OBJECTIVE: To detect possible neuronal damage due to recurrent isolated seizures in patients with epilepsy in a clinical routine setting.
METHODS: We measured the serum concentrations of neurofilament light chain (sNfL) in 46 outpatients with an at least monthly occurrence (self-reported) of generalized tonic-clonic seizures in the six months prior to the study and in 49 patients who had been seizure free (self-reported) for at least one year. We assigned the patients with seizure activity into groups with moderate and high seizure frequency. We measured sNfL with a highly sensitive single molecule array (Simoa).
RESULTS: The majority (94 %) of all patients with epilepsy had sNfL values within the age adjusted reference ranges of our laboratory. Three patients with and three patients without seizure activity (each 3 %) showed elevated sNfL concentrations. Age adjusted sNfL concentrations did not differ significantly between patients with and without seizure activity in the total sample or in the female subgroup. In contrast, NfL concentrations were significantly higher in male patients with seizure activity and highest in the subgroup of those with high seizure activity, but were only above the reference range in two patients. sNfL concentrations did not differ between focal and generalized epilepsies and between genetic and structural etiologies.
CONCLUSIONS: The sNfL concentrations in patients with epilepsy and healthy patients did not differ significantly. The finding of higher sNfL concentrations in males with self-reported seizure activity should be viewed with utmost caution because the difference was small and only two male patients showed sNfL concentrations above the reference range.

Aim: Neurofilament light chain (NfL) is a nonspecific sensitive biomarker of axonal damage.Methods: This case series identified cancer patients with neurological complications who had serum NfL measurements and paired these results to outcomes.Results: NfL serum levels were available in 15 patients with hematological malignancies or solid tumors. The neurological complications studied were immune effector cell-associated neurotoxicity syndrome, immune checkpoint inhibitor-related encephalopathy, anoxic brain injury, Guillain-Barre syndrome, hemophagocytic lymphohistiocytosis, transverse myelitis, paraneoplastic syndrome, central nervous system demyelinating disorder and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. All patients but one with serum NfL >900 pg/ml died during hospitalization.Conclusion: Serum NfL levels consistently corresponded to death, disease severity or recovery in this series.
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Acute coronavirus disease 2019 (COVID-19) is paralleled by a rise in the peripheral levels of neurofilament light chain (NfL), suggesting early nervous system damage. In a cohort of 103 COVID-19 patients, we studied the relationship between the NfL and peripheral inflammatory markers. We found that the NfL levels are significantly predicted by a panel of circulating cytokines/chemokines, including CRP, IL-4, IL-8, IL-9, Eotaxin, and MIP-1ß, which are highly up-regulated during COVID-19 and are associated with clinical outcomes. Our findings show that peripheral cytokines influence the plasma levels of the NfL, suggesting a potential role of the NfL as a marker of neuronal damage associated with COVID-19 inflammation.

Spinocerebellar ataxia type 3 (SCA3) is the most common type of disease related to poly-glutamine (polyQ) repeats. Its hallmark pathology is related to the abnormal accumulation of ataxin 3 with a longer polyQ tract (polyQ-ATXN3). However, there are other mechanisms related to SCA3 progression that require identifying trait and state biomarkers for a more accurate diagnosis and prognosis. Moreover, the identification of potential pharmacodynamic targets and assessment of therapeutic efficacy necessitates valid biomarker profiles. The aim of this review was to identify potential trait and state biomarkers and their potential value in clinical trials. Our results show that, in SCA3, there are different fluid biomarkers involved in neurodegeneration, oxidative stress, metabolism, miRNA and novel genes. However, neurofilament light chain NfL and polyQ-ATXN3 stand out as the most prevalent in body fluids and SCA3 stages. A heterogeneity analysis of NfL revealed that it may be a valuable state biomarker, particularly when measured in plasma. Nonetheless, since it could be a more beneficial approach to tracking SCA3 progression and clinical trial efficacy, it is more convenient to perform a biomarker profile evaluation than to rely on only one.

OBJECTIVE: Ketamine can induce persisting psychosis in a subset of individuals who use it chronically and heavily. Previously, we found that the psychopathology and cognitive impairments in patients with ketamine dependence (KD) exhibiting persistent psychosis (KPP) bear resemblances with schizophrenia, albeit with less severity in those with no persistent psychosis (KNP). Furthermore, we also showed that patients with KD had higher blood levels of neurofilament light chain (NFL), a biomarker for neuroaxonal injury, compared to healthy controls. In this study, we aimed to investigate the differences in NFL levels between patients with KPP and KNP while comparing the levels of individuals with schizophrenia and healthy controls.
METHODS: We enrolled 64 treatment-seeking ketamine-dependent patients (53 with KNP and 11 with KPP), 37 medication-free patients with schizophrenia, and 80 healthy controls. Blood NFL levels were measured by single molecule array immunoassay.
RESULTS: NFL levels were highest in the KPP subgroup, followed by the KNP subgroup, and then the schizophrenia and control groups (mean ± SD: 24.5 ± 24.7, 12.9 ± 10.9, 9.2 ± 12.2, and 6.2 ± 2.2 pg/mL, respectively), with no significant difference observed between the schizophrenia and control groups.
CONCLUSIONS: We found that KD is associated with higher NFL levels compared to schizophrenia, with the KPP subgroup showing the most consistent alterations. The observation of accentuated neuroaxonal pathology in individuals with KPP implies that this clinical manifestation is associated with a specific neurobiological phenotype, despite prior evidence suggesting syndromal similarity between schizophrenia and KPP.

The potential of combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict disability worsening in multiple sclerosis (MS) remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their response to disease-modifying treatments (DMTs). This multicentre study, conducted across thirteen European hospitals, spanned from July 15, 1994, to August 18, 2022, with follow-up until September 26, 2023. We enrolled MS patients who had serum samples collected within 12 months from disease onset and before initiating DMTs. Multivariable regression models were used to estimate the risk of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and Expanded Disability Status Scale (EDSS) score of 3. Of the 725 patients included, median age was 34.2 years (IQR, 27.6-42.4), and 509 patients (70.2%) were female. Median follow-up duration was 6.43 years (IQR, 4.65-9.81). Higher sNfL values associated with an elevated risk of RAW (HR of 1.45; 95% CI 1.19-1.76; P < 0.001), PIRA (HR of 1.43; 95% CI 1.13-1.81; P = 0.003), and reaching an EDSS of 3 (HR of 1.55; 95% CI 1.29-1.85; P < 0.001). Moreover, higher sGFAP levels were linked to a higher risk of achieving an EDSS score of 3 (HR of 1.36; 95% CI 1.06-1.74; P = 0.02) and, in patients with low sNfL values, to PIRA (HR of 1.86; 95% CI 1.01-3.45; P = 0.04). We further examined the combined effect of sNfL and sGFAP levels. Patients with low sNfL and sGFAP values (NLGL) exhibited a low risk of all outcomes and served as reference. Untreated patients with high sNfL levels showed a higher risk of RAW, PIRA, and reaching an EDSS of 3. Injectable or oral DMTs reduced the risk of RAW in these patients but failed to mitigate the risk of PIRA and reaching an EDSS of 3. Conversely, high-efficacy DMTs counteracted the heightened risk of these outcomes, except for the risk of PIRA in patients with high sNfL and sGFAP levels. Patients with low sNfL and high sGFAP values (NLGH) showed an increased risk of PIRA and achieving an EDSS of 3, which remained unchanged with either high-efficacy or other DMTs. In conclusion, evaluating sNfL and sGFAP levels at disease onset in MS may identify distinct phenotypes associated with diverse immunological pathways of disability acquisition and therapeutic response.

BACKGROUND: Growth associated protein-43 (GAP-43) and neurofilaments light (NFL) are biomarkers of synaptic and axonal injury, and are associated with cognitive decline in Alzheimer\'s disease (AD) contiuum. We investigated whether Polygenic Hazard Score (PHS) is associated with specific biomarkers and cognitive measures, and if it can predict the relationship between GAP-43, NFL, and cognitive decline in AD.
METHODS: We enrolled 646 subjects: 93 with AD, 350 with mild cognitive impairment (MCI), and 203 cognitively normal controls. Variables included GAP-43, plasma NFL, and PHS. A PHS of 0.21 or higher was considered high risk while a PHS below this threshold was considered low risk. A subsample of 190 patients with MCI with four years of follow-up cognitive assessments were selected for longitudinal analysis . We assessed the association of the PHS with AD biomarkers and cognitive measures, as well as the predictive power of PHS on cognitive decline and the conversion of MCI to AD.
RESULTS: PHS showed high diagnostic accuracy in distinguishing AD, MCI, and controls. At each follow-up point, high risk MCI patients showed higher level of cognitive impairment compared to the low risk group. GAP-43 correlated with all follow-up cognitive tests in high risk MCI patients which was not detected in low risk MCI patients. Moreover, high risk MCI patients progressed to dementia more rapidly compared to low risk patients.
CONCLUSIONS: PHS can predict cognitive decline and impacts the relationship between neurodegenerative biomarkers and cognitive impairment in AD contiuum. Categorizing patients based on PHS can improve the prediction of cognitive outcomes and disease progression.

BACKGROUND: Neurofilament light chain (NFL), a biomarker of neuroaxonal damage, has been linked to inflammation and depressive disorders, albeit with inconsistent results. We aimed to evaluate the association between serum NFL concentration and clinically relevant depressive symptoms in the general population and to examine the potential involvement of systemic inflammation in this association.
METHODS: The data of 1881 adults aged 20-75 years were extracted from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 cycle. Serum NFL levels were quantified using a highly sensitive immunoassay. Further, markers of systemic inflammation, including systemic immune inflammation index (SII), system inflammation response index (SIRI), and white blood cell (WBC) counts were calculated based on whole blood cell counts. Clinically relevant depressive symptoms were evaluated using the 9-item Patient Health Questionnaire (PHQ-9) with a cut-off score of 10.
RESULTS: After adjusting for potential confounders, we found that each one-unit increase in ln-transformed serum NFL concentration was significantly associated with a 1.37-fold increase in the risk of clinically relevant depressive symptoms (95 % confidence interval [CI]: 1.06, 1.77; p = 0.017). Serum NFL level was significantly related to increased SII (regression coefficient [β] = 0.04, 95%CI: 0.01, 0.08; p = 0.027), SIRI (β = 0.09, 95%CI: 0.05, 0.14; p < 0.001), and WBC (β = 0.05, 95%CI: 0.03, 0.07; p < 0.001), respectively. These significant associations were observed only in elderly participants.
CONCLUSIONS: The cross-sectional study design is limited in causal inference.
CONCLUSIONS: Our findings indicate that serum NFL levels are related to an increased risk of clinically relevant depressive symptoms and higher levels of markers of systemic inflammation.

UNASSIGNED: : There is a growing interest among clinicians and researchers in identifying potential biomarkers associated with autism. Neurofilament light chain (NfL) and Tau protein, which are proteins associated with neurodegeneration and neuroaxonal degeneration, are particularly promising potential biomarker candidates in this field.
UNASSIGNED: : In this study, we compared serum NfL (sNfL) and serum Tau (sTau) levels in Autism spectrum disorder (ASD) patients, their healthy siblings (HS), and healthy controls (HC), aimed to investigate their relationship with ASD severity. Our study included 43 ASD-diagnosed participants, 43 HS participants and 42 HC participants. Clinical characteristics of the participants were assesed by Kiddie Schedule for Affective Disorders and Schizophrenia, Childhood Autism Rating Scale, Aberrant Behavior Checklist, and Strengths and Difficulties Questionnaire. Serum samples were subjected to analysis via enzyme-linked immunosorbent assay to quantitatively measure the levels of NfL and Tau protein.
UNASSIGNED: : sNfL levels in the ASD group were significantly higher than both of the control groups. Regarding sTau levels, no significant difference was found between study and control groups. In addition, NfL and Tau levels were not significantly correlated with ASD symptom severity.
UNASSIGNED: : Our findings may indicate that the sNfl levels associated with neuroaxonal damage may constitue a potential clinical biomarker rather than being an endophenotype phenomena.

We report a case of posterior reversible encephalopathy syndrome in an adult patient fulfilling criteria for proven early Lyme neuroborreliosis.