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Serum neurofilament light as biomarker of seizure-related neuronal injury in status epilepticus.

ABSTRACT: Biomarkers of neuronal damage in status epilepticus (SE) would be of great relevance for clinical and research purposes. In a retrospective cross-sectional study, serum neurofilament light chain (NfL) levels were measured in patients with SE (30 subjects), patients with drug-resistant epilepsy (30 subjects), and healthy controls (30 subjects). Serum NfL levels were higher in patients with SE (median = 26.15 pg/ml) compared to both epilepsy patients (median = 7.35 pg/ml) and healthy controls (median = 6.81 pg/ml; p < .001). In patients with SE, serum NfL levels showed a high correlation with cerebrospinal fluid (CSF) NfL (τ = .68, p < .001) as well as with CSF total tau (t-tau) levels (τ = .627, p < .001); they were higher in SE lasting >24 h (p = .013), in refractory/superrefractory SE (p = .004), and in patients who died within 30 days or who presented a worsening of clinical conditions (p = .001). Values of >28.8 pg/ml predicted 30-day clinical worsening or death (odds ratio [OR] = 10.83, 95% confidence interval [CI] = 1.96-59.83, p = .006) and SE refractoriness (OR = 9.33, 95% CI = 1.51-57.65, p = .016). In conclusion, serum NfL levels are increased in SE and correlate with SE treatment response, duration, and outcomes, therefore representing a promising biomarker of seizure-related neuronal damage.

SUBMITTER: Giovannini G

PROVIDER: S-EPMC9299158 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Serum neurofilament light as biomarker of seizure-related neuronal injury in status epilepticus.

Giovannini Giada G Bedin Roberta R Ferraro Diana D Vaudano Anna Elisabetta AE Mandrioli Jessica J Meletti Stefano S

Epilepsia 20211121 1

Biomarkers of neuronal damage in status epilepticus (SE) would be of great relevance for clinical and research purposes. In a retrospective cross-sectional study, serum neurofilament light chain (NfL) levels were measured in patients with SE (30 subjects), patients with drug-resistant epilepsy (30 subjects), and healthy controls (30 subjects). Serum NfL levels were higher in patients with SE (median = 26.15 pg/ml) compared to both epilepsy patients (median = 7.35 pg/ml) and healthy controls (med ...[more]

PMID: 34806176

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Project description:Aims/hypothesisNo established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.MethodsThis cross-sectional study included 423 adults with type 1 and type 2 diabetes and known diabetes duration of less than 1 year from the prospective observational German Diabetes Study cohort. NFL was measured in serum samples of fasting participants in a multiplex approach using proximity extension assay technology. DSPN was assessed by neurological examination, nerve conduction studies and quantitative sensory testing. Associations of serum NFL with DSPN (defined according to the Toronto Consensus criteria) were estimated using Poisson regression, while multivariable linear and quantile regression models were used to assess associations with nerve function measures. In exploratory analyses, other biomarkers in the multiplex panel were also analysed similarly to NFL.ResultsDSPN was found in 16% of the study sample. Serum NFL levels increased with age. After adjustment for age, sex, waist circumference, height, HbA1c, known diabetes duration, diabetes type, cholesterol, eGFR, hypertension, CVD, use of lipid-lowering drugs and use of non-steroidal anti-inflammatory drugs, higher serum NFL levels were associated with DSPN (RR [95% CI] per 1-normalised protein expression increase, 1.92 [1.50, 2.45], p<0.0001), slower motor (all p<0.0001) and sensory (all p≤0.03) nerve conduction velocities, lower sural sensory nerve action potential (p=0.0004) and higher thermal detection threshold to warm stimuli (p=0.023 and p=0.004 for hand and foot, respectively). There was no evidence for associations between other neurological biomarkers and DSPN or nerve function measures.Conclusions/interpretationOur findings in individuals recently diagnosed with diabetes provide new evidence associating higher serum NFL levels with DSPN and peripheral nerve dysfunction. The present study advocates NFL as a potential biomarker for DSPN.

Project description:BACKGROUND:Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of autosomal dominantly inherited spinocerebellar ataxias (SCAs). No validated blood biomarker is available to assess either disease progression or therapeutic response. Neurofilament light chain (NfL) was recently proposed as a serum biomarker for many neurodegenerative disorders. The present study investigated whether NfL was a promising serum biomarker for SCA3. METHODS:Seventeen SCA3 patients and 9 controls were enrolled in cohort A, and 116 SCA3 individuals (preclinical and patients) and 91 controls were recruited as cohort B. We assessed whether serum NfL correlated with cerebrospinal fluid (CSF) NfL in cohort A and correlations between serum NfL levels and clinical features and brain volumes were determined in cohort B. The single-molecule array method was used to measure serum NfL levels. Disease severity was determined using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). Cerebellar and brainstem volumes were assessed using MRI neuroimaging measurements. RESULTS:Serum/CSF NfL levels in cohort A were elevated in SCA3 patients, and serum and CSF NfL exhibited a significant positive correlation (r = 0.9179, p < 0.0001). Levels of serum NfL in cohort B were significantly higher in preclinical SCA3 (15.03 ± 7.49 vs 6.88 ± 2.72 pg/ mL, p < 0.0001) and manifest SCA3 subjects (37.56 ± 13.47 vs 9.07 ± 6.02 pg/ mL, p < 0.0001) compared to those in controls. Serum NfL concentrations increased from early disease stage to the next stage. Levels of serum NfL in ATXN3 mutation carriers were positively associated with SARA (r = 0.5458, p < 0.0001) and ICARS scores (r = 0.5522, p < 0.0001). Significant negative associations with cerebellar volumes (r = - 0.4217, p = 0.0003) and brainstem volumes (r = - 0.4263, p = 0.0003) were observed. All changes remained significant after adjustment for age and CAG repeat. CONCLUSIONS:Levels of serum NfL were significantly elevated in SCA3 individuals and correlated with disease severity. Serum NfL is a promising serum biomarker of disease onset and progression, and a potential candidate biomarker of treatment response in SCA3.

Dataset Information

Serum neurofilament light as biomarker of seizure-related neuronal injury in status epilepticus.

Publications

Serum neurofilament light as biomarker of seizure-related neuronal injury in status epilepticus.

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