Pub Date : 2025-01-01DOI: 10.1016/j.neurot.2025.e00524
Zade Akras , Jin Jing , M. Brandon Westover , Sahar F. Zafar
Electroencephalography (EEG) is invaluable in the management of acute neurological emergencies. Characteristic EEG changes have been identified in diverse neurologic conditions including stroke, trauma, and anoxia, and the increased utilization of continuous EEG (cEEG) has identified potentially harmful activity even in patients without overt clinical signs or neurologic diagnoses. Manual annotation by expert neurophysiologists is a major resource limitation in investigating the prognostic and therapeutic implications of these EEG patterns and in expanding EEG use to a broader set of patients who are likely to benefit. Artificial intelligence (AI) has already demonstrated clinical success in guiding cEEG allocation for patients at risk for seizures, and its potential uses in neurocritical care are expanding alongside improvements in AI itself. We review both current clinical uses of AI for EEG-guided management as well as ongoing research directions in automated seizure and ischemia detection, neurologic prognostication, and guidance of medical and surgical treatment.
{"title":"Using artificial intelligence to optimize anti-seizure treatment and EEG-guided decisions in severe brain injury","authors":"Zade Akras , Jin Jing , M. Brandon Westover , Sahar F. Zafar","doi":"10.1016/j.neurot.2025.e00524","DOIUrl":"10.1016/j.neurot.2025.e00524","url":null,"abstract":"<div><div>Electroencephalography (EEG) is invaluable in the management of acute neurological emergencies. Characteristic EEG changes have been identified in diverse neurologic conditions including stroke, trauma, and anoxia, and the increased utilization of continuous EEG (cEEG) has identified potentially harmful activity even in patients without overt clinical signs or neurologic diagnoses. Manual annotation by expert neurophysiologists is a major resource limitation in investigating the prognostic and therapeutic implications of these EEG patterns and in expanding EEG use to a broader set of patients who are likely to benefit. Artificial intelligence (AI) has already demonstrated clinical success in guiding cEEG allocation for patients at risk for seizures, and its potential uses in neurocritical care are expanding alongside improvements in AI itself. We review both current clinical uses of AI for EEG-guided management as well as ongoing research directions in automated seizure and ischemia detection, neurologic prognostication, and guidance of medical and surgical treatment.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00524"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.neurot.2024.e00521
Sue J. Hong , Bradley J. De Souza , Kristen K. Penberthy , Lisa Hwang , David E. Procaccini , John N. Kheir , Melania M. Bembea
Extracorporeal membrane oxygenation (ECMO) is a technique used to support severe cardiopulmonary failure. Its potential life-saving benefits are tempered by the significant risk for acute brain injury (ABI), from both primary pathophysiologic factors and ECMO-related complications through central nervous system cellular injury, blood-brain barrier dysfunction (BBB), systemic inflammation and neuroinflammation, and coagulopathy. Plasma biomarkers are an emerging tool used to stratify risk for and diagnose ABI, and prognosticate neurofunctional outcomes. Components of the neurovascular unit have been rational targets for this inquiry in ECMO. Central nervous system (CNS) neuronal and astroglial cellular-derived neuron-specific enolase (NSE), tau, glial fibrillary acidic protein (GFAP) and S100β elevations have been detected in ABI and are associated with poorer outcomes. Evidence of BBB breakdown through peripheral blood detection of CNS cellular components NSE, GFAP, and S100β, as well as evidence of elevated BBB components vWF and PDGFRβ are associated with higher mortality and worse neurofunctional outcomes. Higher concentrations of pro-inflammatory cytokines (IL-1β, IL-6, IFN-γ, TNF-α) are associated with abnormal neuroimaging, and proteomic expression panels reveal different coagulation and inflammatory responses. Abnormal coagulation profiles are common in ECMO with ongoing studies attempting to describe specific abnormalities either being causal or associated with neurologic outcomes; vWF has shown some promise. Understanding these mechanisms of injury through biomarker analysis supports potential neuroprotective strategies such as individualized blood pressure targets, judicious hypercarbia and hypoxemia correction, and immunomodulation (inhaled hydrogen and N-acetylcysteine). Further research continues to elucidate the role of biomarkers as predictors, prognosticators, and therapeutic targets.
{"title":"Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO","authors":"Sue J. Hong , Bradley J. De Souza , Kristen K. Penberthy , Lisa Hwang , David E. Procaccini , John N. Kheir , Melania M. Bembea","doi":"10.1016/j.neurot.2024.e00521","DOIUrl":"10.1016/j.neurot.2024.e00521","url":null,"abstract":"<div><div>Extracorporeal membrane oxygenation (ECMO) is a technique used to support severe cardiopulmonary failure. Its potential life-saving benefits are tempered by the significant risk for acute brain injury (ABI), from both primary pathophysiologic factors and ECMO-related complications through central nervous system cellular injury, blood-brain barrier dysfunction (BBB), systemic inflammation and neuroinflammation, and coagulopathy. Plasma biomarkers are an emerging tool used to stratify risk for and diagnose ABI, and prognosticate neurofunctional outcomes. Components of the neurovascular unit have been rational targets for this inquiry in ECMO. Central nervous system (CNS) neuronal and astroglial cellular-derived neuron-specific enolase (NSE), tau, glial fibrillary acidic protein (GFAP) and S100β elevations have been detected in ABI and are associated with poorer outcomes. Evidence of BBB breakdown through peripheral blood detection of CNS cellular components NSE, GFAP, and S100β, as well as evidence of elevated BBB components vWF and PDGFRβ are associated with higher mortality and worse neurofunctional outcomes. Higher concentrations of pro-inflammatory cytokines (IL-1β, IL-6, IFN-γ, TNF-α) are associated with abnormal neuroimaging, and proteomic expression panels reveal different coagulation and inflammatory responses. Abnormal coagulation profiles are common in ECMO with ongoing studies attempting to describe specific abnormalities either being causal or associated with neurologic outcomes; vWF has shown some promise. Understanding these mechanisms of injury through biomarker analysis supports potential neuroprotective strategies such as individualized blood pressure targets, judicious hypercarbia and hypoxemia correction, and immunomodulation (inhaled hydrogen and N-acetylcysteine). Further research continues to elucidate the role of biomarkers as predictors, prognosticators, and therapeutic targets.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00521"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.neurot.2024.e00497
Enrico De Martino , Adenauer Girardi Casali , Bruno Andry Nascimento Couto , Thomas Graven-Nielsen , Daniel Ciampi de Andrade
High-frequency repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex (M1) is used to treat several neuropsychiatric disorders, but the detailed temporal dynamics of its effects on cortical connectivity remain unclear. Here, we stimulated four cortical targets used for rTMS (M1; dorsolateral-prefrontal cortex, DLPFC; anterior cingulate cortex, ACC; posterosuperior insula, PSI) with TMS coupled with high-density electroencephalography (TMS-EEG) to measure cortical excitability and oscillatory dynamics before and after active- and sham-M1-rTMS. Before and immediately after active or sham M1-rTMS (15 min, 3000 pulses at 10 Hz), single-pulse TMS-evoked EEG was recorded at the four targets in 20 healthy individuals. Cortical excitability and oscillatory measures were extracted at the main frequency bands (α [8–13 Hz], low-β [14–24 Hz], high-β [25–35 Hz]). Active-M1-rTMS increased high-β synchronization in electrodes near the stimulation area and remotely, in the contralateral hemisphere (p = 0.026). Increased high-β synchronization (48–83 ms after TMS-EEG stimulation) was succeeded by enhancement in low-β power (86–144 ms after TMS-EEG stimulation) both locally and in the contralateral hemisphere (p = 0.006). No significant differences were observed in stimulating the DLPFC, ACC, or PSI by TMS-EEG. M1-rTMS engaged a sequence of enhanced phase synchronization, followed by an increase in power occurring within M1, which spread to remote areas and persisted after the end of the stimulation session. These results are relevant to understanding the M1 neuroplastic effects of rTMS in health and may help in the development of informed rTMS therapies in disease.
{"title":"Increase in beta frequency phase synchronization and power after a session of high frequency repetitive transcranial magnetic stimulation to the primary motor cortex","authors":"Enrico De Martino , Adenauer Girardi Casali , Bruno Andry Nascimento Couto , Thomas Graven-Nielsen , Daniel Ciampi de Andrade","doi":"10.1016/j.neurot.2024.e00497","DOIUrl":"10.1016/j.neurot.2024.e00497","url":null,"abstract":"<div><div>High-frequency repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex (M1) is used to treat several neuropsychiatric disorders, but the detailed temporal dynamics of its effects on cortical connectivity remain unclear. Here, we stimulated four cortical targets used for rTMS (M1; dorsolateral-prefrontal cortex, DLPFC; anterior cingulate cortex, ACC; posterosuperior insula, PSI) with TMS coupled with high-density electroencephalography (TMS-EEG) to measure cortical excitability and oscillatory dynamics before and after active- and sham-M1-rTMS. Before and immediately after active or sham M1-rTMS (15 min, 3000 pulses at 10 Hz), single-pulse TMS-evoked EEG was recorded at the four targets in 20 healthy individuals. Cortical excitability and oscillatory measures were extracted at the main frequency bands (α [8–13 Hz], low-β [14–24 Hz], high-β [25–35 Hz]). Active-M1-rTMS increased high-β synchronization in electrodes near the stimulation area and remotely, in the contralateral hemisphere (p = 0.026). Increased high-β synchronization (48–83 ms after TMS-EEG stimulation) was succeeded by enhancement in low-β power (86–144 ms after TMS-EEG stimulation) both locally and in the contralateral hemisphere (p = 0.006). No significant differences were observed in stimulating the DLPFC, ACC, or PSI by TMS-EEG. M1-rTMS engaged a sequence of enhanced phase synchronization, followed by an increase in power occurring within M1, which spread to remote areas and persisted after the end of the stimulation session. These results are relevant to understanding the M1 neuroplastic effects of rTMS in health and may help in the development of informed rTMS therapies in disease.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00497"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.neurot.2024.e00507
Rohan Mathur , Lin Cheng , Josiah Lim , Tej D. Azad , Peter Dziedzic , Eleanor Belkin , Ivanna Joseph , Bhagyashri Bhende , Sudha Yellapantula , Niteesh Potu , Austen Lefebvre , Vishank Shah , Susanne Muehlschlegel , Julian Bosel , Tamas Budavari , Jose I. Suarez
A wide range of acute brain injuries, including both traumatic and non-traumatic causes, can result in elevated intracranial pressure (ICP), which in turn can cause further secondary injury to the brain, initiating a vicious cascade of propagating injury. Elevated ICP is therefore a neurological injury that requires intensive monitoring and time-sensitive interventions. Patients at high risk for developing elevated ICP undergo placement of invasive ICP monitors including external ventricular drains, intraparenchymal ICP monitors, and lumbar drains. These monitors all generate an ICP waveform, but each has its own unique caveats in monitoring and accuracy. Current ICP monitoring and management clinical guidelines focus on the mean ICP derived from the ICP waveform, with standard thresholds of treating ICP greater than 20 mmHg or 22 mmHg applied broadly to a wide range of patients. However, this one-size fits all approach has been criticized and there is a need to develop personalized, evidence-based and possibly multi-factorial precision-medicine based approaches to the problem. This paper provides historical and physiological context to the problem of elevated ICP, provides an overview of the challenges of the current paradigm of ICP management strategies, and discusses advances in ICP waveform analysis, emerging non-invasive ICP monitoring techniques, and applications of machine learning to create predictive algorithms.
{"title":"Evolving concepts in intracranial pressure monitoring - from traditional monitoring to precision medicine","authors":"Rohan Mathur , Lin Cheng , Josiah Lim , Tej D. Azad , Peter Dziedzic , Eleanor Belkin , Ivanna Joseph , Bhagyashri Bhende , Sudha Yellapantula , Niteesh Potu , Austen Lefebvre , Vishank Shah , Susanne Muehlschlegel , Julian Bosel , Tamas Budavari , Jose I. Suarez","doi":"10.1016/j.neurot.2024.e00507","DOIUrl":"10.1016/j.neurot.2024.e00507","url":null,"abstract":"<div><div>A wide range of acute brain injuries, including both traumatic and non-traumatic causes, can result in elevated intracranial pressure (ICP), which in turn can cause further secondary injury to the brain, initiating a vicious cascade of propagating injury. Elevated ICP is therefore a neurological injury that requires intensive monitoring and time-sensitive interventions. Patients at high risk for developing elevated ICP undergo placement of invasive ICP monitors including external ventricular drains, intraparenchymal ICP monitors, and lumbar drains. These monitors all generate an ICP waveform, but each has its own unique caveats in monitoring and accuracy. Current ICP monitoring and management clinical guidelines focus on the mean ICP derived from the ICP waveform, with standard thresholds of treating ICP greater than 20 mmHg or 22 mmHg applied broadly to a wide range of patients. However, this one-size fits all approach has been criticized and there is a need to develop personalized, evidence-based and possibly multi-factorial precision-medicine based approaches to the problem. This paper provides historical and physiological context to the problem of elevated ICP, provides an overview of the challenges of the current paradigm of ICP management strategies, and discusses advances in ICP waveform analysis, emerging non-invasive ICP monitoring techniques, and applications of machine learning to create predictive algorithms.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00507"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.neurot.2025.e00523
Juan E. Tichauer, Maximiliano Rovegno
Acute brain injuries (ABIs) encompass a broad spectrum of primary injuries such as ischemia, hypoxia, trauma, and hemorrhage that converge into secondary injury where some mechanisms show common determinants. In this regard, astroglial connexin and pannexin channels have been shown to play an important role. These channels are transmembrane proteins sharing similar topology and form gateways between adjacent cells named gap junctions (GJs) and pores into unopposed membranes named hemichannels (HCs). In astrocytes, GJs and HCs enable intercellular communication and have active participation in normal brain physiological processes, such as calcium waves, synapsis modulation, regional blood flow regulation, and homeostatic control of the extracellular environment, among others. However, after acute brain injury, astrocytes can change their phenotype and modify the activity of both channels and hemichannels, which can result in the amplification of danger signals, increased mediators of inflammation, and neuronal death, contributing to the expansion of brain damage and neurological deterioration. This is known as secondary brain damage. In this review, we discussed the main biological mechanism of secondary brain damage with a particular focus on astroglial connexin and pannexin participation during acute brain injuries.
{"title":"Role of astrocytes connexins - pannexins in acute brain injury","authors":"Juan E. Tichauer, Maximiliano Rovegno","doi":"10.1016/j.neurot.2025.e00523","DOIUrl":"10.1016/j.neurot.2025.e00523","url":null,"abstract":"<div><div>Acute brain injuries (ABIs) encompass a broad spectrum of primary injuries such as ischemia, hypoxia, trauma, and hemorrhage that converge into secondary injury where some mechanisms show common determinants. In this regard, astroglial connexin and pannexin channels have been shown to play an important role. These channels are transmembrane proteins sharing similar topology and form gateways between adjacent cells named gap junctions (GJs) and pores into unopposed membranes named hemichannels (HCs). In astrocytes, GJs and HCs enable intercellular communication and have active participation in normal brain physiological processes, such as calcium waves, synapsis modulation, regional blood flow regulation, and homeostatic control of the extracellular environment, among others. However, after acute brain injury, astrocytes can change their phenotype and modify the activity of both channels and hemichannels, which can result in the amplification of danger signals, increased mediators of inflammation, and neuronal death, contributing to the expansion of brain damage and neurological deterioration. This is known as secondary brain damage. In this review, we discussed the main biological mechanism of secondary brain damage with a particular focus on astroglial connexin and pannexin participation during acute brain injuries.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00523"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.neurot.2024.e00477
Carlos J. Ballester-Rosado , John T. Le , Trang T. Lam , Anne E. Anderson , James D. Frost Jr. , John W. Swann
Little is known about the mechanisms that generate epileptic spasms following perinatal brain injury. Recent studies have implicated reduced levels of Insulin-like Growth Factor 1 (IGF-1) in these patients’ brains. Other studies have reported low levels of the inhibitory neurotransmitter, GABA. In the TTX brain injury model of epileptic spasms, we undertook experiments to evaluate the impact of IGF-1 deficiencies on neocortical interneurons and their role in spasms. Quantitative immunohistochemical analyses revealed that neocortical interneurons that express glutamic acid decarboxylase, parvalbumin, or synaptotagmin 2 co-express IGF-1. In epileptic rats, expression of these three interneuron markers were reduced in the neocortex. IGF-1 expression was also reduced, but surprisingly this loss was confined to interneurons. Interneuron connectivity was reduced in tandem with IGF-1 deficiencies. Similar changes were observed in surgically resected neocortex from infantile epileptic spasms syndrome (IESS) patients. To evaluate the impact of IGF-1 deficiencies on interneuron development, IGF-1R levels were reduced in the neocortex of neonatal conditional IGF-1R knock out mice by viral injections. Four weeks later, this experimental maneuver resulted in similar reductions in interneuron connectivity. Treatment with the IGF-1 derived tripeptide, (1–3)IGF-1, abolished epileptic spasms in most animals, rescued interneuron connectivity, and restored neocortical levels of IGF-1. Our results implicate interneuron IGF-1 deficiencies, possibly impaired autocrine IGF-1 signaling and a resultant interneuron dysmaturation in epileptic spasm generation. By restoring IGF-1 levels, (1–3)IGF-1 likely suppresses spasms by rescuing interneuron connectivity. Results point to (1–3)IGF-1 and its analogues as potential novel disease-modifying therapies for this neurodevelopmental disorder.
{"title":"IGF-1 impacts neocortical interneuron connectivity in epileptic spasm generation and resolution","authors":"Carlos J. Ballester-Rosado , John T. Le , Trang T. Lam , Anne E. Anderson , James D. Frost Jr. , John W. Swann","doi":"10.1016/j.neurot.2024.e00477","DOIUrl":"10.1016/j.neurot.2024.e00477","url":null,"abstract":"<div><div>Little is known about the mechanisms that generate epileptic spasms following perinatal brain injury. Recent studies have implicated reduced levels of Insulin-like Growth Factor 1 (IGF-1) in these patients’ brains. Other studies have reported low levels of the inhibitory neurotransmitter, GABA. In the TTX brain injury model of epileptic spasms, we undertook experiments to evaluate the impact of IGF-1 deficiencies on neocortical interneurons and their role in spasms. Quantitative immunohistochemical analyses revealed that neocortical interneurons that express glutamic acid decarboxylase, parvalbumin, or synaptotagmin 2 co-express IGF-1. In epileptic rats, expression of these three interneuron markers were reduced in the neocortex. IGF-1 expression was also reduced, but surprisingly this loss was confined to interneurons. Interneuron connectivity was reduced in tandem with IGF-1 deficiencies. Similar changes were observed in surgically resected neocortex from infantile epileptic spasms syndrome (IESS) patients. To evaluate the impact of IGF-1 deficiencies on interneuron development, IGF-1R levels were reduced in the neocortex of neonatal conditional IGF-1R knock out mice by viral injections. Four weeks later, this experimental maneuver resulted in similar reductions in interneuron connectivity. Treatment with the IGF-1 derived tripeptide, (1–3)IGF-1, abolished epileptic spasms in most animals, rescued interneuron connectivity, and restored neocortical levels of IGF-1. Our results implicate interneuron IGF-1 deficiencies, possibly impaired autocrine IGF-1 signaling and a resultant interneuron dysmaturation in epileptic spasm generation. By restoring IGF-1 levels, (1–3)IGF-1 likely suppresses spasms by rescuing interneuron connectivity. Results point to (1–3)IGF-1 and its analogues as potential novel disease-modifying therapies for this neurodevelopmental disorder.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00477"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.neurot.2024.e00508
Barbara Johanne Thomas Nordhjem, Lisa Lyngsie Hjalgrim
{"title":"Cancer-related cognitive impairment and hippocampal functioning: The role of dynamin-1","authors":"Barbara Johanne Thomas Nordhjem, Lisa Lyngsie Hjalgrim","doi":"10.1016/j.neurot.2024.e00508","DOIUrl":"10.1016/j.neurot.2024.e00508","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00508"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.neurot.2024.e00520
Austen T. Lefebvre , Nicole E. Steiner , Carissa L. Rodriguez , Joseph P. Angelo , Eyal Bar-Kochba , Rohan Mathur , Marek Mirski , David W. Blodgett
Acute brain injury (ABI) is a complex disease process that begins with an initial insult followed by secondary injury resulting from disturbances in cerebral physiology. In the metabolically active brain, early recognition of physiologic derangements is critical in enabling clinicians with the insight to adjust therapeutic interventions and reduce risk of ischemia and permanent injury. Current established approaches for monitoring cerebral physiology include the neurologic physical examination, traditional brain imaging such as computed tomography (CT) and magnetic resonance imaging (MRI), electroencephalography (EEG), and bedside modalities such as invasive parenchymal probes and transcranial doppler ultrasound. Diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS), and optical coherence tomography (OCT) are non-invasive optical techniques that have shown promise in measuring clinically relevant changes in cerebral physiology. These new modalities may offer clinicians significant benefits as they are safe, can be utilized at the point-of-care, and provide continuous measurements. This paper reviews major causes of primary and secondary ABI encountered in neurocritical care units, conventional measures of cerebral physiology during ABI, and emerging non-invasive optical techniques that have significant potential for translation to the bedside.
{"title":"Optical approaches for neurocritical care: Toward non-invasive recording of cerebral physiology in acute brain injury","authors":"Austen T. Lefebvre , Nicole E. Steiner , Carissa L. Rodriguez , Joseph P. Angelo , Eyal Bar-Kochba , Rohan Mathur , Marek Mirski , David W. Blodgett","doi":"10.1016/j.neurot.2024.e00520","DOIUrl":"10.1016/j.neurot.2024.e00520","url":null,"abstract":"<div><div>Acute brain injury (ABI) is a complex disease process that begins with an initial insult followed by secondary injury resulting from disturbances in cerebral physiology. In the metabolically active brain, early recognition of physiologic derangements is critical in enabling clinicians with the insight to adjust therapeutic interventions and reduce risk of ischemia and permanent injury. Current established approaches for monitoring cerebral physiology include the neurologic physical examination, traditional brain imaging such as computed tomography (CT) and magnetic resonance imaging (MRI), electroencephalography (EEG), and bedside modalities such as invasive parenchymal probes and transcranial doppler ultrasound. Diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS), and optical coherence tomography (OCT) are non-invasive optical techniques that have shown promise in measuring clinically relevant changes in cerebral physiology. These new modalities may offer clinicians significant benefits as they are safe, can be utilized at the point-of-care, and provide continuous measurements. This paper reviews major causes of primary and secondary ABI encountered in neurocritical care units, conventional measures of cerebral physiology during ABI, and emerging non-invasive optical techniques that have significant potential for translation to the bedside.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00520"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.neurot.2024.e00503
Winnie L. Liu , Lidan Zhang , Soussan Djamasbi , Bengisu Tulu , Susanne Muehlschlegel
In the neurological intensive care unit (neuroICU), patients with severe acute brain injury (SABI) are rendered unable to make their own healthcare decisions. The responsibility of making life-or-death decisions, such as goals of care, is carried by surrogate decision-makers, usually families. In addition to the burden of decision-making, the emotional burden on families is further compounded by prognostication uncertainty, time-pressure for decision-making, and difficulties in understanding and interpreting the patient's values and preferences, ultimately resulting in potential clinician-family communication breakdown. Despite these challenges, there is currently no guidance on how to best approach these difficult decisions. Shared decision-making (SDM) has emerged as the recommended approach to improve clinician-family communication, empowering surrogates to take an active role in decision-making by providing a structured framework for information exchange, deliberation, and treatment decisions. Decision aids (DAs) facilitate SDM by offering balanced, accessible, unbiased information and helping surrogates decide according to patients' values. This review highlights the potential advantage of digital over paper-based DAs, including improved accessibility, interactivity, and personalization, and the integration of emerging technologies to enhance DA effectiveness. Additionally, we review the current digital DAs developed for the neuroICU setting.
{"title":"Development of web- and mobile-based shared decision-making tools in the neurological intensive care unit","authors":"Winnie L. Liu , Lidan Zhang , Soussan Djamasbi , Bengisu Tulu , Susanne Muehlschlegel","doi":"10.1016/j.neurot.2024.e00503","DOIUrl":"10.1016/j.neurot.2024.e00503","url":null,"abstract":"<div><div>In the neurological intensive care unit (neuroICU), patients with severe acute brain injury (SABI) are rendered unable to make their own healthcare decisions. The responsibility of making life-or-death decisions, such as goals of care, is carried by surrogate decision-makers, usually families. In addition to the burden of decision-making, the emotional burden on families is further compounded by prognostication uncertainty, time-pressure for decision-making, and difficulties in understanding and interpreting the patient's values and preferences, ultimately resulting in potential clinician-family communication breakdown. Despite these challenges, there is currently no guidance on how to best approach these difficult decisions. Shared decision-making (SDM) has emerged as the recommended approach to improve clinician-family communication, empowering surrogates to take an active role in decision-making by providing a structured framework for information exchange, deliberation, and treatment decisions. Decision aids (DAs) facilitate SDM by offering balanced, accessible, unbiased information and helping surrogates decide according to patients' values. This review highlights the potential advantage of digital over paper-based DAs, including improved accessibility, interactivity, and personalization, and the integration of emerging technologies to enhance DA effectiveness. Additionally, we review the current digital DAs developed for the neuroICU setting.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00503"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.neurot.2024.e00515
Sidra Tabassum , Silin Wu , Chang-Hun Lee , Bosco Seong Kyu Yang , Aaron M. Gusdon , Huimahn A. Choi , Xuefang S. Ren
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide, with limited effective therapeutic options currently available. Recent research has highlighted the pivotal role of mitochondrial dysfunction in the pathophysiology of TBI, making mitochondria an attractive target for therapeutic intervention. This review comprehensively examines advancements in mitochondrial-targeted therapies for TBI, bridging the gap from basic research to clinical applications. We discuss the underlying mechanisms of mitochondrial damage in TBI, including oxidative stress, impaired bioenergetics, mitochondrial dynamics, and apoptotic pathways. Furthermore, we highlight the complex interplay between mitochondrial dysfunction, inflammation, and blood-brain barrier (BBB) integrity, elucidating how these interactions exacerbate injury and impede recovery. We also evaluate various preclinical studies exploring pharmacological agents, gene therapy, and novel drug delivery systems designed to protect and restore mitochondrial function. Clinical trials and their outcomes are assessed to evaluate the translational potential of mitochondrial-targeted therapies in TBI. By integrating findings from bench to bedside, this review emphasizes promising therapeutic avenues and addresses remaining challenges. It also provides guidance for future research to pave the way for innovative treatments that improve patient outcomes in TBI.
{"title":"Mitochondrial-targeted therapies in traumatic brain injury: From bench to bedside","authors":"Sidra Tabassum , Silin Wu , Chang-Hun Lee , Bosco Seong Kyu Yang , Aaron M. Gusdon , Huimahn A. Choi , Xuefang S. Ren","doi":"10.1016/j.neurot.2024.e00515","DOIUrl":"10.1016/j.neurot.2024.e00515","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide, with limited effective therapeutic options currently available. Recent research has highlighted the pivotal role of mitochondrial dysfunction in the pathophysiology of TBI, making mitochondria an attractive target for therapeutic intervention. This review comprehensively examines advancements in mitochondrial-targeted therapies for TBI, bridging the gap from basic research to clinical applications. We discuss the underlying mechanisms of mitochondrial damage in TBI, including oxidative stress, impaired bioenergetics, mitochondrial dynamics, and apoptotic pathways. Furthermore, we highlight the complex interplay between mitochondrial dysfunction, inflammation, and blood-brain barrier (BBB) integrity, elucidating how these interactions exacerbate injury and impede recovery. We also evaluate various preclinical studies exploring pharmacological agents, gene therapy, and novel drug delivery systems designed to protect and restore mitochondrial function. Clinical trials and their outcomes are assessed to evaluate the translational potential of mitochondrial-targeted therapies in TBI. By integrating findings from bench to bedside, this review emphasizes promising therapeutic avenues and addresses remaining challenges. It also provides guidance for future research to pave the way for innovative treatments that improve patient outcomes in TBI.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 1","pages":"Article e00515"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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