|
1
|
Roberts SSH, Owen PJ, Warmington SA, Trevenen J, Caeyenberghs K, McDonald SJ, Facer-Childs ER, McKay A, Bradshaw EJ, Kara S, Aisbett B, Vincent GE. A systematic review and meta-analysis of sleep following mild traumatic brain injury: A synthesis of the literature according to age and time-since-injury. Sleep Med Rev 2025; 81:102072. [PMID: 40347689 DOI: 10.1016/j.smrv.2025.102072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 11/27/2024] [Accepted: 02/10/2025] [Indexed: 05/14/2025]
Abstract
This systematic review and meta-analysis (PROSPERO: CRD42021287081) compared sleep in individuals with prior mTBI against that of controls. PubMed, Scopus, and EMBASE were searched through to November 2, 2024. Mean differences were calculated for objective (sleep duration, sleep efficiency, sleep stage [N1-3, REM] proportions) and subjective (Pittsburgh Sleep Quality Index [PSQI]) sleep measures, with analyses conducted based on age (adult ≥18y; child <18y) and time-since-injury/recovery phase (<1w, <1m, 1-12m, ≥1y). Qualitative syntheses were also conducted according to age and recovery phase. Sixty-nine studies met criteria. In children and adults, mean differences in objective sleep duration and sleep efficiency were not statistically significant for any recovery phase. Relative to controls, adults with mTBI had proportionately more N1 (Mean diff. [95%CI], 1.28 % [0.63 %,1.93 %], p = 0.014) and less N3 (-1.16 % [-2.08 %,-0.23 %], p = 0.033) sleep at 1-12-month follow-up, and less REM (-3.37 % [-6.28 %,-0.46 %], p = 0.023) at ≥1 year follow-up; however, these statistical differences did not remain when studies confounded by selection bias were removed. Subjectively, relative to controls, adults with mTBI had higher PSQI scores at <1-week (2.53 [1.43,3.62] points, p = 0.005), <1-month (2.26 [1.47, 3.04], p < 0.001), 1-12-month (2.86 [1.26,4.45], p < 0.001) and ≥1-year (2.62 [1.96, 3.28], p < 0.001) follow-up. The literature suggests individuals with prior mTBI have poorer subjective sleep than controls, but supportive objective data are limited. A limitation to consider when interpreting these findings is that a minority (45 %) of studies had low risk of bias. More research examining objective sleep post-mTBI is needed, especially for children with mTBI.
Collapse
Affiliation(s)
- S S H Roberts
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Science, Deakin University, Geelong, Australia; Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia.
| | - P J Owen
- Eastern Health Emergency Medicine Program, Melbourne, Victoria, Australia; Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
| | - S A Warmington
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Science, Deakin University, Geelong, Australia
| | - J Trevenen
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Science, Deakin University, Geelong, Australia
| | - K Caeyenberghs
- Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia
| | - S J McDonald
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia
| | - E R Facer-Childs
- Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Australia
| | - A McKay
- Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Australia; Monash-Epworth Rehabilitation Research Centre, Rehabilitation and Mental Health Division, Epworth HealthCare, Melbourne, Australia
| | - E J Bradshaw
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Science, Deakin University, Geelong, Australia
| | - S Kara
- Axis Sports Medicine Specialists, Auckland, New Zealand
| | - B Aisbett
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Science, Deakin University, Geelong, Australia
| | - G E Vincent
- Appleton Institute, School of Health, Medical and Applied Sciences, Central Queensland University, Adelaide, Australia
| |
Collapse
|
|
2
|
VonDeylen O, Alshaikh E, Wheeler K, Recker R, Malerba P, Valasek A, Yeates KO, Yang J. Sleep quantity and quality during the first week postinjury and time to symptom resolution in youth with concussion. Br J Sports Med 2025; 59:698-705. [PMID: 40011013 DOI: 10.1136/bjsports-2024-109058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2025] [Indexed: 02/28/2025]
Abstract
OBJECTIVE To examine bidirectional associations between objective measures of sleep quantity and quality with postconcussion symptoms (PCS) scores in concussed youth during the first week postinjury and to explore the associations between sleep measures and time to symptom resolution. STUDY DESIGN We conducted a secondary analysis of a prospectively enrolled cohort of youth (11-17 years) with a physician diagnosed concussion within 72 hours of injury. During the first week postconcussion, sleep quantity (time in bed, total sleep time and daytime sleep) and sleep quality (sleep efficiency, WASO and number of awakenings) were measured using an ActiGraph. We evaluated bidirectional temporal associations between the sleep measures and PCS during the first week postinjury using cross-lagged panel models. We assessed the associations between sleep measures and time to symptom resolution using Cox proportional hazard models. RESULTS Participants included 78 concussed youth, 34.6% females, mean age of 14.2 years (SD=2.1). Significant bidirectional associations were observed between PCS and both total sleep time and daytime total sleep in the first week postinjury. Increased daytime sleep was also associated with a decreased likelihood of symptom resolution, adjusted HR (aHR)=0.88, 95% CI=0.78, 0.999. An optimal total sleep time of 418 min per day was associated with a 2.1-fold increased likelihood of symptom resolution (aHR=2.1, 95% CI=1.3, 3.2). CONCLUSIONS Clinicians should provide guidance on sleep hygiene, including limiting daytime sleep/naps and getting the appropriate amount of nighttime sleep acutely postconcussion to aid recovery in youth.
Collapse
Affiliation(s)
- Olivia VonDeylen
- Center for Injury Research and Policy, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
- The Ohio State University College of Nursing, Columbus, Ohio, USA
| | - Enas Alshaikh
- Center for Injury Research and Policy, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Krista Wheeler
- Center for Injury Research and Policy, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Robyn Recker
- Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
| | - Paola Malerba
- Center for Biobehavioral Health, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Amy Valasek
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA
- Sports Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA
| | | | - Jingzhen Yang
- Center for Injury Research and Policy, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA
| |
Collapse
|
|
3
|
Rispoli MG, De Angelis MV, Melchionda D, Manente G. High-risk area for migraine attacks - a new concept in migraine pathophysiology. Front Neurol 2025; 16:1569361. [PMID: 40260134 PMCID: PMC12010771 DOI: 10.3389/fneur.2025.1569361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Accepted: 03/25/2025] [Indexed: 04/23/2025] Open
Abstract
Migraine is a common primary and often disabling neurological disorder, whose pathophysiology is still debated. It does not appear to be an isolated event of head pain but the consequence of recurrent disruption of healthy homeostasis in some brain functions. We propose a new theoretical model, focused on the existence of a "high-risk area" for migraine attacks, which can represent a potential target of non-pharmacologic treatment and prevention. We suggest that migraine arises from the combined effects of three primary factors, namely depressive or unstable mood, unrestful sleep and sympathetic-parasympathetic imbalance with parasympathetic prevalence, alongside with their temporal variability, potentially through dysfunction of homeostatic hypothalamic networks in susceptible individuals. Moreover, these three primary factors contribute to a state of low brain energy, that contains the high-risk area and represents the condition in which migraine attacks rise up. Wearable devices, self-administered questionnaires and clinical tools (i.e., polysomnography, pupillary light reflex, plasma catecholamines dosage) may be used to monitor autonomic nervous system function, mood and sleep and demonstrate the existence of the high-risk area. This will be helpful for patients to understand when they are about to enter in the high-risk area, in order to implement strategies to prevent migraine attacks. This approach would provide a significant advantage in terms of prevention and early treatment.
Collapse
|
|
4
|
Fiorin FDS, Godinho DB, Dos Santos EB, Aguiar AS, Schuch FB, de Mello MT, Radak Z, Fighera MR, Royes LFF. Relationship among depression, fatigue, and sleep after traumatic brain injury: The role of physical exercise as a non-pharmacological therapy. Exp Neurol 2025; 386:115156. [PMID: 39864790 DOI: 10.1016/j.expneurol.2025.115156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 01/15/2025] [Accepted: 01/21/2025] [Indexed: 01/28/2025]
Abstract
Traumatic brain injury (TBI) is a burdensome condition frequently associated with an increased risk of psychiatric disorders. Although the exact molecular signaling pathways have not yet been fully defined, the compromised integrity of functional brain networks in regions such as the prefrontal cortex and anterior cingulate cortex has been linked to persistent symptoms, including depression, fatigue, and sleep disorders. Understanding how TBI affects neural physiology enables the development of effective interventions. One such strategy may be physical exercise, which promotes neural repair and behavioral rehabilitation after TBI. However, there are caveats to consider when interpreting the effects of physical exercise on TBI-induced mental health issues. This review will highlight the main findings from the literature investigating how different physical exercise protocols affect the progression of TBI-induced depression, fatigue, and sleep disturbances. Furthermore, we aim to explore potential neurobiological pathways that explain how physical exercise influences depression, fatigue, and sleep following TBI.
Collapse
Affiliation(s)
- Fernando da Silva Fiorin
- Exercise Biochemistry Laboratory, Center of Physical Education and Sports, Federal University of Santa Maria, Santa Maria, Brazil
| | - Douglas Buchmann Godinho
- Exercise Biochemistry Laboratory, Center of Physical Education and Sports, Federal University of Santa Maria, Santa Maria, Brazil
| | | | - Aderbal S Aguiar
- Biology of Exercise Laboratory, Department of Health Sciences, Federal University of Santa Catarina, Araranguá, Brazil
| | - Felipe Barreto Schuch
- Department of Sports Methods and Techniques, Federal University of Santa Maria, Santa Maria, Brazil; Faculty of Health Sciences, Universidad Autónoma de Chile, Providencia, Chile; Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marco Túlio de Mello
- Sports Training Centre, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Zsolt Radak
- Research Institute of Sport Science, University of Physical Education, Budapest, Hungary
| | - Michele Rechia Fighera
- Exercise Biochemistry Laboratory, Center of Physical Education and Sports, Federal University of Santa Maria, Santa Maria, Brazil
| | - Luiz Fernando Freire Royes
- Exercise Biochemistry Laboratory, Center of Physical Education and Sports, Federal University of Santa Maria, Santa Maria, Brazil; Department of Sports Methods and Techniques, Federal University of Santa Maria, Santa Maria, Brazil.
| |
Collapse
|
|
5
|
Li L, Wu Y, Wu J, Li B, Hua R, Shi F, Chen L, Wu Y. MRI quantified enlarged perivascular space volumes as imaging biomarkers correlating with severity of anxiety depression in young adults with long-time mobile phone use. Front Psychiatry 2025; 16:1532256. [PMID: 40051766 PMCID: PMC11882520 DOI: 10.3389/fpsyt.2025.1532256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Accepted: 01/30/2025] [Indexed: 03/09/2025] Open
Abstract
Introduction Long-time mobile phone use (LTMPU) has been linked to emotional issues such as anxiety and depression while the enlarged perivascular spaces (EPVS), as marker of neuroinflammation, is closely related with mental disorders. In the current study, we aim to develop a predictive model utilizing MRI-quantified EPVS metrics and machine learning algorithms to assess the severity of anxiety and depression symptoms in patients with LTMPU. Methods Eighty-two participants with LTMPU were included, with 37 suffering from anxiety and 44 suffering from depression. Deep learning algorithms were used to segment EPVS lesions and extract quantitative metrics. Comparison and correlation analyses were performed to investigate the relationship between EPVS and self-reported mood states. Training and testing datasets were randomly assigned in the ratio of 8:2 to perform radiomics analysis, where EPVS metrics combined with sex and age were used to select the most valuable features to construct machine learning models for predicting the severity of anxiety and depression. Results Several EPVS features were significantly different between the two comparisons. For classifying anxiety status, eight features were selected to construct a logistic regression model, with an AUC of 0.819 (95%CI 0.573-1.000) in the testing dataset. For classifying depression status, eight features were selected to construct a K nearest neighbors model with an AUC value of 0.931 (95%CI 0.814-1.000) in the testing dataset. Discussion The utilization of MRI-quantified EPVS metrics combined with machine-learning algorithms presents a promising method for evaluating severity of anxiety and depression symptoms in patients with LTMPU, which might introduce a non-invasive, objective, and quantitative approach to enhance diagnostic efficiency and guide personalized treatment strategies.
Collapse
Affiliation(s)
- Li Li
- Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yalan Wu
- Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Jiaojiao Wu
- Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Bin Li
- Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Rui Hua
- Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Feng Shi
- Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, China
| | - Lizhou Chen
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Yeke Wu
- Department of Stomatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| |
Collapse
|
|
6
|
Dharsee S, Hassan A, Noel M, Bender AM, Beauchamp MH, Craig W, Doan Q, Freedman SB, Gravel J, Zemek R, Yeates KO. Cross-Lagged Associations Among Sleep, Headache, and Pain in Pediatric Mild Traumatic Brain Injury: An A-CAP Study. J Head Trauma Rehabil 2025:00001199-990000000-00234. [PMID: 39919247 DOI: 10.1097/htr.0000000000001038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Abstract
OBJECTIVE To test cross-lagged associations among sleep, headache, and pain in pediatric mild traumatic brain injury (mTBI). SETTING, PARTICIPANTS, DESIGN Children and adolescents aged 8.0 to 16.9 years who sustained a mTBI and presented to 1 of 5 pediatric emergency departments across Canada completed assessments at 1-week, 3 months, and 6 months post-injury as part of a larger prospective cohort study. MAIN MEASURES Sleep disturbance was measured using 7 sleep items from the Child Behaviour Checklist. Sleep duration was measured using average weekday and weekend sleep from the Healthy Lifestyle Behaviours Questionnaire. Pain intensity was measured using an 11-point numerical rating scale. Headache severity and associated functional impairment were measured using the Headache Impact Test and 1 item from the Health and Behaviour Inventory. Analyses included trivariate-indicator random-intercept cross-lagged panel models. RESULTS Of 633 recruited children, 563 were included in the current study. Headache showed significant within-person, bidirectional, cross-lagged associations with sleep disturbance and duration, as well as with pain intensity. More specifically, worse headache predicted greater sleep disturbance (1-week to 3 months and 3 months to 6 months: Bs = .47, Ps ≤ .013) and shorter sleep duration (1-week to 3 months: B = -.21, P = .006), while greater sleep disturbance predicted worse headache (1-week to 3 months: B = .08, P = .001). Worse headache also predicted higher pain intensity (1-week to 3 months & 3 months to 6 months: Bs ≥ 1.27, P s < .001), while higher pain intensity predicted worse headache (3 months to 6 months: Bs ≥ .03, Ps ≤ .042). No cross-lagged associations involving sleep disturbance or duration with pain intensity were significant. CONCLUSIONS Significant bi-directional, cross-lagged associations exist between headache and both sleep and pain. The findings suggest that early intervention for headaches may help prevent later sleep disturbance and pain after pediatric mTBI.
Collapse
Affiliation(s)
- Safira Dharsee
- Author Affiliations: Department of Psychology (Ms Dharsee), Department of Psychology (Dr Noel), Faculty of Kinesiology (Dr Bender), Departments of Pediatrics and Emergency Medicine, Cumming School of Medicine (Dr Freedman), Department of Psychology, Alberta Children's Hospital Research Institute, and Hotchkiss Brain Institute (Dr Yeates), University of Calgary, Calgary, Alberta, Canada; Department of Radiology and Diagnostic Imaging (Mr Hassan), University of Alberta, Edmonton, Alberta, Canada; Department of Psychology, Université de Montréal and CHU Sainte-Justine Azrieli Research Center, Montréal, Québec, Canada; Department of Pediatrics (Dr Craig), University of Alberta and Stollery Children's Hospital, Edmonton, Alberta, Canada; Department of Pediatrics (Dr Doan), University of British Columbia and BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada; Department of Pediatric Emergency Medicine, Department of Pediatrics (Dr Gravel), CHU Sainte-Justine Hospital Research Center, Université de Montréal, Montréal, Québec, Canada; Departments of Pediatrics and Emergency Medicine (Dr Zemek), University of Ottawa and Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
7
|
Fu Z, Miao X, Luo X, Yuan L, Xie Y, Huang S. Analysis of the correlation and influencing factors between delirium, sleep, self-efficacy, anxiety, and depression in patients with traumatic brain injury: a cohort study. Front Neurosci 2024; 18:1484777. [PMID: 39554848 PMCID: PMC11564178 DOI: 10.3389/fnins.2024.1484777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 10/14/2024] [Indexed: 11/19/2024] Open
Abstract
Background Patients with traumatic brain injury (TBI) often experience post-injury anxiety and depression, which can persist over time. However, the relationships between anxiety and depression in TBI patients and delirium, sleep quality, self-efficacy, and serum inflammatory markers require further investigation. Objective This study aims to explore the associations of delirium, sleep quality, self-efficacy, and serum inflammatory markers with anxiety and depression in TBI patients, and to examine potential influencing factors. Methods We conducted a cohort study involving 127 patients with TBI. Delirium was assessed using the Confusion Assessment Method (CAM) and CAM-ICU, while anxiety, depression, sleep quality, self-efficacy, and pain were evaluated using the appropriate tools, respectively. Serum inflammatory markers (CRP, TNF-α, IL-6) were collected within 1 day post-injury. Generalized estimating equations (GEE) were used to analyze the relationships between delirium, sleep, self-efficacy, and anxiety/depression. Results The study identified 56 patients with delirium. Patients with delirium differed significantly from those without delirium in age, TBI classification, sleep duration, CRP levels, TNF-α levels, pain, self-efficacy, and insomnia (P < 0.05). The GEE analysis revealed that delirium, CRP levels, self-efficacy, underlying diseases, insomnia, TBI classification, age, and sleep duration were associated with anxiety symptoms in TBI patients at 6 months post-discharge (P < 0.05). Depression in TBI patients at 6 months post-discharge was not associated with delirium or insomnia but correlated with CRP levels, TBI classification, and self-efficacy (P < 0.05). Conclusion TBI patients who experience delirium, insomnia, and low self-efficacy during the acute phase are likely to exhibit more anxiety at the 6-month follow-up. Depression in TBI patients is not associated with delirium or insomnia but is negatively correlated with self-efficacy. CRP levels post-TBI may serve as a biomarker to identify patients at risk of emotional symptoms and potentially accelerate patient recovery.
Collapse
Affiliation(s)
- Zhongmin Fu
- Department of Nursing, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- The First Ward of the Neurosurgery Department, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Xiaoju Miao
- Department of Nursing, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- The First Ward of the Neurosurgery Department, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Xian Luo
- Department of Nursing, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- The First Ward of the Neurosurgery Department, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Lili Yuan
- Department of Nursing, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- The First Ward of the Neurosurgery Department, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yan Xie
- Department of Nursing, West China Hospital of Sichuan University, Chengdu, China
| | - Shiming Huang
- Department of Nursing, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| |
Collapse
|
|
8
|
Burgos AF, Olson PA, Vgontzas A. The Glymphatic System and its Relationship to Migraine. Curr Neurol Neurosci Rep 2024; 24:517-525. [PMID: 39150650 DOI: 10.1007/s11910-024-01368-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/26/2024] [Indexed: 08/17/2024]
Abstract
PURPOSE OF REVIEW We aim to critically review animal and human studies of the glymphatic system in migraine and propose a model for how the glymphatic system may function in migraine, based on the available evidence. RECENT FINDINGS Early studies in animal models report migraine attacks temporarily disrupt glymphatic flow. Human imaging studies suggest chronic migraine may be associated with alterations in glymphatic system function, albeit with conflicting results. Presently, it remains unknown whether repetitive migraine attacks or frequent nights of insomnia impair glymphatic system function over time in those with migraine, and whether alterations in glymphatic function could contribute to worsening migraine disability or risk for cognitive disease. Longitudinal studies of glymphatic function in patients with migraine and insomnia, with inclusion of cognitive assessments, may be informative.
Collapse
Affiliation(s)
| | - Patricia A Olson
- Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Angeliki Vgontzas
- Graham Headache Center, Department of Neurology, Brigham and Women's Faulkner Hospital, Harvard Medical School, 1153 Centre Street Suite 4H, Boston, MA, 02130, USA.
| |
Collapse
|
|
9
|
Ikeda L, Capel AV, Doddaballapur D, Miyan J. Accumulation of Cerebrospinal Fluid, Ventricular Enlargement, and Cerebral Folate Metabolic Errors Unify a Diverse Group of Neuropsychiatric Conditions Affecting Adult Neocortical Functions. Int J Mol Sci 2024; 25:10205. [PMID: 39337690 PMCID: PMC11432090 DOI: 10.3390/ijms251810205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 09/15/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
Cerebrospinal fluid (CSF) is a fluid critical to brain development, function, and health. It is actively secreted by the choroid plexus, and it emanates from brain tissue due to osmolar exchange and the constant contribution of brain metabolism and astroglial fluid output to interstitial fluid into the ventricles of the brain. CSF acts as a growth medium for the developing cerebral cortex and a source of nutrients and signalling throughout life. Together with perivascular glymphatic and interstitial fluid movement through the brain and into CSF, it also acts to remove toxins and maintain metabolic balance. In this study, we focused on cerebral folate status, measuring CSF concentrations of folate receptor alpha (FOLR1); aldehyde dehydrogenase 1L1, also known as 10-formyl tetrahydrofolate dehydrogenase (ALDH1L1 and FDH); and total folate. These demonstrate the transport of folate from blood across the blood-CSF barrier and into CSF (FOLR1 + folate), and the transport of folate through the primary FDH pathway from CSF into brain FDH + ve astrocytes. Based on our hypothesis that CSF flow, drainage issues, or osmotic forces, resulting in fluid accumulation, would have an associated cerebral folate imbalance, we investigated folate status in CSF from neurological conditions that have a severity association with enlarged ventricles. We found that all the conditions we examined had a folate imbalance, but these folate imbalances were not all the same. Given that folate is essential for key cellular processes, including DNA/RNA synthesis, methylation, nitric oxide, and neurotransmitter synthesis, we conclude that ageing or some form of trauma in life can lead to CSF accumulation and ventricular enlargement and result in a specific folate imbalance/deficiency associated with the specific neurological condition. We believe that addressing cerebral folate imbalance may therefore alleviate many of the underlying deficits and symptoms in these conditions.
Collapse
Affiliation(s)
| | | | | | - Jaleel Miyan
- Division of Neuroscience, Faculty of Biology, Medicine & Health, School of Biological Science, The University of Manchester, 3.540 Stopford Building, Oxford Road, Manchester M13 9PT, UK; (L.I.); (A.V.C.); (D.D.)
| |
Collapse
|
|
10
|
Willman J, Kurian AL, Lucke-Wold B. Mechanisms of vascular injury in neurotrauma: A critical review of the literature. World J Meta-Anal 2024; 12:95417. [DOI: 10.13105/wjma.v12.i3.95417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 07/20/2024] [Accepted: 07/29/2024] [Indexed: 09/13/2024] Open
Abstract
One in every two individuals will experience a traumatic brain injury in their lifetime with significant impacts on the global economy and healthcare system each year. Neurovascular injury is a key aspect of neurotrauma to both the brain and the spinal cord and an important avenue of current and future research seeking innovative therapies. In this paper, we discuss primary and secondary neurotrauma, mechanisms of injury, the glymphatic system, repair and recovery. Each of these topics are directly connected to the vasculature of the central nervous system, affecting severity of injury and recovery. Consequently, neurovascular injury in trauma represents a promising target for future therapeutics and innovation.
Collapse
Affiliation(s)
- Jonathan Willman
- College of Medicine, University of Florida, Gainesville, FL 32610, United States
| | - Annu Lisa Kurian
- College of Medicine, Florida State University, Tallahassee, FL 32304, United States
| | - Brandon Lucke-Wold
- Department of Neurosurgery, University of Florida, Gainesville, FL 32611, United States
| |
Collapse
|
|
11
|
Zhuo J, Raghavan P, Li J, Roys S, Njonkou Tchoquessi RL, Chen H, Wickwire EM, Parikh GY, Schwartzbauer GT, Grattan LM, Wang Z, Gullapalli RP, Badjatia N. Longitudinal assessment of glymphatic changes following mild traumatic brain injury: Insights from perivascular space burden and DTI-ALPS imaging. Front Neurol 2024; 15:1443496. [PMID: 39170078 PMCID: PMC11335690 DOI: 10.3389/fneur.2024.1443496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 07/08/2024] [Indexed: 08/23/2024] Open
Abstract
Introduction Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. Methods In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Results Our key findings include: (1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. (2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. (3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information. Conclusion ePVS burden and ALPS index offers distinct values in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.
Collapse
Affiliation(s)
- Jiachen Zhuo
- Center for Advanced Imaging Research, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Prashant Raghavan
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Jiang Li
- Center for Advanced Imaging Research, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Steven Roys
- Center for Advanced Imaging Research, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Rosy Linda Njonkou Tchoquessi
- Center for Advanced Imaging Research, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Hegang Chen
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Emerson M. Wickwire
- Department of Psychiatry and Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Gunjan Y. Parikh
- Program in Trauma, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Gary T. Schwartzbauer
- Program in Trauma, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Lynn M. Grattan
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Ze Wang
- Center for Advanced Imaging Research, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Rao P. Gullapalli
- Center for Advanced Imaging Research, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Neeraj Badjatia
- Program in Trauma, University of Maryland School of Medicine, Baltimore, MD, United States
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, United States
| |
Collapse
|
|
12
|
Jung LB, Wiegand TLT, Tuz-Zahra F, Tripodis Y, Iliff JJ, Piantino J, Arciniega H, Kim CL, Pankatz L, Bouix S, Lin AP, Alosco ML, Daneshvar DH, Mez J, Sepehrband F, Rathi Y, Pasternak O, Coleman MJ, Adler CH, Bernick C, Balcer L, Cummings JL, Reiman EM, Stern RA, Shenton ME, Koerte IK. Repetitive Head Impacts and Perivascular Space Volume in Former American Football Players. JAMA Netw Open 2024; 7:e2428687. [PMID: 39186275 PMCID: PMC12025916 DOI: 10.1001/jamanetworkopen.2024.28687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/27/2024] Open
Abstract
Importance Exposure to repetitive head impacts (RHI) is associated with increased risk for neurodegeneration. Accumulation of toxic proteins due to impaired brain clearance is suspected to play a role. Objective To investigate whether perivascular space (PVS) volume is associated with lifetime exposure to RHI in individuals at risk for RHI-associated neurodegeneration. Design, Setting, and Participants This cross-sectional study was part of the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project, a 7-year multicenter study consisting of 4 US study sites. Data were collected from September 2016 to February 2020 and analyses were performed between May 2021 and October 2023. After controlling for magnetic resonance image (MRI) and processing quality, former American football players and unexposed asymptomatic control participants were included in analyses. Exposure Prior exposure to RHI while participating in American football was estimated using the 3 cumulative head impact indices (CHII-G, linear acceleration; CHII-R, rotational acceleration; and CHII, number of head impacts). Main Outcomes and Measures Individual PVS volume was calculated in the white matter of structural MRI. Cognitive impairment was based on neuropsychological assessment. Linear regression models were used to assess associations of PVS volume with neuropsychological assessments in former American football players. All analyses were adjusted for confounders associated with PVS volume. Results Analyses included 224 participants (median [IQR] age, 57 [51-65] years), with 170 male former football players (114 former professional athletes, 56 former collegiate athletes) and 54 male unexposed control participants. Former football players had larger PVS volume compared with the unexposed group (mean difference, 0.28 [95% CI, 0.00-0.56]; P = .05). Within the football group, PVS volume was associated with higher CHII-R (β = 2.71 × 10-8 [95% CI, 0.50 × 10-8 to 4.93 × 10-8]; P = .03) and CHII-G (β = 2.24 × 10-6 [95% CI, 0.35 × 10-6 to 4.13 × 10-6]; P = .03). Larger PVS volume was also associated with worse performance on cognitive functioning in former American football players (β = -0.74 [95% CI, -1.35 to -0.13]; P = .04). Conclusions and Relevance These findings suggest that impaired perivascular brain clearance, as indicated by larger PVS volume, may contribute to the association observed between RHI exposure and neurodegeneration.
Collapse
Affiliation(s)
- Leonard B Jung
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
| | - Tim L T Wiegand
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
| | - Fatima Tuz-Zahra
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
| | - Yorghos Tripodis
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
- Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University School of Medicine, Boston, Massachusetts
| | - Jeffrey J Iliff
- Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle
- Department of Neurology, University of Washington School of Medicine, Seattle
- VISN 20 Northwest Network Mental Illness Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington
| | - Juan Piantino
- Department of Pediatrics, Division of Child Neurology, Doernbecher Children's Hospital, Oregon Health and Science University, Portland
| | - Hector Arciniega
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Rehabilitation Medicine, NYU Grossman School of Medicine, New York, New York
| | - Cara L Kim
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
| | - Lara Pankatz
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
| | - Sylvain Bouix
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Département de génie logiciel et TI, École de technologie supérieure, Université du Québec, Montreal, Canada
| | - Alexander P Lin
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Center for Clinical Spectroscopy, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Michael L Alosco
- Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts
| | - Daniel H Daneshvar
- Department of Physical Medicine and Rehabilitation, Massachusetts General Hospital, Harvard Medical School, Boston
| | - Jesse Mez
- Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts
| | - Farshid Sepehrband
- Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles
| | - Yogesh Rathi
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston
| | - Ofer Pasternak
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Michael J Coleman
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Charles H Adler
- Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona Scottsdale, Arizona
| | - Charles Bernick
- Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada
| | - Laura Balcer
- Department of Neurology, NYU Grossman School of Medicine, New York, New York
- Department of Population Health, NYU Grossman School of Medicine, New York, New York
- Department of Ophthalmology, NYU Grossman School of Medicine, New York, New York
| | - Jeffrey L Cummings
- Chambers-Grundy Center for Transformative Neuroscience, Pam Quirk Brain Health and Biomarker Laboratory, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas
| | - Eric M Reiman
- Banner Alzheimer's Institute, University of Arizona, Arizona State University, Translational Genomics Research Institute, and Arizona Alzheimer's Consortium, Phoenix
| | - Robert A Stern
- Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts
- Department of Anatomy & Neurobiology, Boston University School of Medicine, Boston, Massachusetts
- Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts
| | - Martha E Shenton
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Inga K Koerte
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston
- Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universität, Munich, Germany
| |
Collapse
|
|
13
|
Conti F, McCue JJ, DiTuro P, Galpin AJ, Wood TR. Mitigating Traumatic Brain Injury: A Narrative Review of Supplementation and Dietary Protocols. Nutrients 2024; 16:2430. [PMID: 39125311 PMCID: PMC11314487 DOI: 10.3390/nu16152430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 07/18/2024] [Accepted: 07/23/2024] [Indexed: 08/12/2024] Open
Abstract
Traumatic brain injuries (TBIs) constitute a significant public health issue and a major source of disability and death in the United States and worldwide. TBIs are strongly associated with high morbidity and mortality rates, resulting in a host of negative health outcomes and long-term complications and placing a heavy financial burden on healthcare systems. One promising avenue for the prevention and treatment of brain injuries is the design of TBI-specific supplementation and dietary protocols centred around nutraceuticals and biochemical compounds whose mechanisms of action have been shown to interfere with, and potentially alleviate, some of the neurophysiological processes triggered by TBI. For example, evidence suggests that creatine monohydrate and omega-3 fatty acids (DHA and EPA) help decrease inflammation, reduce neural damage and maintain adequate energy supply to the brain following injury. Similarly, melatonin supplementation may improve some of the sleep disturbances often experienced post-TBI. The scope of this narrative review is to summarise the available literature on the neuroprotective effects of selected nutrients in the context of TBI-related outcomes and provide an evidence-based overview of supplementation and dietary protocols that may be considered in individuals affected by-or at high risk for-concussion and more severe head traumas. Prophylactic and/or therapeutic compounds under investigation include creatine monohydrate, omega-3 fatty acids, BCAAs, riboflavin, choline, magnesium, berry anthocyanins, Boswellia serrata, enzogenol, N-Acetylcysteine and melatonin. Results from this analysis are also placed in the context of assessing and addressing important health-related and physiological parameters in the peri-impact period such as premorbid nutrient and metabolic health status, blood glucose regulation and thermoregulation following injury, caffeine consumption and sleep behaviours. As clinical evidence in this research field is rapidly emerging, a comprehensive approach including appropriate nutritional interventions has the potential to mitigate some of the physical, neurological, and emotional damage inflicted by TBIs, promote timely and effective recovery, and inform policymakers in the development of prevention strategies.
Collapse
Affiliation(s)
- Federica Conti
- School of Physics, University of Sydney, Sydney, NSW 2050, Australia;
| | - Jackson J. McCue
- School of Medicine, University of Washington, Seattle, WA 98195, USA;
| | - Paul DiTuro
- Department of Exercise Science, University of South Carolina, Columbia, SC 29208, USA
| | - Andrew J. Galpin
- Center for Sport Performance, California State University, Fullerton, CA 92831, USA;
| | - Thomas R. Wood
- Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
- Institute for Human and Machine Cognition, Pensacola, FL 32502, USA
| |
Collapse
|
|
14
|
Ogg M, Coon WG. Self-Supervised Transformer Model Training for a Sleep-EEG Foundation Model. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2024; 2024:1-6. [PMID: 40039051 DOI: 10.1109/embc53108.2024.10782281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/06/2025]
Abstract
The American Academy of Sleep Medicine (AASM) recognizes five sleep/wake states (Wake, N1, N2, N3, REM), yet this classification schema provides only a high-level summary of sleep and likely overlooks important neurological or health information. New, data-driven approaches are needed to more deeply probe the information content of sleep signals. Here we present a self-supervised approach that learns the structure embedded in large quantities of neurophysiological sleep data. This masked transformer training procedure is inspired by high performing self-supervised methods developed for speech transcription. We show that self-supervised pre-training matches or outperforms supervised sleep stage classification, especially when labeled data or compute-power is limited. Perhaps more importantly, we also show that our pre-trained model is flexible and can be fine-tuned to perform well on new EEG recording montages not seen in training, and for new tasks including distinguishing individuals or quantifying "brain age" (a potential health biomarker). This suggests that modern methods can automatically learn information that is potentially overlooked by the 5-class sleep staging schema, laying the groundwork for new sleep scoring schemas and further data-driven exploration of sleep.
Collapse
|
|
15
|
Leclerc C, Gervais C, Hjeij D, Briand MM, Williamson D, Bernard F, Duclos C, Arbour C. Sleep Disruptions in Hospitalized Adults Sustaining a Traumatic Brain Injury: A Scoping Review. J Head Trauma Rehabil 2024; 39:E201-E215. [PMID: 37767918 DOI: 10.1097/htr.0000000000000899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/29/2023]
Abstract
OBJECTIVE Adults sustaining a traumatic brain injury (TBI) are at risk of sleep disturbances during their recovery, including when such an injury requires hospitalization. However, the sleep-wake profile, and internal and external factors that may interfere with sleep initiation/maintenance in hospitalized TBI patients are poorly understood. This review aimed to: (1) identify/summarize the existing evidence regarding sleep and sleep measurements in TBI adults receiving around-the-clock care in a hospital or during inpatient rehabilitation, and (2) identify internal/external factors linked to poor sleep in this context. METHODS A scoping review was conducted in accordance with the PRISMA Scoping Review Extension guidelines. A search was conducted in MEDLINE, PsycINFO, CINAHL, and Web of Science databases. RESULTS Thirty relevant studies were identified. The most common sleep variables that were put forth in the studies to characterize sleep during hospitalization were nighttime sleep time (mean = 6.5 hours; range: 5.2-8.9 hours), wake after sleep onset (87.1 minutes; range: 30.4-180 minutes), and sleep efficiency (mean = 72.9%; range: 33%-96%) using mainly actigraphy, polysomnography, and questionnaires (eg, the sleep-wake disturbance item of the Delirium Rating Scale or the Pittsburgh Sleep Quality Index). Twenty-four studies (80%) suggested that hospitalized TBI patients do not get sufficient nighttime sleep, based on the general recommendations for adults (7-9 hours per night). Sleep disruptions during hospitalization were found to be associated to several internal factors including TBI severity, cognitive status, and analgesia intake. External and modifiable factors, such as noise, light, and patient care, were consistently associated with sleep disruptions in this context. CONCLUSION Although the literature on sleep disturbances in hospitalized TBI patients has been increasing in recent years, many gaps in knowledge remain, including phenotypes and risk factors. Identifying these factors could help clinicians better understand the multiple sources of TBI patients' sleep difficulties and intervene accordingly.
Collapse
Affiliation(s)
- Catherine Leclerc
- Author Affiliations: Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Cœur de Montréal, CIUSSS du Nord-de-l'Île-de-Montréal, Montréal, Québec, Canada (Mss Leclerc and Hjeij, Mr Gervais, and Drs Williamson, Bernard, Duclos, and Arbour); Department of Psychology, Université de Montréal, Montréal, Québec, Canada (Ms Leclerc and Mr Gervais); Faculty of Medicine (Drs Briand and Bernard), Faculty of Pharmacy (Dr Williamson), and Faculty of Nursing (Dr Arbour), Université de Montréal, Montréal, Québec, Canada; Division of Trauma Research, Departments of Surgery and of Neurological Sciences, Hôpital du Sacré-Coeur de Montréal, CIUSSS du Nord-de-l'Île-de-Montréal, Montréal, Québec, Canada (Drs Briand, Bernard, Duclos, and Arbour); and Department of Anesthesiology and Pain Medicine, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada (Dr Duclos)
| | | | | | | | | | | | | | | |
Collapse
|
|
16
|
Zhuo J, Raghavan P, Jiang L, Roys S, Tchoquessi RLN, Chen H, Wickwire EM, Parikh GY, Schwartzbauer GT, Grattan LM, Wang Z, Gullapalli RP, Badjatia N. Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.06.01.24307927. [PMID: 38854000 PMCID: PMC11160843 DOI: 10.1101/2024.06.01.24307927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2024]
Abstract
Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Our key findings include: 1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. 2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. 3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information, highlighting their distinct roles in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.
Collapse
Affiliation(s)
- Jiachen Zhuo
- Center for Advanced Imaging Research, University of Maryland School of Medicine, Baltimore, MD
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Prashant Raghavan
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Li Jiang
- Center for Advanced Imaging Research, University of Maryland School of Medicine, Baltimore, MD
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Steven Roys
- Center for Advanced Imaging Research, University of Maryland School of Medicine, Baltimore, MD
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Rosy Linda Njonkou Tchoquessi
- Center for Advanced Imaging Research, University of Maryland School of Medicine, Baltimore, MD
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Hegang Chen
- Department of Epidemiology & public Health, University of Maryland School of Medicine, Baltimore, MD
| | - Emerson M. Wickwire
- Department of Psychiatry & Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Gunjan Y. Parikh
- Program in Trauma, University of Maryland School of Medicine, Baltimore, MD
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD
| | - Gary T. Schwartzbauer
- Program in Trauma, University of Maryland School of Medicine, Baltimore, MD
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD
| | - Lynn M. Grattan
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD
| | - Ze Wang
- Center for Advanced Imaging Research, University of Maryland School of Medicine, Baltimore, MD
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Rao P. Gullapalli
- Center for Advanced Imaging Research, University of Maryland School of Medicine, Baltimore, MD
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Neeraj Badjatia
- Program in Trauma, University of Maryland School of Medicine, Baltimore, MD
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD
| |
Collapse
|
|
17
|
Ogg M, Coon WG. Self-Supervised Transformer Model Training for a Sleep-EEG Foundation Model. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.01.18.576245. [PMID: 38293234 PMCID: PMC10827180 DOI: 10.1101/2024.01.18.576245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2024]
Abstract
The American Academy of Sleep Medicine (AASM) recognizes five sleep/wake states (Wake, N1, N2, N3, REM), yet this classification schema provides only a high-level summary of sleep and likely overlooks important neurological or health information. New, data-driven approaches are needed to more deeply probe the information content of sleep signals. Here we present a self-supervised approach that learns the structure embedded in large quantities of neurophysiological sleep data. This masked transformer training procedure is inspired by high performing self-supervised methods developed for speech transcription. We show that self-supervised pre-training matches or outperforms supervised sleep stage classification, especially when labeled data or compute-power is limited. Perhaps more importantly, we also show that our pretrained model is flexible and can be fine-tuned to perform well on new tasks including distinguishing individuals and quantifying "brain age" (a potential health biomarker). This suggests that modern methods can automatically learn information that is potentially overlooked by the 5-class sleep staging schema, laying the groundwork for new schemas and further data-driven exploration of sleep.
Collapse
|
|
18
|
Kureshi S, Mendizabal M, Francis J, Djalilian HR. Conservative Management of Acute Sports-Related Concussions: A Narrative Review. Healthcare (Basel) 2024; 12:289. [PMID: 38338173 PMCID: PMC10855441 DOI: 10.3390/healthcare12030289] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/09/2024] [Accepted: 01/22/2024] [Indexed: 02/12/2024] Open
Abstract
This review explores the application of the conservative management model for pain to sports-related concussions (SRCs), framing concussions as a distinct form of pain syndrome with a pathophysiological foundation in central sensitization. Drawing parallels with proven pain management models, we underscore the significance of a proactive approach to concussion management. Recognizing concussions as a pain syndrome allows for the tailoring of interventions in alignment with conservative principles. This review first covers the epidemiology and controversies surrounding prolonged concussion recovery and persistent post-concussion symptoms (PPCS). Next, the pathophysiology of concussions is presented within the central sensitization framework, emphasizing the need for early intervention to mitigate the neuroplastic changes that lead to heightened pain sensitivity. Five components of the central sensitization process specific to concussion injuries are highlighted as targets for conservative interventions in the acute period: peripheral sensitization, cerebral metabolic dysfunction, neuroinflammation, glymphatic system dysfunction, and pain catastrophizing. These proactive interventions are emphasized as pivotal in accelerating concussion recovery and reducing the risk of prolonged symptoms and PPCS, in line with the philosophy of conservative management.
Collapse
Affiliation(s)
- Sohaib Kureshi
- Neurosurgical Medical Clinic, San Diego, CA 92111, USA
- TBI Virtual, San Diego, CA 92111, USA
| | | | | | - Hamid R. Djalilian
- TBI Virtual, San Diego, CA 92111, USA
- Departments of Otolaryngology, Neurological Surgery, and Biomedical Engineering, University of California, Irvine, CA 92697, USA
| |
Collapse
|
|
19
|
Landvater J, Kim S, Caswell K, Kwon C, Odafe E, Roe G, Tripathi A, Vukovics C, Wang J, Ryan K, Cocozza V, Brock M, Tchopev Z, Tonkin B, Capaldi V, Collen J, Creamer J, Irfan M, Wickwire EM, Williams S, Werner JK. Traumatic brain injury and sleep in military and veteran populations: A literature review. NeuroRehabilitation 2024; 55:245-270. [PMID: 39121144 PMCID: PMC11613026 DOI: 10.3233/nre-230380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 06/12/2024] [Indexed: 08/11/2024]
Abstract
BACKGROUND Traumatic brain injury (TBI) is a hallmark of wartime injury and is related to numerous sleep wake disorders (SWD), which persist long term in veterans. Current knowledge gaps in pathophysiology have hindered advances in diagnosis and treatment. OBJECTIVE We reviewed TBI SWD pathophysiology, comorbidities, diagnosis and treatment that have emerged over the past two decades. METHODS We conducted a literature review of English language publications evaluating sleep disorders (obstructive sleep apnea, insomnia, hypersomnia, parasomnias, restless legs syndrome and periodic limb movement disorder) and TBI published since 2000. We excluded studies that were not specifically evaluating TBI populations. RESULTS Highlighted areas of interest and knowledge gaps were identified in TBI pathophysiology and mechanisms of sleep disruption, a comparison of TBI SWD and post-traumatic stress disorder SWD. The role of TBI and glymphatic biomarkers and management strategies for TBI SWD will also be discussed. CONCLUSION Our understanding of the pathophysiologic underpinnings of TBI and sleep health, particularly at the basic science level, is limited. Developing an understanding of biomarkers, neuroimaging, and mixed-methods research in comorbid TBI SWD holds the greatest promise to advance our ability to diagnose and monitor response to therapy in this vulnerable population.
Collapse
Affiliation(s)
- Jeremy Landvater
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Sharon Kim
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Keenan Caswell
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Caroline Kwon
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Emamoke Odafe
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Grace Roe
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Ananya Tripathi
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | | | - Jonathan Wang
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Keith Ryan
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | | | - Matthew Brock
- Wilford Hall Ambulatory Surgical Center, San Antonio, TX, USA
| | - Zahari Tchopev
- Wilford Hall Ambulatory Surgical Center, San Antonio, TX, USA
| | - Brionn Tonkin
- University of Minnesota, Minneapolis, MN, USA
- Minneapolis Veterans Administration Medical Center, Minneapolis, MN, USA
| | - Vincent Capaldi
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Jacob Collen
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | | | - Muna Irfan
- University of Minnesota, Minneapolis, MN, USA
- Minneapolis Veterans Administration Medical Center, Minneapolis, MN, USA
| | - Emerson M. Wickwire
- Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA
| | - Scott Williams
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
- Defense Health Headquarters, Falls Church, VA, USA
| | - J. Kent Werner
- Uniformed Services University of the Health Sciences, Bethesda, MD, USA
- Walter Reed National Military Medical Center, Bethesda, MD, USA
| |
Collapse
|
|
20
|
Hanks R, Ketchum JM, Peckham M, Sevigny M, Sander AM, Martin AM, Agtarap S, Beaulieu CL, Callender L, Hammond FM, Lengenfelder J, Rabinowitz AR, Walker WC, Hoffman JM, Harrison-Felix C, Nakase-Richardson R. Associations of Chronic Pain With Psychosocial Outcomes After Traumatic Brain Injury: A NIDILRR and VA TBI Model Systems Collaborative Project. J Head Trauma Rehabil 2024; 39:18-30. [PMID: 38167716 PMCID: PMC10807629 DOI: 10.1097/htr.0000000000000921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
OBJECTIVE To examine the differences in participation, life satisfaction, and psychosocial outcomes among individuals with traumatic brain injury (TBI) endorsing current, past, or no chronic pain. SETTING Community. PARTICIPANTS Three thousand eight hundred four TBI Model Systems participants 1 to 30 years of age postinjury classified into 1 of 3 groups based on their pain experience: current pain, past pain, no pain completed a Pain Survey at their usual follow-up appointment which on average was approximately 8 years postinjury. DESIGN Multisite, cross-sectional observational cohort study. MAIN OUTCOME MEASURES Sociodemographic and injury characteristics and psychosocial outcomes (ie, satisfaction with life, depression, anxiety, posttraumatic stress disorder [PTSD], sleep quality, community participation). RESULTS Persons with current chronic pain demonstrated higher scores on measures of PTSD, anxiety, and depression, and the lower scores on measures of sleep quality, community participation and satisfaction with life. Those with resolved past pain had mean scores for these outcomes that were all between the current and no chronic pain groups, but always closest to the no pain group. After adjusting for sociodemographic and function in multivariate analysis, having current chronic pain was associated with more negative psychosocial outcomes. The largest effect sizes (ES; in absolute value) were observed for the PTSD, depression, anxiety, and sleep quality measures (ES = 0.52-0.81) when comparing current pain to past or no pain, smaller ES were observed for life satisfaction (ES = 0.22-0.37) and out and about participation (ES = 0.16-0.18). When comparing past and no pain groups, adjusted ES were generally small for life satisfaction, PTSD, depression, anxiety, and sleep quality (ES = 0.10-0.23) and minimal for participation outcomes (ES = 0.02-0.06). CONCLUSIONS Chronic pain is prevalent among individuals with TBI and is associated with poorer psychosocial outcomes, especially for PTSD, depression, anxiety, and sleep disturbance. The results from this study highlight the presence of modifiable comorbidities among those with chronic pain and TBI. Persons who experience persistent pain following TBI may be at greater risk for worse psychosocial outcomes.
Collapse
Affiliation(s)
- Robin Hanks
- Department of Physical Medicine and Rehabilitation, School of Medicine, Wayne State University, Detroit, Michigan (Dr Hanks); Research Department, Craig Hospital, Englewood, Colorado (Drs Ketchum, Agtarap, and Harrison-Felix, Ms Peckham, and Mr Sevigny); H. Ben Taub Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Brain Injury Research Center, TIRR Memorial Hermann, Houston, Texas (Dr Sander); Mental Health and Behavioral Science Service, James A. Haley Veterans' Hospital, Tampa, Florida (Dr Martin); Department of Psychiatry and Behavioral Neurosciences, University of South Florida, Tampa (Dr Martin); Department of Physical Medicine and Rehabilitation, College of Medicine, The Ohio State University, Columbus (Dr Beaulieu); Baylor Scott & White Institute for Rehabilitation, Dallas, Texas (Ms Callender); Department of Physical Medicine and Rehabilitation, Indiana University School of Medicine, Rehabilitation Hospital of Indiana, Indianapolis (Dr Hammond); Department of Physical Medicine Rehabilitation, Rutgers-New Jersey Medical School, Newark (Dr Lengenfelder); Kessler Foundation, East Hanover, New Jersey (Dr Lengenfelder); Department of Physical Medicine and Rehabilitation, Moss Rehabilitation Research Institute, Elkins Park, Pennsylvania (Dr Rabinowitz); Department of Physical Medicine & Rehabilitation, School of Medicine, Virginia Commonwealth University, Richmond (Dr Walker); Department of Rehabilitation Medicine, School of Medicine, University of Washington, Seattle (Dr Hoffman); MHBS/Polytrauma, James A. Haley Veterans Hospital, Tampa, Florida (Dr Nakase-Richardson); Sleep and Pulmonary Division, Department of Internal Medicine, University of South Florida, Tampa (Dr Nakase-Richardson); and Defense Health Agency, Traumatic Brain Injury Center of Excellence, Tampa, Florida (Dr Nakase-Richardson)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
21
|
Ghneim MH, Broderick M, Stein DM. Sleep-Wake Disorders Among Older Adults Following Traumatic Brain Injury. ADVANCES IN NEUROBIOLOGY 2024; 42:85-98. [PMID: 39432038 DOI: 10.1007/978-3-031-69832-3_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/22/2024]
Abstract
Traumatic brain injuries (TBI) are increasingly common in older adults and represent a substantial source of morbidity and mortality for this population. In addition to the impact from the primary insult, TBI can lead to a variety of chronic neurocognitive conditions including dementia, depression, and sleep disturbances. When caused by TBI, these conditions differ importantly from their non-TBI-related counterparts. Much about how TBI relates to the development of these conditions is unknown, and more research is needed to further elucidate optimal treatment strategies.
Collapse
Affiliation(s)
- Mira H Ghneim
- R Adams Cowley Shock Trauma, The University of Maryland School of Medicine, Baltimore, MD, USA.
| | - Meaghan Broderick
- R Adams Cowley Shock Trauma, The University of Maryland School of Medicine, Baltimore, MD, USA
| | - Deborah M Stein
- R Adams Cowley Shock Trauma, The University of Maryland School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
22
|
Zhang J, Liu S, Wu Y, Tang Z, Wu Y, Qi Y, Dong F, Wang Y. Enlarged Perivascular Space and Index for Diffusivity Along the Perivascular Space as Emerging Neuroimaging Biomarkers of Neurological Diseases. Cell Mol Neurobiol 2023; 44:14. [PMID: 38158515 PMCID: PMC11407189 DOI: 10.1007/s10571-023-01440-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 11/12/2023] [Indexed: 01/03/2024]
Abstract
The existence of lymphatic vessels or similar clearance systems in the central nervous system (CNS) that transport nutrients and remove cellular waste is a neuroscientific question of great significance. As the brain is the most metabolically active organ in the body, there is likely to be a potential correlation between its clearance system and the pathological state of the CNS. Until recently the successive discoveries of the glymphatic system and the meningeal lymphatics solved this puzzle. This article reviews the basic anatomy and physiology of the glymphatic system. Imaging techniques to visualize the function of the glymphatic system mainly including post-contrast imaging techniques, indirect lymphatic assessment by detecting increased perivascular space, and diffusion tensor image analysis along the perivascular space (DTI-ALPS) are discussed. The pathological link between glymphatic system dysfunction and neurological disorders is the key point, focusing on the enlarged perivascular space (EPVS) and the index of diffusivity along the perivascular space (ALPS index), which may represent the activity of the glymphatic system as possible clinical neuroimaging biomarkers of neurological disorders. The pathological link between glymphatic system dysfunction and neurological disorders is the key point, focusing on the enlarged perivascular space (EPVS) and the index for of diffusivity along the perivascular space (ALPS index), which may represent the activity of the glymphatic system as possible clinical neuroimaging biomarkers of neurological disorders.
Collapse
Affiliation(s)
- Jun Zhang
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Shengwen Liu
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yaqi Wu
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Zhijian Tang
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yasong Wu
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yiwei Qi
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Fangyong Dong
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yu Wang
- Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| |
Collapse
|
|
23
|
Kim SY, Yeh PH, Ollinger JM, Morris HD, Hood MN, Ho VB, Choi KH. Military-related mild traumatic brain injury: clinical characteristics, advanced neuroimaging, and molecular mechanisms. Transl Psychiatry 2023; 13:289. [PMID: 37652994 PMCID: PMC10471788 DOI: 10.1038/s41398-023-02569-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 07/18/2023] [Accepted: 07/24/2023] [Indexed: 09/02/2023] Open
Abstract
Mild traumatic brain injury (mTBI) is a significant health burden among military service members. Although mTBI was once considered relatively benign compared to more severe TBIs, a growing body of evidence has demonstrated the devastating neurological consequences of mTBI, including chronic post-concussion symptoms and deficits in cognition, memory, sleep, vision, and hearing. The discovery of reliable biomarkers for mTBI has been challenging due to under-reporting and heterogeneity of military-related mTBI, unpredictability of pathological changes, and delay of post-injury clinical evaluations. Moreover, compared to more severe TBI, mTBI is especially difficult to diagnose due to the lack of overt clinical neuroimaging findings. Yet, advanced neuroimaging techniques using magnetic resonance imaging (MRI) hold promise in detecting microstructural aberrations following mTBI. Using different pulse sequences, MRI enables the evaluation of different tissue characteristics without risks associated with ionizing radiation inherent to other imaging modalities, such as X-ray-based studies or computerized tomography (CT). Accordingly, considering the high morbidity of mTBI in military populations, debilitating post-injury symptoms, and lack of robust neuroimaging biomarkers, this review (1) summarizes the nature and mechanisms of mTBI in military settings, (2) describes clinical characteristics of military-related mTBI and associated comorbidities, such as post-traumatic stress disorder (PTSD), (3) highlights advanced neuroimaging techniques used to study mTBI and the molecular mechanisms that can be inferred, and (4) discusses emerging frontiers in advanced neuroimaging for mTBI. We encourage multi-modal approaches combining neuropsychiatric, blood-based, and genetic data as well as the discovery and employment of new imaging techniques with big data analytics that enable accurate detection of post-injury pathologic aberrations related to tissue microstructure, glymphatic function, and neurodegeneration. Ultimately, this review provides a foundational overview of military-related mTBI and advanced neuroimaging techniques that merit further study for mTBI diagnosis, prognosis, and treatment monitoring.
Collapse
Affiliation(s)
- Sharon Y Kim
- School of Medicine, Uniformed Services University, Bethesda, MD, USA
- Program in Neuroscience, Uniformed Services University, Bethesda, MD, USA
| | - Ping-Hong Yeh
- National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, USA
| | - John M Ollinger
- Program in Neuroscience, Uniformed Services University, Bethesda, MD, USA
- National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, USA
| | - Herman D Morris
- Department of Radiology and Radiological Sciences, Uniformed Services University, Bethesda, MD, USA
- Department of Radiology, Walter Reed National Military Medical Center, Bethesda, MD, USA
| | - Maureen N Hood
- Department of Radiology and Radiological Sciences, Uniformed Services University, Bethesda, MD, USA
- Department of Radiology, Walter Reed National Military Medical Center, Bethesda, MD, USA
| | - Vincent B Ho
- Department of Radiology and Radiological Sciences, Uniformed Services University, Bethesda, MD, USA
- Department of Radiology, Walter Reed National Military Medical Center, Bethesda, MD, USA
| | - Kwang H Choi
- Program in Neuroscience, Uniformed Services University, Bethesda, MD, USA.
- Center for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD, USA.
- Department of Psychiatry, Uniformed Services University, Bethesda, MD, USA.
| |
Collapse
|
|
24
|
Gao Y, Liu K, Zhu J. Glymphatic system: an emerging therapeutic approach for neurological disorders. Front Mol Neurosci 2023; 16:1138769. [PMID: 37485040 PMCID: PMC10359151 DOI: 10.3389/fnmol.2023.1138769] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 06/21/2023] [Indexed: 07/25/2023] Open
Abstract
The functions of the glymphatic system include clearance of the metabolic waste and modulation of the water transport in the brain, and it forms a brain-wide fluid network along with cerebrospinal fluid (CSF) and interstitial fluid (ISF). The glymphatic pathway consists of periarterial influx of CSF, astrocyte-mediated interchange between ISF and CSF supported by aquaporin-4 (AQP4) on the endfeet of astrocyte around the periarterioles, and perivenous efflux of CSF. Finally, CSF is absorbed by the arachnoid granules or flows into the cervical lymphatic vessels. There is growing evidence from animal experiments that the glymphatic system dysfunction is involved in many neurological disorders, such as Alzheimer's disease, stroke, epilepsy, traumatic brain injury and meningitis. In this review, we summarize the latest progress on the glymphatic system and its driving factors, as well as changes in the glymphatic pathway in different neurological diseases. We significantly highlight the likely therapeutic approaches for glymphatic pathway in neurological diseases, and the importance of AQP4 and normal sleep architecture in this process.
Collapse
Affiliation(s)
- Ying Gao
- Department of Neurology, Neuroscience Centre, The First Hospital of Jilin University, Changchun, China
| | - Kangding Liu
- Department of Neurology, Neuroscience Centre, The First Hospital of Jilin University, Changchun, China
| | - Jie Zhu
- Department of Neurology, Neuroscience Centre, The First Hospital of Jilin University, Changchun, China
- Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Karolinska University Hospital, Solna, Sweden
| |
Collapse
|
|
25
|
Peters ME, Lyketsos CG. The glymphatic system's role in traumatic brain injury-related neurodegeneration. Mol Psychiatry 2023; 28:2707-2715. [PMID: 37185960 DOI: 10.1038/s41380-023-02070-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 04/03/2023] [Accepted: 04/05/2023] [Indexed: 05/17/2023]
Abstract
In at least some individuals who suffer a traumatic brain injury (TBI), there exists a risk of future neurodegenerative illness. This review focuses on the association between the brain-based paravascular drainage pathway known as the "glymphatic system" and TBI-related neurodegeneration. The glymphatic system is composed of cerebrospinal fluid (CSF) flowing into the brain parenchyma along paravascular spaces surrounding penetrating arterioles where it mixes with interstitial fluid (ISF) before being cleared along paravenous drainage pathways. Aquaporin-4 (AQP4) water channels on astrocytic end-feet appear essential for the functioning of this system. The current literature linking glymphatic system disruption and TBI-related neurodegeneration is largely based on murine models with existing human research focused on the need for biomarkers of glymphatic system function (e.g., neuroimaging modalities). Key findings from the existing literature include evidence of glymphatic system flow disruption following TBI, mechanisms of this decreased flow (i.e., AQP4 depolarization), and evidence of protein accumulation and deposition (e.g., amyloid β, tau). The same studies suggest that glymphatic dysfunction leads to subsequent neurodegeneration, cognitive decline, and/or behavioral change although replication in humans is needed. Identified emerging topics from the literature are as follows: link between TBI, sleep, and glymphatic system dysfunction; influence of glymphatic system disruption on TBI biomarkers; and development of novel treatments for glymphatic system disruption following TBI. Although a burgeoning field, more research is needed to elucidate the role of glymphatic system disruption in TBI-related neurodegeneration.
Collapse
Affiliation(s)
- Matthew E Peters
- Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | - Constantine G Lyketsos
- Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
26
|
Dai Z, Yang Z, Li Z, Li M, Sun H, Zhuang Z, Yang W, Hu Z, Chen X, Lin D, Wu X. Increased glymphatic system activity in patients with mild traumatic brain injury. Front Neurol 2023; 14:1148878. [PMID: 37251219 PMCID: PMC10213560 DOI: 10.3389/fneur.2023.1148878] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 04/24/2023] [Indexed: 05/31/2023] Open
Abstract
Purpose This study aims to investigate the glymphatic system activity changes in patients with mild traumatic brain injury (mTBI), particularly in MRI-negative patients, using analysis along the perivascular space (ALPS) technology. Methods A total of 161 mTBI patients (age: 15-92 years old) and 28 healthy controls (age: 15-84 years old) were included in this retrospective study. The mTBI patients were divided into MRI-negative and MRI-positive groups. ALPS index was calculated automatically using whole-brain T1-MPRAGE imaging and diffusion tensor imaging. The Student's t and chi-squared tests were performed to compare the ALPS index, age, gender, course of disease, and Glasgow Coma Scale (GCS) score between groups. Correlations among ALPS index, age, course of disease and GCS score were computed using Spearman's correlation analysis. Results Increased activity of the glymphatic system was suggested in mTBI patients based on ALPS index analysis, including the MRI-negative patients. There was a significant negative correlation between the ALPS index and age. In addition, a weak positive correlation between the ALPS index and course of disease was also observed. On the contrary, there was no significant correlation between the ALPS index and sex nor between the ALPS index and GCS score. Conclusion Our study demonstrated that the activity level of the glymphatic system was enhanced in mTBI patients, even when their brain MRI scans were negative. These findings may provide novel insights for understanding the pathophysiology of mild TBI.
Collapse
Affiliation(s)
- Zhuozhi Dai
- Department of Radiology, Shantou Central Hospital, Shantou, Guangdong, China
- Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhiqi Yang
- Department of Radiology, Meizhou People's Hospital, Meizhou, Guangdong, China
| | - Zhaolin Li
- Department of Pulmonary and Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Mu Li
- Department of Neurosurgery, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Hongfu Sun
- School of Information Technology and Electrical Engineering, University of Queensland, Brisbane, QLD, Australia
| | - Zerui Zhuang
- Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Weichao Yang
- Department of Radiology, Meizhou People's Hospital, Meizhou, Guangdong, China
| | - Zehuan Hu
- Department of Radiology, Shantou Central Hospital, Shantou, Guangdong, China
| | - Xiaofeng Chen
- Department of Radiology, Meizhou People's Hospital, Meizhou, Guangdong, China
| | - Daiying Lin
- Department of Radiology, Shantou Central Hospital, Shantou, Guangdong, China
| | - Xianheng Wu
- Department of Radiology, Shantou Central Hospital, Shantou, Guangdong, China
| |
Collapse
|
|
27
|
Traumatic Brain Injury Characteristics Predictive of Subsequent Sleep-Wake Disturbances in Pediatric Patients. BIOLOGY 2022; 11:biology11040600. [PMID: 35453799 PMCID: PMC9030185 DOI: 10.3390/biology11040600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/11/2022] [Accepted: 04/13/2022] [Indexed: 12/02/2022]
Abstract
Simple Summary Traumatic brain injury is a leading cause of death and disabilities in children and adolescents. Poor sleep after brain injury can slow recovery and worsen outcomes. We investigated clinical sleep problems following pediatric brain injury. We examined characteristics of the injury and details about the patients that may be risk factors for developing sleep problems. The number of patients that developed problems with their sleep after a brain injury was similar between genders. The probability of insomnia increased with increasing patient age. The probability of ‘difficulty sleeping’ was highest in 7–9 year-old brain-injured patients. Older patients had a shorter time between brain injury and sleep problems compared to younger patients. Patients with severe brain injury had the shortest time between brain injury and development of sleep problems, whereas patients with mild or moderate brain injury had comparable times between brain injury and the onset of poor sleep. Multiple characteristics of brain injury and patient details were identified as risk factors for developing sleep problems following a brain injury in children. Untreated sleep problems after a brain injury can worsen symptoms, lengthen hospital stays, and delay return to school. Identifying risk factors could improve the diagnosis, management, and treatment of sleep problems in survivors of pediatric brain injury. Abstract The objective of this study was to determine the prevalence of sleep-wake disturbances (SWD) following pediatric traumatic brain injury (TBI), and to examine characteristics of TBI and patient demographics that might be predictive of subsequent SWD development. This single-institution retrospective study included patients diagnosed with a TBI during 2008–2019 who also had a subsequent diagnosis of an SWD. Data were collected using ICD-9/10 codes for 207 patients and included the following: age at initial TBI, gender, TBI severity, number of TBIs diagnosed prior to SWD diagnosis, type of SWD, and time from initial TBI to SWD diagnosis. Multinomial logit and negative-binomial models were fit to investigate whether the multiple types of SWD and the time to onset of SWD following TBI could be predicted by patient variables. Distributions of SWD diagnosed after TBI were similar between genders. The probability of insomnia increased with increasing patient age. The probability of ‘difficulty sleeping’ was highest in 7–9 year-old TBI patients. Older TBI patients had shorter time to SWD onset than younger patients. Patients with severe TBI had the shortest time to SWD onset, whereas patients with mild or moderate TBI had comparable times to SWD onset. Multiple TBI characteristics and patient demographics were predictive of a subsequent SWD diagnosis in the pediatric population. This is an important step toward increasing education among providers, parents, and patients about the risk of developing SWD following TBI.
Collapse
|
|
28
|
Howlett JR, Nelson LD, Stein MB. Mental Health Consequences of Traumatic Brain Injury. Biol Psychiatry 2022; 91:413-420. [PMID: 34893317 PMCID: PMC8849136 DOI: 10.1016/j.biopsych.2021.09.024] [Citation(s) in RCA: 133] [Impact Index Per Article: 44.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 09/21/2021] [Accepted: 09/27/2021] [Indexed: 01/04/2023]
Abstract
Traumatic brain injury (TBI) is associated with a host of psychiatric and neurobehavioral problems. As mortality rates have declined for severe TBI, attention has turned to the cognitive, affective, and behavioral sequelae of injuries across the severity spectrum, which are often more disabling than residual physical effects. Moderate and severe TBI can cause personality changes including impulsivity, severe irritability, affective instability, and apathy. Mild TBI, once considered a largely benign phenomenon, is now known to be associated with a range of affective symptoms, with suicidality, and with worsening or new onset of several psychiatric disorders including posttraumatic stress disorder and major depressive disorder. Repetitive head impacts, often in athletic contexts, are now believed to be associated with a number of emotional and behavioral sequelae. The nature and etiology of mental health manifestations of TBI (including a combination of brain dysfunction and psychological trauma and interrelationships between cognitive, affective, and physical symptoms) are complex and have been a focus of recent epidemiological and mechanistic studies. This paper will review the epidemiology of psychiatric and neurobehavioral problems after TBI in military, civilian, and athletic contexts.
Collapse
Affiliation(s)
- Jonathon R Howlett
- VA San Diego Healthcare System, San Diego, La Jolla, California; Department of Psychiatry, University of California San Diego, La Jolla, California.
| | - Lindsay D Nelson
- Department of Neurosurgery & Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Murray B Stein
- VA San Diego Healthcare System, San Diego, La Jolla, California; Department of Psychiatry, University of California San Diego, La Jolla, California; School of Public Health, University of California San Diego, La Jolla, California
| |
Collapse
|
|
29
|
Nelson LD, Stein MB. Mind the Gap: Missing Links in the Understanding of Traumatic Brain Injury and Mental Health. Biol Psychiatry 2022; 91:400-401. [PMID: 35115093 PMCID: PMC8862512 DOI: 10.1016/j.biopsych.2021.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 12/01/2021] [Indexed: 11/02/2022]
Affiliation(s)
- Lindsay D. Nelson
- Departments of Neurosurgery and Neurology, Medical College of Wisconsin, Milwaukee, WI USA
| | - Murray B. Stein
- Department of Psychiatry and School of Public Health, University of California San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, San Diego, CA, USA
| |
Collapse
|