Bibliometric and visual analysis of limb spasm after stroke based on Citespace software

Rui Jin ,Bing-Quan Wang ,Lian-Yi Hu ,Yi-Jun Feng ,Chu-Yi Zhang ,Yin-Tao Zhang ,Xin-Ju Li*

1Tianjin University of Chinese Medicine,Tianjin 301617,China.

Abstract Background:To apply CiteSpace software to the hotspot,trend and cutting-edge dynamics of limb spasm after stroke in nearly 20 years.Methods:From 2000 to 2018,spasming literature in the Web of Science database were searched,and cooperative analysis of authors' national institutions was conducted by using CiteSpace software,keyword analysis and cluster analysis,citation analysis of authors' literature journals,and visual map.Results:2005 articles were retrieved,and the number of articles increased year by year,and the country with the most articles was the United States.Keyword analysis shows that mechanistic research and clinical treatment of spasticity are research hotspots in this field.The most posts are Northwestern Univ and Univ Verona.Conclusion:Through the CiteSpace software analysis of spasticity literature,it is found that the research focus is embodied in the nerve regeneration technology and the standardized clinical study of botulinum toxin type A application,which has certain reference significance for the future research direction of spasticity.

Keywords:limb spasm after stroke;CiteSpace;bibliometry;visual analysis.

Introduction

Cerebral infarction refers to the ischemic necrosis or softening of restricted brain tissue caused by ischemia and hypoxia of blood circulation disorders in the brain,which is a common disease of human cardiovascular and cerebrovascular systems [1].The disease is characterized by high morbidity,high recurrence rate,high disability rate and high mortality rate.Spasticity is a motor disorder characterized by increased spinal reflex activity after upper motor neuron injury,caused by speed-dependent enhanced stretch reflex [2].The clinical manifestations are muscle involuntary contraction reaction,tendon hyperreflexia,muscle stiffness,clonic labor,and abnormal gait posture,resulting in changes in limb movement mode and seriously affecting patients'quality of life [3].Epidemiological studies found that about 78–88% of stroke patients left part of limb movement dysfunction,of which 80%–90% of hemiplegic was accompanied by varying degrees of limb spasticity [4].At present,western medicine treatment of spasms,including drug treatment,surgical treatment,etc.The efficacy of intrathecal baclofen injection is certain,which is limited for local muscle spasm indications and easy to induce epilepsy,while this product is easy to spread to the central system,and the patient is poorly tolerated [5].The clinical efficacy of surgical treatment is not long-lasting and is risky.The Traditional Chinese Medicine (TCM) treatment of spasticity includes acupuncture,moxibustion,traditional Chinese medicine decoction,TCM external treatment and other intervention measures,which have the characteristics of satisfactory curative effect and high safety [6,7].

The study of spasticity after stroke is increasing,but few bibliometric studies have reported it.Therefore,the author retrieved the Web of Science core collection database,took Science Citation Index Expanded and Social Sciences Citation Index (SCIE+SSCI) as the database source,used Citespace software to map the bibliometry visualization,retained the complete operation parameters,and made the operation process scientific,rigorous and reproducible [8].In order to provide scholars with the research hotspots and frontier trends in this field.

Material and Methods

Data Source

Select Database:Web of Science database,search set Science Citation Index Expanded,search start and end time from 2000-01-01-01 to 2018-12-31,search subject word Subject=(stroke ＊ spasticity),export to "other format",record content "full record and referenced references",save in "plain text" file format.

Study Methods

Based on searching the TXT document downloaded from the database,import the CiteSpace software and select Key Path(Pruning) for simplicity.The node type threshold was set with Top N% per slice as 10%,the node type (Node Types) selected authors,countries and institutions to generate cooperative network maps,keyword analysis,authors,journals and literature were cited for analysis,and the visualization map was quickly drawn.

Results

A total of 2,005 English documents were searched,including research papers (article 1556,77.6%),reviews (review 197,9.8%),conference abstracts (meeting abstract 189,9.4%),conference papers (proceedings paper 53,2.6%),editorials(leading article 35,1.7%),and letters from readers (Letter26,1.3%).

It can be seen in Figure 1 that the number of publications increased from 2000 to 2018.From 2016 to 2018 was 4.6 times that of 2000–2002,and the number of publications was increasing year by year,indicating that the research of spasm is paid attention to by scholars.

Figure 1 Issue volume (2000 to 2018)

The authors and all authors were cited for analysis

Run CiteSpace software,set the cropping method "Minimum Spanning Tree (MST)" to obtain the author cooperation map of 49 nodes and 40 connections (Figure 2A),547 nodes and 1035 authors (Figure 2B).The top 5 authors and their posts are Nicola Smania 4,Lisa A Harvey 4,Sheng Li 3,Gerard E Francisco 2,and Julius P A Dewald2.Among the authors' total cited frequency,the top 5 authors and the cited frequency are Bohannon Rw166,Lance Jw 77,Simpson Dm 64,Hesse S 62,and Gracies Jm 60.

Map of national cooperation and institutions

According to the CiteSpace software analysis,click "author" and"Cited author",select the MST cutting method,and obtain 27 nodes and 48 cooperative connections,forming the national cooperative relationship network (Figure 3A),73 nodes and 56 cooperative connections,forming the institutional cooperative relationship network (Figure 3B).Top 5 in national posts:USA(United States of America) 108,England (United Kingdom) 39,Germany (Germany) 35,Italy (Italy) 35,Canada (Canada) 32.

Top 5,Northwestern Univ (Northwestern University) 14,Univ Verona (University of Verona,Italy) 8,Univ Toronto (University of Toronto) 7,Univ Sydney (University of Sydney) 6,RehabilInst Chicago (Chicago Rehabilitation Institute) 6.

Nodes represent the author and the author cited frequency,the country,the larger the node diameter,the higher the volume of the author,the higher the frequency of the author;the connection represents the connection between the node,the thicker the connection,the stronger the closeness and the correlation between the two.

Keyword analysis

Run software select "Keyword",cut "MST",apply "Prunning sliced networks (PSN)" path to simplify,get 226 nodes,1583 connections,frequency sorted from high to low,stroke 298,spasticity 231,rehabilitation 121,reliability 82 and botulinum toxin 82.The "Burst term" analysis of the keywords yielded the strongest burst keywords (Figure 3A)."Log-Likelihood ratio" was used to cluster the keywords and obtain the keyword clustering network map (Figure 3B),with 226 nodes and 1583 connections.

Figure 2 The map of Collaborative networks.(A) Author cooperation network:each node represents an author.The size and diameter of the circle represent the number of articles published by the author.The larger the circle diameter is,the more articles published by the author.The Lines represent a cooperative relationship between authors.(B) The author cited network:node size on behalf of the authors of the cited frequency,the larger the diameter of the cited frequency,the larger the node.(C) The national relationship network:the node size represents the number of articles issued by a country,the larger the node diameter is,the more national papers are issued.(D) Institutional collaboration atlas network:the node size represents the number of messages sent by an organization,the larger the node diameter is,the more the institution will publish.The connection between nodes represents the cooperation between institutions.

Figure 3 The Keyword analysis atlas. (A) Keyword cluster map:each module is a cluster,the larger the module is,the larger the number of keywords of the cluster is,and the words on the module are the name of the cluster.(B)The strongest citation bursts keywords:each line represents a cluster,and the red line segment represents the hot spot and frontier of the research field.The longer the red line segment is,the longer the duration of the hotspot is,and the hot spots are arranged in ascending order according to the starting year and ending year.

The total references were cited

The subject words were retrieved from the Web of Science database and analyzed online,click "cited frequency" to arrange in descending order,and screen the first 10 articles with the highest reference frequency.As shown in Table 1.

Table 1 The 10 most cited articles

Discussions

In the cooperative network analysis of the authors (Figure 2A),Nicola Smania and Lisa A Harvey were concentrated,which shows that the close cooperation between high-yield authors and a stable and long-term cooperative relationship has been established.Their disciplines are concentrated in neurology and rehabilitation medicine and have a certain discipline influence.In the co-cited analysis (Figure 2B),the articles of foreign authors were highly cited and of great academic value.Among them,Bohannon Rw and Lance Jw are leading figures in academic circles,who are generally cited more frequently and influential.The study direction of Bohannon Rw is the effect of rehabilitation training on muscle strength,which includes the assessment of risk factors on strength [9].The research field of Lance Jw is the effects of neurotransmitters on muscle spasms and headaches.

From the perspective of published countries (Figure 2C),the United States has the largest node diameter and a large number of posts,and American scholars have invested more in the field of muscle spasm after stroke than scholars from other countries.Analysis of institutional institutions (Figure 2D),Northwestern Univ (Northwestern University),Univ Verona (University of Verona,Italy),Univ Toronto (University of Toronto),Univ Sydney(University of Sydney),RehabilInst Chicago (Chicago Rehabilitation Institute).To sum up,the academic contributions of these institutions advance the field.

Keywords are highly condensed to the content of the article,The strongest Burst term represents the research hotspot and trend(Figure 3A),which presents recent research on the treatment of spasmodic drugs and limb function [10].Figure 3A clearly shows the transfer of research frontiers in this field,which is sorted by time from the earliest "muscle spasm state" in 2000 to "recovery"in 2006,"toxin type A" in 2010,and "gait" and "gastrocnemius muscle" in 2014 and 2016.It can be seen that with the passage of time,The frontiers of research are evolving from therapeutic approaches to precision medicine.From "recovery" in 2006,to"gait" in 2014,to "gastrocnemius muscle" in 2016,rehabilitation medicine treatment can be seen from the limb function training to biomechanics,the focus to a particular muscle group (Especially of the gastrocnemius muscle) tension heightens,manifests the rehabilitation medicine treatment more and more refined,accurate positioning,through the coordination of mutual antagonism muscle tension,To correct abnormal movement patterns;From "Botulinum toxin" in 2007 to "toxin type A" in 2010,A large number of clinical trials have reported the clinical efficacy observation of Botulinum toxin Type A in the treatment of limb spasm after ischemic stroke.Scholars have been continuously exploring the optimal injection dose of Botulinum Neurotoxin (BoNT).A large number of grade I evidence-based evidence has shown that local injection of BoNT can effectively inhibit muscle tension and improve limb function of patients.

The keywords were cluster analyzed (Figure 3B),and the cluster Silhouette value is 0.7389,indicating that the cluster credibility is high and has a mining value [8].In the 9 categories of keyword clustering,modules # 5 hemiplegia,# 6 spinal cord injury and #7cerebralpalsy cause muscle spasm for SCI and hemiplegia,both pathogenic factors and provide a theoretical basis for epidemiological investigation and prevention and treatment of disease.# 2 neurological rehabilitation and # 9 stroke rehabilitation are mainly used in rehabilitation function training.Rehabilitation therapy is represented by passive bicycles.Studies have found that passive bicycle induces sensory input signals to activate cortical structures,and induces cortical plasticity and reconstruction to improve lower limb motor function [11].Emphasizing the relationship between # 4 body temperature fever and # 8 spasticity limb spasm,the study shows that the spinal cord injury may lead to persistent muscle rigidity,combined with persistent fever symptoms [12];Or the rapid withdrawal of drugs caused by high fever caused by limb rigidity,spasm,increased body temperature may lead to limb spasm,patients should pay attention to prevent infection,to avoid muscle hyperactivity caused by high fever.According to the keyword cluster analysis,from "recovery" to "body temperature",it can be seen that modern medicine should strengthen the standardized application of drugs and pay attention to patient care in the treatment of this disease,so as to make the diagnosis and treatment process more standardized.

Botulinum toxin Type A,short for BoNT-A,has been mentioned in cluster analysis #0 botulinum toxin Type A,keyword analysis and burst keyword analysis.Its drug mechanism:BoNT-A binds to the presynaptic membrane and decomposes into a light chain that acts on SNAP-25 to block Ach release and inhibit muscle depolarization [13].BoNT-A is now used to treat many kinds of muscle spasms,pain and primary hyperhidrosis.BoNT-A selectively induces cleavage of SNAP-25 depending on Ca2+concentration levels and thereby affects protein translocation from the inner to the outer membrane,blocks KCl evoked release of glutamate and substance P,decreases expression of pronociceptive polypeptide mRNAs such as TRPV1 and prodynorphin and upregulates levels of pronociceptive proteins such as purinergic P2X3receptors,which affect axonal transport of toxins in the anterior horn of the spinal cord or sensory areas of the brain Endocytosis [14].Related studies show that BoNT-A inhibits microglial target gene SNAP-23 expression based on p38MAPK,NF-KB,ERK1-2 signaling,and decreases inflammatory factor IL-1β,IL-18,IL-6 and NOS2 levels,up-regulated TLR2 expression [15,16];Meanwhile,BoNT-A inhibits the release of glutamate and neuropeptide neurotransmitters,preventing the transmission of pain signals from the periphery to the central nervous system [17].BoNT-A cannot only inhibit the inflammatory response,but also down-regulate the expression of pain signals,which play a role in reducing pain.The use of botulinum toxin in the treatment of large muscle is limited,which increases the probability of drug resistance.If the drug is injected improperly,it is easy to spread beyond the target muscle,resulting in the risk of unnecessary muscle weakness [18].

As for #3 nerve regeneration,the main techniques are surgical treatment (contralateral transfer of nerve root) and physical therapy (cryoneurolysis).The experimental results show that successful transplantation of the contralateral nerve can effectively improve the spasticity of lower limbs [19].Clinical research confirmed that Guan applied the trans vertebral posterior approach to transplant the contralateral cervical 7 nerve root and directly anastomose the proximal end of the cervical 7 nerve root at both ends in 2020.The results show that the posterior operation could shorten the nerve transfer distance and be conducive to nerve regeneration and functional recovery.The follow-up investigation found that the spasticity degree of the upper limb on the affected side was lower in 5 cases than that before operation,and the pain and temperature sensation of the upper limb on the affected side was improved in 6 cases [20].The safety and feasibility of this test need to be further studied.Cryoneurolysis relieves pain,reverses nerve damage and prevents nerve signal transmission by ablating peripheral nerves at low temperature.Cryoneurolysis directly applies low-temperature ablation of peripheral nerves to relieve pain,reduce reversible nerve damage,prevent nerve signal transmission,and then cause Waller's degeneration of nerve axons under low-temperature,promote nerve axon regeneration and reconstruction,and restore the sensory and muscle function of peripheral nerves.This method is clinically applied to limb spasms and acute and chronic pain.An experimental study showed that demyelination and axonal degeneration were observed in the nerve tissue 2 weeks after the treatment of frozen neurolysis of the tibial nerve in rats.After 16 weeks,the axons were completely regenerated and re-myelinated to realize nerve regeneration,but there was no significant change in the nerve function defect of rats.The application and follow-up in the past 50 years found that this technology has a very low incidence of complications and adverse effects,and there is only the risk of bruising,swelling and local pain [21].Its analgesic effect is better than that of limb spasms.This technology greatly tests the professional skill level of operators,and operators need long-term technical training,which makes it difficult to promote this technology.

As for neuroprotection,the experimental researches focus on the regulation of specific genes,RNA,autophagy and serum receptors on neuroprotection.The current researches show that the Zfp106 gene is involved in nerve-muscle signal expression[22];Or through the editing and splicing of pre mRNA,it blocks the activity of serotonin receptor (5HT2C) and becomes a potential antispasmodic drug [23];LncRNA SNHG12 regulates miR-199a and improves neuroprotection of injured endothelial cells during cerebral ischemia-reperfusion [24];Induce ERK pathway to down regulate the expression of target Sprouty2 and activate astrocyte proliferation,which can promote neuroprotection and regeneration.Intervening the expression of Sprouty2 by gene or siRNA therapy is the future research direction[25];Autophagy is a stress response of cells to adapt to environmental stimuli and metabolic changes.Autophagy plays a two-way regulatory role on neurons.Moderate autophagy plays a protective role by regulating the physiological activities of nerve cells through P13K/Akt/mTOR pathway.On the contrary,excessive autophagy aggravates neuronal damage and affects the release of neurotransmitters [26].In conclusion,in recent years,scientists from various countries have been committed to targeted treatment of the disease to improve the effect of disease diagnosis,treatment and prevention.At present,many methods are still in the laboratory stage and have not been applied in the clinic.

The most frequently cited article isSpasticity after stroke -Its occurrence and association with motor impairments and activity limitations,published in Stroke magazine in 2004.The purpose of this article is to explore the effect of spasms on motor dysfunction in stroke patients.95 stroke patients with the first onset were observed for 5.4 days and 3 months.Among them,18 patients with spasms had the symptoms of tendon hyperreflexia after 3 months,but the patients with spasms did not have obvious motor dysfunction or disability.It is suggested that spasm may affect limb dyskinesia,but spasm is not consistent with clinical manifestations in rehabilitation.In clinical diagnosis and treatment,rehabilitation practitioners should actively search for the cause,provide patients with an individualized rehabilitation diagnosis and treatment program,improve the efficacy of disease diagnosis and treatment,achieve precision medicine,and reduce the burden of medical care.

Conclusions

In this paper,Citespace software was used to analyze the literature on modern medical treatment of limb spasms after stroke in the Web of Science database,which intuitively showed the current situation and development trend of the research in this field and provided some references for promoting the development of this field. Clinical studies have found that BoNT with different structures,molecular sizes and production processes has different clinical efficacy,and BoNT products with different doses cannot be converted into each other,resulting in a waste of resources,which also needs to be solved urgently.Standardized treatment of Botulinum toxin will be a hot spot in clinical research.In experimental studies,contralateral nerve root transfer is the most promising development direction in this field.In the experimental stage,it has been confirmed that this operation can promote the complete regeneration of axons and re-myelination to achieve nerve regeneration.Clinical studies have also reported that transplanting the contralateral cervical 7 nerve root through the posterior vertebral approach can achieve nerve regeneration and recovery,and effectively improve the limb function and spasticity of patients,but a large number of evidence-based evidence is still needed to support.It is hoped that this technology can be applied to clinics as soon as possible and benefit mankind.Precision medicine and targeted treatment of limb spasms after stroke will be the future development trend.