Serum α-synuclein and IL-1β are increased and correlated with measures of disease severity in children with epilepsy: potential prognostic biomarkers?

Abstract

Background: The search for noninvasive biomarkers of neuroinflammation and neurodegeneration has focused on various neurological disorders, including epilepsy. We sought to determine whether α-synuclein and cytokines are correlated with the degree of neuroinflammation and/or neurodegeneration in children with epilepsy and with acquired demyelinating disorders of the central nervous system (CNS), as a prototype of autoimmune neuroinflammatory disorders. Methods: We analyzed serum and exosome levels of α-synuclein and serum proinflammatory and antiinflammatory cytokines among 115 children with epilepsy and 10 acquired demyelinating disorders of the CNS and compared to 146 controls. Patients were enrolled prospectively and blood was obtained from patients within 48 h after acute afebrile seizure attacks or relapse of neurological symptoms. Acquired demyelinating disorders of the CNS include acute disseminated encephalomyelitis, multiple sclerosis, neuromyelitis optica spectrum disorders, and transverse myelitis. The controls were healthy age-matched children. The serum exosomes were extracted with ExoQuick exosome precipitation solution. Serum α-synuclein levels and serum levels of cytokines including IFN-β, IFN-γ, IL-1β, IL-6, IL-10 and TNF-α were measured using single and multiplex ELISA kits. Data were analyzed and compared with measures of disease severity, such as age at disease onset, duration of disease, and numbers of antiepileptic drug in use.

Revisiting the Impact of Neurodegenerative Proteins in Epilepsy: Focus on Alpha-Synuclein, Beta-Amyloid, and Tau

“…Pediatric epilepsy is another persistent brain disorder that exhibits behavioral and cognitive challenges, including intellectual dysfunctions, behavioral problems, and attention deficits [25,59]. In a clinical study of children with epilepsy, upregulated expression of serum α-synuclein was observed, with a positive correlation to the measures of disease severity, suggesting that it may present a plausible prognostic biomarker of the neurodegenerative process [25]. In addition, serum α-synuclein levels were positively correlated to exosome α-synuclein levels, the presumptive fraction of the cerebrospinal fluid (CSF).…”

“…In addition, serum α-synuclein levels were positively correlated to exosome α-synuclein levels, the presumptive fraction of the cerebrospinal fluid (CSF). Interestingly, in children with epilepsy, there was a significant correlation of exosomal α-synuclein with serum interleukin (IL)-6 levels, reflecting that exosomal α-synuclein may contribute to the neurotoxic cycle of neuroinflammation in epilepsy patients [25] based on its ability to directly activate the astrocytic production of IL-6 [60].…”

“…Here, we explore the potential association of the neurodegenerative proteins α-synuclein, beta-amyloid (Aβ), and tau with epilepsy, based on previous clinical and pre-clinical experimental studies [25][26][27][28][29][30], and highlight a novel avenue for research with potential therapeutic targets.…”

Predictive Values of the SeLECT Score and IL-1β for Post-Stroke Epilepsy

“…31 In the clinical aspect, Shi et al indicated that IL-1β levels in cerebrospinal fluid were higher in the epileptic pediatric population than in the controls; 39 Vezzani et al demonstrated that secretion and release of IL-1β was remarkedly upregulated in cerebrospinal fluid and serum of epilepsy patients after tonic-clonic seizures; 40 Ichiyama et al showed that IL-1β levels were remarkedly increased in cerebrospinal fluid of patients with febrile seizures; 41 Uludag et al showed that serum IL-1β levels were significantly elevated in patients with temporal lobe epilepsy or extra-temporal lobe epilepsy, and there is no statistical difference in the degree of elevation of IL-1β between these two groups; 42 Zhang et al found that upregulated expression of IL-1β was independently associated with increased risk of seizure recurrence after the first epileptic seizure in ischemic stroke patients, and moreover the predictive value of IL-1β expression levels for seizure recurrence was high; 18 Choi et al found that serum IL-1β levels were significantly associated with disease severity in children with epilepsy, suggesting the potential of IL-1β as a prognostic biomarker for childhood epilepsy. 43 In this study, the serum IL-1β level was an independent risk factor for PSE in ischemic stroke patients (OR: 1.457, 95% CI: 1.215-1.894) and had a medium predictive value for PSE (AUC: 0.811). The SeLECT score is a new practical prognostic tool to predict the risk of PSE, integrating five items: early seizures, severity of stroke, cortical involvement, territory of middle cerebral artery involvement and large-artery atherosclerotic aetiology.…”

Advances regarding Neuroinflammation Biomarkers with Noninvasive Techniques in Epilepsy

“…Correlation analysis showed that serum levels of IL-1 β were significantly associated with disease severity in children with epilepsy. This set of evidence highlights that serum IL-1 β may represent a biomarker for epilepsy as an ongoing neuroinflammation [ 21 ]. An observational study [ 22 ] reported that IL-6 levels in both serum and CSF were elevated in refractory status epilepticus and acute seizures.…”