The crosstalk between the epigenome and mitochondria as a novel therapeutic target to counteract remote degeneration induced by spinal cord injury
Applications Invited
75
Scopus Publications
Scopus Publications
Predictive factors of long-term dorsal column dysfunction after intramedullary spinal cord tumor resection: a comparative case series Filippo Maria Polli, Marco Battistelli, Alessandro Rapisarda, Michele Di Domenico, Alessio Albanese, Mario Muselli, Marco Luigetti, Giuseppe Maria Della Pepa, Alessandro Olivi Journal of Neurosurgery Spine, 2026 OBJECTIVE Postoperative dorsal column dysfunction (DCD) has been observed in 43.6%–55.1% of patients who have undergone surgery for intramedullary spinal cord tumors (IMSCTs). There is a paucity of evidence regarding the prognosticators of its occurrence. The objective of the present study was to ascertain the prognostic factors associated with long-term DCD following IMSCT resection, with a particular emphasis on the role of the myelotomy technique and intraoperative neuromonitoring (IONM). METHODS A case-control study was conducted on consecutive patients. Patients were stratified based on the surgical technique used for midline myelotomy: dorsal column (DC) dissection and preservation technique (group A) and midline coagulation and incision technique (group B). Somatosensory evoked potentials (SSEPs) were categorized as either present or absent. The groups were then analyzed with respect to the Short Form Health Survey 36 (SF-36), the McCormick Scale (MMS), Douleur Neuropathique 4 Questions, and a 3-domain numeric rating scale for investigating DCD, named the Dorsal-Columns Questionnaire (DCQ). Univariate analyses were conducted for MMS and DCQ scores, with data regarding demographics; neurological examination; symptoms; surgery, including extent of resection, tumor histology, tumor location, myelotomy, and tumor extension; hemosiderin cap, cleavage plane presence; and IONM taken into consideration. IONM was recorded at three time points during the surgical procedure: baseline intraoperative, worst intraoperative, and final intraoperative. RESULTS In total, 37 patients were included. Groups A and B had nonsignificantly different demographic parameters. Group A had superior outcomes in MMS (p = 0.002), SF-36 (p = 0.001), and DCQ (p = 0.031) scores at the last follow-up. Group B experienced a significantly higher incidence of worst intraoperative (p = 0.002) and final intraoperative (p = 0.026) SSEP loss. Univariate analysis documented the following major prognostic factors: myelotomy technique (p = 0.012), capillary hemangioma histology (p = 0.045), and worst intraoperative SSEPs (p = 0.034) for the DCQ; myelotomy technique (p < 0.001), intraoperative (p < 0.001) and final intraoperative (p < 0.001) SSEPs, and follow-up bowel-bladder dysfunction (p = 0.02) for the MMS. Final operative SSEPs were not among DCQ prognosticators (p = 0.213). CONCLUSIONS The DC dissection and preservation myelotomy technique is associated with lower long-term DCD and intraoperative SSEP loss and better health-related quality of life and disability when compared with the midline coagulation and incision technique. The myelotomy technique and intraoperative SSEP disappearance, even if transient, are major determinants of long-term disability and DCDs.
Benign or aggressive? Understanding spinal melanocytomas in comparison to malignant melanoma Alice Ryba, Theresa Mohme, Johannes Kerschbaumer, Emily von Bronewski, Vanessa Hubertus, Vicki M. Butenschoen, Andreas Kramer, Felix C. Stengel, Martin N. Stienen, Marco Battistelli, Filippo Maria Polli, Hanno S. Meyer, Lasse Dührsen, Klaus Christian Mende, Manfred Westphal, Florian Ringel, Bernhard Meyer, Julia Onken, Claudius Thome, Sven O. Eicker, Malte Mohme Journal of Neuro Oncology, 2026 Introduction Spinal melanocytic tumors are rare, with limited data on their clinical course and aggressiveness. Since intraoperative dark pigmentation and infiltrative margins can lead to misclassification of MC as MM—especially in the absence of a known primary—this multicenter study characterizes melanocytomas (MC) and contrasts them with malignant melanoma (MM). Methods We retrospectively analyzed 56 patients with spinal intradural melanocytic tumors (2010–2024) from seven European neurosurgical centers. Clinical, radiological, histological, and surgical features were analyzed. Univariate and multivariate analyses were performed to identify prognostic risk factors. Results The study included 22 patients with spinal MC and 34 patients with MM. Median age was comparable (61 vs. 58 years, p = 0.09), but MC patients had a longer symptom history (13 vs. 1.3 months, p = 0.0001) and more often intramedullary tumors (72.7% vs. 2.9%, p < 0.0001). Gross total resection was achieved in 40.9% of MC cases and 61.8% of MM cases ( p = 0.07), with instrumentation required more often for MM ( p = 0.0022). Ki-67 proliferation index was significantly higher in MM than MC (26.7% vs. 6.6%, p < 0.0001). Postoperative deficits were more frequent in MC (54.6% vs. 14.7%, p = 0.002) and MCs showed higher frequency of ataxia postoperatively (36.4% vs. 11.8%, p = 0.04). MM patients received more adjuvant therapy (88.2% vs. 31.8%, p = 0.0001), with a trend toward higher local recurrence (26.5% vs. 14.7%, p = 0.31). Conclusion Our study demonstrates that MC, though considered benign, carries a high risk of postoperative deficits. Furthermore, GTR was achieved in only 40% of cases, underscoring its locally infiltrative nature and potential for semi-benign biology.
A visual mining analysis of middle meningeal embolization and other factors associated with recurrence requiring re-operation in subdural hematomas: a single-center series Marco Battistelli, Marika Vezzoli, Iacopo Valente, Massimo Benenati, Giuseppe Garignano, Andrea Alexandre, Ludovico Agostini, Samuele Santi, Ottavia Giovinazzo, Leonardo Nardini, Federico Costa, Giorgio Quintino D’Alessandris, Manuela D’Ercole, Alessandro Izzo, Alessandro Rapisarda, Francesco Signorelli, Nicola Montano, Simona Gaudino, Alessandro Olivi, Alessandro Pedicelli, Filippo Maria Polli, Francesco Doglietto Acta Neurochirurgica, 2025 Purpose to comprehensively and hierarchically assess risk factors for recurrence requiring reoperation (RrR) in chronic subdural hematoma (cSDH) in the era of middle meningeal artery embolization (MMAE). Methods Patients treated for a cSDH from January 2019 to October 2024 at Fondazione Gemelli research hospital were considered for inclusion. Clinical, coagulation, radiological, and treatment factors were recorded. MMAE was performed systematically from October 2022, using polyvinyl alcohol (PVA) particles injected directly from the main trunk of MMA. The dataset comprised 45 quantitative and qualitative variables for each cSDH. Variables showing statistical significance (p-value < 0.05) were selected as covariates in two supervised learning frameworks to predict the RrR (outcome, Y ): ( i ) Classification and Regression Tree (CART) and ( ii ) Random Forest (RF) classifier. Results 500 patients were eligible and 233 were included, resulting in 283 treated cSDHs (mean follow-up: 119 days); 129 underwent adjuvant MMAE. 50 cSDH had a RrR (mean time to recurrence: 47 days), of which 41 (82%) in the non-embolized group and 9 (18%) in the embolized group (p-value < 0.001). Adjuvant embolization was the strongest factor associated with RrR, significantly reducing the risk for reintervention. Markwalder grading scale, preoperative cSDH volume, and platelet count (PLT) are strong predictors in non-embolized patients. A critical PLT cut-off of 229 × 10 9 /L strongly impacts RrR risk for substantial cSDH volumes. Conclusions The present results support the routine use of MMAE and the correction of PLT in relation to cSDH volume.
Bed rest duration and development of cerebrospinal fluid leaks after intradural spinal surgery: a meta-analysis of comparative studies Alberto BENATO, Fabio ZEOLI, Flavia BECCIA, Marco BATTISTELLI, Alessandro RAPISARDA, Alessandro OLIVI, Filippo M. POLLI Journal of Cardiovascular Surgery, 2025 INTRODUCTION Postoperative cerebrospinal fluid (CSF) leaks and related complications are a major concern after intradural spinal surgeries. The role of prolonged bed rest in reducing the incidence of these complications has been debated. This meta-analysis aimed to evaluate whether early versus late mobilization affects the incidence of CSF leak-related complications (CLRC) after intradural spinal surgery. EVIDENCE ACQUISITION Following PRISMA guidelines, we conducted a systematic review and meta-analysis of comparative studies on early ambulation (EA) versus prolonged bed rest (PBR) in patients undergoing intradural spinal surgery. Studied considered for inclusion defined EA as mobilization on postoperative day 1, while PBR as mobilization on postoperative day 3. The primary outcome was the incidence of CLRC, defined as pseudomeningocele, durocutaneous fistula, or wound dehiscence. Secondary outcome was the incidence of medical complications. EVIDENCE SYNTHESIS Three retrospective comparative studies with a total of 949 patients were included in the analysis. No significant difference was found in the incidence of CLRC between the EA and PBR groups. Length of hospital stay (LOS) and postoperative medical complications incidence were significantly lower in the EA group. CONCLUSIONS This meta-analysis found that EA does not increase the risk of CLRC compared to PBR, while shortening LOS and reducing medical complications occurrence. These findings suggest that early mobilization could be a safe and effective postoperative strategy, reducing hospital stay and complication rates.
Intraoperative neuromonitorig alert risks in patients submitted to anterior cervical decompression and fusion for cervical spondylotic myelopathy: a single institution cohort-study Marco Battistelli, Alessandro Rapisarda, Massimo Benenati, Fabio Sbaraglia, Massimiliano Visocchi, Nicola Montano, Martina Taglialatela, Federico Costa, Ignazio Friscia, Michele Di Domenico, Mario Muselli, Giuseppe Maria Della Pepa, Marco Rossi, Simona Gaudino, Francesco Doglietto, Filippo Maria Polli European Spine Journal, 2025 Purpose To identify positional and intraoperative significant multimodal intraoperative neurophysiological monitoring (mIONM) alert risk factors during anterior cervical surgery in patients with cervical spine myelomalacia. Methods We analyzed prospectively collected data from the PANDA registry between January 2021 and February 2025. Included were patients undergoing anterior cervical decompression and fusion with MRI-confirmed myelomalacia. A significant alert was defined as a ≥ 50% reduction in MEP and/ SSEP amplitude, a ≥ 10% increase in MEP latency, or a spEMG signal. Patients were categorized into three groups: significant warnings at positioning (Group A), during surgical decompression (Group B), and no significant warnings (Group C). Nineteen anamnestic, clinical, radiological, and surgical factors were evaluated. A standardized anesthesia protocol and alert-response strategy were applied. Results Seventy-six patients (132 operated levels) were included. Four patients belonged to Group A and 12 to Group B. Group A exhibited only MEP alerts and showed higher prevalence of peripheral vascular disorders, C3-C4 surgeries, and poorer motor scores in the most affected muscle group; the latter independently predicted alerts with 100% sensitivity at an mMRC threshold of 4. Group B was characterized by only MEP and EMG alerts, significantly longer symptom duration, and myelomalacia spanning two to three levels. Both factors independently predicted intraoperative alerts and were protective when symptom duration was less than 37 months and myelomalacia involved less than two levels. No SSEP alerts occurred. Conclusion These findings support the use of mIONM during positioning and surgical decompression in anterior cervical procedures for patients with cervical myelomalacia, especially in those with segmental motor deficits, prolonged symptoms, and multilevel myelomalacia.
Successful treatment of a C2 aneurysmal bone cyst with hydroxyapatite and calcium sulfate synthetic bone void filler injection: a case report Marco Battistelli, Alessandro Rapisarda, Nicola Montano, Alessandro Pedicelli, Iacopo Valente, Alessandro Olivi, Filippo Maria Polli Journal of Spine Surgery, 2024 Background: removal. Non-surgical options include selective arterial embolization (SAE) as main treatment, while Denosumab and centrifugated bone marrow emerge as experimental alternatives. We report a case of C2 ABC in a young woman successfully treated with a single injection of biphasic ceramic bone substitute (BCBS) containing hydroxyapatite (HA) and calcium sulfate. Case Description: resection was deemed unnecessary due to the absence of neurological deficits or deformities, as reported throughout literature evidences. Denosumab administration showed interval tumor change, while SAE was hindered by arterial anastomosis, limiting the possibility of obtaining complete embolization, while significantly increasing cerebral ischemic risks. Repeated intralesional iliac crest bone marrow injection proved ineffective. Subsequently, a single BCBS injection was attempted. A 6-month follow-up computed tomography (CT) scan revealed complete cyst ossification, cortical bone remodeling without artifacts, and spinal canal restoration. Conclusions: HA and calcium sulfate BCBS vertebroplasty emerges as a promising alternative to SAE and denosumab when surgery is not indicated or feasible. Its benefits include effectiveness after a single injection, complete ossification, cortical bone restoration, and artifact-free imaging. These features make it valuable also in cases of pathological fractures.
Unsatisfactory Neurological Outcome in an Intramedullary Thoracic Intermediate-Grade Melanocytoma—Systematic Review and Illustrative Case Marco Battistelli, Fulvio Grilli, Alessandro Rapisarda, Michele Di Domenico, Nicola Montano, Marco Gessi, Alessandro Olivi, Alessio Albanese, Filippo Maria Polli Cancers, 2024 Background: Intramedullary melanocytomas are exceedingly rare, with only twenty-four cases reported up to now. They present as local invasive tumors despite their benign biological behavior. Attempting a complete safe resection often results in severe post-operative neurological deficits, as in our case presented here. Methods: A systematic review was conducted across the PubMed and Scopus databases including studies published till February 2024. Results: A total of 19 studies were included, encompassing 24 cases. A similar distribution between sexes was noted (M:F 13:11), with ages ranging from 19 to 79 years. The thoracic segment was most affected, and intermediate-grade melanocytoma (19 cases) was the most common histotype. Radiographically, intramedullary melanocytomas usually appear as hyperintense hemorrhagic lesions peripheral to the central canal with focal nodular enhancement. Intraoperatively, they are black–reddish to tan and are tenaciously adherent lesions. In the sampled studies, IONM employment was uncommon, and post-operative new-onset neurological deficits were described in 16 cases. Adjuvant RT was used in four cases and its value is debatable. Recurrence is common (10 cases), and adjuvant therapies (RT or repeated surgery) seem to play a palliative role. Case presentation: A 68-year-old woman presented with a three-year history of worsening spastic paraparesis and loss of independence in daily activities (McCormick grade 4). An MRI revealed an intramedullary tumor from Th5 to Th7, characterized by T1-weighted hyperintensity and signs of recent intralesional hemorrhage. Multimodal neuromonitoring, comprising the D-Wave, guided the resection of a black–tan-colored tumor with hyper-vascularization and strong adherence to the white matter. During final dissection of the lesion to obtain gross total resection (GTR), a steep decline in MEPs and D-Wave signals was recorded. Post-operatively, the patient had severe hypoesthesia with Th9 level and segmental motor deficits, with some improvement during neurorehabilitation. Histopathology revealed an intermediate-grade melanocytoma (CNS WHO 2021 classification). A four-month follow-up documented the absence of relapse. Conclusions: This literature review highlights that intramedullary T1 hyperintense hemorrhagic thoracic lesions in an adult patient should raise the suspicion of intramedullary melanocytoma. They present as locally aggressive tumors, due to local invasiveness, which often lead to post-operative neurological deficits, and frequent relapses, which overwhelm therapeutic strategies leading to palliative care after several years.
The Role of Psychosomatic Traits in Tailored Workup for Anterior Cervical Discectomy and Fusion—A Case Series Marco Battistelli, Edoardo Mazzucchi, Mario Muselli, Filippo Maria Polli, Gianluca Galieri, Paola Bazzu, Fabrizio Pignotti, Alessandro Olivi, Giovanni Sabatino, Giuseppe La Rocca Journal of Personalized Medicine, 2024 Study design: Prospective study. Objective: To evaluate the influence of preoperatively assessed psychosomatic traits on postoperative pain, disability, and quality of life outcomes. Summary of background data: Anterior cervical discectomy and fusion (ACDF) is a widely employed surgical procedure for treating cervical spondylosis. Despite its effectiveness, various studies have reported non-success rates in terms of alleviating disability and pain. Psychological factors have become increasingly recognized as critical determinants of surgical outcomes in various medical disciplines. The full extent of their impact within the context of ACDF remains insufficiently explored. This case series aims to assess the influence of preoperative psychological profiling on long-term pain, disability and quality of life outcomes. Methods: We conducted a prospective cohort study of prospectively collected data from 76 consecutive patients who underwent ACDF with PEEK inter-fixed cages from July 2019 to November 2021. The preoperative psychological traits were assessed using the Symptom Checklist 90 (SCL-90) questionnaire. The Oswestry Disability Index (ODI), Visual Analogue Scale (VAS), Neck Disability index (NDI), EuroQol-5D (EQ-5D), and Short Form-36 (SF-36) were collected preoperatively, one month postoperatively, and at least one year after the surgical procedure. Results: The correlation analyses revealed associations between psychosomatic traits and multiple preoperative and postoperative outcome measures. The univariate analyses and linear regression analyses demonstrated the influence of the Global Severity Index (GSI) over the final follow-up scores for the ODI, VAS, NDI, EQ-5D, and SF-36. The GSI consistently exhibited a stronger correlation with the final follow-up pain, disability, and quality of life outcomes with respect to the correspondent preoperative values. Conclusion: This study highlights the importance of psychosomatic traits as predictive factors for ACDF outcomes and emphasizes their relevance in preoperative assessment for informing patients about realistic expectations. The findings underscore the need to consider psychological profiles in the preoperative workup, opening avenues for research into medications and psychological therapies. Recognizing the influence of psychosocial elements informs treatment strategies, fostering tailored surgical approaches and patient care.
Safety and Efficacy of Zero-Profile Polyetheretherketone (PEEK) Cages Filled with Biphasic Calcium Phosphate (BCP) in Anterior Cervical Discectomy and Fusion (ACDF): A Case Series Marco Battistelli, Edoardo Mazzucchi, Mario Muselli, Gianluca Galieri, Filippo Maria Polli, Fabrizio Pignotti, Alessandro Olivi, Giovanni Sabatino, Giuseppe La Rocca Journal of Clinical Medicine, 2024 Background: In the evolving landscape of anterior cervical discectomy and fusion (ACDF), the integration of biomechanical advancements and proper fusion-enhancing materials is crucial for optimizing patient outcomes. This case series evaluates the efficacy and clinical implications of employing zero-profile polyetheretherketone (PEEK) cages filled with biphasic calcium phosphate (BCP) in ACDF procedures, focusing on fusion and subsidence rates alongside patient disability, residual pain, and quality of life. Methods: This case series comprises 76 consecutive patients, with a median follow-up of 581 days. The Bridwell classification system was used for assessing fusion rates while subsidence occurrence was recorded, correlating these radiographic outcomes with clinical implications. Results: The results demonstrated a satisfactory fusion rate (76.4% for grades I and II). The subsidence rate was low (6.74% of segments). Significant clinical improvements were observed in pain, disability, and quality-of-life metrics, aligning with the minimum clinically important difference thresholds; however, subgroup analyses demonstrated that subsidence or pseudoarthrosis group improvement of PROMs was not statistically significant with respect to baseline. ANOVA analyses documented that subsidence has a significant weight over final follow-up pain and disability outcomes. No dysphagia cases were reported. Conclusions: These findings underscore the efficacy of zero-profile PEEK cages filled with BCP in ACDF, highlighting their potential to improve patient outcomes while minimizing complications. Pseudoarthrosis and subsidence have major implications over long-term PROMs. The study reinforces the importance of selecting appropriate surgical materials to enhance the success of ACDF procedures.
Improved epilepsy after surgical decompression of the internal carotid artery in a patient with spheno-clinoidal meningioma Bollettino Lega Italiana Contro L Epilessia, 2008
Does recurrent laryngeal nerve anatomy condition the choice of the side for approaching the anterior cervical spine? Journal of Neurosurgical Sciences, 2007