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ObjectiveTo evaluate characteristics relevant to diagnosis of JC polyomavirus-associated progressive multifocal leukoencephalopathy (PML), and PML risk stratification in a large national cohort of patients with multiple sclerosis during therapy with natalizumab.MethodsAnalysis of 292 adverse drug reaction forms on suspected cases of PML reported to the German national competent authority until July 2017. Patients not fulfilling PML diagnostic criteria or with insufficient information available were excluded.ResultsOf the 142 confirmed patients with PML, 72.3% (95% confidence interval [CI] 64.4%–79.1%) were women, and the median age was 43 years (range 19–69). Of these patients, 7.7% (95% CI 4.3%–13.5%) were clinically asymptomatic at time of PML diagnosis. PML was fatal in 9.1% (95% CI 5.3%–15.1%) of the patients. Infratentorial lesions on imaging were reported in 40% (95% CI 32.0%–48.6%) of the patients. JC polyomavirus DNA in CSF was undetectable at time of first analysis in 23.8% (95% CI 17.3%–31.9%) of the patients. Three patients tested negative for anti-JC polyomavirus antibodies within 6 to 18 months before PML diagnosis, with seroconversion confirmed 5.5 months, 7 months (in a post hoc analysis only), or at time of PML diagnosis.ConclusionsJC polyomavirus DNA detection in CSF has limited sensitivity in early PML, and clinical and imaging presentation may be atypical. Thus, critical revision of current PML diagnostic criteria is warranted. Negative anti-JC polyomavirus antibodies in sera do not preclude the later development of PML. This emphasizes the need for close and regular serologic, imaging, and clinical monitoring in patients treated with natalizumab.

Objectives We sought to examine acute and midterm results of closure of multiple interatrial communications with staged device deployment and to review the relevant literature. Background Information about percutaneous methods of closure for multiple defects is limited. Methods We treated 148 patients with multiple defects. Of these, 88 had a relevant left to right shunt (“LRS”), 52 had a presumed paradoxical embolism (“PPE”), five had both (LRS and PPE), and one patient, respectively, had migraine, decompression sickness, and a right to left shunt. After implantation of the first device, closure of additional septal defects was attempted only if indicated clinically. Results Ninety-four patients received a single device and 53 more than one. In four patients, surgical defect closure followed. At the end of follow-up (FU; mean 4.5 ± 3.4 years), complete closure of all defects occurred in 67.6% (62.1% for LRS, 76.5% for PPE). Clinical success (small or trivial residual shunt) was achieved in 86.9% (83.9% for LRS, 90.2% for PPE). Complications included pericardial effusions in 2.7%, recurrent thromboembolic events in 4.8%, and new onset of atrial fibrillation in 10.1%. In a significant number of patients with multiple defects, after single device implantation, the likelihood of complete closure increased with FU time (26% complete closure at 1 month vs. 78% at 24 months). Conclusion Percutaneous closure of multiple interatrial communications is feasible and safe. Importantly, many residual defects close without further intervention at FU. Therefore, staged device delivery is an alternative to simultaneous device implantation, possibly requiring fewer and smaller second devices. © 2012 Wiley Periodicals, Inc.