Introduction

Hyperperfusion syndrome after a carotid endarterectomy (CEA), which Sundt et al. first identified,24) includes atypical migraine, transient focal seizure activity, and intracerebral hemorrhage (ICH). Breen et al.3) reported that ICH's frequency was 2.7% in their series, and a recent review of the literature showed the reported ICH incidence after CEA was less than 1%.18) Impaired autoregulation of the cerebral vascular bed could explain this phenomenon.

Physicians have been performing carotid angioplasty and stenting (CAS) at increasing rates in their carotid stenosis patients, as an alternative to CEA.8)25) Although CAS is minimally invasive and is equivalent to CEA at reducing stroke risk, it has noteworthy potential procedural complications, such as embolic stroke, transient ischemic attack (TIA), allergic reaction to the contrast medium, and a risk of restenosis.14) A few reports have also documented hyperperfusion syndrome after CAS.1)9) ICH is a well-known post-CAS and post-CEA complication, and cerebral tissue autoregulation impairment may be the explanation for this.

Here, we report a rare case of diffuse subarachnoid hemorrhage (SAH) after CAS to treat progressive stroke, which had a fatal postprocedural course, and discuss its possible pathomechanisms.

Case Report

A 78-year-old woman was admitted to our hospital with a drowsy mental status, right hemiparesis (grade III), and global aphasia. Her vascular risk factors were dyslipidemia and a history of uncontrolled hypertension. Her brain computed tomography (CT) scan on admission revealed no intracranial hemorrhage or hydrocephalus, and her brain CT angiography showed multiple stenoses at the vertebral arteries (VAs), right middle cerebral artery (MCA), and the distal portions of both internal carotid arteries (ICAs). Her neck Doppler scan revealed severe stenoses in the proximal ICAs and the distal right common carotid artery (CCA).

A transcranial Doppler (TCD) ultrasound showed decreased mean blood flow velocity (MBFV) in the left MCA, with reversed flows at both ophthalmic arteries and both anterior cerebral arteries (ACAs). Conversely, the MBFVs of the basilar artery, VAs, and left ICA were increased. Magnetic resonance imaging (MRI) and MR angiography revealed acute lacunar infarctions in the left basal ganglia, with severe stenoses at both ICA bulbs (Figs. 1A, B). The patient received a continuous intravenous infusion of heparin (24,000 IU/24 hr) for 2 days, but we substituted an antithrombotic agent, Novastan (argatroban), for heparin due to prolonged activated partial thromboplastin time (aPTT).

One day after admission the patient? mental state and right hemiparesis worsened, and a follow-up brain MRI showed a new, acute infarction in the left insular area. Afterward, her neurological functioning recovered slowly, but a mild hypertension remained, despite our administration of antihypertensive medication. Single photon emission computed tomography(SPECT) showed a multifocal infarction in her left cerebral hemisphere and decreased vascular reserve function.

One week after her admission, her hemiparesis became aggravated again(grade II), and a brain MRI revealed newly-developed, acute infarctions in both basal ganglia and in the left border zone area(Fig. 2A). Prompt cerebral angiography confirmed more than 95% stenosis in the proximal left ICA and 50% stenosis at the origin site in the right ICA, with multifocal stenoses, not an aneurysm or vascular malformation, in the distal right ICA(Fig. 2B). At that point, we carried out left carotid stenting, via a transfemoral approach under local anesthesia, because of the recurrent and gradual aggravation of the patient's hypoperfusional symptoms and the relevant radiological findings. To begin the procedure, we placed a 5F guiding catheter (Headhunt cerebral catheter; Cook) into the left CCA and advanced a 0.014-inch platinum-tip guidewire (Transcend ex; Boston Scientific) through the stenosis into the distal ICA. Next, we deployed a self-expandable stent (Zilver 518 carotid stent, 6.0 X 40 mm; Cook) within the stenosis and administered 1 mg intravenous atropine prior to expanding the stent. We did not use a balloon catheter or protection filter during this procedure. The final angiogram showed marked stenosis improvement, with sufficient left ICA flow (Fig. 3A). Throughout the procedure, we administered 5,000?IU heparin intravenously, and the patient's blood pressure varied between 160/90 mmHg and 140/70 mmHg. However, she did not show any adverse symptoms.

Two hours after CAS, without any warning signs, the patient vomited suddenly, and her mental functioning abruptly deteriorated into a decorticated, rigid state. Her blood pressure increased to 230/130 mHg in spite of our administration of intravenous hydralazine. An immediate brain CT revealed diffuse SAH with hydrocephalus (Fig. 3B). We halted heparin treatment immediately, because laboratory findings showed prolonged aPTT, and performed an emergent external ventricular drainage (EVD), observing a high intraventricular pressure. One day after the EVD, the patient? mental state had deteriorated further. She had a Glasgow Coma Scale score of 3, with fully dilated pupils. The patient subsequently died on the sixth day after carotid stenting. No autopsy was performed due to family members' refusal.

Discussion

The risk factors for hyperperfusion syndrome after CAS include persistent, severe carotid artery stenosis, poor collateral circulation, contralateral carotid artery occlusion, arterial hypertension, and anticoagulation or antiplatelet aggregation treatment.10)11) In the stenotic feeding artery? territory, the arterioles dilate maximally, to compensate for the persistent hypoperfusion, and eventually lose their autoregulation abilities. Immediately after restoration of the stenotic arterial lumen increases the perfusion pressure, the arterioles are unable to constrict due to autoregulation failure, exposing the brain tissue to sudden hyperemia, which results in edema, disruption of connection integrity among the capillaries' individual endothelial cells, and, ultimately, hemorrhage.23)24) Therefore, some authors consider parenchymal hemorrhage to be a new hyperperfusion syndrome criterion and define hyperperfusion syndrome as a neurological deficit, occurring after CAS or CEA and localized ipsilateral of the treated artery.6)16) These parenchymal hemorrhages might sometimes coexist with the SAH, intraventricular hemorrhage, or subdural hemorrhage.1)6)9)15)16)22)

ICH is a severe complication of both surgical and endovascular treatments for extracranial arterial stenoses, but researchers do not yet fully understand its pathophysiology. According to the published data, the intracranial hemorrhage risk after CAS is generally higher than that after CEA.15)16) The post-CAS clinical consequences are also more serious. The recent articles published about ICH after CAS show that this hemorrhage occurs within a few hours after the procedure, in contrast to the CEA findings.5)6)13)16) As expected, our patient's the signs of intracranial bleeding in emerged 2 hours after she underwent the procedure.

To the best of our knowledge, the previous literature includes only four reports of SAH after CAS.1)9)12)22) Researchers have presented several possible pathomechanisms for the occurrence of SAH after CAS in the literature, as follows: 1) Autoregulation impairment, as described for hyperperfusion syndrome with ICH after CEA or CAS, is responsible for SAH after CAS.13)16)17) Persistent hypoperfusion distal to a severe stenosis and maximal vasodilatation with loss of the arterioles' vasoconstriction abilities might result in very high perfusion pressure after CAS, thereby disrupting the capillary endothelial cells' tight junctions and causing SAH. Four further case reports of SAH after CAS support this proposal.1)9)12)22) Schoser et al. 22) reported a patient with SAH after simultaneous angioplasty of multiple extracranial artery stenoses, including both vertebral arteries and the right subclavian artery and a high-grade stenosis of the left ICA. 2) Other findings suggested that high-grade stenosis accompanied by multifocal stenosis of the contralateral ICA, as seen in our patient, may increase blood flow in the collateral vessels and weaken the vessel walls, resulting in angiographic occult microaneurysms. Such findings also suggested increased perfusion pressure after CAS might cause vessel or microaneurysm ruptures subsequent to SAH. 3) The combination therapy of heparin and antithrombotic agents could induce coagulopathy, which might influence the risk of SAH after carotid stenting. Our patient's laboratory data showed aPTT prolongation on the day of CAS. 4) Finally, researchers think long-lasting, uncontrolled arterial hypertension is an additional factor affecting SAH in all of these processes.

Although there has been some debate regarding CEA timing after the onset of ipsilateral TIA or stroke in patients with severe ICA stenosis, the authors of many recent articles have recommended early surgery.2)4)19)20) In particular, the guideline proposed by Sacco et al.21) suggests surgery for CEA, within 2 weeks of the last symptomatic event, in indicated cases. Staged angioplasty will be effective for preventing hyperperfusion syndrome. Yoshimura et al.26) reported staged angioplasty is a simple and effective method for avoiding hyperperfusion syndrome in patients at high risk of hyperperfusion after carotid revascularization. 

Conclusion

Researchers have yet to fully investigate the exact incidence and the pathomechanism of this potentially fatal complication. However, multiple risk factors may predispose individuals to this lethal complication. We conclude such patients require close observation of clinical symptoms, careful treatment of arterial hypertension, and appropriate control of their periprocedural coagulation status. With these precautions, we can reduce these rare but fatal complications, although complete avoidance is impossible.

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