Spinal cord tractography and neuromonitoring-based surgical strategy for intramedullary ependymoma.

Because the spinal cord contains a rich concentration of longitudinal and transversal fibers in a very small area, intramedullary surgery could result in a high likelihood of morbidity. In this video, the authors demonstrate the microsurgical technique and surgical skills used to perform excision of an intramedullary ependyma. The authors also present tools (electrophysiology and neuroimaging) that are useful for surgical decision-making and planning, and thus are used intraoperatively, that allow safer and more effective resection of an intramedullary tumor.

Safety and efficacy of prophylactic levetiracetam for prevention of epileptic seizures in the acute phase of intracerebral haemorrhage (PEACH): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: The incidence of early seizures (occurring within 7 days of stroke onset) after intracerebral haemorrhage reaches 30% when subclinical seizures are diagnosed by continuous EEG. Early seizures might be associated with haematoma expansion and worse neurological outcomes. Current guidelines do not recommend prophylactic antiseizure treatment in this setting. We aimed to assess whether prophylactic levetiracetam would reduce the risk of acute seizures in patients with intracerebral haemorrhage. METHODS: The double-blind, randomised, placebo-controlled, phase 3 PEACH trial was conducted at three stroke units in France. Patients (aged 18 years or older) who presented with a non-traumatic intracerebral haemorrhage within 24 h after onset were randomly assigned (1:1) to levetiracetam (intravenous 500 mg every 12 h) or matching placebo. Randomisation was done with a web-based system and stratified by centre and National Institutes of Health Stroke Scale (NIHSS) score at baseline. Treatment was continued for 6 weeks. Continuous EEG was started within 24 h after inclusion and recorded over 48 h. The primary endpoint was the occurrence of at least one clinical seizure within 72 h of inclusion or at least one electrographic seizure recorded on continuous EEG, analysed in the modified intention-to-treat population, which comprised all patients who were randomly assigned to treatment and who had a continuous EEG performed. This trial was registered at ClinicalTrials.gov, NCT02631759, and is now closed. Recruitment was prematurely stopped after 48% of the recruitment target was reached due to a low recruitment rate and cessation of funding. FINDINGS: Between June 1, 2017, and April 14, 2020, 50 patients with mild-to-moderate severity intracerebral haemorrhage were included: 24 were assigned to levetiracetam and 26 to placebo. During the first 72 h, a clinical or electrographic seizure was observed in three (16%) of 19 patients in the levetiracetam group versus ten (43%) of 23 patients in the placebo group (odds ratio 0·16, 95% CI 0·03-0·94, p=0·043). All seizures in the first 72 h were electrographic seizures only. No difference in depression or anxiety reporting was observed between the groups at 1 month or 3 months. Depression was recorded in three (13%) patients who received levetiracetam versus four (15%) patients who received placebo, and anxiety was reported for two (8%) patients versus one (4%) patient. The most common treatment-emergent adverse events in the levetiracetam group versus the placebo group were headache (nine [39%] vs six [24%]), pain (three [13%] vs ten [40%]), and falls (seven [30%] vs four [16%]). The most frequent serious adverse events were neurological deterioration due to the intracerebral haemorrhage (one [4%] vs four [16%]) and severe pneumonia (two [9%] vs two [8%]). No treatment-related death was reported in either group. INTERPRETATION: Levetiracetam might be effective in preventing acute seizures in intracerebral haemorrhage. Larger studies are needed to determine whether seizure prophylaxis improves functional outcome in patients with intracerebral haemorrhage. FUNDING: French Ministry of Health.

Peri-ictal hypoxemia during temporal lobe seizures: A SEEG study.

Focal seizures originating from the temporal lobe are commonly associated with peri-ictal hypoxemia (PIH). During the course of temporal lobe seizures, epileptic discharges often not only spread within various parts of the temporal lobe but also possibly insula and frontal lobe. The link between spatial propagation of the seizure discharges and PIH is still unclear. The present study investigates the involvement of several brain structures including medial temporal structures, temporal pole, anterior insula, and frontal cortex in the occurrence of PIH. Using quantitative indices obtained during SEEG (stereoencephalography) recordings in 38 patients, we evaluated the epileptogenicity, the spatial propagation, and functional connectivity between those structures during seizures leading to PIH. Multivariate statistical analyses of SEEG quantitative indices showed that temporal lobe seizures leading to PIH are characterized by a strong involvement of amygdala and anterior insula during seizure propagation and a more widespread involvement of medial temporal lobe structures, lateral temporal lobe, temporal pole, and anterior cingulate at the end of the seizures. On the contrary, seizure-onset zone was not associated with PIH occurrence. During seizure propagation, anterior insula, temporal pole, and temporal lateral neocortex activities were correlated with intensity of PIH. Lastly, PIH occurrence was also related to a widespread increase of synchrony between those structures. Those results suggest that PIH occurrence during temporal lobe seizures may be related to the activation of a widespread network of cortical structures, among which amygdala and anterior insula are key nodes.

Predictors of functional outcome after spinal cord surgery: Relevance of intraoperative neurophysiological monitoring combined with preoperative neurophysiological and MRI assessments.

OBJECTIVES: To assess the accuracy of intraoperative neurophysiological monitoring (IONM) in predicting immediate and 3-month postoperative neurological new deficit (or deterioration) in patients benefiting from spinal cord (SC) surgery; and to identify factors associated with a higher risk of postoperative clinical worsening. METHODS: Consecutive patients who underwent SC surgery with IONM were included. Pre and postoperative clinical (modified McCormick scale), radiological (lesion-occupying area ratio), and electrophysiological features were collected. RESULTS: A total of 99 patients were included: 14 (14.1%) underwent extradural surgery, 50 (50.5%) intradural extramedullary surgery, and 35 (35.4%) intramedullary surgery. Cumulatively, multimodal IONM (motor and somatosensory evoked potentials, D-wave whenever possible) significantly predicted postoperative deficits (p<0.001), with a sensitivity, specificity, positive predictive value, and negative predictive value of 0.81, 0.93, 0.83, and 0.92, respectively. Sixty (60.6%) patients displayed no IONM change, whereas 39 (39.4%) displayed IONM worsening. In multivariate analysis, predictors for postoperative clinical worsening were: abnormal preoperative electrophysiological assessment (p=0.03), intramedullary tumor (p<0.001), lesion-occupying area ratio ≥0.7 (p<0.001), and IONM alterations (p<0.001). Three months after the surgical procedure, in patients presenting at least one of the risk factors described above, 45/81 (55.6%) and 19/81 (23.5%) were clinically and electrophysiologically improved, respectively; while 13/81 (16.0%) and 10/81 (12.3%) were clinically and electrophysiologically worsened. CONCLUSION: Multimodal IONM is an essential tool to guide SC surgery, and enables the accurate prediction of postoperative neurological outcome. Specific attention should be given to patients presenting with preoperative electrophysiological abnormalities, large tumor volume, and intramedullary tumor location.

Functional connectivity and epileptogenicity of nodular heterotopias: A single-pulse stimulation study.

OBJECTIVE: Nodular heterotopias (NHs) are malformations of cortical development associated with drug-resistant focal epilepsy with frequent poor surgical outcome. The epileptogenic network is complex and can involve the nodule, the overlying cortex, or both. Single-pulse electrical stimulation (SPES) during stereo-electroencephalography (SEEG) allows the investigation of functional connectivity between the stimulated and responsive cortices by eliciting cortico-cortical evoked potentials (CCEPs). We used SPES to analyze the NH connectome and its relation to the epileptogenic network organization. METHODS: We retrospectively studied 12 patients with NH who underwent 1 Hz or 0.2 Hz SPES of NH during SEEG. Outbound connectivity (regions where CCEPs were elicited by NH stimulation) and inbound connectivity (regions where stimulation elicited CCEPs in the NH) were searched. SEEG channels were then classified as "heterotopic" (located within the NH), "connected" (located in normotopic cortex and showing connectivity with the NH), and "unconnected." We used the epileptogenicity index (EI) to quantify implication of channels in the seizure-onset zone and to classify seizures as heterotopic, normotopic, and normo-heterotopic. RESULTS: One hundred thirty-five outbound and 72 inbound connections were found. Three patients showed connectivity between hippocampus and NH, and seven patients showed strong internodular connectivity. A total of 39 seizures were analyzed: 23 normo-heterotopic, 12 normotopic, and 4 heterotopic. Logistic regression found that "connected" channels were significantly (p = 8.4e-05) more likely to be epileptogenic than "unconnected" channels (odds ratio 4.71, 95% confidence interval (CI) [2.17, 10.21]) and heterotopic channels were also significantly (p = .024) more epileptogenic than "unconnected" channels (odds ratio 3.29, 95% CI [1.17, 9.23]). SIGNIFICANCE: SPES reveals widespread connectivity between NH and normotopic regions. Those connected regions show higher epileptogenicity. SPES might be useful to assess NH epileptogenic network.

Coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy.

OBJECTIVE: To assess the relation between coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy. METHODS: Cross-sectional analysis of data collected in the SAVE study, which included patients with drug-resistant focal epilepsy during long-term EEG monitoring. Patients in whom both coffee consumption and data about seizure frequency, including focal to bilateral tonic-clonic seizures (FBTCS), were available were selected. Coffee consumption was collected using a standardized self-report questionnaire and classified into four groups: none, rare (from less than 1 cup/week to up 3 cups/week), moderate (from 4 cups/week to 3 cups/day), and high (more than 4 cups/day). RESULTS: Six hundred and nineteen patients were included. There was no relation between coffee consumption and total seizure frequency (p = 0.902). In contrast, the number of FBTCS reported over the past year was significantly associated with usual coffee consumption (p = 0.029). Specifically, number of FBCTS in patients who reported moderate coffee consumption was lower than in others. In comparison with patients with moderate coffee consumption, the odds ratio (95%CI) for reporting at least 1 FBTCS per year was 1.6 (1.03-2.49) in patients who never take coffee, 1.62 (1.02-2.57) in those with rare consumption and 2.05 (1.24-3.4) in those with high consumption. Multiple ordinal logistic regression showed a trend toward an association between coffee consumption and number of FBTCS (p = 0.08). CONCLUSIONS AND RELEVANCE: Our data suggest that effect of coffee consumption on seizures might depend on dose with potential benefits on FBTCS frequency at moderate doses. These results will have to be confirmed by prospective studies.

Medicine consumptions and occupational road risk.

BACKGROUND: Whereas an increased risk of road traffic crashes has been highlighted as linked to some medicine consumptions, there is no available data on this risk according to the type of journey (private, commuting or mission). Drivers on occupational journey (commuting or mission) are likely to have different coping behaviors related to the use of medicines than drivers on private journey. The aim of our study was to investigate the association between exposure to ten classes of medicines and the risk of being responsible for a road traffic crash according to the type of journey (private, commuting or mission). METHODS: The data used came from three French national databases: the national police database of injurious crashes, the police reports and the national health care insurance database. A total of 179,269 drivers aged between 18 and 65 years old involved in an injurious crash in France between July 2005 and December 2015 were included in the analyses. Logistic regression models stratified by journey were used to estimate the Odds Ratios (OR) and 95 % confidence intervals (95 % CI), adjusted for potential confounding factors. RESULTS: Medicines exposure levels were generally lower for drivers during occupational journeys, the risk of being responsible for a road traffic crash seems to be higher on commuting or mission journeys than on private journeys for four medicines. Indeed, for antiepileptics the OR was 1.59 [1.01-2.51] for mission journeys, 1.63 [1.24-2.15] for commuting journeys, and 1.47 [1.25-1.73] for private journey. For psycholeptics the OR was 1.02 [0.80-1.28] for mission journey, 1.19 [1.03-1.39] for commuting and 1.17 [1.08-1.26] for private journey. For psychoanaleptics OR was 1.35 [1.02-1.78] for mission journeys, 1.37 [1.17-1.60] for commuting journeys and 1.26 [1.14-1.40] for private journeys. Finally, for other nervous system drugs OR reached 2.04 [1.35-3.07] for mission journeys compared to 1.43 [1.21-1.70] for private journeys. CONCLUSION: Our results encourage the implementation of preventive measures about some treatments and diseases in the context of occupational journeys.

Effective accuracy of stereoelectroencephalography: robotic 3D versus Talairach orthogonal approaches.

OBJECTIVE: Stereoelectroencephalography (SEEG) was first developed in the 1950s by Jean Talairach using 2D angiography and a frame-based, orthogonal approach through a metallic grid. Since then, various other frame-based and frameless techniques have been described. In this study the authors sought to compare the traditional orthogonal Talairach 2D angiographic approach with a frame-based 3D robotic procedure that included 3D angiographic interoperative imaging guidance. MRI was used for both procedures during surgery, but MRI preplanning was done only in the robotic 3D technique. METHODS: All study patients suffered from drug-resistant focal epilepsy and were treated at the same center by the same neurosurgical team. Fifty patients who underwent the 3D robotic procedure were compared to the same number of historical controls who had previously been successfully treated with the Talairach orthogonal procedure. The effectiveness and absolute accuracy, as well as safety, of the two procedures were compared. Moreover, in the 3D robotic group, the reliability of the preoperative MRI to avoid vascular structures was evaluated by studying the rate of trajectory modification following the coregistration of the intraoperative 3D angiographic data onto the preoperative MRI-based trajectory plans. RESULTS: Effective accuracy (96.5% vs 13.7%) and absolute accuracy (1.15 mm vs 4.00 mm) were significantly higher in the 3D robotic group than in the Talairach orthogonal group. Both procedures showed excellent safety results (no major complications). The rate of electrode modification after 3D angiography was 43.8%, and it was highest for frontal and insular locations. CONCLUSIONS: The frame-based, 3D angiographic, robotic procedure described here provided better accuracy for SEEG implantations than the traditional Talairach approach. This study also highlights the potential safety advantage of trajectory planning using intraoperative frame-based 3D angiography over preoperative MRI alone.

SEEG-guided radiofrequency coagulation (SEEG-guided RF-TC) versus anterior temporal lobectomy (ATL) in temporal lobe epilepsy.

BACKGROUND: Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) is a super-selective procedure. Hippocampus has a limited volume and is widely accessible to SEEG so that SEEG-guided RF-TC could be an alternative to the anterior temporal lobectomy (ATL) in case of temporal lobe epilepsy (TLE) syndrome. OBJECTIVE: To compare seizure-free rate at 1-year follow-up between patients undergoing SEEG-guided RF-TC and patients undergoing ATL in TLE over a 15-year period. METHODS: All patients had a drug-resistant epilepsy and underwent SEEG after non-conclusive phase I investigations suspecting a TLE. Two groups were selected according to the procedure which the patients underwent (ATL or SEEG-guided RF-TC); TLE had to be confirmed by SEEG in the two groups. The primary outcome was seizure freedom at 1 year. The secondary outcome was response (at least 50% reduction of seizure frequency) at 1 year. In case of persistent seizures after SEEG-guided RF-TC, ATL was performed. RESULTS: A total of 21 patients underwent SEEG-guided RF-TC and 49 ATL. At 12 months, none of the patients of the SEEG-guide RF-TC group was seizure free, while 37 (75.5%) in the ATL group were so (p < 0.001). Ten patients (47.6%) were responders after 12 months of follow-up after SEEG-guided RF-TC; all patients in the ATL group who were seizure free were responders. CONCLUSION: SEEG-guided RF-TC is not as effective as ATL in TLE. As no memory impairment following SEEG-guided RF-TC was found, patients with dominant mesial involvement for whom hippocampectomy is not an option could benefit from the technique.

Recommendations for the use of electroencephalography and evoked potentials in comatose patients.

Predicting the outcome of a comatose or poorly responsive patient is a major issue for intensive care unit teams, in order to give the most accurate information to the family and to choose the best therapeutic option. However, determining the level of cortical activity in patients with disorders of consciousness is a real challenge. Reliable criteria are required to help clinicians in the decision-making process, especially in the acute phase of coma. In this paper, we propose recommendations for recording and interpreting electroencephalography and evoked potentials in comatose patients based on the literature and the clinical experience of a group of neurophysiologists trained in the management of comatose patients. We propose methodological guidelines and discuss prognostic value of each test as well as the limitations concerning recording and interpretation. Recommendations for the strategy and timing of neurophysiological assessments are also proposed according to various clinical situations.

Epileptogenic networks in nodular heterotopia: A stereoelectroencephalography study.

OBJECTIVE: Defining the roles of heterotopic and normotopic cortex in the epileptogenic networks in patients with nodular heterotopia is challenging. To elucidate this issue, we compared heterotopic and normotopic cortex using quantitative signal analysis on stereoelectroencephalography (SEEG) recordings. METHODS: Clinically relevant biomarkers of epileptogenicity during ictal (epileptogenicity index; EI) and interictal recordings (high-frequency oscillation and spike) were evaluated in 19 patients undergoing SEEG. These biomarkers were then compared between heterotopic cortex and neocortical regions. Seizures were classified as normotopic, heterotopic, or normoheterotopic according to respective values of quantitative analysis (EI ≥0.3). RESULTS: A total of 1,246 contacts were analyzed: 259 in heterotopic tissue (heterotopic cortex), 873 in neocortex in the same lobe of the lesion (local neocortex), and 114 in neocortex distant from the lesion (distant neocortex). No significant difference in EI values, high-frequency oscillations, and spike rate was found comparing local neocortex and heterotopic cortex at a patient level, but local neocortex appears more epileptogenic (p < 0.001) than heterotopic cortex analyzing EI values at a seizure level. According to EI values, seizures were mostly normotopic (48.5%) or normoheterotopic (45.5%); only 6% were purely heterotopic. A good long-term treatment response was obtained in only two patients after thermocoagulation and surgical disconnection. SIGNIFICANCE: This is the first quantitative SEEG study providing insight into the mechanisms generating seizures in nodular heterotopia. We demonstrate that both the heterotopic lesion and particularly the normotopic cortex are involved in the epileptogenic network. This could open new perspectives on multitarget treatments, other than resective surgery, aimed at modifying the epileptic network.

Neural Activity Elicited by a Cognitive Task can be Detected in Single-Trials with Simultaneous Intracerebral EEG-fMRI Recordings.

Recent studies have shown that it is feasible to record simultaneously intracerebral EEG (icEEG) and functional magnetic resonance imaging (fMRI) in patients with epilepsy. While it has mainly been used to explore the hemodynamic changes associated with epileptic spikes, this approach could also provide new insight into human cognition. However, the first step is to ensure that cognitive EEG components, that have lower amplitudes than epileptic spikes, can be appropriately detected under fMRI. We compared the high frequency activities (HFA, 50-150[Formula: see text]Hz) elicited by a reading task in icEEG-only and subsequent icEEG-fMRI in the same patients ([Formula: see text]), implanted with depth electrodes. Comparable responses were obtained, with 71% of the recording sites that responded during the icEEG-only session also responding during the icEEG-fMRI session. For all the remaining sites, nearby clusters (distant of 7[Formula: see text]mm or less) also demonstrated significant HFA increase during the icEEG-fMRI session. Significant HFA increases were also observable at the single-trial level in icEEG-fMRI recordings. Our results show that low-amplitude icEEG signal components such as cognitive-induced HFAs can be reliably recorded with simultaneous fMRI. This paves the way for the use of icEEG-fMRI to address various fundamental and clinical issues, notably the identification of the neural correlates of the BOLD signal.

Efficacy of naloxone in reducing postictal central respiratory dysfunction in patients with epilepsy: study protocol for a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Generalized tonic-clonic seizures (GTCSs) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Experimental and clinical data strongly suggest that the majority of SUDEP results from a postictal respiratory dysfunction progressing to terminal apnea. Postictal apnea could partly derive from a seizure-induced massive release of endogenous opioids. The main objective of this study is to evaluate the efficacy of an opioid antagonist, naloxone, administered in the immediate aftermath of a GTCS, in reducing the severity of the postictal central respiratory dysfunction. METHODS/DESIGN: The Efficacy of Naloxone in Reducing Postictal Central Respiratory Dysfunction in Patients with Epilepsy (ENALEPSY) study is a multicenter, double-blind, randomized, placebo-controlled trial conducted in patients with drug-resistant focal epilepsy who are undergoing long-term video-electroencephalogram (EEG) monitoring (LTM) in an epilepsy monitoring unit (EMU). We plan to randomize 166 patients (1:1) to receive intravenous naloxone (0.4 mg) or placebo in the immediate aftermath of a GTCS. Because inclusion in the study needs to take place prior to the occurrence of the GTCS, and because such occurrence is observed in about one-fourth of patients undergoing LTM, we plan to include a maximum of 700 patients upon admission in the EMU. The primary endpoint will be the proportion of patients whose oxygen saturation is <90 % between 1 and 3 min after the end of a GTCS. Secondary outcomes will include the following: the proportion of patients who show postictal apnea, the occurrence and duration of postictal generalized EEG suppression, the total duration of the postictal coma, postictal pain, and the number of patients who have a second GTCS within 120 min after the intravenous injection. DISCUSSION: The demonstration of naloxone's efficacy on the severity of postictal hypoxemia will have two primary consequences. First, naloxone would be the first and only therapeutic approach that could be delivered immediately to reverse postictal apnea. Second, demonstration that an opioid antagonist can effectively reduce postictal apnea would pave the way for an assessment of a preventive therapy for SUDEP targeting the same pathophysiological pathway using oral administration of naltrexone. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02332447 . Registered on 5 January 2015.

Cortico-cortical and motor evoked potentials to single and paired-pulse stimuli: An exploratory transcranial magnetic and intracranial electric brain stimulation study.

BACKGROUND: Paired-pulse (PP) paradigms are commonly employed to assess in vivo cortical excitability using transcranial magnetic stimulation (TMS) to stimulate the primary motor cortex and modulate the induced motor evoked potential (MEP). Single-pulse cortical direct electrical stimulation (DES) during intracerebral EEG monitoring allows the investigation of brain connectivity by eliciting cortico-cortical evoked potentials (CCEPs). However, PP paradigm using intracerebral DES has rarely been reported and has never been previously compared with TMS. OBJECTIVE: The work was intended (i) to verify that the well-established modulations of MEPs following PP TMS remain similar using DES in the motor cortex, and (ii) to evaluate if a similar pattern could be observed in distant cortico-cortical connections through modulations of CCEP. METHODS: Three patients undergoing intracerebral EEG monitoring with electrodes implanted in the central region were studied. Single-pulse DES (1-3 mA, 1 ms, 0.2 Hz) and PP DES using six interstimulus intervals (5, 15, 30, 50, 100, and 200 ms) in the motor cortex with concomitant recording of CCEPs and MEPs in contralateral muscles were performed. Finally, a navigated PP TMS session targeted the intracranial stimulation site to record TMS-induced MEPs in two patients. RESULTS: MEP modulations elicited by PP intracerebral DES proved similar among the three patients and to those obtained by PP TMS. CCEP modulations elicited by PP intracerebral DES usually showed a pattern comparable to that of MEP, although a different pattern could be observed occasionally. CONCLUSION: PP intracerebral DES seems to involve excitatory and inhibitory mechanisms similar to PP TMS and allows the recording of intracortical inhibition and facilitation modulation on cortico-cortical connections. Hum Brain Mapp 37:3767-3778, 2016. © 2016 Wiley Periodicals, Inc.

Long-lasting seizure-related anxiety in patients with temporal lobe epilepsy and comorbid psychiatric disorders.

Ictal anxiety is a frequent epileptic symptom; it is usually brief, associated with objective clinical signs, and is not positively influenced by external factors, in contrast to psychiatric disorders. These criteria can, however, be misleading, especially in patients with psychiatric comorbidities. We report two patients with a history of drug-resistant right temporal lobe epilepsy, who developed long-lasting psychiatric symptoms, suggestive of exacerbation of their comorbid anxiety disorder. However, intracranial EEG data and [(18)F] FDG-PET suggested that these symptoms were related to seizure activity, highlighting the difficulties in differentiating ictal symptoms from psychiatric episodes in some patients with epilepsy and comorbid psychiatric disorders. [Published with video sequence].