Objective
Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AIJCV) in the diagnosis of natalizumab-associated PML.
Methods
AIJCV was assessed in 37 cases of natalizumab-associated PML and 89 MS-patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme-linked immunosorbent assay, using JCV-VP1 fused to glutathione S-transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AIJCV was calculated as published.
Results
Twenty-six of 37 (70%) patients with natalizumab-associated PML exhibited an AIJCV > 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AIJCV > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AIJCV > 1.5.
Interpretation
Determination of the AIJCV could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML.
Sudden cardiac death (SCD) is one of the most common causes of death worldwide with a higher frequency especially in the young. Therefore, SCD is represented frequently in forensic autopsy practice, whereupon pathological findings in the heart can explain acute death. These pathological changes may not only include myocardial infarction, coronary thrombosis, or all forms of myocarditis/endocarditis but also rare diseases such as hereditary structural or arrythmogenic anomalies, lesions of the cardiac conduction system, or primary cardiac tumours.
The precision of death time estimation by vitreous potassium using 5 different formulas is compared on a random sample of 600 cases. Mean differences, standard deviations and 95% limits of confidence between real and extrapolated time since death were calculated. The best results were obtained using equations with "mean" slopes of about 0,17 or 0,19mmol/l per hour. Equations with a steeper or flatter slope reveal already great mean deviations between real and extrapolated time since death and do not allow a reliable death time estimation.
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