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.

The Chromatin-Oxygen Sensor Gene KDM5C Associates with Novel Hypoxia-Related Signatures in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is a fatal brain tumor without effective drug treatment. In this study, we highlight, for the first time, the contribution of chromatin remodeling gene Lysine (K)-specific demethylase 5C (KDM5C) in GBM via an extensive analysis of clinical, expression, and functional data, integrated with publicly available omic datasets. The expression analysis on GBM samples (N = 37) revealed two informative subtypes, namely KDM5CHigh and KDM5CLow, displaying higher/lower KDM5C levels compared to the controls. The former subtype displays a strong downregulation of brain-derived neurotrophic factor (BDNF)-a negative KDM5C target-and a robust overexpression of hypoxia-inducible transcription factor-1A (HIF1A) gene, a KDM5C modulator. Additionally, a significant co-expression among the prognostic markers HIF1A, Survivin, and p75 was observed. These results, corroborated by KDM5C overexpression and hypoxia-related functional assays in T98G cells, suggest a role for the HIF1A-KDM5C axis in the hypoxic response in this tumor. Interestingly, fluorescence-guided surgery on GBM sections further revealed higher KDM5C and HIF1A levels in the tumor rim niche compared to the adjacent tumor margin, indicating a regionally restricted hyperactivity of this regulatory axis. Analyzing the TCGA expression and methylation data, we found methylation changes between the subtypes in the genes, accounting for the hypoxia response, stem cell differentiation, and inflammation. High NANOG and IL6 levels highlight a distinctive stem cell-like and proinflammatory signature in the KDM5CHigh subgroup and GBM niches. Taken together, our results indicate HIF1A-KDM5C as a new, relevant cancer axis in GBM, opening a new, interesting field of investigation based on KDM5C as a potential therapeutic target of the hypoxic microenvironment in GBM.

Predicting endoscopic third ventriculostomy success in adult hydrocephalus: preliminary assessment of a modified ETV success score for adults (ETVSS-A) in a series of 47 patients.

BACKGROUND: Endoscopic third ventriculostomy is an established treatment for non-communicating hydrocephalus. In carefully selected patients, it can be adopted for the management of communicating variant; however controversy exists in regards to the definition of the appropriate candidates. Predictive score of Endoscopic Third Ventriculostomy Success (ETVSS) has been reported for pediatric and mixed populations only. Our purpose was to define an ETV success score for adult population (ETVSS-A), measuring the strength of correlation between preoperative score retrospectively evaluated and the success rates achieved in a class of adult patients. METHODS: A retrospective analysis of 47 cases which received ETV procedure at our Institution between 2015 and 2018 was run. Demographic data,clinical history,preoperative and postoperative signs were reviewed and ETVSS-A was calculated.Thereafter ETVSS-A results were compared with the actual success rates. RESULTS: Twenty-nine patients (61.7%) presented unchanged or improved clinical status with a mean ETVSS-A of 54.5%; 18 patients (38.3%) worsened with mean ETVSS-A of 37.7%. We found that age, type of hydrocephalus and symptoms of admission are each apart important factors in predicting ETV success: older patients and those with non-obstructive hydrocephalus had the lowest predicted ETV success. In patients in whom ETV was actually successful, the preoperative ETVSS-A was significantly higher as compared to those patients in whom we observed a poor surgical outcome. CONCLUSIONS: From the results of this series, though small and retrospectively analyzed, it seems that ETVSS-A can be considered as a useful instrument to help neurosurgeon in predicting the ETV success and though define a more accurate surgical strategy in cases of hydrocephalus. Wider series and prospective studies are attended to validate these preliminary results.

Malignant Intracerebral Nerve Sheath Tumor Presenting With Intratumoral Hemorrhage.

BACKGROUND: Primary central nervous system sarcomas are rare primitive mesenchymal non-meningothelial tumors. Malignant peripheral nerve sheath tumor accounts for 5% of sarcomas, with an incidence of approximately 0.001% and a recognized association with neurofibromatosis type 1. Its intracranial subtype, the so-called malignant intracerebral nerve sheath tumor (MINST), is even more infrequent. Current knowledge about its clinical presentation and best therapeutic management is poor because of the limited number of cases reported in literature. Commonly, intratumoral hemorrhage occurs at the time of diagnosis and, notably, most patients had intracranial hemorrhage prior to definitive diagnosis. CASE DESCRIPTION: We report a case of MINST in a young boy affected by neurofibromatosis type 1 who presented a spontaneous intracranial hemorrhage, successfully treated with surgery and postoperative adjuvant therapy. The tumor relapsed 1 year after and was successfully retreated with a second surgery. CONCLUSIONS: Malignant intracerebral nerve sheath tumors are rare sarcomas that can be associated with intratumoral hemorrhage at the time of presentation, mostly in patients with neurofibromatosis type 1. Surgery promptly performed, associated with adjuvant therapy, can result in an encouraging survival rate.

P-Tau as prognostic marker in long term follow up for patients with shunted iNPH.

Objective: Diagnosis of idiopathic Normal Pressure Hydrocephalus (iNPH) relies solely on clinical and radiological criteria while, unlike other neurological diseases, the analysis of cerebrospinal fluid markers is not used in clinical practice. Nevertheless, the overlapping of neurodegenerative diseases affects the long-term shunt efficacy and this occurrence should be detected before surgery. Therefore, we performed this study in order to assess the correlation between pre-surgical levels of CSF Beta Amyloid protein, Total Tau protein and Phospho-Tau protein with long-term clinical outcome. Methods: Between March 2012 and May 2016 we prospective evaluated all patients with iNPH according to guidelines criteria and we analysed CSF concentration of these proteins before and during surgery. Two years after surgery we evaluated iNPH score for all patients, grouping them in shunt responders and non-responders. Results: A total of 117 patients were included: Tap Test non-responders were 58 and at two years we had 35 shunt responders and 15 shunt non-responders. We found a significative difference between shunt-responders and shunt non-responders for pre surgical T-Tau (p: 0.02) and for P-Tau (p: 0.01). All the proteins were significantly associated with clinical outcome after surgery with different cut-off values; in particular, having a 'low' value of T-Tau, P-Tau and Aß1-42 resulted in favourable outcome after surgery. Conclusions: Low level of P-Tau is a useful CSF biochemical prognostic factor for good clinical outcome at least two years after shunt; meanwhile a lower Aß1-42 might suggest that the pathophysiology of iNPH could have something in common with other neurodegenerative diseases of the elderly.

Development of Cerebral Endoscopy in Italy: Background, Narration, and Legacy.

Bibliometric analysis shows that neuroendoscopy (NE) overcame its pioneering phase in the late 1980s, and became a significant technological and clinical innovation in the early 1990s. During those years the charge-coupled device digital video cameras were introduced and videoendoscopy had its decisive breakthrough, laying the foundation for NE take-off. NE can be considered an early product of artificial intelligence, as much as neuroimaging and neuronavigation. In Italy, cerebral NE started in 1993 and, despite a couple of years of relative delay, gained ground rapidly thanks also to the personal contribution of Michelangelo Gangemi (1949-2017), to whose memory this article is dedicated. In this paper we try to re-create the history of Italian NE through original documents and other testimonials, in the context of the general worldwide development of NE. The modality of its rapid diffusion throughout our peninsula seems a good paradigm of how cooperation without unnecessary competition can be rewarding and constructive.

[Primary headache and work: concepts of pathophysiology, occupational risk factors, health monitoring and criteria for judging causation]. / Cefalea primaria e lavoro: nozioni di fisiopatologia, fattori occupazionali di rischio, sorveglianza sanitaria e criteri per la formulazione del giudizio di idoneità.

Primary headaches account for 90% of all the forms of headache. The disease is characterized by high occurrence in the working-age population and by significant impact in countries with high economic and social development. These two epidemiological aspects carry significant economic costs that can be estimated calculating loss of working days due to illness and appreciable loss of labour productivity. In an occupational setting several circumstances are known to cause the onset of attacks in workers who already suffer from primary headache. In this sense, the following factors have an important role: interruption of the circadian sleep-wake rhythm, sleep deprivation, physical/mental distress, not ergonomic postures (mainly those involving the cervical-brachial district), prolonged use of display screen, acoustic discomfort. Among chemicals, in the current conditions of exposure, the olfactory characteristics seem of primary importance rather than the more "conventional" mechanism of toxicity. The main aim of this study is to provide useful information to occupational physicians on the management of workers suffering from primary headache, with regard either to the formulation of the judgement of suitability, or to their auxiliary role in the planning and organization of work. A second aim involves the identification of specific preventive measures in order to reduce the probability of occurrence of a headache attack. This also minimizes the risk of accidents and injuries and ensures workers' efficiency. After these considerations, we suggest guidelines for a flow chart (aimed to understand worker's suitability for his/her specific task). This guarantees not only safety and health of workers who suffer from the illness, but also safeguards any third worker from a possible consequence due to less working capacity and reduction of attention of employees working with a headache attack. In conclusion we also identify three critical factors: the diagnosis of the form of primary headache, the characteristics of the work and the effects due to pharmacological therapy. The study and characterization of these elements are a crucial step for a proper formulation of the judgement of suitability to work. We report a decision process for judgement formulation at the end of this article. It is organized with a hierarchical model, the first steps are the clinical examination and history, the last step, if necessary or advisable, is the neurological visit and a periodic verification of the adherence to treatment prescribed and the follow-up.