Feasibility of deconvolution-based multiphase CT angiography perfusion maps in acute ischemic stroke: Simulation and concordance with CT perfusion.

OBJECTIVES: Integration of CT perfusion (CTP) with requisite non-contrast CT and CT angiography (CTA) stroke imaging may allow efficient stroke lesion volume measurement. Using surrogate images from CTP, we simulated the feasibility of using multiphase CTA (mCTA) to generate perfusion maps and assess target mismatch profiles. MATERIALS AND METHODS: Patients with acute ischemic stroke who received admission CTP were included in this study. Four CTP images (surrogate mCTA, one pre-contrast and three post-contrast, starting at the arterial peak then at 8 s intervals) were selected according to the CTP arterial time-density curve to simulate non-contrast CT and mCTA images. Cerebral blood flow (CBF) and Tmax maps were calculated using the same model-based deconvolution algorithm for the standard CTP and surrogate mCTA studies. Infarct and penumbra were delineated with CBF < 20% and Tmax > 6 s threshold, respectively. Classification accuracy of surrogate mCTA target mismatch (infarct <70 ml; penumbra ≥15 ml; mismatch ratio ≥1.8) with respect to standard CTP was assessed. Agreement between infarct and penumbra volumes from standard CTP and surrogate mCTA maps were evaluated by Bland-Altman analysis. RESULTS: Of 34 included patients, 28 had target mismatch and 6 did not by standard CTP. Accuracy of classifying target mismatch profiles with surrogate mCTA was 79% with respect to that from standard CTP. Mean  ±  standard deviation of differences (standard CTP minus surrogate mCTA) of infarct and penumbra volumes were 9.8 ± 14.8 ml and 20.1 ± 45.4 ml, respectively. CONCLUSIONS: Surrogate mCTA ischemic lesion volumes agreed with those from standard CTP and may be an efficient alternative when CTP is not practical.

Primary CNS vasculitis: A systematic review on clinical characteristics associated with abnormal biopsy and angiography.

BACKGROUND: Primary Central Nervous System Vasculitis (PCNSV) remains a diagnostic challenge due to its variable and non-specific clinical manifestations. In part, the clinical heterogeneity of PCNSV may be a consequence of the modalities used for diagnosis; accordingly, there may be different subtypes of PCNSV based on whether the diagnosis was attained by biopsy or cerebral angiography. OBJECTIVE: To examine the frequency of symptoms, laboratory, and radiological features associated with PCNSV, and to identify distinct clinical features between biopsy and angiography defined PCNSV. METHODS: We conducted a systematic review of articles published in the English language from 1991 to 2019 that met all diagnostic criteria of PCNSV. RESULTS: We identified 55 studies, reporting on 907 PCNSV cases. Median age was 45 (IQR 50-36), and 53% were women. Biopsy compared to angiography defined PCNSV had a higher percentage of cognitive impairment, and seizures on initial presentation, and were more likely to have a subacute or progressive onset, abnormal CSF profile, small vessel involvement on angiography, and tumor-like lesions and gadolinium enhancement on MRI. Angiography defined PCNSV were more likely to have an acute onset, focal weakness and visual impairment on initial presentation, medium vessel involvement on angiography, and infarcts on MRI. Brain biopsy was diagnostic of PCNSV in 71% of cases, and demonstrated an alternative diagnosis in 37% of cases, the most common being infection (19%) and lymphoproliferative disease (18%). CONCLUSIONS: This study provides further evidence that there are distinct clinical features between biopsy and angiography defined PCNSV, which may aid in selecting patients for appropriate invasive tests.

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke. METHODS: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018. FINDINGS: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups. INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. FUNDING: Canadian Institutes for Health Research, Alberta Innovates, and NoNO.

Severe Intracranial Involvement in Giant Cell Arteritis: 5 Cases and Literature Review.

OBJECTIVE: Involvement of intracranial arteries in giant cell arteritis (GCA) is rare. We describe the neurologic complications of intracranial GCA (IC GCA) and available treatment options. METHODS: We describe 5 IC GCA cases from 3 Canadian vasculitis centers and review the literature. We searched English-language publications reporting similar patients meeting American College of Rheumatology (ACR) criteria for GCA and having intracranial artery involvement diagnosed by autopsy, magnetic resonance angiography, computed tomography angiography, or conventional angiography. RESULTS: All 5 cases of IC GCA met ACR criteria for GCA; 4 cases had a temporal artery biopsy that was consistent with GCA. All cases experienced cerebrovascular accident(s). Arteritis involved the following vessels: intracranial internal carotid (n = 1), vertebrobasilar arteries (n = 1), or both (n = 3). All cases received aspirin and oral prednisone (preceded by intravenous methylprednisone in 3 cases), combined with an immunosuppressant in 4 cases. All patients survived; 2 had complete neurological recovery, 3 had residual neurologic sequelae. The literature review included 42 cases from 28 publications. The clinical features of the reported cases were similar to those of our 5 cases. However, mortality was 100% in untreated cases (n = 2), 58% in those treated with corticosteroid alone (n = 31), and 40% in those treated with corticosteroid and an immunosuppressant (n = 10). CONCLUSION: IC GCA appears to be associated with neurologic complications and mortality. In some cases corticosteroid alone was not sufficient to prevent neurologic complications. The role of additional immunosuppressive agents needs further investigation.