Efficacy and Safety of Two Salts of Trientine in the Treatment of Wilson’s Disease

Background: Wilson’s disease (WD) is one of the few genetic disorders that can be successfully treated with pharmacological agents. Copper-chelating agents (D-penicillamine and Trientine salts) and zinc salts have been demonstrated to be effective. There are two salts of trientine. Trientine dihydrochloride salt (TETA 2HCL) is unstable at room temperature and requires storage at 2–8 °C. Trientine tetrahydrochloride (TETA 4HCL) is a more stable salt of trientine that can be stored at room temperature. No comparative study between both of the salts of trientine has been performed to date. As the two chemical forms were available in France between 1970 and 2009, we conducted a study to evaluate their efficacy and safety profiles. Methods: This retrospective cohort study was conducted by reviewing data from the national WD registry in France. Forty-three WD patients who received TETA 2HCL or TETA 4HCL monotherapy for at least one year until 2010 were included. The primary endpoints were hepatic and neurological outcomes. Secondary endpoints were the events leading to a discontinuation of medication. Results: Changes in medication were common, leading to the analysis of 57 treatment sequences of TETA 4HCL or TETA 2HCL. The mean duration of treatment sequence was significantly longer in the TETA 4 HCL group (12.6 years) than in the TETA 2HCL group (7.6 years) (p = 0.011). Ten patients experienced both trientine salts: eight stopped TETA 4 HCL (six had a hepatologic phenotype and two had a neurological phenotype) because this treatment was not available anymore (mean duration 7.4 years). Three of these patients already experienced TETA 2 HCL before the sequence. Two patients with a hepatologic phenotype (one had a previous sequence of TETA 4 HCL before) stopped TETA 2 HCL because of cold storage issues (mean duration 42.8 years). The total number of sequences was 57. All of the patients were clinically stable. No difference in efficacy was detected. Both treatments were well tolerated, except for a case of recurrence of lupus erythematosus-like syndrome in the TETA 2HCL group. The major reason for interruption of TETA 4HCL was due to a discontinuation in production of this salt. The reasons for stopping TETA 2HCL were mainly due to adherence issues largely attributed to the cold storage requirement. Conclusions: The two salts of trientine were effective in treating patients with WD. However, interruption of TETA 2HCL was frequent, linked to the cold storage requirement. As adherence to treatment is a key factor in the successful management of WD, physicians need to be even more vigilant in detecting adherence difficulties in patients receiving treatment with TETA 2HCL

The diagnostic value of MRI for ophthalmologic emergencies

There is a concern about the overuse of MRI in emergency services. We report the experience of a tertiary ophthalmology centre with neuro-ophthalmology specialization that benefits from a unique organization with an ophthalmology emergency service (OES), a stroke unit and an MRI working 24h a day

Diagnosis and Outcomes of Late‐Onset Wilson's Disease: A National Registry‐Based Study

Abstract Background Wilson's disease (WD) is usually diagnosed in children and young adults; limited data exist on late‐onset forms. Objective The aim was to characterize the clinical and paraclinical presentations, therapeutic management, and outcomes in patients with late‐onset WD. Methods Patients diagnosed with WD after age 40 years were identified from the French Wilson's Disease Registry (FWDR). Clinical, laboratory, and imaging findings and treatment were reported at diagnosis and last follow‐up. Results Forty‐five patients were identified (median age: 49, range: 40–64) and placed in three groups according to their clinical presentation: neurological (n = 20, median diagnostic delay: 20 months), hepatic (n = 13, diagnostic delay: 12 months), and family screening (n = 12), all confirmed genetically. Six neurological patients had an atypical presentation (1 torticollis, 2 writer's cramps, 2 functional movement disorders, and 1 isolated dysarthria), without T2/fluid‐attenuated inversion recovery brain magnetic resonance imaging (MRI) hyperintensities; 5 of 6 had no Kayser–Fleischer ring (KFR); 5 of 6 had liver involvement. In the neurological group, 84% of patients improved clinically, and 1 developed copper deficiency. In the hepatic group, 77% had cirrhosis; 6 patients required liver transplantation. In the screened group, 43% had mild liver involvement; 3 were not treated and remained stable; 24‐h urinary copper excretion was normal in 33% of patients at diagnosis. Conclusions In the FWDR, late‐onset forms of WD affect 8% of patients, mostly with neurological presentations. Thirty percent of the neurological forms were atypical (isolated long‐lasting symptoms, inconspicuous brain MRI, no KFR). With personalized treatment, prognosis was good. This study emphasized that WD should be suspected at any age and even in cases of atypical presentation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Mitral transcatheter edge to edge repair versus isolated mitral surgery for severe mitral regurgitation: A French nationwide study

International audienceBackground and aims: Mitral valve surgery and more recently mitral transcatheter edge-to-edge repair (TEER) are the two treatments of severe mitral regurgitation in eligible patients. Clinical comparison of both therapies remains limited by the number of patients analysed. The objective of this study was to analyse the outcomes of mitral TEER versus isolated mitral valve surgery at a nationwide level in France.Methods: Based on the French administrative hospital-discharge database, the study collected information for all consecutive patients treated for mitral regurgitation with isolated TEER or isolated mitral valve surgery between 2012 and 2022. Propensity score matching was used for the analysis of outcomes.Results: A total of 57,030 patients were found in the database. After matching on baseline characteristics, 2,160 patients were analysed in each arm. At 3-year follow-up, TEER was associated with significantly lower incidence of cardiovascular death (HR 0.685, 95% CI 0.563-0.832; p < 0.001), pacemaker implantation and stroke. Non-cardiovascular death (HR 1.562, 95% CI 1.238-1.971; p = 0.0001), recurrent pulmonary edema and cardiac arrest were more frequent after TEER. No significant differences between the two groups were observed regarding all-cause death (HR 0.967, 95% CI 0.835-1.118; p = 0.65), endocarditis, major bleeding and atrial fibrillation and myocardial infarction.Conclusions: Our results suggest that TEER for severe mitral regurgitation was associated with lower cardiovascular mortality than mitral surgery at long-term follow-up. Pacemaker implantation and stroke were less frequently observed after TEER

Predictors of Parenchymal Hematoma After Mechanical Thrombectomy

International audienceBackground and Purpose— Parenchymal hematoma (PH) is a rare but dreadful complication of acute ischemic stroke with unclear underlying mechanisms. We aimed to study the incidence and predictors of PH after mechanical thrombectomy. Methods— Data from a prospective observational multicenter registry was screened to identify acute ischemic stroke patients with an anterior circulation large vessel occlusion who underwent mechanical thrombectomy. Clinical, imaging, and procedural characteristics were used for the analysis, including brain imaging systematically performed at 24 hours. PH occurrence was assessed according to ECASS (European Collaborative Acute Stroke Study) criteria. Univariate and multivariable analyses were performed to identify predictors of PH. Results— A total of 1316 patients were included in the study. PH occurred in 153 out of 1316 patients (11.6%) and was associated with a lower rate of favorable outcome and increased mortality. On multivariable analysis, age (per 1 year increase, odds ratio [OR], 1.01; 95% CI, 1.00–1.03; P =0.05), current smoking (OR, 2.02; 95% CI, 1.32–3.09; P <0.01), admission Alberta Stroke Program Early CT Score (per a decrease of 1 point, OR, 1.70; 95% CI, 1.18–2.44; P <0.01), general anesthesia (OR, 1.98; 95% CI, 1.36–2.90; P <0.001), angiographic poor collaterals (OR, 2.13; 95% CI, 1.36–3.33; P <0.001) and embolization in new territory (OR, 2.94; 95% CI, 1.70–5.10; P <0.001) were identified as independent predictors of PH. Conclusions— PH occurred at a rate of 11.6% after mechanical thrombectomy, with high morbidity and mortality. Our study identified clinical, radiological, and procedural predictors of PH occurrence that can serve as the focus of future periprocedural management studies with the aim of reducing its occurrence. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT03776877

Mechanical Thrombectomy for Acute Ischemic Stroke Amid the COVID-19 Outbreak

International audienceBackground and Purpose: The efficiency of prehospital care chain response and the adequacy of hospital resources are challenged amid the coronavirus disease 2019 (COVID-19) outbreak, with suspected consequences for patients with ischemic stroke eligible for mechanical thrombectomy (MT). Methods: We conducted a prospective national-level data collection of patients treated with MT, ranging 45 days across epidemic containment measures instatement, and of patients treated during the same calendar period in 2019. The primary end point was the variation of patients receiving MT during the epidemic period. Secondary end points included care delays between onset, imaging, and groin puncture. To analyze the primary end point, we used a Poisson regression model. We then analyzed the correlation between the number of MTs and the number of COVID-19 cases hospitalizations, using the Pearson correlation coefficient (compared with the null value). Results: A total of 1513 patients were included at 32 centers, in all French administrative regions. There was a 21% significant decrease (0.79; [95%CI, 0.76–0.82]; P <0.001) in MT case volumes during the epidemic period, and a significant increase in delays between imaging and groin puncture, overall (mean 144.9±SD 86.8 minutes versus 126.2±70.9; P <0.001 in 2019) and in transferred patients (mean 182.6±SD 82.0 minutes versus 153.25±67; P <0.001). After the instatement of strict epidemic mitigation measures, there was a significant negative correlation between the number of hospitalizations for COVID and the number of MT cases ( R 2 −0.51; P =0.04). Patients treated during the COVID outbreak were less likely to receive intravenous thrombolysis and to have unwitnessed strokes (both P <0.05). Conclusions: Our study showed a significant decrease in patients treated with MTs during the first stages of the COVID epidemic in France and alarming indicators of lengthened care delays. These findings prompt immediate consideration of local and regional stroke networks preparedness in the varying contexts of COVID-19 pandemic evolution