Neuropathologic changes associated with stereoelectroencephalography depth electrode placement.

BACKGROUND: The aim of this study was to detail the neuropathologic changes resulting from the surgical placement of stereoelectroencephalography (SEEG) leads in an initial small group of epilepsy cases and to raise awareness of this iatrogenic pathology, especially to those medical providers who specialize in the care of epilepsy patients. METHODS: Five consecutive patients who underwent epilepsy resection surgery following SEEG monitoring at OSF Saint Francis Medical Center were included in our report. Resection specimens were examined grossly and entirely submitted for microscopic evaluation by a neuropathologist. Seizure-related pathologies, as well as histologic changes related to SEEG electrode placement, were documented. RESULTS: The patient cohort included two females and three males, with an age range of 9 to 47 years. Neuropathologic examination revealed one or more seizure-related pathologies in each patient's resection specimen. In addition, all brain resection specimens showed multiple microinfarcts, which appeared to correlate with the placement and size of SEEG electrodes. Patchy leptomeningeal chronic inflammation was also seen in most cases. CONCLUSIONS: SEEG electrode placement is an effective procedure for determining epileptogenic regions and guiding subsequent resection surgeries in medically refractory epilepsy. Multiple microinfarcts and chronic inflammation are commonly seen in brain resection specimens following SEEG electrode insertion, but studies detailing these iatrogenic histopathologic changes are lacking. The clinical significance and long-term implications of multiple small foci of electrode-induced injury that remain in the patient's brain after resection of the epileptogenic focus are unknown and may provide a welcome area for future study.

Therapeutic efficacy of matrix metalloproteinase-12 suppression on neurological recovery after ischemic stroke: Optimal treatment timing and duration.

We recently showed that the post-ischemic induction of matrix metalloproteinase-12 (MMP-12) in the brain degrades tight junction proteins, increases MMP-9 and TNFα expression, and contributes to the blood-brain barrier (BBB) disruption, apoptosis, demyelination, and infarct volume development. The objectives of this study were to (1) determine the effect of MMP-12 suppression by shRNA-mediated gene silencing on neurological/functional recovery, (2) establish the optimal timing of MMP-12shRNA treatment that provides maximum therapeutic benefit, (3) compare the effectiveness of acute versus chronic MMP-12 suppression, and (4) evaluate potential sex-related differences in treatment outcomes. Young male and female Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion and reperfusion. Cohorts of rats were administered either MMP-12shRNA or scrambled shRNA sequence (control) expressing plasmids (1 mg/kg; i.v.) formulated as nanoparticles. At designated time points after reperfusion, rats from various groups were subjected to a battery of neurological tests to assess their reflex, balance, sensory, and motor functions. Suppression of MMP-12 promoted the neurological recovery of stroke-induced male and female rats, although the effect was less apparent in females. Immediate treatment after reperfusion resulted in a better recovery of sensory and motor function than delayed treatments. Chronic MMP-12 suppression neither enhanced nor diminished the therapeutic effects of acute MMP-12 suppression, indicating that a single dose of plasmid may be sufficient. We conclude that suppressing MMP-12 after an ischemic stroke is a promising therapeutic strategy for promoting the recovery of neurological function.