Serum neurofilament light chain is a discriminative biomarker between frontotemporal lobar degeneration and primary psychiatric disorders

Journal of Neurology - Due to the significant clinical overlap between frontotemporal lobar degeneration (FTLD) spectrum disorders and late-onset primary psychiatric disorders (PPD), diagnostic...     

Serum neurofilament light chain (NFL) remains unchanged during electroconvulsive therapy

Abstract

Objectives: Although there is consistent evidence that electroconvulsive therapy (ECT) is safe and well tolerated by the majority of patients, some authors still accuse ECT to inevitably cause brain damage and permanent memory loss, assertions that may increase patients’ worries about a useful treatment. Recently, the measurement of neurofilament light chain (NFL) in peripheral blood was technically implemented, permitting longitudinal analysis of this biomarker for axonal damage. NFL is part of the axonal cytoskeleton and is released into the CSF and peripheral blood in the context of neuronal damage.

Methods: In our study, blood from 15 patients with major depressive disorder receiving ECT was collected before the first ECT as well as 24?h and seven days after the last ECT, respectively. NFL concentrations were analysed using the ultrasensitive single molecule array (Simoa) technology.

Results: NFL concentrations did not differ between patients and healthy controls, and there was no significant change in NFL levels in the course of ECT. On the contrary, we even found a slight decrease in absolute NFL concentrations.

Conclusions: Our study confirms the safety of ECT by using a most sensitive method for the detection of NFL in peripheral blood as a biomarker of neuronal damage.     

CSF somatostatin is elevated in patients with postzoster neuralgia

We evaluated the concentration of the neuropeptide somatostatin (SOM) in the CSF of patients with several neurologic diseases. Since SOM is localized in high concentrations in primary sensory pathways, such as the dorsal root ganglia and dorsal horn of the spinal cord, it might be involved in conditions of chronic pain due to functional alterations of nociceptive neurons, such as postinfectious zoster neuralgia. Our study indicated a marked elevation of SOM in patients suffering from postzoster neuralgia compared with controls. Comparison with other neurologic diseases revealed decreased CSF SOM levels in Parkinson's and Alzheimer's disease, unchanged values in patients with amyotrophic lateral sclerosis, and increased concentrations in patients with brain tumors. In neurodegenerative disorders, SOM levels in CSF seemed to reflect the anatomic distribution as well as a reduction or preservation of the peptide in certain brain areas affected by the disease process. In postzoster patients, postinfectious degeneration of dorsal root ganglia cells might cause deafferentation of dorsal horn neurons and activation of SOM-containing systems with increased release either locally from neurons in the dorsal horn of the spinal cord or from descending fiber projections. The results suggested that SOM may take part in the modulation of nociceptive responses.     

Plasma neurofilament light chain concentration is increased and correlates with the severity of neuropathy in hereditary transthyretin amyloidosis

Hereditary transthyretin amyloidosis (ATTRm) causes a disabling peripheral neuropathy as part of a multisystem disorder. The recent development of highly effective gene silencing therapies has highlighted the need for effective biomarkers of disease activity to guide the decision of when to start and stop treatment. In this study, we measured plasma neurofilament light chain (pNfL) concentration in 73 patients with ATTR and found that pNfL was significantly raised in ATTRm patients with peripheral neuropathy compared to healthy controls. Furthermore, pNFL correlated with disease severity as defined by established clinical outcome measures in patients for whom this information was available. These findings suggest a potential role of pNfL in monitoring disease activity and progression in ATTRm patients.     

Serum and cerebrospinal neurofilament light chain levels in patients with acquired peripheral neuropathies

Neurofilament light chain (NFL) levels reflect axonal damage in different inflammatory and neurodegenerative central nervous system conditions, in correlation with disease severity. Our aim was to determine the possible diagnostic and prognostic value of serum and cerebrospinal fluid (CSF) NFL levels in subjects with different forms of acquired peripheral neuropathies (PN). Paired serum and CSF samples of 25 patients with acquired PN were analysed for NFL using an ultrasensitive technique (Quanterix, Simoa, Lexington, MA, USA) and compared with a group of 25 age‐matched healthy subjects. Demographic, clinical, CSF and neurophysiological data were reviewed. Cases with Guillain‐Barré syndrome (N = 5), multifocal motor neuropathy (N = 3), chronic inflammatory demyelinating polyneuropathy (CIDP) and variants (N = 12), anti‐myelin‐associated glycoprotein (MAG) neuropathy (N = 3), both CIDP and anti‐MAG neuropathy (N = 1), and non‐systemic vasculitic neuropathy (N = 1) were studied. NFL levels were significantly (P < 0.001) increased in patients with PN and were higher in the CSF (median: 1407 pg/mL, range: 140.2‐12 661) than in serum (median: 31.52 pg/mL, range: 4.33‐1178). A statistically significant correlation was observed between serum and CSF levels in cases with blood‐nerve‐barrier damage (r = 0.71, P < 0.01), and between serum NFL levels and disease activity at sampling (r = 0.52, P < 0.01) and at last follow‐up (r = 0.53, P < 0.01) in all subjects. The increase of NFL values in both serum and CSF of patients with acquired PN and the significant correlation between serum NFL levels, disease severity and final outcome support the possible role of NFL as disease activity and prognostic biomarker also in peripheral nervous system disorders.     

Serum and CSF biomarkers in acute pediatric neurological disorders

Background: There have been numerous reports regarding serum or cerebrospinal fluid (CSF) biomarkers in various disorders; however, the validities of such biomarkers for more precise diagnoses and prognosis estimates remain to be determined, especially in pediatric patients with neurological disorders. Methods: Serum/CSF S100B, neuron-specific enolase, and total tau (tTau) were measured in various acute pediatric neurological disorders, and their usefulness for diagnostic and prognostic predictions was validated using receiver operating characteristic curves and area under the curve (AUC) analysis. Results: A total of 336 serum and 200 CSF specimens from 313 patients were examined, and we identified statistically significant differences that were relevant from diagnostic and prognostic viewpoints. CSF and serum tTau levels could be good predictors for diagnosis (CSF tTau; AUC = 0.76) and prognosis (serum tTau; AUC = 0.78). Conclusions: Both CSF and serum tTau levels could be useful for precise diagnostic and prognostic estimations in acute pediatric neurological disorders. Further studies are needed to clarify the clinical significance of such biomarkers.     

Mutations in the neurofilament light chain gene (NEFL)--a study of a possible pathogenous effect

Neurofilaments (NFs) have been shown to be involved in the molecular pathology of numerous neurode-generative human disorders. Recently a set of mutations in the neurofilament light gene (NF-L) was reported in patients suffering from axonal and demyelinating forms of Charcot-Marie-Tooth disease (CMT1 and CMT2). Although a few of the NEFL gene sequence variants have been shown to be rather pathogenous mutations than harmless polymorphisms, the status of some of these variants remains unclear. The aim of this study was to analyse a potential pathogenous effect of the mutations in the NEFL gene identified in CMT affected patients.     

Longitudinal serum neurofilament light chain (sNfL) concentration relates to cognitive function in multiple sclerosis patients

Journal of Neurology - Serum neurofilament light chain (sNfL) may be used as a biological marker of disease progression in multiple sclerosis (MS), although longitudinal studies correlating...     

Determination of k/l immunoglobulin light chain ratios in CSF from patients with multiple sclerosis and other neurological diseases

Using antisera against Bence-Jones protein, the concentration of light chains type k and l can be determined in CSF. The calculation of the ratio of type k to type I light chains in CSF represents a sensitive measure for the evaluation of immunological processes involving the CNS. Our results demonstrate that an increase k/l ratio is encountered in 48% of CSF specimen from multiple sclerosis (MS) patients, but also in 50% from patients with other inflammatory diseases involving the CNS, in contrast to only 18% from other neurological diseases. In none of the MS or inflammatory cases is the altered k/l ratio the only indicator of a CNS inflammation, most commonly it is accompanied by an overproportional CSF-IgG elevation (increased QG ratio), an increased cell count or both. For these reasons determination of CSF k/l ratios is helpful in the differentiation of MS and other neurological diseases, but not for the differentiation of other inflammatory CNS diseases from MS.     

The neurofilament light chain gene (NEFL) mutation Pro22Ser can be associated with mixed axonal and demyelinating neuropathy

We report the detailed clinical, electrophysiological and molecular analysis of a patient with Charcot-Marie-Tooth (CMT) disease. DNA sequencing of the coding sequences of the neurofilament light chain polypeptide (NEFL) gene revealed a c.64C > T heterozygous, missense mutation resulting in a Pro22Ser amino acid substitution. Clinical and electrophysiological studies revealed a mixed axonal and demyelinating neuropathy, with widespread demyelination involving both proximal and distal nerve segments. Mutations at this site in the NEFL gene have been previously linked to an axonal neuropathy or distal nerve demyelination. Our results emphasize the complexity of genotype–phenotype correlations in CMT and underline the possible importance of host factors and gene interactions in the development of clinical phenotypes.     

Increased prevalence of autoimmune disorders and autoantibodies in parents of children with opsoclonus-myoclonus syndrome (OMS)

Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease in childhood which can be associated with neuroblastoma. Since autoantibodies have been detected in some patients with OMS, an autoimmune etiology is suspected. We compared the prevalence of autoimmune disorders and autoantibodies in parents of children with OMS and in a group of controls of same age and sex. Autoimmune diseases were found in 15.8% of the parents of OMS children, but only in 2.0% of the controls (p<0.001) There was also an increased prevalence of autoantibodies in the OMS parents (42.8% vs. 8.0%, p<0.001). Thyroid diseases were the most frequent autoimmune diseases found, followed by inflammatory rheumatic diseases. Interestingly, the OMS parents also had significantly more autoantibodies against CNS structures than the controls (p<0.01).These findings support the autoimmune hypothesis of childhood OMS and may also hint to a genetic susceptibility for OMS.