Advancements in Surgical Therapies for Drug-Resistant Epilepsy: A Paradigm Shift towards Precision Care

Neurology and Therapy, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Epilepsy, a prevalent neurological disorder characterized by recurrent seizures, affects millions worldwide, with significant proportion resistant to pharmacological treatments. Surgical interventions have emerged as pivotal in managing drug-resistant epilepsy (DRE), aiming reduce seizure frequency or achieve freedom. Traditional resective surgeries evolved technological advances, enhancing precision and safety. Neurostimulation techniques, such responsive neurostimulation (RNS) deep brain stimulation (DBS), now provide personalized, real-time management, offering alternatives traditional surgery. Minimally invasive ablative methods, laser interstitial thermal therapy (LITT) Magnetic Resonance-guided Focused Ultrasound (MRgFUS), allow for targeted destruction of epileptogenic tissue reduced risks faster recovery times. The use stereo-electroencephalography (SEEG) robotic assistance has further refined surgical precision, outcomes. These advancements mark paradigm shift towards medicine care, promising improved management quality life patients globally. This review outlines the latest innovations surgery, emphasizing their mechanisms clinical implications improve outcomes DRE.

Язык: Английский

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Re-examining the pathobiological basis of gait dysfunction in Parkinson’s disease

Trends in Neurosciences, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Neuromodulation: Update on current practice and future developments

Neurotherapeutics, Год журнала: 2024, Номер 21(3), С. e00371 - e00371

Опубликована: Апрель 1, 2024

During the past decades, neuromodulation has entered clinical practice exponentially with a variety of invasive and non-invasive approaches (Table 1). Most these treatments have shown not only that their adoption results in an improvement quality life (QoL) but also multidisciplinary approach is key to successful implementation. Clinical implementation aside, advanced been used gain better understanding how nervous system works normal pathological conditions. Not surprisingly, like deep brain stimulation (DBS) are now adopted almost all countries worldwide, steady growth numbers implanted patients [1Sarica C. Conner C.R. Yamamoto K. Yang A. Germann J. Lannon M. et al.Trends disparities utilization United States: Nationwide Inpatient Sample analysis from 1993 2017.Lancet Reg Health Am. 2023; 26 (PMID: 37876670; PMCID: PMC10593574)100599https://doi.org/10.1016/j.lana.2023.100599Abstract Full Text PDF PubMed Scopus (2) Google Scholar].Table 1The list techniques constantly expanding.Neuromodulatory approachesInvasiveNon-invasive•Brain-computer interface•Cochlear implant•Deep stimulation•Dorsal root ganglion stimulation•Gastric/Intestinal electrical stimulation•Motor cortex stimulation•Peripheral nerve stimulation∗•Peripheral subcutaneous field stimulation•Retinal stimulation•Responsive neurostimulation•Spinal cord stimulation•Vagus stimulation•Electroconvulsive therapy•Functional stimulation•Low-intensity focused ultrasound stimulation∗∗•Non-invasive vagus (auricular, cervical)•Peripheral stimulation∗•Transcranial alternating current stimulation•Transcranial direct stimulation•Transcutaneous stimulation•Temporal interference magnetic stimulation∗∗Possibly neuromodulatory and/or offered within same program•Intrathecal drug delivery (e.g. ITB)•Intraventricular ITB)•Lumboperitoneal shunt∗∗•Ventriculoperitoneal shunt∗∗•Intestinal pump-based infusion LICG)•Drug ketamine)•Subcutaneous CSAI)Abbreviations: ∗ includes (invasive non-invasive) nerves: trigeminal, hypoglossal, sacral, pudendal, occipital, phrenic ('diaphragm pacing') tibial (usually percutaneous)' ∗∗ non-electrical (acoustic waves, intracranial pressure modulation); CSAI: continuous apomorphine infusion; ITB: intrathecal baclofen; LCIG: levodopa-carbidopa intestinal gel. Open table new tab Abbreviations: Such resulting expansion indications less conservative patient enrollments, given high level evidence supporting early intervention translates greater sustained QoL benefit [2Schuepbach W.M. Rau Knudsen Volkmann Krack P. Timmermann L. al.Neurostimulation for Parkinson's disease motor complications.N Engl J Med. 2013; 368 23406026): 610-622https://doi.org/10.1056/NEJMoa1205158Crossref (1042) Scholar]. In this special issue Neurotherapeutics, we present compilation excellent articles provide comprehensive review both approved experimental therapies. Davidson al. [3Davidson B. Bhattacharya Sarica Darmani G. Raies N. Chen R. al.Neuromodulation – stimulation.Neurotherapeutics. 2024; 3: xxxGoogle Scholar] broad overview technologies, encompassing methods transcranial (TMS), (tDCS), (TUS), surgical such as (DBS), spinal (SCS), (VNS), which significantly treatment neurological disorders by enabling precise modulation neural activity. Techniques TMS tDCS applied diagnostic therapeutic purposes, leveraging ability induce transient or lasting changes excitability address psychiatric disorders. The authors emphasize that, expands, ongoing research trials vital optimizing technologies personalized medicine, enhancing efficacy mechanisms various Durham [4Durham P.G. Butnariu Alghorazi Pinton Krishna V. Dayton P.A. Current investigations blood-brain barrier disruption: review.Neurotherapeutics. (FUS) technology, highlighting its potential brain, could improve underscores efforts optimize technique need further test across emerging applications, Alzheimer's disease, (PD), tumors; prospect holds great promise improving outcomes. Gouveia [5Gouveia F.V. Warsi N.M. Suresh H. Matin Ibrahim G.M. Neurostimulatory epilepsy: stimulation, responsive neurostimulation discuss drug-resistant epilepsy, specifically focusing on VNS, DBS, (RNS). These treatments, include open-loop closed-loop systems, offer options who do respond traditional candidates resection. While VNS most accessible FDA-approved children, DBS RNS show reducing seizure frequency cases, develop biomarkers predicting response. Neudorfer [6Neudorfer Kultas-Ilinsky Ilinsky I. Paschen S. Helmers A.-K. Cosgrove G.R. al.The role thalamus essential tremor.Neurotherapeutics. evolution state targeting tremor (ET), controversies surrounding optimal targets thalamic ventral intermediate nucleus (Vim) posterior subthalamic area (PSA). They historical anatomical basis selecting targets, emphasizing cerebellothalamic tract (CTT) integration modern imaging electrophysiological accuracy. This suggests while Vim focus ET treatment, technological advances indicate PSA, particularly areas adjacent involving CTT, may superior outcomes suppression, refined strategies enhance efficacy. Further developing theme, Silva [7Silva N.A. Barrios-Martinez Yeh F.-C. Hodaie Roque D. Boerwinkle V.L. al.Diffusion functional MRI neuromodulation.Neurotherapeutics. neuromodulation, mainly ablation means high-intensity FUS well optimization through diffusion (dMRI) (fMRI). highlight shift toward conceptualizing nodes specific networks, rather than merely structures, paradigm facilitated dMRI fMRI, improved precision programming Their modalities personalizing conditions, calling fully realize capabilities practice. Martinez-Nunez therapies PD, application, mechanisms, [8Martinez-Nunez A.E. Justich M.-B. Okun M.S. Fasano Emerging disease.Neurotherapeutics. details methods, including TMS, tDCS, electroconvulsive therapy (ECT), alongside Temporal Interference Stimulation FUS. importance consider patient's symptoms, progression, genetic background, aiming more tailored manage PD complex symptomatology. [9Davidson Luka Milosevic Kondrataviciute Kalia L.V. S.K. Neuroscience fundamentals relevant neuromodulation: neurobiology in-depth neurobiological underpinning discussing effects at local, circuit, neurobiochemical levels, (STN) prime target. elaborate influences neuronal activity axons, neurotransmitter release, impacting microenvironment. It affects broader circuits alters oscillatory activities basal ganglia. addresses debate whether exerts disease-modifying robust large-scale prospective determine long-term impact progression conclusively. Noor [10Noor Steina A.K. McIntyre C.M. Dissecting evoked ganglia.Neurotherapeutics. underlying DBS-evoked ganglia, STN globus pallidus internus treatment. recent discovery large amplitude (EP) oscillations opportunities understand human ganglia network highlights DBS-induced antidromic activation externus (GPe) critical driver oscillations, suggesting significant previously underappreciated GPe outlines EPs clinically useful confirming target engagement. Wang [11Bath J.E. Unraveling threads stability: neurophysiology postural control challenges complexities treating instability biomechanical circuitry deficits contribute condition. describe therapies, feedback-based wearable devices, managing instability. implantable devices chronic data collection mechanisms. future interventions where personalized, circuit-based symptom control. Sammartino colleagues [12Sammartino F. MacDonnell North R.B. Vibhor Poree Disease applications stimulation: nonmalignant pain.Neurotherapeutics. SCS established cost-effective neuropathic pain, application conditions post-laminectomy syndrome, peripheral neuropathy, regional pain syndrome. case studies followed demonstrates exhausted conventional treatments. emphasizes therapy, loss over time, explores other syndromes, underscoring evolving landscape management. Saway [13Saway B.F. Palmer Hughes Triano R.E. Gilmore stroke: neuroplasticity brain-computer interfaces.Neurotherapeutics. exciting development facilitate stroke recovery, rooted interfaces (BCIs). BCIs, augment rehabilitation efforts. explore directions field, integrating artificial intelligence personalization effectiveness recovery patients. Finally, Ranjan [14Ranjan Mahoney J.J. Rezai A.R. Neurosurgical indications.Neurotherapeutics. disorders, obsessive-compulsive disorder (OCD), depression, addiction. OCD, uses remain investigational. techniques, testing safety, efficacy, hopes expanding future. With very few exceptions, centers offering nowadays organized classic framework hospitals' operations, whereby different departments (neurology, neurosurgery, psychiatry, etc.) collaborate maintaining distinct space personnel allocation. existence multiple center centralize decision making process related selection right candidate procedure (e.g., ketamine rTMS before ECT depressed patient). Therefore, any tertiary should be able alternative less-invasive options. Furthermore, existing rate complications reduces time individual [15Sorar Hanalioglu Kocer Eser M.T. Comoglu S.S. Kertmen Experience hardware-related surgery: single-center study 181 operated six years.Parkinsons Dis. 2018; 30140425; PMC6081564)056018https://doi.org/10.1155/2018/3056018Crossref (33) academic tend overall outcome [16Deng Yue J.K. D.D. Trends safety cost movement 2002-2014.Br Neurosurg. 2021; 35 (Epub 2020 Jun 1. PMID: 32476485): 57-64https://doi.org/10.1080/02688697.2020.1759776Crossref (9) fast pace requires dedicated expertise, ready change similar well-established neurosurgeon there specialist expertise management treated treatments; e.g., 'functional' neurologist. Establishing subspecialty, educational training curricula students, residents, postgraduate fellowships necessary accreditation certain programs, highlighted priority many experts field. was indeed goal Brain Subspecialty Summit, took place September 14–15, 2023, hosted Brigham & Women's Hospital Harvard Faculty Club, Boston, Massachusetts. meeting attended 54 physicians scientists representing psychology, neurology, partners neuroscience, industry, professional societies, bodies. A unified agnostic advantages. From point view, some can treat post-traumatic Tourettism seizures whom centromedian chosen, problems [17Picillo Rohani Lozano A.M. Two indications, one target: concomitant epilepsy Centromedian/parafascicular stimulation.Brain Stimul. 2017; 10 2017 Jan 12. 28117177): 711-713https://doi.org/10.1016/j.brs.2017.01.577Abstract (4) standpoint, inspire novel paradigms. (an management) freezing gait [18Rohani Kalsi-Ryan Spinal primary progressive gait.Mov Disord. 32 Jul 6. 28681922): 1336-1337https://doi.org/10.1002/mds.27103Crossref (11) Another example classically recently pipeline PD-related Interestingly migraine potentially predict newer indications. Lastly, clearly interdisciplinarity success it contemporary medicine (Fig. Beyond neurologists, psychiatrists neurosurgeons, Table 2 offers partial contributors practitioners whose adds value neuromodulation.Table 2Beyond professionals program.ExpertiseRoleBiomedical engineers, computational scientistDiscovery commercialization stimulating algorithmsEthicistDesign dilemmasGeneticistPrognosis surgery, i.e. 'surgicogenomics' (visanji al., 2022)KinesiologistObjective evaluation gait, balance disturbances.NeuropathologistAnalysis biopsies taken during surgeryNeurophysiologistNeuronal recordings surgery externalized wires LFP recording.NeuroradiologistAnatomical DTI-based targeting, aggregated individualized VTA heatmaps assist neuroimaging-based DBS).PsychologistAssessment around psychosocial introduced life-changing interventions, e.g. disordersRehabilitation physiotherapistsMaximizing benefits gained mobility.Abbreviations: DBS: DTI: tensor (tractography), LFP: local potential, VTA: volume tissue activated. summary, Neurotherapeutics ranging range reviews collectively pivotal several advancing paradigms modulation, hope deemed intractable. All included response, applications. Moreover, promises exploration into neuromodulation's capabilities, especially revolutionize care. aims serve cornerstone space, inspiring collaborations will push boundaries what possible neurotherapeutics.

Язык: Английский

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Advances in Brain Stimulation, Nanomedicine and the Use of Magnetoelectric Nanoparticles: Dopaminergic Alterations and Their Role in Neurodegeneration and Drug Addiction

Molecules, Год журнала: 2024, Номер 29(15), С. 3580 - 3580

Опубликована: Июль 29, 2024

Recent advancements in brain stimulation and nanomedicine have ushered a new era of therapeutic interventions for psychiatric neurodegenerative disorders. This review explores the cutting-edge innovations techniques, including their applications alleviating symptoms main disorders addiction. Deep Brain Stimulation (DBS) is an FDA-approved treatment specific disorders, Parkinson's Disease (PD), currently under evaluation other conditions, such as Alzheimer's Disease. technique has facilitated significant understanding electrical circuitry by enabling targeted providing insights into neural network function dysfunction. In reviewing DBS studies, this places particular emphasis on underlying neurotransmitter modifications area location, particularly focusing dopaminergic system, which plays critical role these conditions. Furthermore, delves groundbreaking developments nanomedicine, highlighting how nanotechnology can be utilized to target aberrant signaling diseases, with focus system. The discussion extends emerging technologies magnetoelectric nanoparticles (MENPs), represent novel intersection between nanoformulation approaches. These innovative offer promising avenues enhancing precision effectiveness treatments non-invasive, delivery agents well on-site, on-demand stimulation. By integrating from recent research technological advances, aims provide comprehensive synergistically applied address complex neuropsychiatric paving way future strategies.

Язык: Английский

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Revolutionizing Neuroimmunology: Unraveling Immune Dynamics and Therapeutic Innovations in CNS Disorders

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(24), С. 13614 - 13614

Опубликована: Дек. 19, 2024

Neuroimmunology is reshaping the understanding of central nervous system (CNS), revealing it as an active immune organ rather than isolated structure. This review delves into unprecedented discoveries transforming field, including emerging roles microglia, astrocytes, and blood–brain barrier (BBB) in orchestrating neuroimmune dynamics. Highlighting their dual both repair disease progression, we uncover how these elements contribute to intricate pathophysiology neurodegenerative diseases, cerebrovascular conditions, CNS tumors. Novel insights microglial priming, astrocytic cytokine networks, meningeal lymphatics challenge conventional paradigms privilege, offering fresh perspectives on mechanisms. work introduces groundbreaking therapeutic innovations, from precision immunotherapies controlled modulation BBB using nanotechnology focused ultrasound. Moreover, explore fusion with neuromodulatory technologies, underscoring new frontiers for personalized medicine previously intractable diseases. By synthesizing advancements, propose a transformative framework that integrates cutting-edge research clinical translation, charting bold path toward redefining management era neuroimmunology.

Язык: Английский

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Delirium after deep brain stimulation for Parkinson’s disease: a meta-analysis of incidence and risk factors

Neurosurgical Review, Год журнала: 2025, Номер 48(1)

Опубликована: Янв. 23, 2025

Язык: Английский

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Abnormal neuronal activity in the subthalamic nucleus contributes to dysarthria in patients with Parkinson's disease

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106830 - 106830

Опубликована: Фев. 1, 2025

This study investigated the subthalamic nucleus (STN) function and deep brain stimulation (DBS) effects on single-unit activity (SUA) in Parkinson's disease (PD) patients with dysarthria. After presurgical speech analysis, we recorded STN neuronal activities while PD (n = 16) articulated Chinese Pinyin consonants. The consonants were categorized by manner place of articulation for SUA cluster analysis. cohort was then divided into normal dysarthria groups based diadochokinetic (DDK) assessments. patterns, represented mean firing rate (FR), peak time, response intensity during articulation, analyzed compared between two groups. Finally, a 7 included to test pattern changes following intraoperative DBS. Clustering analysis patterns demonstrated that neurons encode grouping same distinct clusters. Using k-means clustering, further classified SUAs waveform types: negative spikes (type 1) positive 2). Dysarthria exhibited an increased FR type 1 reduced 2 spikes. During stimulation, showed accelerated DDK, accompanied decrease increase FR. Our findings indicate crucial role consonant encoding at level. Both DDK performance can be modulated

Язык: Английский

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Concordance between imaging and clinical based STN-DBS programming improves motor outcomes of directional stimulation in Parkinson's disease

Journal of Parkinson s Disease, Год журнала: 2025, Номер unknown

Опубликована: Март 16, 2025

Background Advances in STN-DBS technology, among which directional stimulation, improved Parkinson's disease (PD) treatment efficacy, while increasing the clinical programming complexity. Lead localization software may aid stimulation contact selection process. Objective We aimed to assess concordance between imaging-suggested (IGP) and conventional-programming (CP) selected contacts one year after surgery its impact on motor outcomes. Methods Sixty-four PD patients with bilateral were enrolled. was reconstructed Brainlab TM software. For each electrode, vertical level and, when applicable, directionality predicted by lead reconstruction be most effective established compared parameters clinically activated one-year post-surgery. IGP/CP ratio calculated for both contacts. Post-operative modifications of symptoms severity groups concordant discordant programming. Results One-year post-surgery, 80% active 51% directionality. No significant difference outcomes found activation, whereas (c-Direction) showed superior at follow-up than those (d-Direction) (UPDRS-III stimulation-induced improvement: c-Direction = −25.66 ± 13.74 vs. d-Direction −12.54 11.86; p 0.011). Conclusions Visual correctly levels patients. Imaging therefore facilitates classic assuring similar Moreover, better reached parameters, suggesting that visualization can represent an added value particular

Язык: Английский

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Prioritizing Parkinson’s disease risk genes in genome-wide association loci

npj Parkinson s Disease, Год журнала: 2025, Номер 11(1)

Опубликована: Апрель 16, 2025

Abstract Many drug targets in ongoing Parkinson’s disease (PD) clinical trials have strong genetic links. While genome-wide association studies (GWAS) nominate regions associated with disease, pinpointing causal genes is challenging. Our aim was to prioritize additional druggable underlying PD GWAS signals. The polygenic priority score (PoPS) integrates information from MAGMA gene-level associations and over 57,000 features. We applied PoPS East Asian European data prioritized based on PoPS, distance the signal, non-synonymous credible set variants. 46 genes, including well-established ( SNCA , LRRK2 GBA1 TMEM175 VPS13C ), literature evidence supporting a mechanistic link RIT2, BAG3 SCARB2, FYN, DYRK1A, NOD2, CTSB, SV2C, ITPKB relatively unexplored PD. hold potential for repurposing or development. high-confidence links pathogenesis that may represent our next-best candidates developing disease-modifying therapeutics.

Язык: Английский

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Advances in Brain Stimulation and Nanomedicine: Dopaminergic Alterations and Its Role in Neurodegeneration and Drug Addiction

Опубликована: Июль 2, 2024

Recent advancements in brain stimulation and nanomedicine have ushered a new era of therapeutic interventions for psychiatric neurodegenerative disorders. This review explores the cutting-edge innovations techniques, including their applications alleviating symptoms main disorders addiction. Emphasis is placed on underlying neurotransmitter modifications specific area location, particularly focusing dopaminergic system, which plays critical role these conditions. Furthermore, delves into groundbreaking developments nanomedicine, highlighting how nanotechnology can be utilized to target aberrant signaling diseases, with focus system. The discussion extends emerging technologies such as magnetoelectric nanoparticles (MENPs), represent novel intersection between nanoformulation approaches. These innovative offer promising avenues enhancing precision effectiveness treatments by enabling non-invasive, targeted delivery agents well site, on-demand stimulation. By integrating insights from recent research technological advances, this aims provide comprehensive understanding synergistically applied address complex neuropsychiatric disorders, paving way future strategies.

Язык: Английский

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