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The glymphatic system can remove metabolic wastes from the brain, which plays a significant role in maintaining the homeostasis of the central nervous system. It is an important basis for advanced cognitive functions such as learning and memory. Studies have analyzed the function of glymphatic system by diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) recently. Compared with other invasive examinations that require fluorescent tracer technique or the injection of contrast agents, DTI-ALPS can evaluate the hydromechanics of the glymphatic system via quantifying the diffusion rate of water molecules in different directions, which turns out to be a non-invasive in vivo neuroimaging method. The ALPS-index calculated by the DTI-ALPS method is significantly correlated with the cognitive function in diseases of central nervous system and other system and can reflect the dynamic changes of diseases. In general, ALPS-index is expected to become a novel neuroimaging biomarker for predicting prognosis and clinical effects.
Subject(s)
Glymphatic System/diagnostic imaging , Diffusion Tensor Imaging , Brain/diagnostic imaging , Central Nervous System , CognitionABSTRACT
The concept of the glial-vascular unit (GVU) was raised recently to emphasize the close associations between brain cells and cerebral vessels, and their coordinated reactions to diverse neurological insults from a "glio-centric" view. GVU is a multicellular structure composed of glial cells, perivascular cells, and perivascular space. Each component is closely linked, collectively forming the GVU. The central roles of glial and perivascular cells and their multi-level interconnections in the GVU under normal conditions and in central nervous system (CNS) disorders have not been elucidated in detail. Here, we comprehensively review the intensive interactions between glial cells and perivascular cells in the niche of perivascular space, which take part in the modulation of cerebral blood flow and angiogenesis, formation of the blood-brain barrier, and clearance of neurotoxic wastes. Next, we discuss dysfunctions of the GVU in various neurological diseases, including ischemic stroke, spinal cord injury, Alzheimer's disease, and major depression disorder. In addition, we highlight the possible therapies targeting the GVU, which may have potential clinical applications.
Subject(s)
Humans , Neuroglia , Nervous System Diseases , Blood-Brain Barrier , Alzheimer Disease , Glymphatic SystemABSTRACT
Objective:To investigate the correlation between basal ganglia (BG) enlarged perivascular space (EPVS; BG-EPVS) and cognitive and motor longitudinal changes in patients with newly diagnosed Parkinson′s disease and its different motor subtypes [tremor dominant (TD), postural instability and gait disorder (PIGD)].Methods:A total of 131 Parkinson′s disease patients from the Parkinson Progression Markers Initiative (PPMI) database were screened and their clinical data were collected at baseline, 1 year and 2 years of follow-up. The number of EPVS in different brain regions was assessed on axial T 2-weighted images by cranial imaging data, and they were divided into two groups according to the degree of EPVS: BG-EPVS- and BG-EPVS+. Parkinson′s disease patients were divided into TD and PIGD groups by Movement Disorder Society Unified Parkinson′s Disease Rating Scale (MDS-UPDRS) score, and the number and clinical data of EPVS were compared between the two groups, and the correlation between the number and degree of BG-EPVS at baseline and longitudinal changes in clinical outcome measures of Parkinson′s disease and its different motor subtypes (TD, PIGD) was analyzed. Results:BG-EPVS was positively correlated with age ( r=0.32, P<0.01), Hoehn & Yahr stage ( r=0.21, P<0.05), serum neurofilament light chain ( r=0.18, P<0.05) and Epworth Sleepiness Scale score ( r=0.20, P<0.05) in all Parkinson′s disease patients. At baseline and 2 years, the number of BG-EPVS was more in the PIGD group than in the TD group (11.0±4.2 vs 9.0±3.8, t=2.18, P=0.03; 16.3±6.7 vs 12.6±4.6 , t=2.71 , P=0.007;after correction).At baseline, more BG-EPVS in patients with Parkinson′s disease and its motor subtypes (TD, PIGD) was significantly associated with baseline motor outcomes ( β=0.66, P=0.01; β=0.64, P=0.008; β=0.91, P=0.009), but not with cognitive outcomes. By linear mixed effects model analysis, BG-EPVS numbers and moderate to severe BG-EPVS were positively correlated with motor outcomes over time in patients with Parkinson′s disease and its motor subtypes (TD, PIGD) ( β=0.51, P=0.008; β=0.59, P=0.025; β=0.80, P=0.038). After dividing BG-EPVS in Parkinson′s disease patients into different degrees, moderate to severe BG-EPVS was positively correlated with motor outcomes over time ( β=3.30, P=0.031). Conclusion:In this longitudinal study, bigger baseline BG-EPVS numbers were found to be positively associated with longitudinal changes in dyskinesia severity in Parkinson′s disease patients, not with cognitive changes, and be able to predict decline in motor function over a 2-year follow-up period.
ABSTRACT
Parkinson′s disease is a degenerative disease of the central nervous system with abnormal protein deposition in the brain as the main pathological changes. The onset of Parkinson′s disease is related to abnormal deposition protein removal disorders, and the relevant mechanisms are still unclear. The glymphatic system is a metabolic waste and abnormal protein deposition removal system in the brain. In recent years, studies have shown that the changes of aquaporin 4, perivascular space and dural lymphatic vessels in Parkinson′s disease are closely related to the level of relevant pathological proteins in cerebrospinal fluid, leading to the occurrence and development of Parkinson′s disease. The researches on structure and biomarkers of the glymphatic system in Parkinson′s disease in recent years are reviewed in this article.
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Lymphatic system is the transportation way of cerebrospinal fluid and brain interstitial fluid exchange. And this system is a central nervous drainage system which plays an important role in drainaging and discharging of metabolic waste in the brain. The function of this system can be evaluated indirectly by the perivascular space on magnetic resonance imaging. Parkinson′s disease is a common neurodegenerative disorder. It may be helpful to control the progression of the disease if the changes of perivascular space can be dynamically observed in the early or even prodromal stage of the disease. This article reviews the relationship between lymphatic system disfunction and early stage of Parkinson′s disease.
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Objective:To study the effect mechanism of Guilu Erxian gum on Alzheimer's disease （AD） from the perspective of regulating perivascular space （PVS），and to explore the scientific connotation of "essence generating marrow". Method:The 80 patients with AD diagnosed by western medicine and kidney deficiency and marrow empty syndrome diagnosed by traditional Chinese medicine were randomly divided into two groups，with 40 cases in each group. Both groups of patients were orally administered with cholinesterase inhibitor Alison，one tablet （5 mg） each time before sleep at night. On this basis，the control group additionally received placebo，while the treatment group was additionally treated with Guilu Erxian gum for 60 days. The Mini-Mental State Examination scale （MMSE）， Wechsler Memory Scale and Activity of Daily Living Scale （ADL） were used before treatment （0 d），as well as 31 d and 61 d after treatment. The number and diameter of PVS in midbrain，basal ganglia，deep insular white matter and semiovale center were counted and their diameters were measured with use of nuclear magnetic resonance imaging （MRI） for head. In addition，the curative effect was evaluated according to MMSE scores on 61 d. Result:There was no significant difference between the two groups 31 d. On 61 d，MMSE and WMS scores increased，while ADL scores decreased as compared with the conditions on 0 d（<italic>P</italic><0.01），and there were significant differences in the three indexes and clinical effective rate between two groups （<italic>P</italic><0.05，<italic>P</italic><0.01） . In addition，there was no significant difference in the number of PVS as compared with the number before treatment and in the comparison between the two groups after treatment，but there was a significant difference in the diameter of PVS（<italic>P</italic><0.01）. Conclusion:Guilu Erxian gum is effective in the treatment of AD，and it can improve the PVS diameter in patients，which may be related to the mechanism of "essence generating marrow ".
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The Virchow-Robin spaces (VRSs), which are often incidentally observed in modern structural neuroimaging examinations, are small cystic cavities that usually surround the small arteries and arterioles at the level of basal ganglia, the anterior perforated substance and the thalamic-mesencephalic junction. Typically, they have similar physicochemical characteristics to cerebral spinal fluid (CSF) and there is no contrast enhancement on brain CT andMRI images. Its real meaning is unknown, although some contemporary studies have suggested that it might be related to certain traumatic brain injury or several other central nervous system (CNS) disorders, as degenerative diseases. Occasionally, some wide and atypical VRS may be mistaken for primary cystic brain tumors, especially in the context of large and symptomatic lesions, multiple clustered cysts, cortical lesions and if there is adjacent reactive gliosis. The present paper reports four patients who were affected by atypical VRS mimicking brain tumors that required imaging follow-up or even a biopsy to confirm the diagnosis or to indicate the correct approach. Although it is not so unusual, one of them occurred concomitantly and adjacent to a diffuse glioma (co-deleted 1p19q, WHO-GII).
Subject(s)
Humans , Male , Female , Child , Adult , Middle Aged , Dilatation, Pathologic , Glymphatic System/abnormalities , Glymphatic System/surgery , Glymphatic System/diagnostic imaging , Central Nervous System Neoplasms/diagnostic imaging , Glymphatic System/pathologyABSTRACT
Objective To investigate the risk factors of perivascular space change after brain tumor surgery.Methods According to the occurrence of postoperative perivascular space change,80 cases of glioma patients were divided into perivascular space and reconstruction group(observation group,n=38)and normal postoperative perivascular space group(control group,n=42).Compared the general data,sur-gery,tumor related indicators and postoperative complications of the two groups,and analyzed the influencing factors of the perivascular space changes after brain tumor surgery.Results In the observation group,the operation time of the patients was(95.38 ±9.21)min,which was significantly longer than(75.36 ±9.05)min in the control group.The intraoperative blood loss was(290.32 ±45.47)mL in the observation group,which was significantly more than(247.19 ±36.75)mL in the control group,and the difference was statistically significant (P<0.05).The tumor site located in the left hemisphere,tumor volume more than 40.0 cm3,high grade glioma,and proportion of patients with postoperative complications in the observation group were all higher than those of the control group,and the difference between the two groups was statistically significant(P<0.05).Multivariate Logistic regression analysis showed that age,tumor location,tumor volume,patho-logical grade and complications were significantly correlated with the changes of perivascular space after surgery(P<0.05).Conclusion Advanced age,tumor located in the left side of the brain,large tumor volume,severe pathology,postoperative epilepsy,chronic intracranial hy-pertension and other complications were the risk factors affecting the changes of perivascular space in patients with glioma.
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Objective To analyze the distribution of Virchow-Robin spaces (VRS) in migraine by MRI,and to study the effects of the duration of the disease,the attack frequency and the migraine with or without aura on the number of VRS in order to provide imaging support for migraine diagnosis.Methods Fifty migraine patients were enrolled as migraine group and 50 healthy people as control group during January 2013 to December 2016 from Department of Neurology,the Second Affiliated Hospital of Zhengzhou University.The number of VRS in the fronto-parietal subcortical white matter,semioval central,and basal ganglia areas was calculated and compared between groups and within the group by performing a MRI scan of the same sequence,and the impact of the history of migraine,the attack frequency and the migraine with or without aura on the number of VRS was investigated.Results The VRS were found in 48 cases in the migraine group,accounting for 96％,significantly higher than in the control group (41 cases,accounting for 82％),the difference being statistically significant (x2 =5.00,P ＜ 0.05).In the migraine group,the sum of the number of VRS (13.00 (6.75,20.00)) was significantly higher than that of the control group (8.00 (5.00,12.00);Z=3.33,P＜ 0.01).In the migraine group the VRS numbers in the fronto-parietal subcortical white matter,semioval central and basal ganglia areas were 6.00(4.00,12.00),2.00(0.00,4.00)and 4.00 (2.00,6.00) respectively,while the numbers of VRS in the same areas of the control group were 0.00 (0.00,2.00),2.00 (0.75,4.00) and 4.00 (3.50,6.00).The total number of VRS in different areas was significantly different within the two groups (migraine group x2 =39.86,P ＜ 0.01;control group x2 =40.15,P ＜0.01).In the migraine group,the VRS was mainly located in fronto-parietal subcortical white matter,whereas in the control group the VRS was mainly distributed in the basal ganglia.The total number of VRS in the migraine with aura group (20.00 (14.50,26.00)) was more than that in the migraine without aura group (11.00 (6.00,20.00);Z =2.52,P =0.02).The numbers of VRS in the fronto-parietal subcortical white matter,semioval central and basal ganglia areas of the migraine with aura group were 12.00(9.00,14.00),2.00(2.00,6.00) and 4.00(2.50,7.50) respectively;The numbers of VRS in the same areas of the migraine without aura group were 6.00(4.00,10.00),1.00(0.00,4.00) and 4.00 (2.00,6.00) respectively;The numbers of VRS in different areas within the two groups were significantly different (with aura group x2 =16.31,P ＜0.01;without aura group x2 =29.48,P ＜0.01).There were statistically significant differences in the number of VRS among migraine without aura patients with different duration and frequency of episodes.Conclusions The incidence rate of perivascular space in migraine is high.VRS is mainly distributed in the fronto-parietal subcortical white matter,which may provide an imaging assistant basis for the diagnosis of migraine.Migraine with aura is more prone to VRS than those without aura.The disease course and the attack frequency have a certain impact on occurrence of VRS.
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Objective Few studies are reported on the influence of perivascular space enlargement (PVSE) on the prognosis of cerebral infarction. This study was to investigate the clinical correlation of EPVS in the basal ganglia and central semiovale with the prognosis of the first acute cerebral infarction (ACI) with anterior circulation mild small-artery occlusion (SAO).Methods We treated 137 cases of the first ACI with anterior circulation mild SAO in Tangshan Gongren Hospital from August 2015 to October 2016. According to the scores on PVSE in the basal ganglia and central semiovale, we divided the patients into a mild PVSE (score: 0-1) and a severe PVSE group (score: 2-4). Based on the National Institutes of Health Stroke Scale (NHISS) and the modified Rankin Scale (MRS) scores, we classified the outcome of neurological function recovery as good (MRS≥2) and poor (MRS<2) and analyzed the risk factors for the poor prognosis of ACI by logistic regression analysis.Results There were 60 cases of severe and 77 cases of mild PVSE in the in the basal ganglia as compared with 57 cases of severe and 80 cases of mild PVSE in the in the central semiovale. Good prognosis was achieved in 97 cases while poor prognosis observed in 40. Multivariate logistic regression analysis showed that the risk factors for the poor prognosis of ACI included NHISS at the onset (OR=5.393, 95% CI: 1.858-15.654), hypertension (OR=3.729, 95% CI: 1.310-10.610), and the severity of PVSE in the basal ganglia (OR=3.137, 95% CI: 1.343-7.325).Conclusion For the first acute cerebral infarction with anterior circulation mild small-artery occlusion, the severity of PVSE in the basal ganglia is an important factor affecting the recovery of neurological function.
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The perivascular spaces (PVSs) of the brain are lined with pia and contain interstitial fluid. In general, PVSs are small, asymptomatic, and identifiable at all ages. When PVSs are significantly enlarged, they can produce various clinical manifestations such as headache and dizziness. A 67-year-old man was admitted with cognitive impairment and gait disturbance with a 5-month history. Brain MRI showed multiple cystic PVSs in periventricular and subcortical white matter of both hemispheres. Medication with dopaminergic agents produced a moderate clinical improvement, while anticholinesterase was not effective. This case suggests that disseminated polycystic dilated PVSs may present with dementia and Parkinsonism.