As a mature neuromodulation technique with sufficient evidence and wide application， transcranial magnetic stimulation （TMS） has become a highly promising approach for the treatment of insomnia disorder. However， there is still a lack of unified standards for formulation of treatment regimens， technical operations， indications and contraindications， treatment of adverse reactions， and application in special populations. In order to standardize the application of TMS in the diagnosis and treatment of insomnia disorder， Professional Committee of Sleep and Neuromodulation of Chinese Sleep Research Society organized the compilation of the technical specifications. This document systematically elaborates on the technical principles and stimulation modes of TMS， summarizes the clinical evidence for its application in the treatment of primary insomnia disorder and comorbid conditions such as depression and cognitive impairment， clarifies the key points for formulating treatment regimens （including stimulation coils， targets， modes， and intensity）， refines the technical specifications such as treatment room setup， personnel qualifications， operation procedures， and efficacy evaluation， and provides recommendations for the management of adverse reactions and principles for use in special populations， which provides a comprehensive expert consensus and practical guidance for the standardized clinical application of TMS in the treatment of insomnia disorder.

Objective To investigate the correlation between seasonal blood pressure （BP） variability and total burden score of cerebral small vessel disease （CSVD） with different severities. Methods The patients with CSVD who were consecutively admitted were enrolled， and according to the total burden score based on head MRI， they were divided into control group （CSVD 0 points）， mild group （CSVD 1‒2 points）， and moderate-to-severe group （CSVD 3‒4 points）.General information was collected from all patients， as well as 24-hour ambulatory blood pressure monitoring （ABPM） during warm and cold seasons. The correlation between ABPM parameters in different seasons and the imaging burden of different severities of CSVD was analyzed. Results A total of 145 patients were enrolled， with 29 patients in the control group，64 in the mild group， and 52 in the moderate-to-severe group.Compared with the control group， the mild group and the moderate-to-severe group had significantly higher age（F=9.721，P=0.001）， 24-hour systolic blood pressure （SBP） in hot season（F=6.572，P=0.002）， daytime SBP in hot season（F=6.460，P=0.002）， daytime diastolic blood pressure （DBP） in hot season（F=5.802，P=0.004）， nighttime SBP in hot season（F=8.508，P<0.001）. Compared with the control group， the moderate-to-severe group had significantly higher levels of 24-hour DBP in hot season（F=4.564，P=0.012）， nighttime DBP in hot season（F=6.294，P=0.002），24-hour SBP in cold season（F=7.012，P=0.001）， 24-hour DBP in cold season（F=4.527，P=0.012），daytime SBP in cold season（F=5.708，P=0.004），daytime DBP in cold season（F=3.138，P=0.046），nighttime SBP in cold season（F=9.154，P<0.001）， and nighttime DBP in cold season（F=8.006，P=0.001）. Compared with the control group， the mild group and the moderate-to-severe group had a significantly higher proportion of patients with abnormal BP circadian rhythm in hot season （χ2=13.059，P=0.001） and cold season （χ2=10.091，P=0.006）.The ordinal logistic regression analysis showed that age （OR=1.147， 95%CI 1.084‒1.214） was an independent risk factor for CSVD， and compared with the patients with dipper-type blood pressure in hot season， the patients with non-dipper blood pressure pattern had a risk of CSVD increased by 13.282 times （OR=13.282， 95% CI 2.379‒74.159）， while those with reverse-dipper blood pressure pattern had a risk of CSVD increased by 25.569 times（OR=25.569，95%CI 3.061‒213.551）. Conclusion The imaging burden score of CSVD increases with the increase in age and the proportion of abnormal circadian blood pressure pattern in hot season， and both age and abnormal circadian blood pressure pattern in hot season are independent risk factors for the imaging burden of CSVD.

Objective To investigate the value of total cerebral small vessel disease （CSVD） score combined with three-dimensional arterial spin labeling （3D-ASL） in predicting the prognosis of patients with acute ischemic stroke （AIS） after 90 days of intravenous thrombolysis. Methods A total of 189 AIS patients who were consecutively admitted to Department of Neurology， Changshu Hospital Affiliated to Nantong University， from January 2021 to June 2023 and underwent intravenous thrombolysis with alteplase were enrolled， and multimodal brain MRI was performed to assess total CSVD load and cerebral blood flow in the area of responsibility. A multivariate logistic regression analysis was used to identify the independent influencing factors for poor 90-day prognosis in AIS patients undergoing intravenous thrombolysis. The receiver operating characteristic （ROC） curve was used to investigate the value of total CSVD score and 3D-ASL used alone or in combination in predicting the prognosis of AIS. Results The multivariate regression analysis showed that diabetes （OR=3.601，95%CI 1.448‒8.954，P=0.006）， total CSVD score ≥3 points （OR=4.077， 95%CI 1.785‒9.313，P=0.001）， and baseline NIHSS score （for every 1-point increase：OR=1.167， 95%CI 1.061‒1.283， P=0.001） were independent risk factors for poor prognosis in AIS patients on day 90 after intravenous thrombolysis，while ASL hyperperfusion was an independent protective factor against poor prognosis （OR=0.16， 95%CI 0.050‒0.356，P=0.014）.The ROC curve analysis showed that the predictive model based on CSVD score and ASL perfusion had a C-value of 0.844 （95%CI 0.786‒0.902， P<0.05） and thus had the best predictive efficacy. Conclusion Total CSVD score combined with 3D-ASL can more comprehensively reflect the whole brain circulation network and has a better effect than each indicator alone in predicting the 90-day prognosis of AIS patients undergoing intravenous thrombolysis.

Objective To investigate the association of the total burden of cerebral small vessel disease （CSVD） with the level of tumor necrosis factor-α（TNF-α） and prognosis in patients with ischemic stroke （AIS）. Methods A total of 120 patients with AIS who were admitted to our hospital from January 2022 to December 2023 were enrolled as subjects， and all patients underwent cranial MRI scanning. Baseline data and TNF-α level were compared between the patients with different total burden scores of CSVD， and the correlation between TNF-α level and CSVD total burden score was analyzed. TNF-α level and CSVD total burden score were compared between the AIS patients with different prognoses to investigate the influence of TNF-α and CSVD total burden score on the short-term prognosis of AIS， as well as their value in predicting the short-term prognosis of AIS. Results There were significant differences in age， the proportion of patients with hyperlipidemia， the proportion of patients with smoking， and the levels of TNF-α and Hcy between the patients with different CSVD total burden scores （P<0.05）. The level of TNF-α was positively correlated with the number of lacunar cerebral infarcts， Fazekas score of white matter lesions， and EPV score （r=0.654， 0.775， 0.820， P<0.05）， but it had no linear correlation with the number of cerebral microbleeds （r=-0.035，P>0.05）. The logistic regression analysis showed that before correction， age， hyperlipidemia， smoking， TNF-α，and Hcy were significantly correlated with lacunar infarction， white matter lesions， EPV severity， cerebral microbleeds，and CSVD total burden score （P<0.05）， and after correction， TNF-α was still significantly correlated with lacunar infarction， white matter lesions，cerebral microbleeds， EPV severity， and CSVD total burden scores （P<0.05）. There were significant differences in CSVD total burden score and TNF-α between the patients with a good prognosis and those with a poor prognosis（P<0.05）.TNF-α combined with CSVD total burden score had the largest area under the receiver operating characteristic curve（AUC） of 0.912 in predicting the short-term prognosis of AIS，which was significantly higher than the AUC of TNF-α or CSVD total burden score used alone（P<0.05）. Conclusion The increase in TNF-α level has a certain relationship with CSVD total burden score and short-term prognosis in AIS patients， and the combination of TNF-α level and CSVD total burden score has a relatively high clinical application value in predicting the short-term prognosis of AIS patients.
Prognosis

目的 系统评估阻塞性睡眠呼吸暂停（OSA）与脑小血管病（CSVD）影像特征的关系，以期深入探索OSA在CSVD发生、发展中的潜在机制，并为优化临床管理策略提供新的科学依据。方法 收集自2021年5月—2023年10月期间入院的首发缺血性脑卒中合并CSVD的患者。完善头部MRI，评估CSVD影像学特征，并完善睡眠呼吸检测，计算OSA的特异性指标“低氧负荷（HB）”，并与传统指标对比，采用多因素Logistic回归分析研究这些缺氧指标与CSVD之间的关系，并绘制ROC曲线以比较缺氧指标与结局指标的相关性。结果 共纳入243例首发急性缺血性脑卒中患者，男性155例（63.8%），女性88例。多因素Logistic回归分析发现HB（OR=1.037，95%CI 1.020~1.055，P<0.001）和呼吸暂停低通气指数（AHI）（OR=1.044，95%CI 1.020~1.070，P<0.001）均与脑白质高信号（WMH）呈显著正相关。绘制ROC曲线结果显示，HB（AUC=0.722）与WMH的相关性优于AHI（AUC=0.670）。而睡眠期间血氧饱和度低于90%的时间总和（T90）、血氧饱和度下降指数（ODI）与WMH无关。OSA与扩大的血管周围间隙（EPVS）、脑微出血（CMB）、腔隙性脑梗死（LI）无相关性。结论 相较于传统评估指标，HB与WMH关联性更强，可作为OSA患者风险评估的更有效指标，为个体化干预提供精准依据。 Abstract Objective To systematically evaluate the association between obstructive sleep apnea （OSA） and the radiological features of cerebral small vessel disease （CSVD）， to investigate the potential mechanism of OSA in the development and progression of cerebrovascular diseases， and to provide a new scientific basis for optimizing clinical management strategies. Methods The patients with first-episode ischemic stroke and CSVD who were admitted from May 2021 to October 2023 were enrolled according to the inclusion and exclusion criteria. Cranial MRI was performed to evaluate the radiological features of CSVD， and sleep respiration testing was conducted to calculate hypoxic burden （HB）， a specific indicator for OSA， which was compared with traditional indicators. The multivariate logistic regression analysis was used to investigate the association between these hypoxic indicators and CSVD， and the receiver operating characteristic （ROC） curve was plotted to compare the correlation between hypoxic indicators and outcome measures. Results A total of 243 patients with first-episode acute ischemic stroke were enrolled in this study， among whom there were 155 male patients （63.8%） and 88 female patients. The multivariate logistic regression analysis showed that both HB OR=1.037， 95%CI 1.020-1.055， P<0.001） and apnea-hypopnea index （AHI）（OR=1.044， 95% CI 1.020-1.070， P<0.001） were significantly positively correlated with white matter hyperintensities （WMH）.The ROC curve analysis showed that the correlation between HB and WMH （AUC=0.722） was better than that between HB and AHI（AUC=0.670）. However， sleep time with oxygen saturation below 90% and oxygen desaturation index were not associated with WMH. OSA was not associated with enlarged perivascular spaces， cerebral microbleeds， or lacunar infarction. Conclusion Compared with traditional indicators， HB has a stronger correlation with WMH and can be used as a more effective indicator for risk assessment in OSA patients， thereby providing a precise basis for individualized intervention.

Objective To investigate the application value of occupational therapy in cognitive impairment in patients with cerebral small vessel disease. Methods A total of 84 patients with cerebral small vessel disease who were admitted to our hospital from April 2021 to September 2022 and were found to have cognitive impairment were enrolled as subjects， and they were randomly divided into observation group and control group using a random number table， with 42 patients in each group. The patients in the control group received conventional Western medicine treatment， while those in the observation group received occupational therapy in addition to the treatment in the control group. After 8 weeks of continuous treatment， the two groups were compared in terms of treatment outcome， Mini-Mental State Examination （MMSE） score， Montreal Cognitive Assessment （MoCA） score， brain-derived neurotrophic factor （BDNF）， high-sensitivity C reactive protein （hs-CRP）， homocysteine （Hcy）， and cerebral blood perfusion parameters. Results The treatment group had a higher overall response rate than the control group （95.24% vs 73.81%， P<0.05）. After treatment， the observation group had significantly higher MMSE， MoCA， and MBI scores than the control group （P<0.05）. Compared with the control group， the observation group had a significantly lower MTT and significantly higher CBV and CBF （P<0.05）. Compared with the control group， the observation group had a significantly higher level of BDNF and significantly lower levels of hs-CRP and Hcy （P<0.05）. Conclusion Occupational therapy has a marked clinical effect in patients with cerebral small vessel disease and cognitive impairment and can effectively improve cognitive function and cerebral blood perfusion， upregulate the level of BDNF， and reduce the expression of hs-CRP and Hcy. It is of great significance for improving the quality of life and prognosis of patients.
Homocysteine

摘要 目的 探讨脑小血管病（CSVD）患者中运动认知风险综合征（MCR）与神经影像学标志物之间的关系，并评估MCR相关的影像学标志物及比较其与轻度认知功能障碍（MCI）的影像学标志物是否不同。方法 研究回顾性选取了河北医科大学第三医院自2023年4月—2024年11月收治的187例脑小血管病患者。根据是否诊断MCR及MCI进行分组。收集患者的临床资料和影像学数据，使用单变量和多因素Logistic回归分析探讨CSVD患者MCR的影像学特征。结果 CSVD患者中MCR阳性组在体重指数（BMI）、男性比例、高血压、存在腔隙、严重的脑白质高信号（WMH）、严重的基底节区扩大的血管周围间隙（EPVS）和严重CSVD总负荷方面患者比例比MCR阴性组更高（P<0.05）。多因素Logistic回归分析显示，WMH总体积是CSVD患者MCR的独立危险因素（OR=1.038，95%CI 1.003~1.075，P=0.033）。以MCI、MCR两个指标分组显示，MCI+/MCR+较其他组比较，高血压病比例更高（其中MCI-/MCR+组较MCI+/MCR-组比高血压病比例更高），WMH总体积、严重的脑深部及脑室旁WMH、严重的EPVS比例更高（P<0.05）。其中单纯MCR阳性组（MCI-/MCR+）与单纯MCI阳性组（MCI+/MCR-）比较，脑室旁及深部WMH有更高的分级（2级、3级高于MCI+/MCR-组）及更大的总体积（P<0.05）。CSVD总负荷方面差异无统计学意义（P>0.05）。结论 WMH是CSVD患者合并MCR的独立危险因素。MCR与更大的WMH体积相关。本研究强调了MCR的脑白质异常，运动评估在早期痴呆风险分层中的潜力。 Abstract Objective To investigate the association between motoric cognitive risk syndrome （MCR） and neuroimaging markers in patients with cerebral small vessel disease （CSVD）， to assess the imaging markers associated with MCR， and to compare the differences in imaging markers between MCR and mild cognitive impairment （MCI）. Methods A retrospective study was conducted among 187 patients with CSVD who were admitted to Department of Neurology， Hebei Medical University Third Hospital， from April 2023 to November 2024， and they were divided into groups based on whether they were diagnosed with MCR or MCI. Clinical and imaging data were collected， and the univariate and multivariate logistic regression analyses were used to investigate the imaging features of CSVD patients with MCR. Results Compared with the MCR-negative group， the MCR-positive group had significantly higher BMI， proportion of male patients，and proportion of patients with hypertension， lacunar infarcts， severe white matter hyperintensity （WMH）， severe enlarged perivascular space （EPVS） in the basal ganglia， and high CSVD total burden （P<0.05）. The multivariate logistic regression analysis showed that the total volume of WMH was an independent risk factor for MCR in CSVD patients（OR=1.038，95%CI 1.003‒1.075，P=0.033）. Stratification by MCI，MCR showed that compared with the other groups， the MCI+/MCR+ group had a significantly higher proportion of patients with hypertension （the MCI-/MCR+ group had a higher proportion of patients with hypertension than the MCI+/MCR- group）， a significantly higher total volume of WMH， a significantly higher proportion of patients with severe deep brain and paraventricular WMH， and a significantly higher proportion of patients with severe EPVS（P<0.05）.Compared with the MCI+/MCR-group， the MCI-/MCR+ group had significantly higher grades （a significantly higher proportion of patients with grade 2 or 3 WMH than the MCI+/MCR- group） and total volume of periventricular and deep WMH（P<0.05）. There was no significant difference in CSVD total burden between groups（P>0.05）. Conclusion WMH is an independent risk factor for MCR in patients with CSVD. MCR is associated with a larger volume of WMH.This study highlights white matter abnormalities in MCR and the potential of motor function assessment in early risk stratification for dementia.

Objective To explore the changes in serum lactate dehydrogenase （LDH）， monocyte chemoattractant protein-1 （MCP-1）， and transcription factor 4 （TCF4） levels in patients with cerebral small vessel disease complicated by depression and their clinical significance. Methods According to the inclusion and exclusion criteria， 90 patients admitted to the Kailuan General Hospital between January 2022 and August 2024 were selected as the study subjects， including 27 patients diagnosed with cerebral small vessel disease complicated by depression and 63 patients with cerebral small vessel disease uncomplicated by depression. An additional 45 healthy individuals with normal head MRI findings and no mental disorders during the same period at the hospital were selected as the control group. General information was collected from the three groups， including age， body mass index， systolic blood pressure， and diastolic blood pressure.The general information and the levels of serum LDH，MCP-1，and TCF4 in the three groups were compared. The correlations of serum LDH，MCP-1，and TCF4 levels with HAMD score in patients with cerebral small vessel disease and depression were analyzed. Logistic regression was applied to analyze possible factors leading to depression in patients with cerebral small vessel disease.The receiver operating characteristic curve was applied to analyze the efficacy of serum LDH， MCP-1， and TCF4 levels in diagnosing depression in patients with cerebral small vessel disease. Results The levels of serum LDH， MCP-1，and TCF4 were significantly higher in the cerebral small vessel disease complicated by depression group than in cerebral small vessel disease uncomplicated with depression group and the control group （P<0.05）， and these levels were significantly higher in the cerebral small vessel disease uncomplicated with depression group than in the control group （P<0.05）.The serum LDH，MCP-1 and TCF4 were positively correlated with HAMD score in patients with cerebral small vessel disease complicated with depression（r=0.606，0.798，0.672，all P<0.001）.Serum LDH， MCP-1， and TCF4 were influencing factors for depression in cerebral small vessel disease（P<0.05）.The area under the receiver operating characteristic curve of LDH， MCP-1，and TCF4 in combination in the diagnosis of depression in cerebral small vessel disease was 0.917， which was superior to serum LDH， MCP-1， and TCF4 alone （ZLDH-combination=2.457，P=0.014；ZMCP-1-combination=2.384， P=0.017； ZTCF4-combination=2.317， P=0.021）. Conclusion Serum LDH， MCP-1， and TCF4 levels increased in patients with cerebral small vessel disease complicated with depression. Their combination is valuable in the diagnosis of cerebral small vessel disease complicated with depression.
Depression

Objective To investigate the association between fibrinogen-to-albumin ratio （FAR） and the overall burden of cerebral small vessel disease （CSVD）， as well as their value in predicting early neurological deterioration （END） in patients with acute ischemic stroke （AIS）. Methods A total of 103 AIS patients who were admitted to our hospital from January 2023 to March 2025 were enrolled. According to the CSVD total burden score， the patients were divided into low burden group （0-2 points） with 58 patients and high burden group （3-4 points） with 45 patients； According to the presence or absence of END， they were divided into END group with 21 patients and non-END group with 82 patients. The weighted generalized additive model combined with smooth curve fitting was used to investigate the correlation between FAR and CSVD total burden score. A logistic regression analysis was used to explore the association of FAR and CSVD total burden score with the prognosis of END in AIS patients. The receiver operating characteristic （ROC） curve was used to assess the value of FAR and CSVD total burden score in predicting END in AIS patients. The restricted cubic spline method was used to analyze the dose-response relationship between FAR and END in AIS patients. The Bootstrap method was used to investigate the mediating effect of CSVD total burden score in the relationship between FAR and END in AIS patients. Results The high burden group had a significantly higher FAR than the low burden group （P<0.05）， and there was a U-shaped relationship between FAR and CSVD total burden score， with an inflection point of 8.14%. Compared with the non-END group， the END group had a significantly higher proportion of patients with a CSVD total burden score of 3-4 points and a significantly higher FAR （P<0.05）. After adjustment for the covariates such as age and sex， FAR （OR=1.918， 95%CI 1.825‒2.157，P<0.05） and CSVD global burden score （OR=2.167，95%CI 2.051‒2.249， P<0.05） were still independently associated with the risk of END in AIS patients. FAR combined with CSVD total load score had a significantly higher predictive value than either indicator alone， with an area under the ROC curve of 0.951. The mediating effect analysis showed that CSVD total burden score played a mediating effect between FAR and AIS patient prognosis END （P<0.05）. Conclusion There is a significant association between FAR and the overall burden of CSVD， and combined measurement of FAR and CSVD total burden score can significantly enhance the performance in predicting END， thereby providing an important basis for developing individualized treatment strategies in clinical practice.

Objective To investigate the role of the endothelin-1/nitric oxide （ET-1/NO） system in neurological function and cerebral hemodynamics after interventional surgery for cerebral infarction， as well as the association of the levels of ET-1 and NO with neurological recovery and cerebral blood flow after surgery. Methods A total of 108 patients with cerebral infarction who were treated in our hospital from January 2022 to June 2023 were enrolled， and serum samples were collected before surgery and on day 30 after surgery. ELISA was used to measure the levels of ET-1 and NO；National Institutes of Health Stroke Scale（NIHSS） was used to assess neurological function； transcranial Doppler was used to measure cerebral hemodynamic parameters， including mean blood flow velocity， peak systolic velocity， and pulsatility index. A Spearman correlation analysis was used to investigate the correlation of ET-1 and NO with neurological function and cerebral hemodynamics，and the receiver operating characteristic （ROC） curve was used to assess the value of ET-1 and NO in predicting poor neurological function. Results After interventional surgery， there was a significant reduction in the level of ET-1 and a significant increase in the level of NO（both P<0.001）. The patients were divided into good recovery group （NIHSS≤5） and poor recovery group.Compared with the poor recovery group， the good recovery group had a significant reduction in serum ET-1 and a significant increase in serum NO （both P<0.001）. The Spearman correlation analysis showed that the serum level of ET-1 was negatively correlated with neurological recovery and the improvement in cerebral hemodynamics， while the level of NO was positively correlated with these two indicators. The ROC curve analysis showed that ET-1 and NO could effectively predict poor neurological recovery after interventional surgery， with an area under the ROC curve of 0.881 and 0.981，respectively. Conclusion The ET-1/NO system plays an important role in neurological function and cerebral hemodynamics after interventional surgery for cerebral infarction. Reducing ET-1 and increasing NO can facilitate the recovery of neurological function and cerebral blood flow after surgery. The levels of ET-1 and NO can be used as biomarkers for predicting poor postoperative neurological function and provide a scientific basis for optimizing postoperative treatment strategies.
Endothelin-1