Search Results (538)

Background/Objectives: This study aimed to describe temporal trends in deep brain stimulation (DBS) use for Parkinson’s disease (PD), essential tremor (ET), and dystonia; characterize patient age and sex distribution and comorbidity; assess postoperative complications and in-hospital mortality (IHM) after implantation and explantation; and explore sex-specific differences in utilization and outcomes. Methods: We conducted a retrospective nationwide population-based study using the Spanish National Hospital Discharge Database (RAE-CMBD) from 2002 to 2019. All hospital admissions with DBS implantation or explantation/revision and a diagnosis of PD, ET, or dystonia were identified. Sociodemographic variables, the Charlson Comorbidity Index (CCI), length of hospital stay (LOHS), postoperative complications, and IHM were analyzed across three calendar periods and stratified by diagnosis and sex. Results: A total of 4883 admissions for DBS electrode implantations and 497 admissions for DBS explantation/revision were recorded. PD accounted for 82.6% of implantations, followed by ET (11.2%) and dystonia (6.3%). DBS activity increased significantly over time, while median LOHS declined from 12 to 6 days for implantations and from 13 to 5 days for explantations. Overall IHM after implantation was 0.27%, decreasing to 0.05% in 2014–2019; IHM after explantation was 0.6%. Most hospitalizations had low comorbidity (CCI = 0 in 87.8%), although comorbidity increased over time. Men represented approximately 60% of procedures in PD and ET. Women with PD underwent DBS at older ages, despite similar LOHS and IHM. Postoperative complications were recorded in 14.6% of implantations, mainly hardware-related issues (5–6%) and infections (1–2%), whereas infections (33%) and mechanical problems (27%) predominated among explantations. Conclusions: DBS use in Spain has expanded substantially, with shorter hospital stays and very low in-hospital mortality. Sex-related differences in utilization are increasing, and hardware complications and infections remain the most frequent conditions associated with explantation. As complications were identified only during the same hospitalization as the DBS procedure, late post-discharge events are not captured and could be underestimated; patient-level risks cannot be derived. Full article

Major depressive disorder (MDD) is one of the most prevalent mental illnesses and, despite the availability of multiple treatment options, remains difficult to treat for a substantial proportion of patients. Repetitive transcranial magnetic stimulation (rTMS) is an important therapeutic approach for depression, modulating brain activity through targeted magnetic pulses in a non-invasive manner. This review examined scientific evidence from clinical trials, large-scale analyses, and laboratory investigations regarding the effectiveness and safety of rTMS, as well as its role within contemporary therapeutic strategies for depression. In addition to conventional rTMS, the review addresses theta-burst stimulation (TBS), deep TMS, and various approaches aimed at enhancing treatment efficacy or accelerating clinical response, while also discussing the practical utility of different stimulation devices. rTMS applied to specific regions of the prefrontal cortex has demonstrated significant antidepressant effects, and intermittent theta-burst stimulation (iTBS) appears to achieve comparable outcomes within a shorter time frame. Research further indicates that rTMS is associated with neurobiological changes in brain connectivity, modulation of neurotransmitter systems, and the promotion of neuroplasticity. Across studies, rTMS is generally considered safe, with reported adverse effects being mild and transient. However, further research is needed to optimize stimulation protocols, clarify medium and long-term effects, individualize treatment approaches, and determine the durability of therapeutic benefits. Full article

Background: Abrupt cessation of deep brain stimulation (DBS) in Parkinson’s disease (PD), most commonly due to implantable pulse generator (IPG) battery depletion, may lead to DBS withdrawal syndrome (DBS-WDS). However, withdrawal syndrome does not occur in all patients following stimulation cessation. Methods: We retrospectively analyzed 210 PD patients treated with DBS. Patients with documented stimulation cessation were evaluated for the presence of withdrawal syndrome based on established clinical criteria. Demographic, disease-related, and treatment characteristics were assessed, and descriptive analysis was conducted on severe cases requiring intensive care. Results: DBS battery shutdown occurred in 28 patients (13.3%). Most patients did not develop withdrawal syndrome and experienced only transient motor worsening. Severe DBS-WDS requiring intensive care was rare, occurring in only three patients (1.4%). Battery shutdown alone did not predict withdrawal, nor was preoperative levodopa equivalent daily dose associated with withdrawal risk. Conclusions: DBS battery shutdown is usually not accompanied by withdrawal syndrome, and severe DBS-WDS is uncommon. Proactive battery management may help to prevent this rare but serious complication. Full article

Background: Deep brain stimulation (DBS) has traditionally followed diagnosis-driven, nucleus-centered targeting paradigms. Increasing evidence supports a circuit-based framework in which clinical outcomes depend on modulation of symptom-relevant networks rather than diagnostic labels alone. This approach is particularly relevant in mixed movement disorder phenotypes such as dystonic tremor, where the most disabling symptom may not align with the conventional surgical target. Methods: We report a clinically illustrative single case treated using a symptom-oriented, connectome-informed DBS strategy. Clinical phenotype, tremor severity, functional impairment, prior medical and botulinum toxin treatments, and longitudinal outcomes were systematically reviewed. DBS target selection prioritized the dominant, treatment-refractory symptom rather than the underlying dystonia diagnosis. Surgical planning incorporated high-resolution MRI with patient-specific thalamic segmentation using Brainlab Brain Elements^®, followed by postoperative lead localization and volume of tissue activated visualization with the SureTune™ platform. Results: A 54-year-old left-handed woman with long-standing cervical dystonia developed a severe, markedly asymmetric dystonic tremor predominantly affecting the left upper limb, resulting in profound functional disability. Instead of conventional bilateral globus pallidus internus DBS, unilateral right ventral intermediate nucleus (VIM) DBS was selected to engage tremor-related cerebellothalamic circuits. Rapid and marked improvement was observed, with tremor severity reduced to mild levels within 15 days after stimulation onset. At 6-month follow-up, overall tremor severity improved from 49 to 13 points on the Fahn–Tolosa–Marin Tremor Rating Scale, corresponding to a 73.5% reduction. This improvement was associated with restoration of legible handwriting, independent feeding and drinking, and recovery of bimanual fine motor function. Clinical benefit remained stable throughout follow-up, without stimulation-related adverse effects. Conclusions: This case illustrates the feasibility of a symptom-oriented, connectome-informed DBS strategy in selected patients with dystonic tremor. When symptom expression and network involvement are markedly asymmetric, selective unilateral modulation of the tremor-dominant circuit may achieve meaningful and durable functional improvement. Further studies are needed to assess the generalizability of this approach. Full article

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation tool for investigating the neurophysiology of different neurological and neuropsychiatric disorders, including Parkinson’s disease (PD) and other parkinsonian syndromes and movement disorders. Briefly, TMS enables targeted stimulation of specific cortical regions through externally applied magnetic pulses, avoiding surgical intervention (as it occurs in deep brain stimulation) and making it a safe, repeatable, and well-tolerated approach. Over the past two decades, extensive research has explored the clinical utility of TMS in PD, with particular emphasis on motor cortex excitability, synaptic plasticity, and functional connectivity, which are central contributors to both motor and non-motor symptoms in PD patients. In addition, repetitive TMS and related stimulation paradigms have been shown to positively modulate cortical plasticity, i.e., the brain’s capacity to reorganize neural circuits, suggesting potential benefits for longer-term non-pharmacological management and rehabilitation protocols. More recently, studies have also investigated the role of TMS in atypical and secondary parkinsonisms, indicating that it may help characterize distinct neurophysiological abnormalities and provide symptomatic improvement in selected patients. This narrative expert review provides a comprehensive summary of TMS applications across the wide spectrum of parkinsonian syndromes, highlighting not only clinical potential, but also methodological limitations and future research directions. Full article

Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder characterized by complex interactions across molecular, cellular, circuit, and behavioral scales. While experimental and clinical studies have provided critical insights into PD pathology, integrating these heterogeneous data into coherent mechanistic frameworks and translational strategies remains a major challenge. Computational modeling offers a powerful approach to bridge these scales, enabling the systematic investigation of disease mechanisms, candidate biomarkers, and therapeutic strategies. In this review, we survey state-of-the-art computational approaches applied to PD, spanning molecular dynamics and biophysical models, cellular- and circuit-level network models, systems and abstract-level simulations of basal ganglia function, and whole-brain and data-driven models linked to clinical phenotypes. We highlight how multiscale and hybrid modeling strategies connect α-synuclein pathology, mitochondrial dysfunction, oxidative stress, and dopaminergic degeneration to alterations in neural dynamics and motor and non-motor symptoms. We further discuss the role of computational models in biomarker discovery, including imaging, electrophysiological, and digital biomarkers. In particular, eye-movement-based measures are highlighted as quantitative, reproducible behavioral signals that provide principled constraints for individualized computational modeling. We also review the emerging impact of computational approaches on drug discovery, target prioritization, and in silico clinical trials. Finally, we examine future directions toward personalized and precision medicine in PD, emphasizing digital twin frameworks, longitudinal validation, and the integration of patient-specific data with mechanistic and data-driven models. Together, these advances underscore the growing role of computational modeling as an integrative and hypothesis-generating framework, with the long-term goal of supporting data-constrained predictive approaches for biomarker development and translational applications. Full article

Smart devices and multimodal biosignal systems, including electroencephalography (EEG/MEG), ECG-derived heart rate variability (HRV), and electromyography (EMG), increasingly supported by artificial intelligence (AI), are being explored to improve the assessment and longitudinal monitoring of mental health conditions. Despite rapid growth, the available evidence remains heterogeneous, and clinical translation is limited by variability in acquisition protocols, analytical pipelines, and validation quality. This systematic review synthesizes current applications, signal-processing approaches, and methodological limitations of biosignal-based smart systems for mental health monitoring. Methods: A PRISMA 2020-guided systematic review was conducted across PubMed/MEDLINE, Scopus, the Web of Science Core Collection, IEEE Xplore, and the ACM Digital Library for studies published between 2013 and 2026. Eligible records reported human applications of wearable/smart devices or multimodal biosignals (e.g., EEG/MEG, ECG/HRV, EMG, EDA/GSR, and sleep/activity) for the detection, monitoring, or management of mental health outcomes. The reviewed literature after predefined inclusion/exclusion criteria clustered into six themes: depression detection and monitoring (37%), stress/anxiety management (18%), post-traumatic stress disorder (PTSD)/trauma (5%), technological innovations for monitoring (25%), brain-state-dependent stimulation/interventions (3%), and socioeconomic context (7%). Across modalities, common analytical pipelines included artifact suppression, feature extraction (time/frequency/nonlinear indices such as entropy and complexity), and machine learning/deep learning models (e.g., SVM, random forests, CNNs, and transformers) for classification or prediction. However, 67% of studies involved sample sizes below 100 participants, limited ecological validity, and lacked external validation; heterogeneity in protocols and outcomes constrained comparability. Conclusions: Overall, multimodal systems demonstrate strong potential to augment conventional mental health assessment, particularly via wearable cardiac metrics and passive sensing approaches, but current evidence is dominated by proof-of-concept studies. Future work should prioritize standardized reporting, rigorous validation in diverse real-world cohorts, transparent model evaluations, and ethics-by-design principles (privacy, fairness, and clinical governance) to support translation into practice. Full article

Chronic pain is inherently multifactorial, with biological, psychological, and social factors contributing to neuropathic pain (NP) and central sensitization (CS) syndromes. Comorbidity between functional disorders and the lack of clinical biomarkers adds to the challenge of diagnosis and treatment, leading to frustration for healthcare professionals and patients. Available treatments are limited, increasing patient suffering with personal and financial costs. This systematic review examined multisensory processing alterations in chronic pain and reviewed current pharmacological and non-pharmacological interventions. A structured search was conducted on the PubMed database using the keywords Central Sensitization, Fibromyalgia, Complex Regional Pain Syndrome, and Neuropathic Pain, combined with the keywords Vision, Audition, Olfaction, Touch, Taste, and Proprioception. Papers were then filtered to discuss current treatment approaches. Articles within the last five years, from 2018 to 2023, have been included. Papers were excluded if they were animal studies; investigated tissue damage, disease processes, or addiction; or were conference proceedings or non-English. Results were summarized in table form to allow synthesis of evidence. As this study is a systematic review of previously published research rather than a clinical trial or experimental investigation, the risk of bias was assessed independently by at least two reviewers. 138 studies were identified and analyzed. Of these, 96 focused primarily on treatment options for chronic pain and were analyzed for this systematic review. There were a few emerging themes. No one therapy is effective, so a multidisciplinary approach to diagnosis, including pharmacological, somatic, and psychological treatment, is generally predicted to achieve the best outcomes. Cranial neurovascular compromise, especially of the trigeminal, glossopharyngeal, and potentially the vestibulocochlear nerve, is being increasingly revealed with the advancement of neuroimaging. Cortical and deep brain stimulation to evoke neuroplasticity is an emerging and promising therapy and warrants further investigation. Finally, including patients in their treatment plan allows them control and offers the ability to self-manage their pain. Risk of bias limits the ability to judge the quality of evidence. Full article

Background: Gilles de la Tourette syndrome is a neurobehavioral disorder that typically begins in childhood, subsides during puberty, and may reappear in adolescence. Treatment is primarily conservative, involving psychological and pharmacological therapy. Patients who do not respond to conservative therapy may be treated with deep brain stimulation, although this remains an experimental treatment. Methods: In this two-case report we present the first two cases of patients with Gilles de la Tourette syndrome in Slovenia treated with deep brain stimulation of the anteromedial globus pallidus internus. Results: Over an 18-month follow-up period, we observed an improvement in both cases. In the first case, the Yale Global Tic Severity Scale score decreased from 71 (17 for motor tics, 14 for phonic tics, and 40 on the impairment scale) to 44 points (12 motor, 12 phonic, and 20 impairment). In the second case, the score decreased from 72 (16 motor, 16 phonic, and 40 impairment) to 38 points (8 motor, 10 phonic, and 20 impairment). Conclusions: Deep brain stimulation could be a promising treatment for this disorder. However, further research is needed to determine the most suitable patients and targets. Full article

Chronic pain is a pervasive and debilitating condition that affects millions of individuals worldwide. Unlike acute pain, which serves a protective physiological role, chronic pain persists beyond routine tissue healing and often arises without a discernible peripheral cause. Accumulating evidence indicates that chronic pain is not merely a symptom but a disorder of the central nervous system, underpinned by interacting molecular, neurochemical, and network-level alterations. Molecular neuroimaging using PET and MR spectroscopy has revealed dysregulated excitatory–inhibitory balance (glutamate/GABA), altered monoaminergic and opioidergic signaling, and neuroimmune activation (e.g., TSPO-indexed glial activation) in key pain-related regions such as the insula, anterior cingulate cortex, thalamus, and prefrontal cortex. Converging multimodal imaging—including functional MRI, diffusion MRI, and EEG/MEG—demonstrates aberrant activity and connectivity across the default mode, salience, and sensorimotor networks, alongside structural remodeling in cortical and subcortical circuits. Parallel advances in neuromodulation, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), deep brain stimulation (DBS), and emerging biomarker-guided closed-loop approaches, provide tools to perturb these maladaptive circuits and to test mechanistic hypotheses in vivo. This review integrates neuroimaging findings with molecular and systems-level mechanistic insights into chronic pain and its modulation, highlighting how imaging markers can link biochemical signatures to neural dynamics and guide precision pain management and individualized therapeutic strategies. Full article

The “Neuroimaging and Pathology Biomarkers in Parkinson’s Disease” course held on 12–13 September 2025 in Milan, Italy, convened an international faculty to review state-of-the-art biomarkers spanning neurotransmitter dysfunction, protein pathology and clinical translation. Here, we synthesize the four themed sessions and highlights convergent messages for diagnosis, stratification and trial design. The first session focused on neuroimaging markers of neurotransmitter dysfunction, highlighting how positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) provided complementary insights into dopaminergic, noradrenergic, cholinergic and serotonergic dysfunction. The second session addressed in vivo imaging of protein pathology, presenting recent advances in PET ligands targeting α-synuclein, progress in four-repeat tau imaging for progressive supranuclear palsy and corticobasal syndromes, and the prognostic relevance of amyloid imaging in the context of mixed pathologies. Imaging of neuroinflammation captures inflammatory processes in vivo and helps study pathophysiological effects. The third session bridged pathology and disease mechanisms, covering the biology of α-synuclein and emerging therapeutic strategies, the clinical potential of seed amplification assays and skin biopsy, the impact of co-pathologies on disease expression, and the “brain-first” versus “body-first” model of pathological spread. Finally, the fourth session addressed disease progression and clinical translation, focusing on imaging predictors of phenoconversion from prodromal to clinically overt stages of synucleinopathies, concepts of neural reserve and compensation, imaging correlates of cognitive impairment, and MRI approaches for atypical parkinsonism. Biomarker-informed pharmacological, infusion-based, and surgical strategies, including network-guided and adaptive deep brain stimulation, were discussed as examples of how multimodal biomarkers may inform personalized management. Across all sessions, the need for harmonization, longitudinal validation, and pathology-confirmed outcome measures was consistently emphasized as essential for advancing biomarker qualification in multicentre research and clinical practice. Full article

Background/Objectives: Patients with deep brain stimulation (DBS) require regular follow-up. When a sudden loss of therapeutic effect occurs, impedance abnormalities are often the underlying cause. If reprogramming cannot restore clinical benefit, revision surgery may be necessary to replace defective hardware. Since all three major manufacturers are used at our center, we analyzed our patient cohort to determine the incidence and causes of impedance abnormalities. Methods: All 601 patients who underwent de novo DBS implantation in Hamm between 2009 and 2025 were evaluated for impedance abnormalities. In cases requiring revision surgery, the specific cause was identified. The manufacturer, electrodes, and contacts involved were systematically analyzed. Results: A total of 25 of 601 patients required revision surgery. Revision rates were 2.67% in patients with Parkinson’s disease, 6.19% in those with a tremor, and 5.71% in those with dystonia. Across manufacturers, 7.6% of patients with a Medtronic system required revision surgery, compared with 3.4% of patients with an Abbott system and no patients with a Boston Scientific system. The primary causes of revision were electrode-related problems (19/25), followed by extension defects (6/25), connector issues (4/25), and, in one case, a generator defect (1/25). Conclusions: Only 4.16% of patients required revision surgery due to impedance abnormalities. Patients with a tremor and non-segmented electrodes showed a higher incidence than those with Parkinson’s disease or dystonia. Predominantly older Medtronic systems had the highest revision rate, whereas no Boston Scientific systems required revision. In most cases, the electrodes were the primary source of impedance abnormalities. A total of 52% of revisions were performed within two years and 92% were performed within six years of implantation. Full article

Background: Deep brain stimulation (DBS) is increasingly understood as a precision-oriented neuromodulation therapy capable of influencing distributed basal ganglia–thalamo–cortical and cerebellothalamic networks. Although its symptomatic benefits in Parkinson’s disease, essential tremor, and dystonia are well established, the extent to which DBS supports motor learning, adaptive plasticity, and participation in rehabilitation remains insufficiently defined. Traditional interpretations of DBS as a focal or lesion-like intervention are being challenged by electrophysiological and imaging evidence demonstrating multiscale modulation of circuit dynamics. Objectives and methods: DBS may enhance rehabilitation outcomes by stabilizing pathological oscillations and reducing moment-to-moment variability in motor performance, thereby enabling more consistent task execution and more effective physiotherapy, occupational therapy, and speech–language interventions. However, direct comparative evidence demonstrating additive or synergistic effects of DBS combined with rehabilitation remains limited. As a result, this potential is not fully realized in clinical practice due to interindividual variability, limited insight into how individual circuit architecture shapes therapeutic response, and the limited specificity of current connectomic biomarkers for predicting functional gains. Results: Technological advances such as tractography-guided targeting, directional leads, sensing-enabled devices, and adaptive stimulation are expanding opportunities to align neuromodulation with individualized circuit dysfunction. Despite these developments, major conceptual and empirical gaps persist. Few controlled studies directly compare outcomes with versus without structured rehabilitation following DBS. Heterogeneity in therapeutic response and rehabilitation access further complicates the interpretation of outcomes. Clarifying these relationships is essential for developing precision-informed frameworks that integrate DBS with rehabilitative strategies, recognizing that current connectomic and physiological biomarkers remain incompletely validated for predicting functional outcomes. Conclusions: This review synthesizes mechanistic, imaging, and technological evidence to outline a network-informed perspective of DBS as a potential facilitator of rehabilitation-driven functional improvement and identifies priorities for future research aimed at optimizing durable functional restoration. Full article

Background: Variants in the GBA gene represent the most common genetic risk factor for Parkinson’s disease and are associated with a more aggressive disease course. Deep brain stimulation is an established therapy for advanced Parkinson’s disease, yet the influence of GBA status on postoperative outcomes remains incompletely defined. This review aims to summarize the clinical relevance of GBA genotyping prior to DBS and to evaluate its potential contribution to decision-making, risk stratification, and long-term management. Methods: A structured narrative review was conducted. The literature on sequencing methodology, variant interpretation, and postoperative outcomes in GBA-positive and GBA-negative patients was examined. Particular focus was placed on motor, cognitive, and neuropsychiatric outcomes, and on studies comparing trajectories across variant classes. Results: Across all study designs, patients with GBA-associated Parkinson’s disease demonstrated robust motor improvement after DBS, with outcomes comparable to those in non-carriers. Cognitive and neuropsychiatric decline occurred more rapidly in GBA carriers. Recent evidence indicates that cognitive and neuropsychiatric decline is influenced more by the genetic profile than the stimulation procedure. Variant severity appears to influence postoperative trajectories. Long-read sequencing improves detection of recombinant alleles and may refine genotype–phenotype associations. Genotyping provides additional value in counseling, expectation management, and postoperative planning. Conclusions: DBS remains an effective motor therapy for patients with GBA-associated Parkinson’s disease. Current findings indicate GBA genotyping should inform, and not limit, candidate selection. Integration of clinical, cognitive and genetic data supports more individualized management. Methodological advances in sequencing and the development of prediction models may further enhance personalized DBS planning. Full article