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In this review, we retrace the results of 70 years of human cingulate cortex (CC) intracerebral electrical stimulation and discuss its contribution to our understanding of the anatomofunctional and clinical aspects of this wide cortical region. The review is divided into three main sections. In the first section, we report the results obtained by the stimulation of the anterior, middle, and posterior CC, in 30 studies conducted on approximately 1,000 patients from the 1950s to the present day. These studies show that specific manifestations can be reliably associated with specific cingulate subfields, with autonomic, interoceptive, and emotional manifestations clustered in the anterior cingulate, goal-oriented motor behaviors elicited from the anterior midcingulate and a variety of sensory symptoms characterizing the posterior cingulate regions. In the second section, we compare the effect of CC intracerebral electrical stimulation with signs and manifestations characterizing cingulate epilepsy, showing that the stimulation mapping of CC subfields provides precious information for understanding cingulate epileptic manifestations. The last section tackles the issue of the discrepancy emerging when comparing the results of clinical (electrical stimulation, epilepsy) studies-revealing the quintessential affective and motor nature of the CC-with that reported by neuroimaging studies-which focus on high-level cognitive functions. Particular attention will be paid to the hypothesis that CC hosts a "Pain Matrix" specifically involved in pain perception, which we will discuss in the light of the fact that the stimulation of CC (as well as cingulate epileptic seizures) does not induce nociceptive effects.

This study aimed to identify risk factors of postoperative seizure outcome in a consecutive cohort of patients operated on for TSC-related focal epilepsy, by evaluating several presurgical and surgical variables, including also MRI-visible brain abnormalities other than cortical tubers.This retrospective study included 51 patients surgically treated for drug-resistant focal epilepsy with a histological diagnosis of cortical tuber and followed for at least 12 months postoperatively. We investigated the association between several potentially explanatory variables and seizure outcome by univariate and multivariate analysis in the whole cohort and in the subgroups of patients with single and multiple tubers, respectively.The median postoperative follow-up was 115 months (IQR 63-168) and 54.9% of patients were in Engel's class I at final control. In the whole cohort, variables independently associated with an unfavorable seizure outcome (Engel's classes II-IV) were: preoperative non-focal interictal EEG (RR 5, CI 2.46-6.39), presence of sub-ependymal nodules (SEN) (RR 3.53, CI 1.71-4.56) and seizure onset before the first year of age (RR 3.56, CI 0.91-6.89). Non-focal interictal EEG was independently associated with an unfavorable outcome also in the subgroup of patients with multiple tubers (RR 4.34, CI 2.23-5.37), while the presence of SEN (p=0.0221) and of extra-central nervous system lesions (p= 0.0152) predicted an unfavorable seizure outcome in patients with a single tuber.Surgery represents an effective option for seizure control in patients with TSC-related epilepsy. The identification of preoperative risk factors for seizure outcome could be helpful for optimizing patients' selection for surgery and pre-surgical counseling.

Objective. Syntax involves complex neurobiological mechanisms, which are difficult to disentangle for multiple reasons. Using a protocol able to separate syntactic information from sound information we investigated the neural causal connections evoked by the processing of homophonous phrases, i.e. with the same acoustic information but with different syntactic content. These could be either verb phrases (VP) or noun phrases. Approach. We used event-related causality from stereo-electroencephalographic recordings in ten epileptic patients in multiple cortical and subcortical areas, including language areas and their homologous in the non-dominant hemisphere. The recordings were made while the subjects were listening to the homophonous phrases. Main results. We identified the different networks involved in the processing of these syntactic operations (faster in the dominant hemisphere) showing that VPs engage a wider cortical and subcortical network. We also present a proof-of-concept for the decoding of the syntactic category of a perceived phrase based on causality measures. Significance. Our findings help unravel the neural correlates of syntactic elaboration and show how a decoding based on multiple cortical and subcortical areas could contribute to the development of speech prostheses for speech impairment mitigation.

Objective To evaluate the applicability of corticocortical evoked potentials (CCEP) for intraoperative monitoring of the language network in epilepsy surgery under general anesthesia. To investigate the clinical relevance on language functions of intraoperative changes of CCEP recorded under these conditions. Methods CCEP monitoring was performed in 14 epileptic patients (6 females, 4 children) during resections in the left perisylvian region under general anesthesia. Electrode strips were placed on the anterior language area (AL) and posterior language area (PL), identified by structural and functional magnetic resonance imaging. Single-pulse electric stimulations were delivered to pairs of adjacent contacts in a bipolar fashion. During resection, we monitored the integrity of the dorsal language pathway by stimulating either AL by recording CCEP from PL or vice versa, depending on stability and reproducibility of CCEP. We evaluated the first negative (N1) component of CCEP before, during, and after resection. Results All procedures were successfully completed without adverse events. The best response was obtained from AL during stimulation of PL in 8 patients and from PL during stimulation of AL in 6 patients. None of 12 patients with a postresection N1 amplitude decrease of 0%–15% from baseline presented postoperative language impairment. Decreases of 28% and 24%, respectively, of the N1 amplitude were observed in 2 patients who developed transient postoperative speech disturbances. Conclusions The application of CCEP monitoring is possible and safe in epilepsy surgery under general anesthesia. Putative AL and PL can be identified using noninvasive presurgical neuroimaging. Decrease of N1 amplitude >15% from baseline may predict postoperative language deficits.

Identification of eloquent cortices is a prerequisite for the surgical plan but may be challenging, in particular for language areas (LAs), considering the complexity of language function and organization. Electrical intracerebral stimulations (ES) during Stereo-electroencephalography are an essential tool in the localization of LAs and high frequency ES (HFS, 50 Hz) are current gold standard. Low frequencies (1 Hz) are not effective. We aim to investigate different ES frequencies for establishing their utility in localizing LAs.We implemented an observational and prospective study evaluating frequencies lower than 50 and higher than 1 Hz; indicated as "intermediate" frequencies (IFS) performed at 6, 9 and 12 Hz and lasting 15 seconds. We included ten patients and carried out a standardized protocol comparing IFS to HFS.Eighty-six ES were carried out in LAs, positive for a language interference in 61.6% without noteworthy difference between IFS and HFS. Among these, 53.3% IFS vs 21.7% HFS yielded no after-discharge.IFS were similarly effective as HFS, with lower incidence of ADs. Their longer duration facilitated more accurate clinical testing.Our results are promising, suggesting that IFS can be useful in the study of LAs.

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.

This retrospective description of a surgical series is aimed at reporting on indications, methodology, results on seizures, outcome predictors and complications from a 20-year stereoelectroencephalography (SEEG) activity performed at a single epilepsy surgery centre. Prospectively collected data from a consecutive series of 742 SEEG procedures carried out on 713 patients were reviewed and described. Long-term seizure outcome of SEEG-guided resections was defined as a binomial variable: absence (ILAE classes 1–2) or recurrence (ILAE classes 3–6) of disabling seizures. Predictors of seizure outcome were analysed by preliminary uni/bivariate analyses followed by multivariate logistic regression. Furthermore, results on seizures of these subjects were compared with those obtained in 1128 patients operated on after only non-invasive evaluation. Survival analyses were also carried out, limited to patients with a minimum follow-up of 10 years. Resective surgery has been indicated for 570 patients (79.9%). Two-hundred and seventy-nine of 470 patients operated on (59.4%) were free of disabling seizures at least 2 years after resective surgery. Negative magnetic resonance and post-surgical lesion remnant were significant risk factors for seizure recurrence, while type II focal cortical dysplasia, balloon cells, glioneuronal tumours, hippocampal sclerosis, older age at epilepsy onset and periventricular nodular heterotopy were significantly associated with seizure freedom. Twenty-five of 153 patients who underwent radio-frequency thermal coagulation (16.3%) were optimal responders. Thirteen of 742 (1.8%) procedures were complicated by unexpected events, including three (0.4%) major complications and one fatality (0.1%). In conclusion, SEEG is a safe and efficient methodology for invasive definition of the epileptogenic zone in the most challenging patients. Despite the progressive increase of MRI-negative cases, the proportion of seizure-free patients did not decrease throughout the years.

Introduction: Brainstem cavernous malformations (BSCMs) are clusters of dilated sinusoidal channels. Clinical presentation is characterized by focal neurological deficits and/or hemorrhage. The goal of this study is to analyze surgical indications and approaches in a series of patients with BSCM and review pertinent literature and suggest prognostic factors related to the anatomical, clinical, and surgical data collected. Methods: We retrospectively reviewed the clinical data of 55 patients with BSCM, treated at three centers, from January 2006 to March 2016. We collected anagraphic data, pre and postoperative neurological status, pre and postradiological images, surgical procedures, and follow-up results. We summarized the anatomical, clinical, and surgical aspects of the lesions and identified two large groups based on the chosen approach: lateral and medial. Clinical and radiological results were then compared. Results: The series comprised 55 patients. Hemorrhagic onset was observed in all patients. Suboccipital, retrosigmoid, anterior, subtentorial, subtemporal, transvermian, telovelar, far lateral and trans, and infratentorial approaches were performed. Neurological status improved postoperatively in 34 cases at last follow-up. Five patients showed clinical neurological worsening. Total resection was achieved in 46 cases and, during a mean follow-up of 63.4 months, no recurrence or re-bleeding occurred in those patients. The mean follow-up was 63.9 months. The mean modified Rankin Scale at final follow-up was used to analyze the results and draw our conclusions. Conclusions: A reasonable surgical approach, selection, and gentle handling of the surrounding structures are required to prevent impairment of neurologic function and avoid partial resection.

Purpose To determine the safety and efficacy of O-Arm™ intraoperative imaging in maxillofacial surgery of post-traumatic orbital fractures. In order to ensure correct placement of titanium plate, immediately after fixing, viewable, in the axial, sagittal and coronal images. Methods The authors evaluated 5 consecutive adult patients with orbital fractures who required a reoperation involving displacement of titanium mesh between January and December 2015. The displacement or incorrect positioning of titanium mesh was detected at post-operative CT scan or clinical neurological findings. Intraoperative O-Arm™ imaging was used for our patients who underwent secondary maxillofacial orbital fracture surgery due to the failure of first surgical approach. Results An eyelid incision was performed in order to obtain maximal exposure and minimizing cosmetic defects. Any previous fixation device was skeletonized and removed, any improperly reduced fracture was mobilized, reduced and refixated with 1.5 mm plates, screws and titanium mesh. The intra-operative O-Arm™ imaging technique was used at the end of the procedures. In 4 cases it confirmed the appropriateness of the newly obtained reconstruction, in 1 case a first scan showed a suboptimal result and the devices were correctly repositioned, guided by the O-Arm™ images. Conclusions Intraoperative O-Arm™ assisted craniofacial reconstruction surgery improves the assessment of neurovascular structure decompression, skeletal fragment identification, fixation procedures and for the correct re-establishment of facial symmetry in orbital floor fractures.

To retrospectively analyse a single-centre consecutive surgical series of patients with temporal lobe epilepsy (TLE) and negative MRI. To identify factors associated with postoperative seizure outcome among several presurgical, surgical and postsurgical variables. Clinical records of 866 patients who received temporal lobe resections and with a minimum follow-up of 12 months were retrospectively searched for MRI-negative cases. Anamnestic, clinical, neurophysiological, surgical, histopathological and postsurgical data were collected. Seizure outcome was categorised as favourable (Engel’s class I) and unfavourable (Engel’s classes II–IV). Uni- and multivariate statistical analysis was performed to identify variables having a significant association with seizure outcome. Forty-eight patients matched the inclusion criteria. 26 (54.1%) patients required invasive EEG evaluation with Stereo-electro-encephalography (SEEG) before surgery. Histological evaluation was unremarkable in 34 cases (70.8%), revealed focal cortical dysplasias in 13 cases and hippocampal sclerosis in 2. 28 (58.3%) patients were in Engel’s class I after a mean follow-up of 82 months (SD ± 74; range 12–252). Multivariate analysis indicated auditory aura, contralateral diffusion of the discharge at Video-EEG monitoring and use of 18F-FDG PET as variables independently associated with seizure outcome. Carefully selected patients with MRI-negative TLE can be good candidates for surgery. Surgery should be considered with caution in patients with clinical features of neocortical seizure onset and contralateral propagation of the discharge. Use of 18F-FDG PET may be helpful to improve SEEG and surgical strategies. The presented data help in optimising the selection of patients with MRI-negative TLE with good chances to benefit from surgery.

OBJECTIVESurgical treatment of drug-resistant epilepsy originating from the posterior quadrant (PQ) of the brain often requires large multilobar resections, and disconnective techniques have been advocated to limit the risks associated with extensive tissue removal. Few previous studies have described a tailored temporoparietooccipital (TPO) disconnective approach; only small series with short postoperative follow-ups have been reported. The aim of the present study was to present a tailored approach to multilobar PQ disconnections (MPQDs) for epilepsy and to provide details about selection of patients, presurgical investigations, surgical technique, treatment safety profile, and seizure and cognitive outcome in a large, single-center series of patients with a long-term follow-up.METHODSIn this retrospective longitudinal study, the authors searched their prospectively collected database for patients who underwent MPQD for drug-resistant epilepsy in the period of 2005–2017. Tailored MPQDs were a posteriori grouped as follows: type I (classic full TPO disconnection), type II (partial TPO disconnection), type III (full temporooccipital [TO] disconnection), and type IV (partial TO disconnection), according to the disconnection plane in the occipitoparietal area. A bivariate statistical analysis was carried out to identify possible predictors of seizure outcome (Engel class I vs classes II–IV) among several presurgical, surgical, and postsurgical variables. Preoperative and postoperative cognitive profiles were also collected and evaluated.RESULTSForty-two consecutive patients (29 males, 24 children) met the inclusion criteria. According to the presurgical evaluation (including stereo-electroencephalography in 13 cases), 12 (28.6%), 24 (57.1%), 2 (4.8%), and 4 (9.5%) patients received a type I, II, III, or IV MPQD, respectively. After a mean follow-up of 80.6 months, 76.2% patients were in Engel class I at last contact; at 6 months and 2 and 5 years postoperatively, Engel class I was recorded in 80.9%, 74.5%, and 73.5% of cases, respectively. Factors significantly associated with seizure freedom were the occipital pattern of seizure semiology and the absence of bilateral interictal epileptiform abnormalities at the EEG (p = 0.02). Severe complications occurred in 4.8% of the patients. The available neuropsychological data revealed postsurgical improvement in verbal domains, whereas nonunivocal outcomes were recorded in the other functions.CONCLUSIONSThe presented data indicate that the use of careful anatomo-electro-clinical criteria in the presurgical evaluation allows for customizing the extent of surgical disconnections in PQ epilepsies, with excellent results on seizures and an acceptable safety profile.

In December of 2016, a Consensus Conference on unruptured AVM treatment, involving 24 members of the three European societies dealing with the treatment of cerebral AVMs (EANS, ESMINT, and EGKS) was held in Milan, Italy. The panel made the following statements and general recommendations: (1) Brain arteriovenous malformation (AVM) is a complex disease associated with potentially severe natural history; (2) The results of a randomized trial (ARUBA) cannot be applied equally for all unruptured brain arteriovenous malformation (uBAVM) and for all treatment modalities; (3) Considering the multiple treatment modalities available, patients with uBAVMs should be evaluated by an interdisciplinary neurovascular team consisting of neurosurgeons, neurointerventionalists, radiosurgeons, and neurologists experienced in the diagnosis and treatment of brain AVM; (4) Balancing the risk of hemorrhage and the associated restrictions of everyday activities related to untreated unruptured AVMs against the risk of treatment, there are sufficient indications to treat unruptured AVMs grade 1 and 2 (Spetzler-Martin); (5) There may be indications for treating patients with higher grades, based on a case-to-case consensus decision of the experienced team; (6) If treatment is indicated, the primary strategy should be defined by the multidisciplinary team prior to the beginning of the treatment and should aim at complete eradication of the uBAVM; (7) After having considered the pros and cons of a randomized trial vs. a registry, the panel proposed a prospective European Multidisciplinary Registry.

Background Image-guided surgery techniques in spinal surgery are usually based upon fluoroscopy or computed tomography (CT) scan, which allow for a real-time navigation of bony structures, though not of neural structures and soft tissue remains. Objective To verify the effectiveness and efficacy of a novel technique of imaging merging between preoperative magnetic resonance imaging (MRI) and intraoperative CT scan during removal of intramedullary lesions. Methods Ten consecutive patients were treated for intramedullary lesions using a navigation system aid. Preoperative contrast-enhanced MRI was merged in the navigation software, with an intraoperative CT acquisition, performed using the O-arm TM system (Medtronic Sofamor Danek, Minneapolis, Minnesota). Dosimetric and timing data were also acquired for each patient. Results The fusion process was achieved in all cases and was uneventful. The merged imaging information was useful in all cases for defining the exact area of laminectomy, dural opening, and the eventual extension of cordotomy, without requiring exposition corrections. The radiation dose for the patients was 0.78 mSv. Using the authors' protocol, it was possible to merge a preoperative MRI with navigation based on intraoperative CT scanning in all cases. Information gained with this technique was useful during the different surgical steps. However, there were some drawbacks, such as the merging process, which still remains partially manual. Conclusion In this initial experience, MRI and CT merging and its feasibility were tested, and we appreciated its safety, precision, and ease.

Mortality and morbidity due to brain injury in the elderly population is a growing clinical problem: among older patients, those70 years have a considerably higher risk both in terms of mortality and morbidity. Thereafter, the reasons influencing outcome have not been clearly examined: in the present study we addressed these questions considering the main clinical characteristics exerting a significant impact on the outcome of patients aged70, with emphasis for the severity of brain injury and anticoagulant (CAW) treatments.We performed a retrospective analysis of 103 consecutive isolated head injury patients older than 70, admitted at our Department in the period November 2004-November 2009. The clinical variables considered were as follow: age, sex, type of TBI, GCS, pre-TBI use of anti-coagulants (aspirin, warfarin, clopidogrel), INR at admission (INR values were subdivided in values1.25 as at risk for hemorrhagic events and1.25 as normal), initial CT scan classification looking at the presence of subarachnoid hemorrhage (t-SAH) or mass lesions; the main outcome measure was the Glasgow Outcome Scale.The most frequent cause of TBI was accidental fall (65%): 39 were in CAW therapies and in 36 cases the cause of falling down injury was recorded due to a sincopal event (arterial hypotension, atrial fibrillation); in the older patients an accidental fall is significantly related to the TBI, while in the patients aged 70-75 years, TBI is related to a traffic accident (P=0.002). Moreover the cause of TBI correlates with the CAW treatment, the accidental fall being significantly more frequent in patients in CAW treatment (P=0.003). Overall mortality rate is significantly related to an elevated INR class, to presence of t-SAH (16/50 patients) and subdural hematoma (26/46).The results of the present study show that in a population of patients aged70, TBI is a high risk event if patient has concurrent treatment with CAW therapies and if an accidental fall is the cause of TBI. In these cases the finding of t-SAH represents a high-risk parameter for mortality but not for morbidity.

Objective. Stereo-electroencephalography (SEEG) has recently gained importance in analyzing brain functions. Its high temporal resolution and spatial specificity make it a powerful tool to investigate the strength, direction, and spectral content of brain networks interactions, especially when these connections are stimulus-evoked. However, choosing the best approach to evaluate the flow of information is not trivial, due to the lack of validated methods explicitly designed for SEEG. Approach. We propose a novel non-parametric statistical test for event-related causality (ERC) assessment on SEEG recordings. Here, we refer to the ERC as the causality evoked by a particular part of the stimulus (a response window – RW). We also present a data surrogation method to evaluate the performance of a causality estimation algorithm. We finally validated our pipeline using surrogate SEEG data derived from an experimentally collected dataset, and compared the most used and successful measures to estimate effective connectivity, belonging to the Geweke-Granger causality framework. Main results. Here we show that our workflow correctly identified all the directed connections in the RW of the surrogate data and prove the robustness of the procedure against synthetic noise with amplitude exceeding physiological-plausible values. Among the causality measures tested, partial directed coherence (PDC) performed best. Significance. This is the first non-parametric statistical test for ERC estimation explicitly designed for SEEG datasets. The pipeline, in principle, can also be applied to the analysis of any type of time-varying estimator, if there exists a clearly defined RW.

The recent introduction of the 3D endoscope for endonasal surgery has been welcomed because of its promise to overcome the main limitation of endoscopy, namely the lack of stereoscopic vision. This innovation particularly regarded the most complex transnasal surgery of the skull base. We therefore discuss our early experience as ENT surgeons with the use of a purely 3D endoscopic expanded endonasal approach for supradiaphragmatic lesions in 10 consecutive patients. This article will focus on the surgical technique, the complications, the outcome, and more importantly the advantages and limitations of the new device. We believe that the new 3D system shows its main drawback when surgery is conducted in the narrow nasal spaces. Nevertheless, the improved knowledge of the three-dimensional nasal anatomy enabled the ENT surgeon to perform a more selective demolition of the nasal structures even in the anterior part of the nose. The depth perception obtained with the 3D system also permitted a better understanding of the plasticity of the surgical defects, increasing the confidence to perform successful skull base plasties. We believe that, for both the ENT surgeon and the neurosurgeon, the expanded endonasal approach is the main indication for this exciting tool, although larger prospective studies are needed to determine the equality to the 2D HD endoscope in oncological terms.La recente introduzione dell'endoscopia tridimensionale nella chirurgia endonasale è stata accolta con favore con l'aspettativa di superare la principale limitazione dell'endoscopia, ovvero la mancanza di visione stereoscopica. Questa innovazione riguarda soprattutto la complessa chirurgia endoscopica della base cranica. Discutiamo quindi la nostra esperienza preliminare come chirurghi ORL con l'approccio endoscopico endonasale esteso con visione 3D per lesioni sopradiaframmatiche in 10 pazienti consecutivi. Questo articolo discute la tecnica chirurgica, le complicanze, i risultati e soprattutto i vantaggi ed i limiti del nuovo strumento. Riteniamo che il sistema 3D mostri i suoi limiti principali quando la chirurgia è condotta in spazi stretti. Comunque, la maggiore consapevolezza dell'anatomia nasale tridimensionale permette al chirurgo ORL di eseguire una demolizione più selettiva delle strutture nasali, anche nella parte anteriore delle cavità nasali. La percezione della profondità che si ottiene con il sistema 3D permette inoltre una migliore comprensione della morfologia del difetto chirurgico, migliorando le capacità di eseguire una plastica efficace. Nella nostra opinione, sia per i chirurghi ORL che per i neurochirurghi, l'approccio endoscopico endonasale esteso è la principale indicazione per questo strumento innovativo, sebbene siano necessari ulteriori studi su popolazioni più numerose per determinarne la stessa affidabilità della tecnologia 2D HD in termini oncologici.