Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an inherited late-onset neurological disease caused by bi-allelic AAGGG pentanucleotide expansions within intron 2 of RFC1. ...Despite extensive studies, the pathophysiological mechanism of these intronic expansions remains elusive. We screened by clinical exome sequencing two unrelated patients presenting with late-onset ataxia. A repeat-primer polymerase chain reaction was used for RFC1 AAGGG intronic expansion identification. RFC1 mRNA expression was assessed by quantitative reverse transcription-polymerase chain reaction. We identified the first two CANVAS affected patients who are compound heterozygous for RFC1 truncating variants (p.Arg388* and c.575delA, respectively) and a pathological AAGGG expansion. RFC1 expression studies in whole blood showed a significant reduction of RFC1 mRNA for both patients compared to three patients with bi-allelic RFC1 expansions. In conclusion, this observation provides clues that suggest bi-allelic RFC1 conditional loss-of-function as the cause of the disease.
BackgroundNon-ischemic cerebral enhancing (NICE) lesions are exceptionally rare following aneurysm endovascular therapy (EVT).ObjectiveTo investigate the presenting features and longitudinal ...follow-up of patients with NICE lesions following aneurysm EVT.MethodsPatients included in a retrospective national multicentre inception cohort were analysed. NICE lesions were defined, using MRI, as delayed onset punctate, nodular or annular foci enhancements with peri-lesion edema, distributed in the vascular territory of the aneurysm EVT, with no other confounding disease.ResultsFrom a pool of 58 815 aneurysm endovascular treatment procedures during the study sampling period (2006–2019), 21/37 centres identified 31 patients with 32 aneurysms of the anterior circulation who developed NICE lesions (mean age 45±10 years). Mean delay to diagnosis was 5±9 months, with onset occurring a month or less after the index EVT procedure in 10 out of 31 patients (32%). NICE lesions were symptomatic at time of onset in 23 of 31 patients (74%). After a mean follow-up of 25±26 months, 25 patients (81%) were asymptomatic or minimally symptomatic without disability (modified Rankin Scale (mRS) score 0–1) at last follow-up while 4 (13%) presented with mild disability (mRS score 2). Clinical follow-up data were unavailable for two patients. Follow-up MRI (available in 27 patients; mean time interval after onset of 22±22 months) demonstrated persistent enhancement in 71% of cases.ConclusionsThe clinical spectrum of NICE lesions following aneurysm EVT therapy spans a wide range of neurological symptoms. Clinical course is most commonly benign, although persistent long-term enhancement is frequent.
BackgroundNon-ischemic cerebral enhancing (NICE) lesions following aneurysm endovascular therapy are exceptionally rare, with unknown longitudinal evolution.ObjectiveTo evaluate the radiological ...behavior of individual NICE lesions over time.MethodsPatients included in a retrospective national multicentric inception cohort were analyzed. NICE lesions were defined, using MRI, as delayed onset punctate, nodular, or annular foci enhancements with peri-lesion edema, distributed in the vascular territory of the aneurysm treatment, with no other confounding disease. Lesion burden and the longitudinal behavior of individual lesions were assessed.ResultsTwenty-two patients were included, with a median initial lesion burden of 36 (IQR 17–54) on the first MRI scan. Of the 22 patients with at least one follow-up MRI scan, 16 (73%) had new lesions occurring mainly within the first 200 weeks after the date of the procedure. The median number of new lesions per MRI was 6 (IQR 2–16). Among the same 22 patients, 7 (32%) had recurrent lesions. The median persistent enhancement of a NICE lesion was 13 weeks (IQR 6–30). No factor was predictive of early regression of enhancement activity with lesion regression kinetics mainly being patient-dependent.ConclusionsThe behavior of individual NICE lesions was found to be highly variable with an overall patient-dependent regression velocity.
BACKGROUND AND PURPOSE—Although successful reperfusion is usually defined as a modified Thrombolysis in Cerebral Infarction (mTICI) 2B or 3 at the end of the procedure, studies have shown that mTICI ...2B patients had poorer functional outcomes than TICI 3 patients. An mTICI 2C category has been recently introduced for patients with near-complete perfusion except for slow flow in a few distal cortical vessels or presence of small distal cortical emboli after mechanical thrombectomy. The purpose of this study was to evaluate the difference in functional outcome between patients achieving successful reperfusion (ie, mTICI 2B, mTICI 2C, and TICI 3 scores).
METHODS—Ancillary study from the ASTER (Contact Aspiration Versus Stent Retriever for Successful Revascularization) prospective multicenter blinded end point trial. Reperfusion results are reported as the mTICI score, including the mTICI 2C grade. Primary outcome was the percentage of patients with favorable outcome defined as a 90-day modified Rankin Scale score of 0 to 2.
RESULTS—Two hundred ninety patients with successful reperfusion (mTICI ≥2B), harboring ischemic stroke secondary to occlusion of the anterior circulation within 6 hours of onset of symptoms, undergoing mechanical thrombectomy by contact aspiration or stent retriever were included. Favorable outcome (pre-specified as primary outcome of this ancillary study) did not differ significantly between the 3 reperfusion grades, with a similar positive effect of 2C (odds ratio, 1.71; 95% confidence interval, 0.98–3.00) and 3 (odds ratio, 1.73; 95% confidence interval, 0.88–3.41) grades compared with 2B grade. After combining grades 2C and 3, patients had a significantly higher rate of favorable outcome than patients with 2B (odds ratio, 1.72; 95% confidence interval, 1.01–2.90; P=0.043). Favorable outcome rate decreased with increasing onset-to-reperfusion time, with no significant interaction between mTICI 2C/3 grade and onset-to-reperfusion time on favorable outcome.
CONCLUSIONS—Combining mTICI 2C and TICI 3 grades helps to determine a subgroup of patients achieving better functional outcomes than mTICI 2B patients. Achieving mTICI 2C/3 reperfusion should be the new aim of mechanical thrombectomy for anterior circulation LVO.
Summary Introduction Endovascular treatment of small anterior choroidal artery (AChA) aneurysms can be challenging, especially if the AChA arises from the sac. Preserving its patency during ...embolization is as important as obliterating the aneurysm. We describe a variant of the “protective microcatheter technique” (PMT) in a series of six patients with AChA aneurysms where the AChA emerged from the sac. Methods Three different microcatheters (KT) were used. The first microcatheter was placed in the AChA to protect it. A remodeling balloon-catheter was then positioned in the internal carotid artery to stabilize the coils during embolization and to control a potential rupture. The third microcatheter was finally used to coil the aneurysm. Results Mean sac size of anterior choroidal artery aneurysms was 2 × 2 × 2 mm. All aneurysms were successfully occluded. There was neither ischemic complication nor ruptured aneurysm during endovascular treatment. A final angiogram demonstrated AChA patency in all cases. Conclusion The 3KT-PMT for AChA aneurysms appears to be safe and effective to prevent AChA occlusion during aneurysm coiling, especially when the AChA arises from the sac.
OBJECTIVE:Abdominal aortic aneurysm (AAA) rupture is a devastating event, and development of noninvasive methods to detect AAA at risk is needed. Matrix metalloproteinases (MMPs) play a major role in ...AAA growth and their subsequent rupture. This study was aimed to evaluate the ability of P947, a recently developed magnetic resonance imaging (MRI) contrast agent, to target MMPs in vivo in expanding experimental AAAs.
MATERIALS AND METHODS:AAAs were induced in Wistar rats (n = 18) by perfusion of a segment of the abdominal aorta with porcine elastase. After 5 or 6 days of elastase perfusion, when the aortic segment was expanding and showed inflammation with high MMP levels, rats were injected either with P947 (n = 6), P1135, a scramble form of P947 (n = 6), or with the reference contrast agent Gadolinium-DOTA (Gd-DOTA) (n = 3). Sham-operated rats (n = 3) were injected with P947 as controls. Imaging was performed on the animals using a 1.5T MRI scanner before and at different times after injection of contrast agents (100 μmol/kg). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gelatin zymography of culture media conditioned by incubation with perfused aortic segment or control TA from elastase-perfused rats (n = 3) was performed to determine levels of MMP2 and MMP9. In addition, in situ gelatin zymography was used to localize these active MMPs on frozen histologic sections.
RESULTS:The normalized signal enhancement determined on MRI images was higher in the perfused aortic segment of rats injected with P947 (162%) than in rats injected with P1135 (100%) or Gd-DOTA (117%) (P < 0.01 using the Friedman test) from 5 to 125 minutes after injection. The area of contrast enhancement on MRI images colocalized with the fluorescence generated by MMPs in the AAA inflammatory area, as detected by in situ zymography on histologic sections.
CONCLUSION:Our data showed that MRI using P947 allows detection of MMP activity within the inflammatory wall of experimental AAAs, thus representing a potential noninvasive method to detect AAAs with a high risk of rupture.
BACKGROUND AND PURPOSE—Middle cerebral artery M2-segment occlusions represent an important subgroup of patients with acute stroke with large-vessel occlusion. The safety of mechanical thrombectomy, ...especially contact aspiration (CA), in such distal intracranial occlusions is still under debate. We compared reperfusion, adverse events, neurological recovery, and functional outcome of patients with isolated M2 occlusions according to the first-line strategy mechanical thrombectomy devices (CA versus stent retriever SR).
METHODS—This is a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). The primary outcome was successful reperfusion at the end of all endovascular procedures, defined as modified Thrombolysis in Cerebral Infarction (mTICI) scores 2b/3. Secondary outcomes were mTICI 2c/3 and mTICI 3, 90-day functional outcome, assessed with the modified Rankin Scale score. Safety outcomes included 90-day mortality and any symptomatic intracerebral hemorrhage.
RESULTS—Seventy-nine patients were included48 were allocated to the CA group and 31 to the SR group. There were no significant differences between CA and SR groups in reperfusion after all endovascular procedures regarding mTICI 2b/3 (89.6% versus 83.9%; P=0.36), mTICI 2c/3 (54.2% versus 54.8%; P=0.90), and mTICI 3 (35.4% versus 41.9%; P=0.36) rates. There were no significant differences between CA and SR groups in 90-day modified Rankin Scale ≤2 rate (54.4% versus 50.0%; P=0.84), 24-hour change in National Institutes of Health Stroke Scale (mean difference, −3.9; 95% confidence interval, −7.9 to 0.01), and Alberta Stroke Program Early Computed Tomography score (mean difference, 0.9; 95% confidence interval, −0.1 to 2.0) scores. Safety parameters were well balanced between the 2 groups except for a higher 90-day mortality rate in the CA group (19.6% versus 3.3%; P=0.078).
CONCLUSIONS—First-line mechanical thrombectomy with CA compared with SR did not result in an increased successful revascularization rate in patients with acute stroke with isolated M2 occlusion.
BACKGROUND AND PURPOSE—Intravenous thrombolysis (IVT) within 4.5 hours of symptom onset is currently recommended before mechanical thrombectomy (MT). We compared functional outcome, neurological ...recovery, reperfusion, and adverse events according to the use or not of IVT before MT.
METHODS—This is a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). The primary outcome was favorable 90-day functional outcome defined as a modified Rankin Scale of ≤2. Secondary outcomes were successful reperfusion following all procedures and after the first-line procedure, number of device passes, and change in National Institutes of Health Stroke Scale score at 24 hours. Safety outcomes included 90-day mortality and any symptomatic intracerebral hemorrhage.
RESULTS—Three hundred eighty-one patients were included, 250 of whom received IVT before MT (IVT+MT group). There were no significant differences between IVT+MT and MT-alone groups in 90-day favorable functional outcome, in successful reperfusion rate (modified Thrombolysis In Cerebral Infarction 2b or 3), in National Institutes of Health Stroke Scale score improvement at 24 hours, or in hemorrhagic complication rate. The 90-day mortality rate in the IVT+MT group was lower than after MT alone (fully-adjusted risk ratio, 0.59; 95% CI, 0.39–0.88). In a subgroup of patients without anticoagulant medication before stroke onset, we observed in the IVT+MT group a better functional outcome (fully-adjusted risk ratio, 1.38; 95% CI, 1.02–1.89), a higher successful recanalization rate after first-line strategy (fully-adjusted risk ratio, 1.26; 95% CI, 1.05–1.50), and a lower mortality rate (fully-adjusted risk ratio, 0.58; 95% CI, 0.36–0.93).
CONCLUSIONS—Our results show that IVT+MT patients in the ASTER trial have lower 90-day mortality compared with those receiving MT alone. In a selected population of patients without prestroke anticoagulation, we demonstrated that IVT associated with MT might improve functional outcome and recanalization while reducing mortality rates.
Fluid attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) document slowed vascular flow at the level and after the occlusion site patients with acute ischemic stroke (AIS). We aimed ...to assess the accuracy of FVH for the confirmation and location of a large vessel occlusion (LVO).
Three radiologists reviewed the FLAIR sequence of the admission MRI exam of patients with suspected AIS at a single academic center. Readers were provided with the main clinical deficit with National Institute of Health Stroke Severity score and were asked to identify and locate an LVO when appropriate. Kappa coefficients were calculated for agreement along with diagnosis performances of FVH to recognize and locate an LVO with digital subtracted angiography (DSA) as gold standard.
Among 125 patients screened with MRI for a suspected AIS, 96 (81%) were diagnosed with AIS and 47 (38%) patients had an anterior LVO of whom 25 (20%) had a DSA for mechanical thrombectomy. Kappa coefficients for intra- and inter-readers were good to excellent. Overall, the sensitivity and the specificity of the FVH to predict an anterior LVO was 0.98 (95% confidence interval CI: 0.94-1) and 0.86 (95% CI: 0.79-0.96), respectively, while PPV and NPV were 0.87 (95% CI: 0.85-0.95) and 0.98 (0.97-1), respectively. FVH also showed good to excellent accuracy for identifying M1 and M2 versus internal carotid artery occlusion site.
We found that FVH demonstrated excellent diagnostic performances for the identification of LVO and its level with good to excellent reproducibility. This MRI radio marker of occlusion provides additional arguments and may speed-up the detection of potential candidates for MT.
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