Safety and efficacy of mechanical thrombectomy in acute ischemic stroke of anticoagulated patients.

BACKGROUND: Anticoagulated patients (APs) are currently excluded from acute ischemic stroke reperfusion therapy with intravenous recombinant tissue plasminogen activator (IV-rtPA); however, these patients could benefit from mechanical thrombectomy (MT). Evidence for MT in this condition remains scarce. The aim of this study was to analyze the safety and efficacy of MT in APs. METHODS: We analyzed three patient groups from two prospective registries: APs with MT (AP-MT group), non-anticoagulated patients treated with MT (NAP-MT group), and non-anticoagulated patients treated with IV-rtPA and MT (NAP-IVTMT group). Univariate and multivariate logistic regression were used to evaluate treatment efficacy with modified Rankin Scale (mRS) ≤2 and safety (radiologic intracranial hemorrhage (rICH), symptomatic intracranial hemorrhage (sICH) and death rate at 3 months) between groups. RESULTS: 333 patients were included in the study, with 44 (12%) in the AP-MT group, 105 (31%) in the NAP-MT group, and 188 (57%) in the NAP-IVTMT group. Univariate analysis showed that the AP-MT group was older (P<0.001), more often had atrial fibrillation (P<0001), and had a higher ASPECTS (P<0.006 and P<0.002) compared with the NAP-MT group and NAP-IVTMT groups, respectively. Multivariate analysis showed that the AP-MT group had a lower risk of rICH (OR 2.77, 95% CI 1.01 to 7.61, P=0.05) but a higher risk of death at 3 months (OR 0.26, 95% CI 0.09 to 0.76, P=0.01) compared with the NAP-IVTMT group. No difference was found between the AP-MT and NAP-MT groups. CONCLUSIONS: With regard to intracranial bleeding and functional outcome at 3 months, MT in APs seems as safe and efficient as in NAPs. However, there is a higher risk of death at 3 months in the AP-MT group compared with the NAP-IVTMT group.

Understanding the Pathophysiology of Intracranial Aneurysm: The ICAN Project.

BACKGROUND: Understanding the pathophysiologic mechanism of intracranial aneurysm (IA) formation is a prerequisite to assess the potential risk of rupture. Nowadays, there are neither reliable biomarkers nor diagnostic tools to predict the formation or the evolution of IA. Increasing evidence suggests a genetic component of IA but genetics studies have failed to identify genetic variation causally related to IA. OBJECTIVE: To develop diagnostic and predictive tools for the risk of IA formation and rupture. METHODS: The French ICAN project is a noninterventional nationwide and multicentric research program. Each typical IA of bifurcation will be included. For familial forms, further IA screening will be applied among first-degree relatives. By accurate phenotype description with high-throughput genetic screening, we aim to identify new genes involved in IA. These potential genetic markers will be tested in large groups of patients. Any relevant pathway identified will be further explored in a large cohort of sporadic carriers of IA, which will be well documented with clinical, biological, and imaging data. EXPECTED OUTCOMES: Discovering genetic risk factors, better understanding the pathophysiology, and identifying molecular mechanisms responsible for IA formation will be essential bases for the development of biomarkers and identification of therapeutic targets. DISCUSSION: Our protocol has many assets. A nationwide recruitment allows for the inclusion of large pedigrees with familial forms of IA. It will combine accurate phenotyping and comprehensive imaging with high-throughput genetic screening. Last, it will enable exploiting metadata to explore new pathophysiological pathways of interest by crossing clinical, genetic, biological, and imaging information.

Management of acute central retinal artery occlusion: Intravenous thrombolysis is feasible and safe.

Background Although acute central retinal artery occlusion is as a stroke in the carotid territory (retinal artery), its management remains controversial. The aim of this study was to assess the feasibility and safety of intravenous thrombolysis delivered within 6 h of central retinal artery occlusion in French stroke units. Methods We performed a retrospective analysis of patients treated with intravenous alteplase (recombinant tissue-plasminogen activator), based on stroke units thrombolysis registers from June 2005 to June 2015, and we selected those who had acute central retinal artery occlusion. The feasibility was assessed by the ratio of patients that had received intravenous alteplase within 6 h after central retinal artery occlusion onset among those who had been admitted to the same hospital for acute central retinal artery occlusion. All adverse events were documented. Results Thirty patients were included. Visual acuity before treatment was limited to "hand motion", or worse, in 90% of the cases. The mean onset-to-needle time was 273 min. The individuals treated with intravenous alteplase for central retinal artery occlusion represented 10.2% of all of the patients hospitalized for central retinal artery occlusion in 2013 and 2014. We observed one occurrence of major bleeding, a symptomatic intracerebral hemorrhage. Conclusion When applied early on, intravenous thrombolysis appears to be feasible and safe, provided that contraindications are given due consideration. Whether intravenous thrombolysis is more effective than conservative therapy remains to be determined. In order to conduct a well-designed prospective randomized control trial, an organized network should be in place.

Delayed-onset Friedreich's ataxia revisited.

BACKGROUND: Friedreich's ataxia usually occurs before the age of 25. Rare variants have been described, such as late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia, occurring after 25 and 40 years, respectively. We describe the clinical, functional, and molecular findings from a large series of late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia and compare them with typical-onset Friedreich's ataxia. METHODS: Phenotypic and genotypic comparison of 44 late-onset Friedreich's ataxia, 30 very late-onset Friedreich's ataxia, and 180 typical Friedreich's ataxia was undertaken. RESULTS: Delayed-onset Friedreich's ataxia (late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia) had less frequently dysarthria, abolished tendon reflexes, extensor plantar reflexes, weakness, amyotrophy, ganglionopathy, cerebellar atrophy, scoliosis, and cardiomyopathy than typical-onset Friedreich's ataxia, along with less severe functional disability and shorter GAA expansion on the smaller allele (P < 0.001). Delayed-onset Friedreich's ataxia had lower scale for the assessment and rating of ataxia and spinocerebellar degeneration functional scores and longer disease duration before wheelchair confinement (P < 0.001). Both GAA expansions were negatively correlated to age at disease onset (P < 0.001), but the smaller GAA expansion accounted for 62.9% of age at onset variation and the larger GAA expansion for 15.6%. In this comparative study of late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia, no differences between these phenotypes were demonstrated. CONCLUSION: Typical- and delayed-onset Friedreich's ataxia are different and Friedreich's ataxia is heterogeneous. Late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia appear to belong to the same clinical and molecular continuum and should be considered together as "delayed-onset Friedreich's ataxia." As the most frequently inherited ataxia, Friedreich's ataxia should be considered facing compatible pictures, including atypical phenotypes (spastic ataxia, retained reflexes, lack of dysarthria, and lack of extraneurological signs), delayed disease onset (even after 60 years of age), and/or slow disease progression.

Cyclosporine in acute ischemic stroke.

OBJECTIVES: We examined whether IV administration of cyclosporine in combination with thrombolysis might reduce cerebral infarct size. METHODS: Patients aged 18 to 85 years, presenting with an anterior-circulation stroke and eligible for thrombolytic therapy, were enrolled in this multicenter, single-blinded, controlled trial. Fifteen minutes after randomization, patients received either an IV bolus injection of 2.0 mg/kg cyclosporine (Sandimmune, Novartis) or placebo. The primary endpoint was infarct volume on MRI at 30 days. Secondary endpoints included infarct volume according to the site (proximal/distal) of arterial occlusion and recanalization after thrombolysis. RESULTS: From October 2009 to July 2013, 127 patients were enrolled. The primary endpoint was assessed in 110 of 127 patients. The reduction of infarct volume in the cyclosporine compared with the control group was overall not significant (21.8 mL [interquartile range, IQR 5.1, 69.2 mL] vs 28.8 mL [IQR 7.7, 95.0 mL], respectively; p = 0.18). However, in patients with proximal occlusion and effective recanalization, infarct volume was significantly reduced in the cyclosporine compared with the control group (14.9 mL [IQR 1.3, 23.2 mL] vs 48.3 mL [IQR 34.5, 118.2 mL], respectively; p = 0.009). CONCLUSIONS: Cyclosporine was generally not effective in reducing infarct size. However, a smaller infarct size was observed in patients with proximal cerebral artery occlusion and efficient recanalization. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with an acute anterior-circulation stroke, thrombolysis plus IV cyclosporine does not significantly decrease 30-day MRI infarct volume compared with thrombolysis alone.

Relevance of corpus callosum splenium versus middle cerebellar peduncle hyperintensity for FXTAS diagnosis in clinical practice.

Fragile X-associated tremor ataxia syndrome (FXTAS) is caused by FMR1 premutation. The features include ataxia, action tremor and middle cerebellar peduncle (MCP) hyperintensity, the latter being the only major radiological criterion in the diagnosis of definite FXTAS until very recently. The importance of corpus callosum splenium (CCS) hyperintensity was recently reported and this sign is now considered as an additional major radiological diagnostic criterion in the diagnosis of FXTAS. However, little is known about its relevance for the diagnosis of FXTAS in clinical practice. We report a practical justification of the relevance of CCS hyperintensity in parallel with MCP hyperintensity for the diagnosis of FXTAS. Clinical and radiological study of 22 FMR1 premutation carriers with neurological signs that may be encountered in FXTAS compared to series of patients with essential tremor, multiple system atrophy of cerebellar type, Parkinson's disease, Alzheimer's disease and stroke. Among the 22 patients with FMR1 premutation [17 men, 5 women; mean age, 63 ± 7.5 (46-84)], 14 were diagnosed with definite FXTAS with the initial criteria. Considering CCS hyperintensity as a new major radiological criterion permitted the diagnosis of definite FXTAS in 3 additional patients. Overall CCS proved as frequent as MCP hyperintensity (64 versus 64 %), while 23 % of patients had CCS but not MCP hyperintensity, 14 % of patients had CCS hyperintensity but neither MCP, nor brainstem hyperintensity. In contrast with CCS hyperintensity, MCP hyperintensity proved less frequent in women than in men. CCS and MCP hyperintensity were more frequent in FXTAS than in the other neurodegenerative disorders. The combination of CCS and MCP hyperintensity was specific of FXTAS. We confirmed the relevance of CCS hyperintensity in FXTAS and we clarified its interest compared to MCP hyperintensity. Our results support the inclusion of CCS hyperintensity in the diagnostic criteria as a new major radiological criterion.