Retrospective Study on the Impact of Neurovascular Calcifications on Increasing Intracranial Hemorrhage Risk in Acute Ischemic Stroke Patients Treated With Thrombolytic Therapy in the Emergency Department

Objective: Intravenous thrombolysis with alteplase (IV tPA) is an established treatment for acute ischemic stroke, but hemorrhagic transformation remains an important complication. Although numerous parameters have been evaluated to minimize the risk of hemorrhagic transformation, no definitive predictor has yet been identified. This study primarily evaluated the association between CTA-detected neurovascular calcifications and hemorrhagic transformation in patients with acute ischemic stroke treated with intravenous alteplase and secondarily assessed their association with functional outcomes at discharge.
Material and Methods: We retrospectively analyzed 243 patients with acute ischemic stroke who were treated with IV tPA and underwent computed tomography angiography (CTA) between 2018 and 2022. Intracranial internal carotid/carotid siphon calcifications were assessed on CTA by blinded radiologic review using the Kock-elkoren calcification scoring system. The primary outcome was hemorrhagic transformation on follow-up CT, and the secondary outcome was poor functional outcome at discharge, defined as a modified Rankin Scale (mRS) score of 3–6.
Results: Calcifications were more common in older patients, those with hypertension, and those with higher red cell distribution width values. Calcification presence or pattern was not significantly associated with hemorrhagic transformation on follow-up CT. Contralateral calcification was independently associated with poor func-tional outcome at discharge (aOR 2.95, 95% CI 1.09–7.98). In subgroup analyses based on the CTA calcification score, non-intimal calcification was associated with poor functional outcome at discharge on both the ipsilateral and contralateral sides (p=0.03 and p=0.01, respectively). Because symptomatic hemorrhagic transformation occurred in only a small number of patients, hemorrhagic findings should be interpreted cautiously.
Conclusion: In this cohort of patients with acute ischemic stroke treated with intravenous alteplase, the overall presence of intracranial carotid calcification on CTA was not significantly associated with hemorrhagic transformation on follow-up CT. However, a pattern-specific exploratory analysis suggested an inverse association between ipsilateral non-intimal calcification and hemorrhagic transformation, which should be interpreted cautiously given the low number of hemorrhagic events. In contrast, contralateral calcification, particularly a non-intimal pattern, was associated with worse functional outcome at discharge, suggesting possible short-term prognostic value. These findings do not support withholding thrombolytic therapy on the basis of calcification alone, but they indicate that calcification pattern and laterality may merit further investigation in larger studies with 90-day outcomes. Intracranial ICA/carotid siphon calcifications on CTA should not be used in isolation to defer intravenous thrombolysis. In this cohort, calcification patterns appeared more relevant to short-term discharge outcomes than to hemorrhagic transformation risk. These findings are hypothesis-generating and require confirmation in larger multicenter studies.

Keywords: Acute ischemic stroke, alteplase, hemorrhagic transformation, intracranial arterial calcification, intravenous thrombolysis