Rationale:
Mesial Temporal Lobe Epilepsy (MTLE) is one of the most common and clinically significant forms of focal epilepsy, often characterized by drug
resistance and a strong association with structural and functional abnormalities, particularly the hippocampus. Despite advances in imaging and surgical
interventions, the pathophysiology of MTLE remains incompletely understood, and many cases are refractory to anti-seizure medications (ASM).
Recent research has identified autoimmunity as a potential contributor to epileptogenesis in MTLE. Among the implicated autoantibodies, anti-glutamic acid
decarboxylase 65 (anti-GAD65) antibodies have gained attention due to their association with autoimmune epilepsy and temporal lobe involvement. The
precise role of anti-GAD65 antibodies in MTLE pathophysiology remains unclear, but evidence suggests a dual contribution of autoimmune-mediated
dysfunction and secondary structural changes.
In this research, we aim to investigate the role of anti-GAD65 antibodies in MTLE, focusing on their contribution to disease pathogenesis, clinical
characteristics, and potential as biomarkers for autoimmune epilepsy.
Methods:
We have identified 13 patients with the inclusion criteria of focal epilepsy identified by mesial temporal lobe sclerosis (MTLS) on neuroimaging,
and positive GAD65 in serum and/ or cerebrospinal fluid (CSF). Retrospectively, we have assessed the clinical outcome, magnetic resonance imaging and
CSF analysis of these patients following in a tertiary hospital in Saudi Arabia. Moreover, brain tissue obtained was further studied by means of
immunohistochemistry, multiplex fluorescent microscopy and transcriptomic analysis for inflammatory mediators and neuronal degeneration.
Results:
The median age at symptom onset was 11 years, with a female-to-male ratio of 6:7. 58% of patients met criteria for drug-resistant epilepsy. 85%
received immunotherapy, with clinical improvement in only 45%. 4 patients underwent epilepsy surgery, of whom 100% achieved excellent outcome.
Conclusions:
Understanding the involvement of anti-GAD65 antibodies in MTLE could pave the way for novel therapeutic strategies, including
immunomodulation and surgery, which might improve outcomes for patients resistant to conventional ASMs.
Funding: No funding was received.