Introduction: There currently exists no proven neuroprotective agent for ischemic stroke. Minocycline has been shown in numerous pre-clinical studies, and a clinical spinal cord injury trial to have neuroprotective properties. Higher doses, and pre-treatment increased effectiveness. We sought to evaluate the safety of high-dose minocycline during carotid revascularization procedures (CRV): carotid endarterectomy (CEA) and carotid stenting (CAS).

Methods: Patients undergoing CRV where treated with the following minocycline regimen: 800mg PO the night prior to CRV, 700mg IV the morning of CRV, 600mg PO in the afternoon after the CRV, and 500mg and 400mg PO the next morning and afternoon respectively. All patients were clinically monitored for the development of any adverse reactions, and had extensive pre- and post-procedural labwork (including CMP, ECG, troponins). MRI imaging, with a minimum of FLAIR and DWI/ADC sequences, was obtained pre-procedurally (<30 days from procedure), post-procedurally (24 hours from procedure), and at follow-up (2-6 weeks). Additionally, formal neurocognitive evaluations were performed pre-procedurally, within 2-6 weeks after the procedure, and later at follow-up. (NCT02178813, IND118451).

Results: Although the original number of patients to be enrolled was 20, the study was voluntarily suspended after eight patients were screened, and 6 patients receiving the medication during CRVs (4 CEA/ 2 CAS, 4 symptomatic/2 asymptomatic). Two of these 6 patients had unexpected post-procedural carotid occlusions after CEAs, one of them involving bilateral carotids (including the contralateral previously stented carotid). Both these patients were treated with endovascular thrombectomies and stenting. Despite the carotid occlusions, the patients had limited strokes, and made a better than expected recovery.

Conclusions: Based on the limited information derived from this study, it is plausible that high-doses of minocycline may have neuroprotective effects during cerebral ischemia, but may also have thrombogenic effects. A study using lower doses of minocycline in the same setting maybe more appropriate.

Patient Care: Neuroprotective agents are urgently needed for ischemic stroke. The results of the current study provide some preliminary data on the safety and effectiveness of minocycline as a neuroprotective agent during carotid revascularization procedures.

Learning Objectives: By the conclusion of this session, participants should be able to 1)discuss the need for neuroprotective agents in ischemic stroke 2)describe the existing evidence regarding the neuroprotective effects of minocycline. 3) understand results of the current trial and the rationale for planning future studies

References: Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Casha S, Zygun D, McGowan MD, Bains I, Yong VW, Hurlbert RJ. Brain. 2012 Apr;135(Pt 4):1224-36. doi: 10.1093/brain/aws072.