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.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

Neurofilament light level correlates with brain atrophy, and cognitive and motor performance

Peer reviewe

Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients

Background Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. Objectives To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. Methods In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. Results Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1-3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. Conclusions SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.Peer reviewe

Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients

Background Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. Objectives To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. Methods In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. Results Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1-3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. Conclusions SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.</p

Neurofilament light level correlates with brain atrophy, and cognitive and motor performance

Peer reviewe

Neurofilament light level correlates with brain atrophy, and cognitive and motor performance

Publisher Copyright: Copyright © 2023 Kartau, Melkas, Kartau, Arola, Laakso, Pitkänen, Lempiäinen, Koikkalainen, Lötjönen, Korvenoja, Ahlström, Herukka, Erkinjuntti and Jokinen.Background: The usefulness of neurofilament light (NfL) as a biomarker for small vessel disease has not been established. We examined the relationship between NfL, neuroimaging changes, and clinical findings in subjects with varying degrees of white matter hyperintensity (WMH). Methods: A subgroup of participants (n = 35) in the Helsinki Small Vessel Disease Study underwent an analysis of NfL in cerebrospinal fluid (CSF) as well as brain magnetic resonance imaging (MRI) and neuropsychological and motor performance assessments. WMH and structural brain volumes were obtained with automatic segmentation. Results: CSF NfL did not correlate significantly with total WMH volume (r = 0.278, p = 0.105). However, strong correlations were observed between CSF NfL and volumes of cerebral grey matter (r = −0.569, p < 0.001), cerebral cortex (r = −0.563, p < 0.001), and hippocampi (r = −0.492, p = 0.003). CSF NfL also correlated with composite measures of global cognition (r = −0.403, p = 0.016), executive functions (r = −0.402, p = 0.017), memory (r = −0.463, p = 0.005), and processing speed (r = −0.386, p = 0.022). Regarding motor performance, CSF NfL was correlated with Timed Up and Go (TUG) test (r = 0.531, p = 0.001), and gait speed (r = −0.450, p = 0.007), but not with single-leg stance. After adjusting for age, associations with volumes in MRI, functional mobility (TUG), and gait speed remained significant, whereas associations with cognitive performance attenuated below the significance level despite medium to large effect sizes. Conclusion: NfL was strongly related to global gray matter and hippocampal atrophy, but not to WMH severity. NfL was also associated with motor performance. Our results suggest that NfL is independently associated with brain atrophy and functional mobility, but is not a reliable marker for cerebral small vessel disease.Peer reviewe

Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients

Abstract Background:Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. Objectives:To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. Methods:In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. Results:Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1–3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. Conclusions:SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised