Diagnostic Biomarkers of Epilepsy

Sueri, Chiara; Gasparini, Sara; Balestrini, Simona; Labate, Angelo; Gambardella, Antonio; Russo, Emilio; Leo, Antonio; Casarotto, Silvia; Pittau, Francesca; Trimboli, Michele; Cianci, Vittoria; Ascoli, Michele; Cavalli, Salvatore M.; Ferrigno, Giulia; Aguglia, Umberto; Ferlazzo, Edoardo

doi:10.2174/1389201019666180713095251

Cited by 23 publications

(16 citation statements)

References 136 publications

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“…Furthermore, these findings also support our recently suggested theory indicating that in genetic epilepsies, it will be more challenging to obtain permanent treatment effects considering the difficulty to remove the original triggering cause. However, in the future, the determination of a genetic predisposition to develop epilepsy could be used to identify a preventive treatment to stop epileptogenesis or as a biomarker [40].…”

Section: Discussionmentioning

confidence: 99%

Antiepileptogenic effects of Ethosuximide and Levetiracetam in WAG/Rij rats are only temporary

Leo¹,

De²,

Nesci³

et al. 2019

Pharmacological Reports

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Background: WAG/Rij rats represent a validated genetic animal model of epileptogenesis, absence epilepsy and depressive-like comorbidity. Some treatments (e.g. ethosuximide), using specific protocols, prevent the development of spontaneous absence seizures. Accordingly, ethosuximide increases remission occurrence in children with childhood absence epilepsy in comparison to valproic acid. Considering that in this animal model, antiepileptogenic effects are, in some cases, not retained over time, we studied whether the antiepileptogenic effects of both ethosuximide and levetiracetam (which also possesses antiepileptogenic effects in this and other animal epilepsy models) would be retained 5 months after drug suspension. Methods: WAG/Rij rats of ~1 month of age were treated long-term with one of the two drugs at a dose of ~80 mg/kg/day for 17 consecutive weeks; 1 and 5 months after drug suspension, the development of absence seizures as well as depressive-like behaviour were assessed by EEG recordings and the forced swimming test (FST). Results: In agreement with a previous report, both drugs continued to show antiepileptogenic effects 1 month after their discontinuation. Furthermore, ethosuximide improved depressive-like behaviour, whereas in contrast, levetiracetam worsened this symptom. However, none of the drugs maintained their antiepileptogenic effects 5 months after suspension, and in addition, animal behaviour in the FST returned to control conditions. Conclusion: Overall, these results demonstrate that the antiepileptogenic effects of both ethosuximide and levetiracetam on absence seizure development and associated depressive-like behaviour in this model are only temporary.

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Section: Discussionmentioning

confidence: 99%

Antiepileptogenic effects of Ethosuximide and Levetiracetam in WAG/Rij rats are only temporary

Leo¹,

De²,

Nesci³

et al. 2019

Pharmacological Reports

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“…Likewise, pharmacoepidemiologic studies, despite some methodological limitations, have also reported the increased risk of suicide for people taking AEDs [43,44]. Based on this background, the early detection of these pathological abnormalities could be exploited not only to discover potential antiepileptogenic and/or disease-modifying treatments but also to identify biomarkers of illnesses [4,32,45]. To this aim, experimental models represent a valid tool to study these pathological abnormalities underlying the bidirectional link between epileptogenesis and neuropsychiatric comorbidities.…”

Section: Wag/rij Rats and Neuropsychiatric Comorbiditiesmentioning

confidence: 99%

“…Most of the preclinical studies on epileptogenesis have mainly been performed in post-brain insult models, however, genetic models deserve to be considered. As reported, these models could give rise to knowledge on the epileptogenic process, which could be exploited to discover drugs able to counteract epileptogenesis as well as to identify biomarkers of epilepsy [3,4]. Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats represent a well-validated genetic model of absence epilepsy, epileptogenesis and neuropsychiatric comorbidities, in which several studies aimed at understanding the pathological abnormalities involved into the epileptogenic process and/or to identify drugs able to prevent or cure this type of non-convulsive epilepsy [3,[5][6][7].…”

Section: Introductionmentioning

confidence: 99%

WAG/Rij rat model: a resource for the pharmacology of epileptogenesis and related neurological/psychiatric comorbidities

Leo

Nesci

et al. 2019

Neurosci Res Notes

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The discovery of potential antiseizure drugs (ASDs) requires the use of experimental models that can also provide a unique chance for identifying new effective molecules able to prevent and/or cure epilepsy. Most of the preclinical knowledge on epileptogenesis derives from studies performed on post-insult models that are characterized by a recognizable first insult, a silent period lasting until the onset of the first seizure and a chronic period characterized by spontaneous recurrent seizures (SRSs). At odds, genetic models, in which the first insult remains to be identified, have been poorly investigated. Among the genetic models, the WAG/Rij rat was validated as a suitable experimental model of absence epileptogenesis with neuropsychiatric symptomatology, in which, according to our previous hypothesis on SRSs onset, genes could be considered the first ‘insult’ underlying all plastic modifications supporting the occurrences of absence seizures in this strain. In fact, in several genetic models, the initial insult could be described as the mutation leading to epilepsy that, to date, remains to be defined in this strain. The silent period ends at the occurrence of the first SRS, which is approximately at 2-3 months of age in these rats and after that time the chronic phase initiates, in which, absence seizures increase over time underlying likely further epileptogenic processes. In this review, we describe both the features of this experimental model and the effects of several pharmacological treatments against epileptogenesis and its related comorbidities including depressive-like symptoms and cognitive decline.

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“…It would be important to develop accurate and robust non-invasive/less-invasive monitoring capabilities, for example involving peripheral blood biomarkers, to further understand underlying biochemical mechanisms and to improve therapeutic approaches. Inflammation-related sera proteins are proposed to be biomarkers for monitoring epileptogenesis and also to glean therapeutic targets [ 11 ]. Inflammatory cytokine mediator IL-6 levels are increased in epileptic patients when compared to controls [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Inflammation-related sera proteins are proposed to be biomarkers for monitoring epileptogenesis and also to glean therapeutic targets [ 11 ]. Inflammatory cytokine mediator IL-6 levels are increased in epileptic patients when compared to controls [ 11 ]. Creatine kinase (CK) is elevated in the blood of patients experiencing epileptic seizures versus those with non-epileptic seizures [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Distinguishing and Biochemical Phenotype Analysis of Epilepsy Patients Using a Novel Serum Profiling Platform

et al. 2020

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Diagnosis of non-symptomatic epilepsy includes a history of two or more seizures and brain imaging to rule out structural changes like trauma, tumor, infection. Such analysis can be problematic. It is important to develop capabilities to help identify non-symptomatic epilepsy in order to better monitor and understand the condition. This understanding could lead to improved diagnostics and therapeutics. Serum mass peak profiling was performed using electrospray ionization mass spectrometry (ESI-MS). A comparison of sera mass peaks between epilepsy and control groups was performed via leave one [serum sample] out cross-validation (LOOCV). MS/MS peptide analysis was performed on serum mass peaks to compare epilepsy patient and control groups. LOOCV identified significant differences between the epilepsy patient group and control group (p = 10−22). This value became non-significant (p = 0.10) when the samples were randomly allocated between the groups and reanalyzed by LOOCV. LOOCV was thus able to distinguish a non-symptomatic epilepsy patient group from a control group based on physiological differences and underlying phenotype. MS/MS was able to identify potential peptide/protein changes involved in this epilepsy versus control comparison, with 70% of the top 100 proteins indicating overall neurologic function. Specifically, peptide/protein sera changes suggested neuro-inflammatory, seizure, ion-channel, synapse, and autoimmune pathways changing between epilepsy patients and controls.

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Diagnostic Biomarkers of Epilepsy

Abstract: Ongoing research on diagnostic biomarkers of epilepsy is promising and future preclinical and clinical studies are warranted.

Cited by 23 publications

References 136 publications

Antiepileptogenic effects of Ethosuximide and Levetiracetam in WAG/Rij rats are only temporary

Antiepileptogenic effects of Ethosuximide and Levetiracetam in WAG/Rij rats are only temporary

WAG/Rij rat model: a resource for the pharmacology of epileptogenesis and related neurological/psychiatric comorbidities

Distinguishing and Biochemical Phenotype Analysis of Epilepsy Patients Using a Novel Serum Profiling Platform

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