Serum S100B in primary progressive multiple sclerosis patients treated with interferon-beta-1a

S100B belongs to a family of calcium-binding proteins implicated in intracellular and extracellular regulatory activities. This study of serum S100B in primary progressive multiple sclerosis (PPMS) is based on data obtained from a randomized, controlled trial of Interferon β-1a in subjects with PPMS. The key questions were whether S100B levels were associated with either disability or MRI findings in primary progressive MS and whether Interferon β-1a has an effect on their S100B levels. Serial serum S100B levels were measured using an ELISA method. The results demonstrated that serum S100B is not related to either disease progression or MRI findings in subjects with primary progressive MS given Interferon β-1a. Furthermore there is no correlation between S100B levels and the primary and secondary outcome measures

Rostrocaudal Dynamics of CSF Biomarkers

The rostrocaudal gradient (RCG) of markers present in cerebrospinal fluid (CSF) has not been studied adequately due to lack of appropriate control populations and ethical restrictions. The aim of this study is to understand the rostrocaudal gradient of CSF biomarkers. We contacted a study comparing CSF levels of seven biomarkers from cisternal (rostral) and lumbar (caudal) CSF obtained from patients with trigeminal neuralgia and tension-type headache. The RCGs of CSF/serum albumin ratio, 8-isoprostane. GFAP, total tau and beta amyloid protein were higher than one. The RCGs of lactate, VEGF and the heavy chain of neurofilament protein were lower than one. The study provides new values for several commonly examined markers of cisternal CSF. Knowledge of the RCG gradient of different CSF markers is important in interpreting studies reporting ventricular CSF values. © Springer Science+Business Media, LLC 2010

Temporal alterations in cerebrospinal fluid amyloid beta-protein and apolipoprotein E after subarachnoid hemorrhage

Background and Purpose— The mechanism underlying the association between possession of the APOE{epsilon}4 allele and less favorable outcome after subarachnoid hemorrhage (SAH) remains to be determined. After SAH the level of apolipoprotein E (apoE) in the cerebrospinal fluid (CSF) is decreased, and lower levels are associated with more severe injury and less favorable outcome. This study examined serial CSF samples to determine the time course for the decrease in CSF apoE and the relationship between CSF apoE and amyloid ß-protein (Aß), testing the hypothesis that apoE-Aß interactions occur in vivo after SAH.Methods— Enzyme-linked immunosorbent assay was used to assay apoE, Aß1–40, and Aß1–42 in serial ventricular CSF samples from 19 patients with SAH and 13 controls. CSF S100B and {tau} were assayed as surrogate markers of brain injury.Results— There was a sustained decrease in CSF apoE (P<0.001) and Aß (P<0.001) after SAH in contrast to the observed elevation in CSF S100B (P<0.001) and {tau} (P<0.001) concentration. There was significant correlation between CSF Aß concentration and clinical outcome (r=0.65, P<0.01), and the decrease in CSF Aß concentration correlated significantly with that of apoE (r=0.85, P<0.0001).Conclusions— After SAH both apoE and Aß levels decrease in the CSF, supporting the concept that interactions between these proteins occur in vivo. The possibility that apoE and Aß influence outcome after SAH warrants further investigation

Alterations in cerebrospinal fluid apolipoprotein E and amyloid beta-protein after traumatic brain injury

There is evidence that apolipoprotein E (apoE) and amyloid beta-protein (Abeta), which are implicated in the pathology of chronic neurodegenerative disorders, are involved in the response of the brain to acute injury; however, human in vivo evidence is sparse. We conducted a prospective observational study to determine the magnitude and time-course of alterations in cerebrospinal fluid (CSF) apoE and Abeta concentrations after traumatic brain injury (TBI), and the relationship of these changes to severity of injury and clinical outcome. Enzyme linked immunosorbant assay (ELISA) was used to assay apoE, Abeta(1-40) and Abeta(1-42) in serial CSF samples from 13 patients with TBI and 13 controls. CSF S100B and tau were assayed as surrogate markers of brain injury. There was a significant decrease in CSF apoE (p < 0.001) and Abeta (p< 0.001) after TBI contrasting the observed elevation in CSF S100B (p < 0.001) and tau (p < 0.001) concentration. There was significant correlation (r = 0.67, p = 0.01) between injury severity and the decrease in Abeta(1-40) concentration after TBI. In vivo, changes in apoE and Abeta concentration occur after TBI and may be important in the response of the human brain to injury

Cerebrospinal fluid apolipoprotein E concentration decreases after traumatic brain injury

The APOE epsilon4 allele has been associated with unfavorable outcome after several types of acute brain injury, yet the biological mechanisms underlying this observation are poorly understood. Postmortem and experimental brain injury studies suggest the presence of increased amounts of apolipoprotein E (apoE) within the neuropil after acute brain injury. We assayed the concentration of apolipoprotein E in the cerebrospinal fluid (CSF) of non-injured controls and patients with traumatic brain injury (TBI) to determine whether differences exist, and if these differences correlate with injury severity and clinical outcome. CSF apoE and S100B, a marker of injury severity, were measured by enzyme linked immunosorbant assay. CSF was sampled from 27 traumatic brain injury patients (mean age 32, median 25, range 16-65 years) within 3 days of injury, and 28 controls (mean age 40, median 37, range 19-73 years). The TBI patients all had a Glasgow Coma Score (GCS) of less than eight (i.e., severe head injury). Clinical outcome was determined using the Glasgow Outcome Score (GOS). The average concentration of apoE in the CSF of controls was 12.4 mg/L (95% CI: 10.5-14.3 mg/L) and in TBI patients was 3.7 mg/L (95% CI: 2.1-4.1 mg/L; Mann-Whitney: p < 0.0001). In contrast, the concentration of S100B in the CSF of TBI patients was significantly higher than that of controls (Mann-Whitney: p < 0.0001). We speculate that apoE is retained within the parenchyma of the central nervous system in response to injury where in view of previous data, it may have a protective role

Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory activation and biomarker candidates

Huntington's disease (HD) causes widespread CNS changes and systemic abnormalities including endocrine and immune dysfunction. HD biomarkers are needed to power clinical trials of potential treatments. We used multiplatform proteomic profiling to reveal plasma changes with HD progression. Proteins of interest were evaluated using immunoblotting and ELISA in plasma from 2 populations, CSF and R6/2 mice. The identified proteins demonstrate neuroinflammation in HD and warrant further investigation as possible biomarkers

Neuroimaging in encephalitis:analysis of imaging findings and interobserver agreement

AimTo assess the role of imaging in the early management of encephalitis and the agreement on findings in a well-defined cohort of suspected encephalitis cases enrolled in the Prospective Aetiological Study of Encephalitis conducted by the Health Protection Agency (now incorporated into Public Health England).Materials and methodsEighty-five CT examinations from 68 patients and 101 MRI examinations from 80 patients with suspected encephalitis were independently rated by three neuroradiologists blinded to patient and clinical details. The level of agreement on the interpretation of images was measured using the kappa statistic. The sensitivity, specificity, and negative and positive predictive values of CT and MRI for herpes simplex virus (HSV) encephalitis and acute disseminated encephalomyelitis (ADEM) were estimated.ResultsThe kappa value for interobserver agreement on rating the scans as normal or abnormal was good (0.65) for CT and moderate (0.59) for MRI. Agreement for HSV encephalitis was very good for CT (0.87) and MRI (0.82), but only fair for ADEM (0.32 CT; 0.31 MRI). Similarly, the overall sensitivity of imaging for HSV encephalitis was ∼80% for both CT and MRI, whereas for ADEM it was 0% for CT and 20% for MRI. MRI specificity for HSV encephalitis between 3–10 days after symptom onset was 100%.ConclusionThere is a subjective component to scan interpretation that can have important implications for the clinical management of encephalitis cases. Neuroradiologists were good at diagnosing HSV encephalitis; however, agreement was worse for ADEM and other alternative aetiologies. Findings highlight the importance of a comprehensive and multidisciplinary approach to diagnosing the cause of encephalitis that takes into account individual clinical, microbiological, and radiological features of each patient