Review articleImmunological perspectives of temporal lobe seizures
Introduction
There is abundant evidence suggesting that both acute and chronic activation of inflammatory pathways are associated with the occurrence of seizures (Aronica and Crino, 2011, Friedman and Dingledine, 2011, Vezzani et al., 2011, Bauer et al., 2012). Proinflammatory cytokines are induced after experimental seizures and seizures in patients (Vezzani et al., 1999, Peltola et al., 2000a, Lehtimäki et al., 2003, Lehtimäki et al., 2007, Vezzani et al., 2011). There is also evidence for the chronic overproduction of proinflammatory cytokines in epilepsies of differing etiologies (Crespel et al., 2002, Ravizza et al., 2008, Alapirtti et al., 2009, Liimatainen et al., 2009a; reviewed by Vezzani et al., 2011). The activation of immunity mechanisms in seizures is further suggested by the fact that many different autoantibodies are associated with certain epileptic syndromes (Rogers et al., 1994, Bartolomei et al., 1996, Palace and Lang, 2000, Peltola et al., 2000b, Peltola et al., 2000c, Eriksson et al., 2001, Ranua et al., 2004, Liimatainen et al., 2009a, Liimatainen et al., 2009b, Bien and Scheffer, 2011, Irani et al., 2011a, Irani et al., 2011b, Quek et al., 2012). Clinical data indicate inflammatory changes in the brain tissue of posttraumatic epilepsy patients and an increased incidence of epilepsy in autoimmune diseases (Mackworth-Young and Hughes, 1985, Bartfai et al., 2007). Moreover, immunomodulatory drugs may control seizures in the catastrophic epileptic encephalopathies that occur during childhood, such as ACTH treatment for infantile spasms and intravenous immunoglobulin (IVIG) for other refractory epilepsies (Mackworth-Young and Hughes, 1985, Aarli, 2000, Palace and Lang, 2000, Villani et al., 2007, Granata et al., 2011, Özkara and Vigevano, 2011).
In addition to epilepsy, the temporal lobe is the primary affected brain area in both infectious and immunological encephalitides. Both anatomical factors and immunopathological etiologies, such as the relatively simple structure, the proximity of hypophysis–pituitary axis, and the tendency of neurotropic viruses and disorders causing limbic encephalitis to affect this brain region might explain the vulnerability of the temporal lobe. There is also evidence of a different inflammatory response to seizures in blood of patients with temporal lobe epilepsy (TLE) in comparison to those who have extra-TLE (XTLE) (Alapirtti et al., 2009, Liimatainen et al., 2009a).
Section snippets
Neurodegeneration in temporal lobe seizures
TLE is the most common refractory epilepsy type in adults. The relationship between seizure activity and neuronal damage has been assessed in both experimental and clinical studies. Hippocampal circuit alterations, neuronal loss and mossy fiber sprouting induced by repeated seizures, can result in atrophy and long-term consequences, i.e. cognitive decline and intractability in TLE (Cavazos et al., 1991, Cavazos et al., 1994, Kälviäinen and Salmenperä, 2002, Kotloski et al., 2002). An
The role of innate and adaptive immunity in seizure disorders
Inflammation is not a rare phenomenon in the epileptic brain. Brain inflammation constitutes from innate and adaptive arms. The innate immunity refers to an acute reaction of neuronal tissue to a particular stimulus, such as injury or seizures. This reaction includes a release of interleukins (ILs), interferons, complement proteins, prostaglandins (PG), chemokines and adhesion molecules, and activation of intracellular signaling pathways, such as nuclear factor kappa B (NFκB). The cell types
Viral etiology
The tendency of neurotropic viruses and other virus types that are capable of triggering seizures to invade the mesial temporal lobe serves as an example of the vulnerability of this brain region. Patients with viral encephalitis most commonly develop seizures during the acute period, and a proportion will develop remote symptomatic epilepsy. The data suggest that the activation of the immune cascade is an important event in triggering seizures (Leung and Robson, 2007, Getts et al., 2008).
The
Conclusions
In this review we have evaluated the most important mechanisms of inflammatory reactions in TLE. There is evidence that several inflammatory mediators have a specific role in temporal lobe seizures; however, in some circumstances other brain regions are affected as well. From the clinical point of view, in epilepsy patients the significance of the activation of the immune system and the induction of inflammatory mediators is still unclear. The cause–effect relations are difficult to evaluate in
Conflicts of interest
None of the authors has any conflict of interest to disclose.
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