieved after surgery in TSC patients and a presurgical work-up should be done as early as possible after failure of two appropriate AEDs. The presence of infantile spasms, the second most common seizure type in TSC, had initially been a barrier to surgical planning but is now no longer considered a contraindication for surgery in TSC patients. TSC patients undergoing presurgical evaluation range from those with few tubers and good anatomo-electro-clinical correlations to patients with a significant "tuber burden" in whom the limits of the epileptogenic zone is much more difficult to define. Direct surgery is often possible in patients with a good electro-clinical and MRI correlation. For more complex cases, invasive monitoring is often mandatory and bilateral investigations can be necessary. Multiple non-invasive tools have been shown to be helpful in determining the placement of these invasive electrodes and in planning the resection scheme. Additionally, at an individual level, multimodality imaging can assist in identifying the epileptogenic zone. Increased availability of investigations that can be performed without sedation in young and/or cognitively impaired children such as MEG and HR EEG would most probably be of great benefit in the TSC population. Of those selected for invasive EEG, rates of seizure freedom following surgery are close to cases where invasive monitoring is not required, strengthening the important and efficient role of intracranial investigations in drug-resistant TSC associated epilepsy.

Epilepsy surgery: A therapeutic patient education program.

Before the creation of a therapeutic patient education (TPE) program for epilepsy surgery, a needs analysis was conducted with 29 people, including patients (n=13), family members (n=9) and healthcare providers (n=7). Most of them highlighted the psychological difficulties of the surgical process, and the need for considerably more precise information concerning the immediate postoperative period. In addition, several patients and/or family members requested meeting with a patient who had undergone the surgery. The majority of subjects were interested in epilepsy-surgery TPE. These data were important in the creation of our TPE program and, more generally, for the management of these patients.

Epileptic networks in patients with bitemporal epilepsy: the role of SEEG for the selection of good surgical candidates.

OBJECTIVE: In this study we investigated the electrical characteristics of seizures recorded by stereo-EEG (SEEG) in a cohort of patients with bitemporal lobe epilepsy (BTLE), in the attempt to verify the presence/absence of different seizure patterns and to identify good surgical candidates. METHODS: We retrospectively reviewed 14 consecutive patients with medically refractory BTLE confirmed by scalp video-EEG (VEEG) recording of bitemporal independent or non-lateralizing seizure onset. All patients had a comprehensive evaluation including history and neurologic examination, MRI, scalp VEEG and SEEG monitoring. Neuropsychological, Wada testing and FDG-PET were performed in most patients. When temporal lobe resection was performed (7 cases), the postoperative follow-up was of at least 1year. RESULTS: Intracranial EEG (SEEG) revealed that only 4/14 (29%) patients were suffering of unilateral TLE. Two groups of patients with distinct SEEG patterns of seizures were identified: a temporo-mesial origin of seizures was the only SEEG pattern observed in 8 patients (Group 1); in 6 patients seizures originated from multiple onset zones in mesial and lateral temporal cortex or from extra-temporal cortex (Group 2). All patients of group 1 (except one who refused surgery) underwent surgery and had a favorable outcome (6 Engel class I; one Engel's class II). The side of surgery was not necessarily the one responsible for the majority of recorded seizures. It was chosen on the basis of MRI findings and consistency of data from presurgical functional investigations, mostly memory assessment and Wada test. SIGNIFICANCE: In patients with suspected BTLE, SEEG proved to be useful in identifying the origin of seizures. Good surgical outcome can be obtained after unilateral resection in patients with bilateral independent seizure onsets or sequential mesial temporal involvement on SEEG if the side of surgery is chosen considering multimodal data.

Evoked potential study of hippocampal efferent projections in the human brain.

OBJECTIVE: To explore in human potential hippocampal projections within and outside the temporal lobe. METHODS: We performed intra-cerebral electrical stimulations in seven patients investigated by depth electrodes for refractory epilepsy and analyzed the presence of evoked potentials (EPs) in all brain regions explored. Bipolar electrical stimulations, consisting of two series of 25 pulses of 1 ms duration, 0.2 Hz frequency, and 3 mA intensity, were delivered in a total of 36 hippocampal stimulations sites. RESULTS: Reproducible EPs were recorded in several brain regions with variable latencies, amplitudes and morphologies. Within the temporal lobe, EPs were present in the amygdala, entorhinal cortex, temporal pole and temporal neocortex. EPs were also observed in the frontal lobe, anterior cingulate gyrus and orbito-frontal cortex, midcingulate and posterior cingulate gyrus, insula and thalamic pulvinar nucleus. CONCLUSION: Our results demonstrate a large distribution of direct or indirect hippocampal projections. SIGNIFICANCE: This widespread connectivity supports the previous definition of different networks involved mainly in memory and behavioral processes, implicating the temporal lobe, the cingulate gyrus or the prefrontal region. Our data provide some clues to further evaluate potential pathways of propagation of mesial temporal lobe seizure, via the insula or the pulvinar nucleus.

SEEG-guided RF-thermocoagulation of epileptic foci: a therapeutic alternative for drug-resistant non-operable partial epilepsies.

BACKGROUND: Previous literature includes numerous reports of acute stereotactic ablation for epilepsy. Most reports focus on amygdalotomies or amygdalohippocampotomies, some others focus on various extra-limbic targets. These stereotactic techniques proved to have a less favourable outcome than that of standard surgery, so that their rather disappointing benefit/risk ratio explains why they have been largely abandoned. However, depth electrode recordings may be required in some cases of epilepsy surgery to delineate the best region of cortical resection. We usually implant depth electrodes according to Talairach's stereo electroencephalography (SEEG) methodology. Using these chronically implanted depth electrodes, we are able to perform radiofrequency (RF)-thermolesions of the epileptic foci. This paper reports the technical data required to perform such multiple cortical thermolesions, as well as the results in terms of seizure outcome in a group of 41 patients. TECHNICAL DATA: Lesions are placed in the cortex areas showing either a low amplitude fast pattern or spike-wave discharges at the onset of the seizures. Interictal paroxysmal activities are not considered for planning thermocoagulation sites. All targets are first functionally evaluated using electrical stimulation. Only those showing no clinical response to stimulation are selected for thermolesion, including sites located inside or near primary functional area. Lesions are performed using 120mA bipolar current (50 V), applied for 10-30 sec. Each thermocoagulation produces a 5-7mm diameter cortical lesion. A total of 2-31 lesions were performed in each of the 41 patients. Lesions are placed without anaesthesia. RESULTS: 20 patients (48.7%) experienced a seizure frequency decrease of at least 50% that was more than 80% in eight of them. One patient was seizure free after RF thermocoagulation. In 21 patients, no significant reduction of the seizure frequency was observed. Amongst the characteristics of the disease (age and sex of the patient, lobar localization of the EZ) and the characteristics of the thermocoagulations (topography, lateralization, number, morphology of the lesions on MRI) no factor was significantly linked to the outcome. However, the best results were clearly observed in epilepsies symptomatic of a cortical development malformation (CDM), with 67% of responders in this group of 20 patients (p = 0.052). Three transient post-procedure side-effects, consisting of paraesthetic sensations in the mouth (2 cases), and mild apraxia of the hand, were observed. CONCLUSION: SEEG-guided-RF-thermolesioning is a safe technique. Our results indicate that such lesions can lead to a significant reduction of seizure frequency. Our experience suggests that SEEG-guided RF thermocoagulation should be dedicated to drug-resistant epileptic patients for whom conventional resection surgery is risky or contra-indicated on the basis of invasive pre-surgical evaluation, particularly those suffering from epilepsy symptomatic of cortical development malformation.

Multiple sclerosis and epileptic seizures.

BACKGROUND: The association between epilepsy and multiple sclerosis (MS) is not a coincidence. OBJECTIVE: Our objective was to compare MS patients with or without history of seizures. METHODS: In a population of 5041 MS patients, we identified 102 (2%) patients with epileptic seizures. In 67 patients (1.3%), epileptic seizure could not be explained by any cause other than MS. RESULTS: In these 67 patients, the median age at occurrence of the first epileptic seizure was 33 years. Epilepsy was the initial clinical manifestation of MS in seven patients. In total, 62 patients (92.5%) presented only one or a few seizures, and 18 patients (27%) presented at least one episode of status epilepticus, fatal in two. Compared with MS patients without epilepsy, there was no difference in gender, type of MS course and time from onset of MS to the progressive phase. Conversely, the median age at MS onset was earlier (25.0 years vs. 30, p < 0.0001) and there was a trend for a shorter time from MS onset to non-reversible disability. CONCLUSIONS: Our study confirms an increased risk of epileptic seizures in MS patients. It underlines that seizures may be the first observable symptom in MS and the frequency and seriousness of status epilepticus.

Stenting of a cerebral venous thrombosis.

Cerebral venous and sinus thrombosis (CVT) is a rare but potentially alarming condition, which remains a diagnostic and therapeutic challenge. Endovascular procedure may be a therapeutic option when evolution is unfavourable despite medical treatment, but the use of stenting is rarely reported in CVT treatment. We report the case of a man who presented a jugular vein thrombosis responsible for severe intracranial hypertension. Because of clinical worsening despite intravenous heparin and symptomatic treatment, endovascular procedure including the placement of five venous stents, thrombolysis and balloon angioplasty, was performed and led to venous recanalization with successful clinical outcome. The patient is still asymptomatic 3 years later. Our report shows that venous stenting could represent an efficient alternative in the management of decoagulation refractory CVT.

Reciprocal thalamocortical connectivity of the medial pulvinar: a depth stimulation and evoked potential study in human brain.

The thalamic medial pulvinar nucleus (PuM) is fully developed only in primates and reaches its greatest extent in humans. To assess the reciprocal functional connectivity between PuM and cortex, we studied intracerebral-evoked responses obtained after PuM and cortical electrical stimulation in 7 epileptic patients undergoing depth electroencephalographic recordings. Cortical-evoked potentials (CEPs) to PuM stimulation were recorded from all explored cortical regions, except striate cortex, anterior cingulated, and postcentral gyrus. Percentages of cortical contacts pairs responding to PuM stimulation (CEPs response rate) ranged from 80% in temporal neocortex, temporoparietal (TP) junction, insula, and frontoparietal opercular cortex to 34% in mesial temporal regions. Reciprocally, PuM-evoked potentials (PEPs) response rates were 14% after cortical stimulation in insula and frontoparietal opercular cortex, 67% in the TP junction, 76% in temporal neocortex, and 80% in mesial temporal regions. Overall, our study of functional PuM connectivity in the human brain converges with most of the data from anatomical studies in monkeys, except for a strong amygdalohippocampal functional projection to PuM and an unexpected imbalance between some of the reciprocal pathways explored. This functional quantitative approach helps to clarify the functional role of PuM as well as its implication in temporal lobe epileptic seizures.

SEEG-guided thermocoagulations: a palliative treatment of nonoperable partial epilepsies.

OBJECTIVE: Intracranial stereotactic EEG recordings (SEEG) in presurgical epilepsy assessment are currently carried out in our department. The SEEG method generally used for exploration can also be used to perform radiofrequency thermocoagulations (RFTC) of the epileptic foci. To assess the indications of the RFTC procedure in the therapeutic arsenal of drug-resistant epilepsies, we report the results obtained in 41 patients to whom RFTC was proposed as a first therapeutic step before surgery or as a palliative treatment when surgery was not possible. METHODS: RFTC were produced by applying a 50-volt, 110 mA current, during 10-30 seconds within the epileptogenic zone, as identified by the SEEG investigation. Two to 31 RFTC (mean, 12) were performed per patient. The median follow-up was 19 months (range: 4 to 72). RESULTS: Twenty patients (48.7%) experienced a seizure frequency decrease of at least 50%, which was over 80% in eight of them. One patient was seizure-free. The tolerance was excellent. A total of 67% of the 21 patients presenting a cortical development malformation benefited from RFTC (p = 0.052). In the group of noneligible patients for resective surgery (n = 13), six were responders to SEEG-guided RFTC and one of them was seizure-free. CONCLUSIONS: This study suggests that stereotactic EEG-guided radiofrequency thermocoagulations can be proposed only as a palliative procedure, able to bring a substantial improvement of seizure frequency, to drug-resistant patients with epilepsy for whom conventional resection surgery is risky or contraindicated on the basis of invasive presurgical evaluation.

Acute neurological deterioration in ovarioleukodystrophy related to EIF2B mutations: pregnancy with oocyte donation is a potentially precipitating factor.

Mutations in the eukaryotic translation initiation factor 2B (eIF2B) represent a heterogenous group of autosomal recessive leucodystrophy characterized by a diffuse CSF-like aspect of the white matter at MRI designed as vanishing white matter (VWM) and episodes of acute deterioration after stresses. The mild juvenile and adult forms are often associated with primary ovarian failure, a syndrome referred to as ovarioleukodystrophy (OLD). We reported case of a woman with OLD who successfully underwent in vitro fertilization with donated oocytes and embryo transfer. Pregnancy was complicated by a non-convulsive epileptic status leading to the identification of compound heterozygous EIF2B5 mutation (p.Arg113His and p.Arg299His). The patient gave birth to a healthy child by Caesarean section. In conclusion, we report for the first time that in vitro fertilization and embryo transfer can lead to a successful procreation in patients with OLD related to EIF2B mutations. However this procedure must be considered with cautiousness, because of its potential neurological risks.

[Long-term outcome in patients with symptomatic low-grade oligodendrogliomatous tumors treated by cytotoxic agents]. / Effets à long terme de la chimiothérapie chez 7 patients présentant un gliome de bas grade symptomatique.

INTRODUCTION: Whether aggressive treatment or no treatment is the optimal management for low-grade gliomas is controversial. However, symptomatic low-grade gliomas require prompt therapeutic intervention because of neurological impairment, uncontrolled seizures, and deterioration of life quality. METHODS: We report the long-term follow-up, 71 months, of seven patients treated by procarbazine, lomustine and vincristine (PCV) therapy for a symptomatic low-grade oligodendrogliomatous tumor. The mean age at diagnosis was 47 years, the mean time from first symptoms to initiation of PCV therapy was 62 months (range 15-147). RESULTS: All patients initially responded favorably, with improvement of the neurological symptoms and radiological response. Chemotherapy was clinically well tolerated, the main side effect being low hematological toxicity. During the follow-up, no progression was observed in two patients. For the five remaining patients, the time to progression after the PCV induction was 56+/-12 months (range 38 to 73). Four of these patients showed favorable response to a second line of treatment. CONCLUSION: PCV therapy is an interesting therapeutic option for progressively symptomatic low-grade gliomas, even in cases with large tumoral volume. This treatment, of moderate toxicity, improves the quality of life and can result in long-term tumor stabilization.

Hippocampal-orbitofrontal connectivity in human: an electrical stimulation study.

OBJECTIVE: The identification of the pathways involved in seizure propagation remains poorly understood in humans. For instance, the respective role of the orbitofrontal cortex (OFC) and of the commissural pathways in the interhemispheric propagation of mesial temporal lobe seizures (mTLS) is a matter of debate. In order to address this issue, we have directly tested the functional connectivity between the hippocampus and the OFC in 3 epileptic patients undergoing an intra-cranial stereotactic EEG investigation. METHODS: Bipolar electrical stimulations, consisting of two series of 25 pulses of 1 ms duration, 0.2 Hz frequency, and 3 mA intensity, were delivered in the hippocampus. Evoked potentials (EPs) were analysed for each series, separately. Grand average of reproducible EPs was then used to calculate latency of the first peak of each individual potential. RESULTS: Hippocampal stimulations evoked reproducible responses in the OFC in all 3 patients, with a mean latency of the first peak of 222 ms (range: 185-258 ms). CONCLUSIONS: Our data confirm a functional connectivity between the hippocampus and the OFC in human. SIGNIFICANCE: This connectivity supports the potential role of the OFC in the propagation of mTLS.

Intracranial EEG study of seizure-associated nose wiping.

The authors studied the relation between seizure-associated nose wiping (NW) and intracerebral EEG data in 32 patients. NW was more frequent in mesial temporal lobe seizures (TLSs; 65%) than in other TLSs (36%; p < 0.05) and in frontal lobe seizures (3%; p < 0.0001). It was associated with the presence of an amygdala discharge at seizure onset (p < 0.05) and with the recording of an ictal low-voltage fast activity within that structure (p < 0.05), supporting the role of an amygdala dysfunction in the pathophysiology of NW.

[Necrosis of a hypophyseal adenoma and ischemic cerebral vascular accident ]. / Nécrose d'un adénome hypophysaire et accident vasculaire cérébral ischémique.

A 78-year old man developed an acute intracranial hypertension followed by central left facial palsy. CT Scan and MRI revealed an ischemia within the right lenticulostriate arteries territory and a hemorrhagic infarction of a pituitary adenoma without extrinsic carotid artery compression. Neuroophthalmologic examination and hormonal screening were normal. Though pituitary apoplexy and stroke might represent a fortuitous association, several mechanisms underlying such clinical picture are advanced.