Tenecteplase versus Alteplase before thrombectomy: A comprehensive evaluation of clinical and angiographic impact: Insights from the ETIS registry.

INTRODUCTION: Data on prior use of Tenecteplase versus Alteplase in acute stroke management by mechanical thrombectomy are controversial. Our primary objective was to make a comprehensive comparative assessment of clinical and angiographic efficacy and safety outcomes in a large prospective observational study. METHODS: We included stroke patients who were eligible for intravenous thrombolysis and endovascular thrombectomy between 2019 and 2021, from an ongoing registry in twenty comprehensive stroke centers in France. We divided patients into two groups based on the thrombolytic agent used (Alteplase vs Tenecteplase). We then compared their treatment times, and their angiographic (TICI scale), clinical (mRS at three months and sICH) and safety outcomes after controlling for potential confounders using propensity score methods. RESULTS: We evaluated 1131 patients having undergone thrombectomy for the final analysis, 250 received Tenecteplase and 881 Alteplase. Both groups were of the same median age (75 vs 74 respectively), and had the same baseline NIHSS score (16) and ASPECTS (8). There was no significant difference for First Pass Effect (OR 0.93, 95 % CI 0.76-1.14, p = 0.75), time required for reperfusion (OR 0.03, 95 % CI 0.09-0.16, p = 0.49), or for final reperfusion status. Clinically, functional independence at 90 days was similar in both groups (OR 0.82, 95 % CI 0.61-1.10, p = 0.18) with the same risk of sICH (OR 1.36, 95 % CI 0.77-2.41, p = 0.28). However, Tenecteplase patients had shorter imaging-to-groin puncture times (99 vs 142 min, p < 0.05). CONCLUSIONS: Tenecteplase showed no better clinical or angiographic impact on thrombectomy compared to Alteplase. Nevertheless, it appeared associated with a shorter thrombolysis-to-groin puncture time.

Mononeuritis multiplex following immune checkpoint inhibitors in malignant pleural mesothelioma.

Introduction: Mononeuritis multiplex is frequently related to vasculitic neuropathy and has been reported only sporadically as an adverse event of immune checkpoint inhibitors. Methods: Case series of three patients with mononeuritis multiplex-all with mesothelioma-identified in the databases of two French clinical networks (French Reference Center for Paraneoplastic Neurological Syndromes, Lyon; OncoNeuroTox, Paris; January 2015-October 2022) set up to collect and investigate n-irAEs on a nationwide level. Results: Three patients (male; median age 86 years; range 72-88 years) had pleural mesothelioma and received 10, 4, and 6 cycles, respectively, of first-line nivolumab plus ipilimumab combined therapy. In patient 1, the neurological symptoms involved the median nerves, and in the other two patients, there was a more diffuse distribution; the symptoms were severe (common terminology criteria for adverse events, CTCAE grade 3) in all patients. Nerve conduction studies indicated mononeuritis multiplex in all patients. Peripheral nerve biopsy demonstrated necrotizing vasculitis in patients 1 and 3 and marked IgA deposition without inflammatory lesions in patient 2. Immune checkpoint inhibitors were permanently withdrawn, and corticosteroids were administered to all patients, leading to complete symptom regression (CTCAE grade 0, patient 2) or partial improvement (CTCAE grade 2, patients 1 and 3). During steroid tapering, patient 1 experienced symptom recurrence and spreading to other nerve territories (CTCAE grade 3); he improved 3 months after rituximab and cyclophosphamide administration. Discussion: We report the occurrence of mononeuritis multiplex, a very rare adverse event of immune checkpoint inhibitors, in the three patients with mesothelioma. Clinicians must be aware of this severe, yet treatable adverse event.

Cerebral Amyloid Angiopathy-Related Inflammation and Biopsy-Positive Primary Angiitis of the CNS: A Comparative Study.

BACKGROUND AND OBJECTIVES: Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It is unknown whether clinical and radiologic features can differentiate CAA-RI from BP-PACNS and whether both diseases have different relapse rates. The objectives of this study were to compare clinicoradiologic presentations and relapse rates in patients with CAA-RI vs BP-PACNS. METHODS: Patients with CAA-RI and BP-PACNS were enrolled from 2 retrospective multicenter cohorts. Patients with CAA-RI were biopsy-positive or met probable clinicoradiologic criteria. Patients with BP-PACNS had histopathologic confirmation of CNS angiitis, with no secondary etiology. A neuroradiologist read brain MRIs, blinded to the diagnosis of CAA-RI or BP-PACNS. Clinicoradiologic features were compared using univariable logistic regression models. Relapse rates were compared using a univariable Fine-Gray subdistribution hazard model, with death as a competing risk. RESULTS: This study enrolled 104 patients with CAA-RI (mean age 73 years, 48% female sex) and 52 patients with BP-PACNS (mean age 45 years, 48% female sex). Patients with CAA-RI more often had white matter hyperintense lesions meeting the probable CAA-RI criteria (93% vs 51%, p < 0.001), acute subarachnoid hemorrhage (15% vs 2%, p = 0.02), cortical superficial siderosis (27% vs 4%, p < 0.001), ≥1 lobar microbleed (94% vs 26%, p < 0.001), past intracerebral hemorrhage (17% vs 4%, p = 0.04), ≥21 visible centrum semiovale perivascular spaces (34% vs 4%, p < 0.01), and leptomeningeal enhancement (70% vs 27%, p < 0.001). Patients with BP-PACNS more often had headaches (56% vs 31%, p < 0.01), motor deficits (56% vs 36%, p = 0.02), and nonischemic parenchymal gadolinium enhancement (82% vs 16%, p < 0.001). The prevalence of acute ischemic lesions was 18% in CAA-RI and 22% in BP-PACNS (p = 0.57). The features with the highest specificity for CAA-RI were acute subarachnoid hemorrhage (98%), cortical superficial siderosis (96%), past intracerebral hemorrhage (96%), and ≥21 visible centrum semiovale perivascular spaces (96%). The probable CAA-RI criteria had a 71% sensitivity (95% CI 44%-90%) and 91% specificity (95% CI 79%-98%) in differentiating biopsy-positive CAA-RI from BP-PACNS. The rate of relapse in the first 2 years after remission was lower in CAA-RI than in BP-PACNS (hazard ratio 0.46, 95% CI 0.22-0.96, p = 0.04). CONCLUSION: Clinicoradiologic features differed between patients with CAA-RI and those with BP-PACNS. Specific markers for CAA-RI were hemorrhagic signs of subarachnoid involvement, past intracerebral hemorrhage, ≥21 visible centrum semiovale perivascular spaces, and the probable CAA-RI criteria. A biopsy remains necessary for diagnosis in some cases of CAA-RI. The rate of relapse in the first 2 years after disease remission was lower in CAA-RI than in BP-PACNS.