Early Neurological Deterioration in Recent Small Subcortical Infarction：a Prospective Study
Conditions: Cerebral Infarction, Subcortical Infarction, Deterioration, Clinical, Progression
Sponsor: Yuan Gao

 
 
 
 
Official Title: Early neurological deterioration in 
recent small subcortical infarction：a multicenter 
prospective study 
 
 
NCT number: not available 
 
 
Date: December 25, 2022 
 
 
 
 
 
 
 
 
 

Background and objectives 
Recent small subcortical infarction (RSSI) is defined as a small deep 
infarction in the territory of a perforating artery with maximum axial 
diameters (MAD) of less than 20 mm. Although RSSI is generally 
considered to be of a relatively favorable prognosis, about 13.5% to 43% 
of RSSI patients experience early neurological deterioration (END) in the 
acute phase, which often bring adverse effects on long-term outcomes. 
Although a number of risk factors for END have been identified 
previously, however, the risk factors of END and the underlying 
etiological mechanism are still ambiguous, and also the relevant 
intervention measures lack sufficient evidences, which is a thorny 
problem that clinicians have to face. 
In this multicenter, large-sample prospective registry study, the primary 
objective is to investigate the natural course of END in patients with 
RSSI. Exploring the risk factors and potential mechanism of its 
development, and trying to establish a comprehensive predictive model 
for END that integrates multi-dimensional information including clinical 
symptom, demographic data, biochemical biomarker and image data, and 
so as to provide a valuable tool for clinical evaluation and early 
management. Secondary objective is to figure the long term outcome of 
the patients with RSSI and its risk factors. 
Methods  

Study design 
This study is a multicenter, consecutive, prospective, observational, 
cohort study recruiting RSSI patients within 72 hours after symptom 
onset. This study was approved by the Ethics Committee of The First 
Affiliated Hospital of Zhengzhou University. The anticipated duration of 
the study will be about 2 years from June 1, 2022 to June 1, 2024.  
Study population 
Inclusion criteria. 
1. Age ≥ 18 years;  
2. Time from the last seen normal to enrollment ≤ 72 h; 
3. Completion of brain MRI (T1/T2/Flair/DWI/ADC sequences). The 
lesion belonged to the territory of the penetrating artery 
(lenticulostriate area and pons) on the DWI sequence and at least 
one of the vascular examinations such as MRA, CTA or DSA was 
completed. 
Exclusion criteria. 
1. Patients with low imaging quality affecting the evaluation of the 
results;  
2. Intracranial hemorrhagic diseases, vascular malformations, 
aneurysms, brain abscesses, malignant space occupying lesions or 
other non-ischemic intracranial lesions observed by baseline head 
imaging; 

3. Patients with combined malignancy, hematological disease and 
other systemic diseases with possible hypercoagulable state;  
4. mRS score prior to the onset of the disease was≥2 points; 
5. Patients with symptom progression or TIA before completion of 
cranial MRI after admission;  
6. Received or plan to receive acute endovascular treatment after 
onset of the disease; 
7. Pregnant or lactating women; 
8. Participation in another ongoing study; 
9. Those who refused to participate in the study. 
Data collection  
RSSI patients within 72 hours of stroke onset were prospectively and 
consecutively enrolled from June 2022 to June 2023. After enrollment, 
Clinical data will be collected using an online electronic case report Form 
(e-CRF) at baseline and follow-up. Baseline data including demographic, 
first blood pressure, past and family history, past medications use, 
pre-stroke modified Rankin Scale score (mRS), assessment of mRS and 
NIHSS score on admission were recorded. After admission, NIHSS score 
was evaluated twice a day by two certified physicians, who were blinded 
to the study. laboratory tests including routine blood/biochemistry/renal 
function, etc.) Transthoracic echocardiogram, 24-hour Holter and 
neuroimages data including brain MRI/MRA/CTA/DSA, etc. were all 

collected. During hospitalization, the drug therapy 
(antiplatelet/anticoagulation, lipid-lowering, glucose lowering, 
antihypertensive, etc.) were also recorded. Early neurological 
deteriorations (END) were monitored by two certified physicians, who 
were blinded to the imaging, and the primary outcome of our study was 
the occurrence of END, which was defined as any increase of ≥ 2 
points in the total NIHSS score or ≥ 1 point on the motor items of the 
NIHSS within 7 days of hospital admission with blind evaluation. And 
any new cerebrovascular events confirmed during hospitalization were 
recorded. By face-to face or telephone interviews, we extended the follow 
up to 1 year for our secondary outcome as follow. The outcomes will be 
assessed by the neurologists blinded to study images. The quality control 
of all data will be held dynamically by the central center. 
Outcome measures 
Primary outcome 
Any increase of ≥ 2 points in the total NIHSS score or ≥ 1 point on the 
motor items of the NIHSS within 7 days of hospital admission with blind 
evaluation. 
Secondary outcome 
1. percentage of patients with favorable functional recovery, defined 
as an mRS ≤1;  
2. Percentage of patients with new vascular events, defined as any 

stroke (ischemic or hemorrhage);  
3. Percentage of patients with the new clinical vascular events 
(ischemic stroke/ hemorrhagic stroke/ TIA/ MI/ vascular death) as 
a cluster and evaluated individually； 
4. Severe bleeding incidence (GUSTO definition), including fatal 
bleeding and symptomatic intracranial hemorrhage;  
5. Incidence of symptomatic and asymptomatic intracranial 
hemorrhagic events;  
6. All-cause mortality;  
7. cognitive function (MOCA/MMSE score).  
Sample size  
In out cohort study, no specific hypothesis for the primary outcome 
is set, the sample size is estimated based on the number of variables, 
using the method recommended for registry study (10 times number of 
variable). The sample size is estimated as 500 , and increases to 550 
for 10% loss during follow-up.  
Statistical analysis  
Categorical variables will be presented as frequencies and 
percentages, Continuous variables with non-normal distributions will 
be shown as median and interquartile range (IQR), while continuous 
variables with normal distributions as mean and 95% confidence 
interval (CI). For the statistical significance analysis of different 

groups and outcomes, Pearson χ 2 or Fisher’s exact test, Wilcoxon 
tests, and t-tests will be used, where appropriate, with statistical 
uncertainty expressed by means of 95% CI. Cox proportional hazards 
model, Logistic regression model, and Poisson regression model will 
be used to assess the association between outcomes and predictors, 
where appropriate. All associated variables in the univariate analysis 
that reached P <0 .10 were included in the multinomial logistic 
analysis as candidate variables and then removed by a forward 
conditional selection. A two-sided P P<0.05 was considered 
statistically significant. The good prognosis is defned as 0–2 mRS 
score, and poor prognosis as 3–6 mRS score on 12 mon. All analysis 
will be performed using SPSS 26.0 (SPSS, Inc., Chicago, IL).