Treatment-resistant patients with focal epilepsy of unknown cause display reduced neurogranin levels: a preliminary study

Background and purpose – The role of synaptic dysfunction in focal epilepsy of unknown cause is not well understood. Neurogranin is a post-synaptic protein used as a biomarker of synaptic disintegration in patients with dementia. Methods – To evaluate the association between synaptic loss, cognitive impairment and seizure activity in epilepsy, we collected sera of 51 patients with focal epilepsy of unknown cause, 26 with frontal lobe epilepsy (FLE) and 25 with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLEHS), and 25 healthy controls. Serum neurogranin levels were measured by ELISA and we sought for potential correlations between neurogranin levels versus clinical features, cognitive test and quality of life scores of the patients. Results – Neurogranin levels were significantly reduced in MTLE-HS patients as compared to FLE patients and healthy controls but were not correlated with any of the clinical and cognitive variables. Both FLE and MTLE-HS patients with treatment resistance showed significantly reduced neurogranin levels. Conclusion – Our results suggest that MTLE-HS patients suffer from reduced synaptic protein production rather than increased synaptic breakdown. Reduction of neurogranin is associated with resistance to anti-epileptic treatment implying the role of this protein in the control of seizures. Neurogranin might serve as a biomarker for monitorization of seizure activity in focal epilepsies.