Stereoelectroencephalography Implantation Using Frameless Neuronavigation and Varioguide: Prospective Analysis of Accuracy and Safety in a Case Series of 11 Patients.

BACKGROUND: Stereoencephalography (SEEG) is becoming a widespread diagnostic procedure for drug-resistant epilepsy investigation. Techniques include frame-based and robot-assisted implantation, and more recently, frameless neuronavigated systems (FNSs). Despite its recent use, the accuracy and safety of FNS are still under investigation. OBJECTIVE: To assess in a prospective study the accuracy and safety of a specific FNS use for SEEG implantation. METHODS: Twelve patients who underwent SEEG implantation using FNS (Varioguide [Brainlab]) were included in this study. Data were collected prospectively and included demographic data, postoperative complications, functional results, and implantation characteristics (i.e., duration and number of electrodes). Further analysis included accuracy at entry point and target using measurements of the euclidean distance between planned and actual trajectories. RESULTS: Eleven patients underwent SEEG-FNS implantation from May 2019 to March 2020. One patient did not undergo surgery because of a bleeding disorder. The mean target deviation was 4.06 mm, and mean entry point deviation was 4.2 mm, with insular electrodes significantly more deviated. Results excluding insular electrodes showed a mean target deviation of 3.66 mm and a mean entry point deviation of 3.77 mm. No severe complications occurred; a few mild to moderate adverse events were reported (1 superficial infection, 1 seizure cluster, and 3 transient neurologic impairments). The mean implantation duration by electrodes was 18.5 minutes. CONCLUSIONS: Implantation of depth electrodes for SEEG using FNS seems to be safe, but larger prospective studies are needed to validate these results. Accuracy is sufficient for noninsular trajectories but warrant caution for insular trajectories with statistically significantly less accuracy.

Second surgery after vertical paramedian hemispherotomy for epilepsy recurrence.

Background: Vertical Paramedian Hemispherotomy (VPH) is considered an effective surgical treatment for drug-resistant epilepsy with 80% of patients experiencing seizure freedom or worthwhile improvement. Identifying persistent connective tracts is challenging in failed VPH. Methods: We reviewed our series of consecutive patients undergoing VPH for hemispheric drug-resistant epilepsy and included cases with recurrent epileptic seizures undergoing second surgery with at least 6 months of postoperative follow-up. The cases were extensively assessed to propose a targeted complementary resection. Results: Two children suffering from seizure recurrence following hemispherotomy leading to second surgery were included. After complete assessment, persisting amygdala residue was suspected responsible for the epilepsy recurrence in both patients. Complementary resection of the amygdala residue led to seizure freedom for both patients (Engel IA/ILAE Class 1) without complication. Different diagnostic tools are used to assess patients after failed hemispherotomy including routine EEG, prolonged video EEG, MRI (particularly DTI sequences), SPECT or PET scans and clinical evaluation. These tools allow to rule out epileptic foci in the contralateral hemisphere and to localize a potentially persisting epileptogenic zone. Assessment of these patients should be as systematic and integrated as the initial workup. Although our two patients suffered from Rasmussen's encephalitis, seizure recurrence after VPH has been described in other pathologies. Conclusion: Lying deep and medially in the surgical corridor of VPH, the amygdala can be incompletely resected and cause recurrent epilepsy. Complementary selective resection of the amygdala residue may safely lead to success in epilepsy control.

Outcome of Patients with Surgical Site Infection after Craniotomy.

Background: The management of surgical site infection (SSI) after craniotomy remains challenging with few existing recommendations. Patients and Methods: We reviewed the medical files of patients who underwent surgery between 2009 and 2018 to manage infection after craniotomy at our tertiary hospital. The Cox proportional hazards model and the Renyi test were used to investigate the association between relapse or all-cause mortality and selected variables. We compared infections with and without intra-cranial involvement using the Fisher test and the Wilcoxon rank sum test. Results: Seventy-seven episodes of infection were identified in 58 patients. The proportion of relapse was estimated to be 32.2% (± standard deviation [SD] 6.9) at five years. Intra-cranial infection was present in 15.6% of the cases (n = 12). Bone flap was removed in the majority of cases (93.5%) and the overall median duration of antibiotic therapy was six weeks (interquartile range [IQR] 6-12 weeks). Staphylococcus aureus was associated with a higher risk of relapse (p = 0.037). The administration of parenteral antibiotic agents (p = 0.012) and bone flap removal (p = 0.0051) were correlated with less relapse. In contrast, immunosuppressive drug use and radiotherapy were correlated with a higher risk of relapse (p = 0.014 and p = 0.031, respectively) and a higher all-cause mortality (p = 0.0093 and p < 0.0001, respectively). We found no difference between infections with and without intra-cranial involvement. Conclusions: Bone flap removal and parenteral antibiotic agents remain important in the management of SSI after craniotomy and were associated with less relapse in our study. More studies are needed to better determine the optimal treatment of this infection.

Automated electrical source imaging with scalp EEG to define the insular irritative zone: Comparison with simultaneous intracranial EEG.

OBJECTIVE: To evaluate the accuracy of automatedinterictallow-density electrical source imaging (LD-ESI) to define the insular irritative zone (IZ) by comparing the simultaneous interictal ESI localization with the SEEG interictal activity. METHODS: Long-term simultaneous scalp electroencephalography (EEG) and stereo-EEG (SEEG) with at least one depth electrode exploring the operculo-insular region(s) were analyzed. Automated interictal ESI was performed on the scalp EEG using standardized low-resolution brain electromagnetic tomography (sLORETA) and individual head models. A two-step analysis was performed: i) sublobar concordance betweencluster-based ESI localization and SEEG-based IZ; ii) time-locked ESI-/SEEG analysis. Diagnostic accuracy values were calculated using SEEG as reference standard. Subgroup analysis wascarried out, based onthe involvement of insular contacts in the seizure onset and patterns of insular interictal activity. RESULTS: Thirty patients were included in the study. ESI showed an overall accuracy of 53% (C.I. 29-76%). Sensitivity and specificity were calculated as 53% (C.I. 29-76%), 55% (C.I. 23-83%) respectively. Higher accuracy was found in patients with frequent and dominant interictal insular spikes. CONCLUSIONS: LD-ESI defines with good accuracy the insular implication in the IZ, which is not possible with classical interictalscalpEEG interpretation. SIGNIFICANCE: Automated LD-ESI may be a valuable additional tool to characterize the epileptogenic zone in epilepsies with suspected insular involvement.

Insular responses to transient painful and non-painful thermal and mechanical spinothalamic stimuli recorded using intracerebral EEG.

Brief thermo-nociceptive stimuli elicit low-frequency phase-locked local field potentials (LFPs) and high-frequency gamma-band oscillations (GBOs) in the human insula. Although neither of these responses constitute a direct correlate of pain perception, previous findings suggest that insular GBOs may be strongly related to the activation of the spinothalamic system and/or to the processing of thermal information. To disentangle these different features of the stimulation, we compared the insular responses to brief painful thermonociceptive stimuli, non-painful cool stimuli, mechano-nociceptive stimuli, and innocuous vibrotactile stimuli, recorded using intracerebral electroencephalograpic activity in 7 epileptic patients (9 depth electrodes, 58 insular contacts). All four types of stimuli elicited consistent low-frequency phase-locked LFPs throughout the insula, possibly reflecting supramodal activity. The latencies of thermo-nociceptive and cool low-frequency phase-locked LFPs were shorter in the posterior insula compared to the anterior insula, suggesting a similar processing of thermal input initiating in the posterior insula, regardless of whether the input produces pain and regardless of thermal modality. In contrast, only thermo-nociceptive stimuli elicited an enhancement of insular GBOs, suggesting that these activities are not simply related to the activation of the spinothalamic system or to the conveyance of thermal information.

Large Epileptogenic Type IIIb Dysplasia: A Radiological and Anatomopathological Challenge.

BACKGROUND: Type IIIb dysplasia is a subtype of focal cortical dysplasia associated with a tumor, most frequently with gangliogliomas then with dysembryoplastic neuroepithelial tumors (DNETs). Their preoperative diagnosis often remains equivocal since specific features are missing. The functional results (i.e., seizure free) is good with 81%-87% of Engel Ia at 5-year follow-up. CASE DESCRIPTION: A 4-year-old boy presented with a 1-year history of severe, invalidating, drug-resistant epilepsy. Imaging workup demonstrated a huge left limbic lesion, of which diagnosis remained speculative. Because of worsening neurological status, resective surgery was recommended after multidisciplinary discussion. The resection was performed through left transtemporal approach under neuronavigation (C.R.). Postoperative magnetic resonance imaging assessed uncomplicated near-total resection. Histopathological analysis showed combined features of a DNET of nonspecific type and a focal cortical dysplasia. CONCLUSION: We describe a rare condition of type IIIb dysplasia combining a focal cortical dysplasia with a DNET. Preoperative diagnosis of the lesion was of utmost difficultly, thereby rendering mandatory a thorough histopathological examination of resected specimen in the vast majority of cases. Increased recognition of the condition brings up the hypothesis of a genetic continuum or linkage between the 2 conditions. Functional results on seizure activity after ablative surgery are good and maximal safe resection should be the goal.

Tonic thermonociceptive stimulation selectively modulates ongoing neural oscillations in the human posterior insula: Evidence from intracerebral EEG.

The human insula is an important target for spinothalamic input, but there is still no consensus on its role in pain perception and nociception. In this study, we show that the human insula exhibits activity preferential for sustained thermonociception. Using intracerebral EEG recorded from the insula of 8 patients (2 females) undergoing a presurgical evaluation of focal epilepsy (53 contacts: 27 anterior, 26 posterior), we "frequency-tagged" the insular activity elicited by sustained thermonociceptive and vibrotactile stimuli, by periodically modulating stimulation intensity at a fixed frequency of 0.2 Hz during 75 s. Both types of stimuli elicited an insular response at the frequency of stimulation (0.2 Hz) and its harmonics, whose magnitude was significantly greater in the posterior insula compared to the anterior insula. Compared to vibrotactile stimulation, thermonociceptive stimulation exerted a markedly greater 0.2 Hz modulation of ongoing theta-band (4-8 Hz) and alpha-band (8-12 Hz) oscillations. These modulations were also more prominent in the posterior insula compared to the anterior insula. The identification of oscillatory activities preferential for thermonociception could lead to new insights into the physiological mechanisms of nociception and pain perception in humans.

Habituation of phase-locked local field potentials and gamma-band oscillations recorded from the human insula.

Salient nociceptive and non-nociceptive stimuli elicit low-frequency local field potentials (LFPs) in the human insula. Nociceptive stimuli also elicit insular gamma-band oscillations (GBOs), possibly preferential for thermonociception, which have been suggested to reflect the intensity of perceived pain. To shed light on the functional significance of these two responses, we investigated whether they would be modulated by stimulation intensity and temporal expectation - two factors contributing to stimulus saliency. Insular activity was recorded from 8 depth electrodes (41 contacts) implanted in the left insula of 6 patients investigated for epilepsy. Thermonociceptive, vibrotactile, and auditory stimuli were delivered using two intensities. To investigate the effects of temporal expectation, the stimuli were delivered in trains of three identical stimuli (S1-S2-S3) separated by a constant 1-s interval. Stimulation intensity affected intensity of perception, the magnitude of low-frequency LFPs, and the magnitude of nociceptive GBOs. Stimulus repetition did not affect perception. In contrast, both low-frequency LFPs and nociceptive GBOs showed a marked habituation of the responses to S2 and S3 as compared to S1 and, hence, a dissociation with intensity of perception. Most importantly, although insular nociceptive GBOs appear to be preferential for thermonociception, they cannot be considered as a correlate of perceived pain.

Gamma-Band Oscillations Preferential for Nociception can be Recorded in the Human Insula.

Transient nociceptive stimuli elicit robust phase-locked local field potentials (LFPs) in the human insula. However, these responses are not preferential for nociception, as they are also elicited by transient non-nociceptive vibrotactile, auditory, and visual stimuli. Here, we investigated whether another feature of insular activity, namely gamma-band oscillations (GBOs), is preferentially observed in response to nociceptive stimuli. Although nociception-evoked GBOs have never been explored in the insula, previous scalp electroencephalography and magnetoencephalography studies suggest that nociceptive stimuli elicit GBOs in other areas such as the primary somatosensory and prefrontal cortices, and that this activity could be closely related to pain perception. Furthermore, tracing studies showed that the insula is a primary target of spinothalamic input. Using depth electrodes implanted in 9 patients investigated for epilepsy, we acquired insular responses to brief thermonociceptive stimuli and similarly arousing non-nociceptive vibrotactile, auditory, and visual stimuli (59 insular sites). As compared with non-nociceptive stimuli, nociceptive stimuli elicited a markedly stronger enhancement of GBOs (150-300 ms poststimulus) at all insular sites, suggesting that this feature of insular activity is preferential for thermonociception. Although this activity was also present in temporal and frontal regions, its magnitude was significantly greater in the insula as compared with these other regions.

Nociceptive Local Field Potentials Recorded from the Human Insula Are Not Specific for Nociception.

The insula, particularly its posterior portion, is often regarded as a primary cortex for pain. However, this interpretation is largely based on reverse inference, and a specific involvement of the insula in pain has never been demonstrated. Taking advantage of the high spatiotemporal resolution of direct intracerebral recordings, we investigated whether the human insula exhibits local field potentials (LFPs) specific for pain. Forty-seven insular sites were investigated. Participants received brief stimuli belonging to four different modalities (nociceptive, vibrotactile, auditory, and visual). Both nociceptive stimuli and non-nociceptive vibrotactile, auditory, and visual stimuli elicited consistent LFPs in the posterior and anterior insula, with matching spatial distributions. Furthermore, a blind source separation procedure showed that nociceptive LFPs are largely explained by multimodal neural activity also contributing to non-nociceptive LFPs. By revealing that LFPs elicited by nociceptive stimuli reflect activity unrelated to nociception and pain, our results confute the widespread assumption that these brain responses are a signature for pain perception and its modulation.