Definición clínico-patológica de los subtipos de epilepsia temporal medial con esclerosis del hipocampo.El papel de la inmunohistoquímica

Abstract

Background and Objective: Temporal epilepsy with hippocampal sclerosis (ETM-EH) is the most common cause of refractory epilepsy, and the most common indication for surgery. Although effective, surgery fails in up to 40% of patients. The objective of our study was to establish a correlation between the different histological subtypes of ETM-EH and the prognosis, crisis control, side effects and anti-convulsivant drug (FAE) withdrawal in patients with refractory epilepsy. Patients and Method: Clinical histories and anatomopathological specimens of 228 patients with temporal epilepsy surgically obtained at our hospital between 1993 and 2014 were retrospectively analyzed. All patients underwent a standard preoperative evaluation and anterior temporal resection (modified from Spencer). The anatomopathological study included the standard hematoxylin-eosin and immunohistochemical (IHQ) protocol, with special interest in the assessment of neuronal loss with NeuN. Crisis control was assessed according to the scale of results of the ILAE and Engel. The mean follow-up was 8.6 years. Results: At 10 years after the intervention, 67.9% of the patients were crisis-free (ILAE 1) and as long as 77.5% of the patients were crisis-free (Engel 1) at the end of the follow-up. The probability of being without a crisis (ILAE 1) after surgery at 2 (p=0.042), 5 (p=0.001) and 7 years (p=0.22) was higher in classic and severe forms compared to isolated sclerosis CA1 and CA4 forms. Higher neuronal loss measured with the NeuN immunostain in CA1 was associated with better outcome in crisis management (multivariate analysis, p=0.08). Nestin expression was associated with better control of seizures at the end of follow-up (multivariate analysis, p=0.003). The predictive capacity of the model with variables CA1 and nestin immunoreactivity is high, with an area under the ROC curve of 0.774 (ability to predict patients without seizures). The presence of a personal history of epilepsy was associated with greater neuronal loss in CA1 (p=0.028) and CA3 (p=0.034), and the presence of psychic auras was related with greater neuronal loss in CA3 (p=0.025). In our case, the probability of withdrawal the medication was related to the presence of personal history (p=0.003) and, inversely, to neuronal loss in CA1 (p=0.036) and CA3 (p=0.038). The greatest impairment of verbal memory occurred in those patients with lower neuronal loss in CA1 (p=0.023), CA2 (p=0.049) and CA3 (p=0.035). Visual memory loss was inversely related to neuronal loss in CA1 (p=0.046) and CA2 (p=0.031). Decreased hippocampal volume in MRI was related to neuronal loss in CA2 (p=0.024) and CA1 (p=0.023), if the intervened side was left or right, respectively. Conclusions: The results indicate that the classical and severe subtypes have a better prognosis in the control of the crisis against the atypical forms, validating the clinical and prognostic utility of the classification of histological subtypes of EH from the ILAE. The value of the IHQ in the ETM-EH has been demonstrated as a key element to determine the neuropsychological prognosis and crisis management of the patients after the surgery.