Umeå University's logo

Background and aims: Symptomatic carotid stenosis cause approxi-mately 15% of all ischemic stroke. Carotid near-occlusion (CNO) is a severe carotid stenosis causing a diameter reduction (collapse) in the distal internal carotid artery (ICA). CNO accounts for approximatelyone-third of cases with symptomatic carotid stenosis. Despite its clinical relevance, CNO remains as an understudied condition in terms of diagnostics, pathophysiology and risk of recurrent stroke.

The overall aim of this thesis is to advance the understanding of underlying pathophysiology behind stroke in CNO, targeting a potentially embolic mechanism. Moreover, we aim to evaluate the short-term risk of strokeand the accuracy of radiologists in identifying CNO using computed tomography angiography (CTA).

Methods: We conducted four studies using retrospective and prospective data from the “Transatlantic Carotid Near-Occlusion Study cohort” (TACNOS) and the “Umeå Carotid Cohort” (UCC). In the TACNOS cohort,we retrospectively reviewed medical records to assess short-term risk ofrecurrent ipsilateral ischemic stroke (study I) and routine CTA reports to evaluate the diagnostic accuracy of radiologists in identifying CNO on routine CTA (study II). In the UCC cohort, we prospectively assessed theincidence of microembolic signals (MES) on transcranial Doppler (TCD) distal to symptomatic CNO (study III), as a biomarker of embolic mechanism. By use of pooled TACNOS and UCC data, we further investigatedthe potentially embolic mechanism in CNO (study IV), by assessing the prevalence of ipsilateral intracranial medium- or large-vessel occlusions, defined as “ipsilateral presumed embolic vessel occlusions” (iPEVO) on CTA among patients with symptomatic CNO.iv

Results: In study I, 99 of 365 included patients had CNO (42 with full collapse and 57 without full collapse). The 90-day risk of recurrent ipsi-lateral ischemic stroke was 30% in symptomatic CNO with full collapse, 22% in symptomatic CNO without full collapse, compared to 15% in symptomatic conventional ≥50% carotid stenosis (p = 0.012). In study II, routine CTA interpretation by radiologists showed strikingly low diagnostic accuracy for carotid near-occlusion, with sensitivity of only 8-22%.

Of 109 cases with TCD-recordings from the UCC cohort, MES incidencein study III was at least similarly high in symptomatic CNO (46%) compared to symptomatic conventional ≥50% carotid stenosis (27%; p = 0.08) and significantly higher than asymptomatic ≥50% carotid stenosis (6%; p = 0.005). Out of 124 cases with CTA on the same day following stroke onset, the prevalence of iPEVO in study IV was higher in symptomatic CNO with full collapse (89%) and without full collapse (44%) than symptomatic conventional ≥50% carotid stenosis (10%; p < 0.001).

Conclusions: CNO is underrecognized in Sweden. The high short-term risk of recurrent stroke in CNO highlights the urgent need for enhanced education and diagnostic radiological methods. An embolic mechanism behind stroke in CNO appears central, the next key step should be to understand the potential role of concurrent hemodynamic factors to guide future treatment strategies.

Objective: It is unclear whether ischaemic stroke among patients with symptomatic carotid near occlusion is caused by an embolic or haemodynamic mechanism. An embolic mechanism can be reflected by the occurrence of microembolic signals (MES) on transcranial Doppler. This study aimed to compare the incidence of MES between patients with symptomatic near occlusion, symptomatic conventional ≥ 50% stenosis, and asymptomatic ≥ 50% stenosis.

Methods: This cross sectional study included patients with ≥ 50% symptomatic or asymptomatic carotid stenosis. The degree of stenosis was assessed with computed tomography angiography, where near occlusion was diagnosed by feature interpretation. Symptomatic was defined as ipsilateral events within six months. Occurrence of MES was recorded bilaterally in the middle cerebral artery for 30 minutes with transcranial Doppler.

Results: A total of 109 participants with ≥ 50% carotid stenosis were included, comprising 52 with symptomatic ≥ 50% conventional stenosis, 41 symptomatic near occlusion, and 16 asymptomatic ≥ 50% stenosis. The incidence of MES was 46% (19/41; 95% confidence interval [CI] 30 – 62%) among symptomatic near occlusion, 27% (14/52; 95% CI 14 – 39%) among symptomatic ≥ 50% conventional stenosis, and 6% (1/16; 95% CI 0 – 20%) among asymptomatic ≥ 50% carotid stenosis. The incidence of MES tended to be higher among symptomatic near occlusions compared with symptomatic ≥ 50% conventional stenoses (unadjusted odds ratio [OR] 2.3, 95% CI 1.0 – 5.6; p = .054), but was statistically significantly higher after adjustments (adjusted OR 3.9, 95% CI 1.4 – 10.7; p = .009). The MES incidence was higher among symptomatic near occlusions than asymptomatic ≥ 50% stenoses (p = .005).

Conclusion: Microembolic signals appear to be more prevalent in symptomatic near occlusions compared with both symptomatic conventional ≥ 50% carotid stenoses and asymptomatic conventional ≥ 50% carotid stenoses. These findings could reflect a possible embolic mechanism behind ischaemic stroke in symptomatic carotid near occlusion patients, but do not rule out concurrent haemodynamic mechanisms. Additional studies using various markers of both embolic and haemodynamic mechanisms are warranted.

Objective: To assess if intravenous thrombolysis (IVT) affects the risk of recurrent preoperative cerebrovascular events before carotid surgery or stenting in patients with symptomatic ≥ 50% carotid stenosis.

Methods: Three cohorts of symptomatic ≥ 50% carotid stenosis patients were merged. To make the control group relevant, we excluded patients not presenting with stroke on the day of symptom onset. The risk of preoperative cerebrovascular events up to 30 days were compared between the IVT-treated and non-IVT-treated.

Results: 316 patients were included, 64 (20%) treated with IVT. Those treated with IVT had similar risk of recurrent ipsilateral ischemic stroke or retinal artery occlusion (12% at day 7, 12% at day 30) as those not treated (9% at day 7, 15% at day 30; adjusted HR 0.9, 95%CI 0.4-2.2). There was a tendency (p=0.09) towards time-dependency in the data where the recurrence risk was higher in IVT treated at day 0 (6% in IVT-treated, 1% in non-IVT-treated, OR 5.5, 95%CI 1.2-25.4, p=0.03). This was not significant when adjusting for co-factors (adjusted OR 4.4, 95%CI 0.9-21.8, p=0.07) and was offset by a later risk decrease, with no remaining risk difference between IVT-treated and non-IVT treated at day 7.

Conclusions: IVT treatment does not seem to affect the risk of recurrent ipsilateral ischemic stroke in patients with symptomatic ≥ 50% carotid stenosis: The risk is high in both IVT-treated and non-IVT-treated. However, there might be a risk increase on the day of IVT treatment that is offset by a risk decrease during the first week.

Introduction: Carotid-Fetal-Posterior (CFP) syndrome is a posterior cerebral artery (PCA) territory ischemic stroke/TIA caused by symptomatic >= 50% carotid stenosis or occlusion via fetal posterior communicating artery. We aimed to assess the incidence of CFP syndrome and prevalence of CFP syndrome among symptomatic >= 50% carotid stenosis or occlusion as these are unknown.

Methods: We reassessed consecutive CTAs from 4042 persons, and included locally admitted patients with >= 50% carotid stenosis or occlusion. These were assessed for symptoms and signs of possible posterior circulation stroke/TIA (suspicion of CFP syndrome). Among these, those with unilateral PCA territory stroke/TIA, ipsilateral stenosis and fetal/fetal type PCA were considered CFP syndrome.

Results: We included 208 locally admitted patients with >= 50% carotid stenosis or occlusion, 33 (16%) patients had suspicion of CFP syndrome, of which 3 (9%) had CFP syndrome. The prevalence of CFP syndrome was 2.9% of symptomatic >= 50% carotid stenosis or occlusion; incidence was 4.23 per 1 000 000 person-years. Also, we found a lower prevalence of CFP-syndrome (0.9%, p=0.047) among referred patients with symptomatic >= 50% carotid stenosis or occlusion than among locally admitted patients with symptomatic >= 50% carotid stenosis or occlusion.

Discussion/Conclusion: CFP syndrome has a low incidence and low prevalence among symptomatic carotid stenosis cases. Given lower prevalence of CFP syndrome among referred cases than local, CFP-syndrome seems susceptible to underdiagnosis. On the other hand, few cases with suspicion of CFP syndrome had CFP syndrome, why CFP syndrome also seems susceptible to overdiagnosis if detailed assessment is not employed.

Purpose: Create a new definition of near-occlusion with full collapse to predicting recurrent stroke.

Methods: Pooled analysis of two studies. Patients with symptomatic ≥ 50% carotid stenoses were included. Outcome was preoperative recurrent ipsilateral ischemic stroke or retinal artery occlusion within 28 days of presenting event. We analyzed several artery diameters on computed tomography angiography and stenosis velocity on ultrasound.

Results: A total of 430 patients with symptomatic ≥ 50% carotid stenosis were included, 27% had near-occlusion. By traditional definition, 27% with full collapse and 11% without full collapse reached the outcome (p = 0.047). Distal internal carotid artery (ICA) diameter, ICA ratio, and ICA-to-external carotid artery ratio were associated with the outcome. Best new definition of full collapse was distal ICA diameter ≤ 2.0 mm and/or ICA ratio ≤ 0.42. With this new definition, 36% with full collapse and 4% without full collapse reached the outcome (p < 0.001).

Conclusions: Defining near-occlusion with full collapse as distal ICA diameter ≤ 2.0 mm and/or ICA ratio ≤ 0.42 seems to yield better prognostic discrimination than the traditional appearance-based definition. This novel definition can be used in prognostic and treatment studies of near-occlusion with full collapse.

The aim of this study was to compare the angiographic appearance of symptomatic and asymptomatic carotid near-occlusion. We have found no such previous study. The study hypothesis was that among symptomatic patients with ≥ 50% carotid stenosis, near-occlusion is more common and near-occlusions are more severe than among asymptomatic persons with ≥ 50% carotid stenosis. We reassessed consecutive CTAs from 4042 persons, 645 had ≥ 50% carotid stenosis, and 385 (60%) symptomatic. Near-occlusion was similarly common in symptomatic (105, 27%) and asymptomatic (56, 24%) cases. Among near-occlusions, the angiographic appearance was very similar between symptomatic and asymptomatic cases: mean stenosis lumen diameter (0.7 mm), distal ICA diameter (2.1 mm), and ECA ratio (0.79) were the same in both groups. Mean ICA ratio (0.46 and 0.48) and share of full collapse was very similar (45% and 42%). These findings add to the pathophysiological understanding of carotid near-occlusion.

Objective: Assess the sensitivity and specificity of computed tomography angiography (CTA) for carotid near-occlusion diagnosis interpreted in clinical practice against expert assessment.

Methods: CTAs were graded by two expert interpreters for near-occlusion. Findings were compared with clinical reports in 383 consecutive cases with symptomatic ≥ 50% carotid stenosis. In addition, 14 selected CTA exams (8 near-occlusions and 6 controls) were analyzed in a national effort by 13 radiologists experienced with carotid CTA.

Results: In clinical practice, imaging reports were 20% (95% CI 12–28%) sensitive for near-occlusion, ranging 0–58% between different radiologists; specificity was 99%. Among the 13 radiologists reviewing the same 8 near-occlusions, the average sensitivity was 8%, ranging 0–75%; specificity was 100%.

Conclusions: Carotid near-occlusion is systematically under-reported in clinical routine practice, caused by limited application of grading criteria when assessing CTA.

Objective: To assess the risk of recurrent ipsilateral ischemic stroke in patients with symptomatic near-occlusion with and without full collapse.

Methods: Included were consecutive patients eligible for revascularization, grouped into symptomatic conventional ≥ 50% carotid stenosis (n = 266), near-occlusion without full collapse (n = 57) and near-occlusion with full collapse (n = 42). The risk of preoperative recurrent ipsilateral ischemic stroke was analyzed, or, for cases not revascularized within 90 days, 90-day risk was analyzed.

Results: The risk of a preoperative recurrent ipsilateral ischemic stroke or ipsilateral retinal artery occlusion was 15% (95% CI 9–20%) for conventional ≥ 50% stenosis, 22% (95% CI 6–38%) among near-occlusion without full collapse and 30% (95% CI 16–44%) among near-occlusion with full collapse (p = 0.01, log rank test). In multivariate analysis, near-occlusion with full collapse had a higher risk of recurrent ipsilateral ischemic stroke (adjusted HR 2.6, 95% CI 1.3–5.3) and near-occlusion without full collapse tended to have a higher risk (adjusted HR 2.0, 95% CI 0.9–4.5) than conventional ≥ 50% stenosis. Only 24% of near-occlusion with full collapse underwent revascularization, common causes for abstaining were misdiagnosis as occlusion (31%), deemed surgically unfeasible (21%) and low perceived benefit (10%).

Conclusions: Symptomatic carotid near-occlusion has a high short-term risk of recurrent ipsilateral ischemic stroke, especially near-occlusion with full collapse.