Clot Burden Score and Collateral Status and Their Impact on Functional Outcome in Acute Ischemic Stroke

BACKGROUND AND PURPOSE:Collateral status and thrombus length have been independently associated with functional outcome in patients with acute ischemic stroke. It has been suggested that thrombus length would influence functional outcome via interaction with the collateral circulation. We investigated the individual and combined effects of thrombus length assessed by the clot burden score and collateral status assessed by a FLAIR vascular hyperintensity–ASPECTS rating system on functional outcome (mRS).MATERIALS AND METHODS:Patients with anterior circulation acute ischemic stroke due to large-vessel occlusion from the ASTER and THRACE trials treated with endovascular thrombectomy were pooled. The clot burden score and FLAIR vascular hyperintensity score were determined on MR imaging obtained before endovascular thrombectomy. Favorable outcome was defined as an mRS score of 0–2 at 90 days. Association of the clot burden score and the FLAIR vascular hyperintensity score with favorable outcome (individual effect and interaction) was examined using logistic regression models.RESULTS:Of the 326 patients treated by endovascular thrombectomy with both the clot burden score and FLAIR vascular hyperintensity assessment, favorable outcome was observed in 165 (51%). The rate of favorable outcome increased with clot burden score (smaller clots) and FLAIR vascular hyperintensity (better collaterals) values. The association between clot burden score and functional outcome was significantly modified by the FLAIR vascular hyperintensity score, and this association was stronger in patients with good collaterals, with an adjusted OR = 6.15 (95% CI, 1.03–36.81).CONCLUSIONS:The association between the clot burden score and functional outcome varied for different collateral scores. The FLAIR vascular hyperintensity score might be a valuable prognostic factor, especially when contrast-based vascular imaging is not available.

Therapeutic reperfusion with endovascular thrombectomy (EVT) is consistently associated with a better long-term functional outcome in anterior circulation acute ischemic stroke (AIS).¹ Early reperfusion is the mainstay of therapy because it strongly predicts functional outcome.² Many factors impact clinical outcomes, including the extent of clot and collateral supply.^3–7The clot burden score (CBS) assessed by the T2* MR imaging sequence (T2*-CBS), which was adapted from the CTA-CBS,⁸ has been used to assess the extent of the clot⁹ and has been independently associated with functional outcome in patients undergoing EVT.¹⁰Good collaterals have been related to better clinical outcome through 2 distinct mechanisms. First, collaterals are thought to contribute to prolonged penumbra sustenance.^11,12 Second, good retrograde collateral filling beyond the occlusion could promote successful reperfusion by providing more access to thrombolytics at the distal end of the clot and robust collaterals dissolving clot fragments in the distal vasculature.^13,14 The Highly Effective Reperfusion evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration analysis suggested a benefit with EVT across all strata of collateral circulation status;¹⁵ however, patients with poor collaterals are less likely to benefit from EVT than those with better collaterals.Most interesting, FLAIR vascular hyperintensity (FVH) on baseline MR imaging could indicate the formation of a leptomeningeal collateral circulation and serve as a prognostic marker for patients with AIS.^16-18 Both collaterals and the CBS were separately associated with functional outcome in patients undergoing EVT,^10,16 but their combined effect regarding clinical outcome is still poorly understood and has been assessed and quantified only with CTA or contrast-enhanced MRA in patients with AIS.^14,15 Furthermore, the lack of adjustment for possible confounders because of the small number of patients with very low collateral scores might also have influenced results in these studies.The purpose of this study was to determine whether there is an association between the CBS and FVH score and whether the association between the CBS and functional outcome is modified by the FVH score for patients who were treated by EVT for large-vessel occlusion within the framework of the Contact Aspiration versus Stent Retriever for Successful Revascularization (ASTER) and the THRombectomie des Artères CErebrales (THRACE) randomized trials.^19,20     

Defibrotide for Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease Prophylaxis in High-Risk Adult Patients: A Single-Center Experience Study

Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a serious complication after hematopoietic stem cell transplantation (HSCT). SOS/VOD usually occurs within 3 weeks of HSCT, but the 2016 European Society for Blood and Marrow Transplantation diagnosis criteria have been revised to include late forms. Prophylactic use of defibrotide is recommended in the pediatric setting, but its value remains uncertain in the adult population. We report here a single-center series of 63 adult patients considered at high risk for SOS/VOD who received defibrotide prophylaxis in combination with ursodeoxycholic acid between May 2012 and August 2016. The median duration of defibrotide therapy was 23 days. Bleeding occurred in 14 patients (21.5%). Defibrotide prophylaxis was discontinued in 7 patients (10.8%): 4 cases (6.3%) due to bleeding and 3 cases (4.6%) because of the need for antithrombotic therapy. Overall, SOS/VOD occurred in 4 cases (6.3%) within 21 days after HSCT (days 13 and 14) in 2 cases and late-onset SOS/VOD (days 57 and 58) in the other 2 cases. SOS/VOD was moderate in 1 case, very severe in 3 cases, with 2 deaths related to SOS/VOD. Cumulative incidence of grades II to IV acute graft-versus-host disease and transplant-associated thrombotic microangiopathy were 22.2% and 3.2%, respectively. With a median follow-up of 31 months (range, 10.7 to 60.3), the rates of 2-year overall survival, progression-free survival, incidence of relapse, and nonrelapse mortality were 56.5%, 49%, 28.7%, and 22.3%, respectively. In our experience defibrotide prophylaxis is associated with a low incidence of SOS/VOD after allogeneic HSCT in a high-risk adult population with an acceptable safety profile.     

Creutzfeldt--Jakob Disease in Recipients of Human Growth Hormone in the United Kingdom: A Clinical and Radiographic Study

In the past 3 years there have been five further cases, in additionto one case reported in 1985, of Creutzfeldt-Jakob disease inrecipients of human growth hormone in the United Kingdom. Theclinical findings of two of these cases are described, demonstratinga typical presentation with a predominantly cerebellar syndromeat onset which is not commonly a presenting feature of sporadicCreutzfeldt-Jakob disease. In one case a ^99mTc hexamethylpropylenaminesingle photon emission tomographic scan showed marked impairmentof tracer uptake in the basal ganglia and cerebral cortex ata time when the clinical picture was predominantly cerebellar.This technique may be useful in early diagnosis. In the othercase post mortem examination of the brain showed prominent amyloiddeposition in the cerebellum, which has not been described previouslyin pituitary-hormone related Creutzfeldt-Jakob disease. Thepreviously published cases of growth hormone-related Creutzfeldt-Jakobdisease are reviewed and reasons for the particular clinicalpattern seen are discussed.