Pub Date : 2025-01-01Epub Date: 2025-08-12DOI: 10.37349/en.2025.1006106
Dirk M Hermann, Marco Bacigaluppi, Claudio L Bassetti, Gabrio Bassotti, Johannes Boltze, Andrew Chan, Turgay Dalkara, Adam Denes, Exuperio Diez-Tejedor, Richard Dodel, Thorsten R Doeppner, Egor Dzyubenko, Ayman ElAli, Tamas Fulop, Alexander Gerhard, Bernd Giebel, Janine Gronewold, Matthias Gunzer, Thomas Heinbockel, Kaibin Huang, Marcello Iriti, Hans-Otto Karnath, Kasteleijn-Nolst Trenite, Ertugrul Kilic, Giuseppe Lanza, Arthur Liesz, Tim Ullrich Magnus, Jessica Mandrioli, Ayan Mohamud-Yusuf, Thomas Müller, Suyue Pan, Luca Peruzzotti-Jametti, Stefano Pluchino, Ryszard Pluta, Aurel Popa-Wagner, Ameneh Rezayof, Mohamed L Seghier, Xinhua Shu, Vikram Singh, Jussi Sipilä, Mark Slevin, Yamei Tang, Georgios Tsivgoulis, Giustino Varrassi, Chen Wang, Bayram Yilmaz, Maha S Zaki, Jinwei Zhang
Recent progress in translational neuroscience has significantly advanced our understanding of neurological diseases. Research progress closely went in line with innovations in research methods, which have expanded our insights considerably beyond previous limits. However, despite the development of disease-modifying treatments, therapeutic options in brain diseases still lag behind fundamental discoveries in basic neuroscience. This perspective examines the factors that hinder clinical progress in translational neuroscience and provides solutions on how to overcome them. Editorial board members of Exploration of Neuroscience were interrogated about the most prominent challenges they see in translational neuroscience and about possible ways to overcome these issues. Key challenges were seen at the interface between experimental research and clinical studies by several members, both from the basic and applied neuroscience fields, which include the selection of appropriate study readouts and endpoints. The establishment of refined study endpoints, combined with biomarkers capable of predicting treatment responses in human patients, will be crucial for the successful clinical implementation of new therapies. Further obstacles were found in the standardization of experimental models, interventions, and assessments both in animals and humans, as well as in the development of personalized treatment strategies. These challenges can be addressed through more clearly defined experimental procedures that closely match clinical conditions and precision-based approaches that ensure efficient therapeutic responses. As a great opportunity, treatment options targeting pathophysiological processes in multiple brain diseases and disease processes in different organ systems were noted. Significant barriers remain in the funding of investigator-driven clinical trials through public research programs, as well as the education of translational and clinician scientists dedicated to clinical translation. Enhanced communication between experimental neuroscientists and clinicians, with a shared understanding and common language, will be essential for the success of future research endeavors.
{"title":"Most prominent challenges in translational neuroscience and strategic solutions to bridge the gaps: Perspectives from an editorial board interrogation.","authors":"Dirk M Hermann, Marco Bacigaluppi, Claudio L Bassetti, Gabrio Bassotti, Johannes Boltze, Andrew Chan, Turgay Dalkara, Adam Denes, Exuperio Diez-Tejedor, Richard Dodel, Thorsten R Doeppner, Egor Dzyubenko, Ayman ElAli, Tamas Fulop, Alexander Gerhard, Bernd Giebel, Janine Gronewold, Matthias Gunzer, Thomas Heinbockel, Kaibin Huang, Marcello Iriti, Hans-Otto Karnath, Kasteleijn-Nolst Trenite, Ertugrul Kilic, Giuseppe Lanza, Arthur Liesz, Tim Ullrich Magnus, Jessica Mandrioli, Ayan Mohamud-Yusuf, Thomas Müller, Suyue Pan, Luca Peruzzotti-Jametti, Stefano Pluchino, Ryszard Pluta, Aurel Popa-Wagner, Ameneh Rezayof, Mohamed L Seghier, Xinhua Shu, Vikram Singh, Jussi Sipilä, Mark Slevin, Yamei Tang, Georgios Tsivgoulis, Giustino Varrassi, Chen Wang, Bayram Yilmaz, Maha S Zaki, Jinwei Zhang","doi":"10.37349/en.2025.1006106","DOIUrl":"10.37349/en.2025.1006106","url":null,"abstract":"<p><p>Recent progress in translational neuroscience has significantly advanced our understanding of neurological diseases. Research progress closely went in line with innovations in research methods, which have expanded our insights considerably beyond previous limits. However, despite the development of disease-modifying treatments, therapeutic options in brain diseases still lag behind fundamental discoveries in basic neuroscience. This perspective examines the factors that hinder clinical progress in translational neuroscience and provides solutions on how to overcome them. Editorial board members of <i>Exploration of Neuroscience</i> were interrogated about the most prominent challenges they see in translational neuroscience and about possible ways to overcome these issues. Key challenges were seen at the interface between experimental research and clinical studies by several members, both from the basic and applied neuroscience fields, which include the selection of appropriate study readouts and endpoints. The establishment of refined study endpoints, combined with biomarkers capable of predicting treatment responses in human patients, will be crucial for the successful clinical implementation of new therapies. Further obstacles were found in the standardization of experimental models, interventions, and assessments both in animals and humans, as well as in the development of personalized treatment strategies. These challenges can be addressed through more clearly defined experimental procedures that closely match clinical conditions and precision-based approaches that ensure efficient therapeutic responses. As a great opportunity, treatment options targeting pathophysiological processes in multiple brain diseases and disease processes in different organ systems were noted. Significant barriers remain in the funding of investigator-driven clinical trials through public research programs, as well as the education of translational and clinician scientists dedicated to clinical translation. Enhanced communication between experimental neuroscientists and clinicians, with a shared understanding and common language, will be essential for the success of future research endeavors.</p>","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2025-02-25DOI: 10.37349/en.2025.100674
Felipe P Perez, Brett Walker, Jorge Morisaki, Haitham Kanakri, Maher Rizkalla
The use of neurostimulation devices for the treatment of Alzheimer's disease (AD) is a growing field. In this review, we examine the mechanism of action and therapeutic indications of these neurostimulation devices in the AD process. Rapid advancements in neurostimulation technologies are providing non-pharmacological relief to patients affected by AD pathology. Neurostimulation therapies include electrical stimulation that targets the circuitry-level connection in important brain areas such as the hippocampus to induce therapeutic neuromodulation of dysfunctional neural circuitry and electromagnetic field (EMF) stimulation that targets anti-amyloid molecular pathways to promote the degradation of beta-amyloid (Aβ). These devices target specific or diffuse cortical and subcortical brain areas to modulate neuronal activity at the electrophysiological or molecular pathway level, providing therapeutic effects for AD. This review attempts to determine the most effective and safe neurostimulation device for AD and provides an overview of potential and current clinical indications. Several EMF devices have shown a beneficial or harmful effect in cell cultures and animal models but not in AD human studies. These contradictory results may be related to the stimulation parameters of these devices, such as frequency, penetration depth, power deposition measured by specific absorption rate, time of exposure, type of cell, and tissue dielectric properties. Based on this, determining the optimal stimulation parameters for EMF devices in AD and understanding their mechanism of action is essential to promote their clinical application, our review suggests that repeated EMF stimulation (REMFS) is the most appropriate device for human AD treatments. Before its clinical application, it is necessary to consider the complicated and interconnected genetic and epigenetic effects of REMFS-biological system interaction. This will move forward the urgently needed therapy of EMF in human AD.
{"title":"Neurostimulation devices to treat Alzheimer's disease.","authors":"Felipe P Perez, Brett Walker, Jorge Morisaki, Haitham Kanakri, Maher Rizkalla","doi":"10.37349/en.2025.100674","DOIUrl":"10.37349/en.2025.100674","url":null,"abstract":"<p><p>The use of neurostimulation devices for the treatment of Alzheimer's disease (AD) is a growing field. In this review, we examine the mechanism of action and therapeutic indications of these neurostimulation devices in the AD process. Rapid advancements in neurostimulation technologies are providing non-pharmacological relief to patients affected by AD pathology. Neurostimulation therapies include electrical stimulation that targets the circuitry-level connection in important brain areas such as the hippocampus to induce therapeutic neuromodulation of dysfunctional neural circuitry and electromagnetic field (EMF) stimulation that targets anti-amyloid molecular pathways to promote the degradation of beta-amyloid (Aβ). These devices target specific or diffuse cortical and subcortical brain areas to modulate neuronal activity at the electrophysiological or molecular pathway level, providing therapeutic effects for AD. This review attempts to determine the most effective and safe neurostimulation device for AD and provides an overview of potential and current clinical indications. Several EMF devices have shown a beneficial or harmful effect in cell cultures and animal models but not in AD human studies. These contradictory results may be related to the stimulation parameters of these devices, such as frequency, penetration depth, power deposition measured by specific absorption rate, time of exposure, type of cell, and tissue dielectric properties. Based on this, determining the optimal stimulation parameters for EMF devices in AD and understanding their mechanism of action is essential to promote their clinical application, our review suggests that repeated EMF stimulation (REMFS) is the most appropriate device for human AD treatments. Before its clinical application, it is necessary to consider the complicated and interconnected genetic and epigenetic effects of REMFS-biological system interaction. This will move forward the urgently needed therapy of EMF in human AD.</p>","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A short overview of the main features of progressive myoclonus epilepsies (PMEs), such as Lafora disease (LD), neuronal ceroid lipofuscinoses (NCLs), and myoclonus epilepsy with ragged-red fibers (MERRF) is given. The stress of this review paper is put on one of the PME’s, the Unverricht-Lundborg disease (ULD)—EPM1, which is caused by mutations in the human cystatin B gene (stefin B is an alternative protein’s name). However, different other genes/proteins were found mutated in patients presenting with EPM1-like symptoms. By understanding their function and pathophysiological roles, further insights into the underlying processes of EPM1 can be obtained. On a broader scale, common pathophysiological mechanisms exist between ULD, LD and NCLs, such as, reactive glia, synaptic remodeling, neuronal hyperexcitability, impairements in the lysosomal/endocytosis system, cytoskeletal functions, and mitochondria. Oxidative stress is also in common. By understanding the underlying molecular and cellular processes, early interventions, better therapies and eventually, by using modern stem cell, gene editing or replacement methods, a cure can be expected.
本文简要概述了进行性肌阵挛癫痫（PMEs）的主要特征，如拉弗拉病（LD）、神经细胞类脂质沉着病（NCLs）和伴有锯齿状红色纤维的肌阵挛癫痫（MERRF）。本综述论文的重点是其中一种 PME，即 Unverricht-Lundborg 病（ULD）-EPM1，它是由人类胱抑素 B 基因突变引起的（胱抑素 B 是蛋白质的另一个名称）。然而，在出现类似 EPM1 症状的患者中还发现了其他不同基因/蛋白质的突变。通过了解它们的功能和病理生理作用，可以进一步了解EPM1的基本过程。从更广泛的意义上讲，ULD、LD 和 NCL 之间存在共同的病理生理机制，如反应性神经胶质细胞、突触重塑、神经元过度兴奋、溶酶体/内吞系统受损、细胞骨架功能和线粒体。氧化应激也是常见现象。通过了解潜在的分子和细胞过程、早期干预、更好的疗法，以及最终使用现代干细胞、基因编辑或替代方法，有望治愈该病。
{"title":"Molecular and cellular processes underlying Unverricht-Lundborg disease—prospects for early interventions and a cure","authors":"E. Žerovnik","doi":"10.37349/en.2024.00051","DOIUrl":"https://doi.org/10.37349/en.2024.00051","url":null,"abstract":"A short overview of the main features of progressive myoclonus epilepsies (PMEs), such as Lafora disease (LD), neuronal ceroid lipofuscinoses (NCLs), and myoclonus epilepsy with ragged-red fibers (MERRF) is given. The stress of this review paper is put on one of the PME’s, the Unverricht-Lundborg disease (ULD)—EPM1, which is caused by mutations in the human cystatin B gene (stefin B is an alternative protein’s name). However, different other genes/proteins were found mutated in patients presenting with EPM1-like symptoms. By understanding their function and pathophysiological roles, further insights into the underlying processes of EPM1 can be obtained. On a broader scale, common pathophysiological mechanisms exist between ULD, LD and NCLs, such as, reactive glia, synaptic remodeling, neuronal hyperexcitability, impairements in the lysosomal/endocytosis system, cytoskeletal functions, and mitochondria. Oxidative stress is also in common. By understanding the underlying molecular and cellular processes, early interventions, better therapies and eventually, by using modern stem cell, gene editing or replacement methods, a cure can be expected.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":" 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141826841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Depression is on the rise and medication does not always provide satisfactory relief. This raises the question of a treatment gap that has not yet been (sufficiently) addressed. Inflammation and oxidative stress play an important pathophysiological role, which also leads to a deficiency of antioxidants such as vitamin C. This perspective mini-review reflects the results of a PubMed search combining the search terms depression with inflammation, oxidative stress and vitamin C. Vitamin C is an important antioxidant and co-factor for many neuronal metabolic and epigenetic pathways, and a deficiency is associated with depression and cognitive disorders. Inadequate vitamin C blood levels that do not yet result in somatic symptoms may induce neuropsychiatric scurvy, which is associated with increased neuroinflammation and characterized by depression and cognitive impairment. Experimental studies show that vitamin C has multifactorial effects on metabolic pathways relevant to depression. Treatment of vitamin C deficiency, which is more common than appreciated, should be considered in the management of depressed patients. Further studies should investigate whether the pharmacological administration of vitamin C has additional effects beyond the correction of deficiency.
抑郁症呈上升趋势，而药物治疗并不总能提供令人满意的缓解。这就提出了一个尚未（充分）解决的治疗缺口问题。炎症和氧化应激起着重要的病理生理学作用，同时也会导致维生素 C 等抗氧化剂的缺乏。本视角小综述反映了 PubMed 搜索结果，该搜索结合了抑郁症、炎症、氧化应激和维生素 C 等关键词。血液中维生素 C 含量不足但尚未导致躯体症状，可能会诱发神经精神坏血病，这与神经炎症加重有关，并以抑郁和认知障碍为特征。实验研究表明，维生素 C 对与抑郁症相关的代谢途径具有多因素影响。在治疗抑郁症患者时，应考虑治疗维生素 C 缺乏症，因为维生素 C 缺乏症比人们想象的更为常见。进一步的研究应探讨维生素 C 的药理作用是否超出了纠正缺乏症的范围。
{"title":"The role of inflammation and oxidative stress in the pathophysiology of depressions: time to consider vitamin C deficiency","authors":"C. Vollbracht, Marc Werner","doi":"10.37349/en.2024.00050","DOIUrl":"https://doi.org/10.37349/en.2024.00050","url":null,"abstract":"Depression is on the rise and medication does not always provide satisfactory relief. This raises the question of a treatment gap that has not yet been (sufficiently) addressed. Inflammation and oxidative stress play an important pathophysiological role, which also leads to a deficiency of antioxidants such as vitamin C. This perspective mini-review reflects the results of a PubMed search combining the search terms depression with inflammation, oxidative stress and vitamin C. Vitamin C is an important antioxidant and co-factor for many neuronal metabolic and epigenetic pathways, and a deficiency is associated with depression and cognitive disorders. Inadequate vitamin C blood levels that do not yet result in somatic symptoms may induce neuropsychiatric scurvy, which is associated with increased neuroinflammation and characterized by depression and cognitive impairment. Experimental studies show that vitamin C has multifactorial effects on metabolic pathways relevant to depression. Treatment of vitamin C deficiency, which is more common than appreciated, should be considered in the management of depressed patients. Further studies should investigate whether the pharmacological administration of vitamin C has additional effects beyond the correction of deficiency.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"48 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141659977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Depression poses a significant global health burden, yet current therapeutic approaches focusing on monoaminergic neurotransmission often fall short of achieving full remission and managing acute episodes effectively. This article explores novel treatment avenues beyond conventional monoaminergic approaches, focusing on emerging strategies targeting glutamatergic modulation, electrophysiological/magnetic brain stimulation techniques, anti-inflammatory agents, gut-brain axis interventions, gamma-aminobutyric acid (GABA) modulation, and psychedelic-assisted therapy. Through a narrative review of recent literature, this paper elucidates the mechanisms, clinical efficacy, safety profiles, and future directions of these innovative treatments. These insights offer valuable perspectives for advancing depression management and bridging existing therapeutic gaps.
{"title":"Novel treatments of depression: bridging the gap in current therapeutic approaches","authors":"Amit Jagtiani","doi":"10.37349/en.2024.00049","DOIUrl":"https://doi.org/10.37349/en.2024.00049","url":null,"abstract":"Depression poses a significant global health burden, yet current therapeutic approaches focusing on monoaminergic neurotransmission often fall short of achieving full remission and managing acute episodes effectively. This article explores novel treatment avenues beyond conventional monoaminergic approaches, focusing on emerging strategies targeting glutamatergic modulation, electrophysiological/magnetic brain stimulation techniques, anti-inflammatory agents, gut-brain axis interventions, gamma-aminobutyric acid (GABA) modulation, and psychedelic-assisted therapy. Through a narrative review of recent literature, this paper elucidates the mechanisms, clinical efficacy, safety profiles, and future directions of these innovative treatments. These insights offer valuable perspectives for advancing depression management and bridging existing therapeutic gaps.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"122 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141666329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Howan Leung, Josephine W.Y. Ip, J. Lam, Gavin K.W. Lee, Carina C.F. Li, Richard Li, Vincent Mok, Tak H. Tsoi, Chun P. Wong, Steven H.S. Wong, Chun M. Chang, Rainer Freynhagen
Aim: The aim of this study was to validate a Chinese version of the painDETECT questionnaire (PD-Q) for the screening and assessment of neuropathic pain (NeP) in a Hong Kong Chinese population. Methods: The PD-Q was translated and cross-culturally adapted from the original German PD-Q, with forward and backward translation according to standard guidelines followed by cognitive debriefing, and finalized by an expert panel. A multicenter (6-site) observational study was conducted to evaluate the validity of the PD-Q. Patients aged 18 or above with medical conditions giving rise to either neuropathic or nociceptive pain (NoP) provided informed consent to participate in this study. Each patient was evaluated by at least two healthcare professionals for causes of pain, the visual analogue scale (VAS), numeric rating scale (NRS) and the PD-Q. Results: Hong Kong Chinese adults (n = 151) were given the clinical description of NeP (n = 93), NoP (n = 41), or mixed pain (n = 17). The mean age of study subjects was 58.5 years (age range: 26–90 years); 94 subjects (62.3%) were female. The mixed pain group was only analysed qualitatively, with validation based on the remaining 134 patients. Mean PD-Q scores for patients diagnosed with NeP and NoP were 19.9 [standard deviation (SD) = 6.4] and 12.5 (SD = 6.2) respectively. Receiver operating characteristic (ROC) curves were plotted for the upper/lower boundaries. The upper boundary was calculated on the basis of a neuropathic diagnosis and a nociceptive diagnosis. The cut-off point was > 18 (80% sensitivity, 60% specificity), and area under the ROC curve (AUC) was 0.67 (P < 0.001). The lower boundary was calculated on the basis of a nociceptive and a neuropathic diagnosis. The cut-off point was < 13 (90% sensitivity, 50% specificity), and AUC was 0.79 (P < 0.001). Conclusions: The PD-Q is a reliable and valid scale to determine neuropathic components of chronic pain in the Hong Kong Chinese population. Validation in a larger Chinese-speaking population worldwide is necessary.
{"title":"Validation and cultural adaption of the neuropathic pain screening questionnaire painDETECT in Chinese","authors":"Howan Leung, Josephine W.Y. Ip, J. Lam, Gavin K.W. Lee, Carina C.F. Li, Richard Li, Vincent Mok, Tak H. Tsoi, Chun P. Wong, Steven H.S. Wong, Chun M. Chang, Rainer Freynhagen","doi":"10.37349/en.2024.00046","DOIUrl":"https://doi.org/10.37349/en.2024.00046","url":null,"abstract":"Aim: The aim of this study was to validate a Chinese version of the painDETECT questionnaire (PD-Q) for the screening and assessment of neuropathic pain (NeP) in a Hong Kong Chinese population. Methods: The PD-Q was translated and cross-culturally adapted from the original German PD-Q, with forward and backward translation according to standard guidelines followed by cognitive debriefing, and finalized by an expert panel. A multicenter (6-site) observational study was conducted to evaluate the validity of the PD-Q. Patients aged 18 or above with medical conditions giving rise to either neuropathic or nociceptive pain (NoP) provided informed consent to participate in this study. Each patient was evaluated by at least two healthcare professionals for causes of pain, the visual analogue scale (VAS), numeric rating scale (NRS) and the PD-Q. Results: Hong Kong Chinese adults (n = 151) were given the clinical description of NeP (n = 93), NoP (n = 41), or mixed pain (n = 17). The mean age of study subjects was 58.5 years (age range: 26–90 years); 94 subjects (62.3%) were female. The mixed pain group was only analysed qualitatively, with validation based on the remaining 134 patients. Mean PD-Q scores for patients diagnosed with NeP and NoP were 19.9 [standard deviation (SD) = 6.4] and 12.5 (SD = 6.2) respectively. Receiver operating characteristic (ROC) curves were plotted for the upper/lower boundaries. The upper boundary was calculated on the basis of a neuropathic diagnosis and a nociceptive diagnosis. The cut-off point was > 18 (80% sensitivity, 60% specificity), and area under the ROC curve (AUC) was 0.67 (P < 0.001). The lower boundary was calculated on the basis of a nociceptive and a neuropathic diagnosis. The cut-off point was < 13 (90% sensitivity, 50% specificity), and AUC was 0.79 (P < 0.001). Conclusions: The PD-Q is a reliable and valid scale to determine neuropathic components of chronic pain in the Hong Kong Chinese population. Validation in a larger Chinese-speaking population worldwide is necessary.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141343312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O. Lykhmus, O. Kalashnyk, M. Skok, O. Deryabina, Olena Toporova, I. Pokholenko, Oksana Gorbatiuk, Vitalii Kordium
Aim: The aim of this work was to study the effects of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) on inflammation-impaired cognitive functions and the brain of mice. Methods: Young mice (~3-month-old) and aged mice (~18-month-old) were injected with bacterial lipopolysaccharide (LPS) and obtained intravenously donor 106 human umbilical cord MSCs, EVs isolated from a similar amount of MSCs or conditioned medium (CM) of MSCs. Subsequently, the mice were examined in behavioral tests and the mouse brains were analyzed for the levels of pro-inflammatory cytokines, α7 nicotinic acetylcholine receptors (α7 nAChRs) and amyloid beta 1-42 (Aβ1-42). Results: EVs prevented LPS-induced memory impairment in mice, whereas CM provided a weaker and temporal effect. Both EVs and MSCs injected once after regular injections of LPS stably improved memory of young mice. In contrast, both cells and EVs provided only transient effect in aged mice injected with LPS. The brains of aged LPS-treated mice contained elevated amounts of IL-1β and IL-6; both MSCs and EVs decreased them significantly. The brains of non-treated aged mice contained decreased levels of α7 nAChRs and increased levels of Aβ1-42 and α7-bound Aβ1-42 compared to the brains of young mice. LPS treatment decreased α7 nAChRs in both young and aged mice, while both MSCs and EVs restored them up to the control level. In young mice, LPS treatment increased the level of Aβ1-42 and α7-bound Aβ1-42, whereas MSCs and EVs decreased it. In contrast, neither LPS nor MSCs/EVs influenced the elevated level of Aβ1-42 but increased α7-bound Aβ1-42 in the brains of aged mice. Conclusions: Regenerative potential of MSCs and MSC-derived EVs is sufficient to support cognitive functions of LPS-treated young mice but is quite poor for aged animals, possibly, due to decreased levels of α7 nAChRs and accumulated Aβ1-42 in their brains.
{"title":"Extracellular vesicles derived from mesenchymal stem cells ameliorate cognitive impairment caused by neuroinflammation in young but not aged mice","authors":"O. Lykhmus, O. Kalashnyk, M. Skok, O. Deryabina, Olena Toporova, I. Pokholenko, Oksana Gorbatiuk, Vitalii Kordium","doi":"10.37349/en.2024.00045","DOIUrl":"https://doi.org/10.37349/en.2024.00045","url":null,"abstract":"Aim: The aim of this work was to study the effects of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) on inflammation-impaired cognitive functions and the brain of mice.\u0000Methods: Young mice (~3-month-old) and aged mice (~18-month-old) were injected with bacterial lipopolysaccharide (LPS) and obtained intravenously donor 106 human umbilical cord MSCs, EVs isolated from a similar amount of MSCs or conditioned medium (CM) of MSCs. Subsequently, the mice were examined in behavioral tests and the mouse brains were analyzed for the levels of pro-inflammatory cytokines, α7 nicotinic acetylcholine receptors (α7 nAChRs) and amyloid beta 1-42 (Aβ1-42).\u0000Results: EVs prevented LPS-induced memory impairment in mice, whereas CM provided a weaker and temporal effect. Both EVs and MSCs injected once after regular injections of LPS stably improved memory of young mice. In contrast, both cells and EVs provided only transient effect in aged mice injected with LPS. The brains of aged LPS-treated mice contained elevated amounts of IL-1β and IL-6; both MSCs and EVs decreased them significantly. The brains of non-treated aged mice contained decreased levels of α7 nAChRs and increased levels of Aβ1-42 and α7-bound Aβ1-42 compared to the brains of young mice. LPS treatment decreased α7 nAChRs in both young and aged mice, while both MSCs and EVs restored them up to the control level. In young mice, LPS treatment increased the level of Aβ1-42 and α7-bound Aβ1-42, whereas MSCs and EVs decreased it. In contrast, neither LPS nor MSCs/EVs influenced the elevated level of Aβ1-42 but increased α7-bound Aβ1-42 in the brains of aged mice.\u0000Conclusions: Regenerative potential of MSCs and MSC-derived EVs is sufficient to support cognitive functions of LPS-treated young mice but is quite poor for aged animals, possibly, due to decreased levels of α7 nAChRs and accumulated Aβ1-42 in their brains.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141349978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kabir Sheikh, Derryl Miller, Robert Blake, Lisa Smith, Susan Conrad, Deborah Sokol, M. Obeid, Rupa Radhakrishnan, Anna Schultheis, Jeffrey Raskin
New onset refractory status epilepticus (NORSE) is an etiologically heterogeneous condition that is associated with high morbidity and mortality. NORSE is often refractory to medical management prompting a workup for epilepsy surgery. Because NORSE remains etiologically elusive in most cases, surgical evaluations are challenging, especially when the epileptogenic zone (EZ) is not easy to lateralize as can be seen in frontal lobe seizures. Lateralizing a frontal lobe EZ may be challenging due to bilateral synchrony from commissural connections through the corpus callosum and low spatiotemporal resolution of the scalp electroencephalography (EEG). We report a pediatric patient with NORSE presenting with focal impaired awareness seizures clustering into super refractory status epilepticus (SRSE). She required surgical intervention for the treatment of her seizures after failing therapeutic doses of antiseizure medications, anesthetic drips, immunomodulation with methylprednisolone, intravenous immunoglobulin and anakinra, and the ketogenic diet. Despite her semiology being focal, the seizures were not well lateralized on scalp EEG and during phase 2 stereo-EEG (sEEG). Anterior magnetic resonance-guided laser interstitial thermal therapy corpus callosotomy (MRgLITT CC) was performed in a multistage surgical approach to successfully lateralize the EZ with a left-lateralized ictal pattern seen after reimplantation of sEEG electrodes. Our case suggests that minimally invasive MRgLITT CC can be successfully used to lateralize an EZ in frontal lobe epilepsy and that epilepsy surgery should be considered in patients with NORSE with SRSE. We also demonstrate that laser interstitial thermal therapy (LITT), while not always resulting in seizure freedom, can sufficiently disrupt a network to abort status epilepticus and lead to seizure improvements.
新发难治性癫痫（NORSE）是一种病因复杂的疾病，发病率和死亡率都很高。NORSE 通常对药物治疗无效，因此需要进行癫痫手术治疗。由于大多数 NORSE 病例的病因难以捉摸，因此手术评估极具挑战性，尤其是致痫区（EZ）不易侧位时，额叶癫痫发作就会出现这种情况。由于通过胼胝体的共神经连接产生的双侧同步性和头皮脑电图（EEG）的低时空分辨率，额叶 EZ 的侧位可能具有挑战性。我们报告了一名患有 NORSE 的儿科患者，她表现为局灶性意识障碍发作，并聚集成超级难治性癫痫状态（SRSE）。她在服用治疗剂量的抗癫痫药物、滴注麻醉剂、使用甲基强的松龙进行免疫调节、静脉注射免疫球蛋白和阿纳金雷以及生酮饮食失败后，需要进行手术干预来治疗癫痫发作。尽管她的症状是局灶性的，但在头皮脑电图和第二阶段立体脑电图（sEEG）上，癫痫发作的侧位并不明显。我们采用多级手术方法进行了前磁共振引导激光间质热疗胼胝体切开术（MRgLITT CC），成功地将 EZ 侧向化，重新植入 sEEG 电极后出现了左侧化发作模式。我们的病例表明，微创 MRgLITT CC 可成功用于额叶癫痫的 EZ 侧向化，对于 NORSE 伴 SRSE 患者，应考虑进行癫痫手术。我们还证明，激光间质热疗（LITT）虽然并不总能使患者摆脱癫痫发作，但却能充分破坏网络以中止癫痫状态，从而改善癫痫发作。
{"title":"Using magnetic resonance-guided laser interstitial thermal therapy corpus callosotomy to lateralize a seizure focus for staged surgical approach","authors":"Kabir Sheikh, Derryl Miller, Robert Blake, Lisa Smith, Susan Conrad, Deborah Sokol, M. Obeid, Rupa Radhakrishnan, Anna Schultheis, Jeffrey Raskin","doi":"10.37349/en.2024.00044","DOIUrl":"https://doi.org/10.37349/en.2024.00044","url":null,"abstract":"New onset refractory status epilepticus (NORSE) is an etiologically heterogeneous condition that is associated with high morbidity and mortality. NORSE is often refractory to medical management prompting a workup for epilepsy surgery. Because NORSE remains etiologically elusive in most cases, surgical evaluations are challenging, especially when the epileptogenic zone (EZ) is not easy to lateralize as can be seen in frontal lobe seizures. Lateralizing a frontal lobe EZ may be challenging due to bilateral synchrony from commissural connections through the corpus callosum and low spatiotemporal resolution of the scalp electroencephalography (EEG). We report a pediatric patient with NORSE presenting with focal impaired awareness seizures clustering into super refractory status epilepticus (SRSE). She required surgical intervention for the treatment of her seizures after failing therapeutic doses of antiseizure medications, anesthetic drips, immunomodulation with methylprednisolone, intravenous immunoglobulin and anakinra, and the ketogenic diet. Despite her semiology being focal, the seizures were not well lateralized on scalp EEG and during phase 2 stereo-EEG (sEEG). Anterior magnetic resonance-guided laser interstitial thermal therapy corpus callosotomy (MRgLITT CC) was performed in a multistage surgical approach to successfully lateralize the EZ with a left-lateralized ictal pattern seen after reimplantation of sEEG electrodes. Our case suggests that minimally invasive MRgLITT CC can be successfully used to lateralize an EZ in frontal lobe epilepsy and that epilepsy surgery should be considered in patients with NORSE with SRSE. We also demonstrate that laser interstitial thermal therapy (LITT), while not always resulting in seizure freedom, can sufficiently disrupt a network to abort status epilepticus and lead to seizure improvements.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141271446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joham Choque-Velasquez, Uriel Tagle-Vega, Francisco de Jesús García-Mendoza, Emilia Machado-Musri, Mauricio Guerrero-Ocampo, Alder Fernando Valenzuela-Rangel
Epileptic seizures are prevalent in people with brain vascular abnormalities like arteriovenous malformations (AVMs) and cavernous malformations, greatly affecting their quality of life. The connection between intracranial vascular abnormalities and epilepsy is still under debate. Therefore, investigating epilepsy in individuals with AVMs is a crucial and current research area. This review presents a comprehensive examination of recent developments in epilepsy among individuals with brain AVMs. The authors conducted a detailed analysis of the natural progression, epidemiology, diagnostic methods, therapeutic approaches, and post-treatment outcomes for individuals with epilepsy associated with AVMs.
{"title":"Current advances in epilepsy among patients with arteriovenous malformations","authors":"Joham Choque-Velasquez, Uriel Tagle-Vega, Francisco de Jesús García-Mendoza, Emilia Machado-Musri, Mauricio Guerrero-Ocampo, Alder Fernando Valenzuela-Rangel","doi":"10.37349/en.2024.00043","DOIUrl":"https://doi.org/10.37349/en.2024.00043","url":null,"abstract":"Epileptic seizures are prevalent in people with brain vascular abnormalities like arteriovenous malformations (AVMs) and cavernous malformations, greatly affecting their quality of life. The connection between intracranial vascular abnormalities and epilepsy is still under debate. Therefore, investigating epilepsy in individuals with AVMs is a crucial and current research area. This review presents a comprehensive examination of recent developments in epilepsy among individuals with brain AVMs. The authors conducted a detailed analysis of the natural progression, epidemiology, diagnostic methods, therapeutic approaches, and post-treatment outcomes for individuals with epilepsy associated with AVMs.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"75 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140984658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Gonzalez-Fernandez, Vicente Rio-Vazquez, J. G. Perez-Blanco, E. Velarde-Reyes, Liana Portela-Hernandez, Aisel Santos-Santos, Joel Gutiérrez-Gil, J. Hernandez-Caceres
Aim: The aim of this paper is to discuss the main features and first outcomes of a therapeutic platform proposed to implement a public health therapeutic service for patients suffering refractory epilepsy. Methods: The proposal is a three-layer system composed by a new portable therapy device and two software applications. The therapy is transcutaneous electrical vagus nerve stimulation, known as tVNS. The primary layer is composed of tVNS devices, configured for each patient according to the instructions provided by the specialists. The middle layer is named “hospital data collector” (HDC), its main tasks are the patient enrollment, the device setup, and the database maintenance to store therapeutic parameters and session events together with the information cited previously. Each hospital center runs a HDC that is connected to a cloud application named “system cloud application (SCA)” which concentrates all the data supplied by the HDCs. Artificial intelligence methods are integrated in the SCA to predict the treatment effectiveness for every new patient based on the accumulated knowledge from the enrolled previously. Results: A version of the proposed system is running at the Institute of Neurology and Neurosurgery. The sensitivity of the therapeutic device with the proposed treatment protocol reaches 83.33% in the 18-patient pilot trial carried out. Conclusions: The proposed approach seems a useful therapeutic tool based on the pilot trial outcomes. The developed device is comfortable and suitable for the intended use. The proposed system has created the essential conditions to feed and grow a knowledge, a basic element to predict the treatment effectiveness for each new patient. It is a promising option for a refractory epilepsy therapy service.
{"title":"First outcomes of a therapeutic platform for drug resistant epilepsy based on transcutaneous electrical vagus nerve stimulation","authors":"R. Gonzalez-Fernandez, Vicente Rio-Vazquez, J. G. Perez-Blanco, E. Velarde-Reyes, Liana Portela-Hernandez, Aisel Santos-Santos, Joel Gutiérrez-Gil, J. Hernandez-Caceres","doi":"10.37349/en.2024.00041","DOIUrl":"https://doi.org/10.37349/en.2024.00041","url":null,"abstract":"Aim: The aim of this paper is to discuss the main features and first outcomes of a therapeutic platform proposed to implement a public health therapeutic service for patients suffering refractory epilepsy.\u0000Methods: The proposal is a three-layer system composed by a new portable therapy device and two software applications. The therapy is transcutaneous electrical vagus nerve stimulation, known as tVNS. The primary layer is composed of tVNS devices, configured for each patient according to the instructions provided by the specialists. The middle layer is named “hospital data collector” (HDC), its main tasks are the patient enrollment, the device setup, and the database maintenance to store therapeutic parameters and session events together with the information cited previously. Each hospital center runs a HDC that is connected to a cloud application named “system cloud application (SCA)” which concentrates all the data supplied by the HDCs. Artificial intelligence methods are integrated in the SCA to predict the treatment effectiveness for every new patient based on the accumulated knowledge from the enrolled previously.\u0000Results: A version of the proposed system is running at the Institute of Neurology and Neurosurgery. The sensitivity of the therapeutic device with the proposed treatment protocol reaches 83.33% in the 18-patient pilot trial carried out.\u0000Conclusions: The proposed approach seems a useful therapeutic tool based on the pilot trial outcomes. The developed device is comfortable and suitable for the intended use. The proposed system has created the essential conditions to feed and grow a knowledge, a basic element to predict the treatment effectiveness for each new patient. It is a promising option for a refractory epilepsy therapy service.","PeriodicalId":73001,"journal":{"name":"Exploration of neuroscience","volume":"6 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140710604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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