Explore the vast range of titles available.

Neurofilament light chain (NfL) has emerged as a biomarker of neuroaxonal damage in several neurologic conditions. With increasing availability of fourth-generation immunoassays detecting NfL in blood, aspects of pre-analytical stability of this biomarker remain unanswered. This study investigated NfL concentrations in serum and plasma samples of 32 patients with neurological diagnoses using state of the art Simoa technology. We tested the effect of delayed freezing of up to 7 days and statistically determined stability and validity of measured concentrations. We found concentrations of NfL in serum and plasma to remain stable at room temperature when processing of samples is delayed up to 7 days (serum: mean absolute difference 0.9 pg/mL, intraindividual variation 1.2%; plasma: mean absolute difference 0.5 pg/mL, intraindividual variation 1.3%). Consistency of these results was nearly perfect for serum and excellent for plasma (intraclass correlation coefficients 0.99 and 0.94, respectively). In conclusion, the soluble serum and plasma NfL concentration remains stable when unprocessed blood samples are stored up to 7 days at room temperature. This information is essential for ensuring reliable study protocols, for example, when shipment of fresh samples is needed.

Serum neurofilament light chain (sNfL) and its ability to expose axonal damage in neurologic disorders have solicited a considerable amount of attention in blood biomarker research. Hence, with the proliferation of high-throughput assay technology, there is an imminent need to study the pre-analytical stability of this biomarker. We recruited 20 patients with common neurological diagnoses and 10 controls (i.e. patients without structural neurological disease). We investigated whether a variation in pre-analytical variables (delayed freezing up to 24 h and repeated thawing/freezing for up to three cycles) affects the measured sNfL concentrations using state of the art Simoa technology. Advanced statistical methods were applied to expose any relevant changes in sNfL concentration due to different storing and processing conditions. We found that sNfL concentrations remained stable when samples were frozen within 24 h (mean absolute difference 0.2 pg/ml; intraindividual variation below 0.1%). Repeated thawing and re-freezing up to three times did not change measured sNfL concentration significantly, either (mean absolute difference 0.7 pg/ml; intraindividual variation below 0.2%). We conclude that the soluble sNfL concentration is unaffected at 4–8 °C when samples are frozen within 24 h and single aliquots can be used up to three times. These observations should be considered for planning future studies.

Acute transverse myelitis (ATM) is a disease characterized by inflammation of the spinal cord and may have various causes. In the context of this work, the distinction between isolated ATM and initial manifestation of autoimmune-mediated diseases of the central nervous system such as multiple sclerosis (MS) is crucial. Hence, the aim of this work was to identify predictive factors associated with the conversion to definite MS in a collective of individuals after their initial episode of isolated ATM (no initial identified cause). In this retrospective data analysis from the Vienna MS Database, all patients from Jan. 1, 1999, to Dec. 31, 2019, with a diagnosis of isolated ATM (according to the criteria of the Transverse Myelitis Consortium Working Group) who underwent lumbar puncture were extracted. Electronic medical records were reviewed on the availability of clinical data including therapy and follow-up, laboratory results including cerebrospinal fluid (CSF) analysis, evoked potentials (EP) as well as magnetic resonance imaging data. Among 42 patients with the diagnosis of isolated ATM, 12 (29%) were subsequently diagnosed with MS over a median follow-up period of 7.7 years. Univariately, MS converters were younger (32 years [25–39] vs. 42 years [31–50], p = 0.032), had a lower CSF/serum albumin ratio (29 [24–35] vs 37 [27–52], p = 0.037), lower CSF total protein (4.5 [2.8–4.8] vs. 5.5 [3.4–8.5], p = 0.023) and a higher proportion of CSF-specific oligoclonal bands (OCB; 83% vs. 30%, p = 0.002). In the multivariate regression analysis, the presence of CSF-specific OCB emerged as the sole predictive factor of subsequent MS diagnosis (OR: 14.42, 95% CI 1.39 to 149.48, p  = 0.03). In a collective of 42 patients with isolated ATM and an MS conversion rate of nearly 30%, the only but highly predictive factor were CSF-specific OCB. This emphasizes the significance of conducting timely CSF analysis in such patients and underscores the need for tailored monitoring and follow-up strategies in this specific group.

Fabry disease (FD) constitutes a rare, X-linked lysosomal storage disorder affecting multiple organ systems, most notably heart, kidneys, and the central nervous system. Neurofilament light chains (NfL) have emerged as a prime candidate for a body fluid biomarker reflecting neuro-axonal injury. We aimed to evaluate its addition to the diagnostic and monitoring armamentarium in FD. Serum NfL concentrations (sNfL) were measured in 50 people with FD (PwFD) and 30 healthy control subjects (HC) using the Simoa© technology, followed by calculation of Z-scores adjusted for age and body mass index. In addition, clinical disease severity in PwFD was measured using the FOS-MSSI (Fabry outcome study – Mainz severity score index), which comprises clinical and paraclinical parameters. PwFD show elevated sNfL Z-scores compared to HC (PwFD: 1.12 [SD 1.5], HC: 0.01 [SD 1.2], p  < 0.001). In PwFD, males showed higher sNfL Z-scores than females (1.75 [SD 1.5] vs. 0.73 [SD 1.4]). Importantly, sNfL Z-scores were increased in PwFD with ischemic white matter lesions of the CNS (1.5, SD 2.2 vs. 0.5, SD 2.9, p  = 0.03). In our small cohort, sNfL Z-scores correlated fairly with FOS-MSSI (Kendall’s-Tau [τ] = 0.25, p  = 0.01), and, interestingly with serum creatinine (τ = 0.28, p  = 0.005) and estimated glomerular filtration rate (eGFR, τ =-0.28, p  = 0.005). Based on these exploratory results, sNfL might provide value as a biomarker of neuroaxonal damage in FD, possibly reflecting cerebrovascular injury. Additionally, the correlation of sNfL with renal function warrants further investigation.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease. Epstein-Barr virus (EBV) encodes for the EBNA-1 381-452 region that induces autoreactive antibody responses, which are likely critically involved in MS pathogenesis. Here we investigate whether these EBNA-1 381-452 -specific antibodies can serve as a biomarker to identify at-risk individuals for MS. We quantify EBNA-1 381-452 -specific antibody titers from 324 relapsing-remitting MS patients and 324 matched controls in longitudinal follow-up plasma samples, starting from the individual’s EBV-seroconversion. In MS patients, significantly elevated EBNA-1 381-452 -specific IgG titers are identified that are increased already as early as nine months after EBV-seroconversion (OR:5.7; 95% CI: 4.1-8.1; P  < 0.0001) and a median 5.4 years prior to MS diagnosis. Especially, the presence of continuously high EBNA-1 381-452 -specific antibody titers is associated with a more rapid MS diagnosis after EBV-seroconversion ( P  < 0.0001). Thus, the quantification of EBNA-1 381-452 -specific IgG antibody levels may provide a prognostic biomarker to determine the individual’s risk for the diagnosis of MS. Multiple sclerosis (MS) is linked to immune responses triggered by Epstein-Barr virus (EBV). Here, the authors demonstrate that elevated EBNA-1-specific IgG antibody titers, detectable soon after EBV seroconversion, are associated with individual MS risk potentially serving as a prognostic biomarker.

Background Pregnancy and delivery outcomes in women with Fabry disease are not well described. Methods Retrospective cohort-study of women with Fabry disease in Austria using a specific questionnaire and the Austrian Mother–Child Health Passport. Results Out of a total of 44 enrolled women (median age at study entry 44 years, p25: 30, p75: 51), 86.4% showed signs and symptoms of Fabry disease with an increase in pain burden during pregnancy, primarily in women with moderate pain before pregnancy. Thirty-two of 44 women with Fabry disease reported a total of 70 pregnancies (median age at first pregnancy 24 years, p25: 21, p75: 31), 61 (87.1%) of which resulted in 64 live births including 3 sets of twins, six miscarriages (8.6%) in five women, and three induced abortions (4.3%) in two women. Risk factors for poor maternal and foetal outcomes during pregnancy, overrepresented in our cohort as compared to the general population, were hypertension ( n  = 10, 16.4%), proteinuria ( n  = 17, 27.9%) and smoking ( n  = 24, 39.3%). Preeclampsia was reported in 7 pregnancies (11.5%). Fifty-one (79.7%) children were born at term and 13 (20.3%) were preterm (including one neonatal death), with a median gestational age of 39 weeks (p25: 38, p75: 40) and delivery by C-section in 15 pregnancies (24.6%). Thirteen (20.3%) children presented with low birth weight and 18 (28.1%) were small for their gestational age. In comparison to global and national data-sets, preeclampsia, prematurity, low birth weight, being small for their gestational age as well as inpatient stay were significantly more common in patients with Fabry disease. Conclusions Our cohort-study in women with Fabry disease shows an increase of pain burden during pregnancies and clearly points to an increased risk for preeclampsia, prematurity, and neonates small for gestational age. With a substantial number of high-risk pregnancies, neonatal outcomes are somewhat worse in Fabry disease than in the general public. Thus, we provide valuable data enabling informed decision-making in pregnancy counselling for Fabry disease.

Background Neurological symptoms are common in acute mountain sickness (AMS); however, the extent of neuroaxonal damage remains unclear. Neurofilament light chain (NfL) is an established blood biomarker for neuroaxonal damage. Objective To investigate whether plasma (p) NfL levels increase after simulated altitude exposure, correlate with the occurrence of AMS, and might be mitigated by preacclimatization. Methods Healthy subjects were exposed to simulated high altitude (4500 m) by the use of a normobaric hypoxic chamber at the University of Innsbruck two times, that is, within Cycle 1 (C1) over 12 h, and within Cycle 2 (C2) for another 12 h but with a random assignment to prior acclimatization or sham acclimatization. Before each cycle (measurement [M] 1 and 3) and after each cycle (M2 and M4), clinical data (arterial oxygen saturation [SaO2], heart rate, and Lake Louise AMS score [LLS]) and plasma samples were collected. pNfL was measured using single‐molecule array (Simoa) technique. Results pNfL levels did not significantly change within each study cycle, but increased over the total study period (M1: 4.57 [3.34–6.39], M2: 4.58 [3.74–6.0], M3: 5.64, and M4: 6.53 [4.65–7.92] pg/mL, p < 0.001). Subjects suffering from AMS during the study procedures showed higher pNfL levels at M4 (6.80 [6.19–8.13] vs. 5.75 [4.17–7.35], p = 0.048), a higher total pNfL increase (2.88 [1.21–3.48] vs. 0.91 [0.53–1.48], p = 0.022) compared to subjects without AMS. An effect of preacclimatization on pNfL levels could not be observed. Conclusions pNfL increases alongside exposure to simulated altitude and is associated with AMS. Healthy subjects were exposed to simulated high altitude (4500 m) two times, i.e., within Cycle 1 and Cycle 2, the latter with a random assignment to prior acclimatization or sham acclimatization. Before and after each cycle, pNfL was measured. pNfL levels increased over the total study period. Subjects suffering from AMS during the study procedures showed higher pNfL levels at M4 and a higher total pNfL increase.

The kappa free light chain (κ-FLC) index is a well-established biomarker in multiple sclerosis (MS). While the prognostic value of the κ-FLC index has been demonstrated in early relapsing-remitting MS, its prognostic value in primary progressive MS (PPMS) has not yet been investigated. In this multicenter, retrospective cohort study, patients diagnosed with PPMS with diagnostic lumbar puncture and clinical follow-up of at least 12 months were recruited from nine MS centers across five countries. At baseline, age, sex, disease duration, and the number of T2 hyperintense (T2L) and contrast-enhancing T1 lesions (CEL) on MRI were determined. κ-FLC was measured using nephelometry/turbidimetry, and the κ-FLC index was calculated as (CSF κ-FLC/serum κ-FLC)/albumin quotient. At follow-up, the occurrence of disability progression and the administration of disease-modifying treatment (DMT) were registered. The primary endpoint was time to disability progression. A total of 121 PPMS patients were included with a median age of 53 years (25th-75th percentile: 46-59) and a balanced sex distribution (48.8% female). Multivariable Cox regression analysis revealed no significant association between the κ-FLC index and disability progression [hazard ratio (HR) 1.0, p = 0.950]. Prior use of DMT (HR 0.60, p = 0.023) and brain T2L > 9 at baseline (HR 2.22, p = 0.026) were significantly associated with disability progression. The remaining covariates, including age, sex, disease duration, and CEL, showed no significant associations. The κ-FLC index does not predict disability progression in PPMS, contrasting its growing role as a prognostic biomarker in relapsing MS. This highlights phenotypic differences in MS pathophysiology and underscores the need for prognostic biomarkers in PPMS.

Introduction Continuous monitoring is the hallmark of managing chronic disease. Multiple sclerosis (MS), in particular, requires patients to visit their treating neurologists typically twice a year, at least. In that respect, the COVID-19 pandemic made us rethink our communication strategies. This study determined satisfaction with remote visits for people with MS (pwMS) by comparing non-inferiority to conventional visits. Methods TELE MS was a randomized controlled trial that was open to any person with MS. We randomized a volunteer sample of 45 patients. We compared satisfaction with remote visits (via phone or via videochat) with conventional outpatient visits. The primary endpoint was patient satisfaction determined by the Telemedicine Perception Questionnaire (TMPQ, min: 17 and max: 85 points) with the hypothesis of non-inferiority of televisits to conventional visits. Physician satisfaction measured on the PPSM score (Patient and Physician Satisfaction with Monitoring, min: 5 and max: 25 points) was the secondary endpoint. Results The trial met both endpoints. Mean (SD) TMPQ scores in the individual groups were 58 (6.7) points for conventional visits, 65 (7.5) points for phone visits, and 62 (5.5) points for video visits. Physician satisfaction over the whole cohort was similarly high. Median (range) PPSM scores were 23 (16–25) for the whole cohort, 19 (16–25) for conventional visits, 25 (17–25) for phone visits, and 25 (16–25) for video visits. Conclusions Televisits in multiple sclerosis yield a high level of satisfaction for both patients and treating physicians. This concept for remote patient monitoring adopted during the current pandemic may be communicable to other chronic diseases as well. ClinicalTrials.gov identifier: NCT04838990