Surgical outcome in mesial temporal sclerosis correlates with prion protein gene variant.

Background: Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgically remediable epileptic syndrome. Ablation of the cellular prion protein (PrP c ) gene ( PRNP ) enhances neuronal excitability of the hippocampus in vitro and sensitivity to seizure in vivo, indicating that PrP c might be related to epilepsy. Objective: To evaluate the genetic contribution of PRNP to MTLE-HS. Methods: The PRNP coding sequence of DNA from peripheral blood cells of 100 consecutive patients with surgically treated MTLE-HS was compared to that from a group of healthy controls adjusted for sex, age, and ethnicity (n = 180). The presence of PRNP variant alleles was correlated with clinical and presurgical parameters as well as surgical outcome. Results: A variant allele at position 171 (Asn→Ser), absent in controls, was found in heterozygosis (Asn171Ser) in 23% of patients ( p PRNP genotypes were not correlated with any clinical or presurgical data investigated. However, patients carrying the Asn171Ser variant had a five times higher chance of continuing to have seizures after temporal lobectomy (95% CI 1.65 to 17.33, p = 0.005) than those carrying the normal allele. At 18 months after surgery, 91.8% of patients with the normal allele at codon 171 were seizure free, in comparison to 68.2% of those carrying Asn171Ser ( p = 0.005). Conclusions: The PRNP variant allele Asn171Ser is highly prevalent in patients with medically untreatable MTLE-HS and influences their surgical outcome. The results suggest that the PRNP variant allele at codon 171 (Asn171Ser) is associated with epileptogenesis in MTLE-HS.