Comparison of patients with biopsy positive and negative primary angiitis of the central nervous system.

OBJECTIVE: There is limited evidence on when to obtain a central nervous system (CNS) biopsy in suspected primary angiitis of the central nervous system (PACNS). Our objective was to identify which clinical and radiological characteristics were associated with a positive biopsy in PACNS. METHODS: From the multicenter retrospective Cohort of Patients with Primary Vasculitis of the CNS (COVAC), we included adults with PACNS based on a positive CNS biopsy or otherwise unexplained intracranial stenoses with additional findings supportive of vasculitis. Baseline findings were compared between patients with a positive and negative biopsy using logistic regression models. RESULTS: 200 patients with PACNS were included, among which a biopsy was obtained in 100 (50%) and was positive in 61 (31%). Patients with a positive biopsy were more frequently female (OR 2.90, 95% CI 1.25-7.10, p = 0.01) and more often presented with seizures (OR 8.31, 95% CI 2.77-33.04, p < 0.001) or cognitive impairment (OR 2.58, 95% CI 1.11-6.10, p = 0.03). On imaging, biopsy positive patients more often had non-ischemic parenchymal or leptomeningeal gadolinium enhancement (OR 52.80, 95% CI 15.72-233.06, p < 0.001) or ≥ 1 cerebral microbleed (OR 8.08, 95% CI 3.03-25.13, p < 0.001), and less often had ≥ 1 acute brain infarct (OR 0.02, 95% CI 0.004-0.08, p < 0.001). In the multivariable model, non-ischemic parenchymal or leptomeningeal gadolinium enhancement (aOR 8.27, 95% CI 1.78-38.46), p < 0.01) and absence of ≥ 1 acute brain infarct (aOR 0.13, 95% CI 0.03-0.65, p = 0.01) were significantly associated with a positive biopsy. CONCLUSIONS: Baseline clinical and radiological characteristics differed between biopsy positive and negative PACNS. These results may help physicians individualize the decision to obtain a CNS biopsy in suspected PACNS.

Challenging the diagnosis of a posterior circulation dissecting aneurysm.

INTRODUCTION: I ntracranial vertebral dissections have polymorphs clinical presentations and can lead to haemorrhagic complications if they are intracranial. We here describe a case of a thrombosed dissecting aneurysm of postero-inferior cerebellar artery (PICA) revealed by a Wallenberg syndrome preceded by headaches. CASE: A 23-year-old patient, without neurological or vascular past medical history, was admitted for dizziness preceded by headache. The clinical examination on admission revealed an incomplete Wallenberg syndrome, associating hemiface sensitive deficit, Horner's syndrome, dysmetria and nystagmus. The brain MRI showed a latero-medullary infarct with a homolateral PICA thrombosed dissecting aneurysm. CONCLUSION: The diagnosis of intracranial dissecting aneurysms needs particular caution because aneurysm sac thrombosis can give false reassurance on angiographic MR sequences. Moreover, the anatomic features of intracranial artery walls make them prone to sub-adventitial dissection and subsequent subarachnoid haemorrhages. Therefore, antithrombotic therapy should be used with caution, due to the risk of bleeding in these intracranial dissections.

In-hospital ischaemic stroke treated with intravenous thrombolysis or mechanical thrombectomy.

Patients with in-hospital strokes (IHS) may be eligible for recanalization therapies. The objective of this study is to compare outcomes in patients with IHS and community-onset strokes (COS) treated by recanalization therapy. We analysed data prospectively collected in consecutive patients treated by thrombolysis, thrombectomy, or both for cerebral ischemia at the Lille University Hospital. We compared four outcomes measures at 3 months in patients with IHS and COS: (1) modified Rankin scale (mRS) 0-1, (2) mRS 0-2, (3) death, and (4) symptomatic intracranial haemorrhage (ECASS 2 definition). Of 1209 patients, 64 (5.3%) had IHS, with an increasing proportion over time (p = 0.001). Their median onset-to-needle time was 128 min vs. 145 in COS (p < 0.001). They were more likely to have had a recent TIA [odds ratio (OR) 30.1; 95% confidence interval (CI) 11.5-78.7], to have been treated by vitamin K antagonist before (OR 4.2; 95% CI 1.4-12.0) and to undergo mechanical thrombectomy (45 vs. 10%, p < 0.001). They were less likely to have a pre-stroke mRS 0-1 (OR 0.22; 95% CI 0.09-0.50). After adjustment, IHS was not associated with any of the four outcome measures. Patients with IHS are treated 17 min earlier than patients with COS, but, taking into account that they were already in the hospital, delays are still too long. Their outcome does not differ from that of patients with COS, suggesting room for improvement if delays can be reduced. IHS being frequent, pre-specified pathways should be organised.

Tumor-Like Presentation of Primary Angiitis of the Central Nervous System.

BACKGROUND AND PURPOSE: We aimed to describe the clinical and imaging features of patients with tumor-like presentation of primary angiitis of the central nervous system. METHODS: We retrospectively analyzed 10 patients enrolled in the French primary angiitis of the central nervous system cohort, who initially presented tumor-like brain lesions and compared them with other patients within the cohort. RESULTS: The 10 patients with tumor-like presentation in the cohort were younger and had more seizures at diagnosis than the other 75 patients (median of 37 [30-48] years versus 46 [18-79] years; P=0.008; 9 [90%] with seizures versus 22 [29%], P<0.001; respectively). All 10 patients had a biopsy (stereotactic procedure in 7 and open-wedge surgery in 3). Histological findings suggestive of vasculitis were observed in 9 patients in whom conventional cerebral angiography and magnetic resonance angiography were negative. In the remaining patient, vascular imaging demonstrated diffuse bilateral large- and medium-sized vessel involvement (biopsy did not reveal vasculitis). All patients with tumor-like presentation received glucocorticoids, combined with cyclophosphamide in 9 cases. With a median follow-up of 27 (12-130) months, 5 (50%) patients relapsed, but achieved remission again after treatment intensification. CONCLUSIONS: Patients with tumor-like presentation of primary angiitis of the central nervous system represent a subgroup characterized with mainly small-sized vessel disease that requires histological confirmation because vascular imaging is often normal. Although relapses are not uncommon, global outcomes are good under treatment with glucocorticoids and cyclophosphamide.

Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion: the ICARO-3 study.

The aim of the ICARO-3 study was to evaluate whether intra-arterial treatment, compared to intravenous thrombolysis, increases the rate of favourable functional outcome at 3 months in acute ischemic stroke and extracranial ICA occlusion. ICARO-3 was a non-randomized therapeutic trial that performed a non-blind assessment of outcomes using retrospective data collected prospectively from 37 centres in 7 countries. Patients treated with endovascular treatment within 6 h from stroke onset (cases) were matched with patients treated with intravenous thrombolysis within 4.5 h from symptom onset (controls). Patients receiving either intravenous or endovascular therapy were included among the cases. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale (mRS), dichotomized as favourable (score of 0-2) or unfavourable (score of 3-6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 324 cases and 324 controls: 105 cases (32.4 %) had a favourable outcome as compared with 89 controls (27.4 %) [adjusted odds ratio (OR) 1.25, 95 % confidence interval (CI) 0.88-1.79, p = 0.1]. In the adjusted analysis, treatment with intra-arterial procedures was significantly associated with a reduction of mortality (OR 0.61, 95 % CI 0.40-0.93, p = 0.022). The rates of patients with severe disability or death (mRS 5-6) were similar in cases and controls (30.5 versus 32.4 %, p = 0.67). For the ordinal analysis, adjusted for age, sex, NIHSS, presence of diabetes mellitus and atrial fibrillation, the common odds ratio was 1.15 (95 % IC 0.86-1.54), p = 0.33. There were more cases of intracranial bleeding (37.0 versus 17.3 %, p = 0.0001) in the intra-arterial procedure group than in the intravenous group. After the exclusion of the 135 cases treated with the combination of I.V. thrombolysis and I.A. procedures, 67/189 of those treated with I.A. procedures (35.3 %) had a favourable outcome, compared to 89/324 of those treated with I.V. thrombolysis (27.4 %) (adjusted OR 1.75, 95 % CI 1.00-3.03, p = 0.05). Endovascular treatment of patients with acute ICA occlusion did not result in a better functional outcome than treatment with intravenous thrombolysis, but was associated with a higher rate of intracranial bleeding. Overall mortality was significantly reduced in patients treated with endovascular treatment but the rates of patients with severe disability or death were similar. When excluding all patients treated with the combination of I.V. thrombolysis and I.A. procedures, a potential benefit of I.A. treatment alone compared to I.V. thrombolysis was observed.

External validation of the MRI-DRAGON score: early prediction of stroke outcome after intravenous thrombolysis.

BACKGROUND AND PURPOSE: The aim of our study was to validate in an independent cohort the MRI-DRAGON score, an adaptation of the (CT-) DRAGON score to predict 3-month outcome in acute ischemic stroke patients undergoing MRI before intravenous thrombolysis (IV-tPA). METHODS: We reviewed consecutive (2009-2013) anterior circulation stroke patients treated within 4.5 hours by IV-tPA in the Lille stroke unit (France), where MRI is the first-line pretherapeutic work-up. We assessed the discrimination and calibration of the MRI-DRAGON score to predict poor 3-month outcome, defined as modified Rankin Score >2, using c-statistic and the Hosmer-Lemeshow test, respectively. RESULTS: We included 230 patients (mean ±SD age 70.4±16.0 years, median [IQR] baseline NIHSS 8 [5]-[14]; poor outcome in 78(34%) patients). The c-statistic was 0.81 (95%CI 0.75-0.87), and the Hosmer-Lemeshow test was not significant (p = 0.54). CONCLUSIONS: The MRI-DRAGON score showed good prognostic performance in the external validation cohort. It could therefore be used to inform the patient's relatives about long-term prognosis and help to identify poor responders to IV-tPA alone, who may be candidates for additional therapeutic strategies, if they are otherwise eligible for such procedures based on the institutional criteria.

Outcome of patients with atrial fibrillation after intravenous thrombolysis for cerebral ischaemia.

The question of whether i.v. rt-PA is beneficial in patients with ischaemic stroke and atrial fibrillation (AF) remains unresolved. Our objective was to evaluate the outcome of patients with AF who received i.v. rt-PA for stroke in the registries of Lille (France) and Belgrade (Serbia). End-points were poor outcome [modified Rankin Scale (mRS) 3-6], and symptomatic haemorrhagic transformation (sHT) according to ECASS3. Of 734 consecutive patients, 155 (21.2 %) had AF. The unadjusted comparison found patients with AF to be 12 years older, more likely to be women, to have hypertension, and baseline INR > 1.2, and less likely to be smokers. They had higher baseline NIHSS scores, diastolic blood pressure, and serum glucose concentrations, and lower platelet counts. They did not differ for sHT (5.8 vs. 5.5 %; p = 0.893), but they more frequently had poor outcomes (52.3 vs. 35.2 %; p < 0.001) and death (21.9 vs. 9.0 %; p < 0.001). The only independent predictor of sHT was baseline NIHSS (adjOR 1.05 per 1 point increase; 95 % CI 1.01-1.10). Independent variables associated with poor outcome were age (adjOR 1.04 for 1 year increase; 95 % CI 1.03-1.06), baseline NIHSS (adjOR 1.17 per 1 point increase; 95 % CI 1.13-1.21), and sHT (adjOR 47.6; 95 % CI 10.2-250) but not AF. In patients treated with i.v. rt-PA for cerebral ischaemia, those with AF have worse outcomes because they are older and have more severe strokes at admission. This result suggests that we should focus on prevention and research of more aggressive strategies at the acute stage.

Baseline serum glucose concentration and symptomatic haemorrhagic transformation in non-diabetic stroke patients treated by intravenous thrombolysis.

Intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) improves outcome in ischaemic stroke, despite an increased risk of symptomatic haemorrhagic transformation (sHT). A higher baseline serum glucose concentration is associated with an increased risk of sHT. However, as most studies did not exclude diabetic patients, this effect may be partially due to diabetic micro-angiopathy. Our objective was to test the hypothesis that baseline serum glucose concentration is associated with sHT in non-diabetic patients treated by i.v. rt-PA. We analysed the influence of baseline serum glucose concentrations on sHT (ECASS2 definition) in consecutive non-diabetic patients treated by i.v. rt-PA for ischaemic stroke. Secondary end-points were death (<7 days, 8 days to 3 months, all deaths <3 months), and unfavourable outcome at 3 months (modified Rankin scale 2-6 if different from the pre-stroke value). Five hundred and five consecutive patients met inclusion criteria [242 men (47.9 %); median age 71 years (interquartile range, IQR) 57-81; median baseline national institutes of health stroke scale score 12 (IQR 6-17)]. Thirty-seven had sHT (7.3 %). After adjustment, baseline serum glucose concentrations were independently associated with sHT (adjOR: 1.176 for 1 mmol/l increase; 95 % CI: 1.020-1.357: p = 0.025). Increased admission serum glucose concentrations in non-diabetic patients treated by i.v. rt-PA for cerebral ischaemia are associated with sHT. Whether lowering serum glucose lowers the risk of sHT needs to be evaluated.