Lesson learned in endoscopic endonasal dens resection for C1-C2 spinal cord decompression.

PURPOSE: Endoscopic endonasal approach (EEA) is the safest and most effective technique for odontoidectomy. Nevertheless, this kind of approach is yet not largely widespread. The aim of this study is to share with the scientific community some tips and tricks with our ten-year-old learned experience in endoscopic endonasal odontoidectomy (EEO), which remains a challenging surgical approach. MATERIAL AND METHODS: Our case series consists of twenty-one (10 males, 11 females; age range of 34-84 years) retrospectively analyzed patients with ventral spinal cord compression for non-reducible CVJ malformation, treated with EEA from July 2011 to March 2019. RESULTS: The results have recently been reported in a previous paper. The only intraoperative complication observed was intraoperative cerebrospinal fluid (CSF) leak (9.5%), without any sign of post-operative CSF leak. CONCLUSIONS: Considering our experience, EEO represents a valid and safe technique to decompress neural cervical structures. Despite its technical complexity, mainly due to the use of endoscope and the challenging surgical area, with this study we encourage the use of EEO displaying our experience-based surgical tips and tricks.

Spinal epidural capillary hemangioma: case report and review of the literature.

BACKGROUND: Almost all of the epidural hemangiomas reported are cavernous hemangiomas. Purely extradural spinal capillary hemangiomas are very rare. Capillary hemangiomas are hamartomatous malformations that result from proliferations of vascular endothelial cells. Only ten cases have been reported in the English literature, treated with surgical excision. CASE DESCRIPTION: A case of a dorsal extradural spinal capillary hemangioma is described. A total surgical removal has been performed after spinal angiography and embolization. Complete surgical removal should always be the goal in these lesions. Embolization did not show to reduce bleeding during the surgical procedure in this case.

Endoscopic endonasal odontoidectomy: a long-term follow-up results for a cohort of 21 patients.

BACKGROUND: Endoscopic endonasal odontoidectomy (EEO) has been described as a potential approach for craniovertebral junction (CVJ) disease which could cause anterior bulbomedullary compression and encroaching. Due to the atlantoaxial junction's uniqueness and complex biomechanics, treating CVJ pathologies uncovers the challenge of preventing C1-C2 instability. A large series of patients treated with endonasal odontoidectomy is reported, analyzing the feasibility and necessity of whether or not to perform posterior stabilization. Furthermore, the focus is on the long-term follow-up, especially those whom only underwent partial C1 arch preservation without posterior fixation. METHODS: This study is a retrospective analysis of patients with ventral spinal cord compression for non-reducible CVJ malformation, consecutively treated with EEO from July 2011 to March 2019. Postoperative dynamic X-ray and CT scans were obtained in each case in order to document CVJ decompression as well as to exclude instability. The anterior atlas-dens interval, posterior atlas-dens interval and C1-C2 total lateral overhang were measured as a morphological criteria to determine upper cervical spine stability. RESULTS: Twenty-one patients (11:10 F:M) with a mean age of 60.6 years old at the time of surgery (range 34-84 years) encountered the inclusion criteria. For all 21 patients, a successful decompression was achieved at the first surgery. In 11 patients, the partial C1 arch integrity did not require a posterior cervical instrumentation on the bases of postoperative and constant follow-up radiological examination. In 13 cases, an improvement of motor function was recorded at the time of discharge. Only one patient had further motor function improvement at follow-up. Among the patients that did not show any significant motor change at discharge, 4 patients showed an improvement at the last follow-up. CONCLUSIONS: The outcomes, even in C1 arch preservation without posterior fixation, are promising, and it could be said that the endonasal route potentially represents a valid option to treat lesions above the nasopalatine line.

Second-Day Morning Cortisol Levels after Transsphenoidal Surgery Are Accurate Predictors of Secondary Adrenal Insufficiency with Diagnostic Cut-Offs Similar to Those in Non-Stressed Conditions.

INTRODUCTION: Multiple studies tried to identify cortisol cut-offs after pituitary surgery that could accurately assess hypothalamic-pituitary-adrenal (HPA) axis function; however, there is no consensus nowadays. This study aimed to evaluate the accuracy of morning cortisol after transsphenoidal surgery in predicting long-term secondary adrenal insufficiency. METHODS: In our tertiary center, we prospectively determined first- and second-day cortisol after transsphenoidal surgery in 92 patients without preoperative adrenal -insufficiency and not treated with glucocorticoids perioperatively. Definitive diagnosis of secondary adrenal insufficiency was obtained with re-evaluation 3 months after trans-sphenoidal surgery and clinical follow-up of at least 1 year. RESULTS: Ten patients (10.8%) developed long-term postoperative secondary adrenal insufficiency. The ROC curves demonstrated that first-day cortisol had a moderate diagnostic accuracy, while a second-day cortisol ≤9.3 µg/dL (257 nmol/L) showed the best performance in predicting adrenal insufficiency (sensitivity [Se] 88.9%, specificity [Sp] 86.9%, AUC 0.921). Moreover, a second-day cortisol ≤3.2 µg/dL (89 nmol/L) was able to diagnose adrenal insufficiency in 100% of cases (Se 22.2%, Sp 100%) and >14 µg/dL (386 nmol/L) was able to exclude ACTH deficiency (Se 100%, Sp 57.4%). CONCLUSIONS: Adrenal function can be carefully studied on the second day after pituitary surgery, using cut-off values that international guidelines suggested for non-stressed conditions. In fact, second-day cortisol levels ≤3.2 µg/dL (89 nmol/L) and >14 µg/dL (386 nmol/L) are diagnostic of secondary adrenal insufficiency and normal function, respectively. We also suggest performing a definitive re-evaluation with an HPA axis stimulation test when second-day cortisol values are between 3.3 and 14 µg/dL (90-386 nmol/L).

Early Copeptin Determination Allows Prompt Diagnosis of Post-Neurosurgical Central Diabetes Insipidus.

INTRODUCTION: Central diabetes insipidus (CDI) is a frequent complication of pituitary surgery, but its diagnosis lacks standardized criteria. Copeptin, a surrogate marker of arginine vasopressin release, is triggered by psycho-physical stresses such as pituitary surgery. Low postoperative copeptin could predict CDI onset. The aims of this study were the validation of copeptin as a predictor of post-neurosurgical CDI and the identification of the optimal timing for its determination. METHODS: Sixty-six consecutive patients operated for a hypothalamic-pituitary lesion were evaluated. Copeptin was determined preoperatively and at 1, 6, 12, 24 and 48 h post-extubation. Fifty-eight patients were reassessed after 3-6 months post-surgery to confirm transient (3 cases) or permanent CDI (5 cases) diagnosis. RESULTS: A marked copeptin peak was identified at 1 h after extubation, when a value below or equal to 12.8 pmol/L had a good accuracy in identifying CDI cases (AUC 0.866, 95% CI 0.751-0.941). Moreover, a copeptin peak above 4.2 pmol/L excluded permanent forms (AUC 1, 95% CI 0.629-1). Regression analysis identified copeptin as the only significant predictor of CDI (OR 0.86, 95% CI 0.75-0.98, p = 0.02). A copeptin T1/T0 ratio below or equal to 1.47 identified patients at risk of isolated biochemical alterations even in the absence of an overt CDI. CONCLUSIONS: A prompt increase of copeptin is expected at 1 h after extubation. The absence of this peak is a reliable predictor of post-neurosurgical CDI.

Surgical management of pituitary adenomas: does age matter?

PURPOSE: Along with increased life expectancy and improvements in the diagnostic tools and techniques, the number of elderly patients with symptomatic pituitary tumors being evaluated for surgery is increasing. To date, contrasting results of the safety and effectiveness of transsphenoidal surgery in patients over 65 years old were published in the medical literature. An investigation concerning the extension of resection, post operative complications and, recovery rate from endocrinological and visual symptoms in elderly patients who underwent transsphenoidal surgery for pituitary adenoma was conducted. METHODS: A retrospective review, which included a series of 81 patients 65 years old or older who underwent endoscopic endonasal surgery for pituitary adenomas was analyzed. Pre operative and post operative data were collected and patients were then compared among four age groups: 65-69 years old, 70-74 years old, 75-79 years old and 80 years and over. The results were then compared with the findings from the medical literature review. RESULTS: The statistical analysis failed to highlight any difference in terms of clinical presentation or complications among the four age groups, however there seems to be a slightly higher risk of post operative hypopituitarism in patients over 74 years old. CONCLUSION: The results of the study seem to confirm that transsphenoidal surgery for PA is safe and effective among patients that are 65 and over. Moreover, a partial resection is preferred over a gross total one in order to reduce the surgical risk.

Comorbidity of Cervical Spondylogenic Myelopathy and Amyotrophic Lateral Sclerosis: When Electromyography Makes the Difference in Diagnosis.

Cervical spondylogenic myelopathy (CSM) represents a common differential diagnosis for spinal onset Amyotrophic Lateral Sclerosis (ALS). Identifying occurrence of ALS in patients with CSM may be challenging. We evaluated the accuracy of Awaji criteria in the diagnosis of ALS in a cohort of patients with CSM. We screened all patients attending Turin ALS Center during the 2006-2018 period. We selected only patients for whom cervical cord MRI showed radiological signs of CSM. All patients underwent electromyography (EMG), and Awaji criteria were used for diagnosis of clinically probable ALS. All patients were followed up clinically for at least 6 months, and ALS diagnosis was eventually confirmed according to El-Escorial revised criteria, based on disease progression. Of 2,059 patients screened, in 42 cases, MRI showed signs of CSM; CSM incidence and prevalence risks were 0.16 and 2.04%, respectively. Based on clinical progression, 72.7% of patients were diagnosed as CSM and 27.3% as CSM + ALS. At EMG 6 (18.2%) patients fulfilled the criteria for ALS, 5 of them (83.3%) during clinical follow-up were diagnosed as clinical definite ALS + CSM. Accuracy of Awaji criteria in diagnosing ALS was good (AUC = 0.757, p = 0.03). Sensitivity and specificity of Awaji criteria were, respectively, 55.6 and 95.8%. Positive predictive value was 83.3%, while negative predictive value was 85.2%. CSM-ALS comorbidity is a relatively common problem in clinical practice. To better choose patients who could benefit from surgery, EMG should be performed in CSM patients, due to its good accuracy in recognizing ALS.

Benzene affects the response to octreotide treatment of growth hormone secreting pituitary adenoma cells.

Growth hormone (GH) secreting pituitary adenomas are the main cause of acromegaly. Somatostatin analogs are the gold standard of medical therapy; however, resistance represents a big drawback in acromegaly management. We recently demonstrated that benzene (BZ) modifies the aggressiveness of GH-secreting rat pituitary adenoma cells (GH3), increasing GH secretion and altering the synthesis of molecules involved in the somatostatin signaling pathway. Based on these pieces of evidence, this study aimed to evaluate the effects of BZ on octreotide (OCT) efficacy in GH-secreting adenoma cells. In GH3 cells, BZ counteracted the anti-proliferative action of OCT. GH gene expression, unmodified by OCT, remained high in BZ-treated cells as well as after treatment with the association of both. GH secretion, reduced by OCT, was increased after treatment with BZ alone or when the pollutant was used with OCT. The combination of BZ and OCT greatly reduced the gene expression of ZAC1 and SSTR2; and this reduction was also present at a protein level. BZ caused an increase in the protein level of the transcription factor STAT3 and in its phosphorylated form. In the presence of BZ, OCT lost the ability to reduce the phosphorylated protein levels. Finally, in primary cultures of human pituitary adenoma cells, BZ caused an increase in GH secretion. OCT decreased GH secretion, but the addition of BZ reversed the OCT effect. In conclusion, our results suggest that BZ may have an important role in the resistance of pituitary adenomas to the pharmacological treatment with somatostatin analogs.

Cortical bone trajectory screws for circumferential arthrodesis in lumbar degenerative spine: clinical and radiological outcomes of 101 cases.

PURPOSE: The use of cortical bone trajectory (CBT) pedicle screws for circumferential interbody fusion represents a viable alternative for single-level procedure with reduced invasiveness and less tissue destruction than the traditional technique. In addition, CBT screws have a potentially stronger pullout strength because of the greater amount of cortical bone intercepted. Only few series exist evaluating clinical and radiological outcomes of CBT screws. METHODS: This is a retrospective cohort study. All patients that underwent circumferential lumbar interbody fusion with CBT screws in our institution from 2014 to 2017 were reviewed. Patient demographics, clinical outcome with visual analogue scale (VAS) and Oswestry Disability Index (ODI), radiological data such as fusion, lordosis and muscle trauma, operative blood loss, hospital stay and use of fluoroscopy were evaluated. RESULTS: A total of 101 patients undergoing CBT-arthrodesis for degenerative lumbo-sacral disease were reviewed. Mean procedural time was 187 min. The mean operative blood loss and X-ray dose per procedure was 383 ml and 1.60 mg cm2, respectively. The mean hospital stay was 3.47 days. The mean follow-up was 18.23 months. Mean lordosis increment at the treated level was 4.2°. When the follow-up was longer than 12 months (53% of patients), fusion was obtained in 94% of cases. Mean ODI and VAS index improved with statistical significance. CONCLUSIONS: This is to our knowledge that the largest available study regarding CBT for circumferential arthrodesis. Results underlined the safety of this technique and the promising clinical and radiological outcomes that will need a longer follow-up. These slides can be retrieved under Electronic Supplementary material.

Effects of environmental pollutants on signaling pathways in rat pituitary GH3 adenoma cells.

An increased rate of acromegaly was reported in industrialized areas, suggesting an involvement of environmental pollutants in the pathogenesis and behavior of GH-secreting pituitary adenomas. Based on these premises, the aim of the study was to evaluate the effects of some widely diffused pollutants (i.e. benzene, BZ; bis(2-ethylhexyl) phthalate, DEHP and polychlorinated biphenyls, PCB) on growth hormone secretion, the somatostatin and estrogenic pathways, viability and proliferation of rat GH-producing pituitary adenoma (GH3) cells. All the pollutants induced a statistically significant increase in GH secretion and interfered with cell signaling. They all modulated the expression of SSTR2 and ZAC1, involved in the somatostatin signaling, and the expression of the transcription factor FOXA1, involved in the estrogen receptor signaling. Moreover, all the pollutants increased the expression of the CYP1A1, suggesting AHR pathway activation. None of the pollutants impacted on cell proliferation or viability. Present data demonstrate that exposure to different pollutants, used at in vivo relevant concentrations, plays an important role in the behavior of GH3 pituitary adenoma cells, by increasing GH secretion and modulating several cellular signaling pathways. These observations support a possible influence of different pollutants in vivo on the GH-adenoma aggressiveness and biological behavior.

3D HD Endoscopy in Skull Base Surgery: From Darkness to Light.

The introduction of modern endoscopy in neurosurgery brought light to one of the darkest areas: the skull base. In particular, the trans-nasal route allowed skull base surgeons to visualize and dominate the entire midline skull base. We analyzed our surgical series of 199 patients that were affected by several pathologies (pituitary adenomas, clivalchordomas, craniopharyngioma, Rathke's cleft cysts, tuberculum sellaemeningiomas, and craniovertebral junction pathologies with bulbar compression) and treated each by using a 3D-HD endoscope between December 2012 and December 2015 and reviewed the literature. We present our results in terms of tumor resections and decompression inpatients affected by craniovertebral junction pathologies. Analyzing our direct experience, as well as the literature, we can assert that the amount and accuracy of necessary movements in order to achieve a determined target are affected by the screen clarity and image resolution of the device. Additionally, the experience of the surgeon has an important role in the surgical outcome. Moreover, depth perception is critical in order to obtain precise and accurate movements. Our observations and the experts' opinion indicate that this modality provides improved surgical dexterity by affording the surgeon with depth perception while manipulating tissue and maneuvering the endoscope in the endonasal corridor, which is especially crucial in reducing the learning curve of young neurosurgeons.

Comparative analysis of explanted DBS electrodes.

BACKGROUND: Hardware-related complications frequently occur in deep brain stimulation. Microscopy and spectroscopy techniques are effective methods for characterizing the morphological and chemical basis of malfunctioning DBS electrodes. A previous report by our team revealed the morphological and chemical alterations on a malfunctioning explanted electrode when it was compared to a new device. The aim of this preliminary study was to verify whether these morphological and chemical alterations in the materials were a direct result of the hardware malfunctioning or if the failure was correlated to a degradation process over time. METHODS: Two DBS electrodes were removed from two patients for reasons other than DBS system impairment and were analyzed by a scanning electron microscope and by an energy-dispersive X-ray spectroscopy. The results were compared to a malfunctioning device and to a new device, previously analyzed by our group. RESULTS: The analysis revealed that the wear of the polyurethane external part of all the electrodes was directly correlated with the duration of implantation period. Moreover, these alterations were independent from the electrodes functioning and from parameters used during therapy. CONCLUSIONS: This is the first study done that demonstrates a time-related degradation in the external layer of DBS electrodes. The analyses of morphological and chemical properties of the implanted devices are relevant for predicting the possibility of hardware's impairment as well as to improve the bio-stability of DBS systems.

Posteroventrolateral pallidotomy through implanted DBS electrodes monitored by recording local field potentials.

This paper describes the use of globus pallidus internus (Gpi) local field potentials recorded through pre-implanted deep brain stimulation (DBS) electrodes on a patient affected by generalized dystonia. The recordings were made both before and after radiofrequency-induced posteroventrolateral bilateral stereotactic pallidotomy. LFP patterns and macroelectrode impedances were modified after the pallidotomy, along with the improvement of dystonic symptoms. After implantation, the DBS electrodes were used for subsequent bedside pallidotomies that were required by the evolution and/or persistence of symptoms. In our hands, LFPs were safe and effective in monitoring pallidotomy performed through DBS electrodes.

Introducing endoscopic assistance on routinary basis for vestibular schwannomas resection: A single centre acceptance analysis.

OBJECTIVE: The use of endoscopic assistance in retrosigmoid approach for tumors of the cerebellopontine angle brought undoubted technological advantages in skull base surgery. Nonetheless, the use of the endoscope is not as widespread as it could be. The aim of the study is to analyze the impressions of neurosurgeons and otologists with different experience in vestibular schwannoma surgery, experiencing the introduction of the endoscope in surgical daily practice. METHODS: All patients undergoing vestibular schwannoma surgery were recruited in the period from January 2019 to December 2020. The endoscope-assistance and a minimum follow-up of 12 months were considered inclusion criteria. An eight items questionnaire was administered to the surgeons who used endoscope-assistance during surgery. RESULTS: A total number of 20 patients were recruited. Five surgeons experienced the use of 0° and 45° optics in the "pre-resection" and "intra-meatal" phases of the procedures. The survey gave positive feedbacks on the introduction of the endoscope in vestibular schwannoma resection. The main drawback was the difficulty to manage the use of angled optics. CONCLUSIONS: Despite the known limitations of the study, the idea of investigating surgeons' impressions on the use of the endoscope could be another motif to explain why this instrument and its diffusion is limited despite its advantages in vestibular schwannoma surgery.

Facial nerve outcome score: a new score to predict long-term facial nerve function after vestibular schwannoma surgery.

Introduction: Patients' quality of life (QoL), facial nerve (FN), and cochlear nerve (CN) (if conserved) functions should be pursued as final outcomes of vestibular schwannoma (VS) surgery. In regard to FN function, different morphologic and neurophysiological factors have been related to postoperative outcomes. The aim of the current retrospective study was to investigate the impact of these factors on the short- and long-term FN function after VS resection. The combination of preoperative and intraoperative factors resulted in designing and validating a multiparametric score to predict short- and long-term FN function. Methods: A single-center retrospective analysis was performed for patients harboring non-syndromic VS who underwent surgical resection in the period 2015-2020. A minimum follow-up period of 12 months was considered among the inclusion criteria. Morphological tumor characteristics, intraoperative neurophysiological parameters, and postoperative clinical factors, namely, House-Brackmann (HB) scale, were retrieved in the study. A statistical analysis was conducted to investigate any relationships with FN outcome and to assess the reliability of the score. Results: Seventy-two patients with solitary primary VS were treated in the period of the study. A total of 59.8% of patients showed an HB value < 3 in the immediate postoperative period (T1), reaching to 76.4% at the last follow-up evaluation. A multiparametric score, Facial Nerve Outcome Score (FNOS), was built. The totality of patients with FNOS grade A showed an HB value < 3 at 12 months, decreasing to 70% for those with FNOS grade B, whereas 100% of patients with FNOS grade C showed an HB value ≥ 3. The ordinal logistic regression showed three times increasing probability to see an HB value ≥ 3 at 3-month follow-up for each worsening point in FNOS score [Exp(B), 2,999; p < 0.001] that was even more probable [Exp(B), 5.486; p < 0.001] at 12 months. Conclusion: The FNOS score resulted to be a reliable score, showing high associations with FN function both at short- and long-term follow-up. Although multicenter studies would be able to increase its reproducibility, it could be used to predict the FN damage after surgery and the potential of restoring its function on the long-term period.

Relationship between lumbar lordosis, pelvic parameters, PI-LL mismatch and outcome after short fusion surgery for lumbar degenerative disease. Literature review, rational and presentation of public study protocol: RELApSE study (registry for evaluation of lumbar artrodesis sagittal alignEment).

Background: Vertebral arthrodesis for degenerative pathology of the lumbar spine still remains burdened by clinical problems with significant negative results. The introduction of the sagittal balance assessment with the evaluation of the meaning of pelvic parameters and spinopelvic (PI-LL) mismatch offered new evaluation criteria for this widespread pathology, but there is a lack of consistent evidence on long-term outcome. Methods: The authors performed an extensive systematic review of literature, with the aim to identify all potentially relevant studies about the role and usefulness of the restoration or the assessment of Sagittal balance in lumbar degenerative disease. They present the study protocol RELApSE (NCT05448092 ID) and discuss the rationale through a comprehensive literature review. Results: From the 237 papers on this topic, a total of 176 articles were selected in this review. The analysis of these literature data shows sparse and variable evidence. There are no observations or guidelines about the value of lordosis restoration or PI-LL mismatch. Most of the works in the literature are retrospective, monocentric, based on small populations, and often address the topic evaluation partially. Conclusions: The RELApSE study is based on the possibility of comparing a heterogeneous population by pathology and different surgical technical options on some homogeneous clinical and anatomic-radiological measures aiming to understanding the value that global lumbar and segmental lordosis, distribution of lordosis, pelvic tilt, and PI-LL mismatch may have on clinical outcome in lumbar degenerative pathology and on the occurrence of adjacent segment disease.

Cervical Spine Inhomogeneously Enhancing Lesion: Avoiding Confirmation Bias.

Confirmation bias is the tendency to seek information and evidence in order to confirm a preexisting hypothesis while giving less importance and overlook an alternative solution. This report describes the case of a 52-year-old man with a long history of neck pain and bilateral upper limbs paresthesias with a cervical intracanal inhomogeneously enhancing lesion. Despite all the preoperative radiological findings, a spinal meningioma an anterior approach was performed. The mass ended up being a large migrated hernia with the involvement of two levels. Before suggesting treatment, especially surgery, physicians and practitioners need to evaluate all of the possible alternatives in order to optimize patient outcome.

Intraoperative Computed Tomography for C1-C2 Stabilization by Goel-Harms: Analysis of Clinical Efficacy and a Novel Classification of Screw Placement Accuracy.

BACKGROUND: The introduction of intraoperative computed tomography (iCT) could improve the surgical results of C1-C2 stabilization by Goel-Harms, especially in patients with complex deformities. This study aims to investigate the impact of iCT on the accuracy of C1-C2 screw positioning and to develop a score based on multiparametric analysis of imaging data (Cervical Screw Placement Accuracy score [CSPAs]). METHODS: Twenty-one patients were retrospectively evaluated. The data obtained with the use of an iCT were compared with the incidence of cases of malpositioning in the literature. Multiparametric imaging criteria were developed: the 82 screw positions were evaluated using the CSPA criteria and 2 additional variables. The CSPAs was obtained from the aggregation of the CSPAs criteria: optimal (CSPAs ≥8), suboptimal (CSPAs = 6-7), malpositioned (CSPAs ≤5). RESULTS: The average incidence of malpositioning in C1-C2 arthrodesis decreased from 13% without iCT to 1.2% with the aid of iCT, considering a monoparametric value. The CSPAs analysis shows a greater discretion and higher number of well-defined categories of the accuracy of C1-C2 screw position: optimal, 80.3%; suboptimal, 17.1%; and malposition, 2.6%. A correlation was observed between the accuracy of the positioning of both right and left screws in C2. Furthermore, the anatomic site of C2 screws was found to be a predictor of cortical invasion. CONCLUSIONS: The results suggest that the introduction of the iCT is associated with a consistent improvement of the accuracy in the positioning of the screws. A multiparametric score (CSPAs) could improve the assessment of screw placement.

Where We Mentalize: Main Cortical Areas Involved in Mentalization.

When discussing "mentalization," we refer to a very special ability that only humans and few species of great apes possess: the ability to think about themselves and to represent in their mind their own mental state, attitudes, and beliefs and those of others. In this review, a summary of the main cortical areas involved in mentalization is presented. A thorough literature search using PubMed MEDLINE database was performed. The search terms "cognition," "metacognition," "mentalization," "direct electrical stimulation," "theory of mind," and their synonyms were combined with "prefrontal cortex," "temporo-parietal junction," "parietal cortex," "inferior frontal gyrus," "cingulate gyrus," and the names of other cortical areas to extract relevant published papers. Non-English publications were excluded. Data were extracted and analyzed in a qualitative manner. It is the authors' belief that knowledge of the neural substrate of metacognition is essential not only for the "neuroscientist" but also for the "practical neuroscientist" (i.e., the neurosurgeon), in order to better understand the pathophysiology of mentalizing dysfunctions in brain pathologies, especially those in which integrity of cortical areas or white matter connectivity is compromised. Furthermore, in the context of neuro-oncological surgery, understanding the anatomical structures involved in the theory of mind can help the neurosurgeon obtain a wider and safer resection. Though beyond of the scope of this paper, an important but unresolved issue concerns the long-range white matter connections that unify these cortical areas and that may be themselves involved in neural information processing.