Introduction: Childhood Absence Epilepsy, a subtype of genetic generealised
epilepsy, is characterised by sudden and brief episodes of impaired consciousness.
The Leucine-rich glioma-inactivated protein 1 (LGI1) and N-methyl-D-aspartate
receptor (NMDAR) are key proteins involved in regulating neuronal excitability.
In conditions like anti-LGI1 encephalitis and anti-NMDAR encephalitis,
autoantibodies target and disrupt these proteins, causing memory deficits,
behavioural changes, sleep disturbances, and epileptic seizures. However, the roles
of LGI1 and NMDAR dysfunction in the pathophysiology of absence of seizures
remain unclear. This study aims to investigate the effects of LGI1 and NMDAR
antibodies on absence seizures using two experimental models: Genetic Absence
Epilepsy Rats from Strasbourg (GAERS) and a low-dose pentylenetetrazol (PTZ)
model of absence seizures.
Methods: IgG purified from the peripheral blood of healthy controls (HC IgG),
and patients with anti-NMDAR, and anti-LGI1 encephalitis, was administered
intracerebroventricularly into GAERS and Wistar rats every other day for 11
days. Before and after antibody administration, electroencephalography (EEG)
recordings were performed to analyse spontaneous spike-and-wave discharges
(SWDs) in GAERS. In Wistar rats, after the completion of antibody infusions, PTZ
was administered (35 mg/kg) on the 12 th day to induce absence seizures. The
occurrence of PTZ-induced SWDs was quantified.
Results: NMDAR IgG significantly increased the duration and number of SWDs
in GAERS compared to HC IgG. LGI1 IgG had no significant effect, suggesting a
differential role of NMDAR and LGI1 antibodies in modulating SWD activity.
Similarly, NMDAR IgG-treated Wistar rats showed increased susceptibility to PTZinduced
absence seizures, while LGI1 IgG did not cause significant changes in PTZinduced
SWDs.
Conclusion: These results reveal a distinct pro-epileptogenic effect of NMDAR
antibodies in both genetic and pharmacological models of absence epilepsy, while
LGI1 antibodies appear to have a negligible effect. These findings suggest a specific
role for NMDAR dysfunction in absence seizure pathophysiology and support
further investigation into antibody-mediated seizure mechanisms.
Keywords: Autoantibodies, childhood absence epilepsy, genetic absence epilepsy
rat model, LGI1, NMDAR, PTZ, SWDs