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Introduction: Immunosuppressive treatment is effective in most Myasthenia gravis patients, but 10-15% of patients areconsidered refractory due to inadequate response or intolerance to therapy. Eculizumab, a humanized monoclonalantibody directed against C5 complement protein, was approved in Italy to treat Ab-AchR generalized refractoryMG (rMG) in October 2022., Aim: We aim to describe a real-world Italian experience in a population of refractory myasthenia gravis patients with oneyear follow up., Methods: A retrospective data analysis was conducted on patients with refractory generalized MG treated with eculizumabbetween November 2022 and May 2024. Clinical assessment through specific scales (MG ADL - QMG - MGFA -PIS), rescue, and background therapy was recorded after one, three, six, and twelve months., Results: 21 rMG patients were treated with eculizumab with a medium follow up of 10.4 months and 14 patients had at leastone year follow up. A clinically meaningful reduction in total MG-ADL and QMG scores was achieved in the firstmonth. It was maintained throughout the first, third, sixth, and twelfth month along with concomitant reduction ofimmunosuppressive treatments. A drastic reduction of myasthenic exacerbations and crisis was observed duringfollow up and intravenous immunoglobulin treatment was discontinued in all patients except one. The total dailydose of prednisone was significantly reduced., Discussion: This single-center real-world study confirmes safety and effectiveness of eculizumab. Eculizumab improved rapidlyall clinical outcome measures, leading to discontinuation of intravenous immunoglobulin treatment and remarkable immunosuppressant-sparing benefits., Competing Interests: Declarations. Ethical approval: This study was conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practice. Ethical approval was waived by the local Ethics Committee and all the procedures being performed were part of the routine care. All patients provided written informed consent. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Conflict of interest: Dario Ricciardi has received travel funding and speaker honoraria from Alexion, UCB, Argenx. This author has no potential conflict of interest to disclose. Carmen Erra has received travel funding and speaker honoraria from Alexion, UCB, Argenx, Anlylam, CLS Bhering. This author has no potential conflict of interest to disclose. Francesco Tuccillo has received travel funding and speaker honoraria from Alexion, UCB, Argenx. This author has no potential conflict of interest to disclose. Bernardo Maria De Martino has received travel funding and speaker honoraria from Alexion, UCB, Argenx. This author has no potential conflict of interest to disclose. Alessandra Fasolino has no financial disclosure. This author has no potential conflict of interest to disclose. Francesco Habetswallner has received travel funding and speaker honoraria from Alexion, UCB, Argenx. This author has no potential conflict of interest to disclose., (© 2024. Fondazione Società Italiana di Neurologia.)

We describe the case of a 45-year-old female affected by asthma and nasal polyposis who presented to the emergency department because of worsening dyspnea and paresthesia of the left lower limb. Comprehensive instrumental examinations revealed the presence of severe left ventricle dysfunction, intra-cardiac thrombus, deep vein thrombosis, pulmonary embolism, lung infiltrates, polyserositis, and neurological involvements. Finally, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss syndrome, a rare vasculitis of small-medium blood vessels with several organ involvements. Treatment with anticoagulants, corticosteroids, and cyclophosphamide led to a significant clinical improvement. However, a subcutaneous cardiac defibrillator was implanted because of the persistence of severe left ventricular dysfunction and the high cardiovascular risk phenotype. Indeed, several cardiac manifestations may occur in EGPA, particularly in patients with anti-neutrophil cytoplasmic antibody-negative disease. Therefore, clinicians should have high clinical suspicion because cardiac involvement in EGPA results in a poor prognosis if not diagnosed and adequately treated.

Background and Purpose: There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated., Methods: We applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP., Results: According to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and eight motor-predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F-wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor-predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory-predominant CIDP did., Conclusions: The 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Pulmonary vein isolation by cryoablation (PVI-C) is a standard therapy for the treatment of patients with symptomatic atrial fibrillation (AF). AF symptoms are highly subjective; however, they are important outcomes for the patient. The aim is to describe the use and impact of a web-based App to collect AF-related symptoms in a population of patients who underwent PVI-C in seven Italian centers., Methods: A patient App to collect AF-related symptoms and general health status was proposed to all patients who underwent an index PVI-C. Patients were divided into two groups according to the utilization of the App or the non-usage., Results: Out of 865 patients, 353 (41%) subjects composed the App group, and 512 (59%) composed the No-App group. Baseline characteristics were comparable between the two cohorts except for age, sex, type of AF, and body mass index. During a mean follow-up of 7.9±13.8 months, AF recurrence was found in 57/865 (7%) subjects with an annual rate of 7.36% (95% CI:5.67-9.55%) in the No-App versus 10.99% (95% CI:9.67-12.48%) in the App group, p=0.007. In total, 14,458 diaries were sent by the 353 subjects in the App group and 77.1% reported a good health status and no symptoms. In only 518 diaries (3.6%), the patients reported a bad health status, and bad health status was an independent parameter of AF recurrence during follow-up., Conclusions: The use of a web App to record AF-related symptoms was feasible and effective. Additionally, a bad health status reporting in the App was associated with AF recurrence during follow-up., (© 2023. The Author(s).)

Background: There is a paucity of data comparing vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs) at the time of cardiac implantable electronic device (CIED) surgery. Furthermore, the best management of DOACs (interruption vs continuation) is yet to be determined., Objectives: This study aimed to compare the incidence of device-related bleeds and thrombotic events based on anticoagulant type (DOAC vs VKA) and regimen (interrupted vs uninterrupted)., Methods: This was an observational multicenter study. We included patients on chronic oral anticoagulation undergoing CIED surgery. Patients were matched using propensity scoring., Results: We included 1,975 patients (age 73.8 ± 12.4 years). Among 1,326 patients on DOAC, this was interrupted presurgery in 78.2% (n = 1,039) and continued in 21.8% (n = 287). There were 649 patients on continued VKA. The matched population included 861 patients. The rate of any major bleeding was higher with continued DOAC (5.2%) compared to interrupted DOAC (1.7%) and continued VKA (2.1%) (P = 0.03). The rate of perioperative thromboembolism was 1.4% with interrupted DOAC, whereas no thromboembolic events occurred with DOAC or VKA continuation (P = 0.04). The use of dual antiplatelet therapy, DOAC continuation, and male sex were independent predictors of major bleeding on a multivariable analysis., Conclusions: In this large real-world cohort, a continued DOAC strategy was associated with a higher bleeding risk compared to DOAC interruption or VKA continuation in patients undergoing CIED surgery. However, DOAC interruption was associated with increased thromboembolic risk. Concomitant dual antiplatelet therapy should be avoided whenever clinically possible. A bespoke approach is necessary, with a strategy of minimal DOAC interruption likely to represent the best compromise., Competing Interests: Funding Support and Author Disclosures Dr Creta has received speaker fees from Boston Scientific. Dr Finlay has received research support and speaker fees from Abbott Ltd, Medtronic Ltd, and Biosense Webster; is Chief Medical Officer, Founder, and Shareholder of Echopoint Medical Ltd; is Director, Founder, and Shareholder of Rhythm AI; is Founder and Shareholder of Epicardio Ltd; and has received research funding from National Institutes of HealthR Barts BRC funding. Dr Lambiase has received educational grants from Medtronic and Boston Scientific; and is supported by UCLH Biomedicine National Institute for Health and Care Research and Barts BRC funding. Dr Schilling has had research agreements and has received speaker fees from Abbott, Medtronic, Boston Scientific, and Biosense Webster; and is a shareholder of AI Rhythm. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that is used against cognitive impairment in mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the neurobiological mechanisms underlying the rTMS therapeutic effects are still only partially investigated. Maladaptive plasticity, glial activation, and neuroinflammation, including metalloproteases (MMPs) activation, might represent new potential targets of the neurodegenerative process and progression from MCI to AD. In this study, we aimed to evaluate the effects of bilateral rTMS over the dorsolateral prefrontal cortex (DLPFC) on plasmatic levels of MMP1, -2, -9, and -10; MMPs-related tissue inhibitors TIMP1 and TIMP2; and cognitive performances in MCI patients. Patients received high-frequency (10 Hz) rTMS (MCI-TMS, n = 9) or sham stimulation (MCI-C, n = 9) daily for four weeks, and they were monitored for six months after TMS. The plasmatic levels of MMPs and TIMPs and the cognitive and behavioral scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Beck Depression Inventory II, Beck Anxiety Inventory, and Apathy Evaluation Scale, were assessed at baseline (T0) and after 1 month (T1) and 6 months (T2) since rTMS. In the MCI-TMS group, at T2, plasmatic levels of MMP1, -9, and -10 were reduced and paralleled by increased plasmatic levels of TIMP1 and TIMP2 and improvement of visuospatial performances. In conclusion, our findings suggest that targeting DLPFC by rTMS might result in the long-term modulation of the MMPs/TIMPs system in MCI patients and the neurobiological mechanisms associated with MCI progression to dementia.

Background and Purpose: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials., Methods: This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non-infusion days, followed by an additional 24 weeks off-treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale-Revised), a measure of self-sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire-40, ALSAQ-40) and survival. Tolerability and safety were assessed., Results: Seventy-four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ-40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ-40, difference -0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60., Conclusions: The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: The absence of pacing capabilities may reduce the appeal of subcutaneous implantable cardioverter-defibrillator (S-ICD) devices for patients at risk for conduction disorders or with antitachycardia pacing (ATP)/cardiac resynchronization (CRT) requirements. Reports of rates of S-ICD to transvenous implantable cardioverter-defibrillator (TV-ICD) system switch in real-world scenarios are limited., Objective: The purpose of this study was to investigate the need for a subsequent transvenous (TV) device in patients implanted with an S-ICD and its predictors., Methods: All patients implanted with an S-ICD were enrolled from the multicenter, real-world iSUSI (International SUbcutaneouS Implantable cardioverter defibrillator) Registry. The need for a TV device and its clinical reason, and appropriate and inappropriate device therapies were assessed. Logistic regression with Firth penalization was used to assess the association between baseline and procedural characteristics and the overall need for a subsequent TV device., Results: A total of 1509 patients were enrolled (age 50.8 ± 15.8 years; 76.9% male; 32.0% ischemic; left ventricular ejection fraction 38% [30%-60%]). Over 26.5 [13.4-42.9] months, 155 (10.3%) and 144 (9.3%) patients experienced appropriate and inappropriate device therapies, respectively. Forty-one patients (2.7%) required a TV device (13 bradycardia; 10 need for CRT; 10 inappropriate shocks). Body mass index (BMI) >30 kg/m 2 and chronic kidney disease (CKD) were associated with need for a TV device (odds ratio [OR] 2.57 [1.37-4.81], P = .003; and OR 2.67 [1.29-5.54], P = .008, respectively)., Conclusion: A low rate (2.7%) of conversion from S-ICD to a TV device was observed at follow-up, with need for antibradycardia pacing, ATP, or CRT being the main reasons. BMI >30 kg/m 2 and CKD predicted all-cause need for a TV device., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

In this work, we aim to identify sensitive neurophysiological biomarkers of axonal degeneration in CIDP patients. A total of 16 CIDP patients, fulfilling the clinical and neurophysiological criteria for typical CIDP, treated with subcutaneous immunoglobulin (ScIg) (0.4 g/kg/week) were evaluated at baseline (before ScIg treatment) and after long-term treatment with ScIg (24 months) by clinical assessment scales, nerve conduction studies (NCS) and electromyography (EMG). Conventional and non-conventional neurophysiological parameters: motor unit potential (MUP) analysis, MUP thickness and size index (SI)] and interference pattern (IP) features were evaluated after long-term treatment (24 months) and compared with a population of 16 healthy controls (HC). An increase of distal motor latency (DML) and reduced compound motor action potential (CMAP) amplitude and area in CIDP patients suggest axonal damage of motor fibers, together with a significant increase of MUP amplitude, duration and area. Analysis of non-conventional MUP parameters shows no difference for MUP thickness; however, in CIDP patients, SI is increased and IP area and amplitude values are lower than HC. Despite clinical and neurophysiological improvement after ScIg treatment, neurophysiological analysis revealed axonal degeneration of motor fibers and motor unit remodeling. Correlation analysis shows that the axonal degeneration process is related to the diagnostic and therapeutic delay. MUP area and SI parameters can detect early signs of axonal degeneration, and their introduction in clinical practice may help to identify patients with the worst outcome.

Cardiac amyloidosis (CA) manifests as infiltrative cardiomyopathy with a hypertrophic pattern, usually presenting with heart failure with a preserved ejection fraction. In addition, degenerative valvular heart disease, particularly severe aortic stenosis, is commonly seen in patients with CA. However, amyloid fibril deposition might also infiltrate the conduction system and promote the development of electrical disorders, including ventricular tachyarrhythmias, atrio-ventricular block or acute electromechanical dissociation. These manifestations can increase the risk of sudden cardiac death. This review summarises the pathophysiological mechanisms and risk factors for sudden cardiac death in CA and focuses on the major current concerns regarding medical and device management in this challenging scenario., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Introduction and Objectives: Our objective was to compare the rate of complications in thoracolumbar fractures that occurred during the early postoperative period in patients with multiple high-energy trauma according to the time of surgery. As a secondary objective, to estimate which variables were associated with surgery before 72 h., Material and Methods: Retrospective analysis of a series of patients with thoracolumbar fractures and multiple associated injuries in other anatomical regions due to high energy trauma. Surgically treated in an occupational trauma referral center, by the same surgical team and during the period between January 2013 and December 2019., Results: We analyzed a sample of 40 patients (39 men and 1 woman). The rate of complications was independent of surgical delay (before and after 72 h) (p = 0.827). There were statistically significant differences between early and later surgery groups in the variables age, systolic blood pressure, initial SOFA score and presence of neurological damage (p = 0.014; p = 0.029; p = 0.032; p = 0.012). The overall surgical delay was correlated with the SOFA score (p = 0.007)., Conclusion: The rate of early postoperative complications did not show significant differences between the early and late surgery groups. We observed that the patients who had been operated before 72 h from trauma were younger, had more association with neurological syntoms, presented higher blood pressure values and less physiological damage. Surgical delay was positively correlated with SOFA score on arrival., (Copyright © 2021 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: It has been observed that the fourth-generation cryoballoon (CB4) ablation catheter increased the rate of acute real-time recordings of pulmonary vein isolation (PVI) during the ablation for the treatment of atrial fibrillation (AF). The aim of this analysis was to compare the long-term outcome results between patients treated with the CB4 and second-generation cryoballoon (CB2)., Methods: In total, 492 patients suffering from AF, underwent PVI ablation with either the CB2 or CB4 catheter within this examination of the 1STOP real-world Italian project and were included in the analysis. Specifically, 246 consecutive patients treated by CB4 were compared to 246 propensity-matched control patients who underwent PVI using CB2., Results: When comparing the patient cohorts treated with CB2 versus CB4, acute success rate (99.6 ± 4.7% vs. 99.7 ± 3.6%, p = .949) and peri-procedural complications (3.7% vs.1.2%, p = .080) were similar in both groups, respectively. However, procedure time (100 vs.75 min, p < .001) and fluoroscopy duration (21 vs.17 min, p < .001) were all significantly lower in the CB4 treated patient cohort. At the 12-month follow-up, the freedom from AF recurrence after a 90-day blanking period was significant higher in the CB4 as compared with the CB2 group (93.3% vs.81.3%, p < .001)., Conclusions: In summary, usage of the CB4 ablation catheter increased the rate of acute PVI recording capability and resulted in a higher rate of long-term PVI success, as demonstrated by the reduced rate of AF recurrence in comparison to the CB2 cohort at the 12-month follow-up period., (© 2022 Wiley Periodicals LLC.)

An anomalous aortic origin of a coronary artery (AAOCA) from the opposite sinus, with an interarterial course, has been associated with an increased risk of myocardial ischemia and sudden death. As the exact pathophysiology of AAOCA is not well understood, the clinical management is also not well defined. With increased use of non-invasive imaging, the diagnosis of AAOCA is increasing and the association of anomalous origin and atherosclerotic disease is becoming a more important topic. We report a rare case of AAOCA chronic total occlusion (CTO). A 40-year-old Caucasian man was referred for invasive coronary angiography (ICA) due to typical chest pain and positive myocardial scintigraphy. ICA demonstrated CTO of an anomalous right coronary artery (ARCA) originating from the left side of the ascending aorta with an interarterial course. There was no lesion in the left coronary artery. During the procedure, unexpected rupture of the coronary artery occurred after dilatation with a small balloon at low pressure. The complication in this case was handled with good procedural final result but was an occasion for a food for thought. Coronary artery perforations are rare but life-threatening procedural complications that are usually caused by predisposing anatomical and procedural factors. We issue a warning on the risk of complications during complex percutaneous coronary intervention of these arteries, and we reconsidered the pathophysiology of the anomaly in a way that could change the approach to the disease. Based on this complication, we hypothesized that the wall of the artery could be fragile due to histopathological alterations, which could have a role in the pathophysiology of coronary malignancy. Future autopsy studies should be focused on the analysis of the arterial wall of the patient affected by sudden death with this anomaly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cocco, Madonna, Cammalleri, Cocco, De Stefano, Ricciardi, Grigioni and Ussia.)

Background: A few limited case series have shown that the subcutaneous implantable cardioverter-defibrillator (S-ICD) system is safe for teenagers and young adults, but a large-scale analysis currently is lacking., Objectives: The purpose of this study was to compare mid-term device-associated outcomes in a large real-world cohort of S-ICD patients, stratified by age at implantation., Methods: Two propensity-matched cohorts of teenagers + young adults (≤30 years old) and adults (>30 years old) were retrieved from the ELISIR Registry. The primary outcome was the comparison of inappropriate shock rate. Complications, freedom from sustained ventricular arrhythmias, and overall and cardiovascular mortality were deemed secondary outcomes., Results: Teenagers + young adults represented 11.0% of the entire cohort. Two propensity-matched groups of 161 patients each were used for the analysis. Median follow-up was 23.1 (13.2-40.5) months. In total, 15.2% patients experienced inappropriate shocks, and 9.3% device-related complications were observed, with no age-related differences in inappropriate shocks (16.1% vs 14.3%; P = .642) and complication rates (9.9% vs 8.7%; P = .701). At univariate analysis, young age was not associated with increased rates of inappropriate shocks (hazard ratio [HR] 1.204 [0.675-2.148]: P = .529). At multivariate analysis, use of the SMART Pass algorithm was associated with a strong reduction in inappropriate shocks (adjusted HR 0.292 [0.161-0.525]; P <.001), whereas arrhythmogenic right ventricular cardiomyopathy (ARVC) was associated with higher rates of inappropriate shocks (adjusted HR 2.380 [1.205-4.697]; P = .012)., Conclusion: In a large multicenter registry of propensity-matched patients, use of the S-ICD in teenagers/young adults was safe and effective. The rates of inappropriate shocks and complications between cohorts were not significantly different. The only predictor of increased inappropriate shocks was a diagnosis of ARVC., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that is increasingly used as a nonpharmacological intervention against cognitive impairment in Alzheimer's disease (AD) and other dementias. Although rTMS has been shown to modify cognitive performances and brain functional connectivity (FC) in many neurological and psychiatric diseases, there is still no evidence about the possible relationship between executive performances and resting-state brain FC following rTMS in patients with mild cognitive impairment (MCI). In this preliminary study, we aimed to evaluate the possible effects of rTMS of the bilateral dorsolateral prefrontal cortex (DLPFC) in 27 MCI patients randomly assigned to two groups: one group received high-frequency (10 Hz) rTMS (HF-rTMS) for four weeks ( n = 11), and the other received sham stimulation ( n = 16). Cognitive and psycho-behavior scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status, Beck Depression Inventory-II, Beck Anxiety Inventory, Apathy Evaluation Scale, and brain FC, evaluated by independent component analysis of resting state functional MRI (RS-fMRI) networks, together with the assessment of regional atrophy measures, evaluated by whole-brain voxel-based morphometry (VBM), were measured at baseline, after five weeks, and six months after rTMS stimulation. Our results showed significantly increased semantic fluency ( p = 0.026) and visuo-spatial ( p = 0.014) performances and increased FC within the salience network ( p ≤ 0.05, cluster-level corrected) at the short-term timepoint, and increased FC within the left fronto-parietal network ( p ≤ 0.05, cluster-level corrected) at the long-term timepoint, in the treated group but not in the sham group. Conversely, regional atrophy measures did not show significant longitudinal changes between the two groups across six months. Our preliminary findings suggest that targeting DLPFC by rTMS application may lead to a significant long-term increase in FC in MCI patients in a RS network associated with executive functions, and this process might counteract the progressive cortical dysfunction affecting this domain.