Neuroinflammatory pathways as biomarkers and treatment targets

The important role of neuroinflammation in epilepsy featured in a plenary presentation by Prof. Annamaria Vezzani (Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Italy) [1]. About 30% of epilepsy patients are not seizure-free, despite the introduction of 20-30 new anti-epileptic drugs over the past 30 years. Prof. Vezzani argued that the identification of the pathogenic mechanisms of epileptogenesis will allow the design of novel treatments which are apt to prevent or reduce the generation of epileptic seizures.

Neuroinflammation is a maladaptive brain response commonly ignited in human epileptogenic brain regions and is clearly involved in animal models of epilepsy, Prof. Vezzani explained. Experimental studies in animal models showed that -if not adequately controlled- neuroinflammation is involved in the pathogenesis of seizures, neuronal cell loss, and neurological comorbidities. Neuroinflammation has now been related to several types of human epilepsy:

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  • temporal lobe epilepsy with or without hippocampal sclerosis;
  • malformations of cortical development, i.e. hemimegaloencephaly (HME), focal cortical dysplasia (FCD) type II, tuberous sclerosis;
  • Rasmussen's encephalitis;
  • febrile infection-related epilepsy syndrome (FIRES);
  • acute symptomatic seizures and status epilepticus;
  • neonatal febrile seizures;
  • acquired epilepsies;
  • absence seizures and progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1).

Insights into the dynamics of neuroinflammation in epilepsy has generated several potential cellular and molecular targets for developing new drugs, or for repurposing of available anti-inflammatory drugs, acting on key pathogenic mechanisms. Inflammatory mediators such as interleukin (IL)-1β, tumour necrosis factor (TNF), high mobility group box 1, transforming growth factor-β, and prostaglandins can alter neuronal, glial, and blood–brain barrier functions by activating transcriptional and post-translational mechanisms in brain cells. Proof-of-concept target-specific anti-inflammatory interventions in animal models of epilepsy have reported anti-ictogenic, anti-epileptogenic, and disease-modifying therapeutic effects. Prof. Vezzani specifically mentioned the IL-1 receptor antagonist anakinra, which has been administered to several patients [2].

Moreover, blood inflammatory mediators and molecular imaging of neuroinflammation are providing potential diagnostic, prognostic, and predictive biomarkers for epilepsy which are instrumental for patient stratification in future clinical studies.

1. Vezzani A. EAN 2019, PLEN03_1.
2. Jyonouchi H, et al. J Clin Cell Immunol 2016;7:5.

Posted on 27 August, 201917 March, 2021