CSF and Serum Biomarkers of Cerebral Damage in Autoimmune Epilepsy

Nass, Robert D.; Akgün, Katja; Dague, Karmele Olaciregui; Elger, Christian E.; Reichmann, Heinz; Ziemssen, Tjalf; Surges, Rainer

doi:10.3389/fneur.2021.647428

Cited by 14 publications

(7 citation statements)

References 18 publications

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“…Previous studies demonstrated that the average interictal NF-L levels in patients with drug-refractory epilepsy due to structural and other etiologies, genetic epilepsy, or temporal lobe epilepsy with hippocampal sclerosis are comparable to those in controls, although they can be slightly increased in some subpopulations of patients when using a cut-off level of 10 pg/mL [ 51 , 52 , 53 ]. Other studies, however, reported that patients with post-stroke epilepsy or epilepsy related to auto-immune encephalitis have chronically increased serum NF-L levels, even though the levels remain below 100 pg/mL [ 52 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI

Heiskanen

Jääskeläinen

Manninen

et al. 2022

IJMS

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Plasma neurofilament light chain (NF-L) levels were assessed as a diagnostic biomarker for traumatic brain injury (TBI) and as a prognostic biomarker for somatomotor recovery, cognitive decline, and epileptogenesis. Rats with severe TBI induced by lateral fluid-percussion injury (n = 26, 13 with and 13 without epilepsy) or sham-operation (n = 8) were studied. During a 6-month follow-up, rats underwent magnetic resonance imaging (MRI) (day (D) 2, D7, and D21), composite neuroscore (D2, D6, and D14), Morris-water maze (D35–D39), and a 1-month-long video-electroencephalogram to detect unprovoked seizures during the 6th month. Plasma NF-L levels were assessed using a single-molecule assay at baseline (i.e., naïve animals) and on D2, D9, and D178 after TBI or a sham operation. Plasma NF-L levels were 483-fold higher on D2 (5072.0 ± 2007.0 pg/mL), 89-fold higher on D9 (930.3 ± 306.4 pg/mL), and 3-fold higher on D176 32.2 ± 8.9 pg/mL after TBI compared with baseline (10.5 ± 2.6 pg/mL; all p < 0.001). Plasma NF-L levels distinguished TBI rats from naïve animals at all time-points examined (area under the curve [AUC] 1.0, p < 0.001), and from sham-operated controls on D2 (AUC 1.0, p < 0.001). Plasma NF-L increases on D2 were associated with somatomotor impairment severity (ρ = −0.480, p < 0.05) and the cortical lesion extent in MRI (ρ = 0.401, p < 0.05). Plasma NF-L increases on D2 or D9 were associated with the cortical lesion extent in histologic sections at 6 months post-injury (ρ = 0.437 for D2; ρ = 0.393 for D9, p < 0.05). Plasma NF-L levels, however, did not predict somatomotor recovery, cognitive decline, or epileptogenesis (p > 0.05). Plasma NF-L levels represent a promising noninvasive translational diagnostic biomarker for acute TBI and a prognostic biomarker for post-injury somatomotor impairment and long-term structural brain damage.

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Section: Discussionmentioning

confidence: 99%

Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI

Heiskanen

Jääskeläinen

Manninen

et al. 2022

IJMS

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“… 29 There are limited studies that discuss its usage as a serum or plasma marker in epilepsy; however, elevated serum levels have been reported in autoimmune epilepsy. 30 A study on patients with Down syndrome also reported near‐significantly higher levels in those with epilepsy. 31 Elevated serum concentrations were detected in adults with poststroke epilepsy (PSE) when compared to single seizure patients, but not in patients with non‐stroke related epilepsy.…”

Section: Blood Biomarkers Of Epilepsymentioning

confidence: 99%

“…NfL is an established clinical marker of neurodegenerative diseases, including Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis 29 . There are limited studies that discuss its usage as a serum or plasma marker in epilepsy; however, elevated serum levels have been reported in autoimmune epilepsy 30 . A study on patients with Down syndrome also reported near‐significantly higher levels in those with epilepsy 31 .…”

Section: Blood Biomarkers Of Epilepsymentioning

confidence: 99%

Blood biomarkers in epilepsy

Banote

Akel

Zelano

2022

Acta Neuro Scandinavica

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Robust and accessible biomarkers are greatly needed in epilepsy. Diagnostic and prognostic precision in the clinic needs to improve, and there is a need for objective quantification of seizure burden. In recent years, there have been advances in the development of accessible and cost‐effective blood‐based biomarkers in neurology, and these are increasingly studied in epilepsy. However, the field is in its infancy and specificity and sensitivity for most biomarkers in most clinical situations are not known. This review describes advancements regarding human blood biomarkers in epilepsy. Examples of biochemical markers that have been shown to have higher blood concentrations in study subjects with epilepsy include brain proteins like S100B or neuronal specific enolase, and neuroinflammatory proteins like interleukins, and tumor necrosis factor‐alpha. Some of the blood biomarkers also seem to reflect seizure duration or frequency, and levels decrease in response to treatment with antiseizure medication. For most biomarkers, the literature contains seemingly conflicting results. This is to be expected in an emerging field and could reflect different study populations, sampling or analysis techniques, and epilepsy classification. More studies are needed with emphasis put on the classification of epilepsy and seizure types. More standardized reporting could perhaps decrease result heterogeneity and increase the potential for data sharing and subgroup analyses.

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“…19 Higher levels of NfL were recently reported in patients with drug-resistant epilepsy, 20 but not in patients with autoimmune encephalitis and epilepsy. 21 NfL levels in general epilepsy populations is less well researched.…”

Section: Introductionmentioning

confidence: 99%

“…In epilepsy, NfL levels can rise after prolonged febrile seizures, 17 status epilepticus, 18 or tonic–clonic seizures 19 . Higher levels of NfL were recently reported in patients with drug‐resistant epilepsy, 20 but not in patients with autoimmune encephalitis and epilepsy 21 . NfL levels in general epilepsy populations is less well researched.…”

Section: Introductionmentioning

confidence: 99%

Neurofilament light, glial fibrillary acidic protein, and tau in a regional epilepsy cohort: High plasma levels are rare but related to seizures

et al. 2023

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ObjectiveHigher levels of biochemical blood markers of brain injury have been described immediately after tonic–clonic seizures and in drug‐resistant epilepsy, but the levels of such markers in epilepsy in general have not been well characterized. We analyzed neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and tau in a regional hospital‐based epilepsy cohort and investigated what proportion of patients have levels suggesting brain injury, and whether certain epilepsy features are associated with high levels.MethodsBiomarker levels were measured in 204 patients with an epilepsy diagnosis participating in a prospective regional biobank study, with age and sex distribution correlating closely to that of all patients seen for epilepsy in the health care region. Absolute biomarker levels were assessed between two patient groups: patients reporting seizures within the 2 months preceding inclusion and patients who did not have seizures for more than 1 year. We also assessed the proportion of patients with above‐normal levels of NfL.ResultsNfL and GFAP, but not tau, increased with age. Twenty‐seven patients had abnormally high levels of NfL. Factors associated with such levels were recent seizures (p = .010) and epileptogenic lesion on radiology (p = .001). Levels of NfL (p = .006) and GFAP (p = .032) were significantly higher in young patients (<65 years) with seizures ≤2 months before inclusion compared to those who reported no seizures for >1 year. NfL and GFAP correlated weakly with the number of days since last seizure (NfL: rs = −.228, p = .007; GFAP: rs = −.167, p = .048) in young patients. NfL also correlated weakly with seizure frequency in the last 2 months (rs = .162, p = .047).SignificanceMost patients with epilepsy do not have biochemical evidence of brain injury. The association with seizures merits further study; future studies should aim for longitudinal sampling and examine whether individual variations in NfL or GFAP levels could reflect seizure activity.

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CSF and Serum Biomarkers of Cerebral Damage in Autoimmune Epilepsy

Cited by 14 publications

References 18 publications

Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI

Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI

Blood biomarkers in epilepsy

Neurofilament light, glial fibrillary acidic protein, and tau in a regional epilepsy cohort: High plasma levels are rare but related to seizures

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