Free Communications: Pathogenesis

Abstract

Abstract Neurotransmitter Receptor Densities in Patients with Grade II Focal Cortical Dysplasia: Correlation with Clinical Characteristics. 1,2 Michiyo Kageyama, 1 Kazumi Matsuda, 1 Shigeko Nishimura, 1 Yuko Kubota, 1 Takayasu Tottori, 1 Tadahiro Mihara, 1 Kazuichi Yagi, 1 Koichi Baba, 1 Naotaka Usui, 1 Shuichi Umeoka, and 1 Tateki Fujiwara ( 1 Shizuoka Institute of Epilepsy and Neurological Disorders 2 Shizuoka Prefectural Psychiatric Hospital, Shizuoka, Japan ). Purpose: We previously investigated the neurotransmitter receptors in focal cortical dysplasia (FCD) by examining resected cortex samples from patients with intractable epilepsy. Quantitative studies demonstrated decreases in receptor densities in more severely dysplastic lesions, and showed great individual variations in receptor densities especially in Palmini Grade II FCD cases. To find the background of the variation in receptor densities in Grade II FCD, we conducted a quantitative analysis of receptor densities by in vitro autoradiography and examined the correlation with clinical characteristics. Methods: Twenty resected specimens from patients with intractable localization-related epilepsy were obtained. The ages at onset were 0–14 years (means ± SD: 6.5 ± 5.1 years); the ages at operation were 2–31 years (19.1 ± 10.2 years); and the intervals from onset to operation were 2–30 years (12.6 ± 8.6 years). Seizures occurred daily (n = 10), weekly (n = 8), or monthly (n = 2). The specimens were immediately frozen and used for in vitro autoradiography using 3H-CGP39653 as the ligand of N-methyl-d-asparate receptor (NMDAR), 3H-AMPA as the ligand of α-amino-3-hydroxy-5-methyl-4-isoxazol propionate receptor (AMPAR), and 125I-iomazenil as the ligand of the central benzodiazepine receptor (c-BZR). Histopathologic examinations were conducted in the specimens adjacent to those used for receptor density analysis, and confirmed a diagnosis of FCD in all cases. The lesions were classified according to severity of dysplasia into these three groups (Palmini 1994): Grades I, II, and III. In Grade II lesions, the receptor densities were quantified on the autoradiogram. Statistical analyses were performed using Spearman's rank correlation (ρ) to examine the correlation between receptor densities and three clinical characteristics; onset age, operation age, and interval from onset to operation. The correlation between receptor densities and seizure frequency was also analyzed using Kruskal-Wallis test and Scheffe's test as post hoc test. Results: (1) The mean receptor densities (fmol/mg tissue) in Grade II lesions were NMDAR: 42.7 (SD = 20.7); AMPAR: 14.2 (SD = 8.9); and c-BZR: 56.5 (SD = 28.9). (2) c-BZR densities correlated significantly with onset age (ρ= 0.722, p = 0.0016) and interval from onset to operation (ρ= 0.759, p = 0.0009). (3) NMDAR and AMPAR densities showed no significant correlation with clinical characteristics. Seizure frequency did not correlate with any receptor density. Conclusion: A positive correlation was found between c-BZR density and onset age or interval from onset to operation. Since c-BZR density showed a higher correlation with interval from onset to operation than with onset age, c-BZR may increase not only with age but also with disease progression. This result suggests the possible existence of a long-term inhibitory feedback mechanism in response to excitation in the epileptogenic area of Grade II FCD in patients with intractable epilepsy.