Chorea-acanthocytosis associated with two novel heterozygous mutations in the VPS13A gene

Non peer reviewe

Progressive Multifocal Leukoencephalopathy: Current Insights

Cases of PML should be evaluated according to predisposing factors, as these subgroups differ by incidence rate, clinical course, and prognosis. The three most significant groups at risk of PML are patients with hematological malignancies mostly previously treated with immunotherapies but also untreated, patients with HIV infection, and patients using monoclonal antibody (mAb) treatments. Epidemiological data is scarce and partly conflicting, but the distribution of the subgroups appears to have changed. While there is no specific anti-JCPyV treatment, restoration of the immune function is the most effective approach to PML treatment. Research is warranted to determine whether immune checkpoint inhibitors could benefit certain PML subgroups. There are no systematic national or international records of PML diagnoses or a risk stratification algorithm, except for MS patients receiving natalizumab (NTZ). These are needed to improve PML risk assessment and to tailor better prevention strategies.Peer reviewe

JC polyomavirus DNA detection in clinical practice

Peer reviewe

Progressive Multifocal Leukoencephalopathy: Current Insights

Cases of PML should be evaluated according to predisposing factors, as these subgroups differ by incidence rate, clinical course, and prognosis. The three most significant groups at risk of PML are patients with hematological malignancies mostly previously treated with immunotherapies but also untreated, patients with HIV infection, and patients using monoclonal antibody (mAb) treatments. Epidemiological data is scarce and partly conflicting, but the distribution of the subgroups appears to have changed. While there is no specific anti-JCPyV treatment, restoration of the immune function is the most effective approach to PML treatment. Research is warranted to determine whether immune checkpoint inhibitors could benefit certain PML subgroups. There are no systematic national or international records of PML diagnoses or a risk stratification algorithm, except for MS patients receiving natalizumab (NTZ). These are needed to improve PML risk assessment and to tailor better prevention strategies

The Incidence and Predisposing Factors of John Cunningham Virus-Induced Progressive Multifocal Leukoencephalopathy in Southern Finland : A Population-Based Study

Background. The aim of this study was to assess the prevalence, incidence rate (IR), predisposing factors, survival rate, and diagnostic delay of progressive multifocal leukoencephalopathy (PML) across medical specialties. Another objective was to survey how PML diagnosis was made in the studied cases. Methods. This is a cross-sectional retrospective observational study of PML cases across different medical specialties during 2004-2016 in the Finnish Capital Region and Southern Finland. Data were obtained from clinical records, clinical microbiology, pathology and radiology department records, and human immunodeficiency virus (HIV) quality register medical records. Results. A total of 31 patients were diagnosed with PML. The prevalence of PML was 1.56 per 100 000 people and the IR was 0.12 per 100 000 individuals per year during 2004-2016. Hematologic malignancies (n = 19) and HIV/acquired immune deficiency syndrome (n = 5) were the most common underlying diseases, and all patients who had malignant diseases had received cancer treatment. Before PML diagnosis, 21 (67.7%) patients were treated with chemotherapy, 14 (45.2%) patients with rituximab, and 1 patient (3.2%) with natalizumab. Two patients (6.5%) had no obvious immunocompromising disease or treatment. Neither gender, age, first symptoms, previous medication, nor underlying disease influenced the survival of PML patients significantly. The 5-year survival rate was poor, at less than 10%. Conclusions. The majority of PML patients in our study had a predisposing disease or had immunosuppressive or monoclonal antibody therapy. In the future, broader use of immunosuppressive and immunomodulatory medications may increase incidence of PML among patients with diseases unassociated with PML. Safety screening protocols for John Cunningham virus and PML are important to prevent new PML cases.Peer reviewe

Prevalence of adverse pregnancy outcomes after exposure to interferon beta prior to or during pregnancy in women with MS : Stratification by maternal and newborn characteristics in a register-based cohort study in Finland and Sweden

Background: Previous studies reported no increase in the prevalence of adverse pregnancy outcomes after exposure to interferon-beta (IFN-beta). However, no study has investigated if the prevalence of these outcomes after IFN-beta exposure is modified by maternal and newborn characteristics. Our objective was to describe the stratified prevalence of adverse pregnancy outcomes among women with multiple sclerosis (MS) exposed only to IFN-beta or unexposed to any MS disease modifying drugs (MSDMDs). Methods: This population-based cohort study using Finnish (1996-2014) and Swedish (2005-2014) register data included pregnancies of women with MS exposed only to IFN-beta 6 months before or during pregnancy (n=718) or unexposed to MSDMDs (n=1397). The outcome prevalences were described stratified by maternal and newborn characteristics, with 95% confidence intervals (CIs). Confounder-adjusted analyses were performed if the prevalence results indicated modified effect of IFN-beta in specific strata. Results: The stratified analysis indicated that the prevalence of serious (anomaly or stillbirth) and other adverse pregnancy outcomes was similar among the exposed and unexposed, with no statistically significant difference. Among women treated for MS >5 years, serious adverse pregnancy outcomes occurred in 4.3% (95%CI: 1.98.3%) of pregnancies exposed only to IFN-beta 6 months before or during pregnancy and in 2.7% (95%CI: 1.25.0%) of unexposed pregnancies. The confounder adjusted analyses did not support the hypothesis that MSPeer reviewe

Monoklonaaliset vasta-aineet MS-taudin hoidossa

English summaryPeer reviewe

Pregnancy outcomes after exposure to interferon beta : a register-based cohort study among women with MS in Finland and Sweden

Background Our aim was to estimate and compare the prevalence of adverse pregnancy outcomes among pregnant women with multiple sclerosis (MS) exposed to interferon beta (IFNB) and among women with MS unexposed to any MS disease-modifying drug (MSDMD). Methods This cohort study used Finnish (1996-2014) and Swedish (2005-2014) national register data. Women with MS having IFNB dispensed 6 months before or during pregnancy as the only medication were considered as IFNB exposed (only IFNB-exposed), whereas women with MS unexposed to any MSDMD were considered unexposed (MSDMD-unexposed). Prevalence was described and compared using log-binomial or logistic regression and adjusted for potential confounders including maternal age and comorbidity. Results Among 2831 pregnancies, 2.2% of the only IFNB-exposed and 4.0% of the MSDMD-unexposed women had serious adverse pregnancy outcomes [elective termination of pregnancy due to foetal anomaly (TOPFA), major congenital anomaly (MCA) in live, or stillbirth]. After adjustments, the prevalence of serious adverse pregnancy outcomes was lower among the only IFNB-exposed compared with the MSDMD-unexposed [relative risk 0.55, 95% confidence interval (CI) 0.31-0.96]. The prevalence of individual outcomes, including MCA, spontaneous abortions, and stillbirths was not increased with IFNB exposure. Women with MS exposed to IFNB appeared more likely to terminate their pregnancy for reasons other than foetal anomaly, compared with MSDMD-unexposed pregnant MS patients (odds ratio 1.71, 95% CI 1.06-2.78). Conclusion In this large cohort study, no increase in the prevalence of adverse pregnancy outcomes was observed in women with MS exposed to IFNB compared with MS patients unexposed to any MSDMDs. This study together with other evidence led to a change in the labels of the IFNB products in September 2019 in the European Union, and IFNB use today may be considered during pregnancy, if clinically needed.Peer reviewe

Real-world treatment outcomes and safety of natalizumab in Finnish multiple sclerosis patients

Objectives: The primary objective was to evaluate long-term treatment persistence and safety of natalizumab in Finnish multiple sclerosis patients. The secondary objectives were to assess patient characteristics, use of natalizumab-related safety protocol, and treatment persistence in patients with different anti-John Cunningham virus antibody statuses (John Cunningham virus status). Materials & Methods: All adult multiple sclerosis patients in the Finnish multiple sclerosis register who started natalizumab between 1/2006 and 12/2018 were included in this study and followed retrospectively until treatment discontinuation or end of follow-up (12/2019). Results: In total, 850 patients were included. Median duration of natalizumab treatment was 7.8 years in John Cunningham virus negative (n = 229) and 2.1 years in John Cunningham virus positive patients (n = 115; p < 0.001). The most common cause for treatment discontinuation was John Cunningham virus positivity. After natalizumab discontinuation, patients who had a washout duration of less than 6 weeks had fewer relapses during the first 6 months (p = 0.012) and 12 months (p = 0.005) compared with patients who had a washout duration of over 6 weeks. During the median follow-up of 3.6 years, 76% of patients remained stable or improved on their Expanded Disability Status Scale. Conclusions: Treatment persistence was very high among John Cunningham virus negative patients. The study supports long-term effectiveness of natalizumab and a washout duration of less than 6 weeks after discontinuation.Peer reviewe

Abundance of A beta(5-x) x like immunoreactivity in transgenic 5XFAD, APP/PS1KI and 3xTG mice, sporadic and familial Alzheimer's disease

Peer reviewe