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Chen Z, He J, Guo Y, Hao Y, Lv W, Chen Z, Wang J, Yang Y, Wang K, Liu Z, Ouyang Q, Su Z, Hu P, Xiao G. Adherent junctions: Physiology, role in hydrocephalus and potential therapeutic targets. IBRO Neurosci Rep 2025; 18:283-292. [PMID: 39995568 PMCID: PMC11849119 DOI: 10.1016/j.ibneur.2025.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 01/14/2025] [Accepted: 02/03/2025] [Indexed: 02/26/2025] Open
Abstract
In all epithelial cells, the adherent junctions (AJs) with cadherin as the core play an important role in the maintenance of the connection and the formation of apical-basal polarity. The ependymal cells close to the ventricular system rely on AJs with N-cadherin at the core to maintain their normal morphology and function. Therefore, it has an important impact on the function and disease of the central nervous system. Hydrocephalus is a pathological phenomenon of excessive cerebrospinal fluid accumulating in the ventricular system accompanied by continuous ventricular dilatation, which can be divided into obstructive hydrocephalus and communicating hydrocephalus according to the pathogenesis. Obstructive hydrocephalus is often associated with excessive ependymal cells produced by differentiation of radial glial cells. The etiology of communicating hydrocephalus is mainly related to the dyskinesia of cerebrospinal fluid. In addition, the damage of the brain barrier can lead to brain edema and aggravate the symptoms. At present, the researches on the pathogenesis of hydrocephalus are mainly focused on the development of ependymal cells and cilia, while less attention has been paid to molecules such as AJs, which play an important role in maintaining the polarity of ependymal cells. This paper discusses the formation and function of AJs and their role in preventing hydrocephalus by preserving the polarity of ependymal cilia, regulating the number of ependymal cells, and upholding the brain barrier integrity to impede hydrocephalus exacerbation, which provides a new direction for the study of hydrocephalus.
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Affiliation(s)
- Zhiye Chen
- Department of Diagnostic Radiology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan 410008, PR China
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
| | - Jian He
- Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
| | - Yating Guo
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
| | - Yue Hao
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
| | - Wentao Lv
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
| | - Zexin Chen
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
| | - Junqiang Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
| | - Yijian Yang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
| | - Kaiyue Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
| | - Zhikun Liu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
| | - Qian Ouyang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- Department of Neurosurgery, Zhuzhou Hospital, Central South University Xiangya School of Medicine, Zhuzhou, Hunan 412000, PR China
| | - Zhangjie Su
- Department of Neurosurgery, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB21 2QQ, UK
| | - Pingsheng Hu
- Department of Diagnostic Radiology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan 410008, PR China
| | - Gelei Xiao
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
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Jalles C, Guerreiro D, Pona-Ferreira F, Simões RM, Reimão S, Ferreira JJ. Hypokinetic-rigid gait disorders with balance impairment - A walk through clinical and pathophysiological definitions. Parkinsonism Relat Disord 2025; 133:107339. [PMID: 39971644 DOI: 10.1016/j.parkreldis.2025.107339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 02/01/2025] [Accepted: 02/12/2025] [Indexed: 02/21/2025]
Abstract
Hypokinetic-rigid gait disorders with balance impairment are a common clinical phenotype of different syndromes and diseases. However, multiple designations are used across the literature with unclear definitions, which brings heterogeneity and subjectivity to the discussion of such gait disorders. Therefore, there is a need for clear concepts to increase accuracy in clinical diagnosis and allow consistent comparisons and reasoning within research data. We performed a review of concepts, including lower body parkinsonism (LBP), higher level gait disorders, frontal gait disorders, gait apraxia, senile gait and cautious gait. Additionally, we reviewed the basic pathophysiological mechanisms underlying these gait disorders. LBP was found to be mainly associated with dysfunction of the motor thalamocortical circuit and of the mesencephalic locomotor region. We propose that for research purposes, concepts with greater specificity, such as LBP, should be preferentially used to improve the accuracy of studies involving this population. Considering the significant phenotypic and pathophysiological overlap between hypokinetic-rigid gait disorders, a multi-modal approach would be more pertinent to optimize the differential diagnosis in both clinical and research settings.
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Affiliation(s)
- Constança Jalles
- Clinical Pharmacology Unit, Unidade Local de Saúde de Santa Maria, Portugal; Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | | | | | - Rita M Simões
- CNS, Campus Neurológico, Torres Vedras, Portugal; Neurology Department, Unidade Local de Saúde Loures-Odivelas, Portugal
| | - Sofia Reimão
- Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; Imaging University Clinic, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; Neurological Imaging Department, Unidade Local de Saúde de Santa Maria, Portugal
| | - Joaquim J Ferreira
- Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; CNS, Campus Neurológico, Torres Vedras, Portugal.
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Dhawan SS, Hacein-Bey L, Massoud TF. Choroid plexus enlargement in idiopathic normal pressure hydrocephalus and concept proposal for noninvasive volume-reductive therapies. Brain Res 2025; 1857:149593. [PMID: 40157411 DOI: 10.1016/j.brainres.2025.149593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 03/16/2025] [Accepted: 03/19/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Aberrant CSF dynamics in idiopathic normal pressure hydrocephalus (iNPH) are associated with excessive CSF volume and impaired resorption. Yet, the role of choroid plexus (CP) size in development and progression of iNPH remains unknown. Moreover, newer noninvasive CP-targeted volume-reductive treatments for iNPH might benefit selected vulnerable patients to avoid problematic long-term ventricular shunting. However, there are no studies to date that describe CP size in iNPH patients. METHODS We retrospectively studied brain 3T MRIs for 50 iNPH patients and 50 age and sex-matched healthy controls (HCs). We delineated areas and volumes of lateral ventricular CPs, then statistically compared both cohorts, with significance set at p < 0.05. RESULTS In iNPH patients, CP volume (1.58-fold) alone, CP volume normalized to total intracranial volume (1.75-fold), and CP areas at four different locations and their combined values (1.24-fold) were highly significantly larger (p < 0.000) in iNPH patients. CONCLUSION The novel finding of CP enlargement in iNPH should guide and support future investigations into potentially interrelated pathogenetic mechanisms. It also benefits considerations of new noninvasive targeted therapies (such as MR-guided high intensity focused ultrasound, and radiosurgery) to partially ablate CP and reduce its CSF secretion as a conceivable alternative to conventional ventricular shunting.
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Affiliation(s)
- Siddhant S Dhawan
- Division of Neuroimaging and Neurointervention, Department of Radiology, Stanford University School of Medicine, 453 Quarry Road, Palo Alto, CA 94304, USA.
| | - Lotfi Hacein-Bey
- Division of Neuroradiology and Interventional Neuroradiology, Department of Radiology, University of California Davis School of Medicine, 4860 Y Street, Suite 3100, Sacramento, CA 95817, USA.
| | - Tarik F Massoud
- Division of Neuroimaging and Neurointervention, Department of Radiology, Stanford University School of Medicine, 453 Quarry Road, Palo Alto, CA 94304, USA.
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Gama Marques J, Finsterer J. Schizophrenia misdiagnosis after dysmorphophobia in a patient with macrocephaly. Neurocase 2025; 31:49-51. [PMID: 39665466 DOI: 10.1080/13554794.2024.2439022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2024]
Affiliation(s)
- João Gama Marques
- Consulta de Esquizofrenia Resistente (CRE), Hospital Júlio de Matos (HJM), Unidade Local de Saúde São José (ULSSJ), Centro Clínico Académico de Lisboa (CCAL), Lisboa, Portugal
- Clínica Universitária de Psiquiatria e Psicologia Médica (CUPPM), Faculdade de Medicina, Universidade de Lisboa (FMUL), Centro Académico de Medicina de Lisboa (CAML), Lisboa, Portugal
| | - Josef Finsterer
- Neurology Department, Neurology & Neurophysiology Center, Vienna, Austria
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Kelbert J, Nosova K, Kern A, Russell R, Pico A, Mamaril-Davis J, Hussein A, Murthy G, Barbagli G, Bina RW. Idiopathic Normal Pressure Hydrocephalus and Shunt Complications per Valve Type: A Meta-Analysis of Proportions. World Neurosurg 2025; 194:123450. [PMID: 39577651 DOI: 10.1016/j.wneu.2024.11.033] [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: 05/22/2024] [Revised: 11/05/2024] [Accepted: 11/06/2024] [Indexed: 11/24/2024]
Abstract
BACKGROUND Idiopathic normal pressure hydrocephalus is classically recognized by the triad of gait disturbance, cognitive dysfunction, and urinary incontinence. Since ventricular shunting may be affected by valve type, we conducted a meta-analysis to assess the relationship between valve characteristics and outcomes. METHODS English language studies that reported valve types, outcomes, and associated complications were included. Data were extracted and analyzed using R, version 4.3.2. RESULTS Thirteen studies were included. With gravitational valves, meta-analysis yielded 0.04 [0.02, 0.07] for subdural effusions (SDEs), 0.00 [0.00, 0.00] for surgical SDEs, 0.06 [0.03, 0.09] for proximal revisions, and 0.06 [0.03, 0.09] for distal. With differential pressure valves (DPVs) with antisiphon control, meta-analysis showed an incidence of 0.10 [0.07, 0.13] for SDEs, 0.02 [0.01, 0.04] for surgical SDEs, 0.03 [0.01, 0.05] for proximal and 0.04 [0.02, 0.07] for distal revisions. With DPVs without antisiphon control, there was an incidence of 0.17 [0.11, 0.23] for SDEs, 0.11 [0.06, 0.19] for surgical SDEs, 0.00 [0.00, 0.02] for proximal shunt revisions, and 0.05 [0.02, 0.10] for distal shunt revisions. With flow regulated valves, there was an incidence of 0.05 [0.01, 0.12] for SDEs, 0.01 [0.00, 0.05] for surgical SDEs, 0.06 [0.02, 0.11] for proximal revisions, and 0.01 [0.00, 0.05] for distal. CONCLUSIONS Gravitational valves and NPVs are associated with fewer SDEs while DPVs with and without ASDs are associated with more while there were no differences in proximal or distal revisions.
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Affiliation(s)
- James Kelbert
- Department of Neurosurgery, University of Arizona College of Medicine, Phoenix, Arizona, USA.
| | - Kristin Nosova
- Department of Neurosurgery, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Ashley Kern
- Department of Neurosurgery, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Rachel Russell
- Department of Neurosurgery, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Annie Pico
- Department of Neurosurgery, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | | | - Amna Hussein
- Department of Neurosurgery, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Ganesh Murthy
- Department of Neurology, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Giovanni Barbagli
- Department of Neurosurgery, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Robert W Bina
- Department of Neurosurgery, University of Arizona College of Medicine, Phoenix, Arizona, USA
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Yang Z, Luo TT, Dai YL, Duan HX, Chong CM, Tang J. Pharmacological Strategies and Surgical Management of Posthemorrhagic Hydrocephalus Following Germinal Matrix-Intraventricular Hemorrhage in Preterm Infants. Curr Neuropharmacol 2025; 23:241-255. [PMID: 39248058 PMCID: PMC11808585 DOI: 10.2174/1570159x23666240906115817] [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] [Received: 01/03/2024] [Revised: 02/19/2024] [Accepted: 03/19/2024] [Indexed: 09/10/2024] Open
Abstract
Germinal matrix-intraventricular hemorrhage (GM-IVH) is a detrimental neurological complication that occurs in preterm infants, especially in babies born before 32 weeks of gestation and in those with a very low birth weight. GM-IVH is defined as a rupture of the immature and fragile capillaries located in the subependymal germinal matrix zone of the preterm infant brain, and it can lead to detrimental neurological sequelae such as posthemorrhagic hydrocephalus (PHH), cerebral palsy, and other cognitive impairments. PHH following GM-IVH is difficult to treat in the clinic, and no levelone strategies have been recommended to pediatric neurosurgeons. Several cellular and molecular mechanisms of PHH following GM-IVH have been studied in animal models, but no effective pharmacological strategies have been used in the clinic. Thus, a comprehensive understanding of molecular mechanisms, potential pharmacological strategies, and surgical management of PHH is urgently needed. The present review presents a synopsis of the pathogenesis, diagnosis, and cellular and molecular mechanisms of PHH following GM-IVH and explores pharmacological strategies and surgical management.
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Affiliation(s)
- Zhao Yang
- Department of Neurosurgery, Children’s Hospital of Chongqing Medical University. National Research Center for Child Health and Disorders, Chongqing, 400014, China
- Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, 400014, China
| | - Tian Tian Luo
- Department of Neurobiology, Army Medical University (Third military medical university), Chongqing, 400038, China
| | - Ya-Lan Dai
- Department of Neurosurgery, Children’s Hospital of Chongqing Medical University. National Research Center for Child Health and Disorders, Chongqing, 400014, China
- Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, 400014, China
| | - Han-Xiao Duan
- Department of Neurosurgery, Children’s Hospital of Chongqing Medical University. National Research Center for Child Health and Disorders, Chongqing, 400014, China
- Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, 400014, China
| | - Cheong-Meng Chong
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China
| | - Jun Tang
- Department of Neurosurgery, Children’s Hospital of Chongqing Medical University. National Research Center for Child Health and Disorders, Chongqing, 400014, China
- Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, 400014, China
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Yang F, Cai H, Ren Y, Huang K, Gao H, Qin L, Wang R, Chen Y, Zhou L, Zhou D, Chen Q. Association between telomere length and idiopathic normal pressure hydrocephalus: a Mendelian randomization study. Front Neurol 2024; 15:1393825. [PMID: 39741705 PMCID: PMC11686450 DOI: 10.3389/fneur.2024.1393825] [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: 03/02/2024] [Accepted: 12/02/2024] [Indexed: 01/03/2025] Open
Abstract
Objective Idiopathic normal pressure hydrocephalus (iNPH) is highly prevalent among elderly individuals, and there is a strong correlation between telomere length and biological aging. However, there is limited evidence to elucidate the relationship between telomere length and iNPH. This study aimed to investigate the associations between telomere length and iNPH using the Mendelian randomization (MR) method. Methods The genetic variants of telomere length were obtained from 472,174 UK Biobank individuals. Summary level data of iNPH were acquired from 218,365 individuals of the FinnGen consortium. Five MR estimation methods, including inverse-variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode, were used for causal inference. Comprehensive sensitivity analyses were conducted to test the robustness of the results. In addition, multivariable MR was further implemented to identify potential mechanisms in the causal pathway from telomere length to iNPH. Results Genetically determined longer telomere length was significantly associated with decreased risk of iNPH (OR = 0.44, 95% CI 0.24-0.80; p = 0.008). No evident heterogeneity (Cochran Q = 138.11, p = 0.386) and pleiotropy (MR Egger intercept = 0.01, p = 0.514) were observed in the sensitivity analysis. In addition, multivariable MR indicated that the observed association was attenuated after adjustment for several vascular risk factors, including essential hypertension (IVW OR = 0.55, 95% CI 0.30-1.03; p = 0.061), type 2 diabetes (IVW OR = 0.71, 95% CI 0.09-5.39; p = 0.740) and coronary artery disease (IVW OR = 0.58, 95% CI 0.31-1.07; p = 0.082). Conclusion Our MR study revealed a strong negative correlation of telomere length with iNPH. The causal relationship might be driven by several vascular risk factors.
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Affiliation(s)
- Feng Yang
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, China
| | - Hanlin Cai
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, China
| | - Yimeng Ren
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, China
| | - Keru Huang
- Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, China
| | - Hui Gao
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, China
| | - Linyuan Qin
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, China
| | - Ruihan Wang
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, China
| | - Yongping Chen
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, China
| | - Liangxue Zhou
- Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, China
| | - Dong Zhou
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, China
| | - Qin Chen
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, China
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Hasegawa S, Yoshimaru D, Hayashi N, Shibukawa S, Takagi M, Murai H. Analyzing the relationship between specific brain structural changes and the diffusion tensor image analysis along the perivascular space index in idiopathic normal pressure hydrocephalus. J Neurol 2024; 272:56. [PMID: 39666072 DOI: 10.1007/s00415-024-12850-y] [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: 10/19/2024] [Revised: 11/30/2024] [Accepted: 12/02/2024] [Indexed: 12/13/2024]
Abstract
BACKGROUND Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS) evaluates the glymphatic system in patients with idiopathic normal-pressure hydrocephalus (iNPH). However, white matter compression due to ventricular enlargement may affect the ALPS index. This study aimed to investigate the relationship among the ALPS index, white matter changes, and clinical symptoms in patients with iNPH. METHODS We calculated the ALPS index in 30 patients with iNPH, aged 70 and above, using DTI data and correlated it with various clinical and imaging indices, including the Evans index, callosal angle, cognitive tests, gait assessment (timed up-and-go [TUG] test), cerebrospinal fluid (CSF) medullary pressure, and various DTI indices (axial diffusivity [AD], radial diffusivity [RD], mean diffusivity [MD], fractional anisotropy [FA]). RESULTS Significant negative correlations were observed between the ALPS index and the rate of change in step count in the TUG test after the tap test (r = -0.5014, p = 0.0048), as well as CSF medullary pressure (r = -0.4651, p = 0.0096). Positive correlations were identified between the ALPS index and both AD (r = 0.4984, p = 0.0051) and MD (r = 0.3631, p = 0.0486). CONCLUSION A lower ALPS index was associated with gait improvement following the tap test as well as higher CSF medullary pressure. The ALPS index may detect subtle periventricular compression-induced changes in iNPH. Consequently, it could potentially serve as a predictor for tap test effectiveness in patients with iNPH, offering a new perspective on its application in iNPH diagnosis and treatment.
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Affiliation(s)
- Shinya Hasegawa
- Department of Radiology, Chiba Saiseikai Narashino Hospital, 1-1-1 Izumicho, Narashino City, Chiba, 275-8580, Japan.
- Graduate School of Radiological Technology, Gunma Prefectural College of Health Sciences, 23-1 Kamiochicho, Maebashi City, Gunma, 371-0052, Japan.
| | - Daisuke Yoshimaru
- Division of Regenerative Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
- National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.
- Department of Radiology, Tokyo Medical University, Tokyo, Japan.
| | - Norio Hayashi
- Graduate School of Radiological Technology, Gunma Prefectural College of Health Sciences, 23-1 Kamiochicho, Maebashi City, Gunma, 371-0052, Japan
| | - Shuhei Shibukawa
- Department of Radiology, Tokyo Medical University, Tokyo, Japan
- Faculty of Health Science, Department of Radiological Technology, Juntendo University, Tokyo, Japan
- Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan
| | - Mika Takagi
- Department of Radiology, Chiba Saiseikai Narashino Hospital, 1-1-1 Izumicho, Narashino City, Chiba, 275-8580, Japan
| | - Hisayuki Murai
- Department of Neurosurgery, Chiba Saiseikai Narashino Hospital, Chiba, Japan
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Wang K, Tang Z, Yang Y, Guo Y, Liu Z, Su Z, Li X, Xiao G. Zebrafish as a Model Organism for Congenital Hydrocephalus: Characteristics and Insights. Zebrafish 2024; 21:361-384. [PMID: 39510565 DOI: 10.1089/zeb.2024.0148] [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] [Indexed: 11/15/2024] Open
Abstract
Hydrocephalus is a cerebrospinal fluid-related disease that usually manifests as abnormal dilation of the ventricles, with a triad of clinical findings including walking difficulty, reduced attention span, and urinary frequency or incontinence. The onset of congenital hydrocephalus is closely related to mutations in genes that regulate brain development. Currently, our understanding of the mechanisms of congenital hydrocephalus remains limited, and the prognosis of existing treatments is unsatisfactory. Additionally, there are no suitable or dedicated model organisms for congenital hydrocephalus. Therefore, it is significant to determine the mechanism and develop special animal models of congenital hydrocephalus. Recently, zebrafish have emerged as a popular model organism in many fields, including developmental biology, genetics, and toxicology. Its genome shares high similarity with that of humans, and it has fast and low-cost reproduction. These advantages make it suitable for studying the pathogenesis and therapeutic approaches for various diseases, specifically congenital diseases. This study explored the possibility of using zebrafish as a model organism for congenital hydrocephalus. This review describes the characteristics of zebrafish and discusses specific congenital hydrocephalus models. The advantages and limitations of using zebrafish for hydrocephalus research are highlighted, and insights for further model development are provided.
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Affiliation(s)
- Kaiyue Wang
- Department of Neurosurgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, PR China
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, PR China
| | - Zhi Tang
- Department of Neurosurgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, PR China
| | - Yijian Yang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, PR China
| | - Yating Guo
- Department of Neurosurgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, PR China
| | - Zhikun Liu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, PR China
| | - Zhangjie Su
- Department of Neurosurgery, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, United Kingdom
| | - Xuejun Li
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, PR China
| | - Gelei Xiao
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, PR China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, PR China
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10
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Whitley H, Skalický P, Zazay A, Bubeníková A, Bradáč O. Volumes and velocities: Meta-analysis of PC-MRI studies in normal pressure hydrocephalus. Acta Neurochir (Wien) 2024; 166:463. [PMID: 39560792 PMCID: PMC11576626 DOI: 10.1007/s00701-024-06333-2] [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] [Received: 09/19/2024] [Accepted: 10/25/2024] [Indexed: 11/20/2024]
Abstract
PURPOSE : Phase contrast magnetic resonance imaging (PC-MRI) represents an opportunity to non-invasively investigate cerebral spinal fluid (CSF) flow in patients with idiopathic normal pressure hydrocephalus (iNPH). Studies in recent years have explored the diagnostic and prognostic value of PC-MRI derived parameters. This review aims to identify all PC-MRI studies of iNPH published since 2010, synthesise a review based on collated results, and analyse specific flow parameters identified in the selected studies. METHODS Our protocol was prospectively registered on PROSPERO [CRD42020180826]. We systematically searched four databases: Pubmed, Web of Science, Ovid, and Cochrane library to identify all eligible studies. Quality assessment was performed using a modified Newcastle-Ottawa Scale [19]. Systematic review was conducted according to Prisma guidelines. A random-effects model was used to perform meta-analysis on the available flow parameters. RESULTS Eighteen records were identified for inclusion. Five studies were eligible for meta-analysis, representing 107 iNPH patients and 82 controls. CSF flow parameters available for analysis were stroke volume and peak velocity. Both were significantly higher than controls (p = 0.0007 and p = 0.0045 respectively) according to our random-effects analysis, consistent with a model of hyper-dynamic CSF in iNPH. Our systematic review revealed average stroke volumes in iNPH ranging from 43uL to over 200uL. Peak velocity values ranged from 5.9 cm/s to 12.8 cm/s. CONCLUSION Significant increases in stroke volume and peak velocity values in iNPH patients suggest a place for PC-MRI as supplementary evidence in the diagnostic work-up of iNPH. Although shunting reduces aqueductal stroke volume and peak velocity, the ability of pre-shunt values to reliably predict treatment response remains complicated. We suggest that it may be more appropriate to consider a range of values that reflect varying probabilities of shunt success. We recommend that future studies should prioritise standardising PC-MRI protocols, and before then PC-MRI findings should be considered supportive rather than determinative.
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Affiliation(s)
- Helen Whitley
- Charing Cross Hospital, Imperial College Healthcare, London, UK.
- First Faculty of Medicine, Charles University, Nové Město, Czech Republic.
| | - Petr Skalický
- Department of Neurosurgery and Neurooncology, Military University Hospital and Charles University, U Vojenské Nemocnice 1200/1, 162 00, Prague 6, Czech Republic
- Department of Neurosurgery, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic
| | - Awista Zazay
- First Faculty of Medicine, Charles University, Nové Město, Czech Republic
| | - Adéla Bubeníková
- Department of Neurosurgery and Neurooncology, Military University Hospital and Charles University, U Vojenské Nemocnice 1200/1, 162 00, Prague 6, Czech Republic
- Department of Neurosurgery, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic
| | - Ondrej Bradáč
- Department of Neurosurgery and Neurooncology, Military University Hospital and Charles University, U Vojenské Nemocnice 1200/1, 162 00, Prague 6, Czech Republic
- Department of Neurosurgery, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic
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11
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Löbig N, Pagenkopf C, Südmeyer M, Werheid K. Reduced awareness of cognitive deficits in idiopathic normal pressure hydrocephalus and its change following lumbar puncture. Cortex 2024; 179:157-167. [PMID: 39178537 DOI: 10.1016/j.cortex.2024.07.010] [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: 02/14/2024] [Revised: 05/13/2024] [Accepted: 07/25/2024] [Indexed: 08/26/2024]
Abstract
OBJECTIVE Awareness of cognitive deficits is related to executive functions and may, therefore, be sensitive to the effects of lumbar puncture (LP) in idiopathic normal pressure hydrocephalus (iNPH). Although a reduction in awareness of cognitive deficits (RACD) has been previously described in iNPH, there is a lack of systematic, psychometrically validated reports. In this study, we investigated RACD and its LP-related changes in iNPH patients and compared them with those in clinical and healthy control groups. METHODS RACD was assessed before and after lumbar puncture (LP) in 24 patients (14 iNPH, 10 other age-associated cognitive syndromes; AACS) and compared with 23 healthy controls (HC), employing two RACD measures alongside cognitive examination. Local metacognition was measured using a visual percentile-based rating system and operationalized as the t-scaled distance between the participants' task-specific performance estimations and their objective test performance (ΔTSPE). Global metacognition, targeting broader estimates of cognitive functioning (ECF), was quantified by subtracting self- from informant-obtained sum scores on a questionnaire evaluating participants' dysexecutive problems (DEX-DS). Within-group and between-group differences in ΔTSPE and DEX-DS scores were compared non-parametrically, focusing on post-LP changes. RESULTS Averaged ΔTSPE was higher in the patient groups and mirrored the groups' lower objective test performance, while averaged DEX-DS showed no group difference. Following LP, group comparisons revealed iNPH-specific decrease in both RACD measures. CONCLUSION Our study revealed LP-related RACD changes in iNPH patients compared to those in AACS and HC participants. The results suggest a mitigation of impaired metacognitive abilities in iNPH, possibly resulting from LP-induced improvements in (local) metacognitive performance, facilitating ECF adjustment alongside a metacognitively stimulating testing procedure.
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Affiliation(s)
- Nicolas Löbig
- Department of Psychology, Humboldt-Universität zu Berlin, Germany; Clinic of Neurology, Hospital Ernst-von-Bergmann, Potsdam, Brandenburg, Germany.
| | - Claudia Pagenkopf
- Clinic of Neurology, Hospital Ernst-von-Bergmann, Potsdam, Brandenburg, Germany
| | - Martin Südmeyer
- Clinic of Neurology, Hospital Ernst-von-Bergmann, Potsdam, Brandenburg, Germany
| | - Katja Werheid
- Department of Psychology, Bielefeld University, Germany
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12
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Chang T, Huang X, Zhang X, Li J, Bai W, Wang J. A bibliometric analysis and visualization of normal pressure hydrocephalus. Front Neurol 2024; 15:1442493. [PMID: 39144708 PMCID: PMC11322097 DOI: 10.3389/fneur.2024.1442493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 07/18/2024] [Indexed: 08/16/2024] Open
Abstract
Background Normal pressure hydrocephalus (NPH) has drawn an increasing amount of attention over the last 20 years. At present, there is a shortage of intuitive analysis on the trends in development, key contributors, and research hotspots topics in the NPH field. This study aims to analyze the evolution of NPH research, evaluate publications both qualitatively and quantitatively, and summarize the current research hotspots. Methods A bibliometric analysis was conducted on data retrieved from the Web of Science Core Collection (WoSCC) database between 2003 and 2023. Quantitative assessments were conducted using bibliometric analysis tools such as VOSviewer and CiteSpace software. Results A total of 2,248 articles published between 2003 and 2023 were retrieved. During this period, the number of publications steadily increased. The United States was the largest contributor. The University of Gothenburg led among institutions conducting relevant research. Eide P. K. was the most prolific author. The Journal of Neurosurgery is the leading journal on NPH. According to the analysis of the co-occurrence of keywords and co-cited references, the primary research directions identified were pathophysiology, precise diagnosis, and individualized treatment. Recent research hotspots have mainly focused on epidemiology, the glymphatic system, and CSF biomarkers. Conclusion The comprehensive bibliometric analysis of NPH offers insights into the main research directions, highlights key countries, contributors, and journals, and identifies significant research hotspots. This information serves as a valuable reference for scholars to further study NPH.
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Affiliation(s)
- Tengwu Chang
- Department of Neurosurgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumchi, China
| | - Xiaoyuan Huang
- Department of Neurosurgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumchi, China
| | - Xu Zhang
- Xinjiang Second Medical College, Karamay, China
| | - JinYong Li
- Department of Neurosurgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumchi, China
| | - Wenju Bai
- Department of Neurosurgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumchi, China
| | - Jichao Wang
- Department of Neurosurgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumchi, China
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13
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Park E, Lee S, Jung TD, Park KS, Lee JT, Kang K. Changes in postural stability after cerebrospinal fluid tap test in patients with idiopathic normal pressure hydrocephalus. Front Neurol 2024; 15:1361538. [PMID: 38751889 PMCID: PMC11094259 DOI: 10.3389/fneur.2024.1361538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 02/12/2024] [Indexed: 05/18/2024] Open
Abstract
Introduction In patients with idiopathic normal pressure hydrocephalus (iNPH), the characteristics of balance disturbance are not as well understood as those related to gait. This study examined changes in postural stability in quiet standing after the cerebrospinal fluid tap test (CSFTT) in these patients. Furthermore, the study explored the relationship between the amount of spontaneous body sway and both gait and executive function. Materials and methods All patients diagnosed with iNPH underwent CSFTT. We evaluated their center of pressure (COP) measurements on a force plate during quiet standing, both pre- and post-CSFTT. Following the COP measurements, we calculated COP parameters using time and frequency domain analysis and assessed changes in these parameters after CSFTT. At pre-CSFTT, we assessed the Timed Up and Go (TUG) and the Frontal Assessment Battery (FAB). We investigated the relationship between COP parameters and the TUG and FAB scores at pre-CSFTT. Results A total of 72 patients with iNPH were initially enrolled, and 56 patients who responded positively to CSFTT were finally included. Post-CSFTT, significant improvements were observed in COP parameters through time domain analysis. These included the velocity of COP (vCOP), root-mean-square of COP (rmsCOP), turn index, torque, and base of support (BOS), compared to the pre-CSFTT values (p < 0.05). In the frequency domain analysis of COP parameters post-CSFTT, there was a decrease in both the peak and average of power spectral density (PSD) values in both the anteroposterior (AP) and mediolateral (ML) directions below 0.5 Hz (p < 0.05). In addition, the TUG scores showed a positive correlation with vCOP, rmsCOP, turn index, torque, BOS, and both the peak and average PSD values in the AP and ML directions below 0.5 Hz (p < 0.05). The FAB scores demonstrated a negative correlation with vCOP, rmsCOP, turns index, BOS, and both peak and average PSD values in the AP direction below 0.5 Hz (p < 0.05). Conclusion In patients with iNPH who responded to CSFTT, there was an improvement in spontaneous body sway during quiet standing after CSFTT. Increased spontaneous sway is associated with impaired gait and frontal lobe function. This may be linked to impaired cortico-cortical and cortico-subcortical circuits in patients with iNPH.
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Affiliation(s)
- Eunhee Park
- Department of Rehabilitation Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Sanghyeon Lee
- School of Computer Science and Engineering, Kyungpook National University, Daegu, Republic of Korea
| | - Tae-Du Jung
- Department of Rehabilitation Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Ki-Su Park
- Department of Neurosurgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Jong Taek Lee
- School of Computer Science and Engineering, Kyungpook National University, Daegu, Republic of Korea
| | - Kyunghun Kang
- Department of Neurology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
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14
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He Y, Wang Z, Zuo M, Zhang S, Li W, Chen S, Yuan Y, Yang Y, Liu Y. The impact of neurocognitive and psychiatric disorders on the risk of idiopathic normal pressure hydrocephalus: A bidirectional Mendelian randomization study. Brain Behav 2024; 14:e3532. [PMID: 38779749 PMCID: PMC11112403 DOI: 10.1002/brb3.3532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 04/17/2024] [Accepted: 04/17/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND Neurocognitive and psychiatric disorders have been proved that they can comorbid more often with idiopathic normal pressure hydrocephalus (iNPH) than general population. However, the potential causal association between these disorders and iNPH has not been assessed. Thus, our study aims to investigate the causal relationship between them based on a bidirectional Mendelian randomization (MR) analysis. METHODS Random effects of the inverse variance weighted (IVW) method were conducted to obtain the causal association among the neurocognitive disorders, psychiatric disorders, and iNPH. Genome-wide association studies (GWAS) of 12 neurocognitive and psychiatric disorders were downloaded via the OpenGWAS database, GWAS Catalog, and Psychiatric Genomics Consortium, whereas GWAS data of iNPH were obtained from the FinnGen consortium round 9 release, with 767 cases and 375,610 controls of European ancestry. We also conducted the sensitivity analysis in these significant causal inferences using weighted median model, Cochrane's Q test, MR-Egger regression, MR Pleiotropy Residual Sum and Outlier detect and the leave-one-out analysis. RESULTS For most of the neurocognitive and psychiatric disorders, no causal association was established between them and iNPH. We have found that iNPH (odds ratio [OR] = 1.030, 95% confidence interval [CI]: 1.011-1.048, p = .001) is associated with increased risk for schizophrenia, which failed in validation of sensitivity analysis. Notably, genetically predicted Parkinson's disease (PD) is associated with increased risk of iNPH (OR = 1.256, 95% CI: 1.045-1.511, p = .015). CONCLUSION Our study has revealed the potential causal effect in which PD associated with an increased risk of iNPH. Further study is warranted to investigate the association between PD and iNPH and the potential underlying mechanism.
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Affiliation(s)
- Yuze He
- Department of NeurosurgeryWest China HospitalSichuan UniversityChengduChina
| | - Zhihao Wang
- Department of NeurosurgeryWest China HospitalSichuan UniversityChengduChina
| | - Mingrong Zuo
- Department of Pediatric NeurosurgeryWest China Women's and Children's Hospital, Sichuan University West China Second University HospitalChengduChina
| | - Shuxin Zhang
- Department of Critical Care MedicineWest China HospitalSichuan UniversityChengduChina
| | - Wenhao Li
- Department of NeurosurgeryWest China HospitalSichuan UniversityChengduChina
| | - Siliang Chen
- Department of NeurosurgeryWest China HospitalSichuan UniversityChengduChina
| | - Yunbo Yuan
- Department of NeurosurgeryWest China HospitalSichuan UniversityChengduChina
| | - Yuan Yang
- Department of NeurosurgeryWest China HospitalSichuan UniversityChengduChina
| | - Yanhui Liu
- Department of NeurosurgeryWest China HospitalSichuan UniversityChengduChina
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15
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Colvee-Martin H, Parra JR, Gonzalez GA, Barker W, Duara R. Neuropathology, Neuroimaging, and Fluid Biomarkers in Alzheimer's Disease. Diagnostics (Basel) 2024; 14:704. [PMID: 38611617 PMCID: PMC11012058 DOI: 10.3390/diagnostics14070704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/05/2024] [Accepted: 02/17/2024] [Indexed: 04/14/2024] Open
Abstract
An improved understanding of the pathobiology of Alzheimer's disease (AD) should lead ultimately to an earlier and more accurate diagnosis of AD, providing the opportunity to intervene earlier in the disease process and to improve outcomes. The known hallmarks of Alzheimer's disease include amyloid-β plaques and neurofibrillary tau tangles. It is now clear that an imbalance between production and clearance of the amyloid beta protein and related Aβ peptides, especially Aβ42, is a very early, initiating factor in Alzheimer's disease (AD) pathogenesis, leading to aggregates of hyperphosphorylation and misfolded tau protein, inflammation, and neurodegeneration. In this article, we review how the AD diagnostic process has been transformed in recent decades by our ability to measure these various elements of the pathological cascade through the use of imaging and fluid biomarkers. The more recently developed plasma biomarkers, especially phosphorylated-tau217 (p-tau217), have utility for screening and diagnosis of the earliest stages of AD. These biomarkers can also be used to measure target engagement by disease-modifying therapies and the response to treatment.
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Affiliation(s)
- Helena Colvee-Martin
- Wien Center for Alzheimer’s Disease & Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL 33140, USA; (H.C.-M.); (W.B.)
| | - Juan Rayo Parra
- Human & Molecular Genetics, Florida International University, Miami, FL 33199, USA; (J.R.P.); (G.A.G.)
| | - Gabriel Antonio Gonzalez
- Human & Molecular Genetics, Florida International University, Miami, FL 33199, USA; (J.R.P.); (G.A.G.)
| | - Warren Barker
- Wien Center for Alzheimer’s Disease & Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL 33140, USA; (H.C.-M.); (W.B.)
| | - Ranjan Duara
- Wien Center for Alzheimer’s Disease & Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL 33140, USA; (H.C.-M.); (W.B.)
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16
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Li J, Huang N, Zhang X, Peng J, Huang Q. Positive association between omega-3/6 polyunsaturated fatty acids and idiopathic normal pressure hydrocephalus: a mendelian randomization study. Front Genet 2023; 14:1269494. [PMID: 38174046 PMCID: PMC10762850 DOI: 10.3389/fgene.2023.1269494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 12/06/2023] [Indexed: 01/05/2024] Open
Abstract
Background: Idiopathic normal pressure hydrocephalus (iNPH) is a common disease among the elderly, which brings great harm to the health of patients and imposes a huge economic burden on the healthcare system. Research has shown that it is possible to prevent iNPH through nutritional and dietary interventions. Intake of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can reduce the risk of many diseases. In this study, we aimed to explore the association between omega-3/6 PUFAs and iNPH. Methods: We conducted a two-sample Mendelian randomization (MR) study using summary data from publicly available genome-wide association studies (GWAS) to evaluate the potential impact of omega-3 and omega-6 PUFAs on the risk of iNPH in European populations. Inverse variance weighting was used as the main method for MR analysis, with Wald ratio, weighted median, MR-Egger, simple mode, and weighted mode as supplementary methods. In addition, we performed a series of instrument variable strength evaluations and sensitivity analyses to test the reliability of the study results. Finally, we also conducted a linkage disequilibrium score regression (LDSC) analysis to assess the genetic correlation and distinguish between causal associations and shared genetic variants between PUFAs and iNPH. Results: One SD increase in genetically predicted levels of total omega-3 PUFAs (OR: 0.748; 95% CI: 0.597-0.937; p = 0.012; IVW), DHA (OR: 0.709; 95% CI: 0.532-0.945; p = 0.019; IVW), ALA (OR: 0.001; 95% CI: 1.17E-06-0.423; p = 0.026; Wald ratio), and DHA (OR: 0.709; 95% CI: 0.532-0.945; p = 0.019; IVW) were associated with a reduced iNPH risk. LDSC did not reveal any significant genetic correlations. Conclusion: Higher genetically predicted levels of total omega-3 PUFAs, ALA, DHA, and DPA are associated with a reduced risk of iNPH. These findings have important implications for preventing iNPH and future nutritional guidance.
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Affiliation(s)
| | | | | | | | - Qin Huang
- Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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17
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Gędek A, Koziorowski D, Szlufik S. Assessment of factors influencing glymphatic activity and implications for clinical medicine. Front Neurol 2023; 14:1232304. [PMID: 37767530 PMCID: PMC10520725 DOI: 10.3389/fneur.2023.1232304] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 08/22/2023] [Indexed: 09/29/2023] Open
Abstract
The glymphatic system is a highly specialized fluid transport system in the central nervous system. It enables the exchange of the intercellular fluid of the brain, regulation of the movement of this fluid, clearance of unnecessary metabolic products, and, potentially, brain immunity. In this review, based on the latest scientific reports, we present the mechanism of action and function of the glymphatic system and look at the role of factors influencing its activity. Sleep habits, eating patterns, coexisting stress or hypertension, and physical activity can significantly affect glymphatic activity. Modifying them can help to change lives for the better. In the next section of the review, we discuss the connection between the glymphatic system and neurological disorders. Its association with many disease entities suggests that it plays a major role in the physiology of the whole brain, linking many pathophysiological pathways of individual diseases.
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Affiliation(s)
- Adam Gędek
- Department of Neurology, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland
- Praski Hospital, Warsaw, Poland
| | - Dariusz Koziorowski
- Department of Neurology, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland
| | - Stanisław Szlufik
- Department of Neurology, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland
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18
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Ishida T, Murayama T, Kobayashi S. Current research of idiopathic normal pressure hydrocephalus: Pathogenesis, diagnosis and treatment. World J Clin Cases 2023; 11:3706-3713. [PMID: 37383114 PMCID: PMC10294169 DOI: 10.12998/wjcc.v11.i16.3706] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/18/2023] [Accepted: 05/04/2023] [Indexed: 06/02/2023] Open
Abstract
Idiopathic normal pressure hydrocephalus (iNPH) is caused by impaired cerebrospinal fluid absorption in the elderly; it is a surgically treatable form of dementia. Gait disturbance, dementia, and urinary incontinence are the triad of signs for iNPH. In addition to these clinical findings, imaging studies show characteristic ventricular enlargement. High Evans Index and 'disproportionately enlarged subarachnoid hydrocephalus' are other well-known imaging findings of iNPH. If the tap test shows improved symptoms, shunt surgery is performed. The disease was first described by Hakim and Adams in 1965, followed by the publication of the first, second, and third editions of the guidelines in 2004, 2012, and 2020, respectively. Recent studies signal the glymphatic system and classical cerebrospinal fluid (CSF) absorption from the dural lymphatics as aetiological mechanisms of CSF retention. Research is also underway on imaging test and biomarker developments for more precise diagnosis, shunting technique options with fewer sequelae and complications, and the influence of genetics. Particularly, the newly introduced 'suspected iNPH' in the third edition of the guidelines may be useful for earlier diagnosis. However, less well-studied areas remain, such as pharmacotherapy in non-operative indications and neurological findings other than the triadic signs. This review briefly presents previous research on these and future issues.
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Affiliation(s)
- Tetsuro Ishida
- Department of Psychiatry, Japan Health Care College, Sapporo 062-0053, Hokkaido, Japan
| | - Tomonori Murayama
- Department of Psychiatry, Asahikawa Keisenkai Hospital, Asahikawa 078-8208, Hokkaido, Japan
| | - Seiju Kobayashi
- Department of Psychiatry, Shinyukai Nakae Hospital, Sapporo 001-0022, Hokkaido, Japan
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Yang F, Yang L, Fang X, Deng Y, Mao R, Yan A, Wei W. Increased Cerebrospinal Fluid Levels of Soluble Triggering Receptor Expressed on Myeloid Cells 2 and Chitinase-3-Like Protein 1 in Idiopathic Normal-Pressure Hydrocephalus. J Alzheimers Dis 2023:JAD221180. [PMID: 37182875 DOI: 10.3233/jad-221180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
BACKGROUND Neurodegenerative disease pathology is associated with neuroinflammation, but evidence on idiopathic normal pressure hydrocephalus (iNPH) remains limited and cerebrospinal fluid (CSF) biomarker profiles need to be elucidated. OBJECTIVE To investigate whether iNPH pathological mechanisms are associated with greater CSF markers of core Alzheimer's disease pathology (amyloid-β42 (Aβ 42), phosphorylated tau (P-tau)), neurodegeneration (total tau (T-tau)), and neuroinflammation (soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase-3-like protein 1 (YKL-40)). METHODS The study analyzed lumbar CSF samples from 63 patients with iNPH and 20 age-matched orthopedic surgery patients who had no preoperative gait or cognitive impairment (control group). Aβ 42, T-tau, P-tau, sTREM2, and YKL-40 in different subgroups were investigated. RESULTS CSF sTREM2 levels were significantly higher in the iNPH group than in the control group, but no significant between-group difference was noted in YKL-40. Moreover, YKL-40 levels were significantly higher in the tap test non-responders than in the tap test responders (p = 0.021). At the 1-year follow-up after shunt surgery, the CSF P-tau levels were significantly lower (p = 0.020) in those with gait improvement and the CSF sTREM2 levels were significantly lower (p = 0.041) in those with cognitive improvement. In subgroup analysis, CSF sTREM2 levels were strongly correlated with CSF YKL-40 in the iNPH group (r = 0.443, p < 0.001), especially in the tap test non-responders (r = 0.653, p = 0.002). CONCLUSION YKL-40 and sTREM2 are disease-specific markers of neuroinflammation, showing higher CSF levels in iNPH. In addition, sTREM2 is positively associated with YKL-40, indicating that interactions of glial cells play an important role in iNPH pathogenesis.
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Affiliation(s)
- Fuxia Yang
- Department of Neurology, Huadong Hospital Affiliated to Fudan University, Shanghai, China
| | - Lu Yang
- Department of Neurology, Huadong Hospital Affiliated to Fudan University, Shanghai, China
| | - Xuhao Fang
- Department of Neurosurgery, Huadong Hospital Affiliated to Fudan University, Shanghai, China
| | - Yao Deng
- Department of Neurosurgery, Huadong Hospital Affiliated to Fudan University, Shanghai, China
| | - Renling Mao
- Department of Neurosurgery, Huadong Hospital Affiliated to Fudan University, Shanghai, China
| | - Aijuan Yan
- Department of Neurology, Huadong Hospital Affiliated to Fudan University, Shanghai, China
| | - Wenshi Wei
- Department of Neurology, Huadong Hospital Affiliated to Fudan University, Shanghai, China
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Peng S, Liu J, Liang C, Yang L, Wang G. Aquaporin-4 in glymphatic system, and its implication for central nervous system disorders. Neurobiol Dis 2023; 179:106035. [PMID: 36796590 DOI: 10.1016/j.nbd.2023.106035] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 02/06/2023] [Accepted: 02/08/2023] [Indexed: 02/17/2023] Open
Abstract
The clearance function is essential for maintaining brain tissue homeostasis, and the glymphatic system is the main pathway for removing brain interstitial solutes. Aquaporin-4 (AQP4) is the most abundantly expressed aquaporin in the central nervous system (CNS) and is an integral component of the glymphatic system. In recent years, many studies have shown that AQP4 affects the morbidity and recovery process of CNS disorders through the glymphatic system, and AQP4 shows notable variability in CNS disorders and is part of the pathogenesis of these diseases. Therefore, there has been considerable interest in AQP4 as a potential and promising target for regulating and improving neurological impairment. This review aims to summarize the pathophysiological role that AQP4 plays in several CNS disorders by affecting the clearance function of the glymphatic system. The findings can contribute to a better understanding of the self-regulatory functions in CNS disorders that AQP4 were involved in and provide new therapeutic alternatives for incurable debilitating neurodegenerative disorders of CNS in the future.
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Affiliation(s)
- Shasha Peng
- 56 Xinjian southern St, Department of Pharmacology, School of Basical Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Jiachen Liu
- 172 Tongzipo Rd, Xiangya Medical College of Central South University, Changsha, Hunan 410013, China
| | - Chuntian Liang
- 56 Xinjian southern St, Department of Neurology, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Lijun Yang
- 56 Xinjian southern St, Department of Pharmacology, School of Basical Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Gaiqing Wang
- 56 Xinjian southern St, Department of Neurology, Shanxi Medical University, Taiyuan, Shanxi 030001, China; 146 JieFang forth Rd, Department of Neurology, SanYa Central Hospital (Hainan Third People's Hospital), Hainan Medical University, SanYa, Hainan 572000, China.
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21
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Cai H, Zou Y, Gao H, Huang K, Liu Y, Cheng Y, Liu Y, Zhou L, Zhou D, Chen Q. Radiological biomarkers of idiopathic normal pressure hydrocephalus: new approaches for detecting concomitant Alzheimer's disease and predicting prognosis. PSYCHORADIOLOGY 2022; 2:156-170. [PMID: 38665278 PMCID: PMC10917212 DOI: 10.1093/psyrad/kkac019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 11/18/2022] [Accepted: 11/24/2022] [Indexed: 04/28/2024]
Abstract
Idiopathic normal pressure hydrocephalus (iNPH) is a clinical syndrome characterized by cognitive decline, gait disturbance, and urinary incontinence. As iNPH often occurs in elderly individuals prone to many types of comorbidity, a differential diagnosis with other neurodegenerative diseases is crucial, especially Alzheimer's disease (AD). A growing body of published work provides evidence of radiological methods, including multimodal magnetic resonance imaging and positron emission tomography, which may help noninvasively differentiate iNPH from AD or reveal concurrent AD pathology in vivo. Imaging methods detecting morphological changes, white matter microstructural changes, cerebrospinal fluid circulation, and molecular imaging have been widely applied in iNPH patients. Here, we review radiological biomarkers using different methods in evaluating iNPH pathophysiology and differentiating or detecting concomitant AD, to noninvasively predict the possible outcome postshunt and select candidates for shunt surgery.
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Affiliation(s)
- Hanlin Cai
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Yinxi Zou
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Hui Gao
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Keru Huang
- Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Yu Liu
- Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Yuting Cheng
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Yi Liu
- Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Liangxue Zhou
- Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Dong Zhou
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Qin Chen
- Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
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22
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Verghese JP, Terry A, de Natale ER, Politis M. Research Evidence of the Role of the Glymphatic System and Its Potential Pharmacological Modulation in Neurodegenerative Diseases. J Clin Med 2022; 11:jcm11236964. [PMID: 36498538 PMCID: PMC9735716 DOI: 10.3390/jcm11236964] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/07/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
The glymphatic system is a unique pathway that utilises end-feet Aquaporin 4 (AQP4) channels within perivascular astrocytes, which is believed to cause cerebrospinal fluid (CSF) inflow into perivascular space (PVS), providing nutrients and waste disposal of the brain parenchyma. It is theorised that the bulk flow of CSF within the PVS removes waste products, soluble proteins, and products of metabolic activity, such as amyloid-β (Aβ). In the experimental model, the glymphatic system is selectively active during slow-wave sleep, and its activity is affected by both sleep dysfunction and deprivation. Dysfunction of the glymphatic system has been proposed as a potential key driver of neurodegeneration. This hypothesis is indirectly supported by the close relationship between neurodegenerative diseases and sleep alterations, frequently occurring years before the clinical diagnosis. Therefore, a detailed characterisation of the function of the glymphatic system in human physiology and disease would shed light on its early stage pathophysiology. The study of the glymphatic system is also critical to identifying means for its pharmacological modulation, which may have the potential for disease modification. This review will critically outline the primary evidence from literature about the dysfunction of the glymphatic system in neurodegeneration and discuss the rationale and current knowledge about pharmacological modulation of the glymphatic system in the animal model and its potential clinical applications in human clinical trials.
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23
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White H, Webb R, McKnight I, Legg K, Lee C, Lee PH, Spicer OS, Shim JW. TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer's disease. Front Genet 2022; 13:936151. [PMID: 36406122 PMCID: PMC9670164 DOI: 10.3389/fgene.2022.936151] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 10/17/2022] [Indexed: 01/04/2023] Open
Abstract
Symptoms of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD) are somewhat similar, and it is common to misdiagnose these two conditions. Although there are fluid markers detectable in humans with NPH and AD, determining which biomarker is optimal in representing genetic characteristics consistent throughout species is poorly understood. Here, we hypothesize that NPH can be differentiated from AD with mRNA biomarkers of unvaried proximity to telomeres. We examined human caudate nucleus tissue samples for the expression of transient receptor potential cation channel subfamily V member 4 (TRPV4) and amyloid precursor protein (APP). Using the genome data viewer, we analyzed the mutability of TRPV4 and other genes in mice, rats, and humans through matching nucleotides of six genes of interest and one house keeping gene with two factors associated with high mutation rate: 1) proximity to telomeres or 2) high adenine and thymine (A + T) content. We found that TRPV4 and microtubule associated protein tau (MAPT) mRNA were elevated in NPH. In AD, mRNA expression of TRPV4 was unaltered unlike APP and other genes. In mice, rats, and humans, the nucleotide size of TRPV4 did not vary, while in other genes, the sizes were inconsistent. Proximity to telomeres in TRPV4 was <50 Mb across species. Our analyses reveal that TRPV4 gene size and mutability are conserved across three species, suggesting that TRPV4 can be a potential link in the pathophysiology of chronic hydrocephalus in aged humans (>65 years) and laboratory rodents at comparable ages.
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Affiliation(s)
- Hunter White
- Department of Biomedical Engineering, Marshall University, Huntington, WV, United States
| | - Ryan Webb
- Department of Biomedical Engineering, Marshall University, Huntington, WV, United States
| | - Ian McKnight
- Department of Biomedical Engineering, Marshall University, Huntington, WV, United States
| | - Kaitlyn Legg
- Department of Biomedical Engineering, Marshall University, Huntington, WV, United States
| | - Chan Lee
- Department of Anesthesia, Indiana University Health Arnett Hospital, Lafayette, IN, United States
| | - Peter H.U. Lee
- Department of Cardiothoracic Surgery, Southcoast Health, Fall River, MA, United States,Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, United States
| | - Olivia Smith Spicer
- National Institute of Mental Health, National Institute of Health, Bethesda, MD, United States
| | - Joon W. Shim
- Department of Biomedical Engineering, Marshall University, Huntington, WV, United States,*Correspondence: Joon W. Shim,
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24
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Trigo D, Vitória JJ, da Cruz e Silva OAB. Novel therapeutic strategies targeting mitochondria as a gateway in neurodegeneration. Neural Regen Res 2022; 18:991-995. [PMID: 36254979 PMCID: PMC9827793 DOI: 10.4103/1673-5374.355750] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
In recent years, multiple disciplines have focused on mitochondrial biology and contributed to understanding its relevance towards adult-onset neurodegenerative disorders. These are complex dynamic organelles that have a variety of functions in ensuring cellular health and homeostasis. The plethora of mitochondrial functionalities confers them an intrinsic susceptibility to internal and external stressors (such as mutation accumulation or environmental toxins), particularly so in long-lived postmitotic cells such as neurons. Thus, it is reasonable to postulate an involvement of mitochondria in aging-associated neurological disorders, notably neurodegenerative pathologies including Alzheimer's disease and Parkinson's disease. On the other hand, biological effects resulting from neurodegeneration can in turn affect mitochondrial health and function, promoting a feedback loop further contributing to the progression of neuronal dysfunction and cellular death. This review examines state-of-the-art knowledge, focus on current research exploring mitochondrial health as a contributing factor to neuroregeneration, and the development of therapeutic approaches aimed at restoring mitochondrial homeostasis in a pathological setting.
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Affiliation(s)
- Diogo Trigo
- Neuroscience and Signalling Laboratory, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal,Correspondence to: Diogo Trigo, .
| | - José João Vitória
- Neuroscience and Signalling Laboratory, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
| | - Odete A. B. da Cruz e Silva
- Neuroscience and Signalling Laboratory, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
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25
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Pathogenesis of Fungal Infections in the Central Nervous System: Host and Pathogen Factors in Neurotropism. CURRENT FUNGAL INFECTION REPORTS 2022. [DOI: 10.1007/s12281-022-00444-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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26
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Yang Y, Wang C, Chen R, Wang Y, Tan C, Liu J, Zhang Q, Xiao G. Novel therapeutic modulators of astrocytes for hydrocephalus. Front Mol Neurosci 2022; 15:932955. [PMID: 36226316 PMCID: PMC9549203 DOI: 10.3389/fnmol.2022.932955] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 09/06/2022] [Indexed: 11/23/2022] Open
Abstract
Hydrocephalus is mainly characterized by excessive production or impaired absorption of cerebrospinal fluid that causes ventricular dilation and intracranial hypertension. Astrocytes are the key response cells to inflammation in the central nervous system. In hydrocephalus, astrocytes are activated and show dual characteristics depending on the period of development of the disease. They can suppress the disease in the early stage and may aggravate it in the late stage. More evidence suggests that therapeutics targeting astrocytes may be promising for hydrocephalus. In this review, based on previous studies, we summarize different forms of hydrocephalus-induced astrocyte reactivity and the corresponding function of these responses in hydrocephalus. We also discuss the therapeutic effects of astrocyte regulation on hydrocephalus in experimental studies.
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Affiliation(s)
- Yijian Yang
- Department of Neurosurgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Chuansen Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Rui Chen
- Department of Neurosurgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Yuchang Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Changwu Tan
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Jingping Liu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Qinghua Zhang
- Department of Neurosurgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
- The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
- *Correspondence: Qinghua Zhang,
| | - Gelei Xiao
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Gelei Xiao,
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27
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Zhao Z, He J, Chen Y, Wang Y, Wang C, Tan C, Liao J, Xiao G. The pathogenesis of idiopathic normal pressure hydrocephalus based on the understanding of AQP1 and AQP4. Front Mol Neurosci 2022; 15:952036. [PMID: 36204139 PMCID: PMC9530743 DOI: 10.3389/fnmol.2022.952036] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 08/12/2022] [Indexed: 11/21/2022] Open
Abstract
Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder without a recognized cause. Aquaporins (AQPs) are transmembrane channels that carry water through cell membranes and are critical for cerebrospinal fluid circulation and cerebral water balance. The function of AQPs in developing and maintaining hydrocephalus should be studied in greater detail as a possible diagnostic and therapeutic tool. Recent research indicates that patients with iNPH exhibited high levels of aquaporin 1 and low levels of aquaporin 4 expression, suggesting that these AQPs are essential in iNPH pathogenesis. To determine the source of iNPH and diagnose and treat it, it is necessary to examine and appreciate their function in the genesis and maintenance of hydrocephalus. The expression, function, and regulation of AQPs in iNPH are reviewed in this article, in order to provide fresh targets and suggestions for future research.
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Affiliation(s)
- Zitong Zhao
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Jian He
- Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
| | - Yibing Chen
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Yuchang Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Chuansen Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Changwu Tan
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Junbo Liao
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Gelei Xiao
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Gelei Xiao
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Ishida T, Murayama T, Kobayashi S. A case report of nonsurgical idiopathic normal pressure hydrocephalus differentiated from Alzheimer's dementia: Levetiracetam was effective in symptomatic epilepsy. PSYCHIATRY AND CLINICAL NEUROSCIENCES REPORTS 2022. [DOI: https://doi.org/10.1002/pcn5.43] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Tetsuro Ishida
- Department of Psychiatry Japan Health Care University Sapporo Japan
| | - Tomonori Murayama
- Department of Psychiatry Asahikawa Keisenkai Hospital Asahikawa Japan
| | - Seiju Kobayashi
- Department of Psychiatry Shinyukai Nakae Hospital Sapporo Japan
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29
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Ishida T, Murayama T, Kobayashi S. A case report of nonsurgical idiopathic normal pressure hydrocephalus differentiated from Alzheimer's dementia: Levetiracetam was effective in symptomatic epilepsy. PCN REPORTS : PSYCHIATRY AND CLINICAL NEUROSCIENCES 2022; 1:e43. [PMID: 38868682 PMCID: PMC11114388 DOI: 10.1002/pcn5.43] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 07/05/2022] [Accepted: 08/15/2022] [Indexed: 06/14/2024]
Abstract
Background Idiopathic normal pressure hydrocephalus (iNPH) is a common form of dementia that causes gait disturbance, cognitive impairment, and urinary incontinence. iNPH is a "treatable dementia" that can be treated with shunt surgery, but this can be ineffective in some cases and can be accompanied by complications. As a result, many patients with iNPH do not undergo surgery. However, there is insufficient evidence on effective treatments other than surgical therapy. Case Presentation A 75-year-old woman presented to our hospital with a chief complaint of cognitive decline. She showed reduced motivation and inactivity. Brain magnetic resonance imaging showed a high score on the Evans Index (maximum width between bilateral lateral ventricular anterior horns/maximum intracranial cavity in the same slice). The subarachnoid space was enlarged at and below the Sylvian fissure, and narrowed at the higher arcuate region. She was diagnosed with iNPH. However, no shunt surgery was performed; 11 months later, she had a generalized convulsive seizure with loss of consciousness. An electroencephalogram showed generalized epileptic discharges. The possibility of surgery for her iNPH was ruled out. Levetiracetam prevented seizure recurrence and cognitive functions such as spontaneity and motivation were improved. Conclusion It is often assumed that surgery is the only effective treatment for patients with iNPH. However, as in the present case, symptomatic epileptic seizures may be a factor in dementia. Even in the absence of surgical treatment, we should examine the cause of dementia in patients with iNPH and consider pharmacological treatment, including antiepileptic drugs.
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Affiliation(s)
- Tetsuro Ishida
- Department of PsychiatryJapan Health Care UniversitySapporoJapan
| | | | - Seiju Kobayashi
- Department of PsychiatryShinyukai Nakae HospitalSapporoJapan
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30
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Li G, Cao Y, Tang X, Huang J, Cai L, Zhou L. The meningeal lymphatic vessels and the glymphatic system: Potential therapeutic targets in neurological disorders. J Cereb Blood Flow Metab 2022; 42:1364-1382. [PMID: 35484910 PMCID: PMC9274866 DOI: 10.1177/0271678x221098145] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 04/03/2022] [Accepted: 04/14/2022] [Indexed: 02/05/2023]
Abstract
The recent discovery of the meningeal lymphatic vessels (mLVs) and glymphatic pathways has challenged the long-lasting dogma that the central nervous system (CNS) lacks a lymphatic system and therefore does not interact with peripheral immunity. This discovery has reshaped our understanding of mechanisms underlying CNS drainage. Under normal conditions, a close connection between mLVs and the glymphatic system enables metabolic waste removal, immune cell trafficking, and CNS immune surveillance. Dysfunction of the glymphatic-mLV system can lead to toxic protein accumulation in the brain, and it contributes to the development of a series of neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. The identification of precise cerebral transport routes is based mainly on indirect, invasive imaging of animals, and the results cannot always be applied to humans. Here we review the functions of the glymphatic-mLV system and evidence for its involvement in some CNS diseases. We focus on emerging noninvasive imaging techniques to evaluate the human glymphatic-mLV system and their potential for preclinical diagnosis and prevention of neurodegenerative diseases. Potential strategies that target the glymphatic-mLV system in order to treat and prevent neurological disorders are also discussed.
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Affiliation(s)
- Gaowei Li
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Cao
- Department of Neurosurgery, Chengdu Second People's hospital, Chengdu, China
| | - Xin Tang
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jianhan Huang
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Linjun Cai
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Liangxue Zhou
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China
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31
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Abstract
Posthemorrhagic hydrocephalus of prematurity (PHHP) remains a vexing problem for patients, their families, and the healthcare system. The complexity of the pathogenesis of PHHP also presents a unique challenge within the fields of neonatology, neurology and neurosurgery. Here we focus on pathogenesis of PHHP and its impact on the development of CSF dynamics including choroid plexus, ependymal motile cilia and glymphatic system. PHHP is contrasted with infantile hydrocephalus from other etiologies, and with other types of posthemorrhagic hydrocephalus that occur later in life. The important concept that distinguishing ventricular volume from brain health and function is highlighted. The influence of the pathogenesis of PHHP on current interventions is reviewed, with particular emphasis on how the unique pathogenesis of PHHP contributes to the high rate of failure of current existing interventions. Finally, we discuss emerging interventions. A thorough understanding of the pathogenesis of PHHP is essential to developing effective non-surgical therapeutics to prevent the transformation from severe IVH to PHHP.
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Affiliation(s)
- Shenandoah Robinson
- Neonatal Intensive Care Nursery, John's Hopkins Children's Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States; Division of Pediatric Neurosurgery, Departments of Neurosurgery, Neurology and Pediatrics, Johns Hopkins University School of Medicine, Maryland, United States.
| | - Lauren L Jantzie
- Neonatal Intensive Care Nursery, John's Hopkins Children's Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States; Division of Neonatology, Departments of Pediatrics, Neurology and Neurosurgery, Johns Hopkins University School of Medicine, Maryland, United States; Kennedy Krieger Institute, Maryland, United States
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32
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Ji W, Tang Z, Chen Y, Wang C, Tan C, Liao J, Tong L, Xiao G. Ependymal Cilia: Physiology and Role in Hydrocephalus. Front Mol Neurosci 2022; 15:927479. [PMID: 35903173 PMCID: PMC9315228 DOI: 10.3389/fnmol.2022.927479] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 06/20/2022] [Indexed: 01/10/2023] Open
Abstract
Cerebrospinal fluid (CSF), a colorless liquid that generally circulates from the lateral ventricles to the third and fourth ventricles, provides essential nutrients for brain homeostasis and growth factors during development. As evidenced by an increasing corpus of research, CSF serves a range of important functions. While it is considered that decreased CSF flow is associated to the development of hydrocephalus, it has recently been postulated that motile cilia, which line the apical surfaces of ependymal cells (ECs), play a role in stimulating CSF circulation by cilia beating. Ependymal cilia protrude from ECs, and their synchronous pulsing transports CSF from the lateral ventricle to the third and fourth ventricles, and then to the subarachnoid cavity for absorption. As a result, we postulated that malfunctioning ependymal cilia could disrupt normal CSF flow, raising the risk of hydrocephalus. This review aims to demonstrate the physiological functions of ependymal cilia, as well as how cilia immobility or disorientation causes problems. We also conclude conceivable ways of treatment of hydrocephalus currently for clinical application and provide theoretical support for regimen improvements by investigating the relationship between ependymal cilia and hydrocephalus development.
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Affiliation(s)
- Weiye Ji
- Department of Neurosurgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Zhi Tang
- Department of Neurosurgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Yibing Chen
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Chuansen Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Changwu Tan
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Junbo Liao
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Lei Tong
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Gelei Xiao
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
- Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Gelei Xiao,
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Targeting choroid plexus epithelium as a novel therapeutic strategy for hydrocephalus. J Neuroinflammation 2022; 19:156. [PMID: 35715859 PMCID: PMC9205094 DOI: 10.1186/s12974-022-02500-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 06/01/2022] [Indexed: 11/25/2022] Open
Abstract
The choroid plexus is a tissue located in the lateral ventricles of the brain and is composed mainly of choroid plexus epithelium cells. The main function is currently thought to be the secretion of cerebrospinal fluid and the regulation of its pH, and more functions are gradually being demonstrated. Assistance in the removal of metabolic waste and participation in the apoptotic pathway are also the functions of choroid plexus. Besides, it helps to repair the brain by regulating the secretion of neuropeptides and the delivery of drugs. It is involved in the immune response to assist in the clearance of infections in the central nervous system. It is now believed that the choroid plexus is in an inflammatory state after damage to the brain. This state, along with changes in the cilia, is thought to be an abnormal physiological state of the choroid plexus, which in turn leads to abnormal conditions in cerebrospinal fluid and triggers hydrocephalus. This review describes the pathophysiological mechanism of hydrocephalus following choroid plexus epithelium cell abnormalities based on the normal physiological functions of choroid plexus epithelium cells, and analyzes the attempts and future developments of using choroid plexus epithelium cells as a therapeutic target for hydrocephalus.
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Atchley TJ, Vukic B, Vukic M, Walters BC. Review of Cerebrospinal Fluid Physiology and Dynamics: A Call for Medical Education Reform. Neurosurgery 2022; 91:1-7. [PMID: 35522666 DOI: 10.1227/neu.0000000000002000] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 12/05/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The flow of cerebrospinal fluid (CSF) has been described as a unidirectional system with the choroid plexus serving as the primary secretor of CSF and the arachnoid granulations as primary reabsorption site. This theory of neurosurgical forefathers has been universally adopted and taught as dogma. Many neuroscientists have found difficulty reconciling this theory with common pathologies, and recent studies have found that this "classic" hypothesis may not represent the full picture. OBJECTIVE To review modern CSF dynamic theories and to call for medical education reform. METHODS We reviewed the literature from January 1990 to December 2020. We searched the PubMed database using key terms "cerebrospinal fluid circulation," "cerebrospinal fluid dynamics," "cerebrospinal fluid physiology," "glymphatic system," and "glymphatic pathway." We selected articles with a primary aim to discuss either CSF dynamics and/or the glymphatic system. RESULTS The Bulat-Klarica-Orešković hypothesis purports that CSF is secreted and reabsorbed throughout the craniospinal axis. CSF demonstrates similar physiology to that of water elsewhere in the body. CSF "circulates" throughout the subarachnoid space in a pulsatile to-and-fro fashion. Osmolarity plays a critical role in CSF dynamics. Aquaporin-4 and the glymphatic system contribute to CSF volume and flow by establishing osmolarity gradients and facilitating CSF movement. Multiple studies demonstrate that the choroid plexus does not play any significant role in CSF circulation. CONCLUSION We have highlighted major studies to illustrate modern principles of CSF dynamics. Despite these, the medical education system has been slow to reform curricula and update learning resources.
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Affiliation(s)
- Travis J Atchley
- Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Barbara Vukic
- School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Miroslav Vukic
- Department of Neurosurgery, Sisters of Mercy University Hospital, Zagreb, Croatia
| | - Beverly C Walters
- Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA
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Said HM, Kaya D, Yavuz I, Dost FS, Altun ZS, Isik AT. A Comparison of Cerebrospinal Fluid Beta-Amyloid and Tau in Idiopathic Normal Pressure Hydrocephalus and Neurodegenerative Dementias. Clin Interv Aging 2022; 17:467-477. [PMID: 35431542 PMCID: PMC9012339 DOI: 10.2147/cia.s360736] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 04/02/2022] [Indexed: 01/17/2023] Open
Abstract
PURPOSE Idiopathic normal pressure hydrocephalus (iNPH) is the leading reversible cause of cognitive impairment and gait disturbance that has similar clinical manifestations and accompanies to major neurodegenerative disorders in older adults. We aimed to investigate whether cerebrospinal fluid (CSF) biomarker for Alzheimer's disease (AD) may be useful in the differential diagnosis of iNPH. PATIENTS AND METHODS Amyloid-beta (Aß) 42 and 40, total tau (t-tau), phosphorylated tau (p-tau) were measured via ELISA in 192 consecutive CSF samples of patients with iNPH (n=80), AD (n=48), frontotemporal dementia (FTD) (n=34), Lewy body diseases (LBDs) (n=30) consisting of Parkinson's disease dementia and dementia with Lewy bodies. RESULTS The mean age of the study population was 75.6±7.7 years, and 54.2% were female. CSF Aβ42 levels were significantly higher, and p-tau and t-tau levels were lower in iNPH patients than in those with AD and LBDs patients. Additionally, iNPH patients had significantly higher levels of t-tau than those with FTD. Age and sex-adjusted multi-nominal regression analysis revealed that the odds of having AD relative to iNPH decreased by 37% when the Aβ42 level increased by one standard deviation (SD), and the odds of having LBDs relative to iNPH decreased by 47%. The odds of having LBDs relative to iNPH increased 76% when the p-tau level increased 1SD. It is 2.5 times more likely for a patient to have LBD relative to NPH and 2.1 times more likely to have AD relative to iNPH when the t-tau value increased 1SD. CONCLUSION Our results suggest that levels of CSF Aβ42, p-tau, and t-tau, in particularly decreased t-tau, are of potential value in differentiating iNPH from LBDs and also confirm previous studies reporting t-tau level is lower and Aβ42 level is higher in iNPH than in AD.
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Affiliation(s)
- Harun Muayad Said
- Department of Molecular Medicine, Graduate School of Health Sciences, Dokuz Eylul University, Izmir, Turkey
| | - Derya Kaya
- Unit for Brain Aging and Dementia, Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
- Geriatric Science Association, Izmir, Turkey
| | - Idil Yavuz
- Department of Statistics, Dokuz Eylul University, Faculty of Science, Izmir, Turkey
| | - Fatma Sena Dost
- Unit for Brain Aging and Dementia, Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
- Geriatric Science Association, Izmir, Turkey
| | - Zekiye Sultan Altun
- Department of Basic Oncology, Oncology Institute, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Ahmet Turan Isik
- Unit for Brain Aging and Dementia, Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
- Geriatric Science Association, Izmir, Turkey
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Interplay between vascular hemodynamics and the glymphatic system in the pathogenesis of idiopathic normal pressure hydrocephalus, exploring novel neuroimaging diagnostics. Neurosurg Rev 2021; 45:1255-1261. [PMID: 34773535 DOI: 10.1007/s10143-021-01690-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 10/15/2021] [Accepted: 11/04/2021] [Indexed: 10/19/2022]
Abstract
As the aging population continues to grow, so will the incidence of age-related conditions, including idiopathic normal pressure hydrocephalus (iNPH). The pathogenesis of iNPH remains elusive, and this is due in part to the poor characterization of cerebral spinal fluid (CSF) dynamics within the brain. Advancements in technology and imaging techniques have enabled new breakthroughs in understanding CSF physiology, and therefore iNPH pathogenesis. This includes understanding the hemodynamic and microvascular components involved in CSF influx and flow. Namely, the glymphatic system appears to be the great mediator, facilitating perivascular CSF flow via astrocytic aquaporin channels located along the endothelium of the pial vasculature. The interplay between glymphatics and both arterial pulsatilty and venous compliance has also been recently demonstrated. It appears then that CSF flow, and therefore glymphatic function, are highly dependent on cardiocirculatory and vascular factors. Impairment in any one component, whether it be related to arterial pulsatility, microvascular changes, reduced venous drainage, or astrogliosis, contributes greatly to iNPH, although it is likely a combination thereof. The strong interplay between vascular hemodynamics and CSF flow suggests perfusion imaging and cerebral blood flow quantification may be a useful diagnostic tool in characterizing iNPH. In addition, studies detecting glymphatic flow with magnetic resonance imaging have also emerged. These imaging tools may serve to both diagnose iNPH and help delineate it from other similarly presenting disease processes. With a better understanding of the vascular and glymphatic factors related to iNPH pathogenesis, physicians are better able to select the best candidates for treatment.
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Hiraldo-González L, Trillo-Contreras JL, García-Miranda P, Pineda-Sánchez R, Ramírez-Lorca R, Rodrigo-Herrero S, Blanco MO, Oliver M, Bernal M, Franco-Macías E, Villadiego J, Echevarría M. Evaluation of aquaporins in the cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus. PLoS One 2021; 16:e0258165. [PMID: 34597351 PMCID: PMC8486078 DOI: 10.1371/journal.pone.0258165] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 09/21/2021] [Indexed: 11/18/2022] Open
Abstract
Brain aquaporin 1 (AQP1) and AQP4 are involved in cerebrospinal fluid (CSF) homeostasis and might participate in the origin of hydrocephalus. Studies have shown alterations of perivascular AQP4 expression in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD). Due to the overlapping of clinical signs between iNPH and certain neurological conditions, mainly AD, specific biomarkers might improve the diagnostic accuracy for iNPH. The goal of the present study was to analyze and quantify the presence of AQP1 and AQP4 in the CSF of patients with iNPH and AD to determine whether these proteins can be used as biomarkers of iNPH. We examined AQP1 and AQP4 protein levels in the CSF of 179 participants (88 women) classified into 5 groups: possible iNPH (81 participants), hydrocephalus associated with other neurological disorders (13 participants), AD (41 participants), non-AD dementia (32 participants) and healthy controls (12 participants). We recorded each participant's demographic and clinical variables and indicated, when available in the clinical history, the record of cardiovascular and respiratory complications. An ELISA showed virtually no AQP content in the CSF. Information on the vascular risk factors (available for 61 patients) confirmed some type of vascular risk factor in 86% of the patients with possible iNPH and 58% of the patients with AD. In conclusion, the ELISA analysis showed insufficient sensitivity to detect the presence of AQP1 and AQP4 in CSF, ruling out the possible use of these proteins as biomarkers for diagnosing iNPH.
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Affiliation(s)
- Laura Hiraldo-González
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, (HUVR)/Spanish National Research Council (CSIC)/University of Seville, Seville, Spain
| | - José Luis Trillo-Contreras
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, (HUVR)/Spanish National Research Council (CSIC)/University of Seville, Seville, Spain
| | - Pablo García-Miranda
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, (HUVR)/Spanish National Research Council (CSIC)/University of Seville, Seville, Spain
| | - Rocío Pineda-Sánchez
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, (HUVR)/Spanish National Research Council (CSIC)/University of Seville, Seville, Spain
| | - Reposo Ramírez-Lorca
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, (HUVR)/Spanish National Research Council (CSIC)/University of Seville, Seville, Spain
- Department of Physiology and Biophysics, University of Seville, Seville, Spain
| | - Silvia Rodrigo-Herrero
- Clinical Neuroscience Management Unit, Neurology Service, University Hospital Virgen del Rocío, Seville, Spain
| | - Magdalena Olivares Blanco
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, (HUVR)/Spanish National Research Council (CSIC)/University of Seville, Seville, Spain
- Clinical Neuroscience Management Unit, Neurosurgery Service, University Hospital Virgen del Rocío, Seville, Spain
| | - María Oliver
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, (HUVR)/Spanish National Research Council (CSIC)/University of Seville, Seville, Spain
- Clinical Neuroscience Management Unit, Neurosurgery Service, University Hospital Virgen del Rocío, Seville, Spain
| | - Maria Bernal
- Clinical Neuroscience Management Unit, Neurology Service, University Hospital Virgen del Rocío, Seville, Spain
| | - Emilio Franco-Macías
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, (HUVR)/Spanish National Research Council (CSIC)/University of Seville, Seville, Spain
- Clinical Neuroscience Management Unit, Neurology Service, University Hospital Virgen del Rocío, Seville, Spain
| | - Javier Villadiego
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, (HUVR)/Spanish National Research Council (CSIC)/University of Seville, Seville, Spain
- Department of Physiology and Biophysics, University of Seville, Seville, Spain
- Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Seville, Spain
| | - Miriam Echevarría
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, (HUVR)/Spanish National Research Council (CSIC)/University of Seville, Seville, Spain
- Department of Physiology and Biophysics, University of Seville, Seville, Spain
- * E-mail:
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Youn J, Todisco M, Zappia M, Pacchetti C, Fasano A. Parkinsonism and cerebrospinal fluid disorders. J Neurol Sci 2021; 433:120019. [PMID: 34674853 DOI: 10.1016/j.jns.2021.120019] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 08/25/2021] [Accepted: 09/29/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Although various motor manifestations can be seen in patients with cerebrospinal fluid (CSF) disorders, such as hydrocephalus or intracranial hypotension, the clinical presentation with parkinsonism is not clearly elucidated. METHODS We searched the literature for studies describing the occurrence of parkinsonism in subjects with normal pressure hydrocephalus (NPH), obstructive hydrocephalus, and intracranial hypotension. We analyzed the clinical presentation (particularly with respect to bradykinesia, rigidity, rest tremor, and gait disturbance/postural instability) as well as the response to treatment. RESULTS Parkinsonism was most commonly reported in NPH patients. Although gait disturbance/postural instability is a well-known motor symptom of NPH, other cardinal signs include upper limb involvement or asymmetric presentation. As for obstructive hydrocephalus, parkinsonism was mainly observed in subjects with aqueductal stenosis and more often after shunt surgery. Patients with NPH or obstructive hydrocephalus rarely improved with levodopa therapy, while most subjects only improved with shunt surgery. Although the mechanism is still controversial, a functional involvement of nigrostriatal pathway has been hypothesized based on imaging studies and case reports. Brain imaging is also helpful for atypical cases of intracranial hypotension presenting with parkinsonism. Parkinsonism improved after treatment in such cases as well. CONCLUSIONS Studies exploring the relationship between CSF disorders and parkinsonism are mainly descriptive and their quality is generally poor. However, considering that these disorders can be treated, clinicians' awareness of the differential diagnosis is important and future studies better exploring the underlying pathophysiological mechanisms are warranted. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.
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Affiliation(s)
- Jinyoung Youn
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea; Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada
| | - Massimiliano Todisco
- Parkinson's Disease and Movement Disorders Unit, IRCCS Mondino Foundation, Pavia, Italy; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| | - Mario Zappia
- Department of Medical, Surgical Sciences and Advanced Technologies 'G.F. Ingrassia', University of Catania, Catania, Italy
| | - Claudio Pacchetti
- Parkinson's Disease and Movement Disorders Unit, IRCCS Mondino Foundation, Pavia, Italy
| | - Alfonso Fasano
- Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada; Krembil Brain Institute, Toronto, Ontario, Canada.
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39
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Wang C, Wang X, Tan C, Wang Y, Tang Z, Zhang Z, Liu J, Xiao G. Novel therapeutics for hydrocephalus: Insights from animal models. CNS Neurosci Ther 2021; 27:1012-1022. [PMID: 34151523 PMCID: PMC8339528 DOI: 10.1111/cns.13695] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 05/09/2021] [Accepted: 06/02/2021] [Indexed: 02/06/2023] Open
Abstract
Hydrocephalus is a cerebrospinal fluid physiological disorder that causes ventricular dilation with normal or high intracranial pressure. The current regular treatment for hydrocephalus is cerebrospinal fluid shunting, which is frequently related to failure and complications. Meanwhile, considering that the current nonsurgical treatments of hydrocephalus can only relieve the symptoms but cannot eliminate this complication caused by primary brain injuries, the exploration of more effective therapies has become the focus for many researchers. In this article, the current research status and progress of nonsurgical treatment in animal models of hydrocephalus are reviewed to provide new orientations for animal research and clinical practice.
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Affiliation(s)
- Chuansen Wang
- Department of NeurosurgeryXiangya HospitalCentral South UniversityChangshaHunanChina
- Diagnosis and Treatment Center for HydrocephalusXiangya HospitalCentral South UniversityChangshaHunanChina
- National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunanChina
| | - Xiaoqiang Wang
- Department of Pediatric NeurosurgeryXinhua HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Changwu Tan
- Department of NeurosurgeryXiangya HospitalCentral South UniversityChangshaHunanChina
- Diagnosis and Treatment Center for HydrocephalusXiangya HospitalCentral South UniversityChangshaHunanChina
- National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunanChina
| | - Yuchang Wang
- Department of NeurosurgeryXiangya HospitalCentral South UniversityChangshaHunanChina
- Diagnosis and Treatment Center for HydrocephalusXiangya HospitalCentral South UniversityChangshaHunanChina
- National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunanChina
| | - Zhi Tang
- Department of NeurosurgeryHunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaHunanChina
| | - Zhiping Zhang
- Department of NeurosurgeryXiangya HospitalCentral South UniversityChangshaHunanChina
- Diagnosis and Treatment Center for HydrocephalusXiangya HospitalCentral South UniversityChangshaHunanChina
- National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunanChina
| | - Jingping Liu
- Department of NeurosurgeryXiangya HospitalCentral South UniversityChangshaHunanChina
- Diagnosis and Treatment Center for HydrocephalusXiangya HospitalCentral South UniversityChangshaHunanChina
- National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunanChina
| | - Gelei Xiao
- Department of NeurosurgeryXiangya HospitalCentral South UniversityChangshaHunanChina
- Diagnosis and Treatment Center for HydrocephalusXiangya HospitalCentral South UniversityChangshaHunanChina
- National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunanChina
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40
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Leary OP, Svokos KA, Klinge PM. Reappraisal of Pediatric Normal-Pressure Hydrocephalus. J Clin Med 2021; 10:jcm10092026. [PMID: 34065105 PMCID: PMC8125971 DOI: 10.3390/jcm10092026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/04/2021] [Accepted: 05/06/2021] [Indexed: 12/13/2022] Open
Abstract
While normal-pressure hydrocephalus (NPH) is most commonly diagnosed in older adulthood, a significant body of literature has accumulated over half a century documenting the clinical phenomenon of an NPH-like syndrome in pediatric patients. As in adult NPH, it is likely that pediatric NPH occurs due to a heterogeneous array of developmental, structural, and neurodegenerative pathologies, ultimately resulting in aberrant cerebrospinal fluid (CSF) flow and distribution within and around the brain. In this review, we aimed to systematically survey the existing clinical evidence supporting the existence of a pediatric form of NPH, dating back to the original recognition of NPH as a clinically significant subtype of communicating hydrocephalus. Leveraging emergent trends from the old and more recent published literature, we then present a modern characterization of pediatric NPH as a disorder firmly within the same disease spectrum as adult NPH, likely with overlapping etiology and pathophysiological mechanisms. Exemplary cases consistent with the diagnosis of pediatric NPH selected from the senior author’s neurosurgical practice are then presented alongside the systematic review to aid in discussion of the typical clinical and radiographic manifestations of pediatric NPH. Common co-morbidities and modern surgical treatment options are also described.
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Affiliation(s)
- Owen P. Leary
- Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA; (O.P.L.); (K.A.S.)
| | - Konstantina A. Svokos
- Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA; (O.P.L.); (K.A.S.)
| | - Petra M. Klinge
- Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA; (O.P.L.); (K.A.S.)
- Rhode Island Hospital, APC Building 6th Floor, 593 Eddy Street, Providence, RI 02903, USA
- Correspondence:
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