Evaluating the Neuroprotective Effects of Continuous Lumbar Drainage on the Cerebral Perfusion in Patients With an Acute Ischemic Stroke and Hemodynamic Failure Type 2: a Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in BOLD-CVR Between Pre- and Post-CSF Drainage
研究概览
简要总结
This pilot interventional study investigates whether continuous cerebrospinal fluid (CSF) drainage via lumbar drain can improve cerebrovascular reactivity (CVR) in patients with acute ischemic stroke and hemodynamic failure, as assessed by blood oxygenation level dependent (BOLD) MRI.
Patients with acute ischemic stroke frequently exhibit impaired cerebral autoregulation and reduced vascular reserve. In such cases, a low BOLD-CVR response is associated with a high (~40%) risk of recurrent ischemic stroke despite optimal medical therapy. Hemodynamic failure stage 2 (HF2), defined by severely reduced CVR (hemispheric BOLD-CVR ≤ 0.1041), indicates exhausted compensatory capacity and poor perfusion.
Evidence from other neurological conditions suggests that CSF drainage via lumbar drain may transiently lower intracranial pressure, improve perfusion, and enhance autoregulatory function. This study aims to apply these findings to acute stroke patients with hemodynamic compromise.
Eligible patients will undergo BOLD-CVR MRI to assess cerebrovascular reserve. Those meeting HF2 criteria and without contraindications will be offered inclusion. After informed consent (or proxy consent), a lumbar drain will be placed, and continuous CSF drainage performed over ~48 hours. A follow-up BOLD-CVR MRI will assess changes in CVR. In addition, 20 ml of CSF will be extracted to evaluate acute effects on CVR. A historical cohort will be used to control for spontaneous CVR variation over 48 hours.
Primary Objective:
To determine whether continuous CSF drainage improves BOLD-CVR in patients with HF2 following acute ischemic stroke.
Secondary Objectives:
To compare longitudinal BOLD-CVR changes to a historical cohort. To evaluate safety and feasibility of lumbar drainage in this setting. To assess short-term clinical outcomes (NIHSS, mRS) and recurrent events. To assess BOLD-CVR change after 20 ml CSF extraction.
Study Design:
Single-center, open-label, prospective pilot study. Participants serve as their own control, with pre- and post-intervention imaging to evaluate physiological effects. Safety and exploratory clinical data will also be collected.
This proof-of-concept trial aims to generate preliminary evidence for a potential therapeutic strategy in high-risk stroke patients with poor autoregulation. Positive findings could inform future randomized controlled trials.
详细描述
This pilot interventional study explores the physiological and clinical impact of continuous cerebrospinal fluid (CSF) drainage via lumbar drain on cerebrovascular reactivity (CVR) in patients with acute ischemic stroke who exhibit hemodynamic failure, as measured by blood oxygenation level-dependent (BOLD) functional MRI.
Background and Rationale In patients with acute ischemic stroke, failure of autoregulatory capacity and exhaustion of cerebrovascular reserve represent major contributors to secondary ischemic injury and poor outcomes. Despite optimal medical management, patients with documented hemodynamic failure remain at high risk for recurrent ischemic stroke, often exceeding 30-40% within the first months post-event.
BOLD-CVR is a non-invasive MRI-based technique that maps the cerebrovascular response to a vasodilatory stimulus (commonly CO₂ or breath-hold induced hypercapnia). When interpreted using standardized processing pipelines, it offers a quantitative assessment of cerebral hemodynamics and can differentiate between regions with preserved, reduced, or exhausted vascular reserve. In previous research, a hemispheric mean BOLD-CVR ≤ 0.1041 or a middle cerebral artery (MCA) territory mean BOLD-CVR ≤ 0.0778 has been associated with hemodynamic failure stage 2 (HF2).
There is preliminary evidence from other neurological conditions (e.g., idiopathic intracranial hypertension, traumatic brain injury, and subarachnoid hemorrhage) that CSF diversion through lumbar drainage can lead to improved cerebral perfusion and functional outcomes. The proposed mechanism involves a transient reduction in intracranial pressure (ICP), improved compliance, and favorable shifts in cerebral perfusion pressure gradients. However, this strategy has not been evaluated in the context of acute ischemic stroke in patients without hydrocephalus but with severe autoregulatory impairment.
This study hypothesizes that temporary CSF drainage in such patients will improve BOLD-CVR as an imaging marker of vascular reserve and possibly influence clinical outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients > 18 years old
- •Acute ischemic stroke related to a new uni- or bilateral occlusion of the ICA, MCA (M1- and or M2 segment) or both
- •Persisting vascular pathology after the initial treatment.
- •Hemodynamic impairment on the BOLD-CVR done within 48 hours after stroke onset.
- •Capable of providing informed consent as documented by signature, or if unable, the next of kin (legally authorized representative) must be available for medical decision-making.
排除标准
- •Inclusion in any other running scientific study
- •Contraindications for MRI, including but not limited to:
- •o Pacemakers, metallic implants/prostheses, metallic tattoo dyes.
- •Severe glaucoma.
- •Unwillingness or inability to perform breathing maneuvers required for BOLD-CVR assessment.
- •Major cardiopulmonary diseases, including:
- •Severe uncontrolled asthma bronchiale.
- •Severe chronic obstructive pulmonary disease (COPD, GOLD Stage >2).
- •Diffuse interstitial lung disease.
- •Recent myocardial infarction (acute/subacute).
- •Severe heart failure (NYHA class >2).
- •Symptomatic increased intracranial pressure (ICP) or related conditions:
- •Absent/compressed basal cisterns.
- •Compression or displacement of the fourth ventricle.
- •Cerebellar tonsillar herniation (>5mm below the foramen magnum) on initial CT/MRI or on MRI at Day
- •Obstructive hydrocephalus, including:
- •Aqueductal stenosis.
- •Enlarged lateral and third ventricles with a normal fourth ventricle.
- •Presence of intracranial hemorrhage class >1 (per Heidelberg classification).
- •Unilateral or bilateral subdural hematomas.
- •Malignant infarction syndrome (supratentorial or infratentorial).
- •Decreased level of consciousness at enrollment, not due to aphasia
- •New-onset seizures after stroke onset.
- •Extensive lumbar surgery history.
- •Local or systemic infection:
- •Infection at the lumbar drain insertion site.
- •Systemic infection at the time of enrollment.
- •Severe coagulopathy, including:
- •Moderate/severe thrombocytopenia (<100,000 platelets/µL).
- •Hemophilia or other coagulation disorders.
- •Use of anticoagulants (except for platelet aggregation inhibitors) that cannot be stopped.
- •Within 24 hours after intravenous thrombolysis
- •Structural spinal abnormalities, including:
- •Spina bifida.
- •Scoliosis affecting lumbar puncture feasibility.
- •Pregnant (confirmed or verbally suspected) or lactating women.
- •Inability to follow the procedures of the study, including but not limited to:
- •Severe cognitive impairment (e.g., dementia).
- •Psychiatric disorders affecting cooperation.
- •Severe language barriers preventing study compliance.
- •Failure to insert the lumbar drain.
研究组 & 干预措施
Lumbar Drainage in Acute Ischemic Stroke Patients With Hemodynamic Failure (Single Intervention Arm)
Patients with acute ischemic stroke and evidence of hemodynamic failure on BOLD-CVR MRI (hemispheric CVR ≤ 0.1041 or MCA territory CVR ≤ 0.0778) will receive temporary cerebrospinal fluid (CSF) drainage via a lumbar drain. The drain will be placed under sterile conditions by experienced neurosurgical staff and connected to a closed CSF drainage system. Continuous drainage will be performed for approximately 48 to 72 hours under standardized pressure-controlled conditions. Each patient undergoes BOLD-CVR MRI before and after the drainage period to assess changes in cerebrovascular reactivity. Clinical outcomes (NIHSS, mRS) and safety events (e.g., infection, CSF leak) will also be recorded. This arm is open-label and includes only a single group receiving the intervention.
干预措施: Lumbar drain placement (Procedure)
结局指标
主要结局
Change in BOLD-CVR Between Pre- and Post-CSF Drainage
时间窗: From baseline MRI (prior to CSF drainage) to follow-up MRI within 24 hours after completion of drainage (total approx. 2-3 days post-enrollment)
This outcome measures the change in cerebrovascular reactivity (CVR) based on BOLD-MRI performed before and after continuous cerebrospinal fluid (CSF) drainage via lumbar drain. CVR will be quantified as the mean signal response in both the affected hemisphere and the MCA territory during a standardized hypercapnic stimulus (e.g., breath-hold or controlled CO₂). Change will be assessed using validated voxelwise analysis pipelines to determine whether CSF drainage improves impaired vascular reserve in patients with hemodynamic failure. Each patient serves as their own control for evaluating the physiological impact of the intervention.
Change in BOLD-CVR Between Pre- and Post-CSF Drainage
时间窗: From baseline MRI (prior to CSF drainage) to follow-up MRI within 24 hours after completion of drainage (total approx. 2-3days post-enrollment)
This outcome measures the change in cerebrovascular reactivity (CVR) based on BOLD-MRI performed before and after continuous cerebrospinal fluid (CSF) drainage via lumbar drain. CVR will be quantified as the mean signal response in both the affected hemisphere and the MCA territory during a standardized hypercapnic stimulus (e.g., breath-hold or controlled CO₂). Change will be assessed using validated voxelwise analysis pipelines to determine whether CSF drainage improves impaired vascular reserve in patients with hemodynamic failure. Each patient serves as their own control for evaluating the physiological impact of the intervention.
次要结局
- Incidence of Lumbar Drain-Related Complications(From drain placement to 7 days post-removal or hospital discharge, whichever occurs later)
- Hemodynamic Parameters Associated With Lumbar Drainage(From baseline (pre-drainage) to 48 hours post-drainage completion)
- Comparison of BOLD-CVR Change Between Intervention Group and Historical Control Cohort(From baseline MRI (day 0) to follow-up MRI (day 2-3) in both intervention and historical control cohorts)
- Immediate Hemodynamic Impact of Acute CSF Withdrawal on BOLD-CVR(Second BOLD-CVR performed within 30 minutes after post-drainage MRI (typically day 2))
- Incidence of Recurrent Ischemic Stroke(From study enrollment to 90 days post-stroke)
- Neurological and Functional Outcomes at 3 Months as measured using the To evaluate clinical recovery after intervention using the National Institutes of Health Stroke Scale.(From admission to 3-month outpatient follow-up)
- Functional Outcome in Patients with Acute Ischemic Stroke After the Intervention, as Measured by the Modified Rankin Scale(From admission to 3-month outpatient follow-up)
研究者
Christiaan van Niftrik
Dr. sc. med.
University of Zurich