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Background: Dystonia is common in Parkinson disease patients, affecting about 30% of them. Bilateral subthalamic nucleus deep brain stimulation (DBS) can sometimes lead to dystonia, but this relationship is not well understood. Our aim was to provide a better understanding of dystonia's causes and its connection to DBS., Methods: We conducted a retrospective analysis of clinical data from 80 Parkinson disease patients who underwent bilateral subthalamic nucleus stimulation, focusing on dystonia before and after surgery and its relation to medication state (on-dystonia/off-dystonia)., Results: After DBS, off-dystonia had a higher recovery rate than on-dystonia (43.5% vs. 9.1%). Among patients suffering for on-dystonia, 74.4% had it for the first time after surgery; these patients assumed higher doses of levodopa before DBS., Conclusions: Patients with off-dystonia before surgery tend to improve after DBS. Otherwise, DBS could have the role of "additive boost" in the process of sensitization of striato-pallidal pathways and lead to on-dystonia in particular patients., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Essential tremor (ET) is the most common movement disorder. Deep brain stimulation (DBS) targeting the ventral intermediate nucleus (VIM) is known to improve symptoms in patients with medication-resistant ET. However, the clinical effectiveness of VIM-DBS may vary, and other targets have been proposed. The authors aimed to investigate whether the same anatomical structure is responsible for tremor control both immediately after VIM-DBS and at later follow-up evaluations., Methods: Of 68 electrodes from 41 patients with ET, the authors mapped the distances of the active contact from the VIM, the dentatorubrothalamic tract (DRTT), and the caudal zona incerta (cZI) and compared them using Friedman's ANOVA and the Wilcoxon signed-rank follow-up test. The same distances were also compared between the initially planned target and the final implantation site after intraoperative macrostimulation. Finally, the comparison among the three structures was repeated for 16 electrodes whose active contact was changed after a mean 37.5 months follow-up to improve tremor control., Results: After lead implantation, the VIM was statistically significantly closer to the active contact than both the DRTT (p = 0.008) and cZI (p < 0.001). This result did not change if the target was moved based on intraoperative macrostimulation. At the last follow-up, the active contact distance from the VIM was always significantly less than that of the cZI (p < 0.001), but the distance from the DRTT was reduced and even less than the distance from the VIM., Conclusions: In patients receiving VIM-DBS, the VIM itself is the structure driving the anti-tremor effect and remains more effective than the cZI, even years after implantation. Nevertheless, the role of the DRTT may become more important over time and may help sustain the clinical efficacy when the habituation from the VIM stimulation ensues.

Objective: Major depression affects millions of people worldwide and has important social and economic consequences. Since up to 30% of patients do not respond to several lines of antidepressive drugs, deep brain stimulation (DBS) has been evaluated for the management of treatment-resistant depression (TRD). The superolateral branch of the medial forebrain bundle (slMFB) appears as a "hypothesis-driven target" because of its role in the reward-seeking system, which is dysfunctional in depression. Although initial results of slMFB-DBS from open-label studies were promising and characterized by a rapid clinical response, long-term outcomes of neurostimulation for TRD deserve particular attention. Therefore, we performed a systematic review focused on the long-term outcome of slMFB-DBS., Materials and Methods: A literature search using Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria was conducted to identify all studies reporting changes in depression scores after one-year follow-up and beyond. Patient, disease, surgical, and outcome data were extracted for statistical analysis. The Montgomery-Åsberg Depression Rating Scale (ΔMADRS) was used as the clinical outcome, defined as percentage reduction from baseline to follow-up evaluation. Responders' and remitters' rates were also calculated., Results: From 56 studies screened for review, six studies comprising 34 patients met the inclusion criteria and were analyzed. After one year of active stimulation, ΔMADRS was 60.7% ± 4%; responders' and remitters' rates were 83.8% and 61.5%, respectively. At the last follow-up, four to five years after the implantation, ΔMADRS reached 74.7% ± 4.6%. The most common side effects were stimulation related and reversible with parameter adjustments., Conclusions: slMFB-DBS appears to have a strong antidepressive effect that increases over the years. Nevertheless, to date, the overall number of patients receiving implantations is limited, and the slMFB-DBS surgical technique seems to have an important impact on the clinical outcome. Further multicentric studies in a larger population are needed to confirm slMFB-DBS clinical outcomes., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Deep Brain Stimulation (DBS) is an experimental treatment for medication-refractory neuropathic pain. The ventral posteromedial (VPM) and ventral posterolateral (VPL) nuclei of the thalamus are popular targets for the treatment of facial and limb pain, respectively. While intraoperative testing is used to adjust targeting of patient-specific pain locations, a better understanding of thalamic somatotopy may improve targeting of specific body regions including the individual trigeminal territories, face, arm, and leg. To elucidate the somatotopic organization of the ventral nuclear group of the dorsal thalamus using in vivo macrostimulation data from patients undergoing DBS for refractory neuropathic pain. In vivo macrostimulation data was retrospectively collected for 14 patients who underwent DBS implantation for neuropathic pain syndromes at our institution. 56 contacts from 14 electrodes reconstructed with LeadDBS were assigned to macrostimulation-related body regions: tongue, face, arm, or leg. 33 contacts from 9 electrodes were similarly assigned to one of three trigeminal territories: V1, V2, or V3. MNI coordinates in the x, y, and z axes were compared by using MANOVA. Across the horizontal plane of the ventral nuclear group of the dorsal thalamus, the tongue was represented significantly medially, followed by the face, arm, and leg most laterally (p < 0.001). The trigeminal territories displayed significant mediolateral distribution, proceeding from V1 and V2 most medial to V3 most lateral (p < 0.001). Along the y-axis, V2 was also significantly anterior to V3 (p = 0.014). While our results showed that the ventral nuclear group of the dorsal thalamus displayed mediolateral somatotopy of the tongue, face, arm, and leg mirroring the cortical homunculus, the mediolateral distribution of trigeminal territories did not mirror the established cortical homunculus. This finding suggests that the facial homunculus may be inverted in the ventral nuclear group of the dorsal thalamus., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Epilepsy is a widespread neurologic disorder and almost one-third of patients suffer from drug-resistant epilepsy (DRE). Neuromodulation targeting the centromediannucleus of the thalamus (CM) has been showing promising results for patients with generalized DRE who are not surgical candidates. Recently, the effect of CM- deep brain stimulation (DBS) in DRE patients was investigated in the Electrical Stimulation of Thalamus for Epilepsy of Lennox-Gastaut phenotype (ESTEL) trial, a monocentric randomized-controlled study. The same authors described a 'cold-spot' and a 'sweet-spot', which are defined as the volume of stimulation in the thalamus yielding the least and the best clinical response, respectively. However, it remains unclear which structural connections may contribute to the anti-seizure effect of the stimulation., Objective: We investigated the differences in structural connectivity among CM, the sweet-spot and the cold-spot. Furthermore, we tried to validate our results in a cohort of DRE patients who underwent CM-DBS or CM-RNS (responsive neurostimulation). We hypothesized that the sweet-spot would share similar structural connectivity with responder patients., Methods: By using the software FMRIB Software Library (FSL), probabilistic tractography was performed on 100 subjects from the Human Connectome Project to calculate the probability of connectivity of the whole CM, the sweet-spot and the cold-spot to 45 cortical and subcortical areas. Results among the three seeds were compared with multivariate analysis of variance (MANOVA). Similarly, the structural connectivity of volumes of tissue activated (VTAs) from eight DRE patients was investigated. Patients were divided into responders and non-responders based on the degree of reduction in seizure frequency, and the mean probabilities of connectivity were similarly compared between the two groups., Results: The sweet-spot demonstrated a significantly higher probability of connectivity ( p  < 0.001) with the precentral gyrus, superior frontal gyrus, and the cerebellum than the whole CM and the cold-spot. Responder patients displayed a higher probability of connectivity with both ipsilateral ( p  = 0.011) and contralateral cerebellum ( p  = 0.04) than the non-responders., Conclusion: Cerebellar connections seem to contribute to the beneficial effects of CM-neuromodulation in patients with drug-resistant generalized epilepsy., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AF is supported by the Dr. Alfonsina Q. Davies Chair in Epilepsy Research. AAB is a consultant for Medtronic. None of the other authors has any conflicts of interest to disclose., (© The Author(s), 2023.)

Background: Dementia affects more than 55 million people worldwide. Several technologies have been developed to slow cognitive decline: deep brain stimulation (DBS) of network targets in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) have been recently investigated., Objective: This study aimed to review the characteristics of the populations, protocols, and outcomes of patients with dementia enrolled in clinical trials investigating the feasibility and efficacy of DBS., Materials and Methods: A systematic search of all registered RCTs was performed on Clinicaltrials.gov and EudraCT, while a systematic literature review was conducted on PubMed, Scopus, Cochrane, and APA PsycInfo to identify published trials., Results: The literature search yielded 2122 records, and the clinical trial search 15 records. Overall, 17 studies were included. Two of 17 studies were open-label studies reporting no NCT/EUCT code and were analysed separately. Of 12 studies investigating the role of DBS in AD, we included 5 published RCTs, 2 unregistered open-label (OL) studies, 3 recruiting studies, and 2 unpublished trials with no evidence of completion. The overall risk of bias was assessed as moderate-high. Our review showed significant heterogeneity in the recruited populations regarding age, disease severity, informed consent availability, inclusion, and exclusion criteria. Notably, the standard mean of overall severe adverse events was moderately high (SAEs: 9.10 ± 7.10%)., Conclusion: The population investigated is small and heterogeneous, published results from clinical trials are under-represented, severe adverse events not negligible, and cognitive outcomes uncertain. Overall, the validity of these studies requires confirmation based on forthcoming higher-quality clinical trials., (© 2023. Fondazione Società Italiana di Neurologia.)

Objective: To characterize ictal EEG change in the centromedian (CM) and anterior nucleus (AN) of the thalamus, using stereoelectroencephalography (SEEG) recordings., Methods: Forty habitual seizures were analyzed in nine patients with pediatric-onset neocortical drug-resistant epilepsy who underwent SEEG (age 2-25 y) with thalamic coverage. Both visual and quantitative analysis was used to evaluate ictal EEG signal in the cortex and thalamus. The amplitude and cortico-thalamic latencies of broadband frequencies at ictal onset were measured., Results: Visual analysis demonstrated consistent detection of ictal EEG changes in both the CM nucleus and AN nucleus with latency to thalamic ictal EEG changes of less than 400ms in 95% of seizures, with low-voltage fast activity being the most common ictal pattern. Quantitative broadband amplitude analysis showed consistent power changes across the frequency bands, corresponding to ictal EEG onset, while while ictal EEG latency was variable from -18.0 seconds to 13.2 seconds. There was no significant difference between detection of CM and AN ictal activity on visual or amplitude analysis. Four patients with subsequent thalamic responsive neurostimulation (RNS) demonstrated ictal EEG changes consistent with SEEG findings., Conclusions: Ictal EEG changes were consistently seen at the CM and AN of the thalamus during neocortical seizures., Significance: It may be feasible to use a closed-loop system in the thalamus to detect and modulate seizure activity for neocortical epilepsy.

Objectives: Despite the large amount of literature examining the potential influence of subthalamic nucleus deep brain stimulation (STN-DBS) on psychiatric symptoms and cognitive disorders, only a few studies have focused on its effect on personality. We investigated the correlation between total electrical energy delivered (TEED) and the occurrence of depressive traits in patients with Parkinson disease (PD) after one year of DBS., Materials and Methods: Our study involved 20 patients with PD (12 women, mean [±SD] age 57.60 ± 7.63 years) who underwent bilateral STN-DBS, whose personality characteristics were assessed using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), according to the core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD) procedure., Results: We found that despite a marked improvement in motor functions and quality of life after 12 months, patients showed a significant increase in MMPI-2 subscales for depression (D scale and Depression scale) and in other content component scales (low self-esteem, work interference, and negative treatment indicators). Interestingly, only the TEED on the right side was inversely correlated with the changes in scale D (r s  = -0.681, p = 0.007), whereas depressive traits did not correlate with disease duration, levodopa equivalent daily dose (LEDD) reduction, patient's age, or severity of motor symptoms., Conclusions: Our preliminary observations indicate that despite the excellent motor outcome and general improvement in quality of life, DBS treatment can result in patients poorly adjusting to their personal, familiar, and socio-professional life. Different influences and multiple factors (such as TEED, intra/postsurgical procedure, coping mechanisms, and outcome expectations) may affect depressive traits. Further advances are expected to improve stimulation methods., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Deep brain stimulation (DBS) of the thalamic nuclei for the treatment of drug-resistant epilepsy (DRE) has been investigated for decades. In recent years, DBS targeting the anterior nucleus of the thalamus (ANT) was approved by CE and FDA for the treatment of focal-onset DRE in light of the results from the multicentric randomized controlled SANTE trial. However, stereotactic targeting of thalamic nuclei is not straightforward because of the low contrast definition among thalamic nuclei on the current MRI sequences. When the FGATIR sequence is added to the preoperative MRI protocol, the mammillothalamic tract can be identified and used as a visible landmark to directly target ANT. According to the current evidence, the trans-ventricular trajectory allows the placement of stimulating contact into the nucleus more frequently than the trans-cortical trajectory. Another thalamic nucleus whose stimulation for the treatment of generalized DRE is receiving increasing attention is the centromedian nucleus (CM). CM-DBS seems to be particularly efficacious in patients suffering from Lennox-Gastault syndrome (LGS) and the recent monocentric randomized controlled ESTEL trial also described a beneficial "sweet-spot". However, CM targeting is still based on indirect stereotactic coordinates, since acquisition times and post-processing techniques of the actual MRI sequences are not applicable in clinical practice. Moreover, the results of the ESTEL trial await confirmation from similar studies accounting for epileptic syndromes other than LGS. Therefore, novel neuroimaging approaches are advisable to improve the surgical targeting of CM and potentially tailor the stimulation based on the patient's specific epileptic phenotype., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Object: To investigate those parameters affecting early and follow-up functional outcomes in patients undergoing resection of meningiomas and to design a dedicated predictive score, the Milan Bio(metric)-Surgical Score (MBSS) is hereby presented. Methods: Patients undergoing transcranial surgery for intracranial meningiomas were included. The most significant parameters in the regression analyses were implemented in a patient stratification score and were validated by testing its classification consistency with a clinical−radiological grading scale (CRGS), Milan complexity scale (MCS), and Charlson Comorbidity Index (CCI) scores. Results: The ASA score, Frailty index, skull base and posterior cranial fossa locations, a diameter of >25 mm, and the absence of a brain−tumour interface were predictive of early post-operative deterioration and were collected in MBSS Part A (AUC: 0.965; 95%C.I. 0.890−1.022), while the frailty index, posterior cranial fossa location, a diameter of >25 mm, a edema/tumour volume index of >2, dural sinus invasion, DWI hyperintensity, and the absence of a brain−tumour interface were predictive of a long-term unfavourable outcome and were collected in MBSS Part B (AUC: 0.877; 95%C.I. 0.811−0.942). The score was consistent with CRGS, MCS, and CCI. Conclusion: Patients’ multi-domain evaluation and the implementation of frailty indexes might help predict the perioperative complexity of cases; the functional, clinical, and neurological early outcomes; survival; and overall QoL after surgery.

Background: Neuroimaging differentiation of glioblastoma, primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (BM) remains challenging in specific cases showing similar appearances or atypical features. Overall, advanced MRI protocols have high diagnostic reliability, but their limited worldwide availability, coupled with the overlapping of specific neuroimaging features among tumor subgroups, represent significant drawbacks and entail disparities in the planning and management of these oncological patients., Objective: To evaluate the classification performance metrics of a deep learning algorithm trained on T1-weighted gadolinium-enhanced (T1Gd) MRI scans of glioblastomas, atypical PCNSLs and BMs., Materials and Methods: We enrolled 121 patients (glioblastoma: n=47; PCNSL: n=37; BM: n=37) who had undergone preoperative T1Gd-MRI and histopathological confirmation. Each lesion was segmented, and all ROIs were exported in a DICOM dataset. The patient cohort was then split in a training and hold-out test sets following a 70/30 ratio. A Resnet101 model, a deep neural network (DNN), was trained on the training set and validated on the hold-out test set to differentiate glioblastomas, PCNSLs and BMs on T1Gd-MRI scans., Results: The DNN achieved optimal classification performance in distinguishing PCNSLs (AUC: 0.98; 95%CI: 0.95 - 1.00) and glioblastomas (AUC: 0.90; 95%CI: 0.81 - 0.97) and moderate ability in differentiating BMs (AUC: 0.81; 95%CI: 0.70 - 0.95). This performance may allow clinicians to correctly identify patients eligible for lesion biopsy or surgical resection., Conclusion: We trained and internally validated a deep learning model able to reliably differentiate ambiguous cases of PCNSLs, glioblastoma and BMs by means of T1Gd-MRI. The proposed predictive model may provide a low-cost, easily-accessible and high-speed decision-making support for eligibility to diagnostic brain biopsy or maximal tumor resection in atypical cases., 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 Tariciotti, Caccavella, Fiore, Schisano, Carrabba, Borsa, Giordano, Palmisciano, Remoli, Remore, Pluderi, Caroli, Conte, Triulzi, Locatelli and Bertani.)

Objective: To assess organizational and technical difficulties of neurosurgical procedures during the coronavirus disease 2019 (COVID-19) pandemic and their possible impact on survival and functional outcome and to evaluate virological exposure risk of medical personnel., Methods: Data for all urgent surgical procedures performed in the COVID-19 operating room were prospectively collected. Preoperative and postoperative variables included demographics, pathology, Karnofsky performance status (KPS) and neurological status at admission, type and duration of surgical procedures, length of stay, postoperative KPS and functional outcome comparison, and destination at discharge. We defined 5 classes of pathologies (traumatic, oncological, vascular, infection, hydrocephalus) and 4 surgical categories (burr hole, craniotomy, cerebrospinal fluid shunting, spine surgery). Postoperative SARS-CoV-2 infection was checked in all the operators., Results: We identified 11 traumatic cases (44%), 4 infections (16%), 6 vascular events (24%), 2 hydrocephalus conditions (8%), and 2 oncological cases (8%). Surgical procedures included 11 burr holes (44%), 7 craniotomies (28%), 6 cerebrospinal fluid shunts (24%), and 1 spine surgery (4%). Mean patient age was 57.8 years. The most frequent clinical presentation was coma (44 cases). Mean KPS score at admission was 20 ± 10, mean surgery duration was 85 ± 63 minutes, and mean length of stay was 27 ± 12 days. Mean KPS score at discharge was 35 ± 25. Outcome comparison showed improvement in 16 patients. Four patients died. Mean follow-up was 6 ± 3 months. None of the operators developed postoperative SARS-CoV-2 infection., Conclusions: Standardized protocols are mandatory to guarantee a high standard of care for emergency and urgent surgeries during the COVID-19 pandemic. Personal protective equipment affects maneuverability, dexterity, and duration of interventions without affecting survival and functional outcome., (Copyright © 2021 Elsevier Inc. All rights reserved.)