Early Neurological Deterioration in Recent Small Subcortical Infarction

Early Neurological Deterioration in Recent Small Subcortical Infarction：a Prospective Study

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, we ought to investigate the natural course of END in patients with RSSI. Exploring the risk factors and potential mechanism of its occurrence and 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. Simultaneously, our study will provide information for the design of therapeutic randomized controlled trials in the future.

Study Overview

• Status: Recruiting
• Conditions: Progression; Cerebral Infarction; Subcortical Infarction; Deterioration, Clinical
• Intervention / Treatment: Other: no intervention

Detailed Description

RSSI patients within 72 hours of stroke onset were prospectively and consecutively enrolled from Janu 2015 to June 2024. 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 including ①percentage of patients with favorable functional recovery, defined as an mRS ≤1; ②Percentage of patients with new vascular events, defined as any stroke (ischemic or hemorrhage); ③Percentage of patients with the new clinical vascular events (ischemic stroke/ hemorrhagic stroke/ TIA/ MI/ vascular death) as a cluster and evaluated individually. ④Severe bleeding incidence (GUSTO definition), including fatal bleeding and symptomatic intracranial hemorrhage; ⑤ Incidence of symptomatic and asymptomatic intracranial hemorrhagic events; ⑥All-cause mortality; ⑦cognitive function (MOCA/MMSE score). The outcomes will be assessed by the neurologists blinded to study images. The quality control of all data will be held by the central center.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Yuan Gao, doctor; Phone Number: 13949113087; Email: fccgaoy1@zzu.edu.cn

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Yuan Gao, doctor; Phone Number: 13949113087; Email: fccgaoy1@zzu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

prospectively enroll consecutive patients with acute RSSI within 72 hours of onset January 2015 to January 2024.

Description

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 sequences at least). 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 data;
2. Vascular malformations, aneurysms, intracranial hemorrhagic diseases, brain abscesses, malignant space occupying lesions or other non-ischemic intracranial lesions;
3. Patients with combined malignancy, hematological disease and other systemic diseases with possible hypercoagulable state;
4. pre-stroke mRS ≥2 ;
5. END occurred before the completion of brain MRI after admission;
6. Acute endovascular treatment had been received or was planed to be done;
7. Pregnant or lactating women;
8. Participating in another ongoing study;
9. Refused to participate in the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Recent small subcortical infarction within 72 hours from stroke onset to admission; Recent small subcortical infarction (RSSI) is defined as small deep infarctions in the territory of perforating arteries with maximum axial diameters (MAD) of less than 20 mm. In this study, RSSIs in the territories of lenticulostriate area, pons are enrolled.	Other: no intervention; no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Neurological Deterioration	any increase of ≥ 2 points in the total NIHSS score or ≥ 1 point on the motor items of the NIHSS within 7 days after admission	within 7 days after admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with favorable functional recovery	mRS ≤1	12 months
Percentage of patients with new vascular events	any stroke (ischemic or hemorrhage)	12 months
Percentage of patients with new clinical vascular events	ischemic stroke/ hemorrhagic stroke/ TIA/ MI/ vascular death as a cluster and evaluated individually	12 months
Severe bleeding	Severe bleeding incidence (GUSTO definition),including fatal bleeding and symptomatic intracranial hemorrhage.	12 months
All-cause mortality	All-cause mortality	12 months
cognitive function	MOCA/MMSE score	12 months

Collaborators and Investigators

• Sponsor: Yuan Gao
• Investigators: Principal Investigator: Yuan Gao, doctor, The First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: December 25, 2022
• First Submitted That Met QC Criteria: December 25, 2022
• First Posted (Actual): January 11, 2023

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Early Neurological Deterioration; Recent Small Subcortical Infarction
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Brain Ischemia; Stroke; Brain Infarction; Disease Progression; Infarction; Cerebral Infarction; Clinical Deterioration
• Other Study ID Numbers: 2022-KY-1334-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No