Serum Neurofilament Light concentrations are not associated with renal function in secondary progressive multiple sclerosis

BACKGROUND: Neurofilament Light (NFL) is a promising biomarker of neuroaxonal injury. Its utility may be improved by expression relative to age-matched controls and by adjusting for other covariates, such as body mass index. It has recently been suggested that renal function may modulate the rate of clearance of NFL from circulation, which if confirmed would make renal function an important additional covariate to take into account when interpreting NFL data in research or clinical settings. Here we explore the relationship between renal function and NFL in a cohort of patients with secondary progressive multiple sclerosis (SPMS). METHODS: We examined data from patients with SPMS who took part in the MS-STAT randomised controlled trial. We use multivariable linear regression to explore the relationship between serum NFL and renal function, and additionally to examine whether including renal function as a covariate improves the ability of NFL to predict the subsequent rate of whole brain atrophy. RESULTS: Data on renal function and serum NFL was available for 122 patients. Mean eGFR 88 ml/min/1.73 m^{2} (range 38.2–121.9). We found no evidence to support a relationship between renal function and serum NFL in this cohort. Furthermore, the inclusion of eGFR as a covariate in models assessing the relationship between NFL and the rate of whole brain atrophy had no significant effect upon the relationships observed. CONCLUSIONS: We find no evidence for a relationship between renal function and NFL in a cohort of patients with secondary progressive multiple sclerosis. We hypothesise that the previously observed relationships between NFL and renal function related to associations between renal function and subclinical neuropathology, rather than due to modulating clearance of NFL from the circulation, but further research would be required to confirm such mechanisms

Serum Neurofilament Light Protein as a Marker for Diffuse Axonal Injury: Results from a Case Series Study

Diffuse axonal injury (DAI) is an important cause of morbidity in patients with traumatic brain injury (TBI). There is currently no simple and reliable technique for early identification of patients with DAI, or to prognosticate long-term outcome in this patient group. In the present study, we examined acute serum concentrations of neurofilament light (NFL) in nine patients with severe TBI and DAI using a novel ultrasensitive single molecule array (Simoa) assay. The relationships between the NFL concentrations and MRI in the acute stage as well as clinical outcome and magnetic resonance diffusion tensor imaging (MR-DTI) parameters at 12 months were analyzed. We found that the mean NFL concentrations among the patients displayed a 30-fold increase compared with controls, and that NFL completely discriminated between the patients and controls. We also found a relationship between serum NFL and MR-DTI parameters, with higher NFL concentrations in patients with higher trace (R2 = 0.79) and lower fractional anisotropy (FA) (R 2 = 0.83). These results suggest that serum NFL may be a valuable blood biomarker for TBI, reflecting the severity of DAI

EU Peatlands: Current Carbon Stocks and Trace Gas Fluxes

Peatlands in Europe has formed a significant sink for atmospheric CO2 since the last glacial maximum. Currently they are estimated to hold ca. 42 Gt carbon in the form of peat and are therefore a considerable component in the European carbon budget. Due to the generally wet soil conditions in peatlands they are also significant emitters of the strong greenhouse gas (GHG) methane (CH4) and in some cases also of nitrous oxide (N2O). The EU funded CarboEurope-GHG Concerted Action attempts to develop a reliable and complete greenhouse gas budget for Europe and this report aims to provide a review and synthesis of the available information about GHG exchanges in European peatlands and their underlying processes. A best estimate for all the European countries shows that some are currently sinks for atmospheric CO2 while others are sources. In contrast, for CH4 and N2O, only the sources are relevant. Whilst some countries are CO2 sinks, all countries are net GHG emitters from peatlands. The results presented, however, carry large uncertainties, which cannot be adequately quantified yet. One outstanding uncertainty is the distribution of land use types, particular in Russia, the largest European peat nation. The synthesis of GHG exchange, nevertheless, indicates some interesting features. Russia hosts an estimated 41% of European peatlands and contributes most to all GHG exchanges (CO2: 25%, CH4: 52%, N2O: 26%, Total: 37%). Germany is the second-largest emitter (12% of European total) although it contains only 3.2% of European peatlands. The reason is the use of most of the peatland area for intensive cropland and grassland. The largest CO2 emitters are countries with large agricultural peatland areas (Russia, Germany, Belarus, Poland), the largest N2O emitters are those with large agricultural fen areas (Russia, Germany, Finland). In contrast, the largest CH4 emitters are concentrated in regions with large areas of intact mires, namely Russia and Scandinavia. High average emission densities above 3.5 t C-equiv. ha-1 are found in the Southeast Mediterranean, Germany and the Netherlands where agricultural use of peatlands is intense. Low average emission densities below 0.3 t C-equiv. ha-1 occur where mires and peatland forests dominate, e.g. Finland and the UK. This report concludes by pointing at key gaps in our knowledge about peatland carbon stocks and GHG exchanges which include insufficient basic information on areal distribution of peatlands, measurements of peat depth and also a lack of flux datasets providing full annual budgets of GHG exchanges

Serum-neuroproteins, near-infrared spectroscopy, and cognitive outcome after beach-chair shoulder surgery: observational cohort study analyses

BACKGROUND: Cerebral hypoxia may occur during surgery but currently used cerebral oxygenation saturation (rSO2) monitors remain controversial with respect to improving clinical outcome. Novel neuroprotein biomarkers are potentially released into systemic circulation and combined with near-infrared spectroscopy (NIRS) could clarify the presence of per-operative cerebral hypoxia. We investigated changes to serum-neuroprotein concentrations postsurgically, paired with NIRS and cognitive outcome, in patients operated in the beach chair position (BCP). METHODS: A prospective cohort in 28 shoulder surgery patients placed in the BCP. Blood samples were collected before induction of anaesthesia, and 2 hours and 3-5 days postoperatively. We analysed blood-levels of biomarkers including tau and neurofilament light (NFL). We post hoc assessed the cross-wise relationship between biomarker levels and postsurgical changes in cognitive function and intraoperatively monitored rSO2 from NIRS. RESULTS: Serum-NFL decreased from 24.2 pg/mL to 21.5 (P=0.02) 2 hours postoperatively, then increased to 27.7 pg/mL on day 3-5 (P=0.03). Conversely, s-tau increased from 0.77 pg/mL to 0.98 (2 h), then decreased to 0.81 on day 3-5 (P=0.08). In 14/28 patients, episodic rSO2 below 55% occurred, and the duration <55% was correlated to change in s-tau (P<0.05). The cognitive function z-score at 1 week and 3 mo. correlated to the change in tau (P=0.01), but not to NFL. CONCLUSION: Some biomarkers were significantly changed with surgery in the beach chair position. The change was at some points associated to postoperative cognitive decline, and to intraoperative low rSO2. (237)

Plasma neurofilament light chain protein is not increased in forensic psychiatric populations: a pilot study

Introduction: Neurofilament light chain protein (NfL) is a fluid biomarker of neural injury measurable in cerebrospinal fluid and blood. Patients with different neurodegenerative disorders and mild traumatic brain injury display elevated levels of NfL. However, so far, elevated levels of NfL have not been demonstrated in persons with psychiatric disorders. To our knowledge, the occurrence of NfL in the blood has not previously been studied in persons undergoing forensic psychiatric assessment or persons treated in forensic mental health services. Supposedly, these persons suffer from experiences and conditions with a higher risk of neural injury than other psychiatric patients. Methods: In this pilot study, we investigated plasma levels of NfL in 20 persons undergoing forensic psychiatric assessment and 20 patients at a forensic psychiatric hospital. NfL values were compared with control groups of healthy individuals matched for age and sex. Results: The prevalence of increased NfL in both forensic groups was low and did not differ compared with the controls. However, some persons undergoing forensic psychiatric assessment showed slightly elevated values. Discussion: The slightly elevated values were observed in the group investigated closer in time to the index crime, when elevated NfL levels could be expected to be more prevalent due to acute conditions from the time of the offense. This gives reason to look further into this group

The localization of amyloid precursor protein to ependymal cilia in vertebrates and its role in ciliogenesis and brain development in zebrafish

Amyloid precursor protein (APP) is expressed in many tissues in human, mice and in zebrafish. In zebrafish, there are two orthologues, Appa and Appb. Interestingly, some cellular processes associated with APP overlap with cilia-mediated functions. Whereas the localization of APP to primary cilia of in vitro-cultured cells has been reported, we addressed the presence of APP in motile and in non-motile sensory cilia and its potential implication for ciliogenesis using zebrafish, mouse, and human samples. We report that Appa and Appb are expressed by ciliated cells and become localized at the membrane of cilia in the olfactory epithelium, otic vesicle and in the brain ventricles of zebrafish embryos. App in ependymal cilia persisted in adult zebrafish and was also detected in mouse and human brain. Finally, we found morphologically abnormal ependymal cilia and smaller brain ventricles in appa-/-appb-/- mutant zebrafish. Our findings demonstrate an evolutionary conserved localisation of APP to cilia and suggest a role of App in ciliogenesis and cilia-related functions

Obinutuzumab-Induced B Cell Depletion Reduces Spinal Cord Pathology in a CD20 Double Transgenic Mouse Model of Multiple Sclerosis

B cell-depleting therapies have recently proven to be clinically highly successful in the treatment of multiple sclerosis (MS). This study aimed to determine the effects of the novel type II anti-human CD20 (huCD20) monoclonal antibody (mAb) obinutuzumab (OBZ) on spinal cord degeneration in a B cell-dependent mouse model of MS. Double transgenic huCD20xHIGR3 (CD20dbtg) mice, which express human CD20, were immunised with the myelin fusion protein MP4 to induce experimental autoimmune encephalomyelitis (EAE). Both light and electron microscopy were used to assess myelination and axonal pathology in mice treated with OBZ during chronic EAE. Furthermore, the effects of the already established murine anti-CD20 antibody 18B12 were assessed in C57BL/6 wild-type (wt) mice. In both models (18B12/wt and OBZ/CD20dbtg) anti-CD20 treatment significantly diminished the extent of spinal cord pathology. While 18B12 treatment mainly reduced the extent of axonal pathology, a significant decrease in demyelination and increase in remyelination were additionally observed in OBZ-treated mice. Hence, the data suggest that OBZ could have neuroprotective effects on the CNS, setting the drug apart from the currently available type I anti-CD20 antibodies