The role of positron-emission tomography in the diagnosis of giant cell arteritis

Abstract Background: Giant cell arteritis (GCA) is an inflammatory disease of the larger vessels, typically affecting the temporal arteries, but involvement of the carotid and thoracic arteries is not uncommon. Serious complications such as blindness can occur if the disease is left untreated. Currently, the gold standard test for GCA is a temporal biopsy, but this invasive technique is not without risks and frequently inaccurate. We investigate the use of 18-fluoro-desoxyglucose (18F-FDG) positron emission tomography (PET) as a new diagnostic means in GCA. Methods: We performed a literature search in the MEDLINE database for original research articles written in the English language that discussed the use of PET in diagnosing GCA. After applying selection criteria, 9 articles were included for literature review and 4 of these were incorporated in a meta-analysis. Results: 18-FDG uptake in the extracranial arteries is correlated to the presence GCA within patients suspected for vasculitis. In our meta-analysis we found the following results: sensitivity 85% (95% CI; 74-92%, I2=0.0%), specificity 91% (95% CI; 82-96%, I2=31.2%), positive likelihood ratio 7.18 (95% CI; 3.43-15.06, I2 =10.1%) and negative likelihood ratio 0.19 (95% CI; 0.11-0.33, I2= 0.0%). Discussion: 18F-FDG-PET cannot replace temporal artery biopsy at the present time, because of its limited ability to visualise the cranial arteries. However, PET may be provide valuable information when extracranial involvement is suspected, specifically in biopsy-negative patients who are strongly suspected of having GCA

Endovascular Treatment The Role of Dominant Caliber M2 Segment Occlusion in Ischemic Stroke

Background and Purpose—It is unclear whether endovascular treatment (EVT) is beneficial for patient

Acute Endovascular Treatment of Patients With Ischemic Stroke From Intracranial Large Vessel Occlusion and Extracranial Carotid Dissection

Introduction: Carotid artery dissection (CAD) and atherosclerotic carotid artery occlusion (ACAO) are major causes of a tandem occlusion in patients with intracranial large vessel occlusion (LVO). Presence of tandem occlusions may hamper intracranial access and potentially increases the risk of procedural complications of endovascular treatment (EVT). Our aim was to assess neurological, functional and technical outcome and complications of EVT for intracranial LVO in patients with CAD in comparison to patients with ACAO and to patients without CAD or ACAO.Methods: We analyzed data of the MR CLEAN trial intervention arm and MR CLEAN Registry, acquired in 16 Dutch EVT-centers. Primary outcome was the change in stroke severity by comparing the National Institute of Health Stroke Scale (NIHSS) score at 24–48 h after treatment vs. baseline. Secondary outcomes included reperfusion rate and symptomatic intracranial hemorrhage (sICH). We compared outcomes and complications between patients with CAD vs. patients with ACAO and patients without CAD or ACAO.Results: In total, we identified 74 (4.7%) patients with CAD, 92 (5.9%) patients with ACAO and 1398 (89.4%) patients without CAD or ACAO. Neurological improvement at short-term after EVT in patients with CAD was significantly better compared to ACAO (resp. mean −5 vs. mean −1 NIHSS point; p = 0.03) and did not differ compared to patients without CAD or ACAO (−4 NIHSS points; p = 0.62). Rates of successful reperfusion in patients with CAD (47%) was comparable to patients with ACAO (47%; p = 1.00), but was less often achieved compared to patients without CAD or ACAO (58%; p = 0.08). Occurrence of sICH did not differ significantly between CAD patients (5%) and ACAO (11%; p = 0.33) or without CAD/ACAO (6%; p = 1.00).Conclusion: EVT in patients with intracranial LVO due to CAD results in neurological improvement comparable to patients without tandem occlusions. Therefore, carotid artery dissection by itself should not be a contraindication for endovascular treatment in stroke patients with intracranial large vessel occlusion. Although more challenging endovascular procedures are to be suspected in both patients with CAD or ACAO, accurate distinction between CAD and ACAO might influence clinical decision making as better clinical outcome can be expected in patients with CAD

Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke

Objective: The putative mechanism for the favourable effect of endovascular treatment (EVT) on functional outcome after acute ischaemic stroke is preventing follow-up infarct volume (FIV) progression. We aimed to assess to what extent difference in FIV explains the effect of EVT on functional outcome in a randomised trial of EVT versus no EVT (MR CLEAN). Methods: FIV was assessed on non-contrast CT scan 5–7 days after stroke. Functional outcome was the score on the modified Rankin Scale at 3 months. We tested the causal pathway from intervention, via FIV to functional outcome with a mediation model, using linear and ordinal regression, adjusted for relevant baseline covariates, including stroke severity. Explained effect was assessed by taking the ratio of the log odds ratios of treatment with and without adjustment for FIV. Results: Of the 500 patients included in MR CLEAN, 60 died and four patients underwent hemicraniectomy before FIV was assessed, leaving 436 patients for analysis. Patients in the intervention group had better functional outcomes (adjusted common odds ratio (acOR) 2.30 (95% CI 1.62–3.26) than controls and smaller FIV (median 53 vs. 81 ml) (difference 28 ml; 95% CI 13–41). Smaller FIV was associated with better outcome (acOR per 10 ml 0.60, 95% CI 0.52–0.68). After adjustment for FIV the effect of intervention on functional outcome decreased but remained substantial (acOR 2.05, 95% CI 1.44–2.91). This implies that preventing FIV progression explains 14% (95% CI 0–34) of the beneficial effect of EVT on outcome. Conclusion: The effect of EVT on FIV explains only part of the treatment effect on functional outcome. Key Points: • Endovascular treatment in acute ischaemic stroke patients prevents progression of follow-up infarct volume on non-contrast CT at 5–7 days.• Follow-up infarct volume was related to functional outcome, but only explained a modest part of the effect of intervention on functional outcome.• A large proportion of treatment effect on functional outcome remains unexplained, suggesting FIV alone cannot be used as an early surrogate imaging marker of functional outcome

Collateral Circulation and Outcome in Atherosclerotic Versus Cardioembolic Cerebral Large Vessel Occlusion

Background and Purpose- Due to chronic hypoperfusion, cervical atherosclerosis may promote cerebral collateral circulation. We hypothesized that patients with ischemic stroke due to cervical carotid atherosclerosis have a more extensive collateral circulation and better outcomes than patients with cardioembolism. We tested this hypothesis in a population of patients who underwent endovascular treatment for large vessel occlusion. Methods- From the MR-CLEAN Registry (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), we selected consecutive adult endovascular treatment patients (March 2014 to June 2016) with acute ischemic stroke due to anterior circulation large vessel occlusion and compared patients with cervical carotid artery stenosis >50% to those with cardioembolic etiology. The primary outcome was collateral score, graded on a 4-point scale. Secondary outcomes included the modified Rankin Scale (mRS) score and mortality at 90 days. We performed multivariable regression analyses and adjusted for potential confounders. Results- Of 1627 patients in the Registry, 190 patients with cervical carotid atherosclerosis and 476 with cardioembolism were included. Patients with cervical carotid atherosclerosis were younger (median 69 versus 76 years, P<0.001), more often male (67% versus 47%, P<0.001), more often had an internal carotid artery terminus occlusion (33% versus 18%, P<0.001), and a lower prestroke mRS (mRS score, 0-2; 96% versus 85%, P<0.001), than patients with cardioembolism. Stroke due to cervical carotid atherosclerosis was associated with higher collateral score (adjusted common odds ratio, 1.67 [95% CI, 1.17-2.39]) and lower median mRS at 90 days (adjusted common odds ratio, 1.45 [95% CI, 1.03-2.05]) compared with cardioembolic stroke. There was no statistically significant difference in proportion of mRS 0-2 (aOR, 1.36 [95% CI, 0.90-2.07]) or mortality at 90 days (aOR, 0.80 [95% CI, 0.48-1.34]). Conclusions- Patients with stroke due to cervical carotid atherosclerosis had a more extensive cerebral collateral circulation and a slightly better median mRS at 90 days than patients with cardioembolic stroke

Effect of First-Pass Reperfusion on Outcome After Endovascular Treatment for Ischemic Stroke

Background First-pass reperfusion (FPR) is associated with favorable outcome after endovascular treatment. It is unknown whether this effect is independent of patient characteristics and whether FPR has better outcomes compared with excellent reperfusion (Expanded Thrombolysis in Cerebral Infarction [eTICI] 2C-3) after multiple-passes reperfusion. We aimed to evaluate the association between FPR and outcome with adjustment for patient, imaging, and treatment characteristics to single out the contribution of FPR. Methods and Results FPR was defined as eTICI 2C-3 after 1 pass. Multivariable regression models were used to investigate characteristics associated with FPR and to investigate the effect of FPR on outcomes. We included 2686 patients of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. Factors associated with FPR were as follows: history of hyperlipidemia (adjusted odds ratio [OR], 1.05; 95% CI, 1.01-1.10), middle cerebral artery versus intracranial carotid artery occlusion (adjusted OR, 1.11; 95% CI, 1.06-1.16), and aspiration versus stent thrombectomy (adjusted OR, 1.07; 95% CI, 1.03-1.11). Interventionist experience increased the likelihood of FPR (adjusted OR, 1.03 per 50 patients previously treated; 95% CI, 1.01-1.06). Adjusted for patient, imaging, and treatment characteristics, FPR remained associated with a better 24-hour National Institutes of Health Stroke Scale (NIHSS) score (-37%; 95% CI, -43% to -31%) and a better modified Rankin Scale (mRS) score at 3 months (adjusted common OR, 2.16; 95% CI, 1.83-2.54) compared with no FPR (multiple-passes reperfusion+no excellent reperfusion), and compared with multiple-passes reperfusion alone (24-hour NIHSS score, (-23%; 95% CI, -31% to -14%), and mRS score (adjusted common OR, 1.45; 95% CI, 1.19-1.78)). Conclusions FPR compared with multiple-passes reperfusion is associated with favorable outcome, independently of patient, imaging, and treatment characteristics. Factors associated with FPR were the experience of the interventionist, history of hyperlipidemia, location of occluded artery, and use of an aspiration device compared with stent thrombectomy

Clinical and Imaging Determinants of Collateral Status in Patients With Acute Ischemic Stroke in MR CLEAN Trial and Registry

Background and Purpose—Collateral circulation status at baseline is associated with functional outcome after ischemic stroke and effect of endovascular treatment. We aimed to identify clinical and imaging determinants that are associated with collateral grade on baseline computed tomography angiography in patients with acute ischemic stroke due to an anterior circulation large vessel occlusion. Methods—Patients included in the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; n=500) and MR CLEAN Registry (n=1488) were studied. Collateral status on baseline computed tomography angiography was scored from 0 (absent) to 3 (good). Multivariable ordinal logistic regression analyses were used to test the association of selected determinants with collateral status. Results—In total, 1988 patients were analyzed. Distribution of the collateral status was as follows: absent (7%, n=123), poor (32%, n=596), moderate (39%, n=735), and good (23%, n=422). Associations for a poor collateral status in a multivariable model existed for age (adjusted common odds ratio, 0.92 per 10 years [95% CI, 0.886–0.98]), male (adjusted common odds ratio, 0.64 [95% CI, 0.53–0.76]), blood glucose level (adjusted common odds ratio, 0.97 [95% CI, 0.95–1.00]), and occlusion of the intracranial segment of the internal carotid artery with occlusion of the terminus (adjusted common odds ratio 0.50 [95% CI, 0.41–0.61]). In contrast to previous studies, we did not find an association between cardiovascular risk factors and collateral status. Conclusions—Older age, male sex, high glucose levels, and intracranial internal carotid artery with occlusion of the terminus occlusions are associated with poor computed tomography angiography collateral grades in patients with acute ischemic stroke eligible for endovascular treatment

Endovascular Treatment

Background and Purpose- It is unclear whether endovascular treatment (EVT) is beneficial for patients with acute ischemic stroke with occlusion of the M2 segment of the middle cerebral artery. We aimed to compare functional outcomes, technical aspects, and complications of EVT between patients with acute ischemic stroke because of M2 and M1 occlusions in clinical practice. Furthermore, outcome and complications after EVT in dominant and nondominant caliber M2 division occlusions were studied. Methods- Data were obtained from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) which is an ongoing observational study in 16 Dutch centers performing EVT in the Netherlands. Functional outcome was measured with the modified Rankin Scale score at 90 days. Neurological recovery (delta National Institutes of Health Stroke Scale), successful reperfusion rates (extended Thrombolysis in Cerebral Infarction ≥2B), and safety outcomes were also investigated. Associations between occlusion location and outcome were analyzed with ordinal logistic regression models, with adjustment for other prognostic factors. Results- In total, 244 (24%) patients with an M2 and 759 (76%) patients with an M1 occlusion who underwent EVT were analyzed. Functional outcomes were not significantly different between patients with M2 versus M1 occlusions (adjusted common odds ratio, 1.24; 95% CI, 0.87-1.73). Occurrence of symptomatic intracerebral hemorrhage was also similar for M2 and M1 occlusions (6.6% versus 5.9%; P=0.84). Further analysis about dominance of an M2 branch was performed in 175 (72%) patients. Neurological recovery was comparable (mean delta National Institutes of Health Stroke Scale, -2±10 for dominant M2, -5±5 for nondominant M2, and -4±9 [ P=0.24] for M1 occlusions). Furthermore, the effect of reperfusion status on functional outcome was comparable between occlusion divisions (common odds ratio, 1.27; 95% CI, 1.06-1.53 for dominant M2; common odds ratio, 1.32; 95% CI, 0.93-1.87 for nondominant M2; and common odds ratio, 1.35; 95% CI, 1.24-1.46 for M1 occlusions). Conclusions- Outcomes and complication rates after EVT were similar in patients with M2 and M1 occlusions. Although based on observational data and a limited sample size, a similar association of reperfusion status with functional outcome for all subgroups provides no evidence that patients with either a dominant or a nondominant M2 occlusion should be routinely excluded from EVT

Intracranial Carotid Artery Calcification and Effect of Endovascular Stroke Treatment

Background and Purpose- Previous studies suggest that intracranial carotid artery calcification (ICAC) volume might influence the clinical outcome of patients after endovascular treatment (EVT) for acute ischemic stroke. Importantly, ICAC can be subtyped into a medial or intimal pattern that may differentially influence the effect of EVT in patients with acute ischemic stroke. Methods- All 500 patients included in the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular treatment for acute ischemic stroke in the Netherlands) were evaluated. Volume (mm3) and location pattern (tunica intima or tunica media) of ICAC could be determined on baseline noncontrast computed tomography in 344 patients. Functional outcome at 90 days was assessed with the modified Rankin Scale. Next, we investigated the association of ICAC volume and pattern with functional outcome using adjusted ordinal logistic regression models. Effect modification by EVT was assessed with an interaction term between treatment allocation and ICAC aspect. Results- We found evidence for treatment effect modification by ICAC pattern ( P interaction=0.04). Patients with predominantly medial calcification had better functional outcome with EVT than without this treatment (adjusted common odds ratio, 2.32; 95% CI, 1.23-4.39), but we observed no effect of EVT in patients with predominantly intimal calcifications (adjusted common odds ratio, 0.82; 95% CI, 0.40-1.68). We did not find an association of ICAC volume with functional outcome (adjusted common odds ratio per unit increase ICAC volume 1.01 (95% CI, 0.89-1.13). Moreover, we found no evidence for effect modification by ICAC volume ( P interaction=0.61). Conclusions- The benefit of EVT in acute ischemic stroke patients with a medial calcification pattern is larger than the benefit in patients with an intimal calcification pattern. Clinical Trial Registration- URL: http://www.trialregister.nl . Unique identifier: NTR1804. URL: http://www.isrctn.com . Unique identifier: ISRCTN10888758