Focal cortical dysplasia: pathophysiological approach

Childs Nerv Syst. 2006 Aug;22(8):827-33. doi: 10.1007/s00381-006-0136-1. Epub 2006 Jun 9.

Abstract

Overview: Clinical and experimental studies on focal cortical dysplasia (FCD) were carried out.

Materials and methods: For the experimental study, an experimental FCD model of rats was developed. Twenty Wistar rats at 0-2 days after birth were used for the study. Kainic acid (KA) solution was injected stereotaxically into medial and lateral sites of the sensori-motor cortex. Bipolar electrodes were inserted in five rats. Their behavior and electroencephalogram (EEG) were recorded using a digital-video-EEG monitoring system. After observation periods of 1, 2, and 6 months, rats were perfused for pathological study. FCD was observed adjacent to the site of KA injection in all rats more than 1 month after the injection.

Results and discussions: EEG recording demonstrated focal spike discharges in and around the site of injection. However, clinical seizure was not observed. Pathological studies showed decrease in GABA-A receptors and increase in GABA-B receptors not only in the lesion but also in perilesional areas. Fifteen surgical cases of FCD with intractable epilepsy were subjected to the clinical study. Neuro-imaging studies including high-resolution magnetic resonance imaging and single-photon emission computed tomography were performed. Conventional EEG studies demonstrated focal EEG abnormalities with epileptic phenomena. At surgery, intraoperative electrocorticography (ECoG) was performed to localize epileptic foci under neuroleptoanalgesia. Thirteen patients showed epileptiform discharges on preresection ECoG. All foci in non-eloquent areas were resected. Pathological studies including immunohistochemical staining were performed, and the characteristics of the FCD in relation to EEG findings were analyzed. Patients in whom total lesionectomy with complete focus resection was performed had favorable postoperative courses. Nine patients (64.3%) have been seizure-free with reduced medication, and significant improvement was achieved in two patients (14.3%). Electrophysiological examination revealed epileptogenecity not only in the lesions but also in perilesional areas. The immunohistochemical studies showed a decrease in GABA-A receptors and an increase in GABA-B receptors in both the lesions and perilesional areas, but N-methyl-D: -aspartate receptors were almost negative in both areas. Glutamate R1 was decreased in both areas, but glutamate R2 was increased in both areas. These findings support the results of a electrophysiological study.

Conclusions: In conclusion, not only the epileptic property of experimental focal cortical dysplasia but also perilesional epileptogenesis was demonstrated. These findings supported the results of surgery for patients with focal cortical dysplasia. In cases of FCD, total removal of the lesion and resection of the perilesional epileptic focus are needed for a good outcome.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Animals
  • Animals, Newborn
  • Autoradiography / methods
  • Behavior, Animal
  • Brain Diseases* / chemically induced
  • Brain Diseases* / pathology
  • Brain Diseases* / physiopathology
  • Brain Mapping
  • Cerebral Cortex* / drug effects
  • Cerebral Cortex* / pathology
  • Cerebral Cortex* / physiopathology
  • Child
  • Electroencephalography / methods
  • Epilepsy / metabolism
  • Epilepsy / pathology
  • Epilepsy / physiopathology
  • Female
  • Flumazenil / analogs & derivatives
  • Flumazenil / pharmacokinetics
  • Humans
  • Immunohistochemistry / methods
  • Iodine Radioisotopes / pharmacokinetics
  • Kainic Acid
  • Male
  • Nervous System Malformations* / chemically induced
  • Nervous System Malformations* / pathology
  • Nervous System Malformations* / physiopathology
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Iodine Radioisotopes
  • Receptors, N-Methyl-D-Aspartate
  • Flumazenil
  • gamma-Aminobutyric Acid
  • iomazenil
  • Kainic Acid