Antonino Scibilia

Simvastatin Administration Ameliorates Neurobehavioral Consequences of Subarachnoid Hemorrhage in the Rat

In the present study we assessed the neuroprotective effects of simvastatin in a rodent model of experimental subarachnoid hemorrhage (SAH). Based on recent data showing the role of statins not only in lowering the level of cholesterol but also in preventing cardiac and cerebrovascular damage in risk population, and in decreasing vasospasm and delayed ischemia after aneurysmal SAH, we investigated the neuroprotective effects of intraperitoneal administration of simvastatin (40 mg/kg/day for 5 consecutive days) in Sprague-Dawley rats 30 min after SAH, as compared to vehicle-treated SAH animals. We employed a battery of well-characterized tests to assess memory, learning, motivational, balance, and behavioral performances. On days 1-4 post-SAH, simvastatin-treated rats have significantly improved beam balance scores (days 1-2, p<0.001; days 3-4, p<0.01), beam balance times (days 1-4, p<0.01), and latency to traverse the beam (days 1-3, p<0.01; day 2, p<0.005; day 4, p<0.0001) in comparison with control groups that, conversely, were not protected against SAH-related body weight changes. These results demonstrate that the administration of simvastatin may represent a beneficial therapeutic approach able to reduce post-SAH cognitive dysfunction.

Intraoperative neurophysiological mapping and monitoring in spinal tumor surgery: sirens or indispensable tools?

Spinal tumor (ST) surgery carries the risk of new neurological deficits in the postoperative period. Intraoperative neurophysiological monitoring and mapping (IONM) represents an effective method of identifying and monitoring in real time the functional integrity of both the spinal cord (SC) and the nerve roots (NRs). Despite consensus favoring the use of IONM in ST surgery, in this era of evidence-based medicine, there is still a need to demonstrate the effective role of IONM in ST surgery in achieving an oncological cure, optimizing patient safety, and considering medicolegal aspects. Thus, neurosurgeons are asked to establish which techniques are considered indispensable. In the present study, the authors focused on the rationale for and the accuracy (sensitivity, specificity, and positive and negative predictive values) of IONM in ST surgery in light of more recent evidence in the literature, with specific emphasis on the role of IONM in reducing the incidence of postoperative neurological deficits. This review confirms the role of IONM as a useful tool in the workup for ST surgery. Individual monitoring and mapping techniques are clearly not sufficient to account for the complex function of the SC and NRs. Conversely, multimodal IONM is highly sensitive and specific for anticipating neurological injury during ST surgery and represents an important tool for preserving neuronal structures and achieving an optimal postoperative functional outcome.

The Impact of Diffusion Tensor Imaging Fiber Tracking of the Corticospinal Tract Based on Navigated Transcranial Magnetic Stimulation on Surgery of Motor-Eloquent Brain Lesions

BACKGROUND Navigated transcranial magnetic stimulation (nTMS) enables preoperative mapping of the motor cortex (M1). The combination of nTMS with diffusion tensor imaging fiber tracking (DTI-FT) of the corticospinal tract (CST) has been described; however, its impact on surgery of motor-eloquent lesions has not been addressed. OBJECTIVE To analyze the impact of nTMS-based mapping on surgery of motor-eloquent lesions. METHODS In this retrospective case-control study, we reviewed the data of patients operated for suspected motor-eloquent lesions between 2012 and 2015. The patients underwent nTMS mapping of M1 and, from 2014, nTMS-based DTI-FT of the CST. The impact on the preoperative risk/benefit analysis, surgical strategy, craniotomy size, extent of resection (EOR), and outcome were compared with a control group. RESULTS We included 35 patients who underwent nTMS mapping of M1 (group A), 35 patients who also underwent nTMS-based DTI-FT of the CST (group B), and a control group composed of 35 patients treated without nTMS (group C). The patients in groups A and B received smaller craniotomies (P = .01; P = .001), had less postoperative seizures (P = .02), and a better postoperative motor performance (P = .04) and Karnofsky Performance Status (P = .009) than the controls. Group B exhibited an improved risk/benefit analysis (P = .006), an increased EOR of nTMS-negative lesions in absence of preoperative motor deficits (P = .01), and less motor and Karnofsky Performance Status worsening in case of preoperative motor deficits (P = .02, P = .03) than group A. CONCLUSION nTMS-based mapping enables a tailored surgical approach for motor-eloquent lesions. It may improve the risk/benefit analysis, EOR and outcome, particularly when nTMS-based DTI-FT is performed.

Resting-state fMR evidence of network reorganization induced by navigated transcranial magnetic repetitive stimulation in phantom limb pain

Abstract Objectives Repetitive transcranial magnetic stimulation (rTMS) is a promising tool for treatment of chronic pain. We describe the use of navigated rTMS to treat a patient affected by phantom limb pain (PLP) and to modulate brain functional connectivity. We reviewed the literature on the use of rTMS as a tool for relieving central pain by promoting brain plasticity. Methods A 69-year-old patient came to our observation blaming severe pain (Visual Analog scale, VAS, score 9) to a phantom right lower limb. We mapped left primary motor area (PMA) by navigated TMS and assessed connectivity with resting-state functional MR (rsfMR). The patient underwent 30-days navigated rTMS treatment. We applied low-frequency stimulation (1 Hz) over the primary somatosensory area (PSA) and high-frequency stimulation (10 Hz) over PMA and dorsolateral prefrontal cortex (DLPFC) of the left hemisphere. Results This strategy allowed a pain relief with a reduction of 5 points of the VAS score after 1 month. Post-treatment rsfMR showed increased connectivity, mainly in the sensory-motor network and the unaffected hemisphere (P < 0.05). Discussion This report represents a proof-of-concept that navigated rTMS can be effectively used to stimulate selected brain areas in PLP patients in order to promote brain connectivity, and that rsfMR is a useful tool able to analyze functional results. In the literature, we found data supporting the assumption that, in patients affected by PLP, a reduced connectivity in interhemispherical and sensory-motor network plays a role in generating pain and that rTMS has the potential to restore impaired connectivity.

nTMS-Based DTI Fiber Tracking of Motor Pathways

DTI fiber tracking allows for the 3D reconstruction of main white matter fascicles, including the corticospinal tract (CST). Nevertheless, standard diffusion tensor imaging fiber tracking (DTI FT) is limited by the fact that it is based on the selection of anatomical landmarks as seeding regions of interest (ROIs) for tract computation. This reduces the reliability and reproducibility of DTI FT results, especially in brain tumor patients, in which the neural plasticity induced by the tumor itself causes a reorganization of the motor network, resulting in a mismatch between anatomical and functional landmarks. The nTMS technique provides a reliable mapping of the functional organization of the motor cortex that can be successfully used as seeding ROI for the DTI computation of the CST. This improves the reliability and accuracy of the DTI FT of the CST compared to the standard DTI technique. Moreover, it provides the somatotopic organization of the CST, especially improving the visualization of fiber bundles connected to the motor cortical representation of arm and face muscles.

Intraoperative Neurophysiological Monitoring in Spine Surgery: A Significant Tool for Neuronal Protection and Functional Restoration.

Although there is recent evidence for the role of intraoperative neurophysiological monitoring (IONM) in spine surgery, there are no uniform opinions on the optimal combination of the different tools. At our institution, multimodal IONM (mIONM) approach in spine surgery involves the evaluation of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) with electrical transcranial stimulation, including the use of a multipulse technique with multiple myomeric registration of responses from limbs, and a single-pulse technique with D-wave registration through epi- and intradural recording, and free running and evoked electromyography (frEMG and eEMG) with bilateral recording from segmental target muscles. We analyzed the impact of the mIONM on the preservation of neuronal structures and on functional restoration in a prospective series of patients who underwent spine surgery. We observed an improvement of neurological status in 50 % of the patients. The D-wave registration was the most useful intraoperative tool, especially when MEP and SEP responses were absent or poorly recordable. Our preliminary data confirm that mIONM plays a fundamental role in the identification and functional preservation of the spinal cord and nerve roots. It is highly sensitive and specific for detecting and avoiding neurological injury during spine surgery and represents a helpful tool for achieving optimal postoperative functional outcome.

Surgery of language-eloquent tumors in patients not eligible for awake surgery: the impact of a protocol based on navigated transcranial magnetic stimulation on presurgical planning and language outcome, with evidence of tumor-induced intra-hemispheric plasticity

OBJECTIVES Awake surgery and intraoperative monitoring represent the gold standard for surgery of brain tumors located in the perisylvian region of the dominant hemisphere due to their ability to map and preserve the language network during surgery. Nevertheless, in some cases awake surgery is not feasible. This could increase the risk of postoperative language deficit. Navigated transcranial magnetic stimulation (nTMS) and nTMS-based DTI fiber tracking (DTI-FT) provide a preoperative mapping and reconstruction of the cortico-subcortical language network. This can be used to plan and guide the surgical strategy to preserve the language function. The objective if this study is to describe the impact of a non-invasive preoperative protocol for mapping the language network through the nTMS and nTMS-based DTI-FT in patients not eligible for awake surgery and thereby operated under general anesthesia for suspected language-eloquent brain tumors. PATIENTS AND METHODS We reviewed clinical data of patients not eligible for awake surgery and operated under general anaesthesia between 2015 and 2016. All patients underwent nTMS language cortical mapping and nTMS-based DTI-FT of subcortical language fascicles. The nTMS findings were used to plan and guide the maximal safe resection of the tumor. The impact on postoperative language outcome and the accuracy of the nTMS-based mapping in predicting language deficits were evaluated. RESULTS Twenty patients were enrolled in the study. The nTMS-based reconstruction of the language network was successful in all patients. Interestingly, we observed a significant association between tumor localization and the cortical distribution of the nTMS errors (p = 0.004), thereby suggesting an intra-hemispheric plasticity of language cortical areas, probably induced by the tumor itself. The nTMS mapping disclosed the true-eloquence of lesions in 12 (60%) of all suspected cases. In the remaining 8 cases (40%) the suspected eloquence of the lesion was disproved. The nTMS-based findings guided the planning and surgery through the visual feedback of navigation. This resulted in a slight reduction of the postoperative language performance at discharge that was completely recovered after one month from surgery. The accuracy of the nTMS-based protocol in predicting postoperative permanent deficits was significantly high, especially for false-eloquent lesions (p = 0.04; sensitivity 100%, specificity 57.14%, negative predictive value 100%, positive predicitive value 50%). CONCLUSIONS The nTMS-based preoperative mapping allows for a reliable visualization of the language network, being also able to identify an intra-hemispheric tumor-induced cortical plasticity. It allows for a customized surgical strategy that could preserve post-operative language function. This approach should be considered as a support for neurosurgeons whenever approaching patients affected by suspected language-eloquent tumors but not eligible for awake surgery.

Petrosal Meningiomas: Factors Affecting Outcome and the Role of Intraoperative Multimodal Assistance to Microsurgery.

BACKGROUND Petrous meningiomas (PMs) represent a subset of posterior fossa tumors accounting for ∼8% of all intracranial meningiomas. Surgical treatment of PMs is challenging because of their relationships with vital neurovascular structures of the cerebellopontine angle. OBJECTIVE To investigate independent pre- and intraoperative predictors of PM surgery outcome. METHODS We reviewed the surgical and outcome data of patients who underwent microsurgical resection of PMs from 1997 to 2016. From 2007 onward, a multimodal intraoperative protocol consisting of intraoperative neuromonitoring (IONM), endoscopy, and indocyanine green (ICG) videoangiography was applied. Outcome variables included extent of resection, Karnofsky performance status (KPS), overall survival, and progression-free survival (PFS). RESULTS A total of 54 patients were included. Independent predictors of gross total resection (GTR) included retromeatal location (P < .0175; odds ratio [OR] 4.05), absence of brainstem compression (P < .02; OR 3.55), and histological WHO grade I (P < .001; OR 3.47). Nongiant size (P < .012; OR 4.38), and WHO grade I (P < .0001; OR 7.7) were independent predictors of stable or improved KPS. The use of multimodal intraoperative tools to assist surgery independently predicted GTR (P < .002; OR 6.8) and good KPS (P < .018; OR 4.23). Nongiant size (P = .01) and WHO grade I (P = .002) were significantly associated with increased PFS. CONCLUSION Notwithstanding the limitations of a retrospective study, our results suggest that support of microsurgery by a combination of IONM, endoscopy, and ICG videoangiography may improve patient outcome in PM surgery.

Website-visibility of Neurosurgical Centers in Europe. A necessary tool for enhancing scientific network cooperation and information distribution: letter to the editor

Dear Editor, In the field of science, the web-visibility rate of a publication from bibliographic data coincide with the frequency of the websites on which a determined paper is cited after entering full-title into Google® or any other search engine [4]. Applying this concept to the national societies and healthcare centers, it becomes intuitive to understand how web-visibility is strongly correlated with their global visibility [2, 3] and represents a key issue including a social significance [5, 6]. On the heels of web-visibility, the aim of this letter is to describe an overview, drawn in the frame of the European Association of Neurosurgical Societies (EANS), to investigate the European National neurosurgical societies (ENNS) website-visibility. We defined the ENNS website-visibility as the capability of a website to be worthwhile for scientific collaboration as well as for information’s divulgation either for neurosurgeons and patients. Therefore, we tried to measure the ENNS website-visibility conceived as the intersection of three parameters: (1) the possibility of surfing the websites in English language; (2) the accessibility to the Neurosurgical Centers (NCs) through the ENNS websiteslinks; (3) the presence of at least one item among Bnews and events^ and/or Beducational^ (for neurosurgeons) and/or Bpatient info^ sections of the website. On the basis of these three parameters, the ENNS website-visibility was categorized in significant (presence of at least 2/3 items), notsignificant (1/3 only), and insufficient (all absent). Furthermore, the BENNS Web-Visibility of NCs^ rate was defined as the ratio between the numbers of NCs available through ENNS Websites (ENNS Web-visibility of NCs) and the number of NCs identified through a more extensive and less standardized online research on the search engines by using keywords of Bthe Specific Country^ and/or Bneurosurgery^ and/or BChairman’s e-mail addresses^ (webvisibility of NCs). Moreover, we explored the web-visibility of ENNS sections. We identified 38 ENNS through the EANS Website (Table 1). The rates of significant, not-significant, and insufficient website-visibility profiles were respectively 39, 24, and 37%. Only 5 Countries (16%) revealed to hold a full significant website-visibility profile (presence of all analyzed items). Significant and not-significant website-visibility profiles were associated with respectively 100 and 78% information rates; the English surfing rates were respectively 53 and 22% and the NCs accessibility rates were 87% for significant profiles and 0% for not-significant profiles. Through the ENNS websites we identified 521 NCs, while the web-visibility of NCs was 637. Therefore BENNS Web-visibility of NCs^ rate was 80%. The web-visibility of ENNS sections was just 8%. In the contemporary neurosurgical era in which internet reveals to be an indisputably mean for research, education, and patient’s information, the website-visibility possesses an increasing role for ENNS and it contributes to tend to the best clinical and research practice. This overview, drawn in the EANS framework, introduces the concept of website-visibility that represents one of the worthwhile premises for strengthening more and more the evergreen European Neurosurgical Multicenter Cooperation. * Giovanni Raffa giovanni.raffa@unime.it