SUMMARYCortical dysplasia (CD) is one of the most important causes of intractable epilepsy. The precise mechanisms of epileptogenesis in CD are not known. Using CD animal models, we attempted to understand the mechanisms and efficacy of various antiepileptic drugs. In two separate studies, we assessed (1) the effects of levetiracetam (LEV) and vagus nerve stimulation (VNS) on pentylenetetrazol (PTZ)-kindled rats, and (2) the effects of LEV and topiramate (TPM) on rats with CD and hyperthermia (HT). In the HT-induced rats with CD study, LEV and TPM decreased both the intensity of seizures and the number of rats with seizure. In these studies, we used immunocytochemistry (occludin, glial fibrillary acidic protein [GFAP], and P-glycoprotein [Pgp antibodies] and electron microscopy (EM) (sodium fluorescein [NaFlu]) and horseradish peroxidase [HRP]) to assess blood-brain barrier (BBB) integrity. Both LEV and TPM protected BBB. In PTZ-kindled rats with CD, both LEV and VNS reduced the duration of seizures. Immunocytochemistry and EM revealed no BBB impairment in any of the treatment groups. In a second set of experiments, we assessed the relationship between disruption of vascular components and epileptogenesis. Astrocytic albumin uptake in focal epileptogenic lesions with vascular components suggested that dysfunction of the BBB contributes immediately to epileptogenesis, rather than simply resulting from seizure activity. Hemosiderin deposits were seen as potential epileptogenic triggers in vascular malformations (e.g., cavernomas [CA] or arteriovenous malformations [AVMs] with or without a dysplastic cortical component). However, we found strikingly high accumulation of astrocytic albumin deposits in surgically removed brain parenchyma in the vicinity of CAs and AVMs from patients with pharmacoresistant epilepsy, which suggests different pathophysiologic dispersion pathways for hemosiderin and albumin in vascular lesions. KEY WORDS: Cortical dysplasia, Epilepsy, Bloodbrain barrier, Electron microscopy, Immunohistochemistry, Lesion with vascular component.This article presents the results of two separate studies on the involvement of blood-brain barrier (BBB) in epilepsy. The first focuses on the effects of antiepileptic drugs in animal models of cortical dysplasia, to examine if these drugs influence BBB integrity. The second part deals with breakdown of vascular components as a contributing factor in epileptogenesis.
Cortical Dysplasia, Epilepsy, and Treatment StrategiesCortical dysplasia (CD), first described by Taylor et al. (1971), is one of the most important causes of intractable epilepsy. Although the precise mechanisms linking CD to epileptogenesis remain unknown, pathogenetic mechanisms of epileptogenesis in the setting of CD are revealed to be multifactorial. Among the variable clinical manifestations of CD are seizures, developmental delay, and persistent neurologic deficits. Seizures are often medically refractory and disabling. The exact incidence of CD is unknown, since we examine only case reports o...