Immune Mechanism of Epileptogenesis and Related Therapeutic Strategies

Abstract

Immunologic and neuroinflammatory pathways have been found to play a major role in the pathogenesis of many neurological disorders such as epilepsy, proposing the use of novel therapeutic strategies. In the era of personalized medicine and in the face of the exhaustion of anti-seizure therapeutic resources, it is worth looking at the current or future possibilities that neuroimmunomodulator or anti-inflammatory therapy can offer us in the management of patients with epilepsy. For this reason, we performed a narrative review on the recent advances on the basic epileptogenic mechanisms related to the activation of immunity or neuroinflammation with special attention to current and future opportunities for novel treatments in epilepsy. Neuroinflammation can be considered a universal phenomenon and occurs in structural, infectious, post-traumatic, autoimmune, or even genetically based epilepsies. The emerging research developed in recent years has allowed us to identify the main molecular pathways involved in these processes. These molecular pathways could constitute future therapeutic targets for epilepsy. Different drugs current or in development have demonstrated their capacity to inhibit or modulate molecular pathways involved in the immunologic or neuroinflammatory mechanisms described in epilepsy. Some of them should be tested in the future as possible antiepileptic drugs.

Cenobamate and Clobazam Combination as Personalized Medicine in Autoimmune-Associated Epilepsy With Anti-Gad65 Antibodies

“… 6 , 22 In addition, a recent review of developing therapeutic resources for autoimmune-based epileptic syndromes did not identify any specifically targeting AAE with anti-GAD65 antibodies. 23 For this reason, any new therapeutic resource for these patients is of special relevance.…”

Systemic inflammation as a biomarker of seizure propensity and a target for treatment to reduce seizure propensity

“…A plethora of recent reviews has linked inflammation and epilepsy. 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 31 , 32 Although elevated body temperature is probably the best‐known indicator of inflammation that provides predictive information about increased risk of a seizure, we do not know of any study that has assessed how well serum/plasma levels of inflammation‐related proteins convey information about impending seizures.…”

Downregulated formyl peptide receptor 2 expression in the epileptogenic foci of patients with focal cortical dysplasia type IIb and tuberous sclerosis complex

“… 9 , 10 HMGB1 belongs to the damage‐associated molecular patterns (DAMPs) and promotes the upregulation of downstream inflammatory factors in epilepsy, including nuclear factor‐κB (NF‐κB), interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α). 11 In addition, glucocorticoid therapy has achieved the prevention and treatment of epilepsy and epileptic encephalopathy by directly inhibiting the expression and release of IL‐1β and TNF‐α, 12 , 13 but has serious side effects (such as hypertension and osteoporosis). 14 Intriguingly, a recent study suggests that inadequate pro‐resolving progress sustains neuroinflammation during epileptogenesis.…”