Acute-Phase Neurofilament Light and Glial Fibrillary Acidic Proteins in Cerebrospinal Fluid Predict Long-Term Outcome After Severe Traumatic Brain Injury.

BACKGROUND: This study investigated trajectory profiles and the association of concentrations of the biomarkers neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in ventricular cerebrospinal fluid (CSF) with clinical outcome at 1 year and 10-15 years after a severe traumatic brain injury (sTBI). METHODS: This study included patients with sTBI at the Neurointensive Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. The injury was regarded as severe if patients had a Glasgow Coma Scale ≤ 8 corresponding to Reaction Level Scale ≥ 4. CSF was collected from a ventricular catheter during a 2-week period. Concentrations of NfL and GFAP in CSF were analyzed with enzyme-linked immunosorbent assay. The Glasgow Outcome Scale (GOS) was used to assess the 1-year and 10-15-year outcomes. After adjustment for age and previous neurological diseases, logistic regression was performed for the outcomes GOS 1 (dead) or GOS 2-5 (alive) and GOS 1-3 (poor) or GOS 4-5 (good) versus the independent continuous variables (NfL and GFAP). RESULTS: Fifty-three patients with sTBI were investigated; forty-seven adults are presented in the article, and six children (aged 7-18 years) are described in Supplement 1. The CSF concentrations of NfL gradually increased over 2 weeks post trauma, whereas GFAP concentrations peaked on days 3-4. Increasing NfL and GFAP CSF concentrations increased the odds of GOS 1-3 outcome 1 year after trauma (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.07-2.80, p = 0.025; and OR 1.61, 95% CI 1.09-2.37, p = 0.016, respectively). Similarly, increasing CSF concentrations of NfL and GFAP increased the odds for GOS 1-3 outcome 10-15 years after trauma (OR 2.04, 95% CI 1.05-3.96, p = 0.035; and OR 1.60, 95% CI 1.02-2.00, p = 0.040). CONCLUSIONS: This study shows that initial high concentrations of NfL and GFAP in CSF are both associated with higher odds for GOS 1-3 outcome 1 year and 10-15 years after an sTBI, implicating its potential usage as a prognostic marker in the future.

Serum neurofilament light protein predicts clinical outcome in traumatic brain injury.

Axonal white matter injury is believed to be a major determinant of adverse outcomes following traumatic brain injury (TBI). We hypothesized that measurement of neurofilament light protein (NF-L), a protein found in long white-matter axons, in blood samples, may serve as a suitable biomarker for neuronal damage in TBI patients. To test our hypotheses, we designed a study in two parts: i) we developed an immunoassay based on Single molecule array technology for quantification of NF-L in blood, and ii) in a proof-of-concept study, we tested our newly developed method on serial serum samples from severe TBI (sTBI) patients (n = 72) and controls (n = 35). We also compared the diagnostic and prognostic utility of NF-L with the established blood biomarker S100B. NF-L levels were markedly increased in sTBI patients compared with controls. NF-L at admission yielded an AUC of 0.99 to detect TBI versus controls (AUC 0.96 for S100B), and increased to 1.00 at day 12 (0.65 for S100B). Importantly, initial NF-L levels predicted poor 12-month clinical outcome. In contrast, S100B was not related to outcome. Taken together, our data suggests that measurement of serum NF-L may be useful to assess the severity of neuronal injury following sTBI.

In line monitoring of the preparation of water-in-oil-in-water (W/O/W) type multiple emulsions via dielectric spectroscopy.

Multiple emulsions offer various applications in a wide range of fields such as pharmaceutical, cosmetics and food technology. Two features are known to yield a great influence on multiple emulsion quality and utility as encapsulation efficiency and prolonged stability. To achieve a prolonged stability, the production of the emulsions has to be observed and controlled, preferably in line. In line measurements provide available parameters in a short time frame without the need for the sample to be removed from the process stream, thereby enabling continuous process control. In this study, information about the physical state of multiple emulsions obtained from dielectric spectroscopy (DS) is evaluated for this purpose. Results from dielectric measurements performed in line during the production cycle are compared to theoretically expected results and to well established off line measurements. Thus, a first step to include the production of multiple emulsions into the process analytical technology (PAT) guidelines of the Food and Drug Administration (FDA) is achieved. DS proved to be beneficial in determining the crucial stopping criterion, which is essential in the production of multiple emulsions. The stopping of the process at a less-than-ideal point can severely lower the encapsulation efficiency and the stability, thereby lowering the quality of the emulsion. DS is also expected to provide further information about the multiple emulsion like encapsulation efficiency.

Serum glial fibrillary acidic protein is related to focal brain injury and outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (aSAH) stands out from other subtypes of stroke because of the high early mortality and the risk of complications. Serum glial fibrillary acidic protein (s-GFAP) concentrations are increased after stroke. The aim of this study was to investigate whether s-GFAP could be used as a marker of brain damage and outcome after aSAH. METHODS: Serum samples were obtained on a regular basis from 116 adults during a 2-week period after aSAH and analyzed using an enzyme-linked immunosorbent assay. The World Federation of Neurological Surgeons scale was used for neurological evaluation. Outcome was assessed after 1 year and categorized according to the Extended Glasgow Outcome Scale. RESULTS: Increased s-GFAP levels were seen in 81 of the 116 patients. Maximum s-GFAP correlated with World Federation of Neurological Surgeons scale on arrival and on days 10 to 15 (r=0.37, P<0.001 and r=0.47, P<0.001, respectively). Furthermore, maximum s-GFAP levels were increased in the patient group with radiological signs of focal lesions acute or at 1 year, compared with the group without focal lesions (P<0.001 in both comparisons). Patients with secondary events (re-bleeding or ischemia) reached maximum levels later in the series and both maximum and final s-GFAP levels increased compared with the levels in patients without secondary events (P<0.001 in all 3 comparisons). Finally, maximum s-GFAP correlated with outcome (r=-0.48, P<0.001) and s-GFAP was an independent predictor of dichotomized outcome. CONCLUSIONS: s-GFAP provides information about brain injury severity and outcome after aSAH, which can be useful as a complement to clinical data.

Marked increase of beta-amyloid(1-42) and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury.

Severe traumatic brain injury (TBI) may result in widespread damage to axons, termed diffuse axonal injury. Alzheimer's disease (AD) is characterised by synaptic and axonal degeneration together with senile plaques (SP). SP are mainly composed of aggregated beta-amyloid (Abeta), which are peptides derived from the amyloid precursor protein (APP). Apart from TBI in itself being considered a risk factor for AD, severe head injury seems to initiate a cascade of molecular events that are also associated with AD. We have therefore analysed the 42 amino acid forms of Abeta (Abeta1-42) and two soluble forms of APP (alpha-sAPP and ss-sAPP) in ventricular cerebrospinal fluid (VCSF) and Abeta(1-42) in plasma from 28 patients in a serial samples 0-11 days after TBI. The levels of alpha-sAPP, ss-sAPP and Abeta(1-42) were determined using ELISA assays. After TBI, there was a significant stepwise increase in VCSF-Abeta(1-42) up to 1173 % from day 0-1 to day 5-6 and in VCSF-beta-sAPP up to 2033 % increase from day 0-1 to day 7-11. There was also a slight but significant increase of VCSF-beta-sAPP from day 0-1 to day 5-6 and day 7-11. By contrast, the plasma- Abeta(1-42) level is unchanged after injury. The marked increase in VCSFAbeta(1-42) implies that increased Abeta expression may occur as a secondary phenomenon after TBI with axonal damage. The unchanged level of plasma-Abeta(1-42) in contrast to the marked increase in VCSF-Abeta(1-42) after severe TBI, supports the suggestion that plasma Abeta(1-42) does not reflect Abeta metabolism in the central nervous system (CNS).