Review article
Immunological perspectives of temporal lobe seizures

https://doi.org/10.1016/j.jneuroim.2013.08.001Get rights and content

Highlights

  • Activation of innate and adaptive immunity is associated with epilepsy

  • Temporal lobe is specifically vulnerable in different insults

  • Cytokines have anticonvulsive and proconvulsive effects in temporal lobe seizures

  • Different autoantibodies have shown association with temporal lobe seizures

  • Immune reactions of temporal lobe epilepsy differs from extra-temporal lobe epilepsy

Abstract

The temporal lobes are affected in many different neurological disorders, such as neurodegenerative diseases, viral and immunological encephalitides, and epilepsy. Both experimental and clinical evidence suggests a different inflammatory response to seizures in patients with temporal lobe epilepsy (TLE) in comparison to those with extra-TLE (XTLE). Proinflammatory cytokines and several autoantibodies have been shown to be associated with TLE compared to other epilepsy types suggesting the specific role and structure of the temporal lobe. Abundant experience suggests that activation of both innate and adaptive immunity is associated with epilepsy, particularly refractory focal epilepsy. Limbic encephalitis often triggers temporal lobe seizures, and a proportion of these disorders are immune-mediated. Histological evidence shows activation of specific inflammatory pathways in resected temporal lobes of epileptic patients, and certain epileptic disorders have shown increased incidence in patients with autoimmune diseases. Rapid activation of proinflammatory cytokines is observed after single seizures, but there is also evidence of chronic overproduction of cytokines and other inflammatory mediators in patients with TLE, suggesting a neuromodulatory role of inflammation in epilepsy. In this review we summarize current data on the presence and the role of immunological factors in temporal lobe seizures, and their possible involvement in epileptogenesis.

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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