Imaging features and safety and efficacy of endovascular stroke treatment: a meta-analysis of individual patient-level data

Background: Evidence regarding whether imaging can be used effectively to select patients for endovascular thrombectomy (EVT) is scarce. We aimed to investigate the association between baseline imaging features and safety and efficacy of EVT in acute ischaemic stroke caused by anterior large-vessel occlusion. Methods: In this meta-analysis of individual patient-level data, the HERMES collaboration identified in PubMed seven randomised trials in endovascular stroke that compared EVT with standard medical therapy, published between Jan 1, 2010, and Oct 31, 2017. Only trials that required vessel imaging to identify patients with proximal anterior circulation ischaemic stroke and that used predominantly stent retrievers or second-generation neurothrombectomy devices in the EVT group were included. Risk of bias was assessed with the Cochrane handbook methodology. Central investigators, masked to clinical information other than stroke side, categorised baseline imaging features of ischaemic change with the Alberta Stroke Program Early CT Score (ASPECTS) or according to involvement of more than 33% of middle cerebral artery territory, and by thrombus volume, hyperdensity, and collateral status. The primary endpoint was neurological functional disability scored on the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included symptomatic intracranial haemorrhage, parenchymal haematoma type 2 within 5 days of randomisation, and mortality within 90 days. For the primary analysis, we used mixed-methods ordinal logistic regression adjusted for age, sex, National Institutes of Health Stroke Scale score at admission, intravenous alteplase, and time from onset to randomisation, and we used interaction terms to test whether imaging categorisation at baseline modifies the association between treatment and outcome. This meta-analysis was prospectively designed by the HERMES executive committee but has not been registered. Findings: Among 1764 pooled patients, 871 were allocated to the EVT group and 893 to the control group. Risk of bias was low except in the THRACE study, which used unblinded assessment of outcomes 90 days after randomisation and MRI predominantly as the primary baseline imaging tool. The overall treatment effect favoured EVT (adjusted common odds ratio [cOR] for a shift towards better outcome on the mRS 2·00, 95% CI 1·69–2·38; p<0·0001). EVT achieved better outcomes at 90 days than standard medical therapy alone across a broad range of baseline imaging categories. Mortality at 90 days (14·7% vs 17·3%, p=0·15), symptomatic intracranial haemorrhage (3·8% vs 3·5%, p=0·90), and parenchymal haematoma type 2 (5·6% vs 4·8%, p=0·52) did not differ between the EVT and control groups. No treatment effect modification by baseline imaging features was noted for mortality at 90 days and parenchymal haematoma type 2. Among patients with ASPECTS 0–4, symptomatic intracranial haemorrhage was seen in ten (19%) of 52 patients in the EVT group versus three (5%) of 66 patients in the control group (adjusted cOR 3·94, 95% CI 0·94–16·49; pinteraction=0·025), and among patients with more than 33% involvement of middle cerebral artery territory, symptomatic intracranial haemorrhage was observed in 15 (14%) of 108 patients in the EVT group versus four (4%) of 113 patients in the control group (4·17, 1·30–13·44, pinteraction=0·012). Interpretation: EVT achieves better outcomes at 90 days than standard medical therapy across a broad range of baseline imaging categories, including infarcts affecting more than 33% of middle cerebral artery territory or ASPECTS less than 6, although in these patients the risk of symptomatic intracranial haemorrhage was higher in the EVT group than the control group. This analysis provides preliminary evidence for potential use of EVT in patients with large infarcts at baseline. Funding: Medtronic

Autoimmune encephalopathy and drug refractory seizures with the presence of two autoantibodies specific for the neuronal cell surface

Background: An increasing number of autoantibodies are being described in epilepsy and other seizure-related disorders. A pathogenic role of autoantibodies in epilepsy has been suggested based on observations of the efficacy of immunotherapy. Objective: This study aimed to report a new case of autoimmune-mediated encephalopathy and seizures caused by autoantibodies to voltage-gated potassium channels (VGKCs) and voltage-gated calcium channels (VGCCs) (P/Q-type) and the response to immunotherapy. Design: This study follows a case report design. Setting: This study was conducted in a tertiary care center. Patients: Our patient was an eighteen-year-old female with new-onset encephalopathy and refractory seizures. Intervention: Our patient was treated for five days with intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG). Results: After treatment with IVMP and IVIG, our patient showed significant clinical improvement and did not exhibit any seizures during the one-month follow-up period. Conclusions: Here, we report a rare case of an autoimmune encephalopathy and seizures associated with the presence of two surface neuronal autoantibodies. This report highlights the importance of early diagnosis of autoimmune epilepsy, as early immunomodulating treatments improve the outcome

Central Nervous System Brucellosis Granuloma and White Matter Disease in Immunocompromised Patient

Brucellosis is a multisystem zoonotic disease. We report an unusual case of neurobrucellosis with seizures in an immunocompromised patient in Saudi Arabia who underwent renal transplantation. Magnetic resonance imaging of the brain showed diffuse white matter lesions. Serum and cerebrospinal fluid were positive for Brucella sp. Granuloma was detected in a brain biopsy specimen

Multimodality CT based imaging to determine clot characteristics and recanalization with intravenous tPA in patients with acute ischemic stroke

Abstract Acute ischemic stroke (AIS) is a common neurovascular emergency causing significant burden to society. Currently the main focus of AIS treatment is to restore blood flow to at risk brain tissue. For the last twenty years, intravenous tissue plasminogen activator (tPA) was the only proven therapy for patients with AIS. More recently, five randomized clinical trials established the efficacy of endovascular therapy with or without intravenous tPA in selected patient populations with AIS. Not all stroke patients benefit from intravenous tPA or endovascular treatment. Nonetheless, the concept of early recanalization of occluded arteries resulting in better clinical outcomes is well established. In this focused review, we will discuss how imaging modalities such as Non-Contrast CT, CT-Angiography, and CT-Perfusion can potentially help physicians determine which patients are likely to recanalize early with intravenous tPA and therefore benefit from this therapy

sj-pdf-2-eso-10.1177_23969873231201715 – Supplemental material for Endovascular therapy versus best medical management for isolated posterior cerebral artery occlusion: A systematic review and meta-analysis

Supplemental material, sj-pdf-2-eso-10.1177_23969873231201715 for Endovascular therapy versus best medical management for isolated posterior cerebral artery occlusion: A systematic review and meta-analysis by Ahmed Alkhiri, Aser F Alamri, Abdullah R Alharbi, Ahmed A Almaghrabi, Nayef Alansari, Abdulelah A Niaz, Basil A Alghamdi, Amrou Sarraj, Adel Alhazzani and Fahad S Al-Ajlan in European Stroke Journal</p

sj-pdf-1-eso-10.1177_23969873231201715 – Supplemental material for Endovascular therapy versus best medical management for isolated posterior cerebral artery occlusion: A systematic review and meta-analysis

Supplemental material, sj-pdf-1-eso-10.1177_23969873231201715 for Endovascular therapy versus best medical management for isolated posterior cerebral artery occlusion: A systematic review and meta-analysis by Ahmed Alkhiri, Aser F Alamri, Abdullah R Alharbi, Ahmed A Almaghrabi, Nayef Alansari, Abdulelah A Niaz, Basil A Alghamdi, Amrou Sarraj, Adel Alhazzani and Fahad S Al-Ajlan in European Stroke Journal</p

Discrepancy between post-treatment infarct volume and 90-day outcome in the ESCAPE randomized controlled trial.

BACKGROUND: Some patients with ischemic stroke have poor outcomes despite small infarcts after endovascular thrombectomy, while others with large infarcts sometimes fare better. AIMS: We explored factors associated with such discrepancies between post-treatment infarct volume (PIV) and functional outcome. METHODS: We identified patients with small PIV (volume ≤ 25th percentile) and large PIV (volume ≥ 75th percentile) on 24-48-h CT/MRI in the ESCAPE randomized-controlled trial. Demographics, comorbidities, baseline, and 24-48-h stroke severity (NIHSS), stroke location, treatment type, post-stroke complications, and other outcome scales like Barthel Index, and EQ-5D were compared between discrepant cases - those with 90-day modified Rankin Scale(mRS) ≤ 2 despite large PIV or mRS ≥ 3 despite small PIV - and non-discrepant cases . Multi-variable logistic regression was used to identify pre-treatment and post-treatment factors associated with small-PIV/mRS ≥ 3 and large-PIV/mRS ≤ 2. Sensitivity analyses used different definitions of small/large PIV and good/poor outcome. RESULTS: Among 315 patients, median PIV was 21 mL; 27/79 (34.2%) patients with PIV ≤ 7 mL (25th percentile) had mRS ≥ 3; 12/80 (15.0%) with PIV ≥ 72 mL (75th percentile) had mRS ≤ 2. Discrepant cases did not differ by CT versus MRI-based PIV ascertainment, or right versus left-hemisphere involvement ( CONCLUSIONS: Discrepancies between functional ability and PIV are likely explained by differences in age, comorbidities, and post-stroke complications, emphasizing the need for high-quality post-thrombectomy stroke care. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01778335

Abstract WP62: Favorable Clot Characteristics Predict Smaller Infarct Volume in Acute Ischemic Stroke Patients Treated With Reperfusion Therapy

Introduction: Multiple studies have correlated larger final infarct volume (FIV) with worse clinical outcomes. In INTERRSeCT , an international multicenter prospective cohort study, we sought to determine the favorable intracranial clot characteristics predicting smaller infarct volumes. Methods: FIV was measured (24 ±12 hours after baseline imaging) in 605 patients from INTERRSeCT study by blinded readers using Quantomo (Cybertrial Inc, Calgary). Clot Burden Score (CBS) is a 10-point scale with 10 referring to a completely patent ipsilateral anterior circulation from ICA to both M2 arteries, whereas 0 refers to a completely occluded ipsilateral anterior circulation. Residual Flow Grade (RFG) assesses the radiological permeability of the clot to contrast, with grade 0, 1, and 2 defined as no contrast, diffuse ghosting, and hairline lumen, respectively. Both of these scores were assessed by a blinded reader to the FIV. Using ordinal logistic regression, FIV was divided into deciles as the outcome. CBS and RFG were analyzed from 0 to 10, and 0 to 2, respectively. Two models were used, the first has no recanalization status, while the second included it. Results: The median FIVs with and without recanalization were 12.34 ml (IQR: 32.3 ml) and 22.15 ml (IQR: 60.12ml), respectively. CBS and RFG were independently predictive of FIV (p-value= <0.001 and 0.003, respectively). The common ORs for having one decile higher FIV for 1 point increase in CBS and RFG were 0.82 (CI: 0.77, 0.87) and 0.66 (CI: 0.51, 0.86), respectively. After adjusting for recanalization, the common ORs for having one decile higher FIV for 1 point increase in CBS and RFG were 0.83 (CI: 0.78, 0.88) and 0.72 (CI: 0.54, 0.94), respectively. Conclusions: Residual flow grade and clot burden score are fast and practical techniques for practitioners treating acute ischemic stroke patients. Favorable RFG and CBS independently, predict lower infarct volumes regardless of whether recanalization achieved

Abstract 82: Thrombus Migration is a Common Phenomenon With IV TPA and May Have Negative Effects on Outcome When TPA Treatment is Given Before Endovascular Thrombectomy in Proximal Occlusions

Introduction: There is interest in understanding thrombus dynamics from IV TPA prior to endovascular thrombectomy (EVT) given the possible dichotomy amongst sites of occlusion for IV TPA benefit/harm. Kaesmacher et al reported beneficial 5+% rates of early TICI > 2a reperfusion in distal M1 or M2 MCA occlusions with IV TPA. However in more proximal occlusions this was rare; and potentially harmful worsening of perfusion seen with change of occlusion site. We aimed to examine IV TPA related thrombus dynamics including migration further across both proximal and distal occlusions in a multicenter prospective cohort study INTERRSeCT. Methods: Acute ischemic stroke patients with intracranial occlusion who had baseline CTA and follow-up CTA or initial run angio in INTERRSeCT and IV TPA were reviewed. We evaluated change of occlusion site (COS) and classified patients into 4 categories: Complete Recanalization (CR) of primary occlusive lesion with no remaining thrombus; definite Thrombus Migration (dTM) with primary occlusion site moved to a distal artery and occlusion site patent on baseline CTA; probable Thrombus Migration (pTM) with COS evident but initial occlusion extent not visualized; or No Change of occlusion site (NC). Results: A total of 462 IV TPA patients were enrolled, 41% received EVT. Median time from TPA to follow-up imaging was 133 minutes. COS was seen in 50% of cases with CR in 15% and TM in 35% (dTM 12%, pTM 23%). Distal artery occlusion and longer interval of TPA to imaging were independent predictors for COS. In 62 proximal occlusion (ICA and proximal-mid M1 MCA) patients with follow-up imaging within 60 mins after TPA (receiving EVT in 94%), any TM showed a lower rate of 90-day mRS≤2 than NC (47% vs 78%, adjusted OR 0.21, 95%CI 0.04-0.87). No CR was seen in this early group. Conclusions: Thrombus migration is common after IV TPA. Thrombus instability from IV TPA may worsen clinical outcome in proximal occlusions despite early EVT initiation, possibly due to migration of thrombus to distal arteries accelerating infarction or more challenging thrombectomy due to thrombus dispersion. The benefit of IV TPA prior to EVT at comprehensive stroke centers for ICA or prox-mid M1 occlusions require more study in randomized clinical trials