Multiple burr hole and erythropoietin combination therapy: optimal early surgical intervention for patients with acute stroke episode of moyamoya disease or moyamoya syndrome

Abstract

Objective: The optimal timing of bypass surgery for patients with moyamoya disease (MMD) or moyamoya syndrome (MMS) following an acute stroke episode remains unclear, mainly owing to the risk of postoperative complications. In this study, we aim to validate the safety and efficacy of early intervention using multiple burr hole (MBH) and erythropoietin (EPO) therapy, thereby refining the management strategy for patients with acute stroke episode of MMD or MMS.

Methods: We retrospectively analyzed data from 70 patients with MMD or MMS who underwent MBH and EPO therapy. The cohort was divided based on the time interval between the latest neurological deterioration and surgery: early (<30 days) and later (≥30 days) groups. We evaluated and compared perioperative clinical parameters and the extent of neovascularization on a 6-month postoperative angiography. Long-term clinical outcomes, including transient ischemic attack (TIA), infarction, hemorrhage, and seizure, were also analyzed during the follow-up period.

Results: In the cohort, 36 patients (51.4%) were in the early group, whereas 34 (48.6%) were in the later group. The 6-month follow-up angiography demonstrated that 34/47 hemispheres (72.3%) in the early group exhibited successful neovascularization (≥2/3 of MCA territories) compared with the 19/44 (43.2%) hemispheres in the later group (odds ratio [OR] = 3.44; 95% confidence interval [CI]: 1.46-8.45; p < 0.01). In addition, a notable reduction (≥50%) in basal moyamoya vessels was observed in 30/47 hemispheres (63.8%) from the early group vs. 12/44 (27.3%) hemispheres from the later group (OR = 4.71; 95% CI: 1.97-11.82; p < 0.001). During the average follow-up of 56.5 months, only six patients experienced infarction or hemorrhage.

Conclusion: Our dataset suggests that MBH and EPO combination therapy is an effective, minimally invasive, and acceptable treatment, even in the early period of patients with MMD or MMS following an acute stroke episode.

Keywords: erythropoietin; moyamoya disease; moyamoya syndrome; multiple burr hole; surgical intervention.

Figure 1

Criteria to evaluate regional vascularity, reduction of basal moyamoya vessels, and scales used to measure neovascularization. (A) Examples of “impaired” vascularity in the frontal and coronal suture regions and “not impaired” vascularity in the parietal and posterior parietal regions. (B) Angiography showing ≥50% of basal moyamoya vessels 6 months after surgery. (C–E) Preoperative angiography (left) and 6-month follow-up (right). Each of these is an example of Matsushima grades C, B, and A with regional neovascularization status, showing “no replacement,” “balanced,” and “replaced,” respectively.

Figure 2

Survival analysis of adverse events. TIA, transient ischemic attack.

Figure 3

Representative cases. (A–F) A 53-year-old man with recent infarction in the left MCA territory. (A) Diffusion restriction in the left MCA territory, (B) Preoperative DSA for left ICA and ECA demonstrating moyamoya vessels, (C) Reduction in CBF on CTP, (D) Four multiple burr holes at the left hemisphere, (E) Follow-up DSA showing successful revascularization, (F) improvement in CBF on follow-up CTP. (G–L) A 31-year-old woman with right thalamic ICH with IVH. (G) Non-contrast CT at admission, (H,I) preoperative DSA for each hemisphere, (J) Non-contrast CT at discharge, and (K,L) Follow-up DSA showing successful revascularization. MCA, middle cerebral artery; ICA, internal carotid artery; ECA, external carotid artery; DSA, digital subtraction angiography; CBF, cerebral blood flow; CTP, CT perfusion; ICH, intracerebral hemorrhage; IVH, intraventricular hemorrhage; CT, computed tomography.