The Role of Neuron-specific Enolase as a Biomarker of Response in Percutaneous Balloon Compression for Drug-Resistant Trigeminal Neuralgia Benedetta Burattini, Quintino Giorgio D'Alessandris, Alessandro Rapisarda, Alessandro Izzo, Manuela D'Ercole, Giacomo Moretti, Silvia Baroni, Andrea Urbani, Nicola Montano Neurosurgery, 2026 BACKGROUND AND OBJECTIVES: Neuron-specific enolase (NSE) has been identified as a marker of neuronal damage in different clinical conditions. Percutaneous balloon compression (PBC) is a well-established palliative destructive procedure for the treatment of trigeminal neuralgia (TN). The aim of our study was to evaluate the prognostic role of NSE in predicting pain recurrence after PBC for drug-resistant TN. METHODS: We retrospectively analyzed the prospectively collected data of 41 drug-resistant TN patients (21 M, 20 F; mean age 65 ± 13 years) who underwent PBC between December 2020 and June 2023. Serum levels of NSE and other biochemical parameters were collected preoperatively and postoperatively. Clinical factors, including age, sex, TN duration, pain type and side, previous operations, balloon morphology, were assessed. Outcomes included acute pain relief, recurrence rate, and Barrow Neurological Institute pain score at follow-up (FU). RESULTS: Of the 41 patients, 37 (90.2%) achieved acute pain relief. Barrow Neurological Institute pain score was significantly decreased at FU (median 19.00 [12.75-30.25] months) compared with the preoperative one (2.00 [1.00-3.00] and 4.00 [4.00-5.00], respectively; P < .0001). No major complications occurred in the whole cohort. Pain recurrence was observed in 17 patients (41.5%). Postoperative NSE levels significantly increased compared with preoperative levels (P = .0301) especially in patients without recurrence (P = .0057). Using receiver operating characteristic curve analysis, the following cutoff values were identified: Patients with postoperative NSE >10.5 ng/mL or perioperative (postoperative minus preoperative) NSE increase >0.5 ng/mL had significantly reduced recurrence rates (P = .0004 and P = .0004, respectively). Multivariable analyses confirmed postoperative NSE value and perioperative NSE increase as independent negative predictors of pain recurrence (P = .0420 and P = .0308). CONCLUSION: This study identified NSE as a key biomarker for predicting pain recurrence after PBC for drug-resistant TN. We identified clinically relevant cutoff values for postoperative NSE and perioperative NSE increase, which provide practical tools for risk stratification, allowing personalized FU strategies.
High-Frequency Spinal Cord Stimulation for the Treatment of Spasticity: A Preliminary Case Series Alessandro Izzo, Benedetta Burattini, Renata Martinelli, Quintino Giorgio D’Alessandris, Manuela D'Ercole, Maria Filomena Fuggetta, Nicola Montano Brain Sciences, 2026 Background: Spasticity is a complex and multifactorial condition resulting from upper motor neuron injury. It manifests through muscle contractions, pain, limited range of motion, and clonus, which significantly impair daily activities and quality of life. High-frequency spinal cord stimulation (HF SCS) has shown optimal results in treating chronic neuropathic pain, but its potential role in spasticity remains underexplored. This study aimed to evaluate the efficacy of HF SCS in patients with spasticity. Methods: From April 2021 to July 2024, six patients with spasticity from various etiologies underwent SCS implantation at our institution. Clinical evaluations including the use of the Visual Analog Scale (VAS), Douleur Neuropathique 4 (DN4), and the Ashworth score, as well as ambulation ability and clonus episodes, were performed preoperatively and at a minimum of six months post-surgery. Subjective assessments of motor function, including coordination, movement efficiency, and postural transitions, were also recorded. Results: The mean age of patients was 50.12 ± 9.41 years, with follow-up averaging 24.32 ± 10.83 months. Statistically significant improvements were observed in VAS (p = 0.0412) and DN4 (p = 0.0422) scores, alongside a reduction in clonus episodes. All patients reported subjective improvements in coordination, movement efficiency, and postural transitions. Ambulation remained stable or improved in all cases. No perioperative complications or sensory/motor side effects were noted. Conclusions: HF SCS offers a promising approach to managing spasticity, with improvements in motor function, ambulation, and postural transitions. These findings support further investigation into HF SCS for spasticity, with multicenter trials needed to optimize treatment protocols and identify the most responsive patient populations.
Usefulness of 3T MR in surgical planning for deep brain stimulation surgery: a systematic literature review Quintino Giorgio D’Alessandris, Francesco Pambianco, Renata Martinelli, Manuela D’Ercole, Francesca Annunziata, Carla Piano, Francesco Bove, Maria Filomena Fuggetta, Alessandro Izzo, Nicola Montano Neurosurgical Review, 2025 Magnetic resonance imaging (MRI) allows direct visualization and targeting of the subthalamic nucleus (STN) and the globus pallidus interna (GPi) during deep brain stimulation (DBS) surgery for Parkinson’s disease (PD). Compared to standard 1.5T MRI, the availability of MRI machines with higher magnetic field strength, as 3T MRI, could provide surgical advantages for DBS surgery. The aim of the present systematic review was to gather the available evidence on targeting precision and accuracy, and on clinical outcome, of DBS performed using 1.5T vs. 3T MRI. The literature search yielded 289 results. After duplicate removal and title and abstract screening, 15 full-text papers were assessed, ultimately resulting in the inclusion of six studies in the present work. An improved visualization of STN with 3T MRI was described. Two studies analyzed targeting precision, finding no difference between 1.5T and 3T. Targeting accuracy was evaluated using microelectrode recording-based nucleus identification in four studies: three reported an increased accuracy using 3T MRI, and one reported no differences. Clinical outcome was assessed in three papers, and was judged similar between 1.5T and 3T-based DBS. Risk of bias from the included studies was non-negligible. In conclusion, while the use of 3T MRI can foster deep gray nuclei identification during DBS, according to the available evidence the use of 1.5T MRI remains an adequate option. Further research on this topic is needed. Clinical trial number: Not applicable.
Psychological assessment in patients affected by trigeminal neuralgia. A systematic review Renata Martinelli, Sofia Vannuccini, Benedetta Burattini, Quintino Giorgio D’Alessandris, Manuela D’Ercole, Alessandro Izzo, Daniela P. R. Chieffo, Francesco Doglietto, Nicola Montano Neurosurgical Review, 2025 The aim of the present study was to conduct a systematic review regarding the presence and type of psychological comorbidities in patients with trigeminal neuralgia and to determine the potential impact of surgical treatments on these conditions. We reviewed the literature following PRISMA guidelines to identify and critically examine relevant studies. The review question was formulated according to the PICO framework as follows: “For patients affected by trigeminal neuralgia (P) undergoing neuropsychological assessments (I) and potentially undergoing reassessment after surgical treatment (C), is there a correlation between psychological issues and trigeminal neuralgia, and does the treatment of trigeminal neuralgia improve psychological well-being (O)?”. The literature search yielded a total of 316 results. After removing duplicates (n = 73), 243 papers were screened. Following title and abstract screening, 222 records were excluded. Ultimately, 11 studies were deemed relevant to the research purpose. To the best of our knowledge, this is the first systematic review highlighting the significant psychological burden of trigeminal neuralgia, including higher risks of sleep, depressive, and anxiety disorders. Surgical treatments effectively alleviate both pain and psychological symptoms, and multidisciplinary approaches combining psychological support and neuro-rehabilitation with medical or surgical care yield better outcomes. Standardizing psychological assessment and treatment methodologies is crucial for optimizing trigeminal neuralgia management. Clinical trial number: Not applicable.
Repeated radiosurgery for recurrent or refractory trigeminal neuralgia: a systematic review and meta-analysis Federico Valeri, Giuseppe Maria Della Pepa, Fulvio Vincenzo Grilli, Grazia Menna, Nicola Montano, Alessandro Izzo, Pier Paolo Mattogno, Vito Stifano, Silvia Chiesa, Federica Pavoncello, Maria Vittoria Leone, Domenico Lupoi, Federica Murtas, Vincenzo Valentini, Francesco Miccichè, Alessandro Olivi, Francesco Doglietto, Giuseppe Minniti Neurosurgical Review, 2025 Stereotactic Radiosurgery (SRS) is a well-established component of the multimodal approach to treating trigeminal neuralgia (TN), a condition marked by frequent and recurrent episodes despite treatments. As a result, an increasing number of centers are offering patients a second or even third round of SRS. Despite this trend, there remains ongoing debate regarding optimal radiation dosing, target planning, overall treatment efficacy, duration of symptom relief, and the safety of repeated procedures. In this study, we present a systematic review and meta-analysis of the existing literature on repeated stereotactic radiosurgery for patients with refractory and recurrent TN. According to PRISMA guidelines, we extracted data regarding general patients features, pre-radiosurgical treatments, irradiation doses of Radiosurgical cycles, target planning, outcome and complications. Out of 461 patients included, 317 (73%) achieved a Barrow Neurological Institute pain scale (BNI) ≤ III after a second SRS procedure. The mean irradiation dose employed in the second treatment was 68.4 Gy with a cumulative dose of 145.9 Gy. Out of the 317 patients with favourable outcome, 101 (31.9%) relapsed after a mean 19.2 months. Patients who responded to a first SRS course were 6 times more likely to achieve pain control after repeateded SRS. Complications were mild and were mainly represented by V cranial nerve dysfunction in 202 patients (43.8%). No cases of radionecrosis, hydrocephalus, or brainstem damage were reported. With a mean follow-up of 19.2 months, repeat SRS was effective in controlling pain in roughly 47% of patients. Dosimetric analysis showed high variability of irradiation doses and target planning. Although data support the safety of repeated SRS in patients with refractory or recurrent TN, homogeneous treatment protocols and uniformity in data reporting is needed to optimize the potential of repeated SRS.
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.
Unraveling the role of GBA1 genotype in axial signs response to subthalamic deep brain stimulation Francesco Bove, Danilo Genovese, Alessandro De Biase, Alberto Albanese, Angelo Antonini, Carlo Alberto Artusi, Laura Avanzino, Micol Avenali, Luca Baldelli, Giovanna Calandra-Buonaura, Ilaria Cani, Niccolò Casasoli, Francesco Cavallieri, Roberto Cilia, Antoniangela Cocco, Fabiana Colucci, Francesca Di Biasio, Valentina D’Onofrio, Roberto Eleopra, Valentina Fioravanti, Giulia Giannini, Nico Golfre’ Andreasi, Andrea Guerra, Gabriele Imbalzano, Alessandro Izzo, Claudia Ledda, Marco Liccari, Leonardo Lopiano, Maria Chiara Malaguti, Raffaella Minardi, Pierfrancesco Mitrotti, Luigi Michele Romito, Enza Maria Valente, Franco Valzania, Roberta Zangaglia, Paolo Calabresi, Carla Piano, Anna Rita Bentivoglio, , C. Caltagirone, A. Costa, F. R. Giardina, A. Peppe, C. Pellicano, F. E. Pontieri, F. Piras, F. Sommaruga, G. Sancesario, S. Zabberoni, R. Cilia, F. De Giorgi, G. Devigili, R. Eleopra, A. Elia, B. Garavaglia, G. Giaccone, M. Grisoli, V. Leta, F. Moda, B. Reggiori, L. M. Romito, I. Tramacere, S. Piacentini, M. Avenali, R. Bergamaschi, R. Calabrese, S. Cerri, G. Cosentino, G. Cuconato, R. De Icco, C. Galandra, A. Imarisio, P. Mitrotti, C. Pacchetti, I. Palmieri, M. Picascia, A. Pichiecchio, A. Pisani, C. Tassorelli, E. M. Valente, F. Valentino, R. Zangaglia, C. Agliardi, F. Baglio, A. Caronni, F. Guerini, R. Mancuso, A. Mannini, M. Meloni, F. Saibene, S. Sorbi, F. Vannetti, A. Ciammola, L. Maderna, B. Poletti, A. Ratti, V. Silani, N. Ticozzi, F. Triulzi, F. Verde, G. Zebellin, F. Agosta, S. Amadio, V. Broccoli, R. Cardamone, M. Filippi, S. Galantucci, L. Gianolli, M. Morelli, E. Sarasso, J. Sassone, M. R. Terreni, M. A. Volontè, R. Bellazzi, E. Brigonzi, M. Buonocore, R. Campini, F. Cossa, E. Federici, M. Gennuso, E. Losavio, A. Losurdo, C. Lunetta, G. Maggioni, A. Malovini, C. Morasso, M. Nolano, E. Parati, C. Pistarini, D. M. Rossi, M. Terzaghi, V. Tibollo, L. Avanzino, G. Bonanno, L. Boni, C. Campi, E. Capello, G. Ferrara, A. Gaudio, G. Lagravinese, P. Mandich, R. Marchese, F. Massa, S. Morbelli, F. Nobili, P. Origone, E. Pelosin, L. Roccatagliata, L. Trevisan, A. Arcella, G. Battaglia, D. Belvisi, A. Berardelli, D. Centonze, R. Ferese, S. Gambardella, A. Gialluisi, F. Giangaspero, C. Limatola, N. Modugno, P. Pantano, L. Pavone, S. Puglisi Allegra, A. Brigandì, G. Di Lorenzo, V. Lo Buono, S. Marino, S. Silvestro, C. Sorbera, S. Bonassi, F. Brancati, M. F. De Pandis, B. Picconi, P. M. Rossini, F. Stocchi, L. Vacca, A. Albanese, L. Antunovic, A. Cocco, T. De Santis, R. Gatti, S. Lalli, E. Lauranzano, M. Matteoli, R. Mineri, E. Paraboschi, E. Perdixi, L. Politi, P. Polverino, D. Pozzi, G. Savini, A. R. Bentivoglio, F. Bove, P. Calabresi, A. Cimmino, A. De Biase, G. Di Lazzaro, D. Di Giuda, D. Genovese, M. R. Lo Monaco, M. Petracca, C. Piano, F. D. Tiziano, M. G. Vita, G. Arcara, R. Barresi, V. Camparini, P. Cudia, G. Ferrazzi, K. Koutsikos, N. Manzo, F. Pellizzari, A. Arighi, F. Blandini, F. Cogiamanian, M. Castellani, F. Colucci, M. Cribiù, A. Di Fonzo, G. Franco, E. Frattini, C. Losa, F. Mameli, E. Monfrini, E. Scola, I. Trezzi, M. G. Bacalini, L. Baldelli, G. Calandra-Buonaura, I. Cani, L. Caporali, V. Carelli, P. Cortelli, P. Ghedini, P. Guaraldi, G. Giannini, G. Lopane, R. Minardi, A. Fiorentino, F. Nonino, R. Pantieri, P. Parchi, F. Provini, C. Tonon, L. Sambati Npj Parkinson S Disease, 2025 GBA1 variants represent the most common genetic risk factor for Parkinson's disease (PD) and are associated with higher risk of developing cognitive decline and axial motor impairment. While cognitive outcomes following subthalamic deep brain stimulation (STN-DBS) have recently received growing attention, axial signs progression remains poorly defined in this population. In this retrospective multicentric study, we analyzed a cohort of 353 PD patients who underwent bilateral STN-DBS surgery (75 GBA+ and 253 GBA-). 5-year follow-up data were available for 233 patients, including 43 mutated subjects. Lower off-medication UPDRS III score and levodopa responsiveness at baseline were identified as independent predictors of axial signs worsening after DBS, while GBA1 genotype was not identified as risk factor. The presence of GBA1 variants did not exert a detrimental effect on axial signs in PD patients up to five years following STN-DBS, supporting its consideration as a valid therapeutic option in this genetic subgroup.
Intraoperative Local Field Potential Beta Power and Three-Dimensional Neuroimaging Mapping Predict Long-Term Clinical Response to Deep Brain Stimulation in Parkinson Disease: A Retrospective Study Lazzaro di Biase, Carla Piano, Francesco Bove, Lorenzo Ricci, Maria Letizia Caminiti, Alessandro Stefani, Fabio Viselli, Nicola Modugno, Rocco Cerroni, Paolo Calabresi, Anna Rita Bentivoglio, Tommaso Tufo, Vincenzo Di Lazzaro, Maria Concetta Altavista, Livia Brusa, Marco Ciavarro, Francesca Cortese, Manuela D'Ercole, Maria Francesca De Pandis, Daniela Di Giuda, Giovanni Fabbrini, Alessandro Izzo, Rosa Liperoti, Giuseppe Marano, Massimo Marano, Michela Orsini, Michele Paradiso, Antonella Peppe, Mariangela Pierantozzi, Camilla Rocchi, Antonio Suppa, Rita Vadalà, Laura Vacca, Antonio Daniele Neuromodulation, 2023
Neuromodulation for Brain Tumors: Myth or Reality? A Narrative Review Quintino Giorgio D’Alessandris, Grazia Menna, Alessandro Izzo, Manuela D’Ercole, Giuseppe Maria Della Pepa, Liverana Lauretti, Roberto Pallini, Alessandro Olivi, Nicola Montano International Journal of Molecular Sciences, 2023
