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Reappraisal of the role of translabyrinthine (TLAB) surgery in small- and medium-sized vestibular schwannomas (VSs).Retrospective study.Tertiary referral center.A total of 330 consecutive patients diagnosed between 1973 and 2019 with small- and medium-sized VS up to 20 mm in the extrameatal portion submitted to surgical treatment.VS removal through microscopic TLAB approach.Facial nerve function according to the House-Brackmann scale at 12-month follow-up, postoperative complications and entity of tumor resection assessed with postoperative MRI. A comparative analysis of outcomes between two groups of patients was further conducted, according to tumor size: Group A, small-sized (intrameatal or ≤10 mm extrameatal tumors) and Group B, medium-sized VSs (extrameatal between 11 and 20 mm).Complete tumor removal was achieved in all cases. The overall complication rate was 5.5%, being cerebrospinal fluid leak the most frequent. Patients with small-sized VS (n = 121) presented a significantly better facial nerve function than patients with medium-sized tumors (n = 209), showing House-Brackmann Grades I to II in 92.6% versus 73.6% of cases, respectively ( p0.001). A nearly 4.5-fold higher risk of poor facial nerve function at 12 months affects patients with medium-sized tumors (odds ratio, 4.473; 95% confidence interval, 2.122-9.430; p0.001).In the current scenario of multioptional VS management, when hearing preservation is not feasible, early TLAB approach as first-line treatment for small-sized VSs showed favorable results. Factors supporting such proactive surgical treatment include long-term definitive cure, no major complications, good facial nerve outcomes, and the possibility of simultaneous hearing rehabilitation with a cochlear implant.

Purpose:In-depth characterization of recurrent glioblastoma (rGBM) might contribute to a better understanding of the mechanisms behind tumor progression and enable rGBM treatment with targeted drugs.Experimental Design: In this study, GBM samples were collected at diagnosis and recurrence from adult patients treated with Stupp protocol. Expression of mismatch repair (MMR) proteins was evaluated by IHC, followed by whole exome sequencing (WES) of tumor samples showing loss of MSH6 reactivity. Established genetic, epigenetic, and immunologic markers were assessed by standard methods and correlated with loss of MMR proteins and patient survival.Results:Expression of MMR proteins was partially or completely lost in 25.9% rGBM samples. Specifically, 12 samples showed partial or total MSH6 expression reduction. Conversely, 96.4% of GBM samples at diagnosis expressed MMR markers. WES disclosed lack of variants in MMR genes in primary samples, whereas two MSH6-negative rGBM samples shared a c.3438+1G>A* splicing MSH6 variant with a potential loss of function effect. MSH6-negative rGBM specimens had high tumor mutational burden (TMB), but no microsatellite instability. In contrast, GBM samples with partial loss of MMR proteins disclosed low TMB. MMR-deficient rGBM showed significant telomere shortening and MGMT methylation and are characterized by highly heterogeneous MHC class I expression.Conclusions:Multilevel profiling of MMR-deficient rGBM uncovered hypermutated genotype uncoupled from enriched expression of immune-related markers. Assessment of MHC class I expression and TMB should be included in protocols aiming to identify rGBM patients potentially eligible for treatment with drugs targeting immune-checkpoint inhibitors.

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Suppl. Methods: Sanger sequencing, IDH1/2 mutations and Fluorescence in situ hybridization (FISH)

Vagus nerve stimulation (VNS) has been shown to be effective for treatment-resistant depression (TRD). However, long-term (5 years) studies on the efficacy and tolerability of this treatment have been lacking. Here, we report a long-term clinical follow-up of 5 patients with severe and long-standing TRD, who received a VNS implant.Of the initial 6 patients with TRD implanted with VNS at our center, 5 of them were followed for 6 to 12 years after implantation. Primary efficacy outcomes were clinical response and improved functioning at follow-up visits. The primary safety outcome was all-cause discontinuation, and the secondary safety outcomes were the number and the severity of adverse events.The VNS implant was associated with a sustained response (10 years) in terms of clinical response and social, occupational, and psychological functioning in 3 patients. Two patients dropped out after 6 and 7 years of treatment, respectively. Vagus nerve stimulation was well tolerated by all patients, who reported only mild adverse effects. One patient, who discontinued concomitant drug treatment, had a hypomanic episode in the 10th year of treatment. The parameters of the VNS device were fine-tuned when life stressors or symptom exacerbation occurred.Our case series showed that VNS can have long-term and durable effectiveness in patients with severe multiepisode chronic depression, and this could be associated with its neuroplastic effects in the hippocampus. In light of good general tolerability, our findings support VNS as a viable treatment option for TRD.

Despite the increasing incidence rate of vestibular schwannomas (VS), controversies in their management are still present.A 35-item multiple-choice survey investigating the current practice patterns of VS care was sent to the members of the Italian Society of Otolaryngology, Head and Neck Surgery (SIO) and of the Italian Society of Neurosurgery (SINCH).Among 66 respondents, 37 (56.0%) claimed to be actively involved in VS management. Most interviewees (35.1%) declared20 years of experience and 59.5% claimed to work in an academic practice. The number of cases evaluated in each centre per year varied widely, with 54.0% evaluating25 cases/year and only 13.6%100 cases/year. Multidisciplinary care for VS evaluation was confirmed by 50.0% of respondents, and multidisciplinary surgical care by 62.2%. Observation and surgery were the most common management options proposed. Further details regarding VS care are presented.The present study provides the first overview on the current practice patterns of VS care in Italy. Although integrated in most centres, a multidisciplinary model of care needs to be encouraged. Wide heterogeneity in experience and practices is mostly influenced by the surgeon's different specialties and by the lack of shared guidelines.L’attuale gestione dello schwannoma vestibolare in Italia: risultati di una survey nazionale.Nonostante il costante incremento di incidenza dello schwannoma vestibolare (VS), non vi è ancora uniformità nella gestione di tale patologia.Un questionario di 35 domande sulle strategie di trattamento del VS è stato sottoposto ai membri della SIO e della SINCH.Tra i 66 intervistati che hanno risposto al questionario, il 56,0% ha confermato di prendere parte attivamente nel trattamento dello VS. La maggioranza dei partecipanti (35,1%) dichiarava20 anni di esperienza nel settore, e il 59,5% di lavorare in un contesto accademico. Il 54,0% degli intervistati ha affermato di valutare25 casi/anno, mentre solo il 13,6%100 casi/anno. Il 50,0% ha dichiarato di valutare lo VS nell’ambito di un gruppo multidisciplinare, mentre il 62,2% di operare in un contesto multidisciplinare. L’approccio conservativo e la chirurgia si confermavano le strategie terapeutiche più frequentemente proposte.Lo studio presenta una prima panoramica sulle strategie di trattamento dello VS in Italia. Nonostante un modello multidisciplinare di gestione dello VS sia già diffuso in molti centri, è necessario incrementarne ulteriormente lo sviluppo. Le diverse specializzazioni del chirurgo e la mancanza di linee guida condivise contribuiscono a determinare la vasta eterogeneità osservata nella gestione del VS nel nostro Paese.

The interest in surgical routes to the internal auditory canal (IAC) through the external auditory canal for vestibular schwannoma removal has been recently raised by the endoscopic approaches to the lateral skull base. The aim of the study was to reappraise the transmeatal microsurgical approach (TMMa) to the labyrinth and IAC, first described 50 years ago.A retrospective series of 8 consecutive patients treated for intralabyrinthine and intrameatal schwannomas through TMMa is presented. Main outcome measures consisted of surgical indications, postoperative complications, facial nerve status, bed mobilisation time, hospitalisation time and tumour recurrence rate.Surgical indications for TMMa were tumour growth (62.5%) and disabling vertigo (37.5%) in the present series. Complete tumour removal with no complications and postoperative normal facial nerve function was obtained in all cases. Bed mobilisation occurred after a median of 3 postoperative days (IQR 2.2-3.0) and discharge after a median of 5.6 days (IQR 4.7-7.0). After a median follow-up of 13 months (IQR 7.5-27.5), no tumour recurrence was observed.TMMa indications are limited to schwannomas of the labyrinth and IAC, which dropped out from observation protocols due to unmanageable symptoms or growth. Despite the narrow mini-invasive surgical corridor, the TMMa was a safe an effective microsurgical technique in terms of tumour removal and postoperative course.Approccio transmeatale microchirurgico nei neurinomi intralabirintici e intrameatali: rivalutazione di una tecnica.L’interesse per i corridoi chirurgici dal condotto uditivo esterno al condotto uditivo interno (CUI) nel trattamento del neurinoma è incrementato negli ultimi anni grazie alla divulgazione di approcci endoscopici al basecranio laterale. Lo studio si prefigge di rivalutare l’approccio microscopico transmeatale (TMMa) al labirinto e al CUI, descritto in origine circa 50 anni fa.Otto pazienti sottoposti a TMMa per exeresi di neurinomi intralabirintici o intrameatali sono stati inclusi nello studio. Indicazione chirurgica a TMMa, complicanze postoperatorie, funzionalità del nervo facciale, tempo di mobilizzazione dal letto e di degenza, tasso di recidiva sono state le principali misure di outcome analizzate.Crescita tumorale (62,5%) e vertigini incoercibili (37,5%) hanno rappresentato l’indicazione chirurgica più frequente. In tutti i pazienti il tumore è stato rimosso in toto, in assenza di complicanze postoperatorie. La mobilizzazione dal letto è avvenuta dopo 3 giorni (IQR 2,2-3,0), la dimissione dopo 5,6 giorni (IQR 4,7-7,0). All’ultimo follow-up (mediana 13 mesi, IQR 7,5-27,5) non sono state registrate recidive.L’indicazione al TMMa è limitata agli schwannomi intralabirintici e/o estesi al CUI, che escono dal protocollo di osservazione a causa di sintomi invalidanti o crescita. Nonostante l’accesso chirurgico mini-invasivo offra uno spazio limitato di manovra, il TMMa si è dimostrato una opzione di trattamento microchirurgico sicura ed efficace in termini di rimozione tumorale e decorso postoperatorio.

BACKGROUND AND PURPOSE: Tractography of the facial nerve based on single-shell diffusion MR imaging is thought to be helpful before surgery for resection of vestibular schwannoma. However, this paradigm can be vitiated by the isotropic diffusion of the CSF, the convoluted path of the facial nerve, and its crossing with other bundles. Here we propose a multishell diffusion MR imaging acquisition scheme combined with probabilistic tractography that has the potential to provide a presurgical facial nerve reconstruction uncontaminated by such effects. MATERIALS AND METHODS: Five patients scheduled for vestibular schwannoma resection underwent multishell diffusion MR imaging (b-values = 0, 300, 1000, 2000 s/mm2). Facial nerve tractography was performed with a probabilistic algorithm and anatomic seeds located in the brain stem, cerebellopontine cistern, and internal auditory canal. A single-shell diffusion MR imaging (b-value = 0, 1000 s/mm2) subset was extrapolated from the multishell diffusion MR imaging data. The quality of the facial nerve reconstruction based on both multishell diffusion MR imaging and single-shell diffusion MR imaging sequences was assessed against intraoperative videos recorded during the operation. RESULTS: Single-shell diffusion MR imaging–based tractography was characterized by failures in facial nerve tracking (2/5 cases) and inaccurate facial nerve reconstructions displaying false-positives and partial volume effects. In contrast, multishell diffusion MR imaging–based tractography provided accurate facial nerve reconstructions (4/5 cases), even in the presence of ostensibly complex patterns. CONCLUSIONS: In comparison with single-shell diffusion MR imaging, the combination of multishell diffusion MR imaging–based tractography and probabilistic algorithms is a more valuable aid for surgeons before vestibular schwannoma resection, providing more accurate facial nerve reconstructions, which may ultimately improve the postsurgical patient’s outcome.

Secreting pituitary adenomas are tumors for which few treatment options are available, including surgical treatment and management of hormonal imbalance due to altered pituitary secretion. In case of inoperable relapse, radiotherapy or chemotherapeutic treatment can be considered; the effectiveness of these treatments, however, remains limited. In the immunotherapy era, it is necessary to select patients who can benefit from immunotherapeutic treatment. Mismatch repair deficiency is strongly associated with responsiveness to anti-PD-1 in other cancers and can be detected using immunohistochemistry for MLH1, MSH2, MHS6, and PMS2. In this case report, we report a case of rapid disease progression to pembrolizumab in a patient with a MMRd pituitary adrenocorticotropic hormone (ACTH)-secreting adenoma. For the best of our knowledge, we described for the first time, a poor efficacy of pembrolizumab in a patient with ACTH-secreting pituitary adenoma having mismatch repair deficiency probably caused by high levels of cortisol in this patient. Prospective study should be performed to assess the activity of immune checkpoint inhibitor alone or in association with temozolomide in this subsetting of pituitary adenomas.

Though the assessment of cognitive functions is proven to be a reliable prognostic indicator in patients with brain tumors, some of these functions, such as cognitive control, are still rarely investigated. The objective of this study was to examine proactive and reactive control functions in patients with focal brain tumors and to identify lesioned brain areas more at "risk" for developing impairment of these functions. To this end, a group of twenty-two patients, candidate to surgery, were tested with an AX-CPT task and a Stroop task, along with a clinical neuropsychological assessment, and their performance was compared to that of a well-matched healthy control group. Although overall accuracy and response times were similar for patients and control groups, the patient group failed more on the BX trials of the AX-CPT task and on the incongruent trials of the Stroop task, specifically. Behavioral results were associated with the damaged brain areas, mostly distributed in right frontal regions, by means of a lesion-symptom mapping multivariate approach. This analysis showed that a white matter cluster in the right prefrontal area was associated with lower d'-context values on the AX-CPT, which reflected the fact that these patients rely more on later information (reactive processes) to respond to unexpected and conflicting stimuli, than on earlier contextual cues (proactive processes). Taken together, these results suggest that patients with brain tumors present an imbalance between proactive and reactive control strategies in high interfering conditions, in association with right prefrontal white matter lesions.

Assessment of impaired/preserved cortical regions in brain tumours is typically performed via intraoperative direct brain stimulation of eloquent areas or task-based functional MRI. One main limitation is that they overlook distal brain regions or networks that could be functionally impaired by the tumour. This study aims (i) to investigate the impact of brain tumours on the cortical synchronization of brain networks measured with resting-state functional magnetic resonance imaging (resting-state networks) both near the lesion and remotely and (ii) to test whether potential changes in resting-state networks correlate with cognitive status. The sample included 24 glioma patients (mean age: 58.1 ± 16.4 years) with different pathological staging. We developed a new method for single subject localization of resting-state networks abnormalities. First, we derived the spatial pattern of the main resting-state networks by means of the group-guided independent component analysis. This was informed by a high-resolution resting-state networks template derived from an independent sample of healthy controls. Second, we developed a spatial similarity index to measure differences in network topography and strength between healthy controls and individual brain tumour patients. Next, we investigated the spatial relationship between altered networks and tumour location. Finally, multivariate analyses related cognitive scores across multiple cognitive domains (attention, language, memory, decision making) with patterns of multi-network abnormality. We found that brain gliomas cause broad alterations of resting-state networks topography that occurred mainly in structurally normal regions outside the tumour and oedema region. Cortical regions near the tumour often showed normal synchronization. Finally, multi-network abnormalities predicted attention deficits. Overall, we present a novel method for the functional localization of resting-state networks abnormalities in individual glioma patients. These abnormalities partially explain cognitive disabilities and shall be carefully navigated during surgery.

Background: In the last decade, application of the high-definition exoscope to different neurosurgical procedures has been reported in the literature. We described the first experience with the VITOM®-3D (Video Telescope Operating Microscope, Karl Storz Endoscopy, Tuttlingen, Germany) for the surgical treatment of intradural extra-medullary tumors. Methods: Five neurosurgical procedures for the removal of intradural extra-medullary tumors were performed with the VITOM®-3D. Patients' population, feasibility of surgery under the exoscope visualization, VITOM®-3D's technical and optical characteristics, and surgical outcome were analyzed. Results: All surgeries were performed following the common steps of spinal neurosurgical intradural procedures. The exoscope offered excellent, magnified, and brilliantly illuminated high-definition images of the surgical field in all the described cases. All the reported surgical operations were successfully completed under exoscope magnification from both the technical as well as the clinical points of view. No complications potentially related to the use of the exoscope occurred. Working environment ergonomics and trainees learning experience were the most relevant benefits associated with the use of exoscope. Conclusions: VITOM®-3D may represent a valid visualization tool in spinal procedure for intradural extra-medullary tumors. Our preliminary experience can be useful in better define the role of VITOM®-3D in neurosurgery.

To describe our institutional experience in cochlear implantation after vestibular schwannoma (VS) resection, and compare the audiological outcomes between sporadic and neurofibromatosis type 2 (NF2) VS sub-cohorts of patients, and in relation to preoperative contralateral hearing.Seventeen patients (8 sporadic and 9 NF2-associated VSs) who had undergone VS resection and cochlear implant (CI) were analyzed retrospectively. Audiological outcomes at 24 months were correlated with preoperative clinical variables. The results according to VS type (sporadic vs. NF2-associated) and contralateral hearing (impaired vs. normal) were compared.Fourteen CIs were actively used by the patients (77.8%). Twenty-four months after CI activation, the median postoperative PTA (pure tone average) was 45.6 dB nHL and a measurable WRS (Word Recognition Score) was achieved by 44.4% of patients (median WRS = 40%). The median postoperative PTA in the implanted ear resulted better in the group with an impaired contralateral hearing (36.3 dB nHL vs. 78.8 dB nHL, p = 0.019). Good preoperative contralateral hearing status (A-B classes of AAO-HNS) was a negative prognostic factor for CI performance on open-set discrimination (OR = 28.0, 95% CI 2.07-379.25, p = 0.012).CI is a viable rehabilitative option for patients with sporadic or NF2-associated VS. A good contralateral hearing adversely affects CI outcome and should be taken into consideration for patients' selection and rehabilitation programs.

Gliomas are amongst the most common primary brain tumours in adults and are often associated with poor prognosis. Understanding the extent of white matter (WM) which is affected outside the tumoral lesion may be of paramount importance to explain cognitive deficits and the clinical progression of the disease. To this end, we explored both direct (i.e., tractography based) and indirect (i.e., atlas-based) approaches to quantifying WM structural disconnections in a cohort of 44 high- and low-grade glioma patients. While these methodologies have recently gained popularity in the context of stroke and other pathologies, to our knowledge, this is the first time they are applied in patients with brain tumours. More specifically, in this work, we present a quantitative comparison of the disconnection maps provided by the two methodologies by applying well-known metrics of spatial similarity, extension, and correlation. Given the important role the oedematous tissue plays in the physiopathology of tumours, we performed these analyses both by including and excluding it in the definition of the tumoral lesion. This was done to investigate possible differences determined by this choice. We found that direct and indirect approaches offer two distinct pictures of structural disconnections in patients affected by brain gliomas, presenting key differences in several regions of the brain. Following the outcomes of our analysis, we eventually discuss the strengths and pitfalls of these two approaches when applied in this critical field.

Background Although gliomas are strictly confined to the central nervous system, their negative influence over the immune system can extend to peripheral circulation. The immune suppression exerted by myeloid cells is capable of affecting both response to therapy and disease outcome. Here we analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome. Methods Peripheral blood was obtained from 134 low- and high-grade glioma patients before surgery and treatment. Myeloid cell subsets such as total CD14+, CD14+/p-STAT3+, CD14+/PD-L1+, CD15+ cells and 4 myeloid derived suppressor cell (MDSC) subsets, were evaluated by multiparametric flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Principal component analysis was performed to define correlations between myeloid markers. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls, and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters. Results In the blood of glioma patients, changes in myeloid parameters associated with immune suppression were identified and allowed us to define a diagnostic score calculating the risk of being a glioma patient, that included CD15+ cells, MDSC1, MDSC3, p-STAT3 and ARG1 activity. Of note, the same parameters, together with age, can also be used to calculate the risk score in differentiating each glioma grade. Finally, a prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3 and ARG1 activity together with clinical parameters in predicting the patient outcome. Conclusions This work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis and outcome of glioblastoma patients lays the ground for their clinical use for stratification and follow up.

Background Neurofibromatosis type 2 (NF2) is an autosomal dominant, multiple neoplasia syndrome characterized by bilateral vestibular schwannomas (VSs). Endoglin is a proliferation-associated protein expressed in angiogenic endothelial cells. The aim of this study was to investigate endoglin expression in a series of NF2-associated VSs, as compared with a group of sporadic VSs. Methods Using image analysis, vessel cross-sectional area (AA) and density (VD) were calculated from CD105 expression in 7 NF2-associated VSs and 14 size-matched sporadic VSs. Results There were no significant differences between NF2-associated VSs and sporadic cases in terms of AA (P = .28), or VD (P = .39). A positive correlation emerged between tumor growth rate (measured on contrast-enhanced MRI) and VD in the cohort of NF2-associated VSs (rho = 0.95, P = .05). Conclusions Further investigations are needed to ascertain the feasibility of (a) measuring circulating endoglin levels to monitor tumor growth rate and (b) targeting tumor neoangiogenesis with anti-endoglin approaches in NF2-associated VS.

In vestibular schwannoma surgery, the preservation of facial and cochlear nerves is of paramount concern regarding to their effect on patients' quality of life. The rate of nerve function preservation has increased with advancements in surgical technique and neuroimaging and the introduction of intraoperative neuromonitoring. The preoperative depiction of anatomical issues between the nerves and tumor could help in surgical planning. Many studies investigating advanced imaging for cranial nerves detection, in particular diffusion tensor imaging, have been reported in the past decade. A systematic review of the reported data evaluating preoperative facial nerve fiber tracking, followed by intraoperative verification, was conducted. Seventeen studies with 223 patients (mean age, 47.5 years; range 17-77; male/female ratio 1:1.4) met our inclusion criteria. Preoperative facial nerve fiber tracking was obtained for 214 patients (96%), and subsequent intraoperative verification revealed a correct prediction for 187 cases (85.5%). The results from the present review have confirmed that preoperative fiber tracking for facial nerve identification during large vestibular schwannoma surgery is valuable and reliable. However, the included studies were not comparable in terms of images, acquisitions, or postprocessing elaboration. Larger series and homogenous magnetic resonance imaging parameters are required to strengthen these findings.

The choice between sitting and prone position to access the infratentorial space in a suboccipital craniotomy is still a matter of debate. The comparisons in terms of complications and outcome of both positions are scarce, and the pediatric population is indeed more infrequent in these in scientific reviews. In this paper, we assess intraoperative and postoperative complications and neurological outcome in pediatric patients undergoing posterior cranial fossa surgery for pilocytic astrocytoma in sitting and prone position respectively. We retrospectively analyzed 30 consecutive patients undergoing surgery for cerebellar pilocytic astrocytoma at the two neurosurgical units referring to the University of Padova Medical School from 1999 to 2017. Preoperative, intraoperative, and postoperative data were retrieved from our medical archives. The statistical analysis did not show any differences between the two groups in terms of preoperative, intraoperative, and postoperative data. The neurological status at last follow-up was similar in both groups of patients. Our results suggest that both sitting and prone position can be considered safe in suboccipital craniotomies. Further studies are needed to show if there are possible differences between these positions for other frequent pediatric tumors such as medulloblastomas and ependymomas.

Lettera in risposta a: “Approccio transmeatale microchirurgico nei neurinomi intralabirintici e intrameatali: revisione della letteratura”.

Background: Radiological parameters predicting the postoperative neurological outcome after resection of a spinal meningioma (SM) are poorly studied, with controversial results. Methods: Observational multicenter cohort (2011–2018) of adult patients undergoing surgery for resection of SM. Tumor-canal volume ratio (TCR), the areas related to the cord and tumor occupancy at maximum compression, the presence of dural tail, calcifications, signs of myelopathy, and postoperative cord expansion were compared with the modified McCormick scale (mMCS) preoperative and at follow-up. Results: In the cohort (n = 90 patients), cord and tumor occupancy as well as cord compression and tumor volume showed a correlation with preoperative mMCS (p &lt, 0.05, R −0.23, p &lt, 0.001, R 0.35, 0.005, R −0.29, 0.001, R 0.42). Cord occupancy had a strong correlation with cord compression (p &lt, 0.001, R 0.72). Tumor occupancy and TCR were correlated with relative outcome at follow-up (p &lt, 0.005 R 0.3, 0.005 R 0.29). No correlation was found between cord re-expansion and clinical outcome at follow-up. Finally, a correlation was shown between preoperative signs of cord myelopathy and mMCS (p &lt, 0.05 R 0.21) at follow-up. Conclusions: Larger tumors showed lower preoperative functional status and a worse clinical outcome. Moreover, preoperative T2 cord signal changes are correlated with a poorer outcome.

Awake surgery and intraoperative neuromonitoring represent the gold standard for surgery of lesion located in language-eloquent areas of the dominant hemisphere, enabling the maximal safe resection while preserving language function. Nevertheless, this functional mapping is invasive; it can be executed only during surgery and in selected patients. Moreover, the number of neuro-oncological bilingual patients is constantly growing, and performing awake surgery in this group of patients can be difficult. In this scenario, the application of accurate, repeatable and non-invasive preoperative mapping procedures is needed, in order to define the anatomical distribution of both languages. Repetitive navigated transcranial magnetic stimulation (rnTMS) associated with functional subcortical fiber tracking (nTMS-based DTI-FT) represents a promising and comprehensive mapping tool to display language pathway and function reorganization in neurosurgical patients. Herein we report a case of a bilingual patient affected by brain tumor in the left temporal lobe, who underwent rnTMS mapping for both languages (Romanian and Italian), disclosing the true eloquence of the anterior part of the lesion in both tests. After surgery, language abilities were intact at follow-up in both languages. This case represents a preliminary application of nTMS-based DTI-FT in neurosurgery for brain tumor in eloquent areas in a bilingual patient.

OBJECTIVEThe purpose of this study was to analyze the effect of the coronavirus disease 2019 (COVID-19) outbreak and of the subsequent lockdown on the neurosurgical services of the Veneto region in Italy compared to the previous 4 years.METHODSA survey was conducted in all 6 neurosurgical departments in the Veneto region to collect data about surgical, inpatient care and endovascular procedures during the month of March for each year from 2016 to 2020. Safety measures to avoid infection from SARS-CoV-2 and any COVID-19 cases reported among neurosurgical patients or staff members were considered.RESULTSThe mean number of neurosurgical admissions for the month of March over the 2016–2019 period was 663, whereas in March 2020 admissions decreased by 42%. Emergency admissions decreased by 23%. The average number of neurosurgical procedures was 697, and declined by 30% (range −10% to −51% in individual centers). Emergency procedures decreased in the same period by 23%. Subarachnoid hemorrhage and spontaneous intracerebral hemorrhage both decreased in Veneto—by 25% and 22%, respectively. Coiling for unruptured aneurysm, coiling for ruptured aneurysm, and surgery for ruptured aneurysm or arteriovenous malformation diminished by 49%, 27%, and 78%, respectively. Endovascular procedures for acute ischemic stroke (AIS) increased by 33% in 2020 (28 procedures in total). There was a slight decrease (8%) in brain tumor surgeries. Neurosurgical admissions decreased by 25% and 35% for head trauma and spinal trauma, respectively, while surgical procedures for head trauma diminished by 19% and procedures for spinal trauma declined by 26%. Admissions and surgical treatments for degenerative spine were halved. Eleven healthcare workers and 8 patients were infected in the acute phase of the pandemic.CONCLUSIONSThis multicenter study describes the effects of a COVID-19 outbreak on neurosurgical activities in a vast region in Italy. Remodulation of neurosurgical activities has resulted in a significant reduction of elective and emergency surgeries compared to previous years. Most likely this is a combined result of cancellation of elective and postponable surgeries, increase of conservative management, increase in social restrictions, and in patients’ fear of accessing hospitals. Curiously, only endovascular procedures for AIS have increased, possibly due to reduced physical activity or increased thrombosis in SARS-CoV-2. The confounding effect of thrombectomy increase over time cannot be excluded. No conclusion can be drawn on AIS incidence. Active monitoring with nasopharyngeal swabs, wearing face masks, and using separate pathways for infected patients reduce the risk of infection.

Calvaria defects in children present a reconstructive challenge. When autogenous bone is not available, synthetic materials can be used; however, they present many drawbacks limiting their use in infants. Children, especially under the age of two, represent an incomparable limitation and they are infrequently reported in literature. The reconstructive strategies presented in the last decades are different without a clear consensus about the best procedure and material for a specific range of age. We report our experience with resorbable mesh cranioplasty using a polylactic acid / polyglycolic acid resorbable mesh plate with bone matrix in a 3-month old child who previously underwent decompressive craniectomy. This reconstructive strategy failed, and the patient was scheduled for a second procedure. After the case presentation, the literature is reviewed and discussed focusing on infants and young children. Keywords: Craniectomy, Cranioplasty, Infant, Resorbable mesh

Neurocysticercosis is the most frequent parasitic disease of the central nervous system, and its incidence in the developed countries is increasing due to immigration and travels from endemic areas. The intraventricular location has been found to involve up to 61.3% of the patients; moreover, only 22 cases of migrating intraventricular cyst have been reported so far. Despite the rarity of the condition in western countries, its occurrence generates some concerns and the aim of this paper is to update the information concerning pathogenesis, clinical presentation, diagnosis and management of this entity. All the pertinent literature was analysed, focused on the cases of migrating intraventricular neurocysticercosis and its peculiar features. An illustrative case regarding a 14-year-old girl is also presented. Migrating intraventricular neurocysticercosis is a pathognomonic entity usually presenting with hydrocephalus, and its treatment is mainly surgical, preferring an endoscopic approach. When the resection of the intraventricular cyst is not performed, an accurate follow-up is mandatory to detect clinical changes due to a recurrent hydrocephalus or to the effect of the dying cyst on the surrounding area. In case of permanent shunt placement, the cysticidal and steroid treatment is recommended to reduce the risk of shunt failure.

Background The use of surgical cochlear nerve decompression is controversial. This study aimed at investigating the safety and validity of microsurgical decompression via an endoscope-assisted retrosigmoid approach to treat tinnitus in patients with neurovascular compression of the cochlear nerve. Case Description Three patients with disabling tinnitus resulting from a loop in the internal auditory canal were evaluated with magnetic resonance imaging and tests of pure tone auditory, tinnitus, and auditory brain response (ABR) to identify the features of the cochlear nerve involvement. We observed a loop with a caliber greater than 0.8 mm in all patients. Patients were treated via an endoscope-assisted retrosigmoid microsurgical decompression. After surgery, none of the patients reported short-term or long-term complications. After surgery, tinnitus resolved immediately in 2 patients, whereas in the other patient symptoms persisted although they improved; in all patients, hearing was preserved and ABR improved. Conclusion Microsurgical decompression via endoscope-assisted retrosigmoid approach is a promising, safe, and valid procedure for treating tinnitus caused by cochlear nerve compression. This procedure should be considered in patients with disabling tinnitus who have altered ABR and a loop that has a caliber greater than 0.8 mm and is in contact with the cochlear nerve.

Dandy-Walker malformation is a rare condition due to imperforation of the Blake’s pouch during intrauterine brain development, usually leading to early severe hydrocephalus. The association with holocord syringomyelia is rare, and from the Gardner’s first report in 1957, only 23 cases have been described, mostly from autopsy series and pre-MRI period. Besides a worsening of clinical picture, its occurrence generates some concern about the best surgical treatment that varies widely among the literature reports. An 11-year-old girl with Dandy-Walker malformation presented with a holocord syrinx due to the herniation of the lower pole of the posterior fossa cyst through the foramen magnum. After an unsuccessful shunt revision, she underwent a cystoperitoneal shunt with regression of the syrinx and of neurological symptoms at the 12-month follow-up. Previous literature about pathogenesis, treatment, and follow-up is discussed and summarized.

Objectives Vestibular schwannomas (VS) extending into the internal auditory canal (IAC) are currently considered as an unfavorable condition for hearing preservation surgery (HPS) via retrosigmoid (RS) approach due to the poor direct visualization of the facial and cochlear nerves course through the IAC and the fundus during microsurgery. Design The operative steps are described in a surgical instructional video. Setting The surgery took place at a tertiary-care center. Participants Patient is a 45-year-old man who was incidentally diagnosed with an extrameatal VS extending for 9 mm into the left cerebellopontine angle (CPA). Hearing function at diagnoses was excellent, with pure tone average (PTA) = 15 dB and speech discrimination score (SDS) = 100% (class A according to the Tokyo classification) and minimal impairments on auditory brainstem response (ABR). Given these preoperative features in small VS, hearing was the main function to look into in the treatment planning. Initial observation or HPS were proposed. Results The patient underwent surgical excision for HPS via RS approach combined with retrolabyrinthine meatotomy (RLM). RLM enables the complete exposure of the IAC to the fundus, after drilling the bony surface of the posterior IAC wall, under guidance of the anatomical landmarks, namely, the endolymphatic duct, the blue lines of the posterior, and superior semicircular canals, and common crus. Nor intra-, neither postoperative complications occurred. Histologic examination confirmed the diagnosis of VS. A 3-month short-term follow-up revealed a class B hearing function with PTA = 30 dB, SDS = 100%, and normal facial nerve status. Conclusions RLM via RS approach proved to be effective for HPS, enabling the full course of the facial and cochlear nerves through the IAC to be directly exposed.The link to the video can be found at: https://youtu.be/KC1S4pxpLCk.

Pituitary adenomas are usually considered benign tumours, although some of them can exhibit an aggressive behaviour. Patients with clinically aggressive pituitary adenomas are frequently diagnosed with larger masses, and may present an earlier recurrence (or persistence) after surgery. Our aim was to characterise the clinical, histopathological and radiological features of patients with aggressive pituitary adenoma, in order to correlate their clinical behaviour with the response to treatment plan. We considered an aggressive pituitary adenoma on the basis of radiological features (size, local invasion), pathological reports (atypical adenoma: MIB-1 >3%, p53 immunoreactivity, increased mitotic activity) and clinical aspects (response to surgery, radiotherapy and medical treatment). Among our cohort of 582 patients, we considered 102 subjects with aggressive pituitary adenomas (18%, 56 male and 46 female): 14 adrenocorticotrophic hormone (ACTH)-secreting, 18 growth hormone (GH)-secreting, 23 prolactin (PRL)-secreting and 47 non-secreting, with a median follow-up of 5 years. In the whole cohort, 75% of patients with aggressive pituitary adenomas presented invasion of surrounding structure, especially GH-secreting, PRL-secreting and non-secreting. Besides invasion, their remission rate after surgery, radiotherapy or medical treatment was similar, irrespective of hormonal secretion. Surgery was the most performed treatment (overall remission rate of 24%), especially in those patients with ACTH- or GH-secreting adenoma, and 22% of patients were submitted to radiotherapy, with a remission rate of 45% after a median of 3 years. Two consecutive years of medical treatment, in patients with secreting pituitary adenoma, achieved disease control in 41% of them. Considering pathological reports, 24% of cases were defined as atypical adenomas; radiological characteristics, responses to medical treatment and remission rates were similar among patients with typical and atypical adenoma. We proposed a new and comprehensive definition of aggressive pituitary adenoma, based upon radiological, clinical and pathological features. In a selected cohort of patients, radiological invasion resulted in the most common marker to describe the aggressive behaviour of pituitary adenoma. Surgery, radiotherapy and medical treatment (the latter only in secreting adenoma) achieved disease control in half of the patients with aggressive adenoma, especially surgery in those with ACTH-oma and medical treatment in those with GH- and PRL-secreting adenoma. Nevertheless, radiological, clinical or atypical features did not affect the outcome.

Although the diagnosis and treatment of sporadic vestibular schwannoma has improved in recent years, no factors capable of predicting its growth have been identified as yet. Endoglin (CD105) is a proliferation-associated protein expressed in angiogenic endothelial cells, and a potential prognostic indicator for several solid tumors. The aim of the present study was primarily to investigate the expression and role of CD105 in a series of sporadic vestibular nerve schwannomas. In 71 consecutive cases of vestibular schwannoma, vessel cross-sectional area and density were calculated from immunohistochemically assessed CD105 expression using image analysis to correlate them with: (i) tumor dimensions; and (ii) tumor growth rate measured on high-resolution contrast-enhanced MRI (ceMRI). Based on assessments of CD105 expression, a significant positive correlation was identified between vessel cross-sectional area and tumor size at the time of surgery (p = 0.0024), and between vessel density and tumor size (p = 0.013). Vessel cross-sectional area (p = 0.0006) and vessel density (p = 0.003) were significantly greater in tumors measuring ≥10 mm in size than in those10 mm. Conversely, when tumor growth rate could be calculated from two or more ceMRI (38 cases), there was no significant correlation between tumor growth rate and cross-sectional vessel area or vessel density as assessed with CD105. Further investigations are needed to ascertain the feasibility of: (i) using circulating endoglin assay to monitor tumor growth; and (ii) targeting neoangiogenesis with anti-endoglin antibodies in sporadic vestibular schwannoma.