Granule cell dispersion is associated with hippocampal neuronal cell loss, initial precipitating injury, and other clinical features in mesial temporal lobe epilepsy and hippocampal sclerosis

• Published in: Seizure (London, England) Vol. 90; pp. 60 - 66
• Main Authors: Jardim, Anaclara Prada, Duarte, Jeana Torres Corso, Lancellotti, Carmen Lúcia Penteado, Carrete, Henrique, Centeno, Ricardo Silva, Scorza, Carla Alessandra, Cavalheiro, Esper Abrão, Guaranha, Mirian Salvadori Bittar, Yacubian, Elza Márcia Targas
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-08-2021
• Subjects: Dentate gyrus; Granule cell dispersion; Hippocampal sclerosis; Mesial temporal lobe epilepsy; Neuronal cell density; Hippocampal sclerosis; Neuronal cell density; Dentate gyrus; Granule cell dispersion; Mesial temporal lobe epilepsy
• ISSN: 1059-1311; 1532-2688
• DOI: 10.1016/j.seizure.2021.05.024

•Granule cell dispersion is associated with an initial precipitating injury.•Granule cell dispersion is more common in all ILAE HS patterns, except for Type 2.•Granule cell dispersion is associated with hippocampal neuronal loss.•Dentate gyrus width negatively correlated with total hippocampal neuronal density.•CA4 is the only subfield whose neuronal density correlated with dentate gyrus width.
To characterize a 10-year series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) and determine the histopathological characteristic of the association between granule cell dispersion (GCD) and hippocampal neuronal loss.
The study included 108 MTLE/HS patients. Histopathological analyses were performed in NeuN-stained hippocampal sections for HS pattern, neuronal density, dentate gyrus (DG) pathology, and granule cell layer width. Statistical tests investigated the association between DG pathologies and HS patterns, as well as the correlation of DG width with total hippocampal and subfield-specific neuronal densities.
Fifty-six patients (51.9%) presented right HS. All the four ILAE HS patterns were represented (90 Type 1, 11 Type 2, 2 Type 3, and 5 no-HS). Sixty-seven patients (62.0%) presented GCD, 39 (36.1%) normal DG, and 2 (1.9%) narrow DG. GCD was associated with initial precipitating injury, higher numbers of monthly focal seizures and lifetime bilateral tonic-clonic seizures, longer epilepsy duration, and older age at surgery. GCD was prevalent in all HS patterns, except for Type 2 (81.8% normal versus 18.2% GCD, p = 0.005). GCD was associated with total hippocampal and subfield-specific neuronal loss, except for CA1. DG width correlated with total hippocampal (r = -0.201, p = 0.037) and CA4 neuronal densities (r = -0.299, p = 0.002). Patients with HS Type 1 had better surgical outcomes, with 51 (61.4%) seizure-free in the first year post-surgery.
This study confirmed that seizure control in MTLE/HS patients submitted to surgical treatment is comparable worldwide. Moreover, histopathological analyses showed an association between GCD and hippocampal neuronal loss, especially in the CA4 subfield.