Serum neurofilament light chain withstands delayed freezing and repeated thawing

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

Increased serum neurofilament light chain concentration indicates poor outcome in Guillain-Barré syndrome

BACKGROUND Guillain-Barré syndrome (GBS) is an autoimmune disease that results in demyelination and axonal damage. Five percent of patients die and 20% remain significantly disabled on recovery. Recovery is slow in most cases and eventual disability is difficult to predict, especially early in the disease. Blood or cerebrospinal fluid (CSF) biomarkers that could help identify patients at risk of poor outcome are required. We measured serum neurofilament light chain (sNfL) concentrations from blood taken upon admission and investigated a correlation between sNfL and clinical outcome. METHODS Baseline sNfL levels in 27 GBS patients were compared with a control group of 22 patients with diagnoses not suggestive of any axonal damage. Clinical outcome parameters for GBS patients included (i) the Hughes Functional Score (HFS) at admission, nadir, and discharge; (ii) the number of days hospitalised; and (iii) whether intensive care was necessary. RESULTS The median sNfL concentration in our GBS sample on admission was 85.5 pg/ml versus 9.1 pg/ml in controls. A twofold increase in sNfL concentration at baseline was associated with an HFS increase of 0.6 at nadir and reduced the likelihood of discharge with favourable outcome by a factor of almost three. Higher sNfL levels upon admission correlated well with hospitalisation time (rs = 0.69, p < 0.0001), during which transfer to intensive care occurred more frequently at an odds ratio of 2.4. Patients with baseline sNfL levels below 85.5 pg/ml had a 93% chance of being discharged with an unimpaired walking ability. CONCLUSIONS sNfL levels measured at hospital admission correlated with clinical outcome in GBS patients. These results represent amounts of acute axonal damage and reflect mechanisms resulting in disability in GBS. Thus, sNfL may serve as a convenient blood-borne biomarker to personalise patient care by identifying those at higher risk of poor outcome

Seven day pre-analytical stability of serum and plasma neurofilament light chain.

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

Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy

<p>Abstract</p> <p>Background</p> <p>Temporal lobe epilepsy (TLE) is a common form of focal epilepsy. Serum biomarkers to predict cognitive performance in TLE patients without psychiatric comorbidities and the link with gray matter (GM) atrophy have not been fully explored.</p> <p>Methods</p> <p>Thirty-four patients with TLE and 34 sex - and age-matched controls were enrolled for standardized cognitive tests, neuroimaging studies as well as measurements of serum levels of heat shock protein 70 (HSP70), S100ß protein (S100ßP), neuronal specific enolase (NSE), plasma nuclear and mitochondrial DNA levels.</p> <p>Results</p> <p>Compared with the controls, the patients with TLE had poorer cognitive performances and higher HSP70 and S100ßP levels (<it>p </it>< 0.01). The patients with higher frequencies of seizures had higher levels of HSP70, NSE and S100ßP (<it>p </it>< 0.01). Serum HSP70 level correlated positively with duration of epilepsy (σ = 0.413, <it>p </it>< 0.01), and inversely with memory scores in the late registration (σ = −0.276, <it>p </it>= 0.01) and early recall score (σ = −0.304, <it>p </it>= 0.007). Compared with the controls, gray matter atrophy in the hippocampal and parahippocampal areas, putamen, thalamus and supplementary motor areas were found in the patient group. The HSP70 levels showed an inverse correlation with hippocampal volume (R square = 0.22, <it>p </it>= 0.007) after controlling for the effect of age.</p> <p>Conclusions</p> <p>Our results suggest that serum biomarkers were predictive of higher frequencies of seizures in the TLE group. HSP70 may be considered to be a stress biomarker in patients with TLE in that it correlated inversely with memory scores and hippocampal volume. In addition, the symmetric extratemporal atrophic patterns may be related to damage of neuronal networks and epileptogenesis in TLE.</p

Health-related quality of life in multiple sclerosis: temperament outweighs EDSS

Abstract Background The influence of personality on health-related quality of life in patients with multiple sclerosis has been the focus of previous studies showing that introversion and neuroticism were related with reduced health related quality of life. However, no data exist on the impact of temperament on quality of life in this patient group. Methods Between April 2014 and March 2016 139 multiple sclerosis patients were recruited from a specialized outpatient clinic of the general hospital of Vienna. Health-related quality of life was measured by “The Multiple Sclerosis International Quality of Life Questionnaire (MusiQol)”, temperament by “Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Questionnaire – Münster version” (briefTEMPS-M), and disability by the “Expanded disability status scale”. All patients underwent a diagnostic psychiatric semi-structured interview (MINI). Results Known predictors (like disease duration, EDSS, psychiatric co-morbidities, immunomodulatory treatments) explain the proportion of variation in the outcome of MusiQol global index score in 30.9% in multi-variable linear regression analysis. It increased respectively to 40.3, 42.5, and 45.8% if adding the depressive, cyclothymic, or hyperthymic temperament to the list of variables. An increase of depressive and cyclothymic temperament scores significantly reduced global index score of MusiQol (p = 0.005, p = 0.002, respectively), while the hyperthymic temperament significantly raised it (p < 0.001). Conclusion In MS patients, the depressive and cyclothymic temperament predict a lower and hyperthymic temperament an increased health-related quality of life, independent of current disability status, immunomodulatory treatments, and affective co-morbidities