The "state of the art" of intraoperative neurophysiological monitoring: An Italian neurosurgical survey.

Introduction: Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers. Research question: The section of Functional Neurosurgery of the Italian Society of Neurosurgery realized a survey aiming to obtain general data on the current practice of IOM in Italy. Materials and methods: A 22-item questionnaire was designed focusing on: volume procedures, indications, awake surgery, experience, organization and equipe. The questionnaire has been sent to Italian Neurosurgery centers. Results: A total of 54 centers completed the survey. The annual volume of surgeries range from 300 to 2000, and IOM is used in 10-20% of the procedures. In 46% of the cases is a neurologist or a neurophysiologist who performs IOM. For supra-tentorial pathology, almost all perform MEPs (94%) SSEPs (89%), direct cortical stimulation (85%). All centers perform IOM in spinal surgery and 95% in posterior fossa surgery. Among the 50% that perform peripheral nerve surgery, all use IOM. Awake surgery is performed by 70% of centers. The neurosurgeon is the only responsible for IOM in 35% of centers. In 83% of cases IOM implementation is adequate to the request. Discussion and conclusions: The Italian Neurosurgical centers perform IOM with high level of specialization, but differences exist in organization, techniques, and expertise. Our survey provides a snapshot of the state of the art in Italy and it could be a starting point to implement a consensus on the practice of IOM.

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.

Hardware-Related Skin Erosion in Deep Brain Stimulation for Parkinson's Disease: How Far Can We Go? An Illustrative Case Report.

Skin erosion is a hardware-related complication commonly described after deep brain stimulation (DBS). Hardware exposure is often associated with the development of infection that can lead to implant removal. However, in selected cases, it is possible to manage skin erosion without having to remove the hardware. This article presents the case of a patient with recurrent skin erosions above the IPG, who underwent multiple surgeries. Given the failure of less invasive approaches, a more complex surgery with the employment of a pedunculated flap of pectoralis major in order to cover the IPG was attempted. Nevertheless, the IPG removal was finally unavoidable, resulting in a rapid decline in clinical performance. This illustrative case suggests how, in patients with sustained stimulation who benefit from a good degree of autonomy, it may be useful to use invasive surgical techniques to resolve skin erosions and save the DBS system. In spite of everything, sometimes complete or partial removal of the implant still becomes unavoidable, but this can lead to a severe worsening of PD symptoms. Definitive removal of the system should therefore be considered only in cases of frank infection or after failure of all other approaches.

Virtual-Augmented Reality and Life-Like Neurosurgical Simulator for Training: First Evaluation of a Hands-On Experience for Residents.

Background: In the recent years, growing interest in simulation-based surgical education has led to various practical alternatives for medical training. More recently, courses based on virtual reality (VR) and three-dimensional (3D)-printed models are available. In this paper, a hybrid (virtual and physical) neurosurgical simulator has been validated, equipped with augmented reality (AR) capabilities that can be used repeatedly to increase familiarity and improve the technical skills in human brain anatomy and neurosurgical approaches. Methods: The neurosurgical simulator used in this study (UpSurgeOn Box, UpSurgeOn Srl, Assago, Milan) combines a virtual component and a physical component with an intermediate step to provide a hybrid solution. A first reported and evaluated practical experience on the anatomical 3D-printed model has been conducted with a total of 30 residents in neurosurgery. The residents had the possibility to choose a specific approach, focus on the correct patient positioning, and go over the chosen approach step-by-step, interacting with the model through AR application. Next, each practical surgical step on the 3D model was timed and qualitatively evaluated by 3 senior neurosurgeons. Quality and usability-grade surveys were filled out by participants. Results: More than 89% of the residents assessed that the application and the AR simulator were very helpful in improving the orientation skills during neurosurgical approaches. Indeed, 89.3% of participants found brain and skull anatomy highly realistic during their tasks. Moreover, workshop exercises were considered useful in increasing the competency and technical skills required in the operating room by 85.8 and 84.7% of residents, respectively. Data collected confirmed that the anatomical model and its application were intuitive, well-integrated, and easy to use. Conclusion: The hybrid AR and 3D-printed neurosurgical simulator could be a valid tool for neurosurgical training, capable of enhancing personal technical skills and competence. In addition, it could be easy to imagine how patient safety would increase and healthcare costs would be reduced, even if more studies are needed to investigate these aspects. The integration of simulators for training in neurosurgery as preparatory steps for the operating room should be recommended and further investigated given their huge potential.

Fluorescence-Guided Surgery in Glioblastoma: 5-ALA, SF or Both? Differences between Fluorescent Dyes in 99 Consecutive Cases.

BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumor. The extent of resection (EOR) has been claimed as one of the most important prognostic factors. Fluorescent dyes aid surgeons in detecting a tumor's borders. 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) are the most used. Only a few studies have directly compared these two fluorophores. METHODS: A single center retrospective analysis of patients treated for GBM in the period between January 2018 and January 2021 was built to find any differences in terms of EOR, Karnofsky Performance Status (KPS), and overall survival (OS) on the use of 5-ALA, SF, or both. RESULTS: Overall, 99 patients affected by isocitrate dehydrogenase (IDH) wild-type Glioblastoma were included. 5-ALA was administered to 40 patients, SF to 44, and both to 15. No statistically significant associations were identified between the fluorophore and EOR (p = 0.783) or postoperative KPS (p = 0.270). Survival analyses did not show a selective advantage for the use of a given fluorophore (p = 0.184), although there appears to be an advantageous trend associated with the concomitant use of both dyes, particularly after stratification by MGMT (p = 0.071). CONCLUSIONS: 5-Ala and SF are equally useful in achieving gross total resection of the enhancing tumor volume. The combination of both fluorophores could lead to an OS advantage.

A New Implantable Closed-Loop Clinical Neural Interface: First Application in Parkinson's Disease.

Deep brain stimulation (DBS) is used for the treatment of movement disorders, including Parkinson's disease, dystonia, and essential tremor, and has shown clinical benefits in other brain disorders. A natural path for the improvement of this technique is to continuously observe the stimulation effects on patient symptoms and neurophysiological markers. This requires the evolution of conventional deep brain stimulators to bidirectional interfaces, able to record, process, store, and wirelessly communicate neural signals in a robust and reliable fashion. Here, we present the architecture, design, and first use of an implantable stimulation and sensing interface (AlphaDBSR System) characterized by artifact-free recording and distributed data management protocols. Its application in three patients with Parkinson's disease (clinical trial n. NCT04681534) is shown as a proof of functioning of a clinically viable implanted brain-computer interface (BCI) for adaptive DBS. Reliable artifact free-recordings, and chronic long-term data and neural signal management are in place.

Let Me See: Correlation between 5-ALA Fluorescence and Molecular Pathways in Glioblastoma: A Single Center Experience.

BACKGROUND: Despite the aggressiveness of multimodal treatment, glioblastoma (GBM) is still a challenge for neurosurgeons, neurooncologists, and radiotherapists. A surgical approach is still a cornerstone in GBM therapeutic management, as the extent of resection is strongly related both to overall survival and progression-free survival. From this perspective, the use of photodynamic molecules could represent an interesting tool to achieve maximal and safe resection. Being able to trace the lesion's edges, indeed, could allow to improve the extent of resection and to minimize residual tumor while sparing normal tissue. The use of 5-aminolevulinic acid (5-ALA) as a photodynamic tracer is well established due to its strict correlation both with cellularity and metabolic activity of the GBM cell clones. OBJECTIVE: Our study aims to define whether a different molecular asset of GBM (especially investigating IDH 1/2 mutation, proliferation index, and MGMT promoter methylation) results in different fluorescence expression, possibly because of differences in metabolic pathways due to different genotypes. METHODS: Patients undergoing surgery for GBM removal at our Institute (Dep. Of Neurosurgery, Ospedale Città della Salute e della Scienza, University of Turin, Italy) were retrospectively reviewed. Patients with histological diagnosis confirmation and to whom 5-ALA was given before surgery were included. The whole surgical procedure was recorded and then analyzed by three different people (a medical student, a resident, and a senior surgeon with an interest in neurooncology and experience in using 5-ALA) and a score was assigned to the different degrees of intraoperative fluorescence. The degree of fluorescence was then matched with the genotype. RESULTS: A trend of grade 2 fluorescence (i.e., "strong") was observed in the IDH 1/2 wild-type (WT) genotype, suggesting a more intense metabolic activity in this particular subgroup, while, no or weak fluorescence was observed more often in the IDH 1/2 mutated tumors, suggesting a lower metabolic activity. No relations were found between fluorescence grade and MGMT promoter methylation or, interestingly, cellularity. As a secondary analysis, more epileptogenicity of the IDH 1/2 mutated GBM was noticed, similarly to other recent literature. CONCLUSION: Our results do not support the use of 5-ALA as a diagnostic tool, or a way to substitute the molecular profiling, but confirm 5-ALA as a powerful metabolic tracer, able to easily detect the pathological cells, especially in the IDH WT genotype, and in this perspective, further studies will be necessary to better describe the metabolic activity of GBM cells.

Risk of Recurrence of Chronic Subdural Hematomas After Surgery: A Multicenter Observational Cohort Study.

Background: Chronic Subdural Hematoma (CSDH) is a common condition in the elderly population. Recurrence rates after surgical evacuation range from 5 to 30%. Factors predicting recurrence remain debated and unclear. Objective: To identify factors associated with increased risk of recurrence. Methods: Cases of CSDHs that underwent surgical treatment between 2005 and 2018 in the Neurosurgery Units of two major Italian hospitals were reviewed. Data extracted from a prospectively maintained database included demographics, laterality, antithrombotic therapy, history of trauma, corticosteroid therapy, preoperative and postoperative symptoms, type of surgical intervention, use of surgical drain, and clinical outcomes. Results: A total of 1313 patients was analyzed. The overall recurrence rate was 10.1%. The risk of recurrence was not significantly different between patients with unilateral or bilateral CSDH (10.4 vs. 8.8%, p = 0.39). The risk of recurrence was higher in patients that underwent surgical procedure without postoperative drainage (16.1 vs. 5.4%, p < 0.01). No relationship was found between recurrence rates and therapy with antithrombotic drugs (p = 0.97). The risk of recurrence was increasingly higher considering craniostomy, craniectomy, and craniotomy (9.3, 11.3, and 18.9%, respectively, p = 0.013). Lower recurrence rates following Dexamethasone therapy were recorded (p = 0.013). Conclusion: No association was found between the risk of recurrence of CSDH after surgical evacuation and age, use of antithrombotic medication, or laterality. Burr-hole craniostomy was found to be associated with lower recurrence rates, when compared to other surgical procedures. Placement of surgical drain and Dexamethasone therapy were significantly associated with reduced risk of recurrence of CSDHs.

Supratotal Resection of Glioblastoma: Is Less More?

BACKGROUND: A relationship between the extent of resection (EOR) and survival has been demonstrated in patients with glioblastomas (GBMs). However, despite gross total resection (GTR) of the enhancing nodule (EN), GBMs usually relapse, generally near the surgical cavity. OBJECTIVE: The aim of this study was to determine the prognostic role of FLAIR resection of GBMs by analyzing pre- and post-operative MRIs to estimate the EOR of EN, FLAIR-hyperintense regions and total tumor volume (TTV). METHODS: Radiologic and clinical outcomes were analyzed retrospectively. Pre- and post-operative EN volume, pre- and postoperative FLAIR volume (POFV), and pre- and postoperative TTV were analyzed. EOR was then calculated for each component. Time-dependent ROC curves and cut-off values for pre- and post-operative volumes and EOR were calculated. A Kaplan-Meier analysis with the log-rank test and Cox regression analysis were then used to analyze progression-free survival (PFS) and overall survival (OS). RESULTS: We did not find any correlation between EOR of FLAIR-altered regions and patient survival. On the other hand, there were statistically significant relationships between the prognosis and both a preoperative EN volume less than 31.35 cm3 (p=0.032) and a postoperative EN volume less than 0.57 cm3 (p=0.015). Moreover, an EOR of EN greater than 96% was significantly associated with the prognosis (p=0.0051 for OS and p=0.022 for PFS). CONCLUSION: Our retrospective, multi-center study suggests that survival in patients with GBM is not affected by the extent of resection of FLAIR-hyperintense areas.

The Dominant-Subthalamic Nucleus Phenomenon in Bilateral Deep Brain Stimulation for Parkinson's Disease: Evidence from a Gait Analysis Study.

BACKGROUND: It has been suggested that parkinsonian [Parkinson's disease (PD)] patients might have a "dominant" (DOM) subthalamic nucleus (STN), whose unilateral electrical stimulation [deep brain stimulation (DBS)] could lead to an improvement in PD symptoms similar to bilateral STN-DBS. OBJECTIVES: Since disability in PD patients is often related to gait problems, in this study, we wanted to investigate in a group of patients bilaterally implanted for STN-DBS: (1) if it was possible to identify a subgroup of subjects with a dominant STN; (2) in the case, if the unilateral stimulation of the dominant STN was capable to improve gait abnormalities, as assessed by instrumented multifactorial gait analysis, similarly to what observed with bilateral stimulation. METHODS: We studied 10 PD patients with bilateral STN-DBS. A clinical evaluation and a kinematic, kinetic, and electromyographic (EMG) analysis of overground walking were performed-off medication-in four conditions: without stimulation, with bilateral stimulation, with unilateral right or left STN-DBS. Through a hierarchical agglomerative cluster analysis based on motor Unified Parkinson's Disease Rating Scale scores, it was possible to separate patients into two groups, based on the presence (six patients, DOM group) or absence (four patients, NDOM group) of a dominant STN. RESULTS: In the DOM group, both bilateral and unilateral stimulation of the dominant STN significantly increased gait speed, stride length, range of motion of lower limb joints, and peaks of moment and power at the ankle joint; moreover, the EMG activation pattern of distal leg muscles was improved. The unilateral stimulation of the non-dominant STN did not produce any significant effect. In the NDOM group, only bilateral stimulation determined a significant improvement of gait parameters. CONCLUSION: In the DOM group, the effect of unilateral stimulation of the dominant STN determined an improvement of gait parameters similar to bilateral stimulation. The pre-surgical identification of these patients, if possible, could allow to reduce the surgical risks and side effects of DBS adopting a unilateral approach.

Idiopathic delayed-onset edema surrounding deep brain stimulation leads: Insights from a case series and systematic literature review.

INTRODUCTION: Deep brain stimulation (DBS) is effective for some neurological and psychiatric conditions. Idiopathic delayed-onset edema (IDE) surrounding the leads has been anecdotally reported. The etiology, predisposing factors and prognosis of this complication are unknown. We present a multicenter case series of patients with IDE, and a systematic literature review, aimed at defining the pathophysiology and identifying appropriate treatment strategies. METHODS: IDE was defined as edema along the DBS lead, occurring ≥72 h postoperatively, in absence of trauma, vascular events or infection. Information on patients with IDE was collected in a standardized way. A systematic search was performed in Pubmed. RESULTS: Twelve new patients presenting with 14 episodes of IDE are described. From the literature, 38 patients were identified. No common surgical aspects or patient-related factors were identified as risk predictors for the onset of IDE. Symptoms included deterioration of the stimulation effect, seizures and focal neurological signs. Although the condition is self-limiting, with symptoms resolution in 28.5 days on average, three patients underwent surgical revision and seven received antibiotics. CONCLUSIONS: IDE is a rare complication of DBS procedures, presenting from few days to months after surgery. Symptoms can be mild and not-specific, and the condition is self-limiting. The diagnosis of IDE is made after exclusion of vascular events or infections. The pathophysiology is still unexplained. The recognition of this complication can help avoiding unnecessary surgical procedures (system explantation) and antibiotic treatment.

Effects of deep brain stimulation of the subthalamic nucleus on sleep architecture in parkinsonian patients.

Patients affected by Parkinson's disease (PD) often complain of disturbed sleep resulting from nighttime motor disabilities such as nocturnal akinesia, tremor and rigidity, motor behaviour during REM sleep or periodic leg movements (PLM) during sleep. Sleep may also be affected by dopaminergic and anticholinergic drugs or coexisting depressive syndrome. Deep brain stimulation (DBS) of subthalamic nucleus (STN) effectively reduces PD motor disability. The aim of this study is to evaluate the sleep architecture modifications after STN DBS. We assessed five patients (two men and three women, mean age 63.8+/-3.3 years, with a mean history of PD of 13.8+/-4.9 years) who underwent STN DBS. The mean levodopa equivalent dosage (LED) was 1010+/-318 mg before surgery and 116+/-93 mg 3 months after surgery. Polysomnography (PSG) with audiovisual recordings was performed on two separate nights, the first assessment in the week before surgery and the second 3 months after surgery. Three months after surgery, PSG showed an increase in total sleep time, in the longest period of uninterrupted sleep, and in the percentage of stage 3-4 NREM sleep, while there was a reduction of wakefulness after sleep onset. PLM, apnea-hyopnea index and REM sleep behaviour disorder were unaffected by STN DBS. STN DBS seems to be an effective therapeutic option for the treatment of advanced Parkinson's disease because it improves the cardinal symptoms and also seems to improve sleep architecture.