This study aimed to evaluate the utility of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCHL1) and total tau (tTAU) serum concentrations as approximation for cerebrospinal fluid (CSF) concentrations of the respective biomarkers in the context of neuroinflammation and multiple sclerosis (MS). NfL, GFAP, UCHL1 and tTAU concentrations in serum and CSF were measured in 183 patients (122 with neuroinflammatory disease and 61 neurological or somatoform disease controls) using the single molecule array HD-1 analyzer (Quanterix, Boston, MA). Spearman's rank correlations were computed between serum and CSF concentrations. In a second step, the effects of age, BMI, gadolinium-enhancing lesions in MRI, integrity of the blood-brain barrier (BBB) and presence of acute relapse were accounted for by computing partial correlations. The analyses were repeated for a subsample consisting of MS phenotype patients only (n = 118). EDSS, MS disease activity and acute relapse were considered as additional covariates. Receiver operating characteristic (ROC) analysis was performed for each serum/CSF biomarker concentration to assess how well the particular biomarker concentration differentiates MS patients from somatoform disease controls. Correlations between serum and CSF levels as well as area under the curve (AUC) values were compared for the different biomarkers using z-test statistics. Serum concentrations correlated positively with CSF levels for NfL (r = 0.705, p < 0.01) as well as for GFAP (r = 0.259, p < 0.01). Correlation coefficients were significantly higher for NfL than for GFAP (z = 5.492, p < 0.01). We found no significant serum-CSF correlations for UCHL1 or tTAU. After adjusting for covariates, the results remained unchanged. In the analysis focusing only on MS patients, the results were replicated. ROC analysis demonstrated similarly acceptable performance of serum and CSF NfL values in differentiating MS phenotype patients from somatoform disease controls. AUC values were significantly higher for serum and CSF NfL compared to other biomarkers. NfL and GFAP but not UCHL1 or tTAU serum concentrations are associated with CSF levels of the respective biomarker. NfL exhibits more robust correlations between its serum and CSF concentrations as compared to GFAP independently from BBB integrity, clinical and radiological covariates. Both serum and CSF NfL values differentiate between MS and controls.

Background: To mitigate the potential consequences of the coronavirus disease 2019 (COVID-19) pandemic on public life, the German Federal Government and Ministry of Health enacted a strict lockdown protocol on March 16, 2020. This study aimed to evaluate the impact of the COVID-19 pandemic on physical and mental health status and the supply of medical care and medications for people with epilepsy (PWE) in Germany. Methods: The Epi2020 study was a large, multicenter study focused on different healthcare aspects of adults with epilepsy. In addition to clinical and demographic characteristics, patients were asked to answer a questionnaire on the impact of the first wave of the COVID-19 pandemic between March and May 2020. Furthermore, the population-based number of epilepsy-related admissions in Hessen was evaluated for the January-June periods of 2017–2020 to detect pandemic-related changes. Results: During the first wave of the pandemic, 41.6% of PWE reported a negative impact on their mental health, while only a minority reported worsening of their seizure situation. Mental and physical health were significantly more negatively affected in women than men with epilepsy and in PWE without regular employment. Moreover, difficulties in ensuring the supply of sanitary products (25.8%) and antiseizure medications (ASMs; 19.9%) affected PWE during the first lockdown; no significant difference regarding these impacts between men and women or between people with and without employment was observed. The number of epilepsy-related admissions decreased significantly during the first wave. Conclusions: This analysis provides an overview of the general and medical care of epilepsy patients during the COVID-19 pandemic. PWE in our cohort frequently reported psychosocial distress during the first wave of the pandemic, with significant adverse effects on mental and physical health. Women and people without permanent jobs especially reported distress due to the pandemic. The COVID‐19 pandemic has added to the mental health burden and barriers to accessing medication and medical services, as self-reported by patients and verified in population-based data on hospital admissions. Trial registration: German Clinical Trials Register (DRKS), DRKS00022024. Registered October 2, 2020, http://www.drks.de/DRKS00022024

Impaired renal function can influence biomarker levels through mechanisms involving blood–brain barrier integrity and clearance pathways; however, the impact of variations within normal renal function remains unclear. The main aim of this study was to determine whether adjustment for the specific level of renal function is necessary when renal function remains within physiological levels. We studied n = 183 patients (NID n = 122; other neurological diseases n = 39; somatoform controls n = 22) who underwent lumbar puncture at University Hospital Frankfurt. Serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau protein (tTAU), and ubiquitin C-terminal hydrolase-L1 (UCHL1) were measured using the single molecule array (SIMOA) technique. Estimated glomerular filtration rate (eGFR) correlated negatively with CSF GFAP (r = −0.217, p = 0.004) and serum NfL (r = −0.164, p = 0.032). Patients with impaired renal function exhibited higher CSF NfL (p = 0.036) and CSF GFAP (p = 0.026) levels. However, these findings did not remain significant after adjusting for BMI and age. Importantly, in patients with normal renal function, no significant correlations with eGFR and biomarker levels were observed after adjustment. Our findings indicate that serum and CSF concentrations of NfL, GFAP, tTAU, and UCHL1 are not significantly affected by fluctuations in physiological kidney function but emphasize the importance of considering comorbidities in impaired renal function when interpreting biomarker levels.

Background/Objectives: Neurofilament light chain (NfL) is a promising biomarker for monitoring disease activity and treatment response in multiple sclerosis (MS). This meta-regression assesses the relationship between treatment effects on serum/plasma NfL (s/pNfL) and clinical and radiological endpoints in randomized controlled trials (RCTs). Methods: A systematic PubMed search identified RCTs in MS (1999–2023) with ⩾24 months’ duration and s/pNfL data. Extracted outcomes included treatment effects on s/pNfL, annualized relapse rate (ARR), confirmed disability worsening (CDW), magnetic resonance imaging (MRI) new/enlarging T2 lesions, and percentage brain volume change (PBVC). We evaluated the association of treatment effect on the selected outcomes at the trial level by a meta-regression, weighted by trial size and duration. Results: Fifteen RCTs ( n = 6814) were included, nine in relapsing MS (RMS, n = 5221), and six in progressive MS (PMS, n = 1593). Treatment effects on s/pNfL showed a moderate association with treatment effects on MRI new/enlarging T2 lesions ( R ² = 0.42, p = 0.01), ARR ( R ² = 0.33, p = 0.03) and CDW ( R ² = 0.30, p = 0.04), but not with PBVC. In RMS-only trials, association with ARR ( R ² = 0.45, p = 0.05) and CDW ( R ² = 0.50, p = 0.03) was more pronounced. Conclusion: In MS, treatment effects on s/pNfL are moderately associated with therapeutic effects on ARR, MRI new/enlarging T2 lesions, and CDW, whereas no consistent association was observed with PBVC.