Rationale: Biochemical markers of brain injury in blood, such as neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta 42 and 40 peptide (Aβ42 and Aβ40), have been utilized in managing various neurological conditions, including multiple sclerosis and neurodegenerative disorders. However, the role of these blood biomarkers in patients with epilepsy and seizures remains unclear.
The objectives of this study are to evaluate whether serum markers of neurological injury can:
- Differentiate between epileptic and non-epileptic seizures,
- Function as markers of disease severity in patients with epilepsy, and
- Serve as an indicator of recent seizures.
Methods: This was a prospective observational study conducted in adult patients admitted to the epilepsy monitoring unit at Johns Hopkins Hospital. Blood samples were collected upon admission to EMU as a baseline sample and after concluding EMU stay.
Serum NfL, GFAP, and Aβ42 and Aβ40 were tested using Simoa assay kit, with Aβ42/40 ratios calculated. Clinical data included demographics, identification of epilepsy versus psychogenic non-epileptic seizures (PNES), and baseline epilepsy severity in terms of self-reported monthly seizure frequency. We used linear regression to adjust for age to compare baseline biomarker levels in epilepsy to PNES. We looked at the correlation of seizure frequency to biomarker levels using multiple regression analysis. We used t-test to compare the difference in biomarker levels before and after seizure.
Results: Samples from 28 patients were obtained (epilepsy=19, PNES=9). Of those with epilepsy, 5 had generalized onset while 14 had focal onset seizures (lesional=5, non-lesional=9). Patients with epilepsy (PWE) had a mean of 7.3 seizures per month
There was a significant difference in Aβ42/40 ratio (mean epilepsy=0.066, PNES=0.073; p=0.041). There was no significant difference between PWE and PNES for baseline NfL (p=0.244) and GFAP (p=0.201) (Table 1). There was a significant correlation between increasing seizures frequency and lower Aβ42 (p=0.002) but no correlation with Aβ42/40 ratios (p=0.183). There was no significant correlation between seizure frequency and concentration of NfL (p=0.399) or GFAP (p=0.154) (Table 2).
18 patients had repeat samples obtained prior to discharge (PWE=12, PNES=6). Six patients had seizures in the EMU with 5 being focal seizures and 1 generalized tonic clonic There was no significant difference in the change in NfL (p=0.214), GFAP (p=0.424), or Aβ42/40 ratios (p=0.444) before and after seizures.
Conclusions: In this preliminary analysis, PWE demonstrated a lower Aβ42/40 ratio compared to patients with PNES. Additionally, there was a significant correlation between increasing epileptic seizures frequency and lower Aβ42.
There were no differences observed in measures of other serum markers, including NfL and GFAP, between both groups (PWE vs. PNES). There was no change in the level of biomarkers before and after seizures.
Lower Aβ42/40 ratios have been correlated with higher risk of development of Alzheimer's Disease (AD) pathology. Our preliminary findings add further evidence to the bidirectional relationship between AD and epilepsy.
Funding: none