4.1 General Information
We performed a bibliometric analysis of 3037 articles related to cerebral small vessel disease. As shown in Figure 2, the number of global publications on cerebral small vessel disease has shown a steady upward trend. Currently, 143 articles have been published in 2022, although The data for 2022 is incomplete, and it is expected that the production of articles in 2022 will increase, which indicates that research related to cerebral small vessel disease is increasingly attracting the attention of scholars.
Bibliometric analysis takes the global literature pattern and literature characteristics as research objects, including countries, institutions, authors, and journals over a period of time(Liu et al., 2019). In terms of country/regional analysis, research centres in this field are concentrated in Europe, North America and Asia. The USA is the most productive country, with a much higher number of publications than other countries/regions, which is closely linked to funding sponsorship by funding agencies.In terms of research institutions, strengthening the cooperation between different institutions or teams is extremely important for future basic or clinical trials of cerebral small vessel disease. Among the published journals, Stroke, Neurology and Journal Of Stroke Cerebrovascular Diseases are the top 3 journals with the most publications. Andreas, Charidimou, Joanna M Wardlaw, and Hugh S Markus are among the top 3 authors in the field of cerebral small vessel disease by volume.
4.2 Bibliography Analysis
Co-citation analysis is generally used as a method to evaluate the academic influence of journals or scholars, who are all authors with certain academic influence(Dong et al., 2022). Wardlaw JM et al. published the most influential papers with the most citations (438 times). Through further research, it was found that Wardlaw JM et al(Dong et al., 2022) People published several articles mainly on the mechanism, clinical significance and aging and neurodegeneration of cerebral small vessel disease. Lau, KK et al(Lau et al., 2017) (2017) found that a higher total CSVD score was associated with an increased risk of recurrent ischemic stroke. In therapy, Wardlaw, JM et al(Lau et al., 2017) (2019) found emerging targets for new therapies including brain barrier integrity, vascular reactivity, vascular compliance, perivascular inflammation or myelin repair. Shi, YL et al(Shi and Wardlaw, 2016) (2016) believed that new research should consider drugs targeting the endothelium and blood-brain barrier to prevent and treat CSVD. At the same time, changing traditional risk factors and healthy lifestyles are also an important prevention and treatment method.
4.3 Hotspots and Frontiers
Keyword is the most representative term for a concise overview of the topic of the article. Keyword co-occurrence analysis, as a commonly used bibliometric method, can reveal the development trend of research hotspots(Zhou et al., 2021; Sabe et al., 2022).Meanwhile, the keywords with the strongest citation burst can provide a reasonable prediction of the hotspots and frontiers of research on cerebral small vessel disease. Using VOSviewer and Citespace, keywords identified from WoSCC can be grouped into 10 clusters representing the main research directions and frontiers in cerebral small vessel disease(Sabe et al., 2022).According to cluster analysis, the researchers found that the pathogenesis of CSVD has cross effects with chronic cerebral ischemia, endothelial dysfunction, blood brain barrier (BBB) damage, inflammatory response, genetic factors, and neurobiochemical factors. mechanism related to(Thrippleton et al., 2019; Bordes et al., 2022; Bai et al., 2022). Recent subcortical infarct, white matter hyperintensities (WMH), Cerebral microbleed (CMB), enlarged perivascular spaces (PVS), and brain atrophy are six imaging hallmarks of cerebral small vessel disease, and these imaging markers have been shown to be associated with dysfunction(Di Donato et al., 2017; Markus, 2021; Zanon et al., 2021).
The main symptoms of patients with CSVD include lower extremity motor dysfunction characterized by gait disturbance and cognitive dysfunction characterized by impaired executive function(Chen et al., 2019). White matter lesions (WMLs) are more common in the elderly. The symptoms of WMLs are subtle, such as cognitive impairment, dementia and depression. They are usually symmetrically distributed in the white matter including the pons and brain stem on imaging, and also in the deep gray matter(Wu et al., 2022; Hu et al., 2022). White matter hyperintensities (WMH) are the most important predictors of gait dysfunction, and more severe WMH-related defects are located in the internal capsule, Centrum semiovale), periventricular frontal lobe, etc(Rudilosso et al., 2022; Cheng et al., 2022). The number of lacunar infarcts is a predictor of executive dysfunction, presumably due to damage to the frontal-subcortical circuit, decreased connectivity and metabolism within the prefrontal cortex, and ultimately executive dysfunction(Huang et al., 2022; Tian et al., 2022). Cerebral microhemorrhages are an important imaging marker for amyloid cerebrovascular disease (CAA).Hashimoto T found that the number of CMBs is positively correlated with the extent and degree of white matter lesions, and CMBs-related cognitive impairment is mainly reflected in visuospatial perception, executive function, and orientation ability(Best et al., 2022; Nannoni et al., 2022).Another common manifestation of CAA is cognitive impairment, which may be secondary to ischemic injury caused by CAA, which manifests as a spectrum of symptoms ranging from subjective concerns to severe dementia(Mcaleese et al., 2021; Nannoni et al., 2022)。
Arterial stiffness is a common pathological change in cerebral small vessel disease, and arterial stiffness may be one of the causes of cerebral small vessel disease and cognitive impairment(Elyas et al., 2021; Hase et al., 2020). Researchers have found that severe stroke can lead to right paralysis and aphasia, and even can cause dementia. A large area of necrosis can be seen in the left hemisphere, including the presence of neurofibrillary tangles and amyloid plaques in the hippocampus and frequent amyloid plaques in the cerebral cortex, thickening of arterial walls, perivascular spaces are also found Enlargement, arteriosclerosis, microbleeds, and white matter thinning are consistent with features of CSVD and underscore the importance of the gut-vagus-brain axis in late-onset post-stroke dementia(Jiaerken et al., 2021). Furthermore, age- and hypertension-related cerebral small vessel disease are also major determinants of cognitive decline and disability in the elderly(Dobrynina et al., 2022; Goldstein et al., 2022).At present, treatment measures are mainly based on the characteristics of risk factors, the type and severity of biomarkers, and the severity of clinical sequelae. In clinical practice, blood pressure lowering, thrombolysis, and antiplatelet therapy are mostly used(Arba et al., 2019; Pan et al., 2022; Du H et al., 2022). Unlike large vessels, small vessels are difficult to image directly. Therefore, when CT fails to make a definite diagnosis of disease, MRI can display the corresponding parenchymal lesions, which is more helpful for the identification and monitoring of cerebral small vessel disease(van den Brink et al., 2022; Cai et al., 2021)。
The burst map shows that Cortex and gut-brain axi are the latest burst terms in recent years, indicating that these are the latest research hotspots in the field. Gut-brain axi is a two-way pathway between the gastrointestinal system and the central nervous system, involving nerve, endocrine, immune and other aspects. The gut microbiota has a symbiotic relationship with intestinal cells, and plays an important role in basic physiology such as digestion, growth and immune defense.The intestinal microbiota has a symbiotic relationship with enterocytes and plays a role in fundamental physiological processes such as digestion, growth and immune defence.The gut microbiota maintains bidirectional interactions with major parts of the central nervous system through direct and indirect pathways(Tonomura and Gyanwali, 2021). Components of the microbiome may enhance systemic inflammation and amyloid fibril formation, ultimately leading to amyloid deposition, and brain microvasculature inflammation caused by gut microbiome or microbiome metabolites may affect brain parenchyma. Studies have shown that the gut microbiome is associated with characteristics that suggest the presence of CSVD, and that the gut microbiome or its metabolites may influence the presence of CSVD through the microbiome-gut-brain axis(Nelson et al., 2021).
Cerebral small vessel disease is considered a whole-brain disease, and white matter hyperintensity (WMH), a hallmark imaging feature of cerebral small vessel disease, is associated with distant cortical atrophy and cortical thickness(Arba et al., 2019). Cortical thickness has a significant effect on gait performance, with cortical thickness dominated by orbitofrontal and ventrolateral prefrontal cortex, inferior parietal lobe, cingulate area and visual association cortex, positively correlated with stride length(Wang et al., 2022). Thickness of primary and supplementary motor cortex and cingulate cortex was positively correlated with stride frequency, whereas thickness of orbitofrontal and ventrolateral prefrontal cortex, anterior cingulate cortex, especially inferior parietal and superior temporal gyrus were negatively correlated with stride width. Cortical atrophy was associated with cognitive impairment in patients with moderate to severe WML or lacunar infarction, and reducing the severity and progression of white matter hyperintensity may help prevent secondary brain atrophy and cognitive impairment(Lin et al., 2022).
Combined with the results of keyword co-occurrence analysis and burst map, some risk factors and etiologies of cerebral small vessel disease have been identified, but there are still many questions about the exact pathogenesis and the relationship between these risk factors and pathogenesis, and the disease Biomarkers are also evolving. In recent years, the related research on the brain-gut axis has been widely used in the diagnosis and prognostic treatment of various diseases, and the research on the brain-gut axis in encephalopathy has become a new research direction for scientific researchers. The research of cerebral small vessel disease may still be the frontier and hotspot in the future(Nelson et al., 2021).