Efficacy and Safety of Intravenous Thrombolysis in Branch Atheromatous Disease

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.

Inclusion criteria

• aged over 18 years, with acute ischemic stroke and symptom onset no more than 24 hours before admission, who were treated in one of the stroke units of the participating institutions.
• All enrolled patients must have undergone a cerebral MRI for inclusion:

• DWI lesion: single isolated deep subcortical stroke AND
• The affected vessel involves the LSA, PPA, or ACHA, and the infarct lesion on DWI conforms to one of the following characteristics (A, B, OR C):

A. LSA: "Comma-like" infarct lesions with "fan-shaped" extension from bottom to top in the coronary position OR ≥ 3 layers (layer thickness 5 mm) on axial DWI.

B. PPA: Infarct lesion extending from the deep pons to the ventral pons on axial DWI.

C. ACHA: Infarct within the anterior choroidal artery territory.

Exclusion criteria

• Typical recent small subcortical infarction (RSSI) (oval, <20mm in all axes)
• ≥ 50% stenosis on the parent artery (i.e., BA, MCA, or ICA)
• Stroke due to other clearly identified causes or possible cardioembolic etiology.