Efficacy and Safety of Intravenous Thrombolysis in Branch Atheromatous Disease

Acute Ischemic Stroke, DAPT(Dual Antiplatelet Therapy), SAPT(Single Antiplatelet Therapy), Stroke, Thrombolysis

Acute ischemic Stroke, Branch Atheromatous Disease, Thrombolysis, DAPT, SAPT

Rationale and Relevance: Branch Atheromatous Disease (BAD) describes an atherosclerotic occlusion of one of the deep penetrating cerebral arteries, including the lenticulostriate artery (LSA), paramedian pontine artery (PPA), and anterior choroidal artery (ACHA). BAD is frequently associated with early neurological deterioration (END), particularly progressive motor deficits that contribute to increased disability. Despite its clinical relevance, BAD remains underrepresented in major radiomorphological classification systems such as TOAST, which has led to limited evidence and unclear treatment strategies. Previous studies suggest that the efficacy of intravenous thrombolysis (IVT) may be reduced in BAD compared to other stroke etiologies. Objectives: The primary objective of this study is to evaluate the efficacy and safety of IVT compared with single antiplatelet therapy (SAPT) and dual antiplatelet therapy (DAPT) in patients with BAD-related stroke. A secondary objective is to examine the impact of acute-phase blood pressure fluctuations on END and functional neurological outcomes. Design and Methods: This international multicenter study will be conducted retrospectively according to the STROBE guidelines. Eligible patients include those with BAD-related stroke treated at one of the participating centers between 2010 and 2025. Inclusion criteria comprise characteristic diffusion-weighted MRI patterns in predefined vascular territories (LSA, PPA, ACHA) and a symptom onset ≤24 hours before admission. Patients with typical lacunar infarcts or with other identified stroke etiologies will be excluded. Endpoints: Primary endpoints include functional outcome at three months, defined as a favorable outcome with a modified Rankin Scale score of 0-1; occurrence of END, defined as a ≥4-point worsening on the NIHSS within 24-48 hours; and symptomatic intracerebral hemorrhage. Collected data include clinical, imaging, and therapeutic variables, as well as blood pressure trajectories and pre-stroke treatments (as detailed in the study protocol). Statistical Analysis: Analyses will be performed using SPSS and R. Descriptive statistics, univariate analyses, and multivariable models (IPTW and Poisson regression) will be applied. Results will be reported as adjusted relative risks with 95% confidence intervals. Significance: This study will provide the first comprehensive evaluation of IVT versus SAPT/DAPT in BAD-related stroke, and will investigate the clinical impact of blood pressure changes in this specific stroke subtype. The findings aim to support evidence-based treatment recommendations for a currently underrecognized and poorly understood stroke etiology.

Intracranial branch atheromatous disease (BAD )describes an occlusion of deep penetrating intracranial arteries, leading to subcortical infarction. These perforators include the lenticulostriate arteries (LSA), paramedian pontine arteries (PPA), anterior choroidal artery (ACHA), thalamoperforating arteries, and Heubner's artery. This study specifically focuses on BAD affecting the LSA, PPA, and ACHA territories. Unlike classical lacunar infarction, which is typically attributed to lipohyalinotic degeneration or fibrinoid necrosis of small distal perforators (\<200 µm), BAD involves more proximal and larger perforating arteries (approximately 700-800 µm in diameter). The underlying pathophysiology is thought to be predominantly atherosclerotic plaque involvement at or near the origin of the perforating artery from a parent vessel, resulting in progressive luminal narrowing, branch occlusion, or flow impairment. This distinguishes BAD from traditional small vessel disease and places it within a spectrum of intracranial atherosclerotic disease. Despite its distinct vascular mechanism, BAD is not formally classified as a separate etiological subtype in major stroke classification systems such as TOAST or NINDS criteria. As a result, cases are often categorized under "small vessel occlusion" or "stroke of undetermined etiology," contributing to under-recognition and limited systematic evidence regarding optimal management strategies. Clinically, BAD may initially present similarly to lacunar stroke syndromes, particularly pure motor or sensorimotor deficits. However, a main feature is early neurological deterioration (END), typically occurring within the first 24-48 hours after onset. END is characterized by stepwise or progressive worsening of neurological deficits, most commonly motor impairment, which is thought to reflect ongoing ischemia due to dynamic thrombo-atherosclerotic processes, hemodynamic instability, or progressive perforator occlusion. This clinical course is associated with worse functional outcomes and higher rates of long-term disability compared with stable lacunar infarcts. From a therapeutic perspective, optimal acute management of BAD remains uncertain. Intravenous thrombolysis (IVT), while standard for acute ischemic stroke within the therapeutic window, appears to yield less consistent benefit in BAD compared to other stroke subtypes. Given these uncertainties, this study aims to evaluate real-world treatment effectiveness of IVT compared with antiplatelet-based strategies in patients with imaging-confirmed BAD. In addition, the study investigates the potential role of early hemodynamic variability, particularly blood pressure fluctuations, as a modifiable factor influencing END and functional outcome. This is an international, multicenter, retrospective observational cohort study conducted according to STROBE guidelines. Participating stroke centers contribute consecutively treated patients meeting predefined radiological and clinical criteria over a 15-year period. All included patients underwent standardized neuroimaging with MRI, allowing for consistent identification of infarct topography and exclusion of alternative stroke mechanisms. Clinical data, imaging findings, acute treatment strategies, blood pressure profiles, and outcome measures are extracted from institutional stroke databases and anonymized prior to central analysis. Comparative effectiveness analyses will be performed to assess differences between treatment groups, with adjustment for baseline imbalances using appropriate statistical methods, including propensity score-based approaches. Overall, this study seeks to address a gap in stroke literature by providing multicenter evidence on the comparative effectiveness of intravenous thrombolysis versus antiplatelet strategies in BAD, while simultaneously clarifying the prognostic significance of early hemodynamic changes in this under-recognized stroke subtype.

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Austria, Germany, Switzerland