Abstract
Cerebral hyperperfusion syndrome is a potentially life-threatening complication following carotid artery stenting, particularly in patients with impaired cerebrovascular autoregulation. Staged angioplasty has been proposed to reduce this risk by gradually restoring blood flow and promoting recovery of autoregulatory function. However, it remains unclear how autoregulation responds intraoperatively during each stage of staged angioplasty. We report a case of a 79-year-old man with progressive ischemic stroke caused by severe stenosis of the right internal carotid artery. Preoperative cerebral blood flow was reduced in the right hemisphere. Three months after stroke onset, first-stage percutaneous transluminal angioplasty was performed under near-infrared spectroscopy monitoring. Following balloon dilatation, the minimal lumen diameter increased from 0.4 mm to 1.0 mm, and a marked increase in regional cerebral oxygen saturation on the affected side prompted termination of further dilation. Postoperative imaging showed improved perfusion without signs of cerebral hyperperfusion syndrome. Nineteen days later, definitive carotid artery stenting was performed. Although the lumen diameter increased by 2.7 mm during the stenting procedure, there was no sustained increase in regional cerebral oxygen saturation, and no hyperperfusion or neurological symptoms developed. These contrasting intraoperative responses suggested that cerebral autoregulation was impaired before the first-stage percutaneous transluminal angioplasty procedure but had recovered by the time of the second. This case highlights the potential value of real-time near-infrared spectroscopy monitoring in assessing cerebral autoregulation and guiding intraoperative decision-making during staged angioplasty. Timely identification of hyperperfusion risk using this approach may improve the safety of carotid interventions, particularly in high-risk patients with compromised hemodynamic reserve.
Introduction
Cerebral hyperperfusion syndrome (CHS) is a potentially life-threatening complication following carotid artery stenting (CAS) or carotid endarterectomy (CEA).1-3) To mitigate this risk, staged angioplasty (SAP), a two-step approach involving initial percutaneous transluminal angioplasty (PTA) followed by definitive CAS, has been proposed.4,5) SAP aims to avoid abrupt increases in cerebral blood flow (CBF) by allowing gradual restoration of cerebral autoregulation.4,6) Partial dilatation of the stenosis is thought to gradually restore CBF and adapt cerebral autoregulation.7) Changes in cerebrovascular reserve between stages can typically be assessed by perioperative single-photon emission computed tomography (SPECT).6)
Transcranial near-infrared spectroscopy (NIRS) is a technology used clinically to monitor regional cerebral oxygen saturation (rSO2),8) and has been shown to predict CHS after CAS or CEA.9-12) A characteristic pattern, namely a marked increase in ipsilateral rSO2 immediately after revascularization, has been associated with impaired autoregulation.10) However, intraoperative NIRS dynamics during SAP have not been reported, and it remains unclear how autoregulation changes during each stage of SAP.
We report a case of severe carotid stenosis treated with SAP, in which continuous NIRS monitoring revealed a strikingly different rSO2 response pattern between the two procedures. The first-stage PTA induced a rapid increase in ipsilateral rSO2, suggesting impaired autoregulation, whereas the second-stage CAS showed no such change, implying recovery of autoregulatory function. This case highlights the potential utility of intraoperative NIRS for real-time assessment of cerebrovascular autoregulation during SAP and provides insight into CHS pathophysiology in staged carotid revascularization.
Case Report
Preoperative course
A 79-year-old man presented with left-hand weakness 1 hour prior to admission. His medical history included hypertension, poorly controlled type 2 diabetes (hemoglobin A1c [HbA1c] 10.0%), dyslipidemia, and angina pectoris. He was on aspirin and oral hypoglycemic agents. Neurological examination showed mild left hemiparesis. Diffusion-weighted magnetic resonance imaging (MRI) revealed small infarcts in the right precentral gyrus (Figure 1A), and magnetic resonance angiography (MRA) showed poor visualization of the right intracranial internal carotid artery (ICA) (Figure 1B), suggesting severe proximal stenosis. Cervical T1-weighted MRI showed high-intensity intraplaque signals (Figure 1C). Angiography confirmed 74.1% stenosis defined according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) with delayed distal filling (Figure 1D). Baseline 123I-iodoamphetamine (123I-IMP) SPECT revealed slightly reduced CBF in the right middle cerebral artery (MCA) territory (38.2 mL/100 g/min; asymmetry index [AI], 0.96; Figure 1E). The AI was calculated as the ratio of CBF in the affected side to that in the contralateral side. Dual antiplatelet therapy (DAPT; clopidogrel and aspirin) and atorvastatin were initiated. His symptoms improved, and he was discharged after 7 days.
CAS was planned after stabilization of the patient's underlying conditions, but correction of blood pressure and glycemic control required additional time. Three months later, while awaiting scheduled CAS, he was readmitted due to a transient ischemic attack with recurrent left-hand weakness. MRI showed no new infarction, but MRA indicated further progression of stenosis in the right intracranial ICA and MCA (Figure 2A). DAPT was modified by switching clopidogrel to prasugrel. Preprocedural 123I-IMP SPECT demonstrated marked hypoperfusion in the right MCA territory (CBF, 34.0 mL/100 g/min; AI, 0.61; Figure 2B). Considering the high risk of CHS due to ipsilateral hypoperfusion, we opted for SAP instead of one-stage CAS. In addition, antiplatelet therapy was escalated to triple antiplatelet therapy (TAPT; aspirin, prasugrel, and cilostazol) to prevent in-stent restenosis after CAS.13)
First-stage PTA
On day 104 after stroke onset, first-stage PTA was performed under local anesthesia and systemic heparinization. Continuous perioperative NIRS monitoring was conducted using a cerebral oximeter (INVOS 5100C; Somanetics, Troy, MI, USA). Preoperative angiography revealed near occlusion of the right ICA with severe distal flow restriction (Figure 2C). An 8 Fr guiding catheter (Cello; Medtronic, Minneapolis, MN, USA) was introduced via the femoral artery into the right common carotid artery (CCA). A 0.014-inch micro-guidewire (CHIKAI; Asahi Intecc, Aichi, Japan) was navigated through the lesion under balloon occlusion, followed by the placement of a distal protection filter (Spider FX; Medtronic, Minneapolis, MN, USA). Angioplasty was performed with a 2.0/20 mm balloon catheter (SHIDEN; Kaneka Medix, Osaka, Japan) (Figure 2D), increasing the minimal lumen diameter (MLD) from 0.4 mm to 1.0 mm (Figure 2E). Angiography after PTA showed improved visualization of the right MCA with delayed contrast washout (Figure 2F).
During CCA occlusion, right-sided rSO2 decreased by 7% from baseline without neurological intolerance. Three minutes after reperfusion, rSO2 abruptly increased by 11% (Figure 2G), leading us to forgo further dilatation. The patient remained neurologically stable. Systolic blood pressure was maintained below 140 mmHg. Four hours after revascularization, the elevated right/left rSO2 ratio normalized (Figure 2H). Postprocedural MRA showed improved flow in the right ICA and MCA (Figure 2I). SPECT on postoperative day 3 revealed increased CBF in the right MCA territory (44.7 mL/100 g/min; AI, 1.03; Figure 2J). Although the diagnostic criteria for hyperperfusion phenomenon (HPP) were not fully met, the characteristic intraoperative increase in rSO2 suggested a hemodynamic state analogous to HPP, and the patient was managed as being at high risk. To prevent seizures and lesional reocclusion, levetiracetam, edaravone, and argatroban were administered intravenously for 7 days.
Second-stage CAS
Nineteen days later, second-stage CAS was performed under the same conditions as the first procedure, including systemic heparinization, local anesthesia, and NIRS monitoring. Preprocedural angiography showed a slight restenosis and persistent distal flow restriction (Figure 3A). A 9 Fr guiding catheter (Cello, Medtronic) was inserted into the right CCA. After pre-dilatation with a 3.0/20 mm balloon catheter (SHIDEN, Kaneka Medix) under distal protection with a filter device (Spider FX, Medtronic; Figure 3B), the MLD increased from 0.7 mm to 1.3 mm (Figure 3C). A Carotid WALLSTENT (8.0/29 mm; Boston Scientific, Marlborough, MA, USA) was deployed, followed by two post-dilatations using 3.0/20 mm (SHIDEN, Kaneka Medix) and 4.0/30 mm (Rx-Genity, Kaneka Medix) balloons (Figure 3D and 3E). Final angiography showed improved flow with an MLD of 3.4 mm (Figure 3F). In contrast to the findings after the first-stage PTA, angiography of the right ICA after CAS showed normalized visualization of the right MCA and shorter contrast washout (Figure 3G).
During balloon inflations, rSO2 on the right decreased transiently by 7-10%, but increased by only 1% after final post-dilatation (Figure 3H). No sustained rSO2 elevation was observed. Two hours post-revascularization, the right/left rSO2 ratio declined by 9% (Figure 3I). SPECT on postoperative day 1 demonstrated the absence of hyperperfusion (50.7 mL/100 g/min; AI, 0.97; Figure 3J). TAPT was de-escalated to DAPT by discontinuing cilostazol. The patient was discharged 9 days later without any complication or neurological deficit.
Discussion
NIRS is widely used for perioperative monitoring to predict CHS after CAS or CEA.9-12) However, intraoperative NIRS changes during SAP have not been described, and the distinction between stages remains unclear. Matsumoto et al.10) reported that in CHS cases, rSO2 dropped during ICA occlusion and subsequently increased to 124% of baseline. Park et al.12) also described a V-shaped tissue oxygenation index (TOI) curve, with post-reperfusion levels exceeding baseline in CHS. Terakado et al.11) suggested a TOI/baseline threshold of 109% for detecting HPP. During first-stage PTA in our case, rSO2 decreased to 89% during occlusion, then increased to 117% at 3 minutes and to 111% at 5 minutes post-reperfusion, consistent with patterns seen in patients with high-risk CHS. In contrast, no sustained rSO2 elevation occurred during second-stage CAS, suggesting that cerebral autoregulation had recovered after the initial procedure and had mitigated the CHS risk.
CHS is thought to arise from impaired cerebral autoregulation.7) SAP is designed to gradually increase CBF through partial dilation, allowing autoregulatory adaptation. In this case, the increase in baseline right/left rSO2 ratio from 86% before PTA to 91% before CAS supports the idea that sustained recovery of CBF allowed adaptive restoration of cerebrovascular reserve during the interval between two procedures.
Full dilatation in one-stage CAS can lead to abrupt CBF increase and CHS. Moderate dilation with 3.0 mm balloons is often recommended to avoid this,4,6,14,15) though some studies suggest that dilation <2.0 mm may be optimal.5) However, objective criteria for determining adequate dilation are lacking. In our patient, 2.0 mm balloon dilation improved distal flow and induced a marked rSO2 increase, prompting us to withhold further PTA. The absence of post-reperfusion increase in rSO2 and the normalization of AI during definitive CAS implied successful restoration of cerebral autoregulation after initial PTA. Additionally, although definitive CAS achieved a larger post-dilatation diameter, angiographic findings showed reduced visualization of the MCA after CAS compared with that after the first-stage PTA. These findings also support the notion that even limited dilation with a small balloon in the first stage may contribute to the improvement of autoregulatory capacity. Thus, intraoperative NIRS may guide the extent of PTA and help prevent over-dilation of the lesion. Though NIRS does not directly measure autoregulatory function, the absence of a post-reperfusion rSO2 surge, together with stable CBF on SPECT, indirectly supports recovery of autoregulatory capacity.
The optimal interval for SAP remains uncertain. NIRS studies in CHS show TOI normalizing within 5-6 days post-CAS,12,16) while others report improved dynamic autoregulation within 24 hours.17) In our case, the right/left rSO2 ratio returned to baseline within 4 hours after first-stage PTA, indicating a rapid restoration of hemodynamic reserve, whereas the normalized AI (1.03) observed 3 days later might suggest a more gradual recovery process occurring over several days. Additionally, the decreased baseline right/left rSO2 ratio after second-stage CAS mirrored that after first-stage PTA, further supporting the rapid recovery of autoregulation.
From a clinical perspective, this case suggests that temporal changes in rSO2 patterns may reflect the recovery of cerebrovascular autoregulation between staged procedures. Although these findings are based on a single case and cannot establish a definitive criterion, they raise the possibility that serial assessment of NIRS parameters, particularly interhemispheric rSO2 differences and their dynamic response to revascularization, may provide supportive information for determining the optimal timing of the second-stage intervention. Furthermore, integration of NIRS with other modalities such as SPECT and additional bedside hemodynamic assessments may improve the accuracy of evaluating autoregulatory recovery and help optimize the timing and safety of SAP.18)
Several limitations merit consideration. NIRS monitors the anterior circulation via forehead probes, and its accuracy may be influenced by variations in A1 segment development and collateral pathways.19) Additionally, extracranial blood flow and systemic hemodynamic factors may affect the measurements.20) Although using the right-to-left rSO2 ratio may partially mitigate these influences, this approach does not eliminate the inherent limitations of NIRS.
Conflicts of Interest Disclosure
Author Hidenori Endo is a member of the Editorial Board of this journal but was not involved in the editorial decision or peer review of this manuscript.
Patient Consent
The patient has consented to the submission of the case report for submission to the journal.
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