Predicting Traditional Chinese Medicine Rehabilitation in Acute Ischemic Stroke Using Multiphase CT Angiography Collateral Scores

Summary

This study examined whether multiphase CT angiography collateral scores predict the efficacy of traditional Chinese medicine rehabilitation in acute ischemic stroke recovery. The prediction model showed good initial discriminative ability, suggesting potential value for individualized therapeutic decision-making in rehabilitation practice.

Abstract

The present study evaluated the predictive value of multiphase computed tomography (CT) angiography (mCTA) collateral circulation scores in determining the efficacy of traditional Chinese medicine (TCM) rehabilitation therapy during recovery from acute ischemic stroke (AIS). Ninety-two patients treated between April 2021 and June 2023 were assigned to either combined therapy (n = 52), consisting of Western medication plus TCM rehabilitation, or conventional therapy (n = 40) with Western medication alone. Collateral circulation was assessed using Mass, Tan, and ASPECTS scores before and after a 3 month intervention. Multivariate logistic regression identified neutrophil-to-lymphocyte ratio, baseline NIHSS, and collateral scores as independent predictors of therapeutic efficacy. A significant interaction effect was observed between collateral circulation and treatment modality. The resulting prediction model demonstrated good initial discriminative ability (AUC > 0.85, 95% CI) and calibration consistency, suggesting that collateral scoring may support individualized rehabilitation strategies, though larger multicenter studies are required for validation.

Introduction

Acute ischemic stroke (AIS) is a leading cause of mortality and disability worldwide, with incidence rising in aging populations and creating substantial public health challenges^1,2. Collateral circulation plays a crucial role in maintaining perfusion in ischemic regions, limiting secondary tissue injury, and supporting recovery³. Digital subtraction angiography (DSA) is the reference standard for collateral assessment, but its invasiveness limits routine clinical use⁴. Multiphase CT angiography (mCTA) provides a less invasive, temporally resolved alternative that enables pragmatic evaluation of collateral compensation in standard workflows⁵. The Menon (Mass) collateral scale grades filling from 0 (none) to 5 (excellent), and its prognostic utility has been validated in stroke research⁶.

Traditional Chinese Medicine (TCM) rehabilitation, including a modified Buyang Huanwu Decoction and acupuncture, is widely used during AIS recovery. Pharmacological studies suggest that the decoction, which centers on Astragalus membranaceus, improves microcirculation, mitigates oxidative stress, and supports neural repair^7,8. Clinical evidence indicates that this prescription, particularly when combined with acupuncture, can alleviate neurological deficits and hemorheological abnormalities⁹. Acupuncture is posited to regulate qi and blood flow, enhance cerebral oxygen supply, and potentially synergize with TCM formulations to influence collateral dynamics via multiple mechanisms¹⁰.

Because systemic inflammation influences ischemic injury and vascular remodeling, we pre-specified the neutrophil-to-lymphocyte ratio (NLR) as a pragmatic inflammatory biomarker; prior studies have associated higher NLR with a larger infarct burden, poorer functional outcomes, and less favorable collateralization in AIS. Accordingly, NLR was evaluated alongside mCTA collateral metrics within the predictive framework.

This study applied mCTA-based collateral scoring to examine whether TCM rehabilitation is associated with improved recovery during the AIS convalescent phase and to evaluate its predictive utility. We focused on adults (≥18 years) 2 weeks to 6 months after onset who underwent mCTA at admission; practical constraints affecting reproducibility include contraindications to iodinated contrast, the need for standardized electroacupuncture delivery, and the availability of trained raters for consistent scoring. We hypothesized that a combined model integrating collateral scores with clinical markers would demonstrate good initial discriminative ability, while acknowledging that further external validation is required.

Protocol

This study was approved by the Institutional Review Board of Southwest Medical University, and all participants provided written informed consent before enrollment (SWMU-2023-IRB-015). The protocol complied with the Declaration of Helsinki and institutional standards for human subject research. The consumables, equipment, and software used are listed in the Table of Materials.

1. Research subjects

This was a prospective observational cohort of adults in the convalescent phase of acute ischemic stroke (AIS), defined as at least 14 days and no more than 6 months after symptom onset. Between April 2021 and June 2023, ninety-two patients aged 18 years or older with imaging-confirmed AIS who underwent multiphase CT angiography (mCTA) after admission and completed follow-up assessments were included. Eligibility required imaging confirmation of AIS, age of 18 years or older, availability of baseline clinical and imaging data, and feasibility of scheduled neurological follow-up. Patients were excluded if they had undergone endovascular or surgical revascularization for the index event, had severe neurological or psychiatric comorbidities that interfered with assessment, had a known allergy to iodinated contrast media, or were pregnant or lactating. Patients received either conventional Western therapy alone (control; n = 40) or conventional therapy plus a modified Buyang Huanwu Decoction with acupuncture (intervention; n = 52). The assignment was based on clinical indications and patient preference; no random sequence generation or allocation concealment was performed. Baseline covariates were recorded and adjusted in multivariable analyses.

2. Imaging methods (mCTA acquisition and timing)

mCTA was performed on a 64-slice CT scanner; the specific brand, model, and post-processing software are listed once in the Table of Materials. Acquisition parameters were a tube voltage of 120 kV, a slice thickness of 0.625 mm, and a 512 × 512 matrix. Iodinated contrast medium at 370 mg I/mL was injected via an antecubital vein at 5 mL/s, followed by a 50 mL saline flush. Four sequential phases-arterial, venous, late, and delayed-were acquired at intervals of 8-10 s. Images were reconstructed and color-coded by phase on the workstation, and three-dimensional reconstructions were generated when needed. A low-dose protocol minimized radiation while preserving diagnostic image quality. Baseline mCTA was performed at admission to the convalescent program, that is, after any acute-phase intravenous thrombolysis and/or endovascular therapy and at least 14 days after stroke onset; this timing window was applied uniformly across participants.

3. Treatment procedure

All patients received guideline-concordant standard care, including antiplatelet therapy, blood pressure, lipid, and glycemic control, and anticoagulation when indicated. The intervention group additionally received a modified Buyang Huanwu Decoction. The hospital pharmacy prepared the formula once daily and dispensed it three times per day after decoction. The daily crude-herb dosages were Astragalus membranaceus 60 g, Angelica sinensis tail 10 g, red peony root (Paeoniae Rubra) 10 g, Lumbricus 6 g, Ligusticum chuanxiong 6 g, peach kernel (Semen Persicae) 10 g, and safflower (Carthami Flos) 10 g. Crude herbs were soaked for 30 min, decocted twice for 30-40 min each time, and the combined filtrates were adjusted to approximately 600 mL; patients took 200 mL per dose, three times daily, for three months. Processing followed the hospital pharmacopoeial standard operating procedure, and lot numbers were recorded in the Table of Materials. Acupuncture with electroacupuncture was performed once daily for three months using sterile, single-use needles. Acupoints were individualized from a predefined trained menu with procedure logs to enhance standardization: for lower-limb hemiplegia, common selections included Zusanli, Sanyinjiao, Yanglingquan, Weizhong, Taixi, Xuehai, Taichong, Chengshan, and Huantiao; for upper-limb hemiplegia, common selections included Shou Sanli, Neiguan, Quchi, and Hegu; and for speech impairment or facial palsy, common selections included Baihui, Xiaguan, Fengfu, Taiyang, Zanzhu, Renzhong, Lianquan, and Yemen. After qi arrival, needles were retained and electroacupuncture was applied for 40 min using an alternating low/high-frequency "dense-disperse" waveform at 2-100 Hz, with current intensity titrated to patient tolerance. Sterile technique was used throughout, and adverse events were monitored.

4. Safety notes and waste disposal

Procedures involving iodinated contrast followed institutional policy and the manufacturer's Material Safety Data Sheet. Screening before contrast administration included allergy history, renal function assessment according to the institutional estimated glomerular filtration rate threshold, and evaluation for uncontrolled hyperthyroidism. Resuscitation equipment and trained personnel were available during imaging. Used needles and other sharps were discarded in puncture-resistant containers; contrast vials and tubing were disposed of as chemical biohazards under local regulations. Appropriate personal protective equipment was used throughout. All adverse events were prospectively recorded with pre-specified definitions, severity grading, actions taken, and outcomes.

5. Observation indicators

Baseline variables included demographics, comorbidities, smoking and alcohol history, and laboratory indices such as fasting glucose, lipid profile, and the neutrophil-to-lymphocyte ratio. Neurological status was assessed using the National Institutes of Health Stroke Scale within 24 h of admission and again at follow-up by two independent neurologists. Collateral circulation on mCTA was graded using the Menon/Mass score, ranging from 0 to 5, the Tan score, ranging from 0 to 3, and an ASPECTS-based CTA score ranging from 0 to 5, where ASPECTS refers to the Alberta Stroke Program Early CT Score. Two neuroradiologists independently rated images after a calibration session, and inter-rater agreement was quantified using Cohen's kappa. Clinical response was defined by NIHSS reduction, where recovery was at least 91%, marked effect was 46-90%, effective was 18%-45%, and ineffective was less than 17%. The total effective rate equaled the sum of recovery, marked effect, and effective outcomes.

6. Model construction and evaluation

Three logistic regression models were pre-specified. Model 1 comprised clinical variables, Model 2 comprised imaging variables, and Model 3 combined clinical and imaging variables. Discrimination was measured by the area under the receiver-operating-characteristic curve with 95% confidence intervals. Calibration was evaluated by slope and intercept, together with graphical assessment. Decision curve analysis was used to appraise net benefit across threshold probabilities. Internal validation used bootstrap resampling with 1,000 iterations to estimate optimism-corrected performance.

7. Statistical analysis

Continuous variables are presented as mean ± standard deviation and were compared using independent-sample t tests or non-parametric tests when assumptions were not met. Categorical variables were compared using chi-square tests. Variables with P < 0.05 in univariable analyses and clinically relevant covariates were considered in multivariable logistic regression. Multicollinearity was examined using variance inflation factors and tolerance. Missing data were evaluated for extent and patterns; when missingness exceeded 5%, multiple imputation with chained equations with 20 imputations was performed under a missing-at-random assumption, and estimates were pooled using standard rules; otherwise, complete-case analysis was applied. For exploratory univariable comparisons, the false discovery rate was controlled at 5% using the Benjamini-Hochberg method. Analyses were conducted in IBM SPSS Statistics version 22.0 with RRID: SCR_016479. The sample size was feasibility-based; with 92 participants and an effective-response rate of approximately two-thirds, the events-per-variable for the five retained predictors was about 10 to 12, which is consistent with recommended thresholds for stable coefficient estimation.

8. Visual schematic

A workflow diagram illustrating patient enrollment, mCTA acquisition, TCM intervention, collateral scoring, model building, and validation is shown in Figure 1.

Results

General analytic conventions
All statistical tests were two-sided, and 95% confidence intervals (CI) are reported for effect estimates and performance metrics. Where multiple comparisons were performed, false discovery rate (FDR)-adjusted q values are provided in the corresponding tables.

Cohort disposition
During the accrual window, consecutive patients meeting eligibility criteria were screened, enrolled, and followed according to the pre-specified w...

Discussion

This study demonstrated that patients in the intervention group (acupuncture combined with Buyang Huanwu Decoction) exhibited greater improvements in collateral circulation and neurological recovery compared with the control group receiving conventional therapy (see Table 2 and Results)^11,12. Post-treatment collateral scores improved significantly in the intervention group, suggesting that Traditional Chinese Medicine (TCM) rehabilitation may be ...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
64-Slice CT Scanner	CT Scanner for multiphase CT angiography	GE HealthCare	Revolution EVO 64
Electroacupuncture Device	Electroacupuncture machine used for treatment	Lhasa OMS	ITO ES-160
Iodinated Contrast Medium	Contrast medium for CT angiography	GE HealthCare	Optiray 350
mCTA Imaging Software	Post-processing software for mCTA images	Siemens Healthineers	syngo.via
Modified Buyang Huanwu Decoction	TCM decoction containing Astragalus membranaceus, Angelica sinensis, etc.	Hunan Chunkehui Traditional Chinese Medicine Co., Ltd.	CP-A069AA (Astragalus), CP-A025 (Angelica sinensis), CP-A031 (Chuanxiong), CP-A039A (Angelica sinensis), CP-H029a (Lumbricus), CP-B091a (Peach seed), CP-D004 (Safflower)
Sterile Acupuncture Needles	Disposable acupuncture needles used for treatment	Guangzhou Zhixin Chinese Herbal Medicine Co., Ltd.	Vigor Acupuncture Needle 0.20g x 40mm