DISCUSSION
Isolated IAD is an uncommon cause of stroke [
3]. The symptoms vary but its two main manifestations are SAH and cerebral ischemia [
13]. Between 30% and 78% of patients with IAD present with cerebral ischemia without SAH. The underlying stroke mechanism could be hemodynamic, thromboembolic or occlusion of a perforating artery by the mural hematoma [
4].
Treatment guidelines for this condition are not well-established owing to a lack of randomized trials and only observational studies with small sample sizes [
4]. In 2021, the European Stroke Organization (ESO) published suggested guidelines for the management of extracranial and intracranial artery dissection [
6]. The guidelines provide one evidence-based recommendation and three expert consensus statements regarding the management of IAD. In brief, the guidelines are as follows.
Within 4.5 hours of onset and after ruling out standard contraindications, including subtle signs of subarachnoid bleeding on brain imaging, intravenous thrombolysis (IVT) with alteplase may initially be considered in patients with symptomatic IAD with AIS. Given the risk of SAH and the superiority of aspirin over anticoagulants in the acute phase of ischemic stroke, antiplatelet agents have a better risk/benefit ratio than anticoagulants in patients with symptomatic IAD with AIS. EVT for the treatment of the IAD lesions is suggested in AIS with IAD and large vessel occlusion. Early surgical or endovascular intervention is required in patients with IAD and SAH.
The ESO guidelines have some limitations. The guidelines suggest that medical treatment is preferable to active EVT in patients with AIS symptoms unless there is complete large vessel occlusion. However, if EVT is delayed until symptoms and lesions worsen, the procedure becomes more difficult and the prognosis may be worse due to advanced lesions. In case 1, above, we believe that EVT could have yielded better clinical outcomes if it had been performed before the lesion became completely occluded. Furthermore, the guidelines make no mention of bypass surgery as a treatment option. In case 2 of this report, urgent bypass surgery was performed due to progressive neurological deterioration and good results were obtained.
In our two cases, IVT with alteplase was not considered in either of our two cases because more than 4.5 hours had passed since stroke onset when they presented to the emergency department. The patients were loaded with dual antiplatelet agents (aspirin and clopidogrel) after AIS with isolated MCAD was postulated. Despite this initial medical management, their left-side motor weakness was aggravated. Therefore, we performed EVT with stenting for the MCAD lesion in case 1, and urgent STA-MCA anastomosis in case 2.
In case 1, we used a self-expanding stent, followed by intravenous tirofiban (IV antiplatelet) infusion. Kim et al. have reported eight IADs treated with self-expanding stent placement, with 3-month modified Rankin Scale (mRS) scores of 0-2 in all eight [
9]. All their stents were patent and there was no significant residual intra-stent stenosis at angiographic follow-up. Relative to other types, self-expanding stents are easy to deliver and have low radial force, making them a safe and sufficient option for expansion of a collapsed lumen as dissections tend to be compliant and rarely have atheromatous or calcified plaques [
9,
11]. Bernava et al. reported seven IAD cases treated with self-expanding stents and concomitant tirofiban administration [
2]. In their study, mid-term follow-ups showed parent artery patency in 6/7 cases (85.7%), with mRS scores of ≤0-2 at 3 months in 5/7 cases (71.4%) [
2]. In our stent-treated case, both the flow to the right cerebral hemisphere and left-side motor strength initially improved immediately after EVT with stenting and concomitant tirofiban. However, the day after the procedure, the patient’s motor weakness fluctuated. Follow-up TFCA revealed in-stent thrombosis, so intra-arterial tissue plasminogen activator (tPA) injection was performed. The thrombolysis was successful and IV argatroban (direct thrombin inhibitor) was administered in addition to the tirofiban. After that, the patient showed a stable clinical course. Jang et al. suggest that concomitant treatment with argatroban and glycoprotein IIb/IIIa inhibitors are well-tolerated and can provide adequate anticoagulation with an acceptable bleeding risk for patients undergoing percutaneous coronary intervention [
8]. In our case, tirofiban with argatroban anticoagulation was found to be a safe and effective means of preventing in-stent thrombosis. Unfortunately, the patient’s left-side motor weakness deteriorated again the day after thrombolysis. Follow-up TFCA revealed post-stent stenosis. To our knowledge, no other reports have described post-stent stenosis or vasospasm after stenting for IAD presenting with ischemia. In our case, the post-stent stenosis was ameliorated by intra-arterial injection of verapamil, suggesting that post-stent vasospasm was the most likely cause. After this, the patient’s left upper extremity strength improved to 4/4 and she was started on nimodipine (180 mg/d) to prevent vasospasm.
Our experience suggests that vasospasm should be considered when ischemia recurs after stenting for IAD. We found intra-arterial vasodilator injection to be an effective treatment for vasospasm.
In case 2, urgent STA-MCA anastomosis was performed 3 days after symptom onset to prevent further cerebral infarction. There are a few case reports of IAD treated with STA-MCA anastomosis and the indications for surgical intervention are not yet firmly established [
7,
10,
14-
17]. Oka et al. classified patients with IAD presenting as AIS into three types: (A) Single attack with severe outcomes (cannot walk); (B) Single attack with mild to moderate outcomes (can walk); (C) Recurrent attacks with various outcomes. They propose that STA-MCA anastomosis is indicated for type C patients [
15]. In our case, the patient was type C and the bypass surgery prevented further attacks. Ikota et al. have reported a case of AIS due to IAD successfully treated with STA-MCA anastomosis. They state that early bypass surgery could salvage the cortical penumbra in the acute phase. In their case, TFCA 6 months after the surgery revealed spontaneous resolution of the dissection [
7]. In the present case, TFCA on postoperative day 5 showed partial recanalization of the dissection segment, suggesting that, with the concomitant use of antiplatelet agents, retrograde blood flow might stabilize the dissection flap. The patient recovered well without further ischaemic attacks and her left-side hemiparesis had improved significantly from motor grade 2/2 to 4/4 6 months after the surgery.
Both endovascular stenting and STA-MCA anastomosis can be good treatment options for aggravating AIS due to IAD. Endovascular stenting is a shorter less invasive procedure than bypass surgery but carries a risk of arterial rupture if a microcatheter passes through the pseudo-lumen and arterial expansion is performed after stent deployment. Bypass surgery is a longer, more complex operation and requires experience and skill in the necessary neurosurgical techniques. It carries a risk of postoperative hemorrhagic complications due to the prior use of antiplatelet agents. However, since retrograde flow through the bypass graft in the opposite direction to dissection progression can stabilize the dissection flap, it is safer in terms of avoidance of lesion perforation.
Thus, we recommend multi-modal treatment options for IAD presenting as AIS with individualized treatment selection based on patient suitability, intervention timing and the benefits and pitfalls of each option.